Bacterial conjugation, also referred to as bacterial sex, is a major horizontal gene transfer mechanism where the DNA is transferred from a donor to a recipient bacterium by direct contact. Conjugation is universally conserved among bacteria and occurs in a wide range of environments (soil, plant surfaces, water, sewage, biofilms and host-associated bacterial communities). Within these habitats, conjugation drives the rapid evolution and adaptation of bacterial strains by mediating the propagation of various metabolic properties, including symbiotic life-style, virulence, biofilm formation, or resistance to heavy metals and, most importantly, resistance to antibiotics. These properties make of conjugation a fundamentally important process at the center of extensive study. Here, we review the key steps of conjugation by following the life-cycle of the F plasmid during transfer from the donor to the recipient cell. We also discuss our current knowledge of the extent and impact of conjugation within an environmentally and clinically relevant bacterial habitat, bacterial biofilms.

The annual construction and demolition waste (CDW) generated from EU construction sector was 850 million tons, which represented 31% of the total waste generation and about 28% of CDW was ceramics (bricks and tiles). In this study, the feasibility of using CDW brick powder as the precursor of alkali activated mortar (AAM) and extruded polystyrene (XPS) as the lightweight aggregates to form lightweight brick powder AAM (LW-BP-AAM) for non-structural applications was investigated. The thermal conductivity of LP-BPAAM was 0.112 W/m·K with density of about 1,135 kg/m³ which was lower than the counterparts with similar density in literature. The acid resistance of LW-BP-AAM is comparable to conventional fly ash based AAM and superior than ordinary Portland cement. From the scanning electron microscopy with energy dispersive X-ray spectroscopy, there was no severe damage on the surface of LW-BP-AAM but aluminate was removed from the matrix which was further verified in Fourier transform infrared spectroscopy. The mass and strength loss of LP-BP-AAM was 1.5% and 33%, respectively. Although the compressive strength of the LP-BP-AAM was low (about 1.8 MPa), it can be improved by optimising the particle size of the XPS aggregates.

Different organisms, cell types, and even similar cell lines can dramatically differ in resistance to genotoxic stress. This testifies to the wide opportunities for genetic and epigenetic regulation of stress resistance. These opportunities could be used to increas the effectiveness of cancer therapy, develop new varieties of plants and animals, and search for new pharmacological targets to enhance human radioresistance, for example, for -manned deep space expeditions. Based on the comparison of transcriptomic studies in cancer cells, in this review we propose that there is a high diversity of genetic mechanisms of development of genotoxic stress resistance. This review focused onpossibilities and limitations of the proposed regulation of the resistance of normal cells whole organisms to genotoxic and oxidative stress by overexpressing of stress-response genes. Moreover, the existing experimental data on the effect of such overexpression on the resistance of cells and organisms to various genotoxic agents has been analyzed and systematized. We suggest that the recent advances in the development of multiplex and highly customizable gene overexpression technology that utilizes the mutant Cas9 protein and the wealth of available data on gene functions and their signal networks open new opportunities for research in this field.

Background: Bloodstream infections (BSIs) pose a major health risk to hemodialysis patients, significantly contributing to morbidity and mortality. This study aimed to identify the bacterial pathogens responsible for BSIs in this population, analyze clinical and laboratory profiles, and identify risk factors associated with poor outcomes. Methods: This retrospective study was conducted at Sohar Hospital, Oman, analyzing cases from January 2018 to December 2022. Data were obtained from e-health records, focusing on patient demographics, bacterial etiology, antibiotic susceptibility, and clinical outcomes. Statistical analysis included t-tests, Mann-Whitney tests, chi-square, and Fisher’s exact tests, with univariate odds ratios calculated for mortality associations using the R package GTSUMMARY. Results: Among 1332 hemodialysis patients, 148 (11.1%) developed a BSI, with an average age of 60.43±14.46 years. Infections were more common among females (54%) and those over 60 years. The predominant comorbidities were hypertension (86%) and diabetes mellitus (74%). The main causative agents were coagulase-negative staphylococci (29.7%), Staphylococcus aureus (20.3%), Pseudomonas aeruginosa (12.2%), and Klebsiella pneumoniae (8.8%). Gram-negative bacteria showed high susceptibility (80-100%) to carbapenems and piperacillin-tazobactam, while Gram-positive bacteria exhibited 80-100% susceptibility to amoxicillin-clavulanic acid and universal sensitivity to linezolid and vancomycin. Conclusions: BSIs in hemodialysis patients at Sohar Hospital are associated with high morbidity and mortality rates, underscoring the need for prompt empirical antibiotic therapy and targeted treatment adjustments based on culture results. This study highlights critical mortality-associated factors, offering valuable insights for improving patient management and survival outcomes in this vulnerable population.

Emerging research into the human microbiome, an intricate ecosystem of microorganisms residing in and on our bodies, reveals that it plays a pivotal role in maintaining our health, highlighting the potential for microbiome-based interventions to prevent, diagnose, treat, and manage a myriad of diseases. The objective of this review is to highlight the importance of microbiome studies in enhancing our understanding of rare genetic epilepsy and related neurological disorders. Studies suggest that the gut microbiome, acting through the gut-brain axis, impacts the development and severity of epileptic conditions in children. Disruptions in microbial composition can affect neurotransmitter systems, inflammatory responses, and immune regulation, which are all critical factors in the pathogenesis of epilepsy. This growing body of evidence points to the potential of microbiome-targeted therapies, such as probiotics or dietary modifications, as innovative approaches to managing epilepsy. By harnessing the power of the microbiome, we stand to develop more effective and personalized treatment strategies for children affected by this and other rare neurological diseases.

BACKGROUND. Invasive aspergillosis (IA) is a deadly fungal lung infection. Antifungal resistance and treatment side effects are major concerns. Iron chelators are vital for IA management, but systemic use can cause side effects. We developed nanoparticles (NPs) to selectively deliver the iron chelator deferasirox (DFX) for IA treatment. METHODS DFX was encapsulated in poly(lacticco‐ glycolic acid) (PLGA) NPs using a single emulsion solvent evaporation method. NPs were characterized by light scattering and electron microscopy. DFX loading efficiency and release were assessed spectrophotometrically. Toxicity was evaluated using SRB, luciferase, and XTT assays. Therapeutic efficacy was tested in an IA mouse model, assessing fungal burden by qPCR and biodistribution via imaging.RESULTS DFX‐NPs had a size of ~50nm and a charge of ~‐30mV, with a loading efficiency of ~90%. Release kinetics showed DFX release via diffusion and bioerosion. The EC50 of DFX‐NPs was significantly lower (p<0.001) than the free drug, and they were significantly less toxic (p<0.0001) in mammalian cell cultures. In vivo, NPs treatment significantly reduced Af burden (p<0.05). CONCLUSION The designed DFX‐NPs effectively target and kill Af with minimal toxicity to mammalian cells. The significant in vivo therapeutic efficacy suggests these NPs could be a safe and effective treatment for IA.

Cardiovascular risk factors (CRFs) such as hypertension, high cholesterol, and diabetes are increasingly implicated in cognitive decline and cerebral small vessel disease (cSVD). White matter hyperintensities (WMH), a hallmark of cSVD, are strongly linked to cognitive impairment, but their underlying mechanisms remain unclear. Blood-brain barrier (BBB) dysfunction has been proposed as a potential contributor to WMH development. This study aimed to explore the relationships between CRFs, BBB integrity, and WMH burden. We analyzed 155 participants from the Biomarkers and Cognition Study, Singapore, assessing CRFs through blood tests for glucose and lipid profiles, alongside blood pressure measurements. WMH volume was quantified using MRI, and an in vitro assay evaluated the impact of plasma on BBB integrity using human brain microvascular endothelial cells. Results showed that plasma from participants with higher WMH burden correlated with increased BBB disruption, which was further associated with higher blood pressure, elevated blood glucose, and lipid levels. Both periventricular and subcortical WMH were linked to BBB disruption. These findings suggest that CRFs contribute to BBB dysfunction, promoting WMH development and cognitive decline in cSVD. Further research is needed to clarify the precise mechanisms driving these associations.

The emergence of antimicrobial resistance (AMR) in pathogens transmitted through food poses a significant threat to global public health, complicating infection treatment and increasing mortality rates. This review explores the role of resistome mapping as a crucial tool for understanding the transmission dynamics of antimicrobial resistance genes (ARGs) in foodborne pathogens, such as Salmonella, Escherichia coli, Listeria monocytogenes, and Campylobacter spp., as well as various techniques for resistome mapping, such as metagenomic sequencing, PCR-based methods, and whole-genome sequencing (WGS), highlighting the significance of horizontal gene transfer (HGT) as a key mechanism for ARG dissemination in foodborne pathogens. Additionally, we investigated the influence of agricultural practices and environmental factors on AMR development, highlighting the critical need for improved surveillance, antibiotic stewardship, and global collaboration to mitigate the spread of resistant ARGs through the food chain. The perceptions gained from resistome mapping play an essential role in developing effective approaches to address AMR and to ensure food safety.

Soft pneumatic actuators/robotics have received significant interest in the medical and health fields, due to their intrinsic elasticity and simple control strategies enabling desired interaction. However, current soft hand pneumatic exoskeletons often exhibit uniform deformation, mismatch the profile of the interacted objects, and seldom quantify the assistive effects during activities of daily life (ADL), such as extension angle and joint stiffness predicted. The lack of quantification poses challenges to the effective and sustainable advancement of rehabilitation technology. This paper introduces the design, modeling, and testing of pneumatic bioinspired Segmented Composite Proprioceptive Bending Actuators (SCPBAs) for hand rehabilitation in ADL tasks. The actuator’s soft-joint/rigid-bone segmented structure, inspired by the human finger anatomy, provides a superior fit compared to traditional continuous structures. A quasi-static model is established to predict the bending angles based on geometrical parameters. The SCPBAs also include a quantitative evaluation of joint stiffness and extension angle utilizing proprioceptive bending information. Additionally, a soft under-actuated hand exoskeleton equipped with SCPBAs demonstrates its potential in ADL rehabilitation scenarios.

Hepatocellular carcinoma (HCC) is a liver cancer that originates from hepatocytes. It is a primary health issue and one of the most common malignant tumors. The US FDA approved Sorafenib as the first-line anti-cancer drug for advanced HCC patients. A few patients with advanced HCC may benefit from Sorafenib treatment, but most of the patients eventually develop resistance to Sorafenib, which leads to its poor prognosis. Long-noncoding RNAs (lncRNA) have been found to play a critical role in tumorigenesis and the development of HCC, as well as various cancers. It also plays a vital role in tumor drug resistance, while the mechanisms of LncRNAs in HCC sorafenib resistance have not been characterized yet. In this review article, we summarized the molecular mechanisms, such as the involvement of transporters, receptors, cell death regulation, and other factors impacting sorafenib resistance in HCC.

Escherichia coli is a gram-negative commensal bacterium living in human and animal intestines. Its pathogenic strains are cause of high morbidity which can adversely affect people by causing urinary tract infections, food poisoning, septic shock, or meningitis. Humans can contract E. coli by eating contaminated food—such as raw or undercooked raw milk, meat products, and fresh produce sold in open markets—as well as by coming into contact with contaminated settings like wastewater, municipal water, soil, and faeces. Some pathogenic strains of E. coli have been identified in Nigeria such as enterohemorrhagic (EHEC), as well as enterotoxigenic (ETEC), enteropathogenic (EPEC), enteroinvasive (EIEC), enteroaggregative (EAEC), and verotoxigenic (VTEC). This causes acute watery or bloody diarrhoea, stomach cramps, and vomiting. Apart from the virulence profile of E. coli, antibiotic resistance mechanisms such as the presence of blaCTX-M found in humans, animals and environmental isolates which are of great importance and require surveillance and monitoring for emerging threats in resource-limited countries. This review is aimed at understanding the underlying mechanisms of evolution and antibiotic resistance in E. coli in Nigeria and highlighting the use of improving One Health approaches to combat the problem of emerging infectious diseases.

The measurement of the grounding resistance of protection grids in large installations as well as grounding electrodes in urban areas is addressed in this article. The resistance value is obtained using a three-pin array by measuring the fall-of-potential on the ground surface. The resistance measured by this method is corrected using the so-called correction factor that adjusts the measured resistance value to its real value. The proposed measurement method obtains correct values of the grounding resistance even when the auxiliary and potential electrodes of the tree-pin array are close to the electrode to be measured. Thus, it can be applied to large electrodes as well as electrodes in urban areas. Several simulated examples are used to illustrate the method, and some real cases with field measurements are presented for a final validation of the method.

Antimicrobial resistance (AMR) is a global threat associated with high morbidity and mortality, particularly in low- and middle-income countries. Inappropriate use of antimicrobials is one of the major drivers of the AMR pandemic. This study aims to evaluate the rate and quality of antimicrobial prescription and use at the University Teaching Hospital of Kigali, a tertiary referral and teaching hospital. A point prevalence survey (PPS) of antimicrobial prescription was conducted using the Global PPS tool, including the healthcare-acquired infections (HAI)-module. On the day of PPS, 39.3% (145/369) of the patients were prescribed at least one antimicrobial. Out of 259 prescribed antimicrobials, 232 (89.6%) were antibacterials of which 151 (65.1%) belonged to the Watch-group of the WHO AWaRe classification. Top three antibiotics prescribed were cefotaxime (87; 37.5%), parenteral metronidazole (31; 13.4%); and meropenem (23; 9.9%). Stop/review of the prescribed antimicrobials was documented in 27/259 prescriptions (10.4%). Surgical prophylaxis (SP) was prescribed for more than one day in 83.3% of 61. Samples for culture were sent for 27.1% (63/232) of all prescribed antibiotics. This PPS showed a high usage of Watch antibiotics, prolonged surgical prophylaxis and other poor-quality indicators. Therefore, there is an urgent need for antimicrobial stewardship interventions.

The emergence of antimicrobial resistance (AMR) Candida auris presents a formidable global health challenge, causing severe healthcare-associated infections with high mortality rates. Its ability to colonize surfaces and resist standard disinfectants undermines traditional hygiene practices, prompting an urgent need for novel strategies. Ultraviolet C (UVC) light offers a promising approach due to its rapid and broad-spectrum germicidal efficacy. This review comprehensively examines the current knowledge of UVC LED technology in combating C. auris, highlighting its effectiveness, limitations, and potential applications in healthcare hygiene. UVC light has potent activity against C. auris, including multidrug-resistant (MDR) strains. UVC can reduce C. auris on contaminated surfaces, aiding in transmission prevention. This review explores implementation strategies, including mobile UVC systems for targeted disinfection of high-risk areas and equipment, integration into air handling units (AHUs) to continuously disinfect recirculating air, and incorporation into water treatment systems. Current limitations in our understanding of UVC safety and effectiveness necessitate further research to optimize application protocols and ensure treatment safety while maintaining efficacy against C. auris. Integrating UVC disinfection technology into infection control programs holds promise for strengthening hygiene practices that will curb the global spread of C. auris and improve patient outcomes.

In order to study the effect of explosion load on the flexural performance of RC beams, two RC beams of the same size were carried out explosion test and bearing capacity test successively. Piezoelectric intelligent aggregate was embedded in the beams in advance to monitor the damage state of the beams, which realized the whole process of damage monitoring of the concrete inside the structure from explosion damage to compression damage.Based on wavelet packet analysis and residual bearing capacity damage evaluation criteria, the beam damage was quantitatively evaluated, and the bending bearing capacity of RC beam after explosion damage was compared and analyzed.The results show that the change of concrete strain gauge signal, the phenomenon of crack development and the increase of internal crack development index indicate that the RC beam is damaged by explosion load.After explosion damage, the damage index of the beam increases and the residual bending capacity decreases, which proves that the piezoelectric intelligent aggregate sensor can effectively monitor the bending capacity change of the component after explosion damage.

Mucus plugging of the respiratory tract occurs in airway diseases, including asthma, chronic obstructive pulmonary disease and cystic fibrosis. It can cause blockage of airways, leading to breathlessness and lung failure. Here, we demonstrate the effect of BromAc® in dissolving mucus plugs in an novel ex-vivo ovine obstructive lung model using a ventilatory setup. Mucus simulant was filled into the trachea of freshly slaughtered ovine lungs and ventilated via an endotracheal tube (ETT) using Continuous Mandatory Ventilation. Predetermined single or repeated doses of Bromelain, Acetylcysteine (Ac), BromAc® and saline control were administered via an Aerogen® vibrating nebuliser and ventilated for 30 or 60 minutes. Ventilatory recording of resistance, compliance, tidal volume was conducted and rheology pre and post treatment were measured. A significant decline in airway resistance (p&lt;0.0001) compared to saline control was observed when treated with Bromelain, Ac and BromAc®, with the latter showing a stronger mucolytic effect than single agents. The decline in resistance was also effective in shorter timepoint (p&lt;0.05) at lower doses of the drugs. Changes in compliance, peak pressure and tidal volume was not observed post-administration of the drugs. Rheology measurements revealed that BromAc®™ significantly reduced the viscosity of the mucin at the end of 30-minute and 60-minute time points (p&lt;0.001) compared to the saline control. BromAc® showed complete dissolution of the respiratory mucus simulant and improved ventilatory airflow parameters in the ex-vivo ovine model.

According to Young Minds [1] ‘everyone gets angry sometimes’. Their website offers a number of de-escalating strategies, including staying calm, managing responses and setting limits to help young people who most deem resistive. Yet, Young Minds are not alone because such logical advice is ubiquitous in the literature about challenging behaviour despite the fact that in our experience when faced with high states of arousal, most young people tend to act first and deal with the consequences later. It’s not that they are stupid or non-caring, but they are human capable of great feats as well as stupidity. The same is true for any claims that solution focused (SF) conversations can put right the several decades of psychological theory suggesting resistance requires logic and better cognition. By giving the correct thinking skills, young people will walk away from risk, avoid physical confrontation, handle challenging situations like logical thinkers, and generally discount that the process of growing up is part of the challenge. It is with this in mind that over recent years in our current SF practice (with staff group supervision) we have examined the concept of ‘resistance’ and how it can be put to use as a process of collaboration. To do this, we have revisited SF theory that preoccupied many of its pioneers during the 1980’s and 1990’s and attempted to make it useful for the early 2020’s for professionals having conversations with young people, who, in traditional models, are labelled challenging. We want to introduce key differences of solution focused practice and how Anita started to formulate a 6D-SF model (details, dynamics, dimensions, dispositions, dislocations, descriptions) for contemplating how groups of professionals relate to each other and are triggered by challenging behaviour. We do not claim to have proof, logic or exactness on our side, but we’re happy to suggest how our resistance mirrors what many of the staff teams feel and describe when working through their work.

The impact of systemic vascular resistance (SVR) in hypertrophic (HCM) and amyloid cardio-myopathies has been seldom investigated. We studied pressure-strain loop derived myocardial work (MW) indices and SVR in patients with either sarcomere HCM or wild type transthyretin cardiac amyloidosis (ATTR), presented with heart failure and preserved left ventricular ejection fraction (HFpEF) at the outpatient cardiology units at Messina and Catania University Hospitals (Italy). Patients were in sinus rhythm and needed to have good transthoracic ultrasound imaging quality to undergo transthoracic strain-echocardiography. Other than conventional parameters, SVR and GWI (global work index) were measured. Based on cross-tabulation (a way to assess the ventricular-arterial coupling), the patients were then classified in 4 classes according to the cut-off values suggested by previous studies of 1,440 dyne/s/cm-5 for SVR (Stefadouros et al., 1973) and 1576 mm Hg% for GWI (Olsen et al., 2022). Sixty patients, 30 in each group, aged 61±16 years, 78% males, were studied. HCM were younger than ATTR patients and in a better clinical status (23% HCM vs 77% ATTR were NYHA class 3, p<0.001). Overall, 51 patients (85%) showed high SVR, of whom 21 were HCM (70%) and 30 ATTR (100%) (p<0.005). Both, SVR and GWI were impaired (the poorest class C) in 43% HCM patients (with greater left ventricular concentric hypertrophy) vs 93% of ATTR patients (in advanced NYHA class) (p<0.001). In conclusion, assessing SVR and GWI in HFpEF patients with HCM or ATTR can help clinicians to interpret the pathophysiological and clinical features of such complex diseases.

Computational rhinology is a specialized branch of biomechanics leveraging engineering techniques for mathematical modelling and simulation to complement the medical field of rhinology. Computational rhinology has already contributed significantly to advancing our understanding of the nasal function, including airflow patterns, mucosal cooling, particle deposition, and drug delivery, and is foreseen as a crucial element in e.g. the development of virtual surgery as a clinical, patient-specific decision support tool. The current paper delves into the field of computational rhinology from a nasal airflow perspective, highlighting the use of computational fluid dynamics to enhance diagnostics and treatment of breathing disorders. The paper consists of three distinct parts – an introduction to and review of the field of computational rhinology, a review of published literature on in vitro and in silico studies of nasal airflow, and the presentation and analysis of previously unpublished high fidelity CFD simulation data of in silico rhinomanometry. While the two first parts of the paper summarize the current status and challenges in the application of computational tools in rhinology, the last part addresses the gross disagreement commonly observed when comparing in silico and in vivo rhinomanometry results. It is concluded that this discrepancy cannot readily be explained by CFD model deficiencies caused by poor choice of turbulence model, insufficient spatial or temporal resolution, or neglecting transient effects. Hence, alternative explanations such as nasal cavity compliance or drag effects due to nasal hair should be investigated.

This review paper presents a flashback on the evolution of the disease throughout the centuries, describes in summary pathophysiologic mechanisms, discusses briefly the mechanism of action of the diuretics, presents their role in decongesting heart failure patients and unfolds the data behind ultrafiltration in the management of acutely or chronically decompensated heart failure (ADHF), focusing on all the available data and advancements in this field. Acutely decompensated heart failure (ADHF) presents a critical clinical condition characterized by worsening symptoms and signs of heart failure, necessitating prompt intervention to alleviate congestion and improve cardiac function. Diuretics have traditionally been the mainstay for managing fluid overload in ADHF. Mounting evidence suggests that due to numerous causes, such as coexisting renal failure or chronic use of the loop diuretics, an increasing rate of diuretic resistance is noticed and needs to be addressed. There has been a series of trials that combined diuretics of different categories, without the expected results. Emerging evidence suggests that ultrafiltration may offer an alternative or adjunctive approach.

Long span cable-stayed bridge is the main bridge type with a span of more than 400 meters. It is generally designed as a double tower long-span structure with good spanning capacity and economic performance. Wind resistance safety performance is the main index to control the long-span cable-stayed bridge structure. During the operation of long-span cable-stayed bridge structure, because the service life of the cable is far less than the design life of the structure, the wind resistance performance of the structure will inevitably deteriorate significantly, which will seriously affect the structural service performance of symmetric cable-stayed bridge. Based on symmetric reliability theory, this paper takes flutter and static wind stability of long-span cable-stayed bridge structure as the main design control index, uses positive reliability theory to calculate the reliability index of symmetric cable-stayed bridge structure, uses inverse reliability theory to calculate the safety factor of symmetric cable-stayed bridge structure, and evaluates the wind resistant time-varying performance of long-span cable-stayed bridge structure by comprehensively considering the reliability index and safety factor. Taking a practical project of a long-span cable-stayed bridge as a specific case, the wind resistant time-varying reliability of the bridge during its operation for more than 30 years is analyzed, and the parameter sensitivity is analyzed. The results show that the wind resistance performance of the cable-stayed bridge structure is obviously affected by the cable, and the degradation of the cable performance will have an important impact on the wind resistance time-varying performance of the structure, especially the critical wind speed of the structure has obvious time-varying characteristics. The safety factor and reliability index can objectively evaluate the wind resistance time-varying performance of the long-span cable-stayed bridge structure.

In the last decade, an increasing awareness was directed to the role of Vitamin D in non-skeletal and preventive roles for chronic diseases. Vitamin D is a key hormone involved in the regulation of calcium/phosphorous balance and it has been implicated in the pathogenesis of inflammation, insulin resistance and obesity. Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2) are the main form of vitamin D: the active form (1,25-dihydroxyvitamin D) is the result of two hydroxylations that take place in liver, kidney, pancreas and immune cells. Some anti-inflammatory cytokines are produced at higher levels by vitamin D, while some pro-inflammatory cytokines are released at lower levels. Toll-Like Receptor (TLR) expression is increased and a pro-inflammatory state is also linked to low levels of vitamin D. Regardless of how it affects inflammation, various pathways suggest that vitamin D directly improves insulin sensitivity and secretion. The level of vitamin D in the body may change the ratio of pro- to anti-inflammatory cytokines, which would impact insulin action, lipid metabolism, and the development and function of adipose tissue. Many studies have demonstrated an inverse relationship between vitamin D concentrations and pro-inflammatory markers, insulin resistance, glucose intolerance, metabolic syndrome, obesity and cardiovascular disease. It's interesting to note that several long-term studies also revealed an inverse correlation between vitamin D level and the occurrence of diabetes mellitus. Vitamin D supplementation in people has controversial effects, in fact while some studies demonstrated improvements in insulin sensitivity, glucose and lipid metabolism, others revealed no significant effect on glycemic control and inflammation. The aim of this review is to provide insight into the molecular basis of the relationship between vitamin D, insulin-resistance, metabolic syndrome, type 1 and 2 diabetes, gestational diabetes, and cardiovascular diseases.

Conjugative transposons in Gram-negative bacteria have a significant role in the dissemination of antibiotic-resistance-conferring genes between bacteria. This study aims to genomically characterize plasmids and conjugative transposons carrying integrons in clinical isolates of Klebsiella pneumoniae. Genetic composition of conjugative transposons and phenotypic assessment of 50 multidrug-resistant K. pneumoniae isolates from Tertiary-care Hospital (SQUH), Muscat, Oman was investigated. Horizontal transferability was investigated by filter- mating conjugation experiments. Whole genome sequencing (WGS) was performed to determine the sequence type (ST), acquired resistome and plasmidome of integron-carrying strains. Class 1 integron was detected in 96% of isolates and among integron-positive isolates, 18 stains contained variable regions. Horizontal transferability by conjugation confirmed the successful transfer of integrons between cells and WGS confirmed their presence in conjugative plasmids. Dihydrofolate reductase (dfrA14) was the most prevalent (34.8%) gene cassettes in class 1 integrons. MLST analysis detected predominantly ST-231 and ST-395. BlaOXA-232 and blaCTX-M-15 were the most frequently detected carbapenems and beta-lactamases in sequenced isolates. This study highlighted the high transmissibility of MDR-conferring conjugative plasmids in clinical isolates of K. pneumoniae. Therefore, the wise use of antibiotics and the adherence to effective infection control measures are necessary to limit further dissemination of multidrug-resistant organisms.

Foliar fungal diseases in tomatoes include early blight (Alternaria linariae), Septoria leaf spot (Septoria lycopersici), and late blight (Phytophthora infestans) which is oomycetes. These are one of the significant production constraints in tomatoes. We describe the etiology, host range, distribution, symptoms, and disease cycle to understand the biology followed by management practices emphasizing the resistance breeding approach for these diseases. In crop improvement efforts, we provide an analytical review, including conventional and molecular methods for improving this disease resistance. Modern breeding tools, including genomics, genetic transformation, and genome editing, can be used to improve these traits. There is a good possibility of using these tools in the future to improve these traits.

Diabetes mellitus is one of the most common metabolic diseases worldwide, and its long-term complications include neuropathy, referring both to the peripheral and to the central nervous system. Detrimental effects of dysglycemia, especially hyperglycemia, on the structure and function of blood-brain barrier (BBB) seem to be a significant backgrounds of diabetic neuropathy pertaining to the central nervous system (CNS). Effects of hyperglycemia, including excessive glucose influx to insulin independent cells, may induce oxidative stress and secondary innate immunity dependent inflammatory response which can damage cells within the CNS, thus promoting neurodegeneration and dementia. Advanced glycation end products (AGE) may exert similar, pro-inflammatory effects through activating receptors for advanced glycation end products (RAGE), as well as some pattern-recognition receptors (PRR). Moreover, long-term hyperglycemia can promote brain insulin resistance, which may in turn promote Aβ aggregate accumulation and tau hyperphosphorylation. This review is focused on a detailed analysis of the effects mentioned above towards the CNS, with special regard to mechanisms taking part in the pathogenesis of central long-term complications of diabetes mellitus initiated by the loss of BBB integrity.

Epidemics of arboviruses in general, and dengue fever, in particular, are an increasing threat in areas where Aedes (Ae.) aegypti is present. The effectiveness of chemical control of Ae. aegypti is threatened by the increasing frequency of insecticide resistance. The aim of this study was to determine the susceptibility status of Ae. aegypti to public health insecticides and assess the underlying mechanisms driving insecticide resistance. Ae. aegypti eggs were collected in two study sites in the vicinity of houses for two weeks using Gravid Aedes Traps (GATs). After rearing mosquitoes to adulthood, female Ae. aegypti were exposed to the diagnostic doses of permethrin, deltamethrin and bendiocarb, using Centers for Disease Control and Prevention (CDC) bottle bioassays. Unexposed, un-engorged female Ae. aegypti were tested individually for mixed-function oxidase (MFO), glutathione-S-transferase (GST) and esterase activity. Finally, allele-specific PCR (AS-PCR) was used to detect kdr mutations (F1534C, S989P and V1016G) in the voltage-gated sodium channel gene in insecticide-exposed Ae. aegypti. Most traps were oviposition positive; 93.2% and 97% of traps contained Ae. aegypti eggs in the 10ème arrondissement of Cotonou and in Godomey-Togoudo, respectively. Insecticide bioassays assays detected resistance to permethrin and deltamethrin in both study sites and complete susceptibility to bendiocarb. By comparison to the insecticide-susceptibility Rockefeller strain, field Ae. aegypti populations had significantly higher levels of GSTs and significantly lower levels of  and  esterases; there was no significant difference between levels of MFOs. AS-PCR genotyping revealed the presence of the three kdr mutations (F1534C, S989P and V1016G) at high frequencies; 80.9% (228/282) of Ae. aegypti tested had at least one mutation, while the simultaneous presence of all three kdr mutations was identified in 13 resistant individuals. Study findings demonstrated phenotypic pyrethroid resistance, the overexpression of key detoxification enzymes and the presence of several kdr mutations in Ae. aegypti populations, emphasizing the urgent need to implement vector control strategies, targeting arbovirus vector species in Benin.

Background: Monitoring of antibiotic prescription practices in hospitals is essential to assess and facilitate appropriate use. This is relevant to halt the progression of antimicrobial resistance. Methods: Assessment of antibiotic prescribing patterns and completeness of antibiotic prescriptions among out-patients in 2021 was conducted at the University Hospital of Kwame Nkrumah University of Science and Technology in the Ashanti region of Ghana. We reviewed electronic medical records (EMR) of 49,660 patients who had 110,280 encounters in the year. Results: The patient encounters yielded 350,149 prescriptions. Every month, 33-36% of patient encounters resulted in antibiotic prescription, higher than the World Health Organization’s (WHO) recommended optimum of 27%. Almost half of the antibiotics prescribed belonged to WHO’s Watch group. Amoxicillin-clavulanic acid (50%), azithromycin (29%), ciprofloxacin (28%), metronidazole (21%), and cefuroxime (20%) were the most prescribed antibiotics. Antibiotic prescribing parameters (indication, name of drug, duration, dose, route and frequency) were documented in almost all prescriptions. Conclusions: Extending antimicrobial stewardship to the out-patient settings by developing standard treatment guidelines, an out-patient specific drug formulary and antibiograms can promote rational antibiotic use at the hospital. The EMR system of the hospital is a valuable tool for monitoring prescriptions that can be leveraged for future audits.

The aim of this work was to test polyamines as potential natural substrates of the Acinetobacter baumannii chlorhexidine efflux protein AceI using near-UV synchrotron radiation circular dichroism (SRCD) spectroscopy. The Gram-negative bacterium A. Baumannii is a leading cause of hospital-acquired infections and an important foodborne pathogen. A. Baumannii strains are becoming increasingly resistant to antimicrobial agents, including the synthetic antiseptic chlorhexidine. AceI was the founding member of the recently recognised PACE family of bacterial multidrug efflux proteins. Using the plasmid construct pTTQ18-aceI(His₆) containing the A. Baumannii aceI gene directly upstream from a His₆-tag coding sequence, expression of AceI(His₆) was amplified in E. coli BL21(DE3) cells. Near-UV (250-340 nm) SRCD measurements were performed on detergent-solubilised and purified AceI(His₆) at 20 °C. Sample and SRCD experimental conditions were identified that detected binding of the triamine spermidine to AceI(His₆). In a titration with spermidine (0-10 mM) this binding was saturable and fitting of the curve for the change in signal intensity produced an apparent binding affinity (K_D) of 3.97 +/- 0.45 mM. These SRCD results were the first experimental evidence obtained for polyamines as natural substrates of PACE proteins.

It is unclear how important it is to reduce fluoroquinolone consumption in the general population to prevent the spread of fluoroquinolone resistance in Neisseria gonorrhoeae (bystander selection). Methods We assessed bystander selection by using Spearman’s correlation to assess if the country-level prevalence of fluoroquinolone resistance in N. gonorrhoeae was correlated with the prevalence of fluoroquinolone resistance in four other gram-negative species - Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Results Fluoroquinolone resistance in N. gonorrhoeae was positively associated with homologous resistance in all 4 species - A. baumanii. (ρ=0.61, P=0.0003, E. coli (ρ=0.67, P<0.0001), K. pneumoniae (ρ=0.52, P=0.0004) and P. aeruginosa (ρ=0.40, P=0.0206). Positive associations were also found between the national prevalence of fluoroquinolone resistance and fluoroquinolone consumption in the general population in the preceding year for 4 of the 5 species. Conclusions Gonococcal fluoroquinolone resistance can be productively viewed as being part of a syndemic of fluoroquinolone resistance. Strengthening antimicrobial stewardship programs may help retard the spread of fluoroquinolone resistance in N. gonorrhoeae.

Cellular immunotherapy has recently emerged as a fourth pillar in cancer treatment co-joining surgery, chemotherapy and radiotherapy. Where, the discovery of immune checkpoint blockage or inhibition (ICB/ICI), anti-PD-1/PD-L1 and anti-CTLA4-based, therapy has revolutionized the class of cancer treatment at a different level. However, still some cancer patient escape this immune surveillance mechanism and become resistant to ICB-therapy. Therefore, a more advanced or an alternative treatment is required instantly. Despite the functional importance of epitranscriptomics in diverse clinico-biological practices, its role in improving the efficacy of ICB therapeutics has been limited. Consequently, our study encapsulates the evidences, as a possible strategy, to improve the efficacy of ICB-therapy by co-targeting molecular checkpoints especially N6A-modification machineries which could be reformed into RNA modifying drugs (RMD). Here, we have explained the mechanism of individual RNA-modifiers (editor/writer, eraser/remover and effector/reader) in overcoming the issues associated with high-dose antibody toxicities and drug-resistance. Moreover, we have shed light on the importance of suppressor of cytokine signalling (SOCS/CISH) and microRNAs in improving the efficacy of ICB-therapy, with brief insight on the current monoclonal antibodies undergoing clinical trials or already approved against several solid tumor and metastatic cancers. We anticipate our investigation will encourage researchers and clinicians to further strengthen the efficacy of ICB-therapeutics by considering the importance of epitranscriptomics as a personalized medicine.

Malignant melanoma is a lethal skin cancer containing melanoma-initiating cells (MIC), implicated in tumorigenesis, invasion, and drug resistance, and characterized by elevated expression of stem cell markers, such as CD133. We previously showed that siRNA knockdown of CD133 enhances apoptosis induced by the MEK inhibitor trametinib in melanoma cells. The current study investigates underlying mechanisms of CD133’s anti-apoptotic activity in patient-derived BAKP and POT cells, harboring difficult-to-treat NRASQ61K and NRASQ61R drivers, after CRISPR-Cas9 CD133 knockdown or Dox-inducible expression of CD133. To maintain stable expression of CD133, MACS-sorted CD133(+) positive cells were expanded by ROCK-mediated conditional reprogramming of BAKP melanoma cells (BAKR). BAKR showed increased survival via reduced apoptosis after exposure to trametinib or DTIC, compared to BAKP. CRISPR-Cas9- mediated CD133 knockdown in BAKR cells (BAKR-T3) re-sensitized the cells, while CRISPR-Cas9 knockdown of CD133 in parental BAKP and POT cells even further increased trametinib-induced apoptosis (cleaved PARP) by reducing levels of anti-apoptotic BCL-xL, p-AKT, and p-BAD, and increasing pro-apoptotic BAD and active BAX. Dox-induced CD133 overexpression had the opposite effect, and blocked trametinib-induced apoptosis in both cell lines, coincident with elevated p-AKT, p-BAD, BCL-2 and BCL-xL and decreased levels of the active form of BAX and caspases-3 and -9. The roles of CD133 in AKT and BAD phosphorylation, or in the upregulation of anti-apoptotic BCL-2 family members, was further investigated by AKT knockout with siRNA, or inhibition of BCL-2 family members with navitoclax (ABT-263). Similar to CD133 knockdown, AKT1/2 siRNA knockdown in BAKP cells also reduced p-BAD. CD133 knockdown (T3)-mediated reduction of pBAD levels was equivalent in AKT-knockdown or AKT control cells indicating that CD133 may be upstream of AKT signaling. In BAKP cells treated with trametinib and/or ABT-263, effects of ABT-263 mirrored CD133 knockdown, since levels of active BAX and cleaved-PARP in BAKP-SC (CD133-) cells increased to the same level as that exhibited by BAKP-T3 cells (CD133+). CD133 may therefore activate a survival pathway where 1) increased phosphorylation of AKT induces 2) phosphorylation and inactivation of BAD, 3) decrease in the active form of BAX, and 4) reduction in caspase-mediated PARP cleavage, indicating apoptosis suppression leading to drug resistance in melanomas. Targeting survival pathways by which CD133 may confer chemoresistance in MICs can contribute to development of more effective treatments for patients with high-risk melanoma.

Asians are known to more likely than Westerners develop fatty liver and lifestyle-related diseases despite their weight. However, the relationship between fat accumulation and lifestyle-related diseases in non-obese Asians is unknown. Therefore, this study aimed to analyze visceral fat and hepatic fat in participants with a normal body mass index (BMI) and examine their characteristics during a medical checkup. This cross-sectional study was conducted on 663 of 1,142 patients who underwent abdominal ultrasonography and who had an alcohol intake (converted to ethanol) of <30 g/day for males and <20 g/day for females and a BMI of <25 kg/m2 during a health checkup. Participants were classified into four groups: group A, visceral fat accumulation (VFA) (−) and fatty liver (FL) (−) (n = 549); group B, VFA (+) and FL(−) (n = 32); group C, VFA (−) and FL (+) (n = 58); and group D, VFA (+) and FL (+) (n = 24). The frequencies of lifestyle-related disease complications, liver function tests, and liver fibrosis were evaluated among the four groups. Compared with group A (control), groups B, C, and D had higher number of males; BMI; abdominal circumference, ALT, AST, γ-GTP, triglyceride, uric acid, fasting blood sugar levels; and incidence of hyperlipidemia. Groups C and D had higher ALT, HbA1c, cholinesterase, and triglyceride levels; FIB4 index; and number of patients with diabetes mellitus (DM) than groups A and B; however, there was no difference between groups A and B. FL is a risk factor of DM and liver fibrosis in non-obese Japanese individuals; however, VFA only is not a risk factor of DM and liver fibrosis.

Barley mlo mutants are well known for their profound resistance against powdery mildew disease. Recently, mlo mutant plants were generated in hexaploid bread wheat (Triticum aestivum) with the help of transgenic (transcription-activator-like nuclease, TALEN) and non-transgenic (targeted induced local lesions in genomes, TILLING) biotechnological approaches. While full gene knockouts in the three wheat Mlo (TaMlo) homoeologs, created via TALEN, confer full resistance to the wheat powdery mildew pathogen (Blumeria graminis f.sp. tritici), the currently available TILLING-derived Tamlo missense mutants provide only partial protection against powdery mildew attack. Here we studied the infection phenotypes of TALEN- and TILLING-derived Tamlo plants to the two hemibiotrophic pathogens Zymoseptoria tritici, causing Septoria leaf blotch in wheat, and Magnaporthe oryzae pv. Triticum (MoT), the causal agent of wheat blast disease. While Tamlo plants showed unaltered outcomes upon challenge with Z. tritici, we found allele-specific levels of enhanced susceptibility to MoT, with stronger powdery mildew resistance correlated with more invasive growth by the blast pathogen. Surprisingly, unlike barley mlo mutants, young wheat mlo mutant plants do not show undesired pleiotropic phenotypes such as spontaneous callose deposits in leaf mesophyll cells or signs of early leaf senescence. In conclusion, our study provides evidence for allele-specific levels of enhanced susceptibility of Tamlo plants to the hemibiotrophic wheat pathogen MoT.

Imatinib became the standard treatment for chronic myeloid leukemia (CML) about 20 years ago, which was a major breakthrough in stabilizing the pathology and improving the quality of life of patients. However, the emergence of resistance to imatinib and other tyrosine kinase inhibitors leads researchers to characterize new therapeutic targets. Several studies have highlighted the role of histone deacetylase 6 (HDAC6) in various pathologies, including cancer. This protein effectively intervenes in cellular activities by its primarily cytoplasmic localization. In this review, we will discuss the molecular characteristics of the HDAC6 protein, as well as its overexpression in CML leukemic stem cells, which make it a promising therapeutic target for the treatment of CML.

Theaflavins, the characteristic and bioactive polyphenols in black tea, possess the potential improvement effects on insulin resistance-associated metabolic abnormalities including obesity and type 2 diebetes. However, the molecular mechanisms of theaflavins improving insulin sensitivity are still not clear. In this study, we investigated the protective effects and mechanisms of theaflavins on palmitic acid-induced insulin resistance in HepG2 cells. Theaflavins could significantly increase glucose uptake of insulin-resistant cells at noncytotoxic doses. This activity was mediated by upregulating the glucose transporter 4 protein expression, increasing the phosphorylation of IRS-1 at Ser307, and reduced the phosphor-Akt (Ser473) level. Moreover, theaflavins were found to enhance mitochondrial DNA copy number through down-regulate the PGC-1β mRNA level and up-regulate PRC mRNA expression in insulin-resistant HepG2 cells. These results indicated that theaflavins could improve free fatty acid-induced hepatic insulin resistance by promoting mitochondrial biogenesis, and were promising functional food and medicines for insulin resistance-related disorders.

Literature is inconsistent as to how coffee affects the features of the metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. We aimed to compare the in-vivo effects of unfiltered coffee with a selected mixture of its compounds on diet-induced MetS. 24 male Sprague-Dawley rats were fed a high-fat (35% W/W) food plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water in a dosage equal to 4 cups/day in a human. Compared to the controls, only coffee supplementation decreased total food intake, weight gain, and estimated average plasma glucose. Surrogate measures of insulin resistance (fasting insulin, HOMA-IR, and oral glucose tolerance) were improved at endpoint in the coffee group. Circulating triglyceride levels were also reduced by coffee. Histopathological and quantitative measurements indicated lower grades of liver steatosis after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

Biofilm formation in unicellular eukaryotes, such as Candida albicans and Saccharomyces cerevisiae, represents a significant challenge in various sectors, including healthcare, agriculture, and industry. These biofilms are resistant to conventional antimicrobial treatments due to their protective extracellular matrix and complex regulatory mechanisms, such as quorum sensing (QS) and cyclic AMP (cAMP) signaling. Recent advances in the understanding of biofilm formation pathways have led to the identification of novel compounds that target these regulatory mechanisms. This review highlights breakthroughs from 2024 research, focusing on the inhibition of quorum sensing, disruption of extracellular matrix synthesis, and transcriptional/post-transcriptional regulation of biofilm-related genes. The application of these discoveries in Vietnam is particularly promising, given the country's challenges with biofilm-related infections in healthcare and productivity losses in agriculture and aquaculture. Natural product-based approaches, especially those derived from Vietnam's marine biodiversity, offer environmentally sustainable solutions for biofilm control. However, translating these laboratory findings into scalable, cost-effective applications faces challenges such as resistance development, environmental sustainability, and regulatory constraints. This review provides a comprehensive overview of compounds targeting biofilm regulatory mechanisms, evaluates their potential applications in Vietnam, and discusses future research directions, emphasizing the need for interdisciplinary collaboration to address the complexities of biofilm control.

This review aims to show, by an analysis of the literature on the topic, that hyperinsulinemia associated with insulin resistance is a multiple risk factor for type 2 diabetes, cardiovascular diseases, cellular senescence and cancer, and neurodegenerative diseases. This condition is progressively increasing in developed and developing countries, and its prevalence has now exceeded 50% of the general population. Since it is asymptomatic or poorly symptomatic, it can last for many years before manifesting itself in the form of type 2 diabetes mellitus, cardiovascular disease, neoplasm, cognitive impairment or dementia, therefore determining enormous social and health care costs. For these reasons, we strongly believe that a screening plan for this pathology should be implemented, in order to identify affected subjects and promptly start them on preventive treatment.

Helicobacter pylori infection constitutes a silent pandemic of global concern. In the last decades, the alarming increase of multidrug resistance evolved by this pathogen has led to a marked drop in the eradication rates of traditional therapies worldwide, encouraging scientific community to discover and develop new antimicrobial strategies. In the present work, we identified a battery of novel drug-like HsrA inhibitors with MIC values ranging from 0.031 to 4 mg/L against antibiotic-resistant strains of H. pylori. Most of these novel antimicrobials exhibited minor effects against both Gram-negative and Gram-positive species of human microbiota. The most potent anti-H. pylori candidate demonstrated a high therapeutic index, additive effect in combination with metronidazole and clarithromycin, as well as a strong antimicrobial action against Campylobacter jejuni, another clinically relevant pathogen of phylum Campylobacterota. Transcriptomic analysis suggested that in vivo inhibition of HsrA triggered lethal global disturbances in H. pylori physiology, including the arrest of protein biosynthesis, malfunction of respiratory chain, detriment in ATP generation, and oxidative stress. The novel drug-like HsrA inhibitors described here constitute valuable candidates to a new family of narrow-spectrum antibiotics that allow overcoming the current resistome, protecting from dysbiosis, and increasing therapeutic options for novel personalized treatments against H. pylori.

Minimum Inhibitory Concentration (MIC) measures the lowest concentration of antibiotic that inhibits in-vitro growth of microorganisms. Canine pyometra is a frequently occurring reproductive disorder where reliable antibiotics along with surgical excision of uterus predicts better prognosis. Scarce literature is available to facilitate proper antibiotic selection to avoid septicemia in clinical cases. The present study was conducted to determine sensitivity and potency of selected antibacterials based on MIC values against bacterial isolates obtained from Canine Pyometra in Kathmandu district, Nepal by Agar Dilution method. Isolates obtained from 63 intra-uterine samples after ovariohysterectomy were Enterococcus spp (n=41), Klebsiella spp. (n=7), Staphylococcus spp. (n=11) and Streptococcus spp. (n=4). Enrofloxacin and Amikacin were found highly sensitive (0% resistance) with a null hypothesis of resistance to all bacterial isolates and were significantly more potent than other antibacterials tested (p<0.05; Kruskal-Wallis test) based on lower MIC ranks. Similarly, ceftriaxone was found to be least potent and was highly resistant to Enterococcus spp. (75.61%) and completely resistant to other bacterial species tested (100%). Comparative results on sensitivity and potency in the study revealed Enrofloxacin and Amikacin to be better antibacterial of choice in pyometra innervation in in-vitro setting. Further clinical trials considering other equally important variables along with MIC should be conducted to predict actual clinical efficacy of antibacterials during therapeutic management of canine pyometra in Nepal.

In this study, global response analysis was performed to explore the mechanism of action of Usnic acid and its synergy with Norfloxacin, a well-known quinolone antibiotic to which MRSA clinical isolates showed resistance (MIC, 500 µg/mL). Microdilution assay, growth kinetics, microscopic analysis, and cell-based assays consistently showed that Usnic acid possess strong anti-staphylococcal activity (MIC, 7.8 µg/ml), causes cell leakage, modulates efflux pump activity, and synergizes with Norfloxacin against multi-drug resistant clinical isolate MRSA 2071. Whole cell proteome profiling using gel-free based nano-LC-ESI-QTOF-MS/MS revealed several proteins whose expression was significantly modulated by Usnic acid and Norfloxacin alone or in combination. Usnic acid downregulated the abundance of RNA polymerase subunits (RpoB, RpoC), carbamoyl phosphate synthase large subunit (PyrAB), chaperone (GroEL), and adenylosuccinate synthetase (PurA). Interestingly, proteins found to be upregulated in the presence of Usnic acid and Norfloxacin included oxidative stress-related proteins such as peroxidase (Tpx), alkyl hydroperoxide reductase (AphC), and general stress protein (UspA). This study clearly showed that Usnic acid affects numerous cellular targets and can potentiate the action of Norfloxacin. Furthermore, an in-vivo study emphasized the use of Usnic acid to develop as a safe phytopharmaceutical to repurpose old antibiotics through combination therapy against MRSA infections.

Digital marketing adoption in the multinational Fast-Moving Consumer Goods (FMCG) sector presents both challenges and opportunities that significantly impact organizational strategies and market competitiveness. This qualitative study explores the complexities surrounding digital marketing adoption through interviews with 45 participants from multinational FMCG companies. The research investigates key barriers such as organizational resistance, technological constraints, and concerns over data privacy and security, while also examining the benefits of enhanced consumer engagement, global market reach, and data-driven decision making. Findings reveal that organizational resistance remains a formidable barrier, driven by senior management's cautious approach to digital transformation and concerns over return on investment (ROI) amidst rapidly evolving digital landscapes. Technological challenges, including outdated systems and limited budgets for technology upgrades, further hinder comprehensive digital integration. Moreover, navigating regulatory frameworks and addressing consumer trust in data privacy emerge as critical considerations for FMCG companies seeking to leverage digital strategies effectively. Conversely, digital marketing adoption offers substantial opportunities. Enhanced consumer engagement through personalized and interactive campaigns allows companies to strengthen brand-consumer relationships and foster loyalty. The global reach facilitated by digital platforms enables multinational FMCG firms to expand market presence, penetrate new markets, and adapt marketing strategies to diverse consumer preferences worldwide. Data-driven decision making emerges as pivotal, leveraging analytics to optimize marketing strategies, measure campaign effectiveness, and anticipate consumer behaviors in real-time. Strategies for overcoming barriers emphasize building internal digital capabilities through training, recruitment, and cross-functional collaboration. Aligning digital strategies with overarching business objectives and integrating digital efforts with traditional marketing channels are crucial for creating cohesive and effective campaigns. Embracing innovation, flexibility, and agility in adapting to technological advancements are essential for maintaining competitiveness and relevance in a rapidly evolving digital landscape. Looking forward, emerging trends such as AI and machine learning integration for predictive analytics, sustainability-focused marketing initiatives, and the evolution towards omnichannel strategies are poised to reshape digital marketing practices in the FMCG sector. By aligning strategies with these trends, FMCG companies can harness digital technologies to drive sustainable growth, enhance market competitiveness, and meet evolving consumer expectations in a digitally-driven global marketplace.

Cellular senescence has recently been recognized as a hallmark of cancer, reflecting its association with aging and inflammation, its role as a response to deregulated proliferation and oncogenic stress, and its induction by cancer therapies such as radiation, chemotherapy, and targeted agents. While such therapy-induced senescence (TIS) has been linked to resistance, recurrence, metastasis and normal tissue toxicity, TIS has the potential to enhance therapy response and stimulate anti-tumor immunity. In this review, we examine the Jekyll and Hyde nature of senescent cells (SnCs), with a particular focus on how their persistence while expressing the senescence-associated secretory phenotype (SASP) modulates the tumor microenvironment through autocrine and paracrine mechanisms. Via the SASP, the formation of SnCs may alternately mediate resistance or response to conventional therapy. Further, toward fulfilling the unmet potential of cancer immunotherapy, we consider how SnCs may influence tumor inflammation and serve as a source of antigen to potentiate anti-tumor immunity. This new view suggests treatment strategies based on inducing TIS to enhance immune checkpoint blockade. Finally, we describe strategies for mitigating the detrimental effects of senescence, such as modulating the SASP or targeting SnC persistence, toward enhancing the benefits of cancer treatment.

Aluminium alloys are used for fabrication of fuel clad of research grade nuclear reactors as well as of several types of core components of high flux research reactors. In order to carry out design and safety analysis of these components, their mechanical and fracture properties are required by the designer. In this work, experiments have been conducted on tensile specimens machined from an aluminium alloy block to evaluate the material stress-strain curve. For evaluation of fracture properties, experiments have been conducted on disc shaped compact tension specimens in order to determine the fracture toughness of aluminium alloy. From crystal plasticity based finite element analysis and experimental data, a material damage parameter for prediction of crack initiation has been evaluated. The variation of the parameter for various values of initial a/W ratios of the disc-shaped CT specimens have been studied. It was observed that the damage parameter is independent of crack geometry and hence, it qualifies as transferable material property which can be used to predict crack initiation in a component of this material subjected to different kinds of loading conditions. In addition, the JR curves of the disc-shaped CT specimens have also been evaluated from experiments. The material damage parameter has also been used to study the crack initiation in single crystal fracture specimens with two different orientations. It was observed that the [111] orientation is more susceptible to crack initiation and propagation compared to the [100] orientation as the damage parameter is high in the ligament of the specimen ahead of the crack-tip for the same level of load. The results of the experiments and the material damage parameter shall be helpful for integrity analysis of fuel clad of research reactors as well as components of high flux research reactors.

Within the context of sustainable material development for the construction sector, this study explores the viability of panels composed of recycled newspaper-derived cellulose (9%), rice husk (14%), borax (15%), and polyvinyl acetate-based glue (62%). The methods employed involve water absorption and density tests, following ASTM C-1763 and C-303 standards. The fire resistance test conforming to the European standard UNE 23-725-90, and a mold growth test using AOAC 2002.11. The composite is prone to absorbing a significant amount of water when exposed to humid conditions. However, the incorporation of rice husk and borax can provide benefits such as improved moisture resistance compared to other cellulitic insulators, which may be advantageous in specific climates. Also, the developed composite has an intermediate density compared to other polymeric materials. This characteristic presents advantages in applications that demand a balance between strength and lightness. During the fire resistance tests, the samples with borax presented less fire propagation, and superficial damage compared with the specimens without borax. This is important, considering the fireproofing property, required in building materials. The presence of borax in the composite has an inhibitory effect on the growth of fungi and yeasts. These findings are consistent with previous research. Nevertheless, further research and testing are imperative to assess its viability and performance for commercial applications.

Lung adenocarcinoma is the most prevalent form of lung cancer, and drug resistance is a significant obstacle in its treatment. This study aimed to investigate the overexpression of long non-coding RNAs (lncRNAs) as a mechanism that promotes intrinsic resistance in tumor cells from the onset of treatment. Drug-tolerant persister cells (DTP) are a subset of cancer cells that survive and proliferate after exposure to therapeutic drugs, making them an essential object of study for cancer treatment. The molecular mechanisms underlying DTP cell survival are not fully understood; however, long non-coding RNAs (lncRNAs) have been proposed to play a crucial role. DTP cells from lung adenocarcinoma cell lines were obtained after a single exposure to tyrosine kinase inhibitor TKIs (erlotinib or osimertinib). After establishing DTPs, RNA sequencing was performed to investigate the differential expression of the lncRNAs. Some lncRNAs and one mRNA were found to be overexpressed in DTP cells. The clinical relevance of lncRNAs was evaluated in a cohort of patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA). RT-qPCR validated the overexpression of lncRNAs and mRNA in residual DTP cells and LUAD biopsies. Knockdown of these lncRNAs increases the sensitivity of DTP cells to therapeutic drugs. This study provides an opportunity to investigate the involvement of lncRNAs in the genetic and epigenetic mechanisms underlying intrinsic resistance. The identified lncRNAs and CD74 mRNA may serve as potential prognostic markers or therapeutic targets to improve the overall survival of patients with lung cancer.

The subject of the conducted study was focused on the development of new type of technical blends reinforced with natural fillers. The study was divided into two parts, where in the firsts stage of the research unmodified POM was reinforced with different types of natural fillers: cellulose, wood flour and husk particles. In order to select the type of filler intended for further modification, the mechanical characteristics was assessed. The 20% wood flour (WF) filler system was selected as the reinforcement. The second stage of research involved the use of combination of polyoxymethylene POM and poly(lactic acid) PLA. POM/PLA blend (ratio 50/50 %) were modified with elastomeric compound (EBA) and chain extender as reactive compatibilized (CE). The microscopic analysis revealed that for POM/PLA system the filler-matrix interface is characterized by better wettability, which might suggest higher adhesion. The mechanical performance revealed that for POM/PLA-based composites the properties were very close to the results for POM-WF composites; however, there is still large difference in thermal resistance in favor of POM-based materials. The increase in thermomechanical properties for POM/PLA composites occurs after heat treatment. The increasing crystallinity of the PLA phase allows for an significant increase of the head deflection temperature (HDT), even above 125 °C.

The Reactive Spark Plasma Sintering (R-SPS) method is compared in this work with the two-steps SHS-SPS route, based on combination of the Self-propagating High-temperature Synthesis (SHS) with the SPS process, for the fabrication of dense (Hf0.2Mo0.2Ti0.2Ta0.2Nb0.2)B2-SiC and (Hf0.2Mo0.2Ti0.2Ta0.2Zr0.2)B2-SiC ceramics. A multiphasic and inhomogeneous product, containing various borides, is obtained at 2000°C/20min by R-SPS, from transition metals, B4C and Si. In contrast, if the same precursors are first reacted by SHS, and then processed by SPS under the optimized condition of 1800°C/20min, the desired ceramics are successfully attained. Both High-Entropy-Boride/SiC products display densities > 97%, uniform microstructures and contained only small amounts of residual oxides (<2.4 wt.%). The presence of SiC makes the sintering temperature milder, i.e. 150°C below to that needed by the corresponding additive-free system. Fracture toughness is also markedly improved, particularly when considering the Nb-containing system processed at 1800°C/20min, whereas KIC progressively decreases (from 7.35 to 5.36 MPa m1/2) as the SPS conditions become more severe. SiC addition is found to inhibit the volatilization of metal oxides like MoO3 formed during oxidation experiments, thus avoiding mass loss in the ceramics. The benefits above also likely take advantage of the fact that the two composite constituents are synthesized in parallel, according to the SHS-SPS approach, rather than being produced separately and combined subsequently, so that strong interfaces between them are formed.

Banana is one of the most important fruits in the world due to its status as a major food source for more than 400 million people. Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) causes substantial losses of banana crops every year, and molecular host resistance mechanisms are currently unknown. We here performed a genome-wide analysis of the autophagy related protein 8 (ATG8) family in a wild banana species. The banana genome was found to contain 10 MaATG8 genes. Four MaATG8s formed a gene cluster in the distal part of chromosome 4. Phylogenetic analysis of ATG8 families in banana, Arabidopsis thaliana, Citrus, rice, and ginger revealed five major phylogenetic clades shared by all of these plant species, demonstrating evolutionary conservation of the MaATG8 families. The transcriptomic analysis of plants infected with Foc TR4 showed that almost all of the MaATG8 genes were more highly induced in resistant cultivars than in susceptible cultivars. Finally, MaATG8F was found to interact with MaATG4B in vitro (with yeast two-hybrid assays), and MaATG8F and MaATG4B all positively regulated banana resistance to Foc TR4. Our study provides novel insights into the structure, distribution, evolution, and expression of the MaATG8 family in bananas. Furthermore, the discovery of interactions between MaATG8F and MaATG4 could facilitate future researches of disease resistance genes for genetic improvement of bananas.

To estimate the progressive collapse resistance capacity of a multi-column frame tube structure with the assembled truss beam composite floor (ATBCF), the pushdown analysis, and the nonlinear dynamic analysis as well, are conducted for such a structure by using the alternate load path (ALP) method. The bearing capacities of the remaining structures at three different work conditions, which are the side middle column failure, the edge middle column failure, and the corner column failure, are individually studied, and the collapse mechanism for the remaining structures is analyzed from the aspects of the internal force redistribution and the failure mode of the second defense line. Simultaneously, the influence of the column failure time on the dynamic response of the remaining structure and the dynamic amplification coefficient are discussed. The results show that the residual bearing capacity of the remaining structure with the bottom corner column failure is higher than that of the one with the side or edge middle column failure, while the latter has a stronger plastic deformation capacity. When the ALP method is adopted to operate the progressive collapse analysis, it is reasonable to take the column failure time as 0.1 times of the first-order vertical vibration period of the remaining structure, and it is suitable to set the dynamic amplification coefficient as of 2.0, which is the ratio of the maximum dynamic displacement to the static displacement of the remaining structure under the transient loading condition.

Escherichia coli causes several infections like intestinal diarrhea, urinary tract infections, and pneumonia, which are difficult to treat due to the emergence of antimicrobial resistance. The World Health Organisation (WHO) declared carbapenem-resistant E. coli a critical pathogen and called for the development of new antimicrobial agents. Phage therapy, a century-old technique, has been revitalised recently with many successful applications against multi-drug resistant infections. As such, phage therapy is considered one of the most effective alternatives or adjuvants to antibiotics and is also effective in treating multidrug-resistant (MDR) bacterial infections. However, few phages that can kill pathogenic E. coli strains from Southeast Asia have been studied at a molecular level, although the burden of MDR, particularly carbapenem resistance, is high in this region. In this study, three closely related obligately virulent Escherichia phages (øEc_Makalu_001, øEc_Makalu_002, and øEc_Makalu_003) that could infect uropathogenic E. coli were isolated from sewage samples and characterized using morphological as well as sequence-based analysis. Further, a comparative genomic and phylogenetic analysis was done to predict the functional genes and evolutionary relationships. Electron microscopy and genome-based classification revealed that all three phages belonged Krischvirus genus of Straboviridae family. One-step growth curve showed that the latent period of the phages ranged from 15-20 min, the outbreak period was about 50 min, and the burst size ranged between 74-127 PFU/bacterium. Moreover, the phages could tolerate a pH range of 6 to 9 and a temperature range of 25-37°C for up to 180 minutes without significant loss of phage viability. Spotting the purified phages in different clinical isolates showed a broad host-range of isolated Escherichia phages and could lyse up to 30% of the tested pathogenic clinical isolates, including an intra-genus isolate of Klebsiella pneumoniae. The genome organization of all three phages was almost identical and similar to T4-like phage with a full-length genome of ~163 kb. Around 284 coding sequences (CDS) were predicted in each phage, of which only 40% were functional with an average gene length of 951 bp. The coding density in all phages was approximately 95%, while the gene density was 1.73 gene/kbp. Putative lysin, holin, endolysin, and spanin genes were found in the genomes of all three phages, resembling that of T4-like phages implying their phylogenetic relatedness. Furthermore, various in silico sequence analysis tools confirmed that all three phages were strictly virulent with functional lysis modules but devoid of any known virulence or toxin genes, integron-associated genes and antimicrobial-resistance (AMR) genes. In summary, pre-clinical experimental analysis and exploration of genomic features suggest that all three phages may be suitable candidates for therapeutic applications against uropathogenic E. coli.

Discovery and development of effective strategies to treat emerging and often drug resistant strains of viral and microbial pathogens presents one of the greatest challenges of the 21st century. Despite nearly a century of progress in developments in antimicrobial and antiviral therapies, infectious diseases still account for a substantial proportion of deaths worldwide, including over 100 million globally in the recent pandemic to date. In recent decades, the plague of antimicrobial resistance also represents an additional and alarming signal for both human and animal healthcare and signals a renewed sense of urgency in addressing this issue. This has made the search for novel classes of antibiotics, antivirals and therapeutics found to be capable of bypassing the microbial and viral resistance mechanisms necessary to in order to replenish our current arsenal of antimicrobial and antiviral drugs and update our therapeutic regimens. In addition, the tremendous impact exerted by viral infections and related pathologies on our lives during the recent decade has forced scientists to acknowledge the opportunities and challenges associated with tackling infectious diseases by developing effective antiviral agents endowed with novel mechanisms of action. The discovery of new antimicrobial/antiviral agents, as well as the repurposing of existing drugs and therapeutic options will be crucial to fight the ever-increasing resistance of “superbugs”, pathogenic fungi, viruses, and parasites. Proponents of modern biophoton therapy proposed in this paper can trace its origins to the Russian scientist Alexander Gurwitsch, who a century ago observed ultra-weak emissions of light emerging from an onion root and soon found additional living tissues to be emanating similar energetic phenomena, thus energizing research which continues to the present day and projected toward the development of useful applications of the new-found biological photonic phenomena. The purpose of the present paper is to introduce the past experiences, potential applications and highly successful outcomes of biophotonic therapy as an option to treat infectious diseases including HIV, Hepatitis C, MRSA, and others, with emphasis on efficacy of using biophotonic therapies to treat and ameliorate the drug resistant variants of the above infectious agents, including potential applications for the current COVID-19 pandemic and in preparation for the emergence of the next epidemic or pandemic.

Fly ash cement has rarely been used in Japan, mainly because its strength development is slower than ordinary Portland cement. In this research, the effect of the new fly ash cement with both high alite (C3S) cement and fly ash modified by electrostatic belt separation method on cracking resistance of precast concrete prepared by steam curing was studied. The mechanical and shrinkage properties of the proposed fly ash concrete were compared with those of concrete made using OPC cement without fly ash. In order to study the cracking tendency of precast concrete with the proposed fly ash cement, thermal stress analysis was conducted taking into consideration of the experimental data of concrete properties with the different concrete mix proportions. A standard precast concrete box culvert model was used in this 3D FEM analysis and the distribution of temperature and relative humidity in cross section and induced restraint stress during and after steam curing were discussed. Steam-cured concrete with fly ash and high alite cement developed higher compressive strength on the first day of age than concrete with OPC. The proposed fly ash concrete developed high cracking resistance in the early days. On the other hand, the results showed that the drying shrinkage at later ages was the main cause of cracking.

A new approach to the treatment of wound lesions, which are complicated by the presence of polyresistant microflora and a possible immunodeficiency background has been proposed. It involves treating the wound surface with high-intensity pulsed optical radiation of a continuous spectrum, continuously covering the entire UV range (from 200 to 400 nm), visible and near infrared region of the spectrum. A pulsed xenon lamp is used as a radiation source. A description of the design and technical characteristics of the developed device for high-intensity optical irradiation "Zarnitsa-A", which implements the proposed medical technology for wound therapy, is represented. The results of preclinical studies of the apparatus in vitro and in vivo are represented hereinafter. The article shows that the apparatus exposure has pronounced bactericidal and wound-healing properties. The apparatus action reliably provides higher rates of wound healing compared to the use of only a typical antibacterial and wound healing agent – “Levomekol” ointment.

Whole-genome sequencing (WGS) was used for genomic characterization of 110 strains of Listeria innocua isolated from 23 cattle farms, 8 beef abattoirs, and 48 retail outlets in Gauteng province, South Africa. In silico multilocus sequence typing (MLST) was used to identify the isolates' sequence types (STs). BLAST-based analyses were used to identify antimicrobial and virulence genes. The study also linked the detection of the genes to the origin (sources and types of samples) of the L. innocua isolates. The study detected 12 STs, 13 resistance genes, and 23 virulence genes. Of the 12 STs de-tected, ST637 (26.4%), ST448 (20%), 537 (13.6%), and 1085 (12.7%) were predominant, and the frequency varied significantly (P<0.05). All 110 isolates of L. innocua were car-riers of one or more antimicrobial resistance genes, with resistance genes lin (100%), fosX (100%), and tet(M) (30%) being the most frequently detected (P<0.05). Of the 23 virulence genes recognized, 13 (clpC, clpE, clpP, hbp1.svpA, hbp2, iap/cwhA, lap, lpeA, lplA1, lspA, oatA, pdgA, and prsA2) were found in all 110 isolates of L. innocua. Overall, diversity and significant differences were detected in the frequencies of STs, resistance, and virulence genes according to the origins (source and sample type) of the L. innocua isolates. This, being the first genomic characterization of L. innocua recovered from the three levels (farm, abattoir, and retail outlets) of the beef production system in South Africa, provides data on the organism's distribution and potential food safety implications..

Wheat dwarf virus (WDV) causes an important vector transmitted virus disease, which leads to significant yield losses in barley production. Due to the fact, that at the moment no plant protection products are approved to combat the vector Psammotettix alienus and this disease cannot be controlled by chemical means, therefore the use of WDV resistant or tolerant genotypes is the most efficient method to control and reduce negative effects of WDV on barley growth and production. In this study, a set of 480 barley genotypes were screened to identify genotypic differences in response to WDV and five traits were assessed under infected and non-infected conditions. In total, 32 genotypes showed resistance or tolerance against WDV. Subsequently, the phenotypic data of 191 out of 480 genotypes combined with 34,408 single nucleotide polymorphisms (SNPs) in a genome wide association study to identify quantitative trait loci (QTLs) and markers linked to resistance/tolerance to WDV, using Tassel, GAPIT, and FARM CPU. In total, 1, 3, 2, 2 and 1 significantly associated markers on chromosomes 3H, 4H, 5H and 7H identified by all three methods for ELISA-60, relative performance of total grain weight, plant height, number of ears per plant and thousand grain weight, respectively.

Insecticides with novel modes of action are required to complement the pyrethroids currently relied upon for controlling malaria vectors. One example of this is the neonicotinoid clothianidin, which is found in SumiShield™ 50WG used in indoor residual spraying (IRS). In a preliminary experiment, mortality in insecticide susceptible and resistant An. gambiae adults exposed to SumiShield™ 50WG-treated filter papers reached 80% by 3-days post-exposure and 100% by 6-days post-exposure. Next, cement, wood, and mud tiles were treated with SumiShield™ 50WG or K-Othrine® WG250 (deltamethrin IRS formulation) and insecticide resistant and susceptible Anopheles and Aedes were exposed to these surfaces periodically for up to 18-months. Pyrethroid resistant Cx. quinquefasciatus were also exposed at 9 months. Between exposures tiles were stored in heat and relative humidity conditions reflecting those found in the field. On these surfaces, SumiShield™ 50WG was effective at killing both susceptible and resistant An. gambiae for 18 months post-treatment, while mortality amongst the resistant strains when exposed to deltamethrin (K-Othrine® WG250) IRS was not above that of the negative control. Greater efficacy of SumiShield™ 50WG was also demonstrated against insecticide resistant strains of An. funestus compared to deltamethrin, though the potency was lower when compared with An. gambiae. In general, a higher efficacy of SumiShield™ 50WG was observed on cement and mud compared to wood. SumiShield™ 50WG demonstrated poor residual activity against Aedes aegypti and Culex quinquefasciatus. Overall, the results suggest SumiShield™ 50WG is well suited for malaria control.

A recent report from the American Heart Association in 2018 shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin-angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, heart failure among others. It has been suggested that ACE inhibitors can reduce the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that alterations in the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases. In mice, overexpression of ACE in the brain reduces symptoms of the AD-model systems. Thus, we find opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin-angiotensin system; (2) amyloid-degrading enzyme that can hydrolyze beta-amyloid and reduce amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to Alzheimer’s disease to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during the midlife, leading to age-related later events.

The switch from intermittently scanned continuous glucose monitoring (isCGM) to real-time (rt) CGM could improve glycemic management in suboptimal controlled type 1 diabetes patients, but long-term study is lacking. We evaluated retrospectively the ambulatory glucose profile (AGP) in such patients after switching from Free Style libre 1 (FSL1) to Dexcom G4 (DG4) over 1 year. Patients (n=21, 43±15 years, BMI 25±5, HbA1c 8.1±1.0%) had severe hypoglycemia and/or HbA1c≥8%. AGP metrics (time-in-range (TIR) 70-180 mg/dL, time-below-range (TBR)<70 mg/dL or <54 mg/dL, glucose coefficient of variation (%CV), time-above-range (TAR) >180 mg/dL or >250 mg/dL, glucose management indicator (GMI), average glucose) were collected the last 3 months of FSL1 use (M0) and of DG4 for 3, 6 (M6) and 12 (M12) months of use. Values were means ± standard deviation or medians [Q1;Q3]. At M12 versus M0, the higher TIR (50±17 vs. 45±16, P=0.036), and lower TBR<70 mg/dL (2.5 [1.6;5.5] vs. 7.0 [4.5;12.5], P=0.0007), TBR<54 mg/dL (0.7 [0.4;0.8] vs. 2.3 [0.8;7.0], P=0.007) and %CV (39±5 vs. 45±8, P=0.0009), evidenced a long-term effectiveness of the switch. Compared to M6, TBR<70mg/dL decreased, %CV remained stable, while the improvement on hyperglycemia exposure decreased (higher GMI, TAR and average glucose). This switch was a relevant therapeutic option, though a loss of benefit on hyperglycemia stressed the need for optimized management of threshold alarms. Nevertheless, few patients attained the recommended values for AGP metrics, and the reasons why some patients are “responders” vs “non-responders” warrant to be investigated.

(1) Background: Factors reported in literature associated with inappropriate prescribing of antimicrobials, such as physicians with less experience, uncertain diagnosis, and patient caregiver influences on physicians' decisions. Monitoring antimicrobial resistance is critical for identifying emerging resistance patterns, developing, and assessing the effectiveness of mitigation strategies. Improvement in prescribing `antimicrobials would minimize the risk of resistance and, consequently, improve patients' clinical and health outcomes. The purpose of the study is to delineate factors associated with antimicrobial resistance, describe the factors influencing prescriber’s choice during prescribing of antimicrobial, and examine factors related to consequences of inappropriate prescribing of antimicrobial. (2) Methods: Cross-sectional study conducted among healthcare providers (190) in six tertiary hospitals in the Eastern province of Saudi Arabia. The research panel has developed validated and piloted survey specific with closed-ended questions. A value of P &lt;0.05 was considered for statistical significance. All data analysis was performed using Statistical Package for Social Sciences (IBM SPSS version 23.0). (3) Results: 72.7% of the respondents have agreed that poor skills and knowledge are key factors that contribute to the inappropriate prescribing of antimicrobials. All the respondents acknowledged effectiveness and previous experience with the antimicrobial, and reading scientific materials (such as books, articles, and the internet) were key factors influencing physicians’ choice during antimicrobial prescribing. (4) Conclusion: The current study has identified comprehensive education and training needs for healthcare providers about antimicrobial resistance. Using antimicrobials unnecessarily, insufficient duration of antimicrobial use, and using broad spectrum antimicrobials, were reported to be common practices. Further, poor skills and knowledge were a key factor that contributed to the inappropriate use and overuse of antimicrobials and using antimicrobials without physician prescription (self-medication) were the key factors which contribute to AMR from participants’ perspectives. Furthermore, internal policy and guidelines are needed to ensure that the antimicrobials are prescribed in accordance with standard protocols and clinical guidelines.

Plant diseases cause losses of approximately 16% globally. Thus, management measures must be implemented to mitigate losses and guarantee food production. In addition to traditional management measures, resistance induction and biological control have gained ground in agriculture due to their enormous potential. Endophytic fungi colonize plant tissues internally and have the potential to act as biological control agents, as elicitors in the process of resistance induction and in attenuating abiotic stresses. In this review, we list the action of this group of microorganisms as potential agents which can act in controlling plant diseases and describe several examples in which endophytes were able to reduce the damage caused by pathogens and adverse conditions. This is due to their arsenal of molecules generated during the interaction by which they form a kind of biological shield in the plant. Studies on these microorganisms have grown due to the existing diversity and the multiple benefits they can offer. Finally, considering that endophytic fungi can be an important tool in managing diseases due to the large amount of biologically active substances produced, bioprospecting this class of microorganisms is tending to increase and generate valuable products.

This study demonstrated that antibiotic residue in milk can be reduced when dairy farmers use Ethno-veterinary Practices (EVP) based on herbal alternatives to prevent and cure common clinical conditions in cattle instead of antibiotics. Of the 220 farmers selected for the study, 140 were trained and motivated to use validated herbal formulations, 80 were kept as control. Milk samples from the selected farmers (except Thirukanurpatti milk society) tested positive for antibiotic residue in the baseline survey. One year after interventions, the milk from 123 (87.86%) farmers out of 140, were without any detectable antibiotic residue, while samples from 11 farmers (7.85%) were low positive for either Beta-lactams or sulphonamides and 6 (4.29%) were positive for Beta lactams and/or sulphonamides. These 17 (11 + 6) farmers had used antibiotics along with herbal formulations. The milk samples from the control groups were positive for beta lactam and sulphonamide. There was suggestive significance of change in knowledge, attitude and practice of EVP among the farmers from Kerala and Tamil Nadu. A progressive reduction in the incidence of mastitis, enteritis, repeat breeding and cowpox were observed from 2016 to 2019 among the cows treated with EVP. Use of herbal alternative also resulted in a significant reduction in health care expenditure of cattle.

This service improvement project was carried out at LEKMA Hospital, Ghana. Ghana has high levels of antimicrobial resistance (AMR). There is an urgent need to introduce models of care that optimize antibiotic prescribing. Methods Delayed / back-up prescribing is a strategy that could reduce antibiotic use in suspected upper respiratory tract infections. Four different models of delayed / back-up prescribing [no prescription; post-dated prescription (given to patient); post-dated prescription (forwarded to pharmacy); and follow-up appointment for reassessment after 3 days] were implemented in discussion between clinician and patient. Patients were contacted 10 days after their appointment to record compliance, check on their wellbeing, and rate their experience. Results Over a 3-month period (12/2019-02/2020), 142 patients were eligible for delayed / back-up prescribing. The most common clinical diagnoses were sore throat (102/140, 73%), common cold (22/140, 16%) and sinusitis (10/140, 7%). In total, 12 (9%) patients remained symptomatic at day 10, and only one individual in the entire cohort took antibiotics. Most patients (95%) rated their experience as good or very good. Conclusions Delayed / back-up prescribing models can lead to substantial reduction in antibiotic consumption amongst outpatient department patients with suspected upper respiratory tract infections. Delayed / back-up prescribing can be implemented safely in low and middle-income countries.

Mankind faces a coronavirus pandemic originating from a seafood market in Wuhan, China since December 2019. The pathogen was named novel coronavirus (n-CoV) and bats are the identified key reservoir. The coronavirus disease 2019 (COVID-19) quickly spread over China across the globe, turned into a pandemic with exponentially increasing numbers of cases and significant mortality rate. China reacted with lockdowns and strict control measurements to prevent spreading the virus. The treatment of severe cases was hampered by lack of specific vaccines. Vaccine-development and production is a painstaking process and can only be enforced by international cooperation. Different supportive treatment options surfaced due to combinations of antiviral agents with antibiotic drugs. Elderly, male, immune-suppressed patients with co-morbidities showed a high mortality rate. Health literacy, strong immune system, adequate serum 25-hydroxyvitamin D (25(OH)D) concentrations and healthy life style choices can support fast recovery. Antibiotic resistance needs to be addressed by development of new generation antimicrobials against nosocomial infections in preparation for future outbreaks. Plant-biosynthesis of nanomaterials and antiseptics may help in prevention and recovery rate. Prevalence of COVID-19 maybe inversely related to BCG vaccination, endemicity of malaria, humidy and temperature but directly with latitude. Recommendations to prevent the spread of COVID-19 should be followed strictly.

The Colebrook equation is a popular model for estimating friction loss coefficients in water and gas pipes. The model is implicit in the unknown flow friction factor . To date, the captured flow friction factor can be extracted from the logarithmic form analytically only in the term of the Lambert -function. The purpose of this study is to find an accurate and computationally efficient solution based on the shifted Lambert -function also known as the Wright -function. The Wright -function is more suitable because it overcomes the problem with the overflow error by switching the fast growing term of the Lambert -function to the series expansions that further can be easily evaluated in computers without causing overflow run-time errors. Although the Colebrook equation transformed through the Lambert -function is identical to the original expression in term of accuracy, a further evaluation of the Lambert -function can be only approximate. Very accurate explicit approximations of the Colebrook equation that contains only one or two logarithms are shown. The final result is an accurate explicit approximation of the Colebrook equation with the relative error of no more than 0.0096%. The presented approximations are in the form suitable for everyday engineering use, they are both accurate and computationally efficient.

Very little is known about laboratory confirmed blood stream infections (LCBIs) in neonatal intensive care units (NICUs) in resource-limited settings. The aim of this cohort study was to determine the incidence, risk factors, and causative agents of LCBIs in a level-2 NICU in India. The diagnosis of LCBIs was established using the Centre for Disease Control, USA criteria. A predesigned questionnaire containing risk factors associated with LCBIs was filled-in. A total of 150 neonates (43% preterm) were included in the study. The overall incidence of LCBIs was 31%. The independent risk factors for LCBIs were: preterm neonates (relative risk (RR) 2.23), duration of NICU stay more than 14 days (RR 1.75), chorioamnionitis in the mother (RR 3.18), premature rupture of membrane in mothers (RR 2.32), neonate born through meconium-stained amniotic fluid (RR 2.32), malpresentation (RR 3.05), endotracheal intubation (RR 3.41), umbilical catheterization (RR 4.18), and ventilator-associated pneumonia (RR 3.17). The initiation of minimal enteral nutrition was protective from LCBIs (RR 0.22). The predominant causative organisms were gram-negative pathogens (58%). The results of the present study can be used to design antibiotic interventions to reduce LCBIs in resource-limited settings.

The infections of bacterial origin represent a significant problem to public healthcare worldwide both in clinical and community settings. Recent decade was marked by limiting treatment options for bacterial infections due to growing antimicrobial resistance (AMR) acquired and transferred by various bacterial species, especially the ones causing healthcare-associated infections, which has become a dangerous issue noticed by the World Health Organization. Numerous reports shown that the spread of AMR is often driven by several species-specific lineages usually called the ‘global clones of high risk’. Thus, it is essential to track the isolates belonging to such clones and investigate the mechanisms of their pathogenicity and AMR acquisition. Currently, the whole genome-based analysis is increasingly used for these purposes, including epidemiological surveillance and analysis of mobile elements involved in resistance transfer. However, in spite of the exponential growth of available bacterial genomes, their representation usually lack uniformity and availability of supporting metadata, which creates a bottleneck for such investigations. In this dataset, we provide the results of a comprehensive genomic epidemiology analysis of 61,857 genomes of a dangerous bacterial pathogen Klebsiella pneumoniae. Important typing information including multilocus sequence typing (MLST)-based sequence types (STs), assignment of the isolates to known global clones, capsular (KL) and lipooligosaccharide (O) types, presence of CRISPR-Cas systems, and cgMLST profiles are given, and the presence of AMR and virulence genes within the genomes is also reported. This dataset will be useful for researchers in the field of K. pneumoniae genomic epidemiology, resistance analysis and prevention measure development.

Selection is a fundamental part of the plant breeding process, enabling the identification and development of varieties with desirable traits. Thanks to advances in genetics and biotechnology, the selection process has become more precise and efficient, resulting in faster breeding progress and better adaptation of crops to environmental challenges. Genetic parameters related to gene additivity and epistasis play a key role and can influence decisions on the suitability of breeding material. In this study, 188 rapeseed doubled haploid lines were assessed in field conditions for resistance to Leptosphaeria spp. Through next-generation sequencing, a total of 133,764 molecular markers (96,121 SilicoDArT and 37,643 SNP) were obtained. The similarity of the DH lines at the phenotypic and genetic levels was calculated. The results indicate that the similarity at the phenotypic level was markedly different than the similarity at the genetic level. Genetic parameters related to additive gene action effects and epistasis (double and triple) were calculated using two methods: based on phenotypic observations only and using molecular marker observations. All evaluated genetic parameters (additive, additive-additive and additive-additive-additive) were statistically significant for both estimation methods. The parameters associated with the interaction (double and triple) had opposite signs depending on the estimation method.

Potentially, traditional medicine is used to manage multidrug resistance (MDR) bacterial infections. This study determined the antioxidant and antibacterial activities of Thymus schimperi (Ts), Rhamnus prinoides (Rp) and Justicia schimperiana (Js) from Addis Ababa against MDR-Uropathogenic Bacteria. Hydromethanolic extracts were prepared. Quantitative determination of phytochemicals and DPPH, ABTS and FRAP assays for antioxidant activities were carried out. In vitro, antibacterial activity and minimum inhibitory concentration (MIC) were performed. Ts had the highest total phenolic (TPC), flavonoid (TFC) and proanthocyanidin content. GC-MS analyses identified 14 bioactive-compounds: in Ts extract, with hexanedioic acid, bis(2-ethylhexyl) ester, thymol, and o-cymen-5-ol being the most predominant, respectively; in Rp extract (6 compounds; hexanedioic acid, bis(2-ethylhexyl) ester, β-D-glucopyranoside, methyl and desulphosinigrin respectively); and in Js extract (5 bioactive-compounds: hexanedioic acid, mono (2-ethylhexyl) ester, debrisoquine, and 8,11,14-heptadecatrienoate, methyl ester) being predominant, respectively. The extracts' TPC showed a strong negative correlation with the DPPH assay (r= -0.999; p=0.023), while its TFC correlated significantly with the ABTS assay (r=0.999; p= 0.032). Ts showed the highest antibacterial activity against clinical isolates of Escherichia coli and Klebsiella pneumoniae ESBL at 1000 mg/mL, and TS had the lowest MIC (4 mg/mL) among evaluated extracts against E. coli (ATCC25922). In conclusion, Ts and Rp showed activity against patient-isolated MDR-uropathogenic E. coli and K. pneumoniae ESBL.

Vinyltriethoxysilane (VTES) was covalently bonded onto graphene oxide. Several methods, including X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction, were used to demonstrate the presence of VTES on the surface of graphene oxide and the creation of this covalent link. Following that, different quantities of the resultant vinyltriethoxysilane functionalized graphene oxide (VTESFGO) were mixed with polyvinyl alcohol (PVA) to form VTESFGO/PVA nanocomposite films (NCFs) with a 3-dimensional network structure. The creation of these NCFs and the presence of a three-dimensional network were confirmed by Fourier transform infrared spectroscopy. The three-dimensional network structure provided these NCFs extraordinary characteristics. The mechanical and thermal stability, oxygen transfer rate (OTR), and water resistance pressure (WRP) of the NCFs were investigated. The nanocomposite film (NCF) with the highest weight percentage of VTESFGO (3.0 wt.%) was 47.5% more thermally stable than pure PVA, with an oxygen transmission rate of 0.3 cm3/m2 per day and a water resistance pressure of 780 mm/cm2. However, as the weight percentage of VTESFGO increased, the mechanical strength of the NCFs decreased as a result of silanol self-condensation, resulting in particulate formation, as confirmed by scanning electron microscopy.

Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human immunodeficiency virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection from a fatal illness into a manageable chronic disorder. However, the presence of latent reservoirs, multifaceted nature of HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict the efficacy of current cART targeting the distinct stages of the virus life cycle. Therefore, there is an unmet need for discovery of new therapeutics that not only bypass the limitations of the current therapy but also protect the body health at the same time. The main goal for complete HIV-1 eradication is purging latently infected cells from the patients’ bodies. A potential strategy called “lock-in apoptosis” targeting the budding phase of life cycle of virus leading to susceptibility to apoptosis of HIV-1 infected cells for elimination of HIV-1 reservoirs and ultimately for a complete eradication. The current work intends to present the main advantages and disadvantages of United States Food and Drug Administration (FDA) approved anti-HIV-1 drugs as well as plausible strategies for the design and development of more anti-HIV-1 compounds with better potency, favorable pharmacokinetic profiles, and improved safety issues.

Anthracnose stands as the primary obstacle to lupin cultivation, impeding development despite the considerable agronomic, ecological, and economic potential of such legume crops. This review explores recent efforts to unravel the complexities of anthracnose in domesticated lupins, focusing on both the plant perspective and the causative pathogenic agent, Colletotrichum lupini. Leveraging cutting-edge technologies has yielded crucial insights into various facets of this devastating disease, encompassing plant and pathogen biology, genetic and molecular regulations of the interaction, fungal diversity and population dynamics, and screening of plant genetic resources for anthracnose resistance. The lack of effective disease control measures, relying primarily on the use of disease-free seeds, highlights the need to develop anthracnose-resistant varieties. However, challenges arise from the intricacy of lupin's response to the disease, influenced by polygenic inheritance, in spite of loci with major effects, and environmental factors. The slow pace of genetic improvement underscores the need for more efficient breeding processes, including biotechnological approaches. This review offers a comprehensive overview of current progress and knowledge gaps, stressing the urgent need to further enhance understanding of C. lupini pathogenic mechanisms and lupin‘s resistance. Integrating advanced technologies and accelerated research efforts is paramount for achieving efficient disease management and sustainable lupin cultivation in the face of anthracnose challenges.

The skeletal muscle plays a critical role in regulating systemic blood glucose homeostasis. Impaired skeletal muscle glucose homeostasis associated with type 2 diabetes mellitus (T2DM) has been observed to significantly affect the whole-body glucose homeostasis, thereby resulting in other diabetic complications. T2DM does not only affect skeletal muscle glucose homeostasis, but it also affects skeletal muscle structure and functional capacity. Given that T2DM is a global health burden, there is an urgent need to develop therapeutic medical therapies that will aid in the management of T2DM. Prediabetes is a prominent risk factor of T2DM that usually goes unnoticed in many individuals as it is an asymptomatic condition. Hence, research on prediabetes is essential because establishing diabetic biomarkers during the prediabetic state would aid in preventing the development of T2DM, as prediabetes is a reversible condition if it is detected in the early stages. Literature predominantly documents the changes in skeletal muscle during T2DM, but the changes in skeletal muscle during prediabetes remain unknown. In this review, we seek to review the existing literature on prediabetic and T2DM associated changes in skeletal muscle function.

Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) antibodies, have initiated a new era in the treatment of malignant melanoma. ICIs can be used in various settings, including as first-line, adjuvant, and neoadjuvant therapy. In the scope of this review, we examined clinical studies utilizing ICIs in the context of treating oral mucosal melanoma, a rare disease albeit with an extremely poor prognosis, with a specific focus on unraveling the intricate web of resistance mechanisms. The absence of a comprehensive review focusing on ICIs in oral mucosal melanoma is notable. Therefore, this review seeks to address this deficiency by offering a novel and thorough analysis of the current status, potential resistance mechanisms, and future prospects of applying ICIs specifically to oral malignant melanoma. Clarifying and thoroughly understanding these mechanisms will facilitate the advancement of effective therapeutic approaches and enhance the prospects for patients suffering from oral mucosal melanoma.

Methylglyoxal (MGO) is the major compound belonging to reactive carbonyl species (RCS) responsible for the generation of advanced glycation end products (AGEs). Its upregulation followed by deleterious effects at the cellular and systemic level is associated with metabolic disturbances (hyperglycemia/hyperinsulinemia/insulin resistance/hyperlipidemia/inflammatory processes/carbonyl stress/oxidative stress/hypoxia). Therefore, it is implicated in a variety of disorders including metabolic syndrome, diabetes mellitus and cardiovascular diseases. In this review an interplay between pathways leading to MGO generation and scavenging is addressed, in regard to this system’s impairment in pathology. The issues associated with mechanistic MGO involvement in pathological processes, as well as the discussion on its possible causative role in cardiometabolic diseases are enclosed. Finally, the main strategies aimed at MGO and its AGEs downregulation with respect to cardiometabolic disorders treatment are addressed. Potential glycation inhibitors and MGO scavengers are discussed, as well as the mechanisms of their action.

Barley is an important crop grown on almost 49 Mha worldwide in 2021 and is particu-larly significant in Europe where powdery mildew is the most frequent disease on sus-ceptible varieties. The most suitable way for protecting crops is exploiting genetic re-sistance. However, the causal agent Blumeria hordei is an extremely adaptable pathogen. The aims of this research were to increase our knowledge of the rapidly changing path-ogen population and detect rare virulences. Random samples of the pathogen were ob-tained from the air by means of a mobile spore sampler. Spores were collected by driv-ing across the Czech Republic in 2019, 2021 and 2023 and 299 isolates were analyzed on 121 host varieties. No infection occurred on 35 differentials, rare virulence was recorded on 31 varieties and a higher virulence frequency was found on 55 differentials. A core set of differentials along with four additional varieties distinguish 295 pathotypes (Simple Index = 0.987) and virulence complexity of isolates varied from 4 to 19 with an average 10.39. The detection of new virulences, the increasing frequency of previously rare viru-lences and high pathotype diversity as well as high virulence complexity confirm that using nonspecific durable resistance is crucial for successfully breeding commercial va-rieties.

Background: Misconceptions and knowledge gaps about antibiotic use contribute to inappropriate antibiotic use and antimicrobial resistance. Aim: Identifying and prioritizing misconceptions and knowledge gaps about antibiotic use from a healthcare professionals’ perspective. Methods: A modified Delphi study of two rounds with an expert meeting. A literature search was conducted to create statements about misconceptions and knowledge gaps about antibiotic use. These were rated by healthcare professionals from five EU countries representing general practice, out-of-hour services, nursing homes, and pharmacies. Consensus was achieved if ≥80% of the participants rated 4+ on a five-point Likert scale during the second Delphi round. Results. In total, 44 misconceptions were identified through the literature search within four themes: 1) antimicrobial resistance in general, 2) use of antibiotics in general, 3) use of antibiotics for respiratory tract infections, and 4) use of antibiotics for urinary tract infections. Consensus was reached for more than half of the statements within each setting. Conclusions. Experts from different settings and nationalities acknowledge that multiple misconceptions and knowledge gaps can contribute to inappropriate use of antibiotics in the community. These results provide valuable information to use in educational campaigns for patients and healthcare professionals to improve the use of antibiotics.

Helicobacter pylori is a gastric pathogen that infects nearly half of the global population and is recognized as a group 1 carcinogen by the Word Health Organization. The global rise in antibiotic resistance has increased clinical challenges in treating H. pylori infections. Biofilm growth has been proposed to contribute to H. pylori’s chronic colonization of the host stomach, treatment failures, and the eventual development of gastric diseases. Several components of H. pylori have been identified to promote biofilm growth, and several of these may also facilitate antibiotic tolerance, including the extracellular matrix, outer membrane proteins, the coccoid morphology, modulated metabolism, efflux pumps, and virulence factors. Recent developments in therapeutic approaches targeting H. pylori biofilm have shown that synthetic compounds, such as small molecule drugs and plant-derived compounds, are effective at eradicating H. pylori biofilms. These combined topics highlight the necessity for biofilm-based research in H. pylori, to improve current H. pylori targeted therapeutic approaches and alleviate relative public health burden. In this review we discuss recent discoveries that have decoded the life cycle of H. pylori biofilms and current biofilm targeted treatment strategies.

The lungs of tuberculosis (TB) patients contain a spectrum of granulomatous lesions ranging from solid and well vascularized cellular granulomas, to avascular caseous granulomas. In solid granulomas, current therapy kills actively replicating (AR) intracellular bacilli, while in low vascularized caseous granulomas the low oxygen tension stimulates aerobic and microaerophilic AR bacilli to transit into non-replicating (NR), drug-tolerant, extracellular stages. These stages, which do not have genetic mutations and are often referred to as persisters, are difficult to eradicate due to low drug penetration inside caseum and mycobacterial cell walls. The sputum of TB patients contains also viable bacilli called differentially detectable (DD) cells that, unlike persisters, grow in liquid, but not in solid media. This review provides a comprehensive update on drug combinations killing in vitro AR and drug-tolerant bacilli (persisters and DD cells), and sterilizing Mycobacterium tuberculosis-infected BALB/c and caseum-forming C3HeB/FeJ mice. These observations have been important for testing new drug combinations in noninferiority clinical trials, in order to shorten duration of current regimens against TB. In 2022, the World Health Organization, based on one of this trial, supported the use of a 4-month regimen for treatment of drug-susceptible TB as a possible alternative to the current 6-month regimen.

Introduction: The reduced implementation of surveillance programs and limited bedside infectious diseases consultations due to the pressure of COVID-19 pandemic in healthcare systems led to increased rates of irrational use of antimicrobials and incidence of infections by multidrug-resistant microorganisms. The aim of the present study is to evaluate the incidence of antimicrobial resistance and the management of bloodstream infections before and during COVID-19 pandemic at the University General Hospital of Alexandroupolis (Greece). Material-Methods: This is a retrospective study conducted from January 2018 to December 2022. Data were collected from the University Microbiology Laboratory per semester regarding the isolated strains of Gram positive and negative bacteria in blood cultures and respiratory samples in hospitalized patients in medical and surgical wards and in the Intensive Care Unit (ICU). Additionally, bloodstream infections with requested infectious diseases consultation were reported (n=400), determining whether these were carried out via telephone contact or at the patient's bedside. Demographic data, comorbidities, focus of infection, antimicrobial regimen, duration of treatment, length of hospitalization and clinical outcome were analysed. Results: A total of 4569 strains of Gram positive and negative bacteria were isolated. An increasing trend was reported compared to the pre-pandemic period in the incidence of resistant Gram-negative bacteria, particularly in ICUs. Prior antimicrobial use and the rate of hospital-acquired infections were increased significantly during the pandemic. In the pre-pandemic period 2018-2019, a total of 246 infectious diseases consultations were carried out, while during the period 2020-2022 154, with the percentage of telephone consultations 15% and 76% respectively. Detection of the source of infection and timely administration of appropriate antimicrobial agents were more frequently recorded before the pandemic and 28-day mortality was significantly reduced in cases with bedside consultations. Conclusion: Empowering of infectious diseases surveillance programs and committees, rational use of antimicrobials agents and bedside infectious diseases consultations are vital in order to reduce the impact of infections caused by multidrug-resistant strains.

Background: Multi-drug resistance organisms (MDRO) often cause increased morbidity, mortality, and length of stays (LOS). However, there is uncertainty whether the infection of MDRO increase the morbidity, mortality, and ICU-LOS. Objective: This study performed to determine the prevalence of MDRO in ICU, site of infection and the association of MDRO or site of infection with mortality. Secondary outcome was determined by ascertaining the association of MDRO or site of infection with (ICU-LOS). Methods: A retrospective cohort study was performed with adult sepsis patients in ICU. Univariate and multivariate (MVA) logistic regression with cox regression modeling were performed to compute the association of MDRO on ICU-mortality. MVA modelling was performed for ICU-LOS predictors. Results: Out of 228 patients, the isolated MDRO was 97 (42.5%) of which 78% were gram-negative bacteria. The mortality rate among those with MDRO was 85 (37.3%). The hospital acquired infection (HAI) was significantly predictor for ICU-LOS in univariate linear regression (R² = 0.034, P=0.005). In MVA linear regression, both Enterococcus faecalis infection and acinetobacter baumannii (AC) -MDRO were predictors for ICU-LOS with (R² = 0.478, P<0.05). In the univariate cox regression, only the infection with AC- MDRO was a risk factor for ICU-mortality with [ HR =1.802 (95% CI: 1.2 – 2.706; P = 0.005)]. Conclusions: Identifying risk factors for MDRO highlight the appropriate administration of empirical antibiotics and effectively control of source of infection which would reduce mortality and ICU-LOS. The usage of broad- spectrum antibiotics should be limited for those having substantial risk factors to acquire MDRO.

Antimicrobial resistance (AMR) has been a serious threat to human health, and combination therapy is proved to be an economic and effective strategy to fight the resistance. However, the abuse of drug combinations would conversely accelerate the spread of AMR. In our previous work, it had been concluded that the mutant selection indexes (SIs) of one agent against a specific bacterial strain are closely related to the proportions of two agents in a drug combination. To discover probable correlations, predictors and laws for further proposing feasible principles and schemes guiding the AMR-preventing practice, here three aspects were further explored. First, the power function (y=ax^b, a > 0) correlation between the SI (y) of one agent and the ratio value (x) of two agents in a drug combination was further established based on the mathematical and statistical analyses for those experimental data, and two rules a₁ × MIC₁ = a₂ × MIC₂ and b₁ + b₂ = -1 were discovered from both equations of y=a₁x^b1 and y=a₂x^b2 respectively for two agents in drug combinations. Simultaneously, it was found that one agent with larger MPC alone for drug combinations show greater potency for narrowing itself MSW and preventing the resistance. Second, a new concept as mutation-preventing selection index (MPSI) was proposed and used for evaluating the mutation-preventing potency difference of two agents in drug combinations, and the positive correlation between the MPSI and the mutant prevention concentration (MPC) or minimal inhibitory concentration (MIC) was subsequently established. Inspired by this, the significantly positive correlation, contrary to previous reports, between the MIC and the corresponding MPC of antimicrobial agents against pathogenic bacteria was established using one hundred and eighty-one of data pairs reported. These results together of above three aspects indicate that the MPCs in alone and combination are very important indexes for drug combinations to predict the mutation-preventing effects and the trajectories of collateral sensitivity, and while the MPC of an agent can be roughly calculated from its corresponding MIC. Subsequently, the former conclusion was further verified and improved by the antibiotic exposure to forty-three groups designed as different drug concentrations and various proportions. The results further proposed that the C/MPC for the agent with larger proportion in drug combinations can be considered as a predictor and is the key to judge whether the resistance and the collateral sensitivity occur to two agents. Based on these above correlations, laws, and their verification experiments, some principles were proposed, and a diagram of the mutation-preventing effects and the resistant trajectories for drug combinations with different concentrations and ratios of two agents was presented. Simultaneously, the reciprocal of MPC alone (1/MPC), proposed as the stress factors of two agents in drug combinations, together with their SI in combination, is the key to predict the mutation-preventing potency and control the trajectories of collateral sensitivity. Finally, a preliminary scheme for antimicrobial combinations preventing the AMR was further proposed for subsequent improvement research and clinic popularization, based on the above analyses and discussion. Moreover, some similar conclusions were speculated for triple or multiple drug combinations.

Concrete is the most commonly used construction material due to its various advantages, such as versatility, familiarity, strength and durability and it will continue to be in demand far into the future. However, with today’s sensitivity to the environmental protection, this material is facing unprecedented challenges due to its high greenhouse gas emission mainly during cement production. This paper investigates one of the promising cement replacement materials, alkali activated cement (AAC) concrete. Being produced mainly from byproduct materials and having a comparable structural performance to conventional concrete, AAC concrete has a potential to transform the construction industry. Mechanical properties such as compressive and flexural strength and the relationship between them are studied. Different source materials such as fly ash (FA), ground granulated blast furnace slag (GGBS), silica fume (SF) and Metakaolin (MK) are used. The effect of the source materials and the activator solutions on the concrete performance is studied. Furthermore, the freeze-thaw resistance of the concrete is studied. The results of the study showed that the behavior of AAC depends highly on the source material combinations as well as type used. The effect of the alkaline solution is also dependent on the source material used. Mixes with higher GGBS content in general showed the highest strength while mixes with MK showed the highest flexural strength. The results from the freeze-thaw test showed that proper design of AAC concrete with a lower water content is critical to achieve a good resistance.

Researchers have developed and used several three-dimensional (3D) culture systems, including spheroids, organoids, and tumoroids. Drug resistance is a crucial issue involving recurrence in cancer patients. Many studies on anticancer drugs have been done in 2D culture systems, where-as 3D cultured tumoroids have many advantages for assessing drug sensitivity and resistance. Here, we aim to investigate whether Cisplatin (a DNA crosslinker), Imatinib (a multiple tyro-sine kinase inhibitor), and 5-Fluorouracil (5-FU: an antimetabolite) alter tumoroid growth of metastatic colorectal cancer (mCRC). To establish a liquid-based 3D multiplexing reporter assay system, LuM1 (a murine mCRC cell line) was stably transfected with the Mmp9 promoter-driven ZsGreen reporter gene, which was designated as LuM1/m9 cells and cultured in NanoCulture Plate (NCP), a 3D culture device. The larger tumoroids were not sensitive to Cisplatin and ex-pressed ABCG2 (a marker of cancer stem cells, a.k.a. a drug efflux transporter), whereas smaller cell-aggregates were more sensitive to Cisplatin. Both Imatinib and Cisplatin significantly in-creased tumoroid growth (larger than 300 μm2) and Mmp9 promoter activity and were not cytotoxic to the mCRC tumoroids. On the other hand, 5-FU was cytotoxic to the tumoroids and significantly inhibited tumoroid growth, although not completely. Thus, platinum resistance and imatinib resistance in mCRC were modeled using the liquid-based 3D cultured tumoroid system. The tumoroid culture is useful and easily accessible for the assessment of drug sensitivity and resistance.

Many cellular functions important for tumor initiation and progression are mediated by members of the integrin family, a diverse family of cell adhesion receptors. With recent studies emphasising on the role of the tumor microenvironment (TME) in tumor initiation and progression, it is not surprising that a lot of attention is being given to integrins. Several integrins are under trial with many demonstrating appealing activity in patients with different cancers. A deeper knowledge of the functions of integrins within the tumor microenvironment is still required, and might lead to better inhibitors being discovered. Integrin expression is commonly dysregulated in many tumors with integrins playing key roles in signaling as well as promotion of tumor cell invasion and migration. This review report new data on the differential expression of integrins within solid tumors using two publicly available resources: The Cancer Genomic Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA). In this analysis, I investigated the expression of integrin alpha 2 (ITGα2), ITGα3, ITGβ4 and ITGβ6 in tumor tissues versus adjacent normal tissues. This analysis showed that integrins were differentially expressed in cervical squamous cell carcinoma (CESC), head and neck squamous cell carcinoma (HNSC), esophageal carcinoma (ESCA) and lung adenocarcinoma (LUAD). This analysis showed that ITGα2 and ITGβ6 expression are upregulated in CESC and ESCA, ITGα3 is upregulated in HNSC and ESCA whilst ITGβ4 is highly expressed in CESC, HNSC, ESCA and LUAD tumor tissues compared to adjacent normal tissues. Integrins also play a major role in adhesion of circulating tumor cells to new sites and the resulting formation of secondary tumors. Furthermore, integrins have demonstrated the ability to promoting stem cell-like properties in tumor cells as well as drug resistance. Anti-integrin therapies rely heavily on the doses or concentrations used as these determine whether the drugs act as antagonists or as integrin agonists. This review offers the latest synthesis in terms of current knowledge of integrins functions within the tumor microenvironment and potential targets for different cancers.

Stress Granules formation is a pro-survival mechanism helping cells to cope with environmental challenges. Stress Granules have been studied for two decades in fundamental research, and are now being examined in the context of human pathogenesis. Here, we review studies highlighting stress granules’ involvement in cancer development through translational pattern modification.

1. Heterospecific pollen interference has recently been proposed as a mechanism contributing to the success of alien invaders, as heterospecific pollen of alien plants interferes with the reproduction of natives by reducing fruit and seed set. However, no study has looked at the opposite interaction. Moreover, few studies have considered the roles of phylogenetic and trait distances between pollen donors and recipients. 2. We did a large multi-species experiment in which we used alien and native species both as pollen recipients and as pollen donors, and included phylogenetic as well as trait distance as explanatory variables. 3. We found that both alien and native recipients suffered from heterospecific pollen from donors of the opposite status in terms of seed and fruit set. Phylogenetic distance and trait distance both affected heterospecific pollen interference, but the effect depended on recipient and donor statuses. 4. We conclude that heterospecific pollen interference affects both native and alien recipients, thus indirectly altering community composition and increasing biotic resistance against invaders.

Pasmo is one of the most widespread diseases threatening flax production. To identify genetic regions associated with pasmo resistance (PR), a genome-wide association study was performed on 370 accessions from the flax core collection. Evaluation of pasmo severity was performed in the field from 2012 to 2016 in Morden, MB, Canada. Genotyping-by-sequencing has identified 258,873 single nucleotide polymorphisms (SNPs) distributed on all 15 flax chromosomes. Marker-trait associations were identified using ten different statistical models. A total of 692 unique quantitative trait nucleotides (QTNs) associated with 500 putative quantitative trait loci (QTL) were detected from six phenotypic PR datasets (five individual years and average across years). Different QTNs were identified with various statistical models and from individual PR datasets, indicative of the complementation between analytical methods and/or genotype × environment interactions of the QTL effects. The single-locus models tended to identify large-effect QTNs while the multi-loci models were able to detect QTNs with smaller effects. Among the putative QTL, 67 had large effects (3-23%), were stable across all datasets and explained 32-64% of the total variation for PR in the various datasets. Forty-five of these QTL spanned 85 resistance gene analogs including a large toll interleukin receptor, nucleotide-binding site, leucine-rich repeat (TNL) type gene cluster on chromosome 8. The number of positive effect QTL (NPQTL) in accessions was significantly correlated with PR (R²=0.55), suggesting additive effects. NPQTL was also significantly associated with morphotype (R²=0.52) and major positive effect QTL were present in the fiber type accessions. The 67 large effect QTL are suited for marker-assisted selection and the 500 QTL for effective genomic prediction in PR molecular breeding.

This paper gives a new unified formula for the Newtonian fluids valid for all pipe flow regimes from laminar to the fully rough turbulent. It includes laminar, unstable sharp jump from laminar to turbulent, and all types of the turbulent regimes: smooth turbulent regime, partial non-fully developed turbulent and fully developed rough turbulent regime. The formula follows the inflectional form of curves as suggested in Nikuradse’s experiment rather than monotonic shape proposed by Colebrook and White. The composition of the proposed unified formula consists of switching functions and of the interchangeable formulas for laminar, smooth turbulent and fully rough turbulent flow. The proposed switching functions provide a smooth and a computationally cheap transition among hydraulic regimes. Thus, the here presented formulation represents a coherent hydraulic model suitable for engineering use. The model is compared to existing literature models, and shows smooth and computationally cheap transitions among hydraulic regimes.

Today, Colebrook’s equation is mostly accepted as an informal standard for modeling of turbulent flow in hydraulically smooth and rough pipes including transient zone in between. The empirical Colebrook’s equation relates the unknown flow friction factor (λ) with the known Reynolds number (R) and the known relative roughness of inner pipe surface (ε/D). It is implicit in unknown friction factor (λ). Implicit Colebrook’s equation cannot be rearranged to derive friction factor (λ) directly and therefore it can be solved only iteratively [λ=f(λ, R, ε/D)] or using its explicit approximations [λ≈f(R, ε/D)]. Of course, approximations carry in certain error compared with the iterative solution where the highest level of accuracy can be reached after enough number of iterations. The explicit approximations give a relatively good prediction of the friction factor (λ) and can reproduce accurately Colebrook’s equation and its Moody’s plot. Usually, more complex models of approximations are more accurate and vice versa. In this paper, numerical values of parameters in various existing approximations are changed (optimized) using genetic algorithms to reduce maximal relative error. After this improvement computational burden stays unchanged while accuracy of approximations increases in some of the cases very significantly.

This paper explores various aspects of microbiology and immunology, focusing on the epidemiology and molecular characterisation of infectious diseases in the Caribbean and South America. Key areas of investigation include tuberculosis (TB), nosocomial infections, Salmonella infections, and bloodborne pathogens. A retrospective study in Jamaica underscores the high mortality rates in HIV-positive TB patients and the need for early HIV diagnosis and integrated care. Research in Trinidad and Tobago reveals the genetic diversity of Mycobacterium tuberculosis strains, highlighting high HIV-TB co-infection rates. The paper also examines the challenges posed by nosocomial infections, particularly those caused by antibiotic-resistant Gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA), and emphasises the importance of infection control. In addition, the study investigates Salmonella prevalence in poultry in Jamaica and the risks associated with foodborne infections. The paper further explores transfusion-transmitted infections and the development of IgM antibodies in egg whites for bacterial antigen detection. Lastly, it addresses immune responses in patients with immunodeficiency disorders, such as severe combined immunodeficiency (SCID) and chronic granulomatous disease (CGD), highlighting their susceptibility to a wide range of infections.

The current work is dedicated to the search for new high-energy materials (HEMs) with improved characteristics which are gained through agglomeration with salts. The research was performed by Becke’s three-parameter hybrid functional approach with non-local correlation provided by Lee, Yang, and Parr and cc-pVTZ basis set. The geometry, total energy, and heat of formation of the most stable compounds forming due to 3-amino-5-[(2, 4, 6-trinitrophenyl) amino]-1H-1, 2, 4-triazole (APATO) within salts selected were obtained to foresee its influence on resistance to shock stimuli, detonation pressure, and velocity of the materials under study. Results obtained allow us to foresee that only agglomeration with precise salts could lead to significant improvement in the stability of the specific high-energy materials and the resistance to shock stimuli. We also show that the agglomeration leads to better energetic properties of the above compound, although the improvement could be insignificant in some cases.

The infections caused by various bacterial pathogens both in clinical and community settings represent a significant threat to public healthcare worldwide. The growing resistance to antimicrobial drugs acquired by bacterial species causing healthcare-associated infections has already become a life-threatening danger noticed by the World Health Organization. Several groups or lineages of bacterial isolates usually called ‘the clones of high risk’ often drive the spread of resistance within particular species. Thus, it is vitally important to reveal and track the spread of such clones and the mechanisms by which they acquire antibiotic resistance and enhance their survival skills. Currently, the analysis of whole genome sequences for bacterial isolates of interest is increasingly used for these purposes, including epidemiological surveillance and developing of spread prevention measures. However, the availability and uniformity of the data derived from the genomic sequences often represents a bottleneck for such investigations. In this dataset, we present the results of a comprehensive genomic epidemiology analysis of 17,546 genomes of a dangerous bacterial pathogen Acinetobacter baumannii. Important typing information including multilocus sequence typing (MLST)-based sequence types (STs), intrinsic blaOXA-51-like gene variants, capsular (KL) and oligosaccharide (OCL) types, CRISPR-Cas systems, and cgMLST profiles are presented, as well as the assignment of particular isolates to nine known international clones of high risk. The presence of antimicrobial resistance genes within the genomes is also reported. These data will be useful for researchers in the field of A. baumannii genomic epidemiology, resistance analysis and prevention measure development.

Chronic kidney disease (CKD) is a progressive condition of kidney dysfunction due to diverse causes of injury. In healthy kidneys, protein-bound uremic toxins (PBUTs) are cleared from the systemic circulation by proximal tubule cells through the concerted action of plasma membrane transporters that facilitate their urinary excretion, but the endogenous metabolites are hardly removed with kidney dysfunction and may contribute to CKD progression. Accumulating evidence suggests that senescence of kidney tubule cells influences kidney fibrosis, the common endpoint for CKD with an excessive accumulation of extracellular matrix (ECM). Senescence is a special state of cells characterized by permanent cell cycle arrest and limitation of proliferation, which promotes fibrosis by releasing senescence-associated secretory phenotype (SASP) factors. The accumulation of PBUTs in CKD causes oxidative stress and increases the production of inflammatory (SASP) factors that could trigger fibrosis. Recent studies provide some clues that PBUTs may also promote senescence in kidney tubular cells. This review provides an overview on how senescence contributes to CKD and the involvement of PBUTs in this process, and how kidney senescence can be studied, Finally, some suggestions for future therapeutic options for CKD while targeting senescence are given.

Bacteria’s ability to withstand the detrimental effects of antimicrobials may take the form of resistance or tolerance with the minimum inhibitory concentration (MIC), the mutant prevention concentration (MPC), and the mutant selection window as salient concepts. Isolates exposed for 30 days to different concentrations of selected antibiotics, biocides, and heavy metals, singly and in combination, were additionally exposed to very high (15 × MIC) concentrations of ampicillin., and their tolerance was calculated the time to kill 99.9% of the isolate population (MDK99.9). These values were increased by 30 to 50% in test isolates compared to the untreated control. BAC 10-exposed isolates had the highest tolerance increase, and the tolerance appeared to originate from two sources, i.e., stochastic persistence and genetic-induced persistence, involving multiple genes using diverse mechanisms. The mutant selection window of the isolates to ampicillin, amoxicillin, and oxytetracycline also slightly increased compared to the control, indicating the amplification of persister cells during the 30-day exposure. These findings indicate that bacterial exposure to sub-inhibitory concentrations of environmental chemical stressors may not always result in the development of antimicrobial resistance but could initiate this process by selecting for persisters that could evolve into resistant isolates.

Abstract: Background: The diagnosis of nasal airway disorders relies on questionnaires, subjective data, and objective data. Interpretation of objective data obtained from measurement technology is not well understood by providers and researchers who use the equipment to test nasal airway function, justifying the need to cre-ate a new clinical tool. The Davidson Airway Function & Nasal Evaluation (DAFNE) Scoring System is a web-based scoring system that allows healthcare providers (MDs, PAs, PTs, APRNs, DMDs, DDSs, SLPs, and DCs) and researchers who treat nasal obstruction and breathing disorders to make more accurate diagnostic decisions, select the appropriate treatment for individualized patient care, monitor treatment progression and outcomes, and show how to approach a collaborative care model with other healthcare professionals. The current technologies, such as 4-phase rhinomanometry, use a simple approach that relies on a measurement tracing intersecting a color-coded y-axis on a four-quadrant graph with diagnostic numeric data output de-scribing nasal airflow and resistance. This is a good source of biofeedback demonstrating abnormal nasal breathing patterns but lacks interpretation guidelines to describe the severity of disease. The more sophisti-cated proprietary DAFNE approach uses multiple parameters which include airflow restriction, speed, vol-ume, and patient characteristics to identify patients’ disease progression much more accurately. Additionally, it explains how to segregate patients into appropriate treatment options which minimizes risks and compli-cations associated with sleep and breathing disorders while improving patient outcomes. Methods: Electronic searches of PubMed, MEDLINE, EMBASE Cochrane Library, and Scopus of publications between 1988-2022 were necessary to identify studies which determined the ranges of nasal function measurement parameters among three airway measurement technologies used in writing the DAFNE Score algorithm. The performance of DAFNE was evaluated compared to the research data and patient demographics used in previous studies. Results: By using primary outcome measurements from the literature, we were able to create a reliable, re-peatable, and validated tool to facilitate patient identification, treatment stratification, and collaboration for sleep and nasal breathing dysfunction. Subsequently, we found DAFNE could be used to identify the appro-priateness of a sleep study. Conclusions: DAFNE Scoring System has demonstrated the ability to detect high risk patients in the pediatric and adult populations susceptible of sleep apnea and breathing dysfunction needing a sleep study and treatment to improve nasal airway function and sleep. DAFNE Scoring System should be used as an adjunct tool in routine clinical practice and research to further understand the technol-ogy data output, identify patients at risk, stratify treatment options, progress, and stabilization after treatment, and how to collaborate with other healthcare providers to improve patient outcomes.

Background: The Davidson Airway Function &amp; Nasal Evaluation (DAFNE) Scoring System was developed as an intuitive and research-based scoring system that could be validated through beta testing and easily introduced to healthcare providers of several subspecialties who treat nasal obstruction and breathing disorders (MDs, PAs, PTs, APRNs, DDSs, and DCs). This scoring system was shown to increase the knowledge of airway function, nasal measurement parameters, and identification of proper treatment options for sleep and breathing disorders. The basis for the DAFNE score was developed from a systematic review of nasal measurement data. Methods: Electronic searches of PubMed, MEDLINE, EMBASE Cochrane Library, and Scopus of publications between 1988-2022 were used to identify studies validating nasal function measurement parameters to create the algorithm for the DAFNE Score™. The systematic review was accomplished using the 2020 ‘Preferred Reporting Items for Systematic Reviews’ (PRISMA) guidelines. Results: Twenty studies met the inclusion criteria for systematic review. Primary outcomes measurements demonstrated reliability, repeatability and validity of the DAFNE measurement technologies, data and output. Conclusions: The data analysis and systematic review uncovered a need and framework to develop and validate a web-based software algorithm for global access to improve the understanding of data interpretation of nasal measurements from three nasal measurement technologies. DAFNE Scoring should be used as an adjunct tool in routine clinical practice and research to further understand the technology data output and how to collaborate with other healthcare providers to improve patient outcomes.

The three-armed cluster-randomized trial ARena (Sustainable reduction of antibiotic-induced antimicrobial resistance) aimed to foster appropriate antibiotic use and reduce overprescribing in German ambulatory care to counter antibiotic resistance. Multi-faceted interventions targeted primary care physicians, teams and patients. This study examined effectiveness of the implementation program. ARena was conducted in 14 primary care networks with 196 practices. All arms received data-based feedback on antibiotics prescribing and quality circles. Arms II and III received different add-on components each. Primary outcome examined is the prescribing rate for systemic antibiotics for cases with non-complicated acute infections (upper respiratory tract, bronchitis, sinusitis, tonsillitis, otitis media). Secondary outcomes refer to prescribing of quinolones and guideline-recommended antibiotics. Based on pseudonymized quarterly claims data, mixed logistic regression models examined pre-post intervention antibiotic prescribing rate changes and compared to matched standard care. A significant rate reduction (arm I 11.7%; arm II 9.9%; arm III 12.7%) and significantly lower prescribing rates were observed for all arms (20.1%, 18.9% and 23.6%) compared to matched standard care (29.4%). Fluoroquinolone prescribing was reduced in all intervention arms and rates for recommended substances generally increased. No significant post-interventional difference between intervention arms was detected. Findings indicate implementation program impact compared to standard care. Trial registration: ISRCTN, ISRCTN58150046

As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.

This review paper gives Excel functions for highly precise Colebrook’s pipe flow friction approximations developed by users. All shown codes are implemented as User Defined Functions – UDFs written in Visual Basic for Applications – VBA, a common programming language for MS Excel spreadsheet solver. Accuracy of the friction factor computed using nine to date the most accurate explicit approximations is compared with the sufficiently accurate solution obtained through an iterative scheme which gives satisfying results after sufficient number of iterations. The codes are given for the presented approximations, for the used iterative scheme and for the Colebrook equation expressed through the Lambert W-function (including its cognate Wright ω-function). The developed code for the principal branch of the Lambert W-function has additional and more general application for solving different problems from variety branches of engineering and physics. The approach from this review paper automates computational processes and speeds up manual tasks.