A novel series of thiazole based-1,3,4-thiadiazoles were designed and prepared via the reaction of the 2-(4-methyl-2-phenylthiazole-5-carbonyl)-N-phenylhydrazinecarbothioamide with the appropriate hydrazonoyl chlorides. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Thirteen new 1,3,4-thiadiazoles have been evaluated for their anticancer activity against liver carcinoma cell line (HepG2). Also, their structure activity relationship (SAR) was studied. The 1,3,4-thiadiazoles 12d, 12c, 6g,18b, 6c, and 6f(IC₅₀ = 0.82, 0.91, 1.06, 1.25, 1.29 and 1.88 µM, respectively) have promising antitumor activity against liver carcinoma cell line (HepG2).

Epilepsy is known to cause alterations in neural networks. However, many details of these changes remain poorly understood. The objective of this study was to investigate changes in the properties of hippocampal CA1 pyramidal neurons and their synaptic inputs in a rat lithium-pilocarpine model of epilepsy. In the chronic phase of the model, we found a marked loss of pyramidal neurons in the CA1 area. However, the membrane properties of the neurons remained essentially unal-tered. The results of the electrophysiological and morphological studies indicate that the direct pathway from the entorhinal cortex to CA1 neurons is reinforced in epileptic animals, whereas the inputs to them from CA3 are either unaltered or even diminished. In particular, the dendritic spine density in the str. lacunosum moleculare, where the direct pathway from the entorhinal cortex ter-minates, was found to be 2.5 times higher in epileptic rats than in control rats. Furthermore, the summation of responses upon stimulation of the temporoammonic pathway was enhanced by approximately twofold in epileptic rats. This enhancement is believed to be a significant con-tributing factor to the heightened epileptic activity observed in the entorhinal cortex of epileptic rats using an ex vivo 4-aminopyridine model.

Spinal cord tumors, though rare, present formidable challenges in clinical management due to their intricate nature. Traditional treatment modalities like surgery, radiation therapy, and chemotherapy have been the mainstay for managing these tumors. However, despite significant advancements, challenges persist, including the limitations of surgical resection and the potential side effects associated with radiation therapy. In response to these limitations, a wave of innovative approaches is reshaping the treatment landscape for spinal cord tumors. Advancements in gene therapy, immunotherapy, and targeted therapy are offering groundbreaking possibilities. Gene therapy holds the potential to modify the genes responsible for tumor growth, while immunotherapy harnesses the body's own immune system to fight cancer cells. Targeted therapy aims to strike a specific vulnerability within the tumor cells, offering a more precise and potentially less toxic approach. Additionally, novel surgical adjuncts are being explored to improve visualization and minimize damage to surrounding healthy tissue during tumor removal. These developments pave the way for a future of personalized medicine for spinal cord tumors. By delving deeper into the molecular makeup of individual tumors, doctors can tailor treatment strategies to target specific mutations and vulnerabilities. This personalized approach offers the potential for more effective interventions with fewer side effects, ultimately leading to improved patient outcomes and a better quality of life. This evolving landscape of spinal cord tumor management signifies the crucial integration of established and innovative strategies to create a brighter future for patients battling this complex condition.

Polystyrene (PS) is an extremely stable polymer with relatively high molecular weight and a strong hydrophobic character that makes it highly resistant to biodegradation. In this study, PS was subjected to biodegradation tests by Tenebrio Molitor (T. Molitor) and Zophobas Morio (Z. Morio) larvae. Specifically, six different experimental diets were compared: (i) T. Molitor fed with bran; (ii) T. Molitor fed only PS; (iii) T. Molitor fed only PS treated with H2O2; (iv) Z. Morio fed with bran; (v) Z. Morio fed only PS and (vi) Z. Morio fed only PS treated with H2O2. Therefore, the mass change of the larvae and the survival rate were measured periodically, while the frass collected after 15 and 30 days were analyzed by different analyses, such as spectroscopy (FTIR), spectrometry (molecular weight and polydispersity), and microscopy (scanning electron microscopy observations). The obtained results suggest that in the case of T. Molitor larvae, larvae feeding on bran showed the highest survival rate of ~94 % at 30 days, while in the case of the Z. Morio larvae, the highest survival rate was exhibited by larvae eating PS-H2O2. Although not strongly pronounced, the Mw and Mn of PS frass of both T. Molitor and Z. Morio larvae decreased over 30 days, suggesting the Ps biodegradation. Finally, the morphological analysis shows that PS samples isolated from the frass of T. Molitor and Z. Morio larvae showed completely different, rough and irregularly carved surface structures, in comparison to PS before biodegradation.

Lower limb exoskeletons have the potential to reduce the prevalence of work-related musculoskeletal disorders; however, they often lack user-oriented control strategies. Human-in-the-loop (HITL) controls can adapt an exoskeleton’s assistance in real-time, to optimize the user-exoskeleton interaction. This study presents a HITL control for a knee exoskeleton to minimize the users’ physical effort, a parameter innovatively evaluated by their interaction torque with the exoskeleton (a muscular effort indicator) and metabolic cost. This work innovates by estimating the user’s metabolic cost within the HITL control through a machine-learning model. The regression model was able to estimate the metabolic cost, in real-time, with a root-mean-squared error of 0.66 W/kg and a mean absolute percentage error of 26%, making faster (10s) and less noisy estimations than a respirometer (K5, Cosmed) device. The HITL reduced the user’s metabolic cost and interaction torque by 7.3% and 32.3%, respectively, when compared to a zero-torque control. The developed HITL control surpassed both a non-exoskeleton and a zero-torque condition regarding the user’s physical effort, even for a simple task such as slow walking. Furthermore, the user-specific control enabled a lower metabolic cost than the non-user-specific assistance. This proof-of-concept demonstrated the potential for HITL controls in assisted working.

Vimentin has been reported to play diverse roles in cell processes such as spreading, migration, and cell-matrix adhesion. Here, we use vimentin knock out cells (Vim KO) to assess how vimentin impacts cell spreading, morphology, and myofibroblast transformation of human corneal fibro-blasts. Overall, loss of vimentin did not significantly impact corneal fibroblast spreading, as indicated by Vim KO morphology and mechanical activity (traction force). However, we found that Vim KO cells had reduced elongation in response to PDGF as compared to controls. Furthermore, absence of vimentin did not completely block TGFβ induced myofibroblast transformation, since αSMA protein expression was detected in Vim KO cells. Nonetheless, the degree of transformation and amount of αSMA protein was reduced as compared to control cells. Proteomics showed that Vim KO cells cultured in TGFβ had a similar pattern of protein expression as controls. One exception included periostin, an ECM protein associated with wound healing and fibrosis in other cell types, which was highly expressed only in Vim KO cells. We also demonstrate for the first time that LRRC15, a protein previously associated with myofibroblast transformation of cancer-associated fibroblasts, is also expressed by corneal myofibroblasts. Overall, our data shows that vimentin has a limited, yet measurable impact on corneal fibroblast spreading and myofibroblast transformation. We also identified novel proteins that may regulate corneal myofibroblast transformation in the presence and/or absence of vimentin.

Synaptic transmission is essential for nervous system function and the loss of synapses is a known major contributor to dementia. Alzheimer’s disease dementia (ADD) is characterized by synaptic loss in the mesial temporal lobe and cerebral neocortex, brain areas associated with memory and cognition. The association of synaptic loss and ADD was established in the late 1980s and it has been estimated that 30-50% of neocortical synaptic protein is lost in ADD, but there has not yet been a quantitative profiling of different synaptic proteins in different brain regions in ADD from the same individuals. Very recently, PET imaging of synapses is being developed, accelerating the focus on the role of synaptic loss in ADD and other conditions. In this study, we quantified densities of two synaptic proteins, the presynaptic protein SNAP25 and the postsynaptic protein PSD95 in human brain using enzyme-linked immunosorbent assays (ELISA). Protein was extracted from the cingulate, hippocampus, frontal, visual, and entorhinal cortex from cognitively unimpaired controls, subjects with mild cognitive impairment (MCI) and demented subjects with different levels of Alzheimer’s pathology. SNAP25 is significantly reduced in ADD when compared to controls in frontal cortex, visual cortex and cingulate; while hippocampus showed a smaller, non-significant reduction and entorhinal cortex concentrations were not different. In contrast, all brain areas showed lower PSD95 concentrations in ADD when compared to non-demented controls, although in hippocampus this failed to reach significance. Interestingly, cognitively unimpaired cases with high levels of AD pathology had higher levels of both synaptic proteins in all brain regions. SNAP25 and PSD95 concentrations significantly correlated with densities of neurofibrillary tangles, amyloid plaques and Mini Mental State Examination scores. Our results suggest that synaptic transmission is affected by ADD in multiple brain regions. Differences were less marked in entorhinal cortex and hippocampus, most likely due to a ceiling effect imposed by the very early development of neurofibrillary tangles in older people in these brain regions.

This prospective observational cohort pilot study included 22 cats diagnosed with partial traumatic brachial plexus injury (PTBPI), aiming to explore the response of an early intensive neurorehabilitation protocol in a clinical setting. This protocol included functional electrical stimulation (FES), locomotor treadmill training and kinesiotherapy exercises, starting at the time with highest probability of nerve repair. The synergetic benefits of this multimodal ap-proach were based on the potential structural and protective role of proteins and release of neurotrophic factors. Furthermore, parametrization of FES was according to the presence or absence of deep pain. Results have shown that 72.6% (16/22) cats achieved ambulation, with 9 cats within 15 days, 2 cats until 30 days and 5 cats until 60 days. During the 4 years follow-up, there was evidence of improvement on both muscle mass and muscle weakness, in addition to the disappearance of neuropathic pain. Notably, after the 60 days of neurorehabilitation, 3 cats improved ambulation after arthrodesis of the carpus. Thus, early rehabilitation, with FES ap-plied at the first weeks after injury and accurate parametrization according to the deep pain perception, is suggestive to help in functional recovery and ambulation, reducing probability of amputation.

Background: Nurses are essential members of the healthcare workforce and were among the first line carers for patients in community and hospital settings during the COVID-19 pandemic. As a result, they were at a heightened risk of contracting the disease, resulting in a significant number of reported deaths among them. Several preventive measures were adopted to contain the spread of this potentially lethal virus. This study aims to explore the knowledge, attitudes, and practices (KAP) of nurses regarding hand hygiene, mask wearing, and social distancing measures in healthcare settings in Barbados during the COVID-19 pandemic. Method: An online survey of nurses working in public hospitals and polyclinics (public primary care clinics) of Barbados from December 2020 to July 2021, was conducted. Participants completed a questionnaire capturing socio-demographic information and knowledge and practices related to hand hygiene, using face masks, and social distancing . Each correct response received one mark. Overall knowledge scores were categorized as poor (<60%), average (60-80%), or good (>80-100%). Results: Of 192 participants, the majority were female (82.8%) and had >5 years of experience (82%). Findings revealed that 45.8% had poor knowledge of hand hygiene, and the knowledge of 43.8% of respondents was average. Multivariable logistic regression showed that, after adjustment for age and gender, registered nurses had 2.1 times increased odds (95% CI 1.0, 4.2) of having good knowledge compared to other nursing categories. Regarding mask-wearing, 53.6% of nurses had average and 27.1% had good knowledge. Multivariable logistic regression showed that, after adjustment for age and gender, registered nurses had 3.3 times increased odds (95% CI 1.5, 7.4) of having good knowledge compared to nursing assistants. 68.6% of respondents followed the correct steps of handwashing every time, and 98.3% wore a mask in public places. More than half of the nurses (51.2%) kept a safe distance from others to avoid spreading SARS-CoV-2; one-third were in a crowded place(s) in the past three months, and 55.8% usually followed guidelines for social isolation as recommended by WHO. Conclusion: The study identified knowledge deficiencies related to hand hygiene and wearing masks among nurses. It is imperative to provide additional training on infection control measures.

Abstract Introduction. Burnout syndrome develops as a consequence of chronic stress among employees. The study objectives were to examine burnout syndrome and to evaluate the quality of life among security employees of the professional private security sector in Central Serbia. Methods. A multicenter cross-sectional questionnaire-based study was performed. The questionnaire for staff employed at institutions who are in direct contact with people (Human Services Survey, MBI-HSS) and Short Form 36 Health Survey-(SF-36). Results. A total of 353 respondents participated in the study. The response rate was 80%. Approximately one-third (32.6%) had symptoms of total burnout, and a much higher number of responders had a moderate or high level of burnout on individual subscales:- depersonalization (high 82.4%, moderate 16.2%) and emotional exhaustion (high 66.3%, moderate 19.8%) and, slightly more than one-third (34.5%) had low personal achievement, while about one-third (32.9%) had moderate personal achievement. Female sex and older age were associated with a higher risk of total burnout and the development of emotional exhaustion. Male sex, higher education, and managerial position were associated with higher personal achievement and lower risk of total burnout. Male sex, marital union, two or more children, and direct contact with clients were significantly associated with a lower quality of life of employees. Conclusion. Female sex and older age were associated with a higher risk of total burnout and the development of emotional exhaustion. Male sex, university education and managerial position were associated with greater personal achievement and were protective factors in relation to the development of burnout. Male sex, marital union, two or more children, and direct contact with clients were significantly associated with lower quality of life of employees. Keywords: burnout syndrome; security employees; professional private sector; quality of life

Zika virus (ZIKV) is a widespread mosquito-borne pathogen. Phylogenetically, two lineages of the ZIKV are distinguished: African and Asian-American. The latter became the cause of the 2015-2016 pandemic with severe defeat to newborns. In West African countries the African lineage has been found, but there is evidence of the emergence of Asian-American lineage in Cape Verde and Angola. This highlights the need not only to monitor the ZIKV, but also to sequence the isolates. In this article, we present a case report of Zika fever in a pregnant woman from Guinea, identified in 2018. Viral RNA was detected by qRT-PCR in serum sample. In addition, seroconversion of anti-Zika IgM and IgG antibodies was detected in repeated blood samples. Subsequently, the virus was isolated in C6/36 cell line. The detected ZIKV belonged to the African lineage, the Nigerian sublineage. The strains with the closest sequences were isolated from mosquitoes in Senegal in 2011 and 2015. In addition, we conducted serological screening of 116 blood samples collected from patients presenting to the hospital of Faranah with fevers during the period 2018-2021. As a result, it was found that IgM-positive patients occurred each year, seroprevalence varied between 5.6% and 17.1%.

Background. Private security refers to the security protection services that private security organizations provide to control crimes, protect lives and other assets, and to maintain order at their employers’ facilities. The objective of the study was to analyze the burnout syndrome and the quality of life among security employees of the professional private security sector in Central Serbia. Methods. A multicenter cross-sectional questionay-based study was performed in seven different cities in central Serbia. The study included the representative sample of security staff employed. The study was performed in the period from March 3, 2019 to April 30, 2019. Results. A total of 353 respondents (330 male and 23 female) participated in the study. The Response rate was 80%. Men were significantly older than women: 44.09±11.44 vs. 36.91±7.92 (F=8.752; p=0.003). Approximately one third (32.6%) had symptoms of total burnout and a much higher number of responders had moderate or high level of burnout in individual subscales; in emotional exhaustion (high 66.3%, moderate 19.8%), in depersonalisation (high 82.4%, moderate 16.2%) and slightly more than one third 34.5% had low personal achievement, about one third 32.9% had moderate personal achievement. Our study has shown that female sex and older age were associated with higher risk of total burnout and for the development of emotional exhaustion. Male sex, university education and managerial position were associated with higher personal achievement and lower risk of of total burnout because this subscale is inversely correlated with the burnout. Male sex, marritual union, two and more childreen and direct contact with clients were significantly associated with lower quality of life of employees. Conclusion. Nearly one third (32.6%) of security employees had symptoms of total burnout. Female sex and older age were associated with higher risk of total burnout and for the development of emotional exhaustion. Male sex and higher level of education were associated with greater personal achievement. Managerial position and higher education were protective factors in relation to the development of burnout. Male sex, marritual union, two and more childreen, direct contact with clients were significantly associated with lower quality of life of employees. security staff, professional private sector, quality of life

Advanced MRI methods and PET using radiolabeled amino acids provide valuable information in addition to conventional MR imaging for brain tumor diagnostics. These methods are particularly helpful in challenging situations such as the differentiation of malignant processes from benign lesions, the identification of non-enhancing glioma subregions, the differentiation of tumor progression from treatment-related changes, and the early assessment of response to anticancer therapy. The debate over which of the methods is preferable in which situation is ongoing and has been addressed in numerous studies. Currently, most radiology and nuclear medicine departments perform these examinations independently of each other leading to multiple examinations for the patient. The advent of hybrid PET/MRI allowed a convergence of the methods but to date simultaneous imaging has reached little relevance in clinical neuro-oncology. This is partly due to the limited availability of hybrid PET/MRI scanners, but is also due to the fact that PET is a second-line examination in brain tumors. PET is only required in equivocal situations, and spatial co-registration of PET examinations of the brain to previous MRI is possible without disadvantage. A key factor for the benefit of PET/MRI in neuro-oncology is a multimodal approach that provides decisive improvements in the diagnostics of brain tumors compared with a single modality. This systematic review focuses on studies that were able to demonstrate the additive value of amino acid PET and ‘advanced’ MRI in the diagnosis of brain tumors. Available studies suggest that the combination of amino acid PET and advanced MRI improves grading and the histomolecular characterization of newly diagnosed tumors. However, data concerning the delineation of tumor extent and biopsy guidance are of limited value. A clear additive diagnostic value of amino acid PET and advanced MRI can be achieved regarding the differentiation of tumor recurrence from treatment-related changes. Here, PET-guided evaluation of advanced MR methods seems to be helpful. In summary, there is growing evidence that a multimodal approach can achieve decisive improvements in the diagnostics of brain tumors, for which hybrid PET/MRI offers optimal conditions.

The ongoing emergence of SARS-CoV-2 virus variants remains a source of concern because it is accompanied by the potential for increased virulence as well as evasion of immunity. Here we show that, although having an almost identical spike gene sequence as another Omicron variant (BA.5.2.1), a BA.4 isolate lacked all the typical disease characteristics of other isolates seen in the Golden Syrian hamster model despite replicating almost as effectively. Animals infected with BA.4 had similar viral shedding profiles to that seen with BA.5.2.1 (up to day 6 post infection) but they all failed to lose weight or present with any other significant clinical signs. We hypothesize that this lack of detectable signs of disease during infection with BA.4 was due to a small (nine nucleotide) deletion (∆686-694) in the viral genome (ORF1ab) responsible for production of non-structural protein 1 which resulted in the loss of three amino acids (aa 141-143).

Pattern recognition techniques form the heart of most, if not all, incoherent linear shift-invariant systems. When an object is recorded using a camera, the object information gets sampled by the point spread function (PSF) of the system, replacing every object point with the PSF in the sensor. The PSF is a sharp Kronecker Delta-like function when the numerical aperture (NA) is large with no aberrations. When the NA is small, and the system has aberrations, the PSF appears blurred. In the above case, if the PSF is known, then the object information can be obtained by scanning the PSF over the recorded object intensity pattern and looking for pattern matching conditions through a mathematical process called correlation. In this study, a recently developed deconvolution method, the Lucy-Richardson-Rosen algorithm (LR2A), has been implemented to computationally refocus images recorded in the presence of spatio-spectral aberrations. The performance of LR2A was compared against the Lucy-Richardson algorithm and non-linear reconstruction. LR2A exhibits a superior deconvolution capability even in extreme cases of spatio-spectral aberrations and blur. Experimental results of deblurring a picture captured using high-resolution smartphone cameras are presented. LR2A was implemented to significantly improve the performances of the widely used deep convolutional neural networks for image classification.

To assess the efficacy of washing cloth masks, we simulated SARS-CoV-2 contamination in tricoline fabric and tested decontaminants to reduce viral particles. Viral suspensions using two variants (B.1.1.28 and P.1) were inoculated in these fabrics, and the inactivation kinetics were evaluated after washing with various household disinfection products (Soap powder, Lysoform®, Hypochlorite sodium and 70% Alcohol), rinse numbers, and exposure times. Afterward, the fabrics were washed in sterile water, viral RNA extracted and amplified using RT-qPCR. Finally, viral replication in cell cultures was examined. Our findings show that all biocidal treatments successfully disinfected the tissue tested. Some products showed less reduction in viral loads, Soap powder (1.60 x 104, 1.04 x 103), Soap powder and Lysoform® (1.60 x 104, 1.04 x 103) and Alcohol 70% (1.02 x 103, 5.91 x 101) respectively. However, when sodium hypochlorite was used, this reduction was significantly increased (viral inactivation in 100% of the washes). After the first wash, the reduction of viral particles was greater for the P.1 variant than for the B.1.1.28 variant (W = 51759, p 0.05). In conclusion the sodium hypochlorite role on cloth masks disinfection may also have implications for future health emergencies as well as recommended by WHO.

Triglycerides of waste cooking oil reacted with methanol in refluxing toluene to yield mixtures of diglycerides, monoglycerides and fatty acid methyl esters (FAMEs) in the presence of 20% (w/w) catalyst/oil using the hydrophilic sulfonated silica (SiO₂-SO₃H) catalyst alone or with the addition of 10% (w/w) co-catalyst/oil [(Bun4N)](BF₄) or Aliquat 336]. The addition of the ammonium salts to the catalyst lead to a decrease in the amounts of diglycerides in the products, but the concentrations of monoglycerides increased. Mixtures of [(Bun4N)](BF4)/catalyst were superior to catalyst alone or Aliquat 336/catalyst for promoting the production of mixtures with high concentrations of FAMEs. The same experiments were repeated using DMSO as the solvent. The use of the more polar solvent resulted in excellent conversion of the triglycerides to FAME esters with all three-catalyst media. A simplified mechanism is presented to account for the experimental results.

Abstract: In 2016, we conducted an entomological survey in a railway transect between Banfora and Ouagadougou, Burkina Faso. The aim was to evaluate the risk factors for arbovirus epidemics, including vector infection status, in areas representative of the country. Aedes aegypti mosquitoes were collected at larval stage from four study sites and reared until adult stage and kept in RNAlater for detection of arbovirus RNA. In the laboratory, the mosquito specimens were screened for dengue virus (DENV) and chikungunya virus (CHIKV) using one step real-time qRT-PCR. We detected one DENV-2 positive pool from Ouagadougou, giving a minimum infec-tion rate (MIR) of 16.67, and 6 CHIKV positive pools, giving a MIR of 66.67 from Ouagadougou, but also in Banfora and Boromo. The qRT-PCR is a useful tool for the surveillance of arboviruses of public health importance in Burkina Faso and may be incorporated into disease surveillance and control programs in Burkina Faso.

The human gut microbiome includes beneficial, commensal and pathogenic bacteria that possess antimicrobial resistance (AMR) genes and exchange these predominantly through conjugative plasmids. Escherichia coli is a significant component of the gastrointestinal microbiome and is typically non-pathogenic in this niche. In contrast, extra-intestinal pathogenic E. coli (ExPEC) including ST131 may occupy other environments like the urinary tract or bloodstream where they express genes enabling AMR and host adhesion like type 1 fimbriae. The extent to which non-pathogenic gut E. coli and infectious ST131 share AMR genes and key associated plasmids remains understudied at a genomic level. Here, we examined AMR gene sharing between gut E. coli and ST131 to discover an extensive shared preterm infant resistome. In addition, individual ST131 show extensive AMR gene diversity highlighting that analyses restricted to the core genome may be limiting and could miss AMR gene transfer patterns. We show that pEK499-like segments are ancestral to most ST131 Clade C isolates, contrasting with a minority with substantial pEK204-like regions encoding a type IV fimbriae operon. Moreover, ST131 possess extensive diversity at genes encoding type 1, type IV, P and F17-like fimbriae, particular within subclade C2. The type, structure and composition of AMR genes, plasmids and fimbriae varies widely in ST131 and this may mediate pathogenicity and infection outcomes.

The world is facing a major health crisis, the global pandemic of COVID-19 caused by the SARS-CoV-2 coronavirus, for which no approved antiviral agents or vaccines are currently available. Here we describe a collection of codon-optimized coding sequences for SARS-CoV-2 cloned into Gateway-compatible entry vectors, which enable rapid transfer into a variety of expression and tagging vectors. The collection is freely available via Addgene. We hope that widespread availability of this SARS-CoV-2 resource will enable many subsequent molecular studies to better understand the viral life cycle and how to block it.

Coronaviruses are an extensive family of viruses that can cause disease in both animals and humans. The current classification of coronaviruses recognizes 39 species in 27 subgenera that belong to the family Coronaviridae. From those, at least seven coronaviruses are known to cause respiratory infections in humans. Four of these viruses can cause common cold-like symptoms, while others that infect animals can evolve and become infectious to humans. Three recent examples of this viral jumps include SARS CoV, MERS-CoV and SARS CoV-2 virus. They are responsible for causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the most recently discovered coronavirus disease during 2019 (COVID-19).COVID-19, a respiratory disease caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The rapid spread of the disease has taken the scientific and medical community by surprise. Latest figures from 14 April 2020 show more than 2 million people had been infected with the virus, causing more than 120,000 deaths in over 210 countries worldwide. The large amount of information we receive every day concerning this new disease is so abundant and dynamic that medical staff, health authorities, academics and the media are not able to keep up with this new pandemic. In order to offer a clear insight of the extensive literature available, we have conducted a comprehensive literature review of the SARS CoV-2 Virus and the Coronavirus Diseases 2019 (COVID-19).

Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Re-purposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), human immunodeficiency virus 1 (HIV-1), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FluAV), niclosamide against HSV-2, brequinar against HIV-1, and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vivo tests.

Electrostatic endothelial cell seeding has evolved as an exceptional technique to improve the efficiency of cell seeding in terms of frequency of attached cells and the amount of cell adhesion for the treatment of vascular diseases. In the recent times, both untreated and superhydrophilic thin film nitinol (TFN) have exhibited strong prospect as substrates for creation of small-diameter endovascular grafts due to their hallmark properties of superelasticity, ultra low-profile character, grown hemocompatible oxide layer with the presence of a uniform endothelial layer on the surface. The purpose of the current study is to understand the effects of endothelial cell seeding parameters (i.e., applied voltage, incubation time, substrate chemistry and cell suspension solution) to investigate the cell seeding phenomenon and to improve the cell adhesion and growth on the TFN surface under electrostatic transplantation. Both parallel plate and cylindrical capacitor models were used along with the Taguchi Design of Experiment (DOE) methods to design in vitro test parameters. A novel in vitro system for cylindrical capacitor model was created using a micro flow pump, micro incubation system, and silicone tubings. The augmented endothelialization on thin film nitinol was developed to determine the effect of cell seeding and deployed in a 6 Fr intravascular catheter setup. Cell viability along with morphology and proliferation of adhered cells were evaluated using fluorescent and scanning electron microscopy. Our results demonstrated that the maximum number of cells attached on STFN in the catheter was observed in 5V with the 2 hr exposure of in the cell culture medium (CCM) solution. The condition showed 5V voltage with 0.68×10-6 µC electrostatic charge and 5.11 V·mm-1 electric field. Our findings have first demonstrated that the electrostatic endothelialization on the superhydrophilic thin film nitinol endograft within the catheter prior to the endovascular procedure could enhance the biocompatibility for low-profile endovascular applications.

In the frame of our diversity-oriented research on multitarget small molecule anticancer agents, utilizing convergent synthetic sequences terminated by Sonogashira coupling reactions, a preliminary selection of representative alkyne-tethered vindoline hybrids was synthesized. The novel hybrids with additional pharmacophoric fragments of well-documented anticancer agents, including FDA-approved tyrosine-kinase inhibitors (imatinib and erlotinib) or ferrocene or chalcone units, were evaluated for their antiproliferative activity on malignant cell lines MDA-MB-231 (triple negative breast cancer), A2780 (ovarian cancer), HeLa (human cervical cancer) and SH-SY5Y (neuroblastoma) as well as human embryonal lung fibroblast MRC-5 served as reference non-malignant cell line for the assessment of the therapeutic window of the tested hybrids. The biological assays identified a trimethoxyphenyl-containing chalcone-vindoline hybrid (36) as a promising lead compound exhibiting submicromolar activity on A2780 cells with a marked therapeutic window. These results suggest that ovarian cancer might be considered as a prioritized target of treatment with 36.

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

We previously found that chronic adenosine A1 receptor stimulation with N6-Cyclopentyladenosine increased α-synuclein misfolding and neurodegeneration in a novel α-synucleinopathy model, a hallmark of Parkinson’s disease. Here, we aimed to synthesize a dimer caffeine-indan linked by a 6-carbon chain to cross the blood-brain barrier and tested its ability to bind α-synuclein, reducing misfolding, behavioural abnormalities, and neurodegeneration in our rodent model. Behavioural tests and histological stains assessed neuroprotective effects of the dimer compound. A rapid synthesis of the 18F-labelled analogue enabled Positron Emission Tomography and Computed Tomography imaging for biodistribution measurement. Molecular docking analysis showed that the dimer binds to α-synuclein N- and C-termini and the non-amyloid-β-component (NAC) domain, similar to 1-aminoindan, and this binding promotes a neuroprotective α-synuclein “loop” conformation. The dimer also binds to the orthosteric binding site for adenosine within the adenosine A1 receptor. Immunohistochemistry and confocal imaging showed the dimer abolished α-synuclein upregulation and aggregation in the substantia nigra and hippocampus, and the dimer mitigated cognitive deficits, anxiety, despair, and motor abnormalities. The 18F-labelled dimer remained stable post-injection and distributed in various organs, notably in the brain, suggesting its potential as a Positron Emission Tomography tracer for α-synuclein and adenosine A1 receptor in Parkinson’s disease therapy.

The COVID-19 pandemic underscores the significance of vaccine hesitancy in shaping vaccination outcomes. Understanding the factors underpinning COVID-19 vaccination hesitancy is crucial for tailoring effective vaccination strategies. This cross-sectional study, conducted in three communities across the United States and Lebanon, employed surveys to assess respondents' knowledge, attitudes, and perceptions regarding COVID-19 infection and vaccination. Among the 7,196 participants, comprising 6,775 from the US and 422 from Lebanon, vaccine hesitancy rates were comparable at 12.2% and 12.8%, respectively. Notably, a substantial proportion of respondents harbored misconceptions, such as attributing the potential to alter DNA (86.4%) or track individuals (92.8%) to COVID-19 vaccines, and believing in the virus's artificial origins (81%). Primary determinants of hesitancy included perceptions that the vaccine poses greater risk than the infection itself (aOR = 8.7 and 9.4, respectively) and negative recommendations from healthcare providers (aOR = 6.5 and 5.4, respectively). Conversely, positive endorsements from healthcare providers were associated with reduced hesitancy (aOR = 0.02 and 0.4, respectively). Targeting healthcare providers to dispel misinformation and elucidate COVID-19 vaccine risks holds promise for enhancing vaccination uptake.

This is a single center retrospective study to assess safety and tolerability of continuous inhaled iloprost use as rescue therapy for refractory pulmonary hypertension (PH) in critically ill neonates and infants. Retrospective chart review was performed on 58 infants and data was collected at baseline, 1, 6, 12, 24, 48, and 72 hours of iloprost initiation. Primary outcomes were change in heart rate (HR), fraction of inspired oxygen (FiO2), mean airway pressures (MAP), blood pressure (BP) and oxygenation index (OI). Secondary outcomes were need for extracorporeal membrane oxygenation (ECMO) and death. 51 patients treated for > 6 hours were analyzed in 2 age groups, neonate (≤28 days: n=32) and infant (29-365 days: n=19). FiO2 (p

Kisspeptin (KISS1) and its cognate receptor (KISS1R) are implicated in the progression of various cancers. However, a theranostic radiopharmaceutical targeting the KISS1 receptor (KISS1R) has yet to be explored. A gallium-68 labelled kisspeptin-10 (KP10) has potential as a pan-tumor radiopharmaceutical for the detection of cancers. Furthermore, a lutetium-177 labelled KP10 could find therapeutic application in treating oncological diseases. We attached DOTA to the NH2-terminus of KP10 as we posited that this modification would not impair biological activity and showed that receptor stimulation of inositol phosphate accumulation in HEK293 transfected with the KISS1R gene was similar for KP10 and DOTA-KP10. We describe optimization of radiolabeling with gallium-68 and lutetium-177 and stability in serum, plasma, and whole blood. Pharmacokinetics was established with µPET/CT and ex vivo measurements. Dynamic studies with µPET/CT demonstrated that background clearance for the radiopharmaceutical was rapid with a blood half-life of 18 ± 3 minutes. DOTA-KP10 demonstrated preserved functionality at KISS1R and good blood clearance. These promising results advocate the further development of KP10 structures which have high binding affinity along with proteolytic resistance.

The retinal pigment epithelium (RPE) is a monolayer of epithelial cells lying between the neural retina and the choroid and is essential for photoreceptor function and viability. Quail Coturnix japonica is a convenient experimental animal model for the study of age and pathological retina processes to an accelerated time regime. The three main types of pigment granules present in the RPE are melanin-containing melanosomes, lipofuscin-containing lipofuscin granules, and mixed melanolipofuscin granules containing both melanin and lipofuscin. It’s known that with aging and pathology in RPE cells the content of melanosomes decreases but lipofuscin and melanolipofuscin granules accumulate. We examined melanolipofuscin granules in macular areas of the quail retina by transmission electron microscopy in young, middle-aged, and old birds, and in middle-aged birds irradiated with blue LED light (450 nm, 4 J/cm2). It has been shown that during photooxidative stress caused by the action of blue light on the quail eye, active fusion of melanosomes and lipofuscin granules occurs with formation of various types, including giant, mixed melanolipofuscin-like granules. Irradiation result in almost twofold decrease in the number of lipofuscin granules and synchronous increase in the number of melanolipofuscin-like granules. Increased accumulation of melanolipofuscin-like granules was also observed in non-irradiated old birds. It is assumed that the decrease in the number of melanosomes in the RPE during aging and photo-oxidative stress is associated with their fusion with lipofuscin granules and subsequent degradation of melanin by reactive oxygen species formed in melanolipofuscin-like granules. The disappearance of melanin deprives the RPE cells of light-filtering and antioxidant protection, and significantly increases the risk of their oxidative stress.

Background: Online survey-based observational cross-sectional study aimed at elucidating experience and attitudes of unstructured population regarding diagnostic imaging. Methods: Invitations to participate were distributed using mixed-mode design to deidentified residents aged 18 years and older. Main outcome measures included morbidity structure and incidence of diagnostic imaging administrations. Results: Respondents (n = 1069) aged 44.3 ± 14.4 years; 32.8% suffered from cardiovascular diseases (CVD); 9.5% had chronic respiratory pathology; 28.9% considered themselves healthy. Respondents with COVID-19 history (49.7%) reported higher rates of computed tomography (CT) (p &lt; .0001), magnetic resonance imaging (MRI) (p &lt; .001), and ultrasound (p &lt; .05). COVID-19 history in CVD respondents shifted imaging administrations towards CT and MRI (p &lt; .05). Every tenth respondent received MRI, CT, and ultrasound on paid basis; 29.0% could not pay for diagnostic procedures; 13.1% reported unavailable MRI. Professional status significantly affected the pattern of diagnostic modalities (p &lt; .05). MRI and CT availability differed between respondents in urban and rural areas (p &lt; .0001). History of technogenic events predisposed responders to overestimate diagnostic value of fluorography (p &lt; .05). Conclusions: Preparedness to future pandemics requires development of community-based outreach programs focusing on people's awareness regarding medical imaging safety and diagnostic value.

Ambulatory heart rate (HR) monitors that acquire electrocardiogram (ECG) or/and photoplethysmographm (PPG) signals from the torso, wrists, or ears are notably less accurate in tasks associated with high levels of movement compared to clinical measurements. However, reliable estimation of HR can be obtained through data fusion from different sensors. These methods are especially suitable for multimodal hearable devices, where heart rate can be tracked from different modalities, including electrical ECG, optical PPG, and sounds (heart tones). Combined information from different modalities can compensate for single source limitations. In this paper, we evaluate the possible application of data fusion methods in hearables. We assess data fusion for heart rate estimation from simultaneous in-ear ECG and in-ear PPG, recorded on eight subjects while performing 5-minute sitting and walking tasks. Our findings show that data fusion methods provide a similar level of mean absolute error as the best single-source heart rate estimation but with much lower intra-subject variability, especially during walking activities. We conclude that data fusion methods provide more robust HR estimation than a single cardiovascular signal. These methods can enhance the performance of wearable devices, especially multimodal hearables, in heart rate tracking during physical activity.

Background: Number of investigations, which are focused on arbuscular mycorrhiza fungi (AMF) biodiversity is still limited. The analysis of AMF taxa in the North Caucasus, a temperate biodiversity hotspot, used to be limited by the genera level. The aim of this study was to define AMF biodiversity at the species level in the North Caucasus biotopes. Methods: Molecular genetic identification of fungi was carried out with ITS1 and ITS2 regions as barcodes, sequencing by Illumina MiSeq, analysis of phylogenetic trees for individual genera, searching the operational taxonomic units (OTUs) with identification at the species level. Sequences from MaarjAM and NCBI GenBank were used as references. Results: We analyzed >10 million reads in soil samples for 3 biotopes to estimate fungal biodiversity. 50 AMF species from 20 genera were found. The valley biotopes (disturbed ecosystems, grasslands) were characterized by a greater AMF diversity, as well as the number of OTUs and species, in comparison with the forest biotopes. Conclusion: Our hypothesis is that high AMF biodiversity for the river valley can be associated with a higher percentage of annual plants in these biotopes, as well as with the active development of restorative successional processes.

Non-ulcerated cutaneous leishmaniasis (NUCL) is an atypical and peculiar clinical form of the disease that was first described by Ponce et al. (1988) in Honduras (Central America), where iso-lated or disseminated popular and/or nodular skin lesions are commonly seen in adolescents and young adults. Leishmania (L.) chagasi was then incriminated as the causal agent of the disease, as well as of American visceral leishmaniasis (AVL), although NUCL has been shown to be more prevalent than AVL in the region. Considering, however, the dubious taxonomic character of the causal agent of NUCL, as there is no evidence of this form of disease associated with L. (L.) cha-gasi in South America, this study aimed to carry out a retrospective taxonomic analysis on a se-ries of studies on the diagnostic approach to the Honduran parasite in loco (El Tigre island, Amapala municipality, west coast of Honduras), where taxonomic characters of a biological (in vitro and in vivo), epidemiological (vector and canine reservoir), clinical-immunological (im-munopathological features of in situ skin lesion and systemic infection) and molecular (ge-nomic/phylogenetic analyses) nature were considered. The findings, particularly those of mo-lecular nature, such as: the Honduran parasite showed to be more ancestral (molecular clock analysis of the DNA polymerase alpha subunit gene) than all viscerotropic ones [L. (L.) chagasi, L. (L.) donovani and L. (L.) infantum], as well as presenting an absolutely unprecedented structural variation on chromosome 17 and the highest frequency of genomic SNPs (more than twice the number seen in the Brazilian parasite), in addition to representing a different phylogenetic lin-eage (mainly in the NJ - RNA Pol II tree) from those viscerotropic ones, have pointed to the characterization of a new leishmanine parasite, Leishmania (Leishmania) poncei n. sp. (Kinetoplas-tea: Trypanosomatidae), in honor of Professor Ponce, who was the first researcher to describe NUCL in Honduras.

Glycated hemoglobin (HbA1c) is used to assess glycemic control in Type 1 diabetes (DM1) patients. Apolipoproteins play an essential role in DM1 pathophysiology and may be associated with complications, as well as HbA1c. This cross-sectional observational study consisting of 81 children and adolescents of both sexes diagnosed with DM1 investigated the relationship between body fat distribution and lean mass with HbA1C and apolipoprotein values analyzing biochemical and body composition measurements. Shapiro-Wilk test with Lilliefors correction, non-parametric Mann-Whitney test, and others were used with a significance level of 5%. The sample had a diagnosis time of 4.32 years and high blood glucose levels (mean 178.19 mg/dL) and HbA1c (mean 8.57%). Subjects also had a moderate level of adiposity, as indicated by arm and thigh fat areas. The study also found significant differences in the distribution of patients concerning levels of apolipoproteins A and B, with a smaller proportion of patients having undesirable levels. Finally, the study found a significant difference in the distribution of patients with estimated cardiovascular risk based on the ApoB/ApoA-1 ratio. Conclusively, visceral fat in children and adolescents with DM1 may increase the risk of DM1 long-term complications owing to its association with elevated HbA1C and apolipoprotein values.

Many studies of hypervelocity impact craters have described the characteristics of quartz grains shock-metamorphosed at high pressures of > 10 GPa. In contrast, few studies have investigated shock metamorphism at lower shock pressures. In this study, we test the hypothesis that low-pressure shock metamorphism occurs in near-surface nuclear airbursts and that this process shares essential characteristics with crater-forming impact events. To investigate low-grade shock microstructures, we compared quartz grains from Meteor Crater, a 1.2-km-wide impact crater, to those from near-surface nuclear airbursts at the Alamogordo Bombing Range, New Mexico in 1945 and Kazakhstan in 1949/1953. This investigation utilized a comprehensive analytical suite of high-resolution techniques, including transmission electron microscopy (TEM) and electron backscatter diffraction (EBSD). Meteor Crater and the nuclear test sites all exhibit quartz grains with closely-spaced, sub-micron-wide fractures that appear to have formed at low shock pressures. Significantly, these micro-fractures are closely associated with Dauphiné twins and are filled with amorphous silica (glass), widely considered a classic indicator of shock metamorphism. Thus, this study confirms that glass-filled shock fractures in quartz form during near-surface nuclear airbursts, as well as crater-forming impact events, and by extension, it suggests that they may form in any near-surface cosmic airbursts in which the shockwave is coupled to Earth’s surface. The robust characterization of such events is crucial because of their potential catastrophic effects on the Earth’s environmental and biotic systems.

The novel severe acute respiratory coronavirus-2 (SARS-Cov-2) constitutes the causative agent of coronavirus disease-2019 (COVID-19). Several mechanisms have been proposed regarding the development of cardiovascular complications during and after acute COVID-19 infection. COVID-19, caused by SARS-CoV-2, has emerged as one of the deadliest pandemics in modern history. Several clinical and pathophysiologic mechanisms have been proposed for development of cardiovascular complications during and after acute COVID-19 infection. The myocardial injury in patients with COVID-19 has been attributed to coronary spasm, microthrombi formation, plaque rupture, hypoxic injury or cytokine storm disposing the same pathophysiology with the three clinical variants of Kounis syndrome. One of the main proposed mechanisms for development of cardiovascular complications is the angiotensin converting enzyme 2 (ACE2) and its interactions with the renin-aldosterone system (RAAS) and the kinin-kallikrein system (KKS). The ACE2 receptors are expressed throughout the human body located mainly in heart, blood vessels endothelium, lungs, intestines, testes and neurons. The SARS-CoV-2 directly invades the endothelial cells that contain ACE2 receptors and constitutes the main pathway through which the virus enters the endothelial cells. This leads to downregulation of the ACE2 receptors and causes angiotensin II accumulation leading to prothrombotic effects such as hemostatic imbalance via activation of the coagulation cascade, impaired fibrinolysis, thrombin generation, vasoconstriction, endothelial and platelet activation, and pro-inflammatory cytokine release. Indeed, angiotensin I exerts no direct biological function except that its high levels can stimulate catecholamine production. It is metabolized to its biologically active byproduct angiotensin II, a potent vasoconstrictor, by angiotensin converting enzyme (ACE) through cleavage of the two terminal amino acids. SARS-CoV-2 infection prevents the counterbalancing action of the KKS system that normally causes vasodilation and regulates tissue repair, inflammation, cell proliferation, and platelet aggregation. All this cascade leads to the following cardiovascular events: cardiac arrhythmias, cardiac arrest, cardiomyopathy, cytokine storm, heart failure, ischemic myocardial injuries and microvascular disease, Kounis syndrome, long COVID, myocardial fibrosis, myocarditis, new onset hypertension, pericarditis, postural orthostatic tachycardia syndrome (POTS), pulmonary hypertension, stroke, Takotsubo Syndrome, venous thromboembolism and thrombocytopenia. In this narrative review we describe and elucidate when and how the COVID-19 affects the human cardiovascular system, in various areas on the human body that are vulnerable in every category of patients including children and athletes.

The interest on amorphous carbon thin films with low secondary electron yield (SEY) has been increasing in the last years, to mitigate electron multipacting in particle accelerators and in RF devices. Previous works found that the SEY increases with the hydrogen amount and correlates with the Tauc gap. In this work, we analyse films produced by magnetron sputtering with different contents of hydrogen and deuterium, incorporated via target poisoning and sputtering of CxDy molecules. XPS was implemented to estimate the phase composition of the films. The maximal SEY was found to decrease linearly with the fraction of the graphitic phase in the films. These results are supported by Raman scattering and UPS. The graphitic phase decreases almost linearly for hydrogen and deuterium concentrations between 12% and 46% (at.), but abruptly decreases when the concentration reaches 53%. This vanishing of the graphitic phase is accompanied by a strong increase of SEY and of the Tauc gap. These results suggest that the SEY is not dictated directly by the concentration of H/D but by the fraction of graphitic phase. The results are supported by a model used to calculate SEY of films consisting of a mixture of graphitic and polymeric phases.

Many studies of hypervelocity impact craters have described the characteristics of quartz grains shock-metamorphosed at high pressures of >10 GPa, but in contrast, few studies have investigated shock metamorphism at lower shock pressures. In this study, we test the hypothesis that low-pressure shock metamorphism occurs in near-surface nuclear airbursts and that this process shares important characteristics with impact-cratering events. To investigate low-grade shock microstructures, we compared quartz grains from Meteor Crater, a 1.2-km-wide impact crater, to those from near-surface nuclear airbursts at the Alamogordo Bombing Range, New Mexico in 1945 and Kazakhstan in 1949/1953. This investigation utilized a comprehensive analytical suite of high-resolution techniques, including transmission electron microscopy (TEM) and electron backscatter diffraction (EBSD). Meteor Crater and the nuclear test sites all exhibit metamorphosed quartz grains with closely-spaced, sub-micron-wide fractures that appear to have formed at low shock pressures. Importantly, these micro-fractures are closely associated with Dauphiné twins and are filled with amorphous silica (glass), widely considered to be a classic indicator of shock metamorphism. Thus, this study confirms that glass-filled shock fractures in quartz form during near-surface nuclear airbursts, as well as crater-forming impact events, and by extension, it suggests they also may form in near-surface cosmic airbursts.

To develop a modern plague vaccine, we used hypo-endotoxic Yersinia pestis bacterial ghosts (BGs) with combinations of genes encoding the bacteriophage ɸX174 lysis-mediating protein E and/or holin-endolysin systems from λ or L-413C phages. Expression of the protein E gene resulted in the BGs that retained the shape of the original bacterium. Co-expression of this gene with genes coding for holin-endolysin system of the phage L-413C caused formation of structures resembling collapsed sacs. Such structures, which have lost their rigidity, were also formed as a result of the expression of only the L-413C holin-endolysin genes. Similar holin-endolysin system from phage λ containing mutated holin gene S and intact genes R-Rz coding for the endolysins caused generation of mixtures of BGs that had (i) practically preserved and (ii) completely lost their original rigidity. The addition of protein E to the work of this system shifted the equilibrium in the mixture towards the collapsed sacs. The collapse of the structure of BGs can be explained by endolysis of peptidoglycan sacculi. Immunizations of laboratory animals with the variants of BGs followed by infection with a wild-type Y. pestis strain showed that bacterial envelopes protected only cavies. BGs with peptidoglycan maximally hydrolyzed had a greater protectivity compared to BGs with preserved peptidoglycan skeleton.

Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Current patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, SI-compliant standard provides a way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, based on an expert-scientific consensus and expressed according to this new measurement standard. These recommendations are supported by a comprehensive analysis of the sensitivity of human ‘non-visual’ responses to ocular light, are centred on an easily measured quantity (melanopic equivalent daylight (D65) illuminance), and provide a straightforward framework to inform lighting design and practice.

There is evidence that optimal nutrition is fundamental to human health and in the prevention of non-communicable diseases (NCDs) later in adult life. The identification, production and consumption of functional foods worldwide can increase health benefits for all who can access and afford such foods subject to advice from nutritionists. Recent meetings organized by the health agencies, give a crucial opportunity to make nutrition, a central part of the post-2015 sustainable human and agricultural development agenda. The aim of discussions in these meetings was to provide functional crops and foods to achieve optimal health by prevention of NCDs. It is possible that these efforts might ensure that the goals and targets set in the agenda are adequate to address the many challenges of global undernutrition as well as obesity which are major risk factors of NCDs. In many developing and middle income countries, food security provided by the governments, in one sense understandably, gave least consideration to functional foods supply and the prevention of obesity and metabolic syndrome, resulting in to emergence of NCDs. The Thailand Declaration reiterates that commitments to eradicate hunger and undernutrition as well as over-nutrition, and to increase investments in effective interventions; designers foods and designers crops. However, in planning coherent policies, our past experience on rapidly absorbed, energy-rich processed foods should be taken in to account while developing sustainable food systems. The food industry should be educated to exploit the expertise of food scientists and health professionals in designing functional foods taking cognizance of manufacturing and processing. Similarly, agriculture scientists may be actively involved in educating farmers so as to grow cash crops providing functional foods. The aim should be to achieve an increase in the availability of functional foods to an extent, or by a policy, by which such foods are available to poors, at affordable cost to prevent hunger and undernutrition and related diseases as well as NCDs. In addition our efforts might help in developing an international consensus on how to approach the development of new designer foods by farmers and food industry to produce low glycemic index foods. Such efforts may establish an international framework for the prevention of NCDs, so that human susceptibility to these diseases is substantially diminished.

The study conducted in this paper is focused on a predominantly residential area of the City of Ljubljana – Koseze, which is characterized by generally favorable (bio)climatic conditions. Nonetheless, thermal satellite imaging showed that residential neighborhoods within the Koseze district display unexpected variations in summer temperatures. This observation called into question the benefits of existing bioclimatic features and indicated the need to investigate and compare two neighborhoods with similar urban parameters, with the aim to identify morphological differential characteristics impacting urban heat island (UHI) intensity. By applying the study methodology based on a literature review, surveys of key precedents, detailed mapping in two Koseze locations, in situ measurements, observations and recordings, thermal imaging and the analyses of statistical data, as well as by defining the four main categories of morphological urban parameters – structure, cover, fabric and metabolism, it was concluded that both neighborhoods have common morphological elements mitigating the UHI effect. Additionally, it was found that the neighborhood with higher UHI intensity has several less favorable features, such as busier roads, larger surface of parking corridors, and the existence of underground parking space. The traffic as an element of urban morphology hence represents the main cause of differences among UHI levels in the two Koseze neighborhoods.

Land Surface Temperature (LST) is routinely retrieved from remote sensing instruments using semi-empirical relationships between top of atmosphere (TOA) radiances and LST, using ancillary data such as total column water vapor or emissivity. These algorithms are calibrated using a set of forward radiative transfer simulations that return the TOA radiances given the LST and the thermodynamic profiles. The simulations are done in order to cover a wide range of surface and atmospheric conditions and viewing geometries. This work analyses calibration strategies, considering some of the most critical factors that need to be taken into account when building a calibration dataset, covering the full dynamic range of relevant variables. A sensitivity analysis of split-windows and single channel algorithms revealed that selecting a set of atmospheric profiles that spans the full range of surface temperatures and total column water vapor combinations that are physically possible seems beneficial for the quality of the regression model. However, the calibration is extremely sensitive to the low-level structure of the atmosphere indicating that the presence of atmospheric boundary layer features such as temperature inversions or strong vertical gradients of thermodynamic properties may affect LST retrievals in a non-trivial way. This article describes the criteria established in the EUMETSAT Land Surface Analysis – Satellite Application Facility to calibrate its LST algorithms applied both for current and forthcoming sensors.

Fabrication of durable materials with excellent oil adsorption capacity and separation performance for the treatment of oily wastewater is meaningful based on smart responsiveness. Herein, a solvent-responsive melamine sponge (MS) was developed via silanization followed by the in-situ growth of zeolitic imidazolate framework-8 (ZIF-8). Detailed characterization of the resultant composite MS was conducted using scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The multiscale hierarchical MS substrate exhibited highly hydrophobic property in the pH range of 1-11, along with a satisfactory adsorption capacity in the range of 65.4-134.2 g/g for different oils. The modified surface transformed from superhydrophobicity/superlipophilicity to superhydrophilicity/underwater superoleophobicity upon ethanol wetting, reverting to its original superhydrophobic state upon drying. The separation flux of the MS substrate was above 1.5×104L/m2h for both oil and water removal, along with the separation efficiency more than 98.7%. No obvious changes of the separation performance after 50 successive immiscible oil/water separation indicated the excellent durability and robustness of the anchored ZIF-8 nanoparticles on the surface of modified MS substrate. More importantly, oil-in-water emulsion separation was successfully carried out via the ZIF-8 MS composite with a high separation efficiency over 99.1%. The developed smart sponge with high oil absorption capacity, excellent chemical stability and fire resistance exhibited a wide range of potential practical applications in the convenient treatment of oily wastewater.

Objectives: To investigate the etiology of amyotrophic lateral sclerosis (ALS) in an adult female patient. Methods: We conducted trio genome sequencing on a 35-year-old woman with progressive weakness in her left upper limb, as well as on her parents. Prior to sequencing, we performed a comprehensive neurological work-up on the patient, including neurological exam, electrophysiology, biomarker assessment, and brain and spinal cord MRI. Results : The propositus experienced weakness and atrophy in her left hand 6 months before the evaluation. This was associated with brisk reflexes and Hoffman sign in the same arm. Electroneuromyography revealed lower motor neuron involvement in three body regions. Neurofilament light chains were elevated in her cerebrospinal fluid. Brain imaging showed asymmetrical T2 hyperintensity of the corticospinal tracts and T2 linear hypointensity of the precentral gyri. Genome trio sequencing identified a likely pathogenic de novo variant in the propositus’s KIF1A gene (NM_001244008.2): c.574A&gt;G, p.(Ile192Val). Discussion: Pathogenic variants in the KIF1A gene have been associated with a wide range of neurological manifestations called KIF1A-associated neurological diseases (KAND). The present report describe a likely pathogenic de novo variant in KIF1A associated with ALS, expanding the phenotypic spectrum of KAND and our understanding of the pathophysiology of ALS.

Laser-induced fluorescence spectroscopy (LIFS) is actively used for remote sensing of atmospheric aerosols and currently is one of the most sensitive and selective techniques for determining small concentrations of substances inside particles. The use of high-power femtosecond laser sources for LIFS-based remote sensing of aerosol contributes to the development of new-generation fluorescence atmospheric lidars since it makes it possible overcoming the energy threshold for the nonlinear-optical effects of multiphoton absorption in particles and receiving the emission signal at long distances in the atmosphere. Our study is aimed to the development and experimental demonstration the technique of nonlinear laser-induced fluorescence spectroscopy (NLIFS) based on the remote excitation of aerosol fluorescent emission stimulated by a spatially-structured high-power femtosecond laser pulse. Importantly, for the first time to our knowledge, we demonstrate the advances of using stochastically-structured plasma-free intense light channels (postfilaments) specially formed by propagation of femtosecond laser radiation through a turbulent air layer for improving NLIFS efficiency. A multiple increase in the received signal of two-photon-excited fluorescence of polydisperse dyed aqueous aerosol by the structured postfilaments is reported.

In this paper, the time-resolved model of photoacoustic signal for samples with a complex inner structure is derived including local non-equilibrium of structural elements with multiple degrees of freedom, i.e. structural entropy of the system. The local non-equilibrium is taken into account through the fractional operator. By analyzing the model for two types of time-dependent excitation, a very short pulse and a very long pulse, it is shown that the rates of non-equilibrium relaxations in complex samples can be measured by applying the derived model and time-domain measurements. Limitations of the model and further directions of its development are discussed.

Macrophages are well known for the involvement in the biocompatibility, as well as biodistribution, of nano(bio)materials. Although there are a number of rodent cell lines, they may not fully recapitulate primary cell responses; particularly for those of human cells. Isolation of tissue resident macrophages, from humans, is difficult and may result in insufficient cells with which to determine the possible interaction with nano(bio)materials. Isolation of primary human monocytes, and differentiation to monocyte-derived macrophages, may provide a useful tool with which to study, further, these interactions. To that end, we developed a standard operating procedure for this differentiation, as part of the REFINE project, and used it to measure the secretion of bioactive molecules from M1 and M2 differentiated monocytes in response to model nano(bio)materials, following an initial assessment of pyrogenic contamination which may confound, potential, observations. The SOP was deployed in two partner institutions with, broadly, similar results. The work presented here shows the utility of this assay but, highlights the relevance of donor variability in responses to nano(bio)materials. Whilst donor variability can provide some, logistical, challenges to application of such assays, this variability is much closer to the heterogeneous cells that are present in vivo, compared to homogeneous, non-human, cell lines.

The assortment of low-cost 3D printers for “in-practice” use, e.g., for clear aligner therapies, is ever increasing. To address concerns about the accuracy of orthodontic models produced on such printers when cost efficient modes of 3D printing are employed, this study examined the effect of print model body type and print angulation on accuracy. Six printing-configuration groups were included: 2 model types (solid or hollow shell) combined with 3 print angles (0°, 70°, or 90°) with 10 models/group; all models were printed with 100-µm layer thickness using a digital light processing-based 3-dimensional printer. Eleven selected structures and distances were measured on the printed models with a digital microscope and compared to the same measures on a digitized master model. The clinically-acceptability range was set at ±0.25 mm difference from the master model for single tooth measurements (intra-tooth) and ±0.5 mm for cross-arch measurements (inter-tooth). For individual measurements across all models, 98% fell within clinical acceptability. For mean measurements within each model group, only canine height for the shell-0° model had a mean difference (0.26 mm ± 0.03) outside the clinically acceptable range for intra-tooth measurements. Standard deviations for all intra-tooth measurements were within 0.07 mm. While none of the mean inter-tooth measurements exceeded the acceptability range, the standard deviations were larger (0.04 to 0.30 mm). Accuracy of orthodontic models for clear aligner therapies was not impacted beyond the clinically acceptable range when altering model body type and print angulation to improve efficiency of 3D printing. These findings suggest greater flexibility of the practitioner to alter print settings to address time and cost efficiency in various clinical scenarios and still maintain clinically acceptable model accuracy.

In the dynamic interplay between people and their physical environments, the Global South stands as a mosaic undergoing a multitude of transformative influences in architecture and urbanism where examining social sustainability becomes imperative. While prevailing attention remains on environmental and economic sustainability, this study addresses a persistent gap in the urban literature by focusing on the dynamic and manifold nature of social sustainability. Positioning itself within the context of sustainable development, the study links the pursuit of social aspects of sustainability with selected unique urban contexts from the Global South. Five cases that include Alexandria (Egypt), Tripoli (Libya), Basra (Iraq), Lilongwe (Malawi), and Accra (Ghana) are discussed through multi-layered investigations that involve attitude surveys, interviews, focus groups, participatory systematic observations, and behavioral mapping, engaging directly with inhabitants and stakeholders. Uncovering people-place narratives in the identified contexts, the cases are developed into five knowledge typologies that serve as practical tools for planning and design decision-making, policy formulation, and academic discourse. Discussions are conceived to demonstrate the transformative role people-place narratives play in fostering a more sustainable and equitable urban future. Conclusions are drawn to offer practical insights for stakeholders involved in various capacities in shaping the urban landscape of the Global South.

Beyond factors such as smoking and obesity, the risk of getting gastrointestinal cancer is passed down from parents to offspring, inherited by a gene mutation, predisposing them to develop cancer in their lifetime. Here we describe the clinical history of family members affected by gastrointestinal pathologies often leading to cancer. In the epidemiological study, the cohort of members of this family shared a high risk of developing gastrointestinal diseases. The subjects were monitored from May 2006 to December 2017 by collecting periodically clinical and endoscopic data, and determining both auto-modification of lymphocyte Poly(ADP-ribose)Polymerase as early signal of DNA damage, and erythrocyte membrane lipid composition (Fat Profile). Both biomarkers were demonstrated to be non invasive and easy tools, to monitor over time family members, first the oldest members (nine siblings), and thereafter their offspring, whose cell status evolved from physiological even to cancerous one. All subjects developed gastrointestinal pathologies of different kind and seriousness. Some diseases evolved to cancer, sometimes as a sudden and lethal event. The results of the two molecular approaches, agreed and even predicted the clinical and imaging paths. This cohort study supported the hypothesis that both noninvasive molecular analyses can predict altered cell states and support clinical and imaging tests.

X-ray free electron lasers deliver photon pulses that are bright enough to observe diffraction from extremely small crystals, at a time scale outrunning their destruction. As crystals are continuously replaced, this technique is termed serial femtosecond crystallography (SFX). Due to its high pulse repetition rate, the European XFEL enables the collection of rich and extensive data sets, suited to study various scientific problems including ultrafast processes. The enormous data rate, data complexity, and the nature of the pixelized multi-modular area detectors at European XFEL pose severe challenges to users. To streamline the analysis of SFX data, we developed the semi-automated pipeline EXtra-Xwiz around the established CrystFEL program suite, processing diffraction patterns on detector frames into structure factors. Here we present EXtra-Xwiz, and introduce its architecture and use by means of a tutorial. Future plans for its development and expansion are also discussed.

Background: Understanding the physicians’ knowledge, attitudes and antimicrobial prescribing behaviour is a crucial step towards designing strategies for optimal use of these agents. Methods: A cross-sectional online survey was conducted among clinicians across India between “May to July 2022” using a self-administered questionnaire in English comprising of 35 questions pertaining to demographic characteristics, knowledge, attitude and practices domains. Results. A total of 544 responses were received from 710 physicians contacted. 60 percent participants were males with mean age of 34.7 years. Mean ± SD scores for knowledge, attitude and practices domains were 8±1.6, 20.2±3.5 and 15.3±2.1, respectively. Higher scores were associated with basic [odds ratio (95% C.I.), P value: 2.95 (1.21, 7.2), 0.02], medical and allied sciences [2.71 (1.09, 6.67), 0.03] and central zone [3.75 (1.39, 10.12), 0.009]. A substantial proportion of dissatisfactory responses were found regarding hospital antibiograms, antibiotics effective against anaerobes, WHO AWaRe classification of antibiotics, and role of infection prevention and control (IPC) measures in containment of antimicrobial resistance (AMR). Conclusions. There is a need to sensitize and educate clinicians on various issues related to antimicrobial use such as antibiograms, double anaerobic cover, IPC practices and guideline-based recommendations to curb the AMR pandemic.

Three-choice preferences for fermented sorghum teas (FST) were examined among 11 adult Ossabaw pigs. The objectives for experiments 1 and 2 (respectively) were to determine preference for: 1) one of three types of FST (white vs. sumac vs. roasted sumac), and 2) isocaloric control (+control; made isocaloric with sucrose), blended FST (3Tea; equal parts of white, sumac, and roasted-sumac), or a negative control (-control; distilled water; avoidance). Pigs were first conditioned to navigate a three-choice preference maze. For experiment 1, no clear preference behaviors for tea-type were observed. Pigs consumed nearly all the teas, but pigs consumed the least amount of tea in the first session. Pigs spent the most time with their heads in the bowl when 3Tea was offered, followed by +control, and the least time was -control.  Regardless of tea-type, adult pigs show a strong preference for FST, even over +control, which was sweetened water. Adult pigs likely prefer the complexity of flavors, rather than the sweetness alone.  Future projects that explore the health benefits of this sorghum formula will not be impeded by avoidance among adult pigs.

F-type ATP synthases play a key role in oxidative and photophosphorylation processes producing adenosine triphosphate (ATP) for most biochemical reactions in living organisms. In contrast to the mitochondrial FOF1-ATP synthases those of chloroplasts are known to be mostly monomers with approx. 15% fraction of oligomers interacting presumably non-specifically in a thylakoid membrane. To shed light to the nature of this difference we studied interactions of the chloroplast ATP synthases using small-angle X-ray scattering (SAXS) method. Here, we report evidence of I-shaped dimerization of solubilized FOF1-ATP synthases from spinach chloroplasts at different salinity. The structural data were obtained by SAXS and showed dimerization in response to changes in ionic strength. The best model describing SAXS data was two ATP-synthases connected through F1/F1’ parts, presumably via their δ-subunits, forming dimers with the “I” shape. Such I-shaped dimers might possibly connect the neighboring lamellae in thylakoid stacks assuming that the FOF1 monomers comprising such dimers are embedded in different thylakoid membranes. If this type of dimerization exists in nature, it might be one of the pathways of inhibition of chloroplast FOF1-ATP synthase for preventing of ATP hydrolysis in dark, when salinity in plant chloroplasts is rising. Together with a redox switch inserted into a γ-subunit of chloroplast FOF1 and lateral oligomerization, an I-shaped dimerization might comprise a subtle regulatory process of ATP synthesis and stabilize the structure of thylakoid stacks in chloroplasts.

The Golden Syrian hamster (Mesocricetus auratus) is now commonly used in preclinical research for the study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the assessment of vaccines, drugs and therapeutics. Here we show that hamsters inoculated via the intranasal route with the same infectious virus dose of prototypical SARS-CoV-2 administered in a different volume present with different clinical signs, weight loss and viral shedding, with a reduced volume resulting in reduced severity of disease similar to that obtained by a 500-fold reduction in challenge dose. The tissue burden of virus and the severity of pulmonary pathology were also significantly affected by different challenge inoculum volumes. These findings suggest that direct comparison between the severity of SARS-CoV-2 variants or studies assessing the efficacy of treatments determined by hamster studies cannot be made unless both the challenge dose and inoculation volume are matched when using the intranasal route. Additionally, analysis of sub-genomic and total genomic RNA PCR data demonstrated no link between sub-genomic and live viral titres and that sub-genomic analyses do not provide any information beyond that provided by more sensitive total genomic PCR.

Physical processes play important roles in controlling eutrophication and oligotrophication. In stratified lakes, internal waves can cause vertical transport of heat and nutrients without breaking the stratification, through boundary mixing events. Such is the case in tropical Valle de Bravo (VB) lake, where strong diurnal winds drive internal waves, boundary mixing and hypolimnetic warming during stratification periods. We monitored VB during 18 years (2001-2018) when important water-level fluctuations (WLF) occurred, affecting mixing and nutrient flux. Mean hypolimnetic temperature increase (0.06–1.04°C month-1) occurred in all the stratifications monitored. We analyzed temperature distributions and modeled the hypolimnion heat budget to assess vertical mixing between layers (26,618–140,526 m-3h-1), vertical diffusivity coefficient KZ (6.2x10-7–3.3x10-6 m2s-1) and vertical nutrient entrainment to epilimnion on monthly scale. Stability also varied as a function of WLF. Nutrient flux to the epilimnion ranged 0.36–5.99 mg m-2d-1 for soluble reactive phosphorus (SRP) and 5.8–97.1 mg m-2d-1 for dissolved inorganic nitrogen (DIN). During low water-level years, vertical nutrient fluxes increase and can account for up to &gt;40% of the total external nutrients load to the lake. Vertical mixing changes related to WLF affect nutrient recycling, their flux to sediments, ecosystemic metabolic balance and planktonic composition of VB.

The purpose of this work is to investigate the protein kinase inhibitory activity of constituents from ethyl acetate soluble fraction of Acacia auriculiformis stem bark. Column chromatography, gel filtration and NMR spectroscopy were used to purified and characterized betulin from the extract. Betulin which is a known inducer of apoptosis was screened against a panel of 16 disease-related protein kinases. Betulin was shown to inhibit Abelson murine leukemia viral oncogene homolog 1 (ABL1) kinase, casein kinase 1epsilon (CK1epsilon), glycogen synthase kinase 3alpha/β (GSK-3alpha/β), Janus kinase 3 (JAK3), NIMA Related Kinase 6 (NEK6) and vascular endothelial growth factor receptor 2 kinase (VEGFR2) and with activity in µM range. The effect of betulin on the cell viability of doxorubicin-resistant K562R chronic myelogenous leukemia cells was then verified to underline its putative use as anti-cancer compound. Betulin was shown to modulate the mitogen-activated protein (MAP) kinase pathway similarly to imatinib mesylate, a well-known inhibitor of ABL1 kinase. The interaction of betulin and ABL1 was studied by molecular docking showing an interaction of the inhibitor with the ATP binding pocket. Altogether, these data demonstrate that betulin is a multi-target inhibitor of protein kinases, an activity that can contribute to the anticancer properties of the natural compound and notably for treatment of leukemia.

Chronic kidney disease (CKD) affects >10% of the adult population. Each year approximately 120,000 Americans develop end-stage kideny disease and initiate dialysis, which is costly and associated with functional impairments, worse health-related quality of life, and high early-mortality rates exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6-0.8 g/kg/day comprised of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, can be promising. The scientific premise of the PLADO is based on the observations that high protein diets with high meat intake are not only associated with higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of hyperkalemia, given constipation from the typical low fiber intake. Plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk in CKD patients. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm.

Genomic medicine is moving from research to the clinic. There is a lack of evidence about the impact of genomic medicine interventions on health outcomes. This is due in part to a lack of standardized outcome measures that can be used across different programs to evaluate the impact of interventions targeted to specific genetic conditions. The eMERGE Outcomes working group (OWG) developed measures to collect information on outcomes following the return of genomic results to participants for several genetic disorders. These outcomes were compared to outcome intervention pairs for genetic disorders developed independently by the ClinGen Actionability working group (AWG). In general, there was concordance between the defined outcomes between the two groups. The ClinGen outcomes tended to be higher level and the AWG scored outcomes represented a subset of outcomes referenced in the accompanying AWG evidence review. eMERGE OWG outcomes were more detailed and discrete, facilitating collection of relevant information from health records. This paper demonstrates that common outcomes for genomic medicine interventions can be identified. Further work is needed to standardize outcomes across genomic medicine implementation projects and make these publicly available to enhance dissemination and assist in making precision public health a reality.

Stable suspensions of metal/metalloid oxide nanoparticles (Me-NPs) obtained by laser ablation of 99.99% pure elemental aluminum, titanium or silicon under a layer of deionized water were used separately, or in three binary combinations, or in a ternary combination to induce subchronic intoxications in rats. To this end, the Me-NPs were repeatedly injected intraperitoneally (i.p.) 18 times during 6 weeks before measuring a large number of functional, biochemical, morphological and cytological indices for the organism’s status. In many respects, the Al₂O₃-NP was found to be the most toxic species alone and the most dangerous component of the combinations studied. Mathematical modeling with the help of the Response Surface Methodology showed that, as well as in the case of any other binary toxic combinations previously investigated by us, the organism’s response to a simultaneous exposure to any two of the Me-NP species under study was characterized by a complex interaction between all possible types of combined toxicity (additivity, subadditivity or superadditivity of unidirectional action and different variants of opposite effects) depending on which outcome a given type was estimated for and on effect and dose levels. With any third MeO-NP species acting in the background, the type of combined toxicity displayed by the other two remained virtually the same or changed significantly, becoming either more or less unfavorable. Various harmful effects produced by the [Al₂O₃-NP+TiO₂-NP+SiO₂-NP]-combination, including its genotoxicity, were substantially attenuated by giving the rats per os during the entire exposure period a complex of innocuous bioactive substances expected to increase the organism’s antitoxic resistance.

Gas and power networks are tightly coupled and interact with each other due to physically interconnected facilities. In an integrated gas and power network, a contingency observed in one system may cause iterative cascading failures, resulting in network wide disruptions. Therefore, understanding the impacts of the interactions in both systems is crucial for governments, system operators, regulators and operational planners, particularly, to ensure security of supply for the overall energy system. Although simulation has been widely used in the assessment of gas systems as well as power systems, there is a significant gap in simulation models that are able to address the coupling of both systems. In this paper, a simulation framework that models and simulates the gas and power network in an integrated manner is proposed. The framework consist of a transient model for the gas system and a steady state model for the power system based on AC-Optimal Power Flow. The gas and power system model are coupled through an interface which uses the coupling equations to establish the data exchange and coordination between the individual models. The bidirectional interlink between both systems considered in this studies are the fuel gas offtake of gas fired power plants for power generation and the power supply to LNG terminals and electric drivers installed in gas compressor stations and underground gas storage facilities. The simulation framework is implemented into an innovative simulation tool named SAInt (Scenario Analysis Interface for Energy Systems) and the capabilities of the tool are demonstrated by performing a contingency analysis for a real world example. Results indicate how a disruption triggered in one system propagates to the other system and affects the operation of critical facilities. In addition, the studies show the importance of using transient gas models for security of supply studies instead of successions of steady state models, where the time evolution of the line pack is not captured correctly.

Background: Emerging and re-emerging infectious diseases that infect wildlife, such as African swine fever, avian influenza, and SARS-CoV-2, have highlighted the necessity for wildlife health surveillance (WHS) due to their direct and indirect impacts on wildlife species, ecosystems, domestic animals, and human health. While global policies and guidelines exist, a critical gap remains in local-to-national implementation of WHS systems. A group of local, national, and global actors in WHS have formed a working group to address this gap. Methods and Findings: The working group reports on a theory of change (ToC) developed to implement WHS from local to global scales. Through brainstorming, plenary exercise, and building on peer-reviewed science and existing surveillance systems, we identified six transformative pathways to be implemented via collaborations across scales and contexts: mindset change, policy and investment, user-driven science, user-driven technologies, capacity enhancement, and mobilization of a global community of practice. Interpretation: This ToC serves as a roadmap to develop effective WHS systems that support adaptive management and implementation. WHS is fundamental to understanding the impacts of health threats to biodiversity and human and domestic animal health. This ToC presents an approach to operationalize integration of wildlife health into collaborative One Health surveillance. Funding: The Science for Nature and People Partnership.

The integration of Artificial Intelligence (AI) in healthcare has transformed clinical practices by improving the accuracy of diagnosis, optimizing surgical procedures, improving the patient experience, and accelerating drug development. This article provides a comprehensive overview of the many applications of artificial intelligence (AI) across several industries, including fast diagnostics, where ML algorithms greatly enhance the accuracy and velocity of disease diagnosis. State-of-the-art robotic-assisted minimally invasive surgical procedures that shorten patients' hospitalization and improve their chances of recovery, cutting-edge AI applications in healthcare monitoring, and medication development. The article also looks at the primary challenges that AI in healthcare will inevitably encounter, such as differences in product quality, a shortage of skilled workers, privacy and ethical issues, and the need for improved regulatory frameworks. Despite the challenges, AI contributes significant advantages to the healthcare industry, providing novel and remarkable contributions to the efficiency of medical procedures and the progress of medical outcomes. The paper emphasizes the importance of cooperation in overcoming current challenges and enhancing the acceptability of AI technology in clinical settings. This will ensure that AI-driven innovations continue to enhance the standards of patient care.

Counter-current spontaneous imbibition of water is a critical oil-recovery mechanism. In the laboratory, the Amott test is a widely used technique to assess efficacy of brine imbibition into oil-saturated core plugs. The classic Amott-cell methodology was designed to estimate ultimate oil recovery, but not the recovery dynamics that provides essential information about the imbibition mechanisms. Retention of oil droplets at the external core surface and delayed onset of oil production are the two key artifacts of the classic Amott experiment. This retention, referred to here as the ``external-surface oil holdup effect'', often results in stepwise recovery curves that obscure true dynamics of spontaneous imbibition. To address these holdup drawbacks of the classic Amott method, we modified the Amott cell and experimental procedure. For the first time, using water-wet Indiana limestone cores saturated with brine and mineral oil, we showed that our improvements of the Amott method enabled accurate and reproducible measurements of oil-recovery dynamics. We used the Generalized Extreme Value (GEV) statistics to describe oil-production histories from water-wet heterogeneous limestone cores with finite initial water saturations, for the first time. We demonstrated that our four-parameter GEV model accurately described the recovery dynamics, and that optimal GEV parameter values systematically reflected the key characteristics of the oil-rock system, such as oil viscosity and rock permeability. These findings gave us a more fundamental understanding of spontaneous, counter-current imbibition mechanisms and insights into what constitutes a predictive model of counter-current water imbibition into oil-saturated rocks with finite initial water saturation.

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide. Two vaccines targeting the elderly and pregnant women have been recently approved employing the prefusion form of the RSV-fusion protein (F). However, there are currently no vaccines for infants. Studies have shown a fusion-inactive prefusogenic F form is significantly more immunogenic and produces higher antibody titers to both the prefusion and postfusion structures of the F protein. Here we have developed RSV virus-like particles (RSV-VLPs) consisting of prefusogenic F, RSV glycoprotein and matrix proteins, produced them using the baculovirus expression system, and studied their protective efficacy in Balb/c mice. Morphology and successful assembly of VLPs were confirmed by transmission electron microscopy and western blot. Mice immunized with VLPs developed high levels of serum IgG and neutralizing antibodies as compared with mice immunized with inactivated virus. The VLP vaccine also induced higher levels of IFNγ and IL4, elicited limited proliferation of CD4+ and CD8+ T cells but higher cytotoxic-T-lymphocyte responses. VLP immunization abolished lung pathology in the mice after RSV challenge. Overall, our results indicate that RSV-VLPs consisting of prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

Effective therapeutics for Alzheimer's disease (AD) are in great demand worldwide. In our previous work, we responded to this need by synthesizing novel drug candidates consisting of 4-amino-2,3-polymethylenequinolines conjugated with butylated hydroxytoluene via fixed-length alkylimine or alkylamine linkers (spacers) and studying their bioactivities pertaining to AD treatment. Here, we report significant extensions of these studies, including the use of variable-length spacers and more detailed biological characterizations. Conjugates were potent inhibitors of acetylcholinesterase (AChE, minimum IC50 15.1±0.2 nM) and butyrylcholinesterase (BChE, minimum IC50 5.96±0.58 nM), with weak inhibition of off-target carboxylesterase. Conjugates with alkylamine spacers were more effective cholinesterase inhibitors than alkylimine analogs. Optimal inhibition for AChE was exhibited by cyclohexaquinoline and for BChE by cycloheptaquinoline. Increasing spacer length elevated potency against both cholinesterases. Structure-activity relationships agreed with docking results. Mixed-type reversible AChE inhibition, dual docking to catalytic and peripheral anionic sites, and propidium iodide displacement suggested the potential of hybrids to block AChE-induced β-amyloid (Aβ) aggregation. Hybrids also exhibited inhibition of Aβ self-aggregation in the thioflavin test; those with a hexaquinoline ring and C8 spacer were the most active. Conjugates demonstrated high antioxidant activity in ABTS and FRAP assays as well as inhibition of luminol chemiluminescence and lipid peroxidation in mouse brain homogenates. Quantum-chemical calculations explained antioxidant results. Computed ADMET profiles indicated favorable blood-brain barrier permeability suggesting CNS activity potential. Thus, the conjugates could be considered promising multifunctional agents for potential treatment of AD.

In this perspective, we give an overview of several less explored structural and optical characterisation techniques useful for biomaterials. New insights into the structure of natural fibres such as spider silk can be gained with minimal sample preparation. Electromagnetic radiation (EMR) over a broad range of wavelengths (from X-ray to THz) provides information of the structure of the material at cor- respondingly different length scales (nm-to-mm). When the sample features, such as the alignment of certain fibres, cannot be characterised optically, polarisation analysis of the optical images can provide further information on feature alignment. The 3D complexity of biological samples necessitates that there be feature measure- ments and characterisation over a large range of length scales. We discuss the issue of characterising complex shapes by analysis of the link between the color and struc- ture of spider scales and silk. For example, it is shown that the green-blue color of a spider scale is dominated by the chitin slab’s Fabry-P ́erot type reflectivity rather than the surface nanostructure. The use of a chromaticity plot simplifies complex spectra and enables quantification of the apparent colors. All the experimental data presented herein are used to support the discussion on the structure-color link in the characterisation of materials.

The antibiotic tetracycline demeclocycline (DMC) was recently reported to rescue α-synuclein (α-Syn) fibril-induced pathology. However, the antimicrobial activity of DMC precludes its po-tential use in long-term neuroprotective treatments. Here, we synthesized a DMC derivative with residual antibiotic activity and improved neuroprotective effects. The molecule, called de-rivative demeclocycline (DDMC), was obtained by the removal of both dimethylamino substitu-ents at position 4 and the reduction of the hydroxyl group at position 12a on ring A of DMC. The modifications strongly diminished its antibiotic activity against Gram-positive and Gram-negative bacteria. Moreover, this compound preserved the low toxicity of DMC in dopaminergic cell lines while improving its ability to interfere with α-Syn amyloid-like aggregation, showing the highest effectiveness of all tetracyclines tested. Likewise, DDMC demonstrated the ability to reduce seeding induced by the exogenous addition of α-Syn preformed fibrils (α-SynPFF ) in ex vitro models and in SH-SY5Y-α-Syn-tRFP cells. In addition, in the presence of DDMC, α-SynPFF were less inflammogenic, as they dampened the release of tumor necrosis factor α (TNF-α) and glutamate by microglial cells compared to control fibrils. Our results suggest that DDMC may be a promising drug candidate for hit-to-lead development and preclinical studies in PD and other synucleinopathies.

Addressing factors modulating COVID-19 is crucial since abundant clinical evidence shows that outcomes are markedly heterogeneous between patients. This requires identifying the factors and understanding how they mechanistically influence COVID-19. Here, we describe how eleven selected factors influence COVID-19 by applying the Adverse Outcome Pathway (AOP) framework well-established in regulatory toxicology. This framework aims to model the sequence of events starting from an initial interaction of a stressor with the organism and the progress through key biological events leading to an adverse health outcome. Several linear AOPs depicting pathways from the binding of the virus to ACE2 up to clinical outcomes observed in COVID-19 patients have been developed and integrated into a network offering a unique overview of the mechanisms underlying the disease. As SARS-CoV-2 infectibility and ACE2 activity are the major starting points and inflammatory response is central in the development of COVID-19, we evaluated how eleven intrinsic and extrinsic factors modulate those processes impacting clinical outcomes. Applying this AOP-aligned approach enables the identification of current knowledge gaps orientating for further research and allows to propose biomarkers to identify of high-risk patients. This approach also facilitates expertise synergy from different disciplines to address public health issues.

The vast majority of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia. Although cachexia results from concurrent loss of adipose and muscle tissue, most studies focus on muscle alone. Emerging data demonstrate the prognostic value of fat loss in cachexia. Here we sought to identify the muscle and adipose gene profiles and pathways regulated in cachexia. Matched rectus abdominis muscle and subcutaneous adipose tissue were obtained at surgery from patients with benign conditions (n=11) and patients with PDAC (n=24). Self-reported weight loss and body composition measurements defined cachexia status. Gene profiling was done using Ion proton sequencing. Results were queried against external datasets for validation. 961 DE genes were identified from muscle and 2000 from adipose tissue, demonstrating greater response of adipose than muscle. In addition to known cachexia genes such as FOXO1, novel genes from muscle, including PPP1R8 and AEN correlated with cancer weight loss. All the adipose correlated genes including SCGN and EDR17 are novel for PDAC cachexia. Pathway analysis demonstrated shared pathways but largely non-overlapping genes in both tissues. Age related muscle loss predominantly had a distinct gene profiles compared to cachexia. This analysis of matched, externally validate gene expression points to novel targets in cachexia.

Research into the neurobiological and psychosocial mechanisms involved in fibromyalgia (FM) has progressed remarkably in recent years. Despite this, currents accounts of FM fail to capture the complex, dynamic and mutual crosstalk between neurophysiological and psychosocial domains. We conducted a comprehensive review of the existing literature in order to synthesise current knowledge on FM, explore and highlight multi-level links and pathways among different systems and build bridges between existing approaches. An extensive panel of international experts in neurophysiology and psychosocial aspects of FM discussed the collected evidence and progressively refined and conceptualized its interpretation. Fibromyalgia is a complex condition resulting from the dynamic interplay between multiple systems and processes. We provided an updated overview of the most relevant observations in FM to date as well as the potential pathways by which they exert they are related and exert their mutual influence, to produce the manifestations commonly associated with FM. This review constituted the first step towards and supported the development of a much needed model capable of integrating the main factors implicated in FM into a single, unified model that may prove valuable in understanding and managing FM.

Scanning magnetic microscopy is a new tool that has recently been used to map magnetic fields with good spatial resolution and field sensitivity. This technology has great advantages over other instruments; for example, its operation does not require cryogenic technology, which reduces its operational cost and complexity. Here, we describe the construction of a customizing scanning magnetic microscope based on commercial Hall-effect sensors at room temperature that achieves a spatial resolution of 200 µm. Two scanning stages on the x- and y-axes of precision, consisting of two coupled actuators, control the position of the sample, and this microscope can operate inside or outside a magnetic shield. We obtained magnetic field sensitivities better than 521 nT_rms/√Hz between 1 and 10 Hz, which correspond to a magnetic momentum sensitivity of 9.20 × 10^–10 Am². In order to demonstrate the capability of the microscopy, polished thin sections of geological samples, samples containing microparticles and magnetic nanoparticles were measured. For the geological samples, a theoretical model was adapted from the magnetic maps obtained by the equipment. Vector field maps are valuable tools for the magnetic interpretation of samples with a high spatial variability of magnetization. These maps can provide comprehensive information regarding the spatial distribution of magnetic carriers. In addition, this model may be useful for characterizing isolated areas over samples or investigating the spatial magnetization distribution of bulk samples at the micro and millimeter scales. As an auxiliary technique, a magnetic sweep map was created using Raman spectroscopy; this map allowed the verification of different minerals in the samples. This equipment can be useful for many applications that require samples that need to be mapped without a magnetic field at room temperature, including rock magnetism, the nondestructive testing of steel materials and the testing of biological samples. The equipment can not only be used in cutting-edge research but also serve as a teaching tool to introduce undergraduate, master's and Ph.D. students to the measurement methods and processing techniques used in scanning magnetic microscopy.

Objective: We determined, in stable ambulatory heart failure with preserved ejection fraction (HFpEF) subjects and matched controls, the capability of a novel blood based cardiac-specific cBIN1 Score (CS) to diagnose heart failure and prognosticate future hospitalization. Background: Heart failure (HF) poses a costly health care burden worldwide with rising prevalence. Abnormal calcium signaling is intrinsic to HF pathophysiology and correlates with reduced expression of a cardiac membrane scaffolding protein, cardiac bridging integrator 1 (cBIN1). We hypothesize that CS, a numerical score derived from plasma cBIN1 concentration, is a diagnostic and prognostic biomarker of HF. Methods: Plasma cBIN1 is quantified by an ELISA test, and CS is calculated as the natural log of the normalized reciprocal of plasma cBIN1 concentration. We determined CS among 52 clinically stable individuals with HFpEF (LVEF ≥ 50%) (mean age 57 ± 15 years old, 63% men) and 104 age and sex matched volunteers with no known history of HF. We obtained plasma concentrations of NT-proBNP, a marker of volume status, as comparison. Baseline co-morbidities and one year longitudinal clinical information were obtained through electronic medical records. Results: Median CS is 0 (IQR -0.4 – 0.6) in the control cohort and is increased to 1.8 in the HFpEF cohort (IQR 1.5 – 2.3, p < 0.0001). For HFpEF diagnosis, CS has a receiver operating characteristic (ROC) area under the curve (AUC) of 0.94 (95% CI 0.95 – 0.99) and NT-proBNP of 0.89 (95% CI 0.83 – 0.95). Kaplan-Meier analysis of one year cardiovascular hospitalizations reveals that HFpEF patients with CS ≥ 1.8 have a hazard ratio (HR) of 4.0 (95% CI 1.4 – 11.2, p=0.009). Combining CS ≥ 1.8 with NT-proBNP ≥ 300 pg/mL, increases HR to 21.4 (95% CI 2.7 – 171.6, p=0.004). Conclusions: In a cohort of stable ambulatory HF patients with cardiomyopathies of multiple etiologies and preserved ejection fraction, a positive CS correlates with worsening myocardial health and predicts future hospitalization. CS, a marker of cardiac muscle health, provides a novel index to informing the management of stable ambulatory HF patients.

DiFX is a software VLBI correlator currently adopted by several main correlation sites around the globe. After the launch of the RadioAstron Space-VLBI mission in 2011, an extension was necessary to handle processing of an orbiting antenna, to be correlated with supporting ground arrays. We present here a branch of the main DiFX distribution (2.4), recently uploaded on the publicly available repository, that MPIfR developed to process data of the three AGN-imaging RadioAstron key science projects. It can account for general relativistic correction of an orbiting antenna with variable position/velocity, providing a routine to covert the native RDF format to the more common M5B one. Also, a fringe-finding algorithm able to manage arbitrary large fringe-search window is included, allowing one to increase the search space normally adopted by common software packages like HOPS.

Vegetative desiccation tolerance has evolved within the genus Craterostigma and Lindernia. A centre of endemism and diversification for these plants appears to occur in ancient tropical montane rainforests of east Africa in Kenya and Tanzania. Lindernia subracemosa, a desiccation-sensitive relative of C. plantagineum, occurs in these rainforests and experiences adequate rainfall and thus does not require desiccation tolerance. However, sharing this inselberg habitat, another species Lindernia brevidens does retain vegetative desiccation tolerance and is also related to the resurrection plant C. plantagineum found in South Africa. Leaf material was collected from all three species at different stages of hydration: fully hydrated, half-dry (ca. 45% relative water content), and fully desiccated. Cell wall monosaccharide datasets were collected from all three species. Comprehensive microarray polymer profiling (CoMPP) was performed using ca. 27 plant cell wall specific antibody and carbohydrate binding module probes. Global datasets do not show significant differences between the selected species suggesting that cell wall modifications in response to vegetative desiccation involve subtle cell wall remodelling not reflected by compositional analysis and that the plants and their walls are constitutively protected against desiccation.

The success of composite materials is attributed to the nature of bonding at the nanoscale and the resulting structure-related properties. This study reports the interaction, electronic, and optical properties of diamond nanothread/polymers (cellulose and epoxy) and boron nitride nanotube/calcium silicate hydrate composites using density functional theory modeling. Our findings indicate that the interaction between the nanothread and polymer is due to van der Waals-type bonding. Minor modifications in the electronic structures and absorption spectra are noticed. Conversely, the boron nitride nanotube and calcium silicate hydrate composite display an electron-shared type of interaction. The electronic structure and optical absorption spectra of the diamond nanothread and boron nitride nanotube in all configurations studied in the aforementioned composite systems are well maintained. Our findings offer an electronic-level perspective into the bonding characteristics and electronic-optical properties of diamond nanothread/polymer and boron nitride nanotube/calcium silicate hydrate composites for developing next-generation materials.

Exosomes, natural nanovesicles that contain a cargo of biologically active molecules such as lipids, proteins, and nucleic acids, are released from cells to the extracellular environment. They then act as autocrine, paracrine, or endocrine mediators of communication between cells by delivering their cargo into recipient cells and causing downstream effects. Exosomes are greatly enriched in miRNAs, which are small non-coding RNAs that act as cytoplasmic posttranscriptional repression agents, modulating the translation of mRNAs into proteins, as well as nuclear transcriptional gene activators. Neuronal exosomal miRNAs have important physiologic functions in the Central Nervous System (CNS), including cell-to-cell communication, synaptic plasticity, and neurogenesis, as well as modulating stress and inflammatory responses. Stress-induced changes of exosomal functions include effects on neurogenesis and neuroinflammation, which can lead to the appearance of various neuropsychiatric disorders, such as schizophrenia, major depression, bipolar disorder, and Alzheimer's and Huntington’s's diseases. The current knowledge regarding the roles of exosomes in the pathophysiology of common mental disorders is discussed in this review.

To mitigate pyrethroid resistance in mosquito vectors of emerging and re-emerging human pathogens, there is an urgent need to discover insecticides with novel modes of action. Natural alternatives, such as extracts derived from plants, may serve as substitutes for traditional synthetic insecticides if they prove to be sustainable, cost-effective, and safe for non-target organisms. Hemp (Cannabis sativa) is a sustainable plant known to produce various secondary metabolites with insecticidal properties, including terpenoids and flavonoids. The goal of this study was to assess the larvicidal activity of hemp leaf extract on 1st instar mosquito larvae from both pyrethroid-susceptible (PS) and pyrethroid-resistant (PR) strains of Aedes aegypti Another goal was to identify which components of the extracts were responsible for any observed larvicidal activity. We found that methanol extract of hemp leaves induced similar concentration-dependent larvicidal activity against PS (LC50: 4.4 ppm) and PR (LC50: 4.3 ppm) strains within 48 hours. Partitioning of the dried leaf extract between methanol and revealed that full larvicidal activity was restricted to the methanol fraction. Analysis of this fraction by gas chromatography-mass spectrometry and nuclear magnetic resonance showed it to be dominated by cannabidiol (CBD). Larvicidal assays using authentic CBD confirmed this compound was primarily responsible for the toxicity of hemp leaf extract against both strains. We conclude that hemp leaf extracts and CBD have the potential to serve as viable sources for the development of novel mosquito larvicides.

Willow (Salix spp.) trees, found worldwide, contain secondary metabolites that are valuable as dietary supplements for animal feed and as anti-parasitic compounds. We quantified secondary metabolites (phenolic, flavonoids, and salicylic acid) in ethanolic extracts from leaves and branches of three Salix acmophylla genotypes and investigated their potential to inhibit Eimeria sp. sporulation, a major concern in ruminants. The total phenolic content of willow leaves and branches was similar in two of three different genotypes. The total flavonoid content of the branches was significantly higher than that of leaves of the same genotype; however, the salicylic acid content was significantly higher in leaves than in branches. Importantly, all extracts exhibited significant inhibition of Eimeria sporulation, where over 70% inhibition was obtained at concentrations as low as 750 ppm. The sporulation inhibition by branch or leaf extracts exceeded 80% for leaves and 90% for branches at concentrations above 1250 ppm. The study highlights the potential of using Salix extracts as bioactive compounds for biological control of coccidiosis in ruminants and emphasizes the importance of genotype-specific variations in secondary metabolite profiles. We conclude that all parts of S. acmophylla can provide secondary metabolites that act as a coccidiostat to treat Eimeria in goats.

Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managing these injuries, spanning from simple to complex physiotherapy techniques, conservative treatments including steroidal and non-steroidal anti-inflammatory drugs, hyaluronic acid, and polyacrylamides, to the promising regenerative therapies such as hemoderivatives and stem cell-based therapies. Each therapeutic modality is scrutinized for its benefits, limitations, and potential synergistic actions to facilitate their most effective application for intended healing/regeneration of the injured tissue/organ and subsequent patient recovery. While stem cell-based therapies emerge as particularly promising for equine musculoskeletal injuries, a multidisciplinary approach is underscored throughout the discussion, emphasizing the importance of considering various therapeutic modalities in tandem.

The antimicrobial properties of the new strains of microorganisms isolated from natural sources of various ecological niches in the Moscow Region and the Republic of Tatarstan were studied. An antifungal activity of isolates was established in a test culture of toxin-producing microscopic fungi that cause various plant diseases: Fusarium oxysporum, Aspergillus flavus, Penicillium spp. and Candida albicans. Of the 46 studied microorganisms, 4 isolates (Bacillus subtilis, Propionibacterium freudenreichii, Lactobacillus plantarum and Streptomyces spp.) showed an ability to produce biologically active metabolites with a pronounced antimicrobial potential. This is promising in the growth and protection of the Scots pine, pedunculate oak and small-leaved linden forest crops from diseases caused by fungi Lophodermium pinastri Chev. and Microsphaera alphitoides stimulation. Based on selected isolates, a Bacterial product LRV composition has been developed. A Scots pine, pedunculate oak and small-leaved linden seedlings single and double foliar treatment with Bacterial product LRV at a concentration of 10 ml/l led to an increase in the growth of an above-ground part by 31.8, 51.9 and 25.4 %, respectively, and an underground part – by 25.0, 37.2 and 25.7 %, respectively, compared with the control. The weight of seedling at the end of the study exceeded the control variant by an average of 26.0, 44.0 and 78.0 %, respectively. A use of a plant protection Bacterial product LRV did not have a significant effect on a powdery mildew and Schütte disease damage to forest crops. A Biogeosystem Technique methodology has been developed to improve a long-term forest growing.

World is now experiencing a major health calamity due to the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV- 2). The foremost challenge facing the scientific community is to explore the growth and transmission capability of the virus. Use of artificial intelligence (AI), such as, deep learning, in (i) rapid disease detection from x-ray/computerized tomography (CT)/ high-resolution computed tomography (HRCT) images, (ii) accurate prediction of the epidemic patterns and their saturation throughout the globe, (iii) identification of the epicenter in each country/state and forecasting the disease from social networking data, (iv) prediction of drug-protein interactions for repurposing the drugs, and (v) socio-economic impact and prediction of future relapses, has attracted much attention. In the present manuscript, we describe the role of various AI-based technologies for rapid and efficient detection from CT images complementing quantitative real time polymerase chain reaction (qRT-PCR) and immunodiagnostic assays. AI-based technologies to anticipate the current pandemic pattern, possibility of future relapses and socio-economic impact are also discussed. We inspect how the virus transmits depending on different factors, such as, population density and mobility among others. We depict how AI-based mobile app for contact tracing and surveys can prevent the transmission. A modified deep learning technique can assess affinity of the most probable drugs to treat COVID-19. Here a few effective antiviral drugs, such as, Geneticin, Avermectin B1, and Ancriviroc among others, have been reported with their appropriate validation from previous investigations.

Staphylococcus aureus is a gram-negative bacterium that causes superficial and deep infections that can be mild or potentially fatal. Recently, the bacterium has gained significant attention due to the increased incidence of multidrug-resistant (MDR) strains that make treatment with antibiotics dif-ficult. Owing to the MDR strains, alternative therapies such as antimicrobial photodynamic therapy (PDT) have emerged as good options to treat non-systemic infections. PDT combines a photosensi-tiser (PS) with light and oxygen to generate free radicals that destroy bacterial structures such as the plasma membrane, matrix, and genetic material. This systematic review aimed to identify the ef-fectiveness of PDT delivered using different types of hydrogels for treating wounds, burns, and contamination by S. aureus. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Bibliographic research was conducted using the PubMed, Web of Science, and Scopus databases. Only full articles published in English between 2013 and 2024 from any country of origin (without restrictions) were included. The research was carried out from 15 June 2023 to 15 June 2024 and did not use any automatic biblio-graphic search tool. The articles collected were identified using keywords and selected using in-clusion and exclusion criteria in accordance with the PRISMA protocol. Seven articles were in-cluded that presented a good set of evidence associated with the use of PDT against S. aureus in in vitro and in vivo studies. To conclude, PDT can effectively complement antimicrobial therapy against S. aureus, in the healing of wounds and burns. The effectiveness of this technique depends on the PS used, hydrogel type, and lesion location. Some studies have already demonstrated the ef-fectiveness of PDT but most were in vitro and a few in vivo. Further studies are required to demonstrate the safety and efficacy of PDT delivered via hydrogels in in vivo models of bacterial infection.

The study assesses the direct effects of climate change by 2060, including extreme events, on the productivity of regional crop farming and livestock in Greece, and the broader socio-economic effects on the agri-food and other sectors. Different approaches (i.e., agronomic models, statistical regression models, equations linking thermal stress to livestock output) were combined to estimate the effects on productivity from changes in the average values of climatic parameters, and subsequently the direct economic effects from this long-term climate change. Recorded damages from extreme events together with climatic thresholds per event and crop were combined to estimate the direct economic effects of these extremes. The broader socio-economic effects were then estimated through input-output analysis. Under average levels of future extreme events, the total direct economic losses for the Greek agriculture due to climate change will be significant, from €437 million/ year to €1 billion/ year. These losses approximately double when indirect effects on other sectors using agricultural products as inputs (e.g., food and beverage, hotels, restaurants) are considered, and escalate further under a tenfold impact of extreme events. Losses in the GDP and employment are moderate at the national level, but significant in regions where the contribution of agriculture is high.

Metabolic syndrome (MetS) refers to the group of several interconnected risk factors that collectively double the risk of cardiovascular disease. Epilepsy is linked to MetS across all age groups, though its prevalence differs across various studies. This can be understood from the perspective of seizure-related metabolic abnormalities, long-term antiepileptic drugs (AEDs) use, and a more sedentary lifestyle due to epilepsy. The factors that are considered in developing MetS for patients with epilepsy (PWE) are age, residence, level of physical activity, food intake status, epilepsy subtype, epilepsy duration, current (AEDs) use, drug responsiveness status, body-mass index (BMI), total cholesterol and LDL-cholesterol levels. A deeper understanding of the epilepsy-AED-MetS connection and the exploration of lifestyle interventions hold the promise of significantly improving the overall health and well-being of PWE. Clinicians managing PWE should closely monitor various risk factors for developing MetS and consider them when selecting AED treatment.

Considering the age of the dogs, it was expected that elderly animals would have stiffer thyroids than adults. The aim of this study was to evaluate the thyroid glands of healthy dogs using 2D shear wave elastography in order to establish qualitative and quantitative parameters of tissue stiffness in dogs of different age groups. The B-mode ultrasound and elastography findings were correlated with the weight and sex of the patients, allowing a reference range to be established for different groups of dogs. 31 dogs of different breeds, sexes and sizes were evaluated. Animals with clinical signs or ultrasound findings indicative of endocrine disease or thyroid lesions were not included in the study. Using QelaXtoTM 2D software, shear wave velocity data in m/s and color elastograms were evaluated and calculated. A healthy thyroid has a blue color elastogram, indicative of low stiffness, and there was no distinction between adult and elderly dogs, genders or sizes. The reference range for the shear wave velocity of thyroid tissue assessed by 2D shear wave elastography can be between 1.6 and 2.0 m/s with a variation of ±0.889 in adult and elderly dogs.

Workplace bullying is common among nurses affecting negatively several work-related variables, such as job burnout and job satisfaction. However, no study until now has examined the impact of workplace bullying on quiet quitting among nurses. Thus, our aim was to examine the direct effect of workplace bullying on quiet quitting and to investigate the mediating effect of coping strategies on the relationship between workplace bullying and quiet quitting in nurses. We conducted a cross-sectional study with a convenience sample of 650 nurses in Greece. We collected our data during February 2024. We used the Negative Acts Questionnaire-Revised, the Quiet Quitting Scale and the Brief COPE to measure workplace bullying, quiet quitting and coping strategies, respectively. We found that workplace bullying and negative coping strategies were positive predictors of quiet quitting, while positive coping strategies was a negative predictor of quiet quitting. Our mediation analysis showed that positive and negative coping strategies partially mediated the relationship between workplace bullying and quiet quitting. In particular, positive coping strategies caused competitive mediation, while negative coping strategies caused complimentary mediation. Nurses’ managers and policy makers should improve working conditions by reducing workplace bullying and strengthening positive coping strategies among nurses.

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic blasts/LSCs from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to get a deeper insight and segregation between leukemic and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34⁺/CD38^- hematopoietic stem cells (HSCs) or CD34⁺ cells with a strong coexpression of CD45RA/CD123, respectively. CD34⁺ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

This study aimed to investigate the fatigue performance and interfacial strengthening mechanisms of Al6061-to-Cu dissimilar lap joints via electromagnetic pulse welding (EMPW). The load-bearing capacity of the joints at discharge voltages of 14 kV and 16 kV was superior to that of 12 kV. Furthermore, the fatigue life of the 14 kV joints was one order of magnitude higher compared to the 12 kV joints. SEM observation of the fatigue fracture surface revealed the presence of typical "tire-mark" fatigue striations only in the 14 kV joint, indicating higher ductility and the ability to withstand extended plastic deformation. Notably, ultra-fine nanocrystalline Al2Cu phase, amorphous phase, and numerous dislocations hindered EBSD acquisition in the transition zone. Nevertheless, dense low-angle grain boundaries (LAGBs) and refined grains were examined at the bonding interface. This suggests that the high-velocity collision caused severe plastic deformation and led to the formation of substructures. The interfacial strength was attributed not only to the "wave-like" or "inverted hook-like" diffusion layer but also to the presence of refined grains along the interface and nanocrystalline Al2Cu in the transition zone. Furthermore, the hybrid nanocrystalline-amorphous microstructure strengthened the joint by regulating the balance between strength and ductility.

Obesity is a troubling public health problem worldwide as it increases risks of respiratory complications, systemic arterial hypertension, type 2 diabetes mellitus, sleep disorders, cardiovascular diseases, and metabolic syndrome (MetS). As a measure to counteract comorbidities associated with severe obesity, bariatric surgery stands out. This study aimed to investigate the adiponectin/leptin ratio in women with severe obesity with and without MetS undergone Roux-en-Y Gastric Bypass (RYGB) and to characterize the biochemical, glucose, and inflammatory parameters of blood in women with severe obesity before and after RYGB. Were enrolled female with severe obesity undergoing RYGP with MetS (n=11) and without (n=39). Anthropometric data and blood samples were obtained before and 6 months after RYGB to analyze total cholesterol, low-density lipoprotein (LDL), high- density lipoprotein (HDL), non-HDL total cholesterol, and glucose; and circulating levels of adiponectin and leptin. Significant reductions in weight, body mass index, and glucose, total cholesterol, LDL, and leptin were observed after surgery, with higher levels of HDL, adiponectin, and adiponectin/leptin ratio observed after surgery compared to preoperative values. This study demonstrated that weight loss induced by RYGB in patients with severe obesity with or without MetS improved biochemical and systemic inflammatory parameters, particularly the adiponectin/leptin ratio.

A variational analysis of dispersion medium (electrolytes and surfactants) was carried out for the best nucleotide interactions with the presence of nanoparticles and the ability to formation of homogeneous coatings upon drying / lyophilization. Using UV-spectroscopy and transmission electron microscopy, the processes of immobilization of nucleotides on the surface of nanoparti-cles of the composition ZrO2-3mol% Y2O3 (YSZ) in the presence of various dispersing agents were investigated. Promising dispersing agents were established, the optimal composition of suspen-sions based on DNA nucleotides and YSZ nanoparticles, which is potentially suitable for adaptive technologies of bionanoelectronics, was selected. The aim of the work is to obtain and study functional media for molecular electronics based on heterojunctions biological molecule – wide-gap dielectric.

A variational analysis of dispersion medium (electrolytes and surfactants) was carried out for the best nucleotide interactions with the presence of nanoparticles and the ability to formation of homogeneous coatings upon drying / lyophilization. Using UV-spectroscopy and transmission electron microscopy, the processes of immobilization of nucleotides on the surface of nanoparti-cles of the composition ZrO2-3mol% Y2O3 (YSZ) in the presence of various dispersing agents were investigated. Promising dispersing agents were established, the optimal composition of suspen-sions based on DNA nucleotides and YSZ nanoparticles, which is potentially suitable for adaptive technologies of bionanoelectronics, was selected. The aim of the work is to obtain and study functional media for molecular electronics based on heterojunctions biological molecule – wide-gap dielectric.

Several hypotheses have been presented on the origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from its identification as the agent causing the current coronavirus disease 19 (COVID-19) pandemic. So far, no hypothesis has managed to identify the origin, and the issue has resurfaced. Here we have unfolded a pattern of distribution of several mutations in the SARS-CoV-2 proteins across different continents comprising 24 geo-locations. The results showed an evenly uneven distribution of unique protein variants, distinct mutations, unique frequency of common conserved residues, and mutational residues across the 24 geo-locations. Furthermore, ample mutations were identified in the evolutionarily conserved invariant regions in the SARS-CoV-2 proteins across almost all geo-locations we have considered. This pattern of mutations potentially breaches the law of evolutionary conserved functional units of the beta-coronavirus genus. These mutations may lead to several novel SARS-CoV-2 variants with a high degree of transmissibility and virulence. A thorough investigation on the origin and characteristics of SARS-CoV-2 needs to be conducted in the interest of science and to be prepared to meet the challenges of potential future pandemics.

Background: The methods used in low- and middle-income countries (LMICs) household surveys have not changed in four decades; however, LMIC societies have changed substantially and now face unprecedented rates of urbanisation and urbanisation of poverty. This mismatch may result in unintentional exclusion of vulnerable and mobile urban populations. We compare three survey method innovations with standard survey methods in Kathmandu, Dhaka, and Hanoi, and summarize feasibility of our innovative methods in terms of time, cost, skill requirements, and experiences. Methods: We used descriptive statistics and regression techniques to compare respondent characteristics in samples drawn with innovative versus standard survey designs and household definitions, adjusting for sample probability weights and clustering. Feasibility of innovative methods was evaluated using a thematic framework analysis of focus group discussions with survey field staff, and via survey planner budgets. Results: We found that a common household definition excluded single adult (46.9%) and migrant headed households (6.7%), as well as non-married (8.5%), unemployed (10.5%), disabled (9.3%), and studying adults (14.3%). Further, standard two-stage sampling resulted in fewer single adult and non-family households than an innovative area-microcensus design; however, two-stage sampling resulted in more tent and shack dwellers. Our survey innovations provided good value for money and field staff experiences were neutral or positive. Staff recommended streamlining field tools and pairing technical and survey content experts during fieldwork. Conclusions: This evidence of exclusion of vulnerable and mobile urban populations in LMIC household surveys is deeply concerning, and underscores the need to modernize survey methods and practices.

The technology-driven world of the 21^st century is currently confronted with a major threat to humankind in the form of the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As of April 22, 2020, COVID-19 has claimed 169, 006 human lives and had spread to over 200 countries with more than 2,471,136 confirmed cases. The perpetually increasing figures associated with COVID-19 are disrupting the social and economic systems globally. The losses are unmatched and significantly higher compared to those from previously encountered pathogenic infections. Previously, two CoVs (SARS-CoV and Middle East respiratory syndrome-CoV) affected the human population in 2002 and 2012 in China and Saudi Arabia, respectively. Based on genomic similarities, animal-origin CoVs, primarily those infecting bats, civet cats, and pangolins, were presumed to be the source of emerging human CoVs, including the SARS-CoV-2. The cohesive approach amongst virologists, bioinformaticians, big data analysts, epidemiologists, and public health researchers across the globe has delivered high-end viral diagnostics. Similarly, vaccines and therapeutics against COVID-19 are currently in the pipeline for clinical trials. The rapidly evolving and popular technology of artificial intelligence played a major role in confirming and countering the COVID-19 pandemic using digital technologies and mathematical algorithms. In this review, we discuss the noteworthy advancements in the mitigation of the COVID-19 pandemic, focusing on the etiological viral agent, comparative genomic analysis, population susceptibility, disease epidemiology, animal reservoirs, laboratory animal models, disease transmission, diagnosis using artificial intelligence interventions, therapeutics and vaccines, and disease mitigation measures to combat disease dissemination.

Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutane-ous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG cytotoxic effect on bone marrow-derived mac-rophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound's efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction of lesion size and de-crease of parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index=432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and results in parasite clearance from ears and lymph nodes. It also diminished in-flammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-g, TNF) and the regulatory cytokine, IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusion: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.

The aim of this study was to analyze the relationship between healthy vascular aging (HVA) and the Mediterranean diet alongside other lifestyles in a Spanish population aged 35 to 75 years without previous cardiovascular diseases. Methods: Cross-sectional descriptive study with 501 individuals aged 35 to 75 years recruited from five health centers by random sampling stratified by age and sex (55.90±14.24 years, 49.70% men). HVA was determined in two steps. Step 1: Subjects with vascular damage to the carotid arteries or peripheral arterial disease were classified as non-HVA. Step 2: The study population was classified by age and sex using the percentiles of the vascular aging index (VAI), with VAI ≤p25 considered HVA and >p25 considered non-HVA. The VAI was estimated using the following formula (VAI = (log (1.09) × 10 cIMT + log (1.14) cfPWV) × 39.1 + 4.76. Carotid-femoral pulse wave velocity (cfPWV) was measured with the SphygmoCor® device and carotid intima-media thickness using Sonosite Micromax® ultrasound. Mediterranean diet (MD) adherence, alcohol and tobacco use were recorded through validated questionnaires. Physical activity was assessed with the ActiGraph-GT3X® accelerometer. Results: The mean VAI value was 61.23±12.86; (Men 63.47±13.75 and women 59.04±11.54; p

Chitosan is a biodegradable polymer derived from chitin, that is a versatile material for various biological applications for its attractive properties such as biocompatibility, biodegradability, and non-toxicity. Furthermore, chitosan possesses Second Harmonic Generation properties, that are useful for bio-sensing applications. In this work we explored the possibility to exploit chitosan-based nanospheres as SHG-based bio-sensors, and also as carriers of 89Sr radionuclide, an Active Pharmaceutical Ingredient for radiopharmaceutical treatments in cancer therapy. To load opportunely the Sr ion on the nanospheres, we used a fructose-based Metal Organic Framework, of formula [Sr(C6H12O6)2(H2O)2]Cl2·H2O, because the sugar was able to drive the Sr ions on the chitosan matrix. The Sr-loaded chitosan nanospheres were synthetized, characterized, and their SHG response was measured. The results encouraged us to propose the nanospheres for theranostic purposes, i.e. at the same time valuable for both therapy and diagnostic applications.