The dye effluent is usually difficult to be degraded by conventional wastewater treatment in leather industry. In order to develop efficient and cost-effective treatment methods, we evaluate the effect of white-rot fungus immobilization for dye decolorisation in this paper. The Phanerochaete chrysosporium BKM-F-1767 was used for immobilization. This research found that the white-rot fungus immobilization had an obviously decolorisation effect in dye wastewater treatment, and plant carriers such as sorghum stalk and corn cob were helpful to the growth of Phanerochaete chrysosporium in white-rot fungus immobilization. Due to the stability and recyclability, the white-rot fungus co-immobilization was considered as the most suitable treatment for decolorisation of dye effluent which enjoyed the advantages of both adsorption immobilization and entrapment immobilization. Furthermore, the dye decolorisation evaluation was carried out to find the most suitable carrier for co-immobilization, and it found that sorghum stalk - calcium-alginate gel spherical particle (SS-CGPB) has better decolorisation effect than corn cobs - calcium-alginate gel spherical particle (CC-CGPB), and the dye decolorisation rate was 86.77%. After 5 cycles, the dye decolorisation rate was 85.87% which indicated the SS-CGPB preserved functional integrity successfully. By further analyzing the biodegradation process with white-rot fungus immobilization, the intermediate products were observed and the degradation pathway of acid golden yellow dye molecular was proposed. The results showed that the C-N single bonds attached to the central benzene in the dye molecule were attacked and destroyed in white-rot fungus co-immobilization treatment, thus the structure of dye molecule could be successfully degraded into small molecules which would be more easily treated by conventional treatment methods. Therefore, the white rot fungus co-immobilization might be appropriate for pre-treatment as an important biotechnology for the advanced treatment of dye effluent.

Irish beef farms have experienced poor viability longitudinally, with officially acknowledged ‘crisis’ levels in 2013. In response, beef Producer Organisation (PO) legislation was introduced. Through the lens of international evidence in the literature about how POs function, this paper presents an analysis of Irish stakeholders’ views in the context of a public consultation process. While stakeholders indicate the need for individual POs to collaborate, little emphasis is placed on other factors necessary for success: collaboration with other chain actors; and market differentiation of products. Stakeholders identified primary threats as poor engagement on the part of both farmers and processors/purchasers.

Crotoxin (CTX), the predominant toxin in Crotalus durissus terrificus snake venom (CdtV), has anti-inflammatory and immunomodulatory effects. Despite its inhibitory action on neutrophil migration and phagocytosis, CTX does not directly affect the production of reactive oxygen species (ROS) by the neutrophils. In contrast, it enhances the generation of reactive oxygen and nitrogen intermediates by macrophages. Given the importance of macrophage-neutrophil interactions in innate antimicrobial defense, the aim of this study was to investigate the effect of CTX on neutrophil ROS production and killing activity, either through CTX-treated macrophage co-culture or conditioned medium of CTX-treated macrophages. The results showed an important modulatory action of CTX on the neutrophil function as well as neutrophil-macrophage interactions, as demonstrated by the increased production of hydrogen peroxide, hypochlorous acid, nitric oxide and TNF-α, along with the increased fungicidal activity of neutrophils.

Urban areas face daunting economic challenges that have increased in scope in recent years. At the same time, cities provide for opportunities for growth and value creation. The interplay of these challenges and opportunities represents the area of intervention for policymakers and researchers. However, the traditional approach to urban policy, deriving from the managerial and economic policy theories, shows difficulties mainly related to the capacity to counterbalance the interests and expectations of a multitude of stakeholders participating to the value co-creation process and to bring all different components to synergically contribute to the sustainability of the system. The Author proposes an innovative approach to urban public policy, by adopting the theoretical corpus of the Viable Systems Approach ("VSA"). Urban planning will be particularly analysed, as systemic components of urban areas, with the aim to investigate the decision-making processes for an integrated, efficient, effective and sustainable management of the territory as a multidimensional, multisectoral and multi-stakeholder entity. By recovering different settings, the VSA intends the co-creation of value as the capacity of the viable systems to increase its surviving chances in its own context. The value derives, first of all, from the strategic decisions aimed at finding both dyadic and context consonance. Through its strategic decisions, the Governing Body of the territory develops a specific system as the overall synthesis of all possible systems organised within a specific area, identifying pattern of development agreed by the several stakeholders of the territory. In the dynamics of value co-creation in systemic multi-subjective organizations, where the level of complexity is particularly significant, the research for consonance among different stakeholders is particular important in order to achieve the most value for the territory. In this respect, the VSA may constitute a valid tool, helping to find the necessary capacities to imagine evolutionary paths towards new competencies.

The present work investigates primarily the morphology evolution of the body-centered-cubic (BCC)/B2 phases in AlxNiCoFeCr high-entropy alloys (HEAs) with increasing Al content, which has been neglected so far. There exist two types of microscopic morphologies of BCC and B2 phases in this HEA series: one is the weave-like morphology induced by the spinodal decomposition, and the other is the microstructure of a spherical disordered BCC precipitation on the ordered B2 matrix that appears in HEAs with a much higher Al content. The shape of coherent precipitates is found to be closely related to the lattice misfit between BCC and B2 phases, which is sensitive to Al. The mechanical properties, including the compressive yielding strength and microhardness of the AlxNiCoFeCr HEAs, are also discussed in light of the concept of the valence electron concentration (VEC).

Community Acquired Urinary Tract Infections account for 15% of all outpatient use of antibiotics, women are primarily affected; major causative microorganisms are uro-pathogenic E. Coli. Treatment is indicated for cystitis and pyelonephritis and includes B-lactams (amoxicillin-clavulanic acid or third generation cephalosporins), fluoroquin-olones (ciprofloxacin or levofloxacin), nitrofurantoin, fosfomycin, and trime-thoprim-sulfamethoxazole. Resistance to antibiotic treatment is of concern, several mecha-nisms have been associated with the acquisition of genes that confer antimicrobial re-sistance to fluoroquinolones, which often are associated with other patterns of resistance, especially in extended spectrum beta lactases (ESBL) producers. Several studies have ad-dressed the prevalence of uropathogens producing ESBL, but only a few have focused on resistance against fluoroquinolones and to our knowledge, none has been addressing the prevalence of isolates mutations that confer antimicrobial resistance to fluoroquinolones. The focus of the present review was to analyze recent published papers that describe the E. coli phylotype causing community acquired UTIs in association to fluoroquinolones re-sistance.

Arterivirus can establish persistent infection in animals such as equids, pigs, nonhuman primates, rodents, and possums. Some Arterivirus can even cause overt and severe diseases such as Equine Arteritis in horses and Porcine Reproductive and Respiratory Syndrome in pigs, leading to huge economic losses. Arterivirus have evolved viral proteins to antagonize the host cell’s innate immune responses by inhibiting type I interferon (IFN) signaling, assisting viral evasion and persistent infection. So far, the role of the Arterivirus glycoprotein 5 (GP5) protein in IFN signaling inhibition remains unclear. Here, we investigated the inhibitory activity of 47 Arterivirus GP5 proteins derived from various hosts. We demonstrated that all GP5 proteins showed conserved activity for antagonizing TIR-domain-containing adapter protein inducing interferon-β (TRIF)-mediated IFN- signaling through TRIF degradation. In addition, Arterivirus GP5 proteins showed conserved inhibitory activity against IFN-β signaling, induced by either pig or human TRIF. Furthermore, certain Arterivirus GP5 proteins could inhibit the induction of IFN-stimulated genes. These findings highlight the role of Arterivirus GP5 proteins in supporting persistent infection.

Human papillomavirus (HPV), a DNA virus, causes one the most common sexually transmitted infections (STI), spreading through direct sexual contact to the anogenital and oropharyngeal regions. Although most infected individuals may be asymptomatic and naturally undergo viral clearance, in some individuals HPV causes carcinogenesis of the infected epithelia. HPV now accounts for over 70% of oropharyngeal carcinomas (OPC). More than 90% of these OPC are associated with HPV 16, one of the 14 high-risk subtypes. In recent years, HPV positive (HPV+) OPC has been one of the most rapidly rising cancers, by new cancer incidence rates, especially among men. The HPV driven OPCs present some unique infection driven cellular and molecular features, constituting distinct preventive, therapeutic and prognostic strategies, in contrast to HPV negative (HPV-) OPC. In this manuscript, we drive through the role of HPV, from a sexually transmitted infection to malignancy transformation landscape, while parsing through the significant immune response environment. In this comprehensive review we collate key literature around transmission and epidemiology of HPV, while addressing the current state of clinical management, diagnosis, prevention and screening strategies, that can help shed light on this critical area.

We analyze a time-delayed SIQR model that considers the transportation-related infections and entry-exit screening. This model aims to determine the measures for preventing and controlling major emergent infectious diseases and the associated costs. We calculate the basic reproduction number (R0), apply the linearization method, and construct an appropriate Lyapunov function to determine the stability of the disease-free equilibrium in the local and global. We collect COVID-19 infection data from two regions in the United States in 2020 for data fitting, obtain a set of optimal parameter values, and show that the model is suitable for simulating the outbreak and spread of emerging infectious diseases. We find that transportation-related infections increase the basic reproduction number, enhancing the impact on disease spread. Entry-exit screening effectively suppress the spread of disease by reducing the basic reproduction number. Furthermore, we investigate the influence of the incubation period on disease and find that a shorter incubation period results in a shorter duration but a larger scale of infection, and the peaks are reduced. We conduct a sensitivity analysis of the R0 and propose three measures to prevent the spread of new infectious diseases based on the most sensitive parameters: wearing masks, implementing urban closures, and administering medication to sick but not yet hospitalized patients promptly. In the case of COVID-19, we use Pontryagin’s minimum principle to get time-varying control measures to control the spread of the outbreak. Optimal control effectively controls the development and deterioration of the disease. Finally, several control measures are compared through cost-effectiveness analysis, and the results show that wearing masks is the most cost-effective measure. Our study provides some practical guidance for controlling the spread of major emerging infectious diseases.

Omicron SARS-CoV-2 variants have dominated the strains of COVID-19 circulating worldwide for the last two years. Although the mortality rate of the COVID-19 Omicron variants is only approximately half that of previous variants, vaccines effective against Omicron are needed. Demonstrating that a SARS-CoV-2 vaccine can protect against Omicron in an in vivo infection model, particularly in that of Syrian hamsters, is important for the preclinical characterization of SARS-CoV-2 vaccines. Here, we report on the evaluation of W-PreS-O for its ability to protect Syrian hamsters against infection by Omicron. W-PreS-O is a chimeric vaccine based on a single fusion protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron adsorbed to aluminum hydroxide. The Syrian hamsters were immunized three times at three-week intervals with W-PreS-O or with aluminum hydroxide (placebo), and then they were infected with Omicron BA.1. Non-infected and non-vaccinated animals served as controls. Neutralizing antibody (nAB) titers, weight, lung symptoms (i.e., edema and pneumonia index), and viral loads, as measured using RT-PCR in the upper and lower respiratory tracts, were determined. In addition, infectious virus titers from the lungs were measured using a plaque-forming assay. W-PreS-O-vaccinated hamsters developed robust nABs against Omicron, showed almost no development of pneumonia, and had significantly reduced infectious virus titers in the lungs. Importantly, the viral loads in the nasal cavities of W-PreS-O-vaccinated hamsters were close to or above the PCR cycle threshold considered to be non-infectious. Our data provide compelling evidence demonstrating that the W-PreS-O vaccine has protective effect against Omicron in a Syrian hamster in vivo infection model. W-PreS-O is therefore a highly promising candidate vaccine for Omicron infections, and it should be further evaluated in clinical studies.

From the existing millions of fungal species only a few cause disease. In this study, we investigated invasive fungal infections in the head and neck over a 19-year period (2005 to 2024) at a large academic healthcare system. Among 413 cases, 336 were noninvasive, and 77 were invasive. The highest incidence of invasive infections occurred in the sinonasal cavities, with a 15-fold difference compared to other sites. Most infections affected adults over 40 years old. The most common organisms were Mucorales (51%), hyaline molds (29%), and Candida (11%). Risk factors included malignancy, transplant, diabetes, and illicit drug use. Mortality was high in patients with malignancy and/or transplant. Infections affecting the mandible were usually a complication of osteoradionecrosis and were associated with coinfection of Candida and Actinomyces. At other sites, infections were rare and were usually the result of penetrating injuries or immunosuppression. Treatment typically involved a combination of antifungals and surgical procedures.

Acute kidney infection (AKI) occurred by tubular necrosis and glomerular dysfunction caused by many factors. SARS CoV-2 infection identified to cause fatal AKI. This paper aims to review the effect of covid-19 infection on the failure of the kidney and its mechanism. It identified that the SARS-CoV-2 received by the targeted cell by Angiotensin-converting enzyme 2 (ACE2). After the virus received by the target cells, it induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, and interferons (IFN) by immune cells and causes cytokine storm. The pro-inflammatory cytokines are again responsible to induce the secretion of cyclooxygenase‑2 (COX‑2), which causes inflammation and pain as well it stimulates the iNOS enzyme to produce NO which allows the vasodilation of renal arteries. The increased production of NO by iNO enhanced the vasodilation of arteries, and allows the adhesion of neutrophils to the artery, and causes damage to glomerulus and tubules. Hence, the most likely sustainable intervention could be the application of angiotensin-converting enzyme 2 (ACE2) inhibition by the receptors of the target cells in these vital organs to reduce sever destruction during treatment at the early stage of infection.

Background : Probiotics are composed of microorganisms that have positive effects on health when consumed in prescribed quantities. Lately, studies have attempted to establish this role of probiotics in enhancing health. Aim : The aim of this study was to compare the antifungal activity of 3 different probiotics against Candida albicans.Methodology :This was an in-vitro study. 3 types of commercially available probiotics - Bifilac, Pre pro HS and VSL-3 were cultured separately with Candida albicans and were placed under incubation. The maximum zone of inhibition was recorded for each of the probiotic solutions.Results : In this study, it was found that among the three probiotic products, Bifilac exhibited a maximum zone of inhibition of 13mm at concentration of 100µL against C. albicans, while Pre pro HS and VSL-3 showed zone of inhibition of 11mm at concentrations of 50µL and 100µL, respectively.Conclusion : Within the limits of the present study, This study could prove that probiotics can be considered as an alternative and safe treatment option for treatment of Oral candidiasis infections.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare immune-mediated relapsing-remitting disease of the central nervous system. The usage of rituximab, to prevent NMOSD relapses, is common in Sweden, but the knowledge on long-term efficacy and risk for severe infections are limited. We performed a retrospective cohort study with medical chart review of rituximab-treated NMOSD patients at the Karolinska University Hospital, Sweden, to assess the occurrence of relapses and severe infectious events (SIE). Furthermore, we collected data on CD19+ lymphocyte, and IgG levels during therapy. A total of 42 NMOSD patients; 24 with aquaporin -4 antibodies (AQP4+), eight with myelin oligodendrocyte glycoprotein antibodies (MOG+) and 10 with absence of antibodies (double-seronegative) were included. During a mean treatment time of 4.4 years, 37% AQP4+, 75% MOG+, and 60% double-seronegative patients experienced 1 relapse. SIEs were common with 46% of AQP4+, 25% of MOG+, and 40% of double-seronegative patients affected. Incomplete CD19+ lymphocyte suppression did not predict a relapse and there was no correlation between IgG levels and SIEs. In conclusion, our data demonstrated a high risk for both relapses and SIEs in rituximab-treated NMOSD patients highlighting the need for close clinical vigilance of disease activity and infections during treatment.

Objectives. Invasive fungal spondylodiscitis (IFSD) is rare and could be lethal in certain circumstances. Previous literature revealed limited data concerning the outcomes. This study aimed to establish a risk-scoring system. Methods. A total of 53 patients were included in the study from a multi-centered database in Taiwan. All the clinicopathological and laboratory data were retrospectively analyzed. Variables strongly related to 1-year mortality were identified using a multivariate Cox proportional hazards model. A receiver operating characteristic curve was used to express the performance of our IFSD scoring model. Results. Five strong predictors were included in the IFSD score: predisposing immunocompromised state, the initial presentation of either radiculopathy or myelopathy, initial laboratory findings of WBC > 12.0 or < 0.4 103/uL, hemoglobin < 8 g/dL, and evidence of candidemia. 1-year mortality rates for patients with IFSD Scores of 0, 1, 2, 3, and 4 were 0%, 16.7%, 56.3%, 72.7%, and 100%, respectively. The area under the curve of the receiver operating characteristic curve was 0.823. Conclusions. We developed a practical scoring model with easily obtained demographic, clinical, and laboratory parameters to predict the probability of 1-year mortality in patients with IFSD. However, more large-scale and international validations would be necessary before this scoring model is commonly used.

Innovative strategies to control malaria are urgently needed. Exploring the interplay between the Plasmodium sp. parasites and host red blood cells (RBC) offers opportunities for novel antimalarial interventions. Pyruvate kinase deficiency (PKD), characterized by heightened 2,3-diphosphoglycerate (2,3-DPG) concentration, has been associated with protection against malaria. Elevated 2,3-DPG levels, a specific mammalian metabolite, may hinder glycolysis, prompting us to hypothesize its potential contribution to PKD-mediated protection. We investigated the impact of the extracellular supplementation of 2,3-DPG on the Plasmodium falciparum intraerythrocytic developmental cycle in vitro. Results showed an inhibition of parasite growth, resulting from significantly less progeny from 2,3-DPG-treated parasites. We analyzed differential gene expression and the transcriptomic profile of P. falciparum trophozoites, from in vitro cultures submitted or not submitted to the action of 2,3-DPG, using Nanopore Sequencing Technology. The presence of 2,3-DPG in the culture medium was associated to a significant differential expression of 71 genes, mostly associated to GO terms nucleic acid binding, transcription, or monoatomic anion channel. Further, several genes related to the cell cycle control were downregulated in treated parasites. These findings suggest that the presence of this RBC-specific glycolytic metabolite impact the expression of genes transcribed during the parasite trophozoite stage and the number of merozoites released from individual schizonts, which supports the potential role of 2,3-DPG in the mechanism of protection against malaria by PKD.

Background: Urinary tract infection (UTI) is one of the commonest bacterial infections among reproductive age females. Untreated UTI in reproductive age female is associated with sexual dysfunction, cystitis, pyelonephritis and Pelvic inflammatory disease. At present, the antimicrobial resistance emergency has quadrupled worldwide and poses a serious threat to the treatment of patients. Thus, this study aimed to determine bacterial profile, antibiotic susceptibility pattern and associated risk factors of urinary tract infection among reproductive age females attending the Logbaba District Hospital Methods: A hospital-based cross-sectional study was conducted from January – July, 2023. Convenient sampling was employed to recruit 259 reproductive age females. Sociodemographic and risk factors information were obtained using a well-structured questionnaire. Mid-stream urine was collected and inoculated on cystine lactose electrolyte deficient media. Isolates were identified using API 20. Antibiotic sensitivity testing was performed using modified kirby-bauer susceptibility testing technique. Multivariate logistic regression model was used to assessed risk factors. A p-value < 0.05 was considered as statistically significant. Results: The overall prevalence of UTI among reproductive age females was 82/259 (31.66%). Symptomatic and asymptomatic patients reported a prevalence of 50/121(41.32%) and 32/138 (23.19%), respectively. Ages ranging from 21-30 years (AOR: 2.53 ,95% CI 1.32 – 4.43, p=0.006) and 31 – 40 years (AOR: 0.19 , 95% CI: 0.14- 0.54; p <0.0001), student (AOR: 1.8, 95% CI: 1.21 - 2.75; p = 0.010), history of UTI (5.34, 95% CI = 1.86 - 18.15; p = 0.03), symptomatic (AOR = 2.86, 95% CI1.78 - 4.67, p <0.0001) and secondary education (AOR: 0.13, 95% CI 0.08 - 0.32; p<0.0001) were predictors to UTI. Klebsiella Pneumoniae was the most frequent species 27 (32.9%), follow by E coli 22(26.8%), Staphylococcus aureus 16 (19.5%), CONS 8 (9.8%), Proteus mirabilis 6 (7.3 %) and Pseudomonas aeruginosa 3(3.7%). Majority of the isolates were sensitive to cefotaxime (87.80%), imipenem (85.7%), vancomycin (79.27%), Ofloxacillin (76.83%), Ceftriaxone (75.61%), Ciprofloxacin (74.39%), Gentamicin (71.95%) and Doxycycline (69.51%), and resistant to Amoxicillin (51.22%), cotrimoxazole (47.56%) and Azithromycin (31.71%) , All the isolates were multidrug drug resistant (100%) and Klebsiella Pneumoniae and E coli were the most multidrug drug resistant species Conclusion: In the present study, the prevalence of urinary tract infection among reproductive age females was high and considerably a high proportion of multidrug resistance was observed. This result will have a significant impact on the selection of appropriate antimicrobial agents for the treatment of urinary tract infection in the study area.

Vancomisin resistant enterococcus(VRE), is a resistant microorganism which colonizates and causes infections in hospitalized patients. It was aimed to show the spread of vancomycin-resistant Enterococcus (fVREfm) step-by-step in all intensive care units, which started with the growth of vancomycin-resistant Enterococcus faecium (VREfm) on 02.12.2021 in the blood culture of a patient hospitalized in the anesthesia intensive care unit of our hospital and was found to have reached epidemic size in the surveys. Rectal swab samples were taken from all patients hospitalized in intensive care units, VRE colonization was determined and the VanA and VanB resistance genes associated with vancomycin resistance of VREfm isolates were determined by PCR method, and clonal association analysis was performed by Arbitrarily Primed-PCR (AP-PCR) and Pulsed-Field Gel Electrophoresis. In our study, VRE was detected in 61 of 2601 rectal swab samples. 54 (85.52%) of the VRE isolates were Enterococcus faecium, 3 (4.91%) was Enterococcus faecalis, 3 (4.91%) was Enterococcus gallinorum, 1 (1.63%) was Enterococcus casseliflavus. It was determined that all of the 54 VREfm isolates, which were the most detected among all VRE isolates, carried the vanA gene. In the clonal association analysis of the isolates by AP-PCR and PFGE methods, it was found that they had 12 different genotypes, 48 of them were included in any cluster, the clustering rate was 88.8%, and the largest cluster was genotype 1 cluster with 36 isolates. Of the 54 patients with VREfm isolated recently, 18.51 percent of the clinical samples were isolated before the survey, and 9.24% were isolated after the survey. It was determined that 100% of VREfm isolates were resistant to ampicillin, levofloxacin, ciprofloxacin, high-level gentamicin, trimethoprim-sulfamethoxazole, teicoplanin, 7.4% to tigecycline and 1.85% to linezolid. In our study, in the clonal association analysis performed by isolating VREfm in rectal swab samples, it was found that 88.8% of the samples were indistinguishably similar and the increase in the number of VREfm infections after the index case in our hospital was associated with the epidemic. VREfm infections cause long term hospitalization, costs and also deaths, which shows the seriousness of the event, and the importance of the combination of epidemiological and molecular analysis in epidemic research.

Urinary tract infections (UTIs) are the second most common bacterial infection with high recurrence rates. A major causative agent of UTIs is uropathogenic Escherichia coli (UPEC), which can form persistent biofilms on urothelial surfaces and/or urinary catheters. Biofilms are inherently tolerant to antimicrobials, making them difficult to eradicate. Ciprofloxacin hybrids functionalised with nitroxides have previously shown enhanced biofilm eradication activity in vitro. Here, we evaluate a ciprofloxacin di-nitroxide hybrid (CDN11), previously reported to have antibiofilm activity against UPEC, as a potential UTI therapeutic in various infection models. We report potent CDN11 activity against mature biofilms formed by cystitis strain UTI89 inside polyethylene catheters. In infected human bladder cell monolayers, CDN11 afforded a 3-log reduction in UPEC colony forming units (CFU) compared to controls, including intracellular bacteria. Infected mouse bladders carrying biofilm-like intracellular UPEC reservoirs had reduced bacterial burdens following treatment with CDN11 ex vivo. Activity trends for CDN11 were comparable throughout all models, indicating that our testing pipeline was robust. New antimicrobial development is arduous and requires large investments of time and money. The pipeline described here could be readily used in testing new compounds, fast tracking the development of novel UTI therapeutics.

Our aim is to provide an insight of the procedures and the dynamics that lead the spread of contagious diseases through populations. Our simulation tool can increase our understanding on the spatial parameters which affect the diffusion of a virus. SIR models are based on the hypothesis that populations are “well mixed”. Our model constitutes an attempt to focus on the effects of the specific distribution of the initially infected individuals through the population and provide insights, considering the stochasticity of the transmission process. For this purpose, we represent the population using a square lattice of nodes. Each node represents an individual that may or may not carry the virus. Nodes that carry the virus can only transfer it to susceptible neighboring nodes. This important revision of the common SIR model provides a very realistic property: the same number of initially infected individuals can lead to multiple paths, depending on their initial distribution in the lattice. This property creates better predictions and probable scenarios to construct a probability function and appropriate confidence intervals. Finally, this structure permits realistic visualizations of the results to understand the procedure of contagion and spread of a disease and the effects of any measures applied.

Urinary tract infections are among the most frequent infectious diseases and require screening of a great amount of urine samples from patients. However, a high percentage of samples results as negative after urine culture plate test (CPT), demanding a simple and fast preliminary technique to screen out the negative samples. We propose a digital holographic microscopy (DHM) method to inspect fresh urine samples flowing in a glass capillary for 3 minutes, recording holograms at 2 frames per second. After digital reconstruction, bacteria, white and red blood cells, epithelial cells and crystals were identified and counted and the samples were classified as negative or positive according to clinical cutoff values. Taking CPT as reference, we processed 180 urine samples and compared the results with those of urine flow cytometry (UFC). Using standard evaluation metrics for our screening test, we found similar performance for DHM and UFC, indicating DHM as a suitable and fast screening technique retaining several advantages. As a benefit of DHM, the technique is label-free and does not require sample preparation. Moreover, the phase and amplitude images of the cells and other particles present in urine are digitally recorded and can serve for further investigation afterwards.

Heart transplantation is a treatment of choice for patients with severe heart failure. Infection transmission from a donor to a recipient remains a prominent problem in organ transplantation. However, the risk of SARS-CoV-2 transmission through nonlung organ transplantation is still unclear. In the article we present a case of a 28-year-old pregnant woman who developed heart failure soon after recovery from SARS-CoV-2 infection in the third trimester of gestation. In the postpartum period the disease worsened and the patient required cardiac transplantation. We examined the recipient's heart and diagnosed left ventricular noncompaction cardiomyopathy. Immunohistochemical analysis showed the SARS-CoV-2 antigen expression in the donor’s heart before transplantation and after the surgery the endomyocardial biopsy was taken. Moreover, an ultrastructural assessment of the endomyocardial specimen revealed endothelial and pericyte injury and single particles on the surface of endothelium consistent with SARS-CoV-2. Recent findings were associated these damages with SARS-CoV-2 infection. The present study describes the rare case of SARS-CoV-2 transmission from donor to recipient through a heart transplant and resulting in endothelial cell and pericyte activation and humoral immune response activation.

Background & aims. The fourth dose of anti-SARS-CoV-2 vaccine slightly improved the humoral response among previously seronegative liver transplant (LT) recipients. Mycophenolate (MMF) treatment worsens the vaccination response. This study aimed to evaluate whether temporary MMF interruption might improve immunogenicity of the fourth anti-SARS-CoV-2 BNT16b2 vaccine dose in nonresponsive LT recipients. Methods. LT recipients negative for anti-spike glycoprotein-specific immunoglobulin G receptor-binding domain (s-RBD) antibodies after the third vaccine dose were enrolled. Anti-SARS-CoV-2 spike-specific T cell responses were measured before and two months following the fourth vaccine dose, and anti-SARS-CoV-2-s-RBD antibodies also 6 months thereafter. MMF was suspended two weeks before and after vaccination. Results. Five LT recipients were enrolled. After a mean of 78 days after vaccination, all patients tested positive for anti-SARS-CoV-2-s-RBD antibodies. The mean antibody titer was 8944 UI/ml. The positive antibody response was maintained during a mean of 193 days of follow-up. Three patients developed a positive T cell response. Two patients (one positive for T cell response) developed a self-limited SARS-CoV-2 infection. Conclusions. Suspending MMF prior to the fourth dose of anti-SARS-CoV-2 mRNA vaccine seems feasible and safe. This procedure could restore vaccine-induced immunogenicity in a large portion of previously nonresponsive LT recipients.

Macrophage-derived chemokine belongs to the CC subfamily. It is produced by dendritic cells (DCs) and macrophages with or without external stimulation. We have previously shown a statistically significant depletion of MDC/CCL22 concentrations in a number of studies concerning COVID-19. These shifts in concentrations demonstrated stability unrelated to the SARS-CoV-2 genetic variant and remained noticeable even in convalescent patients. In this work, we analyze MDC/CCL22 dynamics in various diseases, including those that manifest with inflammation in lung tissue. In addition, we provide our hypothesis on such a decrease in MDC/CCL22 concentrations in COVID-19. If its secretion by producer cells is unperturbed, then it is possible for viral products to bind to this chemokine and to block its functional activity. There is, however, another possible explanation directly linked to depletion in DC subpopulations and the inhibition of their function. We also discuss MDC/CCL22's role in the immunology of novel coronavirus infection, based on both our own data and other studies.

Background: The objective of the present study was to evaluate the formation of biofilm in bone patellar tendon bone grafts (BPTB grafts) and to compare it to the formation of biofilm formation in quadrupled hamstring anterior cruciate ligament grafts (4xHt graft). Methods: A descriptive in vitro study was conducted. One 4xHt graft and one BPTB graft were prepared. They were then contaminated with a strain of S. epidermidis. Later, a quantitative analysis was carried out by means of microcalorimetry and sonication with plating. Additionally, a qualitative analysis was carried out by means of electron microscopy. Results: No significant differences were found between the bacterial growth profiles of 4xHt graft and BPTB graft in microcalorimetry and colony counting. In the samples analyzed with electron microscopy, no specific biofilm growth pattern was identified upon comparing BPTB graft to 4xHt graft. Conclusions: There were no significant differences at either the quantitative or qualitative level when comparing bacterial growth in BPTB graft to that in 4xHt graft. Therefore, the presence of sutures in 4xHt graft cannot be established as a predisposing factor for increased biofilm growth in this in vitro study.

By using the Sala-i-Martin version of extreme bounds analysis, which is based on the cumulative density function, cross-sectional evidence is presented on the robust determinants of the infection and case mortality rates of Covid-19. The results show that, for most part, different factors determine the infection and mortality rates in developed and developing countries. However, common factors are also apparent, including the risk environment, the number of tests per million and the percentage of population over 65. Notwithstanding the possibility that the official data represent a partial reflection of the truth, it is concluded that the results presented in this study provide useful information that may aid decision-making in the fight against the pandemic.

Staphylococci sp. have become the primary pathogens implicated in infective endocarditis, especially within high-income nations. Coupled with the increasing burden of healthcare with aging populations and the protracted course the infections may take, these infections contribute to a significant challenge for healthcare. A systematic review was conducted using relevant search criteria from PubMed, Ovid’s version of MEDLINE, and EMBASE, and data were tabulated from randomized controlled trials (RCT), observational cohort studies, meta-analysis, and basic research articles. The review was registered with the OSF register of systematic reviews and followed the PRISMA reporting guidelines. 35 studies met the inclusion criteria and were included in the final systematic review. The role of Staphylococcus aureus and its interaction with the protective shield and host protection functions is identified and highlighted in several studies. The interaction between infective endocarditis pathogens, vascular endothelium, and blood constituents is also explored giving rise to the potential use of antiplatelets as preventative and/or curative agents. Several factors allow Staphylococcus aureus infections to proliferate within the host with numerous promoting and perpetuating agents. The complex interaction with the hosts' innate immunity also potentiates its virulence. Ameliorating these molecular pathways may serve as a therapeutic avenue for the prevention and treatment of these infections in the near future.

Viruses feature an evolutionary shaped minimal genome that is obligately dependent on the cellular transcription and translation machinery for propagation. To suppress host cell immune responses and ensure efficient replication, viruses employ numerous tactics to favor viral gene expression and protein synthesis. This necessitates a carefully balanced network of virus- and host-encoded components, of which the RNA-based regulatory mechanisms have emerged as particularly interesting albeit insufficiently studied, especially in unicellular organisms. Here, recent advances that further our understanding of RNA-based translation regulation, mainly through post-transcriptional chemical modification of ribonucleosides, codon usage, and (virus-encoded) transfer RNAs, will be discussed in the context of viral infection.

Improving access to sexual health services is critical in light of rising sexually transmitted infections (STIs). We evaluated a Hub and Spoke model for improving access to sexual health services in three general practices in Victoria, Australia. The primary outcome was the impact on HIV and STI (chlamydia, gonorrhoea, syphilis) testing. Segmented linear regression analysis was conducted to examine the trends in the total HIV/STI tests before (from January 2019 to June 2020) and post-implementation (from July 2020 to July 2021). We evaluated the feasibility and acceptability of integrating this model into the general practices using semi-structured individual interviews. There was a statistically significant rise in testing for HIV and STIs in all general practices: post-implementation, there was an increase of an average of 11.2 chlamydia tests per month (p=0.026), 10.5 gonorrhoea tests per month (p=0.001), 4.3 syphilis tests per month (p=0.010), and 5.6 HIV tests per month (p=0.010). Participants reported increases in knowledge level and confidence in offering STI testing and managing more variety of sexual health cases. This study demonstrated the feasibility of implementing a hub and spoke model to enable GPs to deliver sexual health care with support from a sexual health specialist service.

Globally, over the past several months millions of persons contracted the coronavirus disease 2019 (COVID-19) resulting in significant mortality. Health care systems are negatively impacted including the care of individuals with cancers and other chronic diseases such as chronic active hepatitis, cirrhosis and hepatocellular carcinoma. There are various probable pathogenic mechanisms that have been presented to account for liver injury in COVID-19 patients such as hepatotoxicity cause by therapeutic drugs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the bile duct cells and hepatocytes, hypoxia and systemic inflammatory response. Liver biochemistry tests such as AST, ALT, GGT and ALP are deranged in COVID-19 patients with liver injury. Hepatocellular damage results in the elevation of serum AST and ALT levels in early onset disease while a cholestatic pattern that develops as the disease progress causes higher levels of ALP, GGT, direct and total bilirubin. These liver biochemistry tests are prognostic markers of disease severity and should be carefully monitored in COVID-19 patients. We conducted a systematic review of abnormal liver biochemistry tests in COVID-19 and the possible pathogenesis involved. Significant findings regarding the severity, hepatocellular pattern, incidence and related clinical outcomes in COVID-19 patients are highlighted.

Objective: To analyze the clinical and economic impact of community-onset urinary tract infections (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae requiring hospitalization. Methods: A retrospective cohort study included all adults with UTI caused by K. pneumoniae admitted to a tertiary care hospital in Barcelona, Spain, between 2011 and 2015. Demographic, clinical and economic data were analyzed. Results: One hundred and seventy-three episodes of UTI caused by K. pneumoniae were studied; 112 were non-ESBL-producing and 61 ESBL-producing. Multivariate analysis identified ESBL production, acute confusional state associated with UTI, shock, and time to adequate treatment as risk factors for clinical failure during the first 7 days. Economic analysis showed differences between ESBL-producing and non-ESBL-producing K. pneumoniae for the total cost of hospitalization per episode (mean 6,718 € vs 3,688 € respectively). Multivariate analysis of the higher costs of UTI episodes found statistically significant differences for ESBL production and time to adequate treatment. Conclusion: UTI caused by ESBL-producing K. pneumoniae requiring hospitalization, and time to adequate antimicrobial therapy are associated with worse clinical and economic outcomes.

In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio and other indices reflecting death rate, there is a consistent downward trend from mid-April to mid-August. The downward trend can be an illusion caused by biases and limitations of data or it could faithfully reflect a declining death rate. A variety of explanations for this trend are possible, but a systematic analysis of the testable predictions of the alternative hypotheses has not yet been attempted. We state six testable alternative hypotheses, analyse their testable predictions using public domain data and evaluate their relative contributions to the downward trend. We show that a decline in the death rate is real; changing age structure of the infected population and evolution of the virus towards reduced virulence are the most supported hypotheses and together contribute to major part of the trend. The testable predictions from other explanations including altered testing efficiency, time lag, improved treatment protocols and herd immunity are not consistently supported, or do not appear to make a major contribution to this trend although they may influence some other patterns of the epidemic.

Coinfections with bacteria or fungi may be a frequent complication of COVID-19, although coinfections with Candida species in COVID-19 patients remain rare. We report the 53-day clinical course of a complicated type-2 diabetes patient diagnosed with COVID-19, who developed bloodstream infections initially due to methicillin-resistant Staphylococcus aureus, secondly to multidrug-resistant Gram-negative bacteria, and lastly to a possibly fatal Candida glabrata. Development of FKS-associated pan-echinocandin resistance in the C. glabrata isolated from the patient after 13 days of caspofungin treatment aggravated the situation. The patient died of septic shock shortly before the prospect of receiving potentially effective antifungal therapy. This case emphasizes the importance of early diagnosis and monitoring for antimicrobial drug-resistant coinfections to reduce their unfavorable outcomes in COVID-19 patients.

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

Dual-method use is the most reliable form of protection against unintended pregnancies and HIV/STIs. Although dual-method use remains uncommon among women in stable relationships, some women do practice it. In this study, we explored the barriers that make dual-method use rare and the behaviors of women who practice dual-method use using a positive deviance framework in Uganda. We screened 150 women using highly effective contraceptives at five health facilities. We identified nine women who practiced dual-method use and 141 women who did not. In a qualitative study, we conducted in-depth interviews with all nine women practicing dual-method use and 10 women randomly selected out of the 141 who did not. We performed a thematic analysis using the positive deviance framework. Regardless of practicing dual-method use or not, women faced perceived barriers against dual-method use, such as partner’s objection, distrust, shyness about introducing condoms into marital relationships, and limited access to condoms. However, women practicing dual-method use had higher levels of risk perception about unintended pregnancies and HIV/STIs. They also engaged in unique behaviors, such as influencing their partners’ condom use by initiating discussions, educating their partners on sexual risks and condom use, and obtaining condoms by themselves. These findings will be useful in developing effective community-led and peer-based interventions promoting dual-method use to reduce the dual burden of unintended pregnancies and HIV/STIs among women in Uganda.

Background: SARS-CoV-2 has resulted in a global pandemic, COVID-19. The disease has spread outrageously from Wuhan, china to rest of the world affecting millions of people. The human transmission is mainly known to occur by aerosols. As almost every dental procedure is associated with aerosol production, oral health care professionals are at a high risk of getting the infection. An attempt has been made to render cohesive practical suggestions for dental professionals amid COVID-19 outbreak. Objectives: The paper aims at providing evidence based information in managing dental patients during this pandemic. Material and Methods: The paper provides a broad overview of predominant findings based on electronic database search regarding COVID-19 outbreak and its effect on dental practice. Conclusion: Dental care should not be neglected due to the pandemic. Thorough knowledge about the disease and its prevention will not only help us in providing care to these patients but will also help in preventing the nosocomial spread of infection.

Severe COVID-19 is associated with viraemia and multiple organ disease. Similar clinicopathological features have been previously seen in SARS and MERS. Clinically, the severity of SARS, MERS and COVID-19 has been associated with the presence of SARS-CoV, MERS-CoV or SARS-CoV2 viraemia in affected patients. In vitro work has looked at the pattern of viral entry and release from polarised epithelial cells infected by coronaviruses. This work has demonstrated a correlation between the severity of a coronavirus infection and the ability of the virus to reach and infect the basal surface of host cells. It has been postulated that this ability helps the virus invade the bloodstream of the host, resulting in a systemic infection with multiple organ involvement. Here we propose that basal surface release and entry of COVID-19 into and out of cells at epithelial-endothelial interface plays a key pathogenic role in severe COVID-19 disease.

Viral infections are a natural part of our existence. They can affect us in many ways that are the result of the interaction between the viral pathogen and our immune system. Most times the resulting immune response is beneficial for the host. The pathogen gets cleared thus protecting our vital organs with no other consequences. Conversely, the reaction of our immune system against the pathogen can cause organ damage (immunopathology) or lead to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the “fertile field” hypothesis, terms defined in our review. On the flip side, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”, also defined here. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototypes showing that the interaction of our immune system with viruses can either accelerate or prevent autoimmunity. Studies using mouse models of LCMV have helped conceive and establish several concepts that we today know and explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established during the course LCMV are described in this short review.

Background: Low-income families often depend on fuels such as wood, coal, and animal dung for cooking. Such solid fuels are highly polluting and are a primary source of indoor air pollutants (IAP). We examined the association between solid fuel use (SFU) and acute respiratory infection (ARI) among under-five children in Afghanistan and the extent to which this association varies by socioeconomic status (SES) and gender. Materials and Methods: This is a cross-sectional study based on de-identified data from Afghanistan’s first standard Demographic and Health Survey conducted in 2015. The sample consists of ever-married mothers with under-five children in the household (n=27,565). We used mixed-effect Poisson regression models with robust error variance accounting for clustering to examine the associations between SFU and ARI among under-five children after adjusting for potential confounders. We also investigated potential effect modification by SES and sex. Additional analyses were conducted using an augmented measure of the exposure to IAP accounting for both SFU and the location of cooking/kitchen (High Exposure, Moderate, and No Exposure). Results: Around 70% of households reported SFU, whereas the prevalence of ARI was 17.6%. The prevalence of ARI was higher in children living in households with SFU compared to children living in households with no SFU (adjusted prevalence ratio [aPR]= 1.10; 95%CI: 0.98, 1.23). We did not observe any effect modification by SES or child sex. When using the augmented measure of exposure incorporating the kitchen’s location, children highly exposed to IAP had a higher prevalence of ARI compared to unexposed children (aPR 1.17; 95% CI: 1.03, 1.32). SES modified this association with the strongest associations observed among children from the middle wealth quintile. Conclusion: The findings have significant policy implications and suggest that ARI risk in children may be reduced by ensuring clean cookstove as well as clean fuels and acting on the socio-environmental pathways.

Hepatitis-C is one of the most common viral diseases caused by hepatitis C virus (HCV). It is responsible for millions of deaths each year in the developing world. The common dissemination paths of HCV include the use of contaminated water and transfusion of infected blood. Control of this virus has become a challenge for scientists and health professionals due to its versatility and adaptability in different host environments. Along with other problems, lack of efficient diagnosis, quantification and genotyping of viral strains are the major hindrances in a management of this notorious epidemic. The knowledge of HCV genotype and an amount of virus in patient’s blood are pre-requisites to determine the duration and method of treatment. In this review, we discuss the implications of HCV molecular diagnostic methods and their clinical applications. We conclude that while, several commercial and home-brewed methods are available for this purpose, and there is a visible vacuum for cost effective, robust, sensitive assays that can detect multiple viral genotypes in a single reaction. We are of the view that the level of sensitivity offered by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) technique is unequivocal as compared to other techniques. Therefore, researchers may explore further possibilities using this technique in the management of HCV.

The urinary tract infection (UTI) is the most common bacterial infection, especially in women. The increased incidence of UTIs, at the last decades have paralleled with the growing emergence of antibiotic resistance. The aim is to evaluate aqueous garlic extract (AGE) susceptibility against multidrug-resistant (MDR) bacteria isolated in urine of women. The investigation of antibacterial propriety and time kill effect of AGE was performed by the well method, microdilution method and spectrophotometer assay. Antibiotics susceptibility assay revealed that the nine MDR bacteria had high resistance against Amoxicillin/ clavulanic acid (100%) and Erythromycin (100%), Cefotaxime (83.33%) and Ceftazidime (83.33%). AGE exhibited potent antibacterial activity against the nine MDR bacteria tested. In Gram-negative bacteria, the inhibition diameters ranged from 20 ± 3 to 32 ± 4 mm, with Minimum Inhibitory Concentrations (MICs) ranging from 10% to 12.5% (w/v) and Minimum Bactericidal Concentration (MBCs) was 12.5 % (w/v). Gram-positive bacteria exhibited diameters ranging from 38 ± 2 to 45 ± 1 mm; MIC and MBC values ranged from 05 to 10 % (w/v) and were found more susceptible than Gram-negative bacteria. To conclude, this investigation shown that AGE have high potential antibacterial to use as an alternative to treat women UTIs.

Pathogenic Salmonella strains have a set of virulence factors allowing them to generate systemic infections and damage in a variety of hosts. Among these factors, bacterial proteins secreted by specialized systems are used to penetrate the host’s intestinal mucosa, through the invasion and destruction of specialized epithelial M cells in the intestine. On the other hand, numerous studies have demonstrated that humans, as well as experimental animal hosts, respond to Salmonella infection by activating both innate and adaptive immune responses. Here, through live cell imaging of S. Typhimurium infection of zebrafish larvae, we showed that besides the intestinal colonization, a deformed cloacae region and a concomitant accumulation of S. Typhimurium cells was observed upon bacterial infection. The swelling led to a persistent inflammation of infected larvae, although the infection was non-lethal. The in vivo inflammation process was confirmed by the co-localization of GFP-tagged S. Typhimurium with mCherry-tagged neutrophils at 72 hours post exposition. Our live-cell analyses suggest that Salmonella Typhimurium induce cloacitis-like symptoms in zebrafish larvae. Typhimurium induce cloacitis-like symptoms in zebrafish larvae.

This qualitative study explores the role of supply chain partnerships in enhancing brand value through collaborative marketing efforts. By analyzing diverse cases from industries including consumer electronics, apparel, automotive, and food and beverage, the research examines how different forms of partnerships—strategic alliances, co-marketing, joint ventures, and supplier integrations—contribute to brand value. The study employed a multiple case study design, incorporating semi-structured interviews, document analysis, and participant observations to gather data. The findings reveal that these partnerships enable companies to leverage complementary strengths, resulting in enhanced innovation, product quality, sustainability, market reach, and ethical standards. Collaborative marketing strategies such as joint product launches, sustainable branding campaigns, and co-developed customer programs are identified as key drivers of brand value, effectively increasing brand awareness, customer loyalty, market share, and perceived quality. Despite challenges like coordination complexity, goal misalignment, cultural differences, and cost management issues, the benefits realized—such as improved brand image, faster time-to-market, and reduced costs—demonstrate the substantial value of effective supply chain partnerships. The study underscores the importance of strategic alignment between supply chain activities and brand objectives, highlighting that successful partnerships foster deeper consumer engagement and stronger market positions. This research provides actionable insights for companies seeking to optimize their supply chain collaborations to enhance brand value, offering a foundation for future studies and practical applications in supply chain management and marketing. The findings contribute to a deeper understanding of how supply chain partnerships can be strategically managed to drive brand excellence in a competitive market environment.

Background: Pediatric forearm fractures represent a substantial proportion of childhood injuries, requiring effective and minimally invasive treatments. Our study investigated the mid-term outcomes of biodegradable poly-L-lactide-co-glycolide (PLGA) intramedullary implants in managing diaphyseal forearm fractures in children. Methods: A follow-up cohort study was conducted with 38 patients treated with PLGA implants. Control examinations were performed one year post-operation, assessing bone healing through radiographic evaluations and functional outcomes using injured and uninjured limb range of motion (ROM) comparisons. Scarring was evaluated employing the Vancouver Scar Scale (VSS), and satisfaction via a questionnaire. Results: Children were predominantly female (76.4%), with a mean age of 9.71 (SD: 2.69) years. Effective fracture stabilization and bone healing were found in all patients, with a minor reduction (mean difference of -1.5°, p = 0.282) in elbow flexion on the operated side (139.3°) compared to the intact (140.8°). Elbow extension presented negligible average changes (0.2°, p= 0.098). Forearm movements were slightly reduced on the operated side (mean pronation: 80.8° vs. 83.7°, p= 0.166; average supination: 83.5° vs. 85.7°, p= 0.141). Wrist palmar flexion and dorsiflexion showed no significant differences. VSS ratings indicated minimal scarring (mean guardian and doctor scores were 1.13 and 0.55, respectively, p= 0.020), and all patients reported satisfaction with the treatment outcomes. Conclusion: Biodegradable implants are effective for pediatric forearm fractures, providing stable bone healing while preserving functional ROM with minimal scarring and high patient satisfaction. PLGA proved to be a viable alternative to traditional metal implants, eliminating secondary removal surgeries.

In the global carbon cycle, atmospheric carbon emissions, both ‘natural’ and anthropogenic, are balanced by carbon uptake (i.e. sequestration) that mostly occurs via photosynthesis, plus a much smaller proportion via geological processes. Since the formation of the Earth about 4.54 billion years ago the ratio between emitted and sequestered carbon has varied considerably with atmospheric CO₂ levels ranging from 100,000 ppm to a mere 100 ppm. Over this time, a huge amount of carbon has been sequestered due to photosynthesis and essentially removed from the cycle, being buried as fossil deposits of coal, oil and gas. Relatively low atmospheric CO₂ levels were the norm for the past 10 million years, and during the past million years they averaged about 220 ppm. More recently, the Holocene epoch, starting ~11,700 years ago, has been a period of unusual climatic stability with relatively warm, moist conditions and low atmospheric CO₂ levels of between 260 and 280 ppm. During the Holocene, stable conditions facilitated a social revolution with domestication of crops and livestock leading to urbanisation and development of complex technologies. As part of the latter process, immense quantities of sequestered fossil carbon have recently been used as energy sources, resulting in a particularly rapid increase in CO₂ emissions after 1950 CE to the current value of 424 ppm, with further rises to >800 ppm predicted by 2100. This is already perturbing the previously stable Holocene climate and threatening future food production and social stability. Today, the global carbon cycle has been shifted such that carbon sequestration is no longer keeping up with recent anthropogenic emissions. In order to address this imbalance it is important to understand the roles of high-capacity carbon sequestration systems, such as natural forests and tropical croplands, and to devise strategies to facilitate net CO₂ uptake.

Currently, there is a tenacious need to find new ways to purify water by eliminating bacterial biofilms, textile dyes, and toxic water pollutants. These contaminants pose significant risks to both human health and the environment. To address this issue, in this study, we have developed an eco-friendly approach that involves synthesizing Cobalt-doped Cerium Iron Oxide (CCIO) nanocomposite (NC) using an aqueous extract of Gossypium arboreum L. stalks. The resulting nanoparticles can be used to effectively purify water and tackle the challenges associated with these harmful pollutants. Nanoparticles excel in water pollutant removal by providing high surface area for efficient adsorption, versatile design for simultaneous removal of multiple contaminants, catalytic properties for organic pollutant degradation, and magnetic features for easy separation, offering cost-effective and sustainable water treatment solutions. CCIO nanocomposite has been synthesized by green co-precipitation method due to biomolecules and co-enzymes present in the aqueous extract of Gossypium arboreum L. stalk; a single-step procedure completed in 5 h reaction time. Further, the synthesis of nanocomposites was confirmed by various characterization techniques such as Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), Field emission scanning electron microscopy (FE-SEM), Transmission electron microscopy (TEM), Thermogravimetric analysis (TGA), Dynamic light scattering (DLS), and Energy Dispersive X-Ray (EDX). CCIO NCs were discovered to have a spherical shape and an average size of 40 nm. Based on DLS zeta potential analysis, CCIO NCs were found to be anionic. Also, CCIO NCs showed significant antimicrobial and antioxidant activity. Overall, considering the physical and chemical properties, the application of CCIO NCs in the adsorption of various dyes (~91 %) and water pollutants (chromium = ~ 60 %) has been considered since they exhibit great adsorption capacity owing to their microporous structure which can be a step forward in water purification.

This research explores the behaviors of Generation Z consumers in China, particularly focusing on their interaction with companies through social media for the joint creation of value. Adopting a qualitative methodology, the research initially constructs a scale for assessing co-creation of value on social media platforms. Subsequently, it delves into the motivational aspects of users' engagement in these co-creative activities. The study unveils a range of utilitarian and hedonic motivations that drive Generation Z's value co-creation actions on social media. Insights derived from the findings offer both theoretical and practical implications for the field.

Viral co-infections, where a host is infected by multiple viruses simultaneously, are common in the human population. Human viral co-infections can lead to complex interactions between viruses and the host immune system, affecting the clinical outcome and posing challenges for treatment. Understanding the types, mechanisms, impacts, and identification methods of human viral co-infections is crucial for the prevention and control of viral diseases. In this review, we first introduce the significance of studying human viral co-infections and summarize the current research progress and gaps in this field. We then classify human viral co-infections into four types based on the pathogenic properties and species of the viruses involved. Next, we discuss the molecular mechanisms of viral co-infections, focusing on virus-virus interactions, host immune responses, and clinical manifestations. We also summarize the experimental and computational methods for identifying viral co-infections, emphasizing the latest advances in high-throughput sequencing and bioinformatics approaches. Finally, we highlight the challenges and future directions in human viral co-infection research, aiming to provide new insights and strategies for the prevention, control, diagnosis, and treatment of viral diseases. This review provides a comprehensive overview of the current knowledge and future perspectives on human viral co-infections, and underscores the need for interdisciplinary collaborations to address this complex and important topic.

Spinocerebellar ataxia type 3 is a neurodegenerative disease caused by an abnormal expansion of CAG repeats in the disease gene ATXN3, leading to prolonged polyglutamine (polyQ) tracts in the respective protein ataxin-3. The polyQ-expanded protein forms polyQ-containing aggregates in several brain regions which leads to neuronal cell loss. Autophagy is thought to play a significant role in clearing these polyQ-containing protein aggregates. Therefore, the autophagy mechanism was investigated in SCA3 with focus on the autophagic protein p62/sequestosome-1. Human and mouse RNA sequencing data were analyzed to determine RNA expression level of autophagic genes. Additionally, autophagy was studied in the SCA3 304Q knock-in mouse model and through several cell culture experiments using HEK-293T cells transfected with ATXN3 of differ-ent polyQ lengths. For cell culture experiments, autophagy was induced with rapamycin treat-ment, proteasomal degradation was blocked with MG132 and degradation of autophagic pro-teins was investigated using cycloheximide treatment. Here, we report an increased autophagy impairment with SCA3 disease progression seen in HEK-293T cells transfected with ATXN3 plasmid with expanded polyQ tracts, higher aged 304Q-knock-in mice, or human post-mortem brain material. Furthermore, co-localized aggregation of the autophagic protein p62 and the dis-ease protein ATXN3 was observed in the course of SCA3 disease. Therefore, we suggest a signifi-cant role for p62 in aggregate formation seen in the neurodegenerative disease SCA3.

This study investigates the influence of economic growth on CO2 emissions levels in three developed countries—Argentina, Equatorial Guinea, and South Korea—based on their status as high-income countries. We test the environmental Kuznets curve (EKC) hypothesis using the time series approaches to check the relationship and direction of causality among the variables over a sample spanning 1974–2020. The results show an inverted U-shaped short-run relationship in all three countries. In the long run, only South Korea supports the EKC hypothesis. Further, Granger causality results indicate the existence of causality. These long-run causal relationships between economic growth and emissions recommend one policy implication that wealthy governments must expand investments in renewable clean energy projects and R&D, with regulatory measures to suppress harmful environmental procedures and support environmentally friendly development.

A bridged 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) derivative (PN-DOPO) in combination with aluminum phosphates coated sepiolite (Sep@AlPO4) was used to improve the flame retardancy, thermal stability and mechanical properties of poly (ethylene oxide) (PEO)/poly (butylene adipate-co-terephthalate) (PBAT) blends. The synergistic effects of PN-DOPO and Sep@AlPO4 on the fire resistance, thermal decomposition behavior and mechanical properties of PEO/PBAT composites were investigated systematically. The results indicated that 5 wt % Sep@AlPO4 combined with 10 wt% PN-DOPO into PEO/PBAT achieved a V-1 rating in UL-94 test and the LOI value increased to 23.7%, meanwhile, the peak-heat release rate (p-HRR), av-HRR and total heat release (THR) values of PEO/PBAT/PN10%/Sep5% composites decreased by 35.6%, 11.0% and 23.0% compared with those of PEO/PBAT, respectively. The thermogravimetric analysis (TGA) results confirmed that PN-DOPO/Sep@AlPO4 could enhance the initial thermal stability and char yield of PEO/PBAT matrix, and TGA/Fourier transform infrared spectrometry (TGA-FTIR) results revealed that the composites exhibited the absorption peaks of phosphorous-containing groups and an increase in gas-phase volatiles during the thermal decomposition process. The digital photographs and morphological structures of char residues demonstrated that PN-DOPO and Sep@AlPO4 mixtures benefited to the formation of a more continuous and dense carbon layer on the composites surface during combustion. Rheological behavior revealed that a higher storage modulus, loss modulus and complex viscosity of PEO/PBAT/PN-DOPO/Sep@AlPO4 composites could also promote the cross-linking structure during burning. Furthermore, the PEO/PBAT/PN-DOPO/Sep@AlPO4 composites exhibited excellent mechanical properties in terms of elongation at break and flexural performance than the PEO/PBAT system. All the results demonstrated that PEO/PBAT system modified by the combination of PN-DOPO and Sep@AlPO4 not only exhibited excellent synergistic effect on the flame retardance, but also had good improvement on thermal stability and mechanical properties, indicating the potential application in areas requiring fire safety.

The devastating effects of COVID-19 permeates virtually all aspects of life across geographic boundaries. As the lockdown is eased, and reinstated, across many parts of the world, attention is now shifting towards how to navigate the ‘now normal’ rather than the ‘next normal,’ of doing business with a view to achieving sustainable development. This study highlights some of the challenges and opportunities for micro, small, and medium enterprises (MSMEs) in times of crisis such as COVID-19. Conceptual by orientation, the study provides a broad overview of trends in crises times, drawing upon a range of qualitative accounts. The overarching message is the current direction of travel for MSMEs in sustaining their bottom-line, not after the crisis, but at this particular moment in time. The study highlights some implications for ‘pivoting,’ in order to cushion the impact of the pandemic on efforts to capacitate MSMEs in leveraging value co-creation with the consumers. The implications of the here and now are discussed.

K-Rb-83Kr based atomic co-magnetometer for measuring moving MEGs is theoretically studied in this paper. Parameters such as the spin exchange rates, the spin dephasing rates and the polarization of the nuclear spins are studied to configure the co-magnetometer. Results show that the nuclear spin could generate around 700 nT magnetic field under which the nuclear spin could compensate wide range of magnetic fields. We also showed the hybrid optical pumping vapor cell fabrication process in this paper. Alkali metals were mixed in a glove box and then was connected to the alkali vapor cell fabrication system. The vapor cell fabrication process is illustrated in this paper.

Transition metal alloys have emerged as promising electrocatalysts due to their ability to modulate key parameters such as d-band electron filling, Fermi level energy, and interatomic spacing, thereby influencing their affinity towards reaction intermediates. However, the structural stability of alloy electrocatalysts during alkaline hydrogen evolution reaction (HER) remains a subject of debate. In this study, we systematically investigate the structural evolution and catalytic activity of the c-Co/Co3Mo electrocatalyst under alkaline HER conditions. We reveal that the instability of the Co3Mo alloy and H0.9MoO3 during alkaline HER leads to the destruction of the crystal structure, resulting in the formation of hexagonal cobalt (h-Co) from hexagonal Co(OH)2 as an intermediate species. Furthermore, we explore the re-adsorption and surface coordination of the Mo element, which enhances the catalytic activity for alkaline HER. This work provides valuable insights into the dynamic behavior of alloy-based electrocatalysts, shedding light on their structural stability and catalytic activity during electrochemical reduction processes

Drought is one of the most serious abiotic stressors in the environment, restricting agricultural production by reducing plant growth, development, and productivity. To investigate such a complex and multifaceted stressor and its effects on the plants, a systems biology-based approach is necessitated, entailing the generation of co-expression networks, identification of highly-priority transcription factors (TFs) dynamic mathematical modeling, and computational simulations. Here, we studied a high-resolution drought transcriptome of Arabidopsis. We revealed distinct temporal transcriptional signatures and demonstrated the involvement of specific biological pathways. Generation of a large-scale co-expression network followed by network centrality analyses identified 117 TFs that possess critical properties of hubs, bottlenecks, and high clustering coefficients nodes. Dynamic transcriptional regulatory modeling on integrated TF-target and transcriptome datasets uncovered major transcriptional events during the course of drought stress. Mathematical transcriptional simulations allowed us to ascertain the activation status of major TFs as well as the transcriptional intensity and amplitude of their target genes. Finally, we validated our predictions by providing experimental evidence of gene expression under drought stress for a set of four TFs and their major target genes using qRT-PCR. Taken together, we provided a systems-level perspective on the dynamic transcriptional regulation during drought stress in Arabidopsis and uncovered numerous novel TFs that can potentially be used in future genetic crop engineering programs.

Escherichia coli and Shigella are common diarrhea-causing pathogens in children and adults. Enteroinvasive Escherichia coli (EIEC) shares a similar pathogenic mechanism with Shigella. However, EIEC are less virulent than Shigella. The aim of this work was to get a better understanding of the virulence differences between EIEC and S. flexneri. We investigated i) the bacterial gene co-expression networks (GCNs) and ii) the the transcriptional modules (WGCNA) of Caco-2 cells infected with EIEC or with S. flexneri during a three-hour period of bacterial infection. The GCN analysis showed that EIEC and S. flexneri networks presented different topologies. Additionally, the EIEC network revealed that pINV genes are not connected with chromosomal genes. WGCNA and eigengene analysis showed enterocyte gene expression variation along the three-hour bacterial post-infection period. Additionally, at one-hour post-infection EIEC induced a higher number of gene expression changes in Caco-2 cells than S. flexneri. Several of these genes are involved in autophagy. This study showed that the lower virulence of EIEC is associated with a lack of functional cooperation between pINV and chromosomal genes, differently from what was observed in S. flexneri. Consequently, EIEC becomes less efficient in subverting host-cell bacterial recognition as well as defense mechanisms such as autophagy.

Heat shock proteins (HSPs) are a family of molecular chaperones that regulate essential protein refolding and triage decisions to maintaining protein homeostasis. Numerous co-chaperone proteins directly interact and modify the function of HSPs, and these interactions impact the outcome of protein triage, impacting everything from structural proteins to cell signaling mediators. The chaperone/co-chaperone machinery protects against various stressors to ensuring cellular function in the face of stress. However, coding mutations, expression changes, and post-translational modifications of the chaperone/co-chaperone machinery can alter the cellular stress response. Importantly, these dysfunctions appear to contribute to numerous human diseases. Therapeutic targeting of chaperones is an attractive but challenging approach due to the vast functions of HSPs, likely contributing to the off-target effects of these therapies. Current efforts focus on targeting co-chaperones to develop precise treatments for numerous diseases caused by defects in protein quality control. This review focuses on the recent developments regarding selected HSP70/HSP90 co-chaperones, focusing on cardioprotection, neuroprotection, and cancer. We also discuss therapeutic approaches that highlight both the utility and challenges of targeting co-chaperones.

The fusion of "innovation theory" and "ecology" gave birth to a large number of studies on "innovation ecology", which mainly studies how to build an industrial ecological chain at the regional level, focusing on self-evolution, achieving ecological balance, and enabling the regional economy to take the path of sustainable innovation. This type of research borrows a lot of concepts from ecology, and very vividly describes the competition and cooperation relationships formed by various agents in the innovation system, laying a good foundation for qualitative analysis of the inherent dynamics of innovation development. However, many studies focus on the analogous description of ecosystems and economic systems, lacking scientifically and rigorously quantitative empirical research as a support. This paper uses network-based indicators such as degree, cluster coefficient, and betweenness centrality to measure the function and position of high-tech enterprises in the Z-Park in a business environment, so as to clarify the socio-economic meaning of the topological structure of the regional innovation system. On this basis, it provides theoretical references for regional innovation development and sustainable development policy formulation.

We present a normative methodology, for value-pricing B2B services, using a Nash Equilibrium mechanism. Value is fundamental to any service, yet it has defied a definition. The literature is conspicuously silent on how to define value, but abounds in richly descriptive characterizations. To overcome this deficit, we focus on the financial economics of service-value. We formulate an axiomatic definition and a differential equation that embodies the idea of service-value. We specify a set of value axioms and multidisciplinary postulates that coherently form our service-value constructs. Value-pricing is challenging. It is natural that providers desire a high price and customers want a low price. Realistically, both will agree on a win-win price. To uncover this price, we specify an algorithm to reveal the Nash Equilibrium. Once agreed, it validates providers’ and customers’ commitments, and payment obligations. Service value is cocreated by both provider and customer. For a reciprocal process, its treatment is remarkably asymmetric favoring the customer. We argue that one-sided descriptions of value-in-use and value-proposition are limiting mental models. We propose the additional ideas of value-from-use and value-supposition to strengthen the conceptual symmetry of cocreation. Our work reveals a critical gap in service science, metrology. Metrology, the science of measurements, is absent from service-science. Service-value is silent on the questions of quantities, units, scales, measurement principles and instruments. We argue for a call to action for Service Metrology. We sketch a roadmap of actionable suggestions to get started.

Recently, Indium Tin Oxide, a highly transparent, well conductive, and CMOS-compatible material, has been paying strong attention to the thermo-optic controlled silicon photonics industry because it allows a miniature of the gap between the core silicon and the heater, thus enabling reducing the electric power consumption and enhancing the switching speed. In this article, we propose an ultralow loss and small-size ITO microheater for the phase shift tuning. The designated microheater is manipulated in realizing a numerical co-design of compact and high bandwidth three-mode converter and three-mode selective router. Simulation results illustrate the 3-dB bandwidth for the three-mode converter and three-mode selective router as much as 100-nm and 40-nm during crosstalk under -25 dB, respectively. Besides, co-designed devices attain relatively large fabrication tolerances corresponding to width and height tolerances of ±50 nm and ±5 nm. In addition, the proposed devices consumed less than 90 mW total power consumption and took a fast switching time below 8 μs. Moreover, both two co-designs can be integrated into an estimated compact footprint of 8 μm2160 μm. Such excellent performances demonstrate the attractive potential of ITO as low-loss thermo-optic phase shifters and open an alternative way for enabling ultrafast and high-speed mode division multiplexing systems and very large-scale photonic integrated circuits.

The extracts from the aerial parts of Helianthus salicifolius A. Dietr and Helianthus tuberosus L. collected in June were obtained using carbon dioxide supercritical fluid extraction with water as co-solvent. The antimicrobial activity in vitro of these extracts were determined against the reference species of Gram-positive and Gram-negative bacteria as well as fungi, representing by the yeast species of Candida spp. The following parameters were estimated: minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC). Both extracts were found to possess antimicrobial activity with MIC = 0.62-5 mg mL-1 for bacteria and MIC = 5-10 mg mL-1 for yeasts, showing bactericidal (MBC/MIC = 2-4) or fungicidal effect (MFC/MIC = 1-2 ). The highest activity was observed against S. aureus ATCC 29213 (MIC = 0.62 mg mL-1 for H. salicifolius extract; MIC = 2.5 mg mL-1 for H. tuberosus extract). Bactericidal effect of both extracts against S. aureus ATCC 29213 was confirmed by time-kill assay. Higher antioxidant activity was found for H. tuberosus extract (EC50 = 0.332 mg mL-1) as compared to that of H. salicifolius (EC50 = 0.609 mg mL-1). The total polyphenol content (TPC) expressed as gallic acid equivalents (GAE) was 13.75 ± 0.50 mg GAE (g of H. salicifolius extract)-1 and 33.06 ± 0.80 mg GAE (g of H. tuberosus extract)-1. There was a correlation between the antioxidant potential of both extracts and TPC but not between antistaphylococcal activity and TPC. The obtained data suggest potential application of these extracts as the natural preparations with the biocidal activity, including those with antistaphylococcal activity. Besides, both extracts may be regarded as potential natural conservants in cosmetics as well as natural preservatives in food.

Quebec is the third-largest wine grape producing province in Canada, and the industry is constantly expanding. Traditionally, 90% of the grapevine cultivars grown in Quebec were rustic or semi-rustic and largely dominated by winter hardy interspecific hybrid Vitis sp. cultivars. Over the years, the winter protection techniques adopted by growers and climate changes have offered an opportunity to establish V. vinifera L. cultivars (e.g. Pinot Noir). We characterized the virome of leafroll-infected interspecific hybrid cultivar and compared it to the virome of V. vinifera cultivar to support and facilitate the transition of the industry. A dsRNA sequencing method was used to sequence symptomatic and asymptomatic grapevine leaves of different cultivars. The results suggested a complex virome in terms of composition, abundance, richness, and phylogenetic diversity. Three viruses, grapevine Rupestris stem pitting-associated virus, grapevine leafroll-associated virus (GLR) 3 and 2 and hop stunt viroid (HSVd) largely dominated the virome. However, their presence and abundance varied among grapevine cultivars. The symptomless grapevine cultivar Vidal was frequently infected by multiple virus and viroid species and different strains of the same virus, including GLR virus 3 and 2. Our data shows that viruses and viroids associated with the highest number of grapevines expressing symptoms included HSVd, GLR3 and GLR2, in gradient order. However, co-occurrence analysis revealed that the presence of GLR species was randomly associated with the development of virus-like symptoms. These findings and their implication for grapevine leafroll disease management were discussed.

This study reports on empirical findings of participatory design workshops for the development of a supportive user experience design system in the automotive. Identifying and addressing this area with traditional research methods is problematic due to the different UX design perspectives that might be conflicting and the related automotive domain limitations. To help resolve this problem, we conducted research with 12 User Experience (UX) designers through individual participatory prototyping activities to gain insights on their explicit, observable, tacit and latent needs. These activities allowed us to explore their motivation to use different technologies; the system's architecture; detailed features of interactivity and describe user needs including Efficiency, Effectiveness, Engagement, Naturalness, Ease of Use, Information retrieval, Self-Image awareness, Politeness, and Flexibility. Our analysis led us to design implications that translate participants' needs into UX design goals, informing practitioners on how to develop relevant systems further.

Collision avoidance is an important feature in advanced driver-assistance systems, aiming at providing correct, timely and reliable warnings before an imminent collision (objects, vehicles, pedestrians, etc.). A co-simulation framework is proposed in this paper to address the design and evaluation of collision avoidances in a cyber-physical system. The co-simulation framework is supported on the interaction between SCANeR and Matlab/Simulink. From the best of authors’ knowledge, two main contributions are reported in this paper. Firstly, the modelling and simulation of virtual on-chip LIDAR sensors in a cyber-physical system (CPS) considering traffic scenarios is presented. The CPS is designed and implemented in SCANeR. Secondly, an obstacle recognition library with three specific Artificial Intelligence-based methods is also designed based on sensory information database provided by SCANeR. Three methods for collision avoidance detection are considered, i.e.; a multi-layer perceptron neural network, a self-organization map and a support vector machine. Finally, a comparison among these methods for detecting obstacles before different weather conditions is done with very promising results in terms of accuracy. The best results are achieved using the multi-layer perceptron in sunny and fog conditions, the support vector machine in rainy and self-organized map in snowy conditions.

Mass transfer restrictions of scaffolds are currently hindering the development of three-dimensional (3D), clinically viable, and tissue engineered constructs. For this situation, a 3D poly(lactide-co-glycolide)/hydroxyapatite porous scaffold, which was much favorable for transfer of nutrients to and waste products from the cells in the pores, was developed in this study. The 3D scaffold had an innovative structure, including macropores with diameters of 300−450 μm for cell ingrowth and microchannels with diameters of 2−4 μm for nutrition and waste exchange. The mechanical strength in wet state was strong enough to offer the structural support. The typical structure was more beneficial for the attachment, proliferation, and differentiation of rabbit bone marrow mesenchymal stem cells (rBMSCs). The alkaline phosphatase (ALP) activity and calcium (Ca) deposition were evaluated on the differentiation of rBMSCs, and the results indicated that the microchannel structure was very favorable for differentiating rBMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, there was rapid healing in the defects treated with the 3D porous scaffold with microchannels, where the bridging by a large bony callus was observed at 12 weeks post-surgery. Based on the results, the 3D porous scaffold with microchannels was a promising candidate for bone defect repair.

Antibiotic-loaded bone cement has been traditionally advocated as a key step for the success of one-stage hip revision surgery, while cementless techniques have been recently proposed with and without the use of local antibacterials as an equally successful alternative. Aim of this review is to investigate the effective role of local antimicrobial protection for one-stage cemented and cementless hip revision surgery. Twelve studies reporting the results of cemented single-stage procedure at a minimum two years follow-up were reviewed. When pooling together the data, no infection recurrence was observed on average in 83.3% of the patients (range 75.0% to 100%). Only two papers, both from the same French group, included patients treated without the use of antibiotic-loaded bone cement, with an average infection control of 95.9% in a total of 195 patients. This figure appears better that the 80.7% infection control obtained by pooling together all the remaining studies. Concerning cementless one-stage revision, a total of 17 studies, reporting on 521 patients, showed an average 90.0% (range 56.8% to 100%) no infection recurrence, at a minimum two years follow-up. Eight papers reported the outcomes of cementless implants without any local antibacterial protection and nine more described four different techniques for local antimicrobial implant protection. No comparative study investigated cementless revision with or without local antibacterial protection. Pooled data showed an average infection control of 86.7%, without the application of local antibacterials, compared to 90.1% to 100% with local antimicrobial protection, depending on the technology used. However, due to the relatively low number of patients treated with each local antimicrobial protection, no statistical difference could be found, either considering local antibacterial strategies alone or pooled together. No side effect had been reported by any local antibacterial technique. This review points out that local antibacterial protection for one-stage hip revision surgery, although safe and largely performed in the clinical setting, appears still to rely mainly on experts’ opinion and on observational series with no prospective or comparative trial, hence no definitive conclusion can be drawn concerning its effective role in one-stage hip revision surgery.

The menace of human papillomavirus (HPV) infections among low- and middle-income countries with no access to free HPV vaccine is a public health concern. HPV is one of the most common Sexually Transmitted Infections (STIs) in Nigeria with high-risk HPV-16 and 18 genotypes. In this study, we explored the predictors of self-reported HPV infections and HPV genital warts infection among a population of students, non-academic staff, and academic staff of Ibrahim Badamasi Babangida (IBB) university located in Lapai, Nigeria. We also assessed their knowledge about HPV infections and genotypes, and sexual behaviors. An online cross-sectional study was conducted by setting up a structured questionnaire on google form and it was distributed to the University community via Facebook and other social media platforms of the university. The form captured questions on HPV infection, knowledge about HPV infection and genotypes, as well as sexual health of the participants. All variables were described using frequencies and percentage distribution, chi-squared test statistics was used to explore the association between HPV infection (medical records of HPV infection) and the participants’ profile, and logistic regression analysis was performed to examine the factors associated with HPV genital warts infection among the population. This study reveals those participants between the ages of 26 – 40 years (81.3%) and those currently not in a union (26.4%) who have self-reported having HPV-16 and -18 genotypes. Also, participants between 26 – 40 years of age (OR: 0.45, 95%CI: 0.22 – 0.89) reported to be carriers of HPV genital warts. Therefore, this study reveals the factors associated with HPV infection and genital warts peculiar to IBB university students and staff. Hence, we suggest the need for HPV awareness programs and free HPV vaccine availability at IBB university.

Our study investigated the innate immune response to Toxoplasma gondii infection by assessing microglial phenotypic changes and sickness behavior as inflammatory response markers post-ocular tachyzoite instillation. Disease progression in Swiss albino mice was compared with documented outcomes in BALB/c mice using identical ocular route and parasite burden (2x105 tachyzoites), with saline as control. Contrary to expectations, Swiss albino mice displayed rapid, lethal disease progression, marked by pronounced sickness behaviors and mortality within 11-12 days post-infection, while survivors showed no apparent signs of infection. Comparative analysis revealed T. gondii-infected BALB/c mice exhibited reduced avoidance of feline odors, while in-fected Swiss albino mice showed enhanced avoidance responses. There was a significant increase in microglial cells in the dentate gyrus molecular layer of infected Swiss albino mice compared to BALB/c mice and their respective controls. Hierarchical cluster and discriminant analyses iden-tified three microglial morphological clusters, differentially affected by T. gondii infection across strains. BALB/c mice exhibited increased microglial branching and complexity, while Swiss al-bino mice showed reduced shrunk microglial arbors, diminishing morphological complexity. These findings highlight strain-specific differences in disease progression and inflammatory reg-ulation, indicating lineage-specific mechanisms in inflammatory responses, tolerance, and re-sistance. These elements are critical in devising control measures for toxoplasmosis.

This study aims to explore the associations between pediatric adverse events (PAEs) and hospital and patient characteristics within the inpatient hospital setting, focusing solely on the framework of pediatric quality indicators (PDIs) from the Agency for Healthcare Research and Quality (AHRQ). Specifically, the study focuses on NQI 03 Neonatal Blood Stream Infection (NBSI). The analysis utilizes discharge data from the Healthcare Cost and Utilization Project (HCUP) Kids’ Inpatient Databases (KID) for the year 2019. Through this analysis, the study seeks to answer research questions regarding associations between hospital characteristics and patient characteristics with NQI 03. The methodology employs bivariate and multivariate logistic regression models to analyze patient-level encounters of NBSI. The results indicate that smaller, rural, and non-teaching hospitals exhibit significantly lower odds of NQI 03 compared to large hospitals. Various individual factors such as gender, age, race, service lines, payment sources, and major operating room procedures also demonstrate differing levels of significance in relation to NQI 03, warranting further investigation. This study provides contextual expansion on the findings and offers valuable insights into PAEs in the inpatient hospital setting, specifically focusing on NBSI within the PDIs framework. It highlights areas for developing evidence-based interventions and guidelines for clinicians and policymakers. Ultimately, the findings contribute to the growing understanding of factors influencing NBSI and emphasize the importance of targeted strategies for improving pediatric patient safety.

Ethanolic extracts of propolis collected from Apis mellifera hives have been shown to reduce Nosema ceranae infection in honey bee workers. This study aimed to determine the propolis concentration that optimizes the control of N. ceranae infection in honey bee workers. Newly emerged worker bees were individually fed 2 μL of 50% sucrose solution (w/v) containing 105 N. ceranae spores per bee, and treated with 0%, 25%, 50%, and 75% ethanolic extracted propolis in 50% sucrose solution (v/v). The treated bees were maintained in cages at 34 ± 2˚C and 55 ± 5% RH throughout the study. The number of dead bees was counted and removed from the cages daily for 30 days to generate survival curves. The number of N. ceranae spores per bee (infectivity) was quantified using a hemocytometer, and the number of infected bees per hundred bees (infection rate) was determined. The survival rates of N. ceranae infected bees fed 25%, 50%, and 75% propolis (NP1, NP2, NP3, respectively) were significantly higher than those of infected bees not fed propolis (NO). Furthermore, the infectivity and infection rates of NP2 and NP3 groups were significantly lower than those of the NO group. The infectivity and infection rates of the NP1 group were not different than those of the NO group. Our data suggest that 50% and 75% propolis extracts are appropriate concentrations for treating N. ceranae infection in honey bees. Ethanolic extracted propolis can be an alternative treatment for N. ceranae infection in Western honey bees.

The fate of critically sick patients with infections in intensive care units (ICUs) is significantly influenced by antimicrobial resistance, which has become a serious concern in developing nations. This observational study was conducted at the IBN Sina Specialised Hospital in Dhaka, Bangladesh, over a 12-month period from January 2021 to December 2021, in order to track the pattern of antibiotic resistance among the patients admitted to the intensive care unit (ICU). Aspiration pneumonia (29%) and diabetes mellitus (24%), among 200 patients, were the most common main diagnoses. 65 samples (or 26%) of the 250 samples had 85 bacteria identified from them. Urine (14.12%) and tracheal aspirate (64.71%) were the most frequently found sites of infection. In the sample from the tracheal aspirate, Pseudomonas spp. (30.59%), Escherichia coli (24.71%), Acinetobacter spp. (20%), and Klebsiella spp. (14.12) were the most frequently isolated microorganisms. The following antibiotics were shown to have the highest overall patterns of resistance: levofloxacin (68.24), amikacin (64.71), meropenem (49.41), ceftazidime (75.29), ciprofloxacin (78.82), and gentamicin (82.35). The most effective antibiotic against Klebsiella species was meropenem (64.61%), while Acinetobacter species were mostly susceptible to cotrimoxazole (64.67%) and piperacillin + tazobactam (60.50%). Most susceptible to netilmicin (70.48%) and meropenem (49.32%) were Escherichia coli, while Pseudomonas spp. were mostly responsive to colistin (55.14%) and netilmicin (52.25%). Antibiotic resistance is common among intensive care unit (ICU) patients, and most isolated microbes have resistance to traditional medicines.

Severe COVID-19 is a major cause of morbidity and mortality worldwide, especially to those with co-morbidities, the elderly and the immunocompromised. However, the molecular determinants critical for severe COVID-19 progression remain to be fully elucidated. Meta-analysis of transcriptomic RNAseq and single-cell sequencing datasets comparing between severe and mild COVID-19 patients have demonstrated that the early expansion of myeloid-derived suppressor cells (MDSCs) could a key feature of severe COVID-19 progression. Besides serving as potential early prognostic biomarkers for severe COVID-19 progression, several studies have also indicated the functional roles of MDSCs in severe COVID-19 pathogenesis and possibly even long COVID. Given the potential links between MDSCs and severe COVID-19, we examined the existing literature summarizing the characteristics of MDSCs, the evidence of MDSCs in facilitating severe COVID-19 pathogenesis and discuss the potential therapeutic avenues that can be explored to reduce the risk and burden of severe COVID-19. We also provide a web app where users can visualise the temporal changes of specific genes or MDSC-related gene sets during severe COVID-19 progression and disease resolution at https://temporal-severe-covid.streamlit.app/, based on our previous study described by Ong et al., 2021.

Background: Data on the benefits of rapid microbiological testing on antimicrobial consumption (AC) and antimicrobial resistance patterns(ARP) are scarce. We evaluated the impact of a protocol based on rapid techniques on AC and ARP in intensive care (ICU) patients. Methods: Retrospective pre(2018) and post-intervention(2019-21) study in ICU patients. A rapid diagnostic algorithm was applied from 2019 in patients with lower respiratory tract infection. Incidence of nosocomial infection, ARP, and AC as DDD(defined daily dose) were monitored. Results: A total of 3635 patients were included, 987(pre-intervention) and 2648(post-intervention). A median age was 60 years, 64% male, with APACHE II of 19 points and SOFA of 3 points. Overall ICU mortality of 17.2% without differences between the periods. An increase in the number of infections was observed in the post-intervention period(44.5% vs 17.9%, p<0.01), especially due to an increase in ventilator-associated pneumonia(44.6% vs 25%,p<0.001). AC decreased from 128.7 DDD in 2018 to 66.0 DDD in 2021(Rate Ratio=0.51). A recovery of P.aeruginosa susceptibility of 23% for Piperacillin/tazobactam and 31% for Meropenem was observed. Conclusion: The implementation of an algorithm based on rapid microbiological diagnostic techniques allowed a significant reduction in AC and ARP without affecting the prognosis of critically ill patients.

From the first isolation of the cystovirus bacteriophage Φ6 from Pseudomonas syringae 50 years ago, we have progressed to a better understanding of the structure and transformations of the many parts of the virion. The three-layered virion encapsulating the tripartite double stranded RNA (dsRNA) genome, breaches the cell envelope on infection, generates its own transcripts, and coopts the bacterial machinery to produce its proteins. The generation of new virions starts with a procapsid with a contracted shape, followed by packaging single stranded RNA segments with concurrent expansion of the capsid, and finally replication to reconstitute the dsRNA genome. The outer two layers are then added, and the fully formed virions released by cell lysis. Most of the procapsid structure composed of the proteins P1, P2, P4 and P7 is now known, as well as its transformations to the mature, packaged nucleocapsid. The outer two layers are less well studied. One additional study investigated the binding of the host protein YajQ to the infecting nucleocapsid, where it enhances the transcription of the large RNA segment that codes for the capsid proteins. Finally, we relate the structural aspects of bacteriophage Φ6 top those of other dsRNA viruses, noting the similarities and differences.

Objectives: To evaluate the relationship between the type of conization, the volume and dimensions of the cone, with the persistence/recurrence of CIN 2-3, presence of affected margins and post-cone HR-HPV positivity. Methods: 227 women treated with LLETZ and histologically confirmed CIN2-3 were evaluated between 1996 and 2006 and followed up until June 2016. Age, type of resection according to IFCPC 2011, volume, cone dimensions, margins were studied. of resection, post-cone high-risk human papillomavirus (HR-HPV) status and viral load. Determinants of HR-HPV positivity were estimated using unconditional logistic regression and time to recurrence was assessed using Kaplan-Meier curves. Results: Persistent/recurrent CIN2-3 was found in 12 cases (5.2%), type 1 conization was performed in 81 patients, with 5 recurrences (6.1%), type 2 in 101 patients, with 6 recurrences (5 .9%) and type 3 resection in 45 women, with 1 recurrence (2.2%). Volume and dimensions were not associated with recurrence. The Log-Rank Test did not show a significant difference between the 3 treatments (p= 0.18). The free margins in type 1 were 37%, in type 2 resection 61% and in type 3 71% (p=0.001). Resection type 1 had 15% HR-HPV post positive cone, type 2 reached 16% and type 3 had 9%, this difference being non-significant (p=0.58). The incidence of recurrence at 36 months in type 1 resection was 0.08%, in type 2 treatment it was 0.04% and in type 3 resection it was 0.0%. Conclusions : Type 3 resection had a higher proportion of free margins and lower post-cone HR-HPV positivity, with a lower incidence of persistence/recurrence.

Recurrent infections after root canal treatments often involve Enterococcus faecalis, a microorganism closely associated with therapy failures due to its biofilm production, survival in nutrient-deprived conditions, and antibiotic tolerance. Essential oils (EOs), which display anti-inflammatory, antimicrobial, and antibacterial properties, exhibit inhibitory effects on the growth of many microorganisms including E. faecalis. This study assessed the in vitro efficacy of combining antibiotics (Gentamicin 1.5mg/ml, Streptomycin 2.5 mg/ml, Ampicillin 5 mg/ml, and Kanamycin 2.5 mg/ml) with Cinnamon (1.25% to 5%) or Clove (25% to 50%) EOs using disk diffusion tests. Disks were treated with EOs-only, antibiotics-only, or EO-antibiotic combinations, placed on BEA agar plates, incubated for 24 hours, and zones of inhibition were measured against E. faecalis. Results showed robust growth inhibition by cinnamon and clove EOs across all tested concentrations. Furthermore, there were synergistic antimicrobial effects when gentamicin, streptomycin and kanamycin were combined with 2.5% and 50% concentrations of cinnamon and clove EOs, respectively, leading to significant growth inhibition of E. faecalis by 139% to 193% compared to using antibiotics or EOs alone. Clove EO showed positive synergism with three antibiotics (gentamicin, streptomycin, and kanamycin) whereas cinnamon EO showed synergism with two antibiotics (streptomycin and kanamycin). These findings suggest that combining cinnamon and clove EOs with aminoglycoside antibiotics can significantly reduce the expansion of E. faecalis compared to antibiotics alone. Further in vivo studies should determine the safety, efficacy, and treatment duration, with the potential to reduce antibiotic dosages and associated toxicity while preventing recurrent infections.

Patients undergoing dialysis through a permanent catheter often experience infection or malfunction. However, few studies have clarified the predictors of permanent catheter patency survival in patients undergoing hemodialysis. We assessed the relationship between parameters of body composition monitoring (BCM) determined before the initiation of dialysis and the patency survival of the permanent catheters inserted in 179 patients who commenced hemodialysis between January 14, 2020 and August 31, 2021. The relationships between permanent catheter patency at 6 weeks and BCM parameters, laboratory tests, age, sex, comorbidities, and medications at baseline were studied using Kaplan–Meier survival curves. Permanent catheter patency was observed to be superior at high extracellular-to-intracellular (ECW/ICW) ratio (P<0.005). After adjustment for covariates, the ECW/ICW ratio remained an independent factor associated with permanent catheter patency survival. When patients with non-patent catheters were subdivided into infection and malfunction groups, and the associations of BCM parameters were evaluated in those groups, the ECW/ICW ratio was not significantly associated with permanent catheter patency survival in the infection group (P = 0.327); instead, a significant association was found for the lean tissue index (P<0.001). In the malfunction group, the ECW/ICW ratio remained significantly associated with permanent catheter patency survival (P < 0.001).

Chronic hepatitis B (CHB) infection and the Hepatitis B virus X protein (HBx) are major risk factors associated with hepatocellular carcinoma (HCC). In CHB infection, HBx induces mitochondrial dysfunction, exhaustion and impaired function in hepatocytes. Restoring hepatocyte health along with reduction in virus replication could be an ideal treatment for CHB. Thiourea derivatives are well known for their antiviral property though their effect on mitochondrial and/ or hepatocyte health remains obscure. This study focus on the repurposing of thiourea derivatives (DSA-00, DSA-02, and DSA-09) on hepatocyte replenishment. HepG2.2.15 cells were treated with thiourea derivatives, alongside Entecavir (ETV). The proteomics analysis showed both DSA-00 and ETV were enriched with proteins associated with antiviral responses. In addition, DSA-00 additionally showed increase in proteins linked to mitochondrial response. Whereas DSA-02 exhibited association with innate immune system and citric acid cycle and DSA-09 displayed pathways similar to DSA-00 and ETV. Treated groups exhibited enhanced bio-energetic and antiviral response as compared to the untreated group. FACS analysis revealed the restoration of exhausted hepatocytes by thiourea derivatives through targeting mitochondria. Our findings suggest that thiourea derivatives hold potential as a novel therapeutic agent that seems to restore mitochondrial health along with anti-viral response in CHB.

More than 3 years have passed since the emergence of COVID-19. On May 8, 2023, COVID-19 in Japan was downgraded to Category 5 by the Infectious Disease Control Law. In Japan, at the beginning of the COVID-19 pandemic in 2020, cases of infection and deaths from severe disease were few compared with those of Western countries. However, in the medical field, screening for COVID-19 was given top priority, resulting in confusion and proving disadvantageous for many patients, also the overreaction to COVID-19 as the most important issue in society can be attributed largely to statements by infectious disease experts. In addition, the mRNA vaccine emerged in 2021, and most of the population was vaccinated up to two times within a short period of less than 1 year because infectious disease experts strongly promoted vaccination. After 2022, when vaccination progressed, and the Omicron strain, which is an attenuated strain, became the mainstay of the SARS-CoV-2, the number of severe cases of COVID-19 decreased significantly; however, the number of infected people increased dramatically instead. A significant portion of the population is thought to have hybrid immunity due to vaccination plus natural infection and maintains high antibody titers. Henceforth, additional vaccination should be given preferentially to those who will benefit most from it. Conversely, measures against COVID-19 caused serious damage to the economy and society. Policies that not only address countermeasures against infection, but also those that encompass the economy and society as a whole are necessary.

Background: Skin and soft tissue infections (SSTI) are common presentations to the emergency department. However, this is less common after contact with contaminated water, both salt or fresh. This review presents the diagnosis and the management of water-related soft tissue sepsis in this vulnerable and difficult to treat subgroup of necrotizing soft tissue sepsis. Methods: A summative literature overview regarding bacterial and fungal SSTI after contact with contaminated water, with practical diagnostic and management aspects addressed. Results: The literature indicates that these remain difficult to treat wounds and organisms. An approach using appropriate diagnostic tools with both medical and surgical management strategies is provided. Conclusion: SSTI due to water contamination of wounds involve unusual organisms with unusual resistance patterns and require a nuanced and directed diagnostic approach with adaptation of the normal antibiotic or antifungal selection to achieve cure, along with aggressive debridement and wound care.

Staphylococci sp. have become the primary pathogens implicated in infective endocarditis, especially within high-income nations. This along with the increasing burden of healthcare, aging populations and the protracted course the infections may take, contribute to a significant challenge for healthcare systems. A systematic review was conducted using relevant search criteria from PubMed, Ovid’s version of MEDLINE, and EMBASE, and data were tabulated from randomized controlled trials (RCT), observational cohort studies, meta-analysis, and basic research articles. The review was registered with the OSF register of systematic reviews and followed the PRISMA reporting guidelines. 35 studies met the inclusion criteria and were included in the final systematic review. The role of Staphylococcus aureus and its interaction with the protective shield and host protection functions was identified and highlighted in several studies. The interaction between infective endocarditis pathogens, vascular endothelium, and blood constituents was also explored giving rise to the potential use of antiplatelets as preventative and/or curative agents. Several factors allow Staphylococcus aureus infections to proliferate within the host with numerous promoting and perpetuating agents. The complex interaction with the hosts' innate immunity also potentiates its virulence. Ameliorating these molecular pathways may serve as a therapeutic avenue for the prevention and treatment of these infections in near future.

Chorioamnionitis (CA) at term of pregnancy can have infectious and/or inflammatory origin and is associated with adverse outcomes. Triple I (Intrauterine Inflammation, Infection or both, TI) has been proposed to reduce the overdiagnosis of infection and the neonatal overtreatment. The aim of the study is to identify clinical and histological variables predicting adverse outcomes when TI has been suspected and/or confirmed. This retrospective cohort study included 404 pregnancies ≥37 g.a. that were divided into 5 all-inclusive and mutually exclusive groups. TI was defined according to NICHD definition of 2015 and it could be confirmed (TI+) or not (TI-) by histological examination. Signs of infection/inflammation not respecting the definition of TI were classified as “Clinical suspicion”, supported (CS+) or not (CS-) by histology. Histological chorioamnionitis (HCA) without clinical manifestation represented fifth group. Whole Placental Involvement (WPLI), was defined as a histological inflammation involving maternal and fetal side. There were 113 TI+, 30 TI-, 186 CS+, 35 CS- and 40 isolated HCA. WPLI was diagnosed in 133 cases (39.2%). Composite neonatal outcome (CNO) occurred in 114 cases (28.2%) while composite maternal outcome (CMO) occurred in 192 cases (47.5%). TI+ compared to CS+ was more predictive of CNO (p=0.001), CMO (p<0.001) and WPLI (p=0.005). WPLI was related both to CNO (p<0.001) and CMO (p=0.046). TI+ and WPLI showed similar sensitivity but different specificity in predicting CNO. At logistic regression, CNO was independently predicted by TI+ (OR 2.21; p=0.001) and by WPLI (OR 2.23; p=0.001). TI, compared to CS, is a better predictor of CNO and can be useful for the identification of newborns at risk.

Chronic hepatitis B infection remains a significant worldwide health burden, placing persons at risk for hepatocellular cancer and hepatic fibrosis. Chronic hepatitis B virus (CHB) infection is characterized by elevated levels of immunosuppressive regulatory T cells (Tregs), which can inhibit the function of effector T cells and lead to an insufficient immune clearance response against HBV in the host. Theoretically, suppression of Treg functionality and percentage could increase anti-HBV reactivity in CHB-infected patients, although this has not yet been explored. We attempted to enhance our previously established anti-CHB protocol utilizing the GM-CSF+IFN-α+rHBVvac regimen (GMI-HBVac) by incorporating Mafosfamide (MAF), which has been utilized in anticancer therapy in the past. Intravenous administration of MAF to rAAV8-1.3HBV-infected mice resulted in a dose-dependent reduction of Tregs in the blood, rebounding to pretreatment levels 10 days later. To determine the efficacy of anti-CHB, 2ug/ml MAF was combined with the GMI-HBVac in an HBV-infected animal model as an anti-Treg treatment. When rAAV8-1.3HBV-infected mice were immunized with MAF+GMI-HBVac, peripheral blood Tregs decreased significantly, leading to dendritic cell activation, HBV-specific T cell proliferation, and upregulation of IFN-gamma producing CD8+T cells. In addition, MAF+GMI-HBVac vaccination stimulates T cell infiltration in HBV-infected liver. These conditions may contribute to an enhanced immune response and the clearance of HBV-associated antigens, including serum HBsAg, serum HBcAg, and HBcAg+ hepatocytes. Overall, this is the first indication that MAF was utilized as an adjuvant to deplete Tregs and paired with GMI-HBVac as a unique therapeutic vaccine regimen against established CHB mice to produce a functional cure, as seen by the remarkable clearance of HBsAg.

COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalised patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed by white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells and platelets. Immune cells, cytokines, chemokines and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate pro-inflammatory and pro-coagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated “cytokine storm”, platelets, red blood cells, and coagulation pathways close the inflammation-endotheliopathy-thrombosis axis, contributing to SARS-CoV-2 associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism, chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalised patients with severe disease, that would target the crossroads of inflammatory and coagulation pathways.

Monkeypox virus infection is a recognized public health emergency. Little research has been done on treatment options for this disease. Until recently, there was not a single published work describing the usage of specific drugs in human patients with monkeypox virus infection. This paper gives the first bibliometric analysis of monkeypox treatment options based on data available on PubMed and Scopus. It also reviews the specific drugs used in the treatment of monkeypox. That includes data on Tecovirimat, Cidofovir, Brincidofovir, and Vaccinia Immune Globulin. Tecovirimat is a promising option in progressive disease in terms of efficacy and safety. However, Brincidofovir has been associated with discontinuation of treatment. Cidofovir is also not the preferred drug among physicians. Currently, Tecovirimat can be further used for the management of aggravating cases. More studies should be conducted on Tecovirimat to treat this condition, mainly through controlled trials.

Background: COVID-19 has placed tremendous pressure on the global public health system and has changed daily life. Aim: To examine the relationships between the perceived threat, perceived stress, coping responses and infection control practices towards the COVID-19 pandemic among university students in China. Methods: Using a cross-sectional survey, 4,392 students were recruited from six universities in two regions of China. Methods: Data were collected via an online platform using self-reported questionnaires. Hierarchical multiple regression analyses were performed to predict the variables on COVID-19 infection control practices. Results: Pearson correlation coefficients showed a significant negative relationship between perceived stress and COVID-19 infection control practices. A significant positive relationship was observed between wishful thinking and empathetic responding, and infection control practices. Hierarchical multiple regression analyses revealed that gender, geographical location, perceived stress and emotion-focused and relationship-focused coping responses were predictors of COVID-19 infection control practices. Conclusions: The findings suggest that university students displayed moderate levels of stress, using wishful thinking and empathetic responses as coping strategies. Counselling services should therefore emphasise reassurance and empathy. Male university students tended to be less compliant with social distancing. Both counselling and public health measures should recognise the importance of gender differences. Nurses should integrate these findings into future health program planning and interventions.

The scientific, private and industrial sectors use a wide variety of technological platforms available to achieve protection against SARS-CoV-2, including vaccines. However, the virus evolves continually into new highly virulent variants, which might overcome the protection provided by vaccines and may re-expose the population to infections. Mass vaccinations should be continued in combination with more or less obligation mandatory non-pharmaceutical interventions. Therefore, the key questions to be answered are: (i) How to identify the primary and secondary infections of SARS-CoV-2? (ii) Why are neutralizing antibodies not long-lasting in both the cases of natural infections and post-vaccinations? (iii) Which are the factors responsible for this decay in neutralizing antibodies? (iv) What strategy could be adapted to develop long-term herd immunity? (v) Is the Spike the only vaccine candidate or a vaccine cocktail is better?

Persistent Pain after Spinal Surgery can be successfully addressed by Spinal Cord Stimulation (SCS). International guidelines strongly recommend that a lead trial be performed before any permanent implantation. Recent clinical data highlight some major limitations of this approach. First, it appears that patient outcomes, WITH OR WITHOUT lead trial, are similar. In contrast, during trialing, infection rate drops drastically within time and can compromise the therapy. Using composite pain assessment experience and previous research, we hypothesized that ma-chine learning models could be robust screening tools and reliable predictors of long-term SCS efficacy. We developed several algorithms including logistic regression, Regularized Logistic Regression (RLR), naive Bayes classifier, artificial neural networks, random forest and gradient boosted trees to test this hypothesis and to perform internal and external validations, the objec-tive being to confront model predictions with lead trial results using a 1-year composite out-come from 103 patients. While almost all models have demonstrated superiority on lead trial-ing, the RLR model appears to represent the best compromise between complexity and inter-pretability in prediction of SCS efficacy. These results underscore the need to use AI based-predictive medicine, as a synergistic mathematical approach, aimed at helping implanters to optimize their clinical choices on daily practice.

The interaction of the nervous, immune, and endocrine systems is crucial in the maintenance of homeostasis in vertebrates, and vital in mammals. The spleen is a key organ that regulates the neuroimmunoendocrine system. The Taenia crassiceps mouse system is an excellent experimental model to study the complex host-parasite relationship, particularly sex-associated susceptibility to infection. The aim of the present study was to determine the changes in neurotransmitters, cytokines, sex steroids, and sex-steroid receptors in the spleen of cysticercus-infected male and female mice, and the association of these different components with whole parasite counts. We found that parasite load was higher in female in comparison to male mice. The levels of the neurotransmitter epinephrine were significantly decreased in infected male animals. The expression of IL-2 and IL-4 in the spleen was markedly increased in infected mice; however, the expression of Interleukin (IL)-10 and Interferon (IFN)-γ decreased. We also observed sex-associated differences between non-infected and infected mice. Interestingly, the data show that estradiol levels increased in infected males but decreased in females. Our studies provide evidence that infection leads to changes on neuroimmunoendocrine molecules in the spleen during infection. These changes are dimorphic and impact the establishment, growth, and reproduction of T. crassiceps. Our findings support the key role of the neuroimmune network in determining sex-associated susceptibility to the helminth parasite.

To gain new insights into the potential of mother-to-child transmission of Zika virus (ZIKV) through breast milk or breastfeeding practices, we systematically searched regional and international databases and screened 1,658 non-duplicate records describing women with suspected or confirmed ZIKV infection, intending to breastfeed or give breast milk to an infant. Fourteen studies met our inclusion criteria and inform this analysis. These studies reported on 97 mother-children pairs who provided breast milk for ZIKV assessment. Seventeen breast milk samples from different women were found positive for ZIKV via RT-PCR, and ZIKV replication was found in cell cultures from five out of seven breast milk samples from different women. Only three out of six infants who had ZIKV infection were breastfed, no evidence of clinical complications were found to be associated with ZIKV RNA in breast milk. This review updates our previous report by synthesizing the evidence from 12 new articles and we find no evidence of mother-to-child transmission through breast milk intake or breastfeeding. As the certainty of the present evidence is low, additional studies are still warranted to completely understand any potential of transmission of ZIKV through breastfeeding.

Purpose: During the COVID-19 pandemic, the health care workers (HCWs) at the frontline have been largely exposed to infected patients, running an high risk of being infected by the SARS-CoV-2 virus. This study investigates the epidemiological, clinical and lifestyles characteristics that might play roles in the susceptibility of HCWs to COVID-19 in a hit Italian hospital. Methods:Demographic, lifestyle, work-related and comorbidities data of 1447 HCWs which underwent a nasopharyngeal swab for SARS-CoV-2 were retrospectively collected. For the 164 HCWs positive for SARS-CoV-2, data about safety in the workplace, symptoms and clinical course of COVID-19 were also collected. Cumulative incidence of SARS-CoV-2 infection was estimated. Risk factors for SARS-CoV-2 infection were assessed using a multivariable Poisson regression. Results: The cumulative incidence of SARS-CoV-2 infection among the screened HCWs was 11.33 (9.72-13.21). Working in a COVID-19 ward, being a former smoker (vs being a person who never smoked) and BMI were positively associated with SARS-CoV-2 infection, whereas being a current smoker was negatively associated with this variable. Conclusions: Assuming an equal accessibility and proper use of PPE of all the HCWs of our Hospital, the great and more prolonged contact with COVID-19 patients remains the crucial risk factor for SARS-CoV-2. Therefore, increased and particular care needs to be focused specifically on the most exposed HCWs groups, which should be safeguarded. Furthermore, in order to limit the risk of asymptomatic spread of SARS-CoV-2 infection, the HCWs mild symptoms of COVID-19 should be considered when evaluating the potential benefits of universal staff testing

Effects of the convection flow, atmospheric diffusivity and humidity on evolution and travel distances of exhaled aerosol clouds by an infected person are considered. The aim of this work is to evaluate the importance of aerosol transmission routes and the effectiveness of the 2-metre separation distance policy. A potential impact of use of face masks on the infection transmission rate, and an opportunity to reduce infection in hospitals, care homes and other public spaces by appropriate monitoring and filtering of air are also considered. The results obtained demonstrate that aerosol particles generated by coughing and sneezing can travel over 30 m. Modelling of the evolution of aerosol clouds generated by coughing and sneezing enables us to evaluate the deposition dose of aerosol particles in healthy individuals. For example, a person in a public place (e.g. supermarket or car park) can accumulate in the respiratory system up to 200 virus copies in 2 min time by breathing in virus laden aerosols. Wearing face mask considerably reduces the deposited load down to 2 virus copies per 2 min. The modelling also suggests that it should be possible to measure virus causing COVID-19 (SARS-CoV-2) within aerosol particles in hospitals and public places, e.g. care homes and supermarkets.

The Coronavirus disease (COVID-19) caused by a novel coronavirus, SARS-CoV-2, has been declared as a global pandemic. Due to its infection rate and severity, it has emerged as one of the major global threats of the current generation. To support the current combat against the disease, this research aims to propose a Machine Learning based pipeline to detect the COVID-19 infection using the lung Computed Tomography scan images (CTI). This implemented pipeline consists of a number of sub-procedures ranging from segmenting the COVID-19 infection to classifying the segmented regions. The initial part of the pipeline implements the segmentation of the COVID-19 affected CTI using Social-Group-Optimization and Kapur’s Entropy thresholding, followed by k-means clustering and morphology-based segmentation. The next part of the pipeline implements feature extraction, selection and fusion to classify the infection. PCA based serial fusion technique is used in fusing the features and the fused feature vector is then employed to train, test and validate four different classifiers namely Random Forest, k-Nearest Neighbors (KNN), Support Vector Machine with Radial Basis Function, and Decision Tree. Experimental results using benchmark datasets show a high accuracy (> 91%) for the morphology-based segmentation task and for the classification task the KNN offers the highest accuracy among the compared classifiers (> 87%). However, this should be noted that this method still awaits clinical validation, and therefore should not be used to clinically diagnose the ongoing COVID-19 infection.

Background & Objectives: The global pandemic caused by novel coronavirus SARS-CoV-2 has claimed several lives worldwide. With the virus gathering rapid spread, the world has witnessed increasing number of confirmed cases and mortality rate, India is not far behind with approximately 37,000 affected individuals as on May 2, 2020. The ongoing pandemic has raised several questions which need to be answered by analysis of transmission of the infection. The data has been collected on daily basis from WHO and other sites. We have represented the data collated graphically using statistical packages, R and other online softwares. The present study provides a holistic overview of the spread of COVID-19 infection in India. Methods: Real-time data query was done based on daily observations using publicly available data from reference websites for COVID-19 and other government official reports for the period (15^th February, 2020 to April 28^th, 2020). Statistical analysis was performed to draw important inferences regarding COVID-19 trend in India. Results: A decrease in growth rate of cases due to COVID-19 in India post lockdown and improvement in recovery rate during the month of April was identified. The case fatality rate was estimated to be 3.22% of the total reported cases. State-wise analysis revealed a deteriorating situation in states of Maharashtra and Gujarat among others as cases continued to increase rapidly there. A positive linear correlation between the number of deaths and total cases and exponential relation between population density and number of cases reported per square km was established. Interpretation & Conclusions: Despite early preventive measures taken up by the Government of India, the increasing number of cases in India is a concern. This study compiles state-wise and district-wise data to report the daily confirmed cases, case fatalities and strategies adopted in the form of case studies. Understanding the transmission spread of SARS-CoV-2 in a diverse and populated country like India will be crucial in assessing the effectiveness of control policies towards the spread of COVID-19 infection.

In the war against the COVID-19 pandemic, the world is experiencing severe resource constraints. Although transmission routes are well understood, we suspect that they cause different disease consequences. We evaluate them in different forms to understand how they affect infection rates and disease severity. In determining how they affect disease outcome, we evaluated target tissue vulnerability, functional role, defense mechanisms, viral concentration, infection vicinity to target vital tissue, and host factors. We found that direct lung infection is the most lethal transmission route followed by bronchi infection. Transmissions by physical contacts, foods, and blood by low viral concentration (as expected in normal human activities) pose lower or much lower risks unless the infection is followed by subsequent lung exposures. After adding transmission route, treatment timings, and improper treatments into the list of known risk factors, we found that death rate and disability rate for young or healthy persons are nearly zero. We show that population based medical model improperly shifts nominal death rate from few vulnerable people to the population resulting in unnecessary population panic, and such panic is responsible for shutting down human activities and the world economy. Finally, we examined limitations in population-based mitigating measures and proposed for governmental and private adoption community guidelines, which are mainly to enable vulnerable people avoid exposures, prevent non-vulnerable people from serving as viral transmitters, get rid of high-risk exposure modes in working environment, improve safety for people in buses, ships and planes, and reduce death and disability rates for infected people.

Hepatitis B virus (HBV) infection is a major factor in development of various liver diseases such as hepatocellular carcinoma (HCC). Among HBV encoded proteins, HBV X protein (HBx) is known to play key role in development of HCC. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear transcription factor which is critical for hepatocyte differentiation. However, the expression level as well as its regulatory mechanism in HBV infection have yet to be clarified. Here, we observed the suppression of HNF4α in cells which stably express HBV whole genome or HBx protein alone, while transient transfection of HBV replicon or HBx plasmid had no effect on the HNF4α level. Importantly, in the stable HBV- or HBx-expressing hepatocytes, the downregulated level of HNF4α was restored by inhibiting ERK signaling pathway. Our data showed that HNF4α was suppressed during long-term HBV infection in cultured HepG2-NTCP cells as well as in mouse model following hydrodynamic injection of pAAV-HBV or in mice intravenously infected with rAAV-HBV. Importantly, HNF4α downregulation increased cell proliferation which contributed to the formation and development of tumor in xenograft nude mice. The data presented here provided several proofs for the effect of HBV infection in manipulating HNF4α regulatory pathway in HCC development.

Multiple lines of evidence indicate that CD8$^+$ T cells are important in the control of HIV-1 (HIV) replication. However, CD8$^+$ T cells induced by natural infection cannot eliminate the virus or reduce viral loads to acceptably low levels in most infected individuals. Understanding the basic quantitative features of CD8$^+$ T-cell responses induced during the course of HIV infection may therefore inform us about the limits that HIV vaccines, which aim to induce protective CD8$^+$ T-cell responses, must exceed. Using previously published experimental data from a cohort of HIV-infected individuals with sampling times from acute to chronic infection we defined the quantitative properties of CD8$^+$ T-cell responses to the whole HIV proteome. In contrast with a commonly held view, we found that the relative number of HIV-specific CD8$^+$ T-cell responses (response breadth) changed little over the course of infection (first 400 days post-infection), with moderate but statistically significant changes occurring only during the first 35 symptomatic days. This challenges the idea that a change in the T-cell response breadth over time is responsible for the slow speed of viral escape from CD8$^+$ T cells in the chronic infection. The breadth of HIV-specific CD8$^+$ T-cell responses was not correlated with the average viral load for our small cohort of patients. Metrics of relative immunodominance of HIV-specific CD8$^+$ T-cell responses such as Shannon entropy or the Evenness index were also not significantly correlated with the average viral load. Our mathematical-model-driven analysis suggested extremely slow expansion kinetics for the majority of HIV-specific CD8$^+$ T-cell responses and the presence of intra- and interclonal competition between multiple CD8$^+$ T-cell responses; such competition may limit the magnitude of CD8$^+$ T-cell responses, specific to different epitopes, and the overall number of T-cell responses induced by vaccination. Further understanding of mechanisms underlying interactions between the virus and virus-specific CD8$^+$ T-cell response will be instrumental in determining which T-cell-based vaccines will induce T-cell responses providing durable protection against HIV infection.

Actinobaculum massiliense, a Gram-positive anaerobic coccoid rod colonizing the human urinary tract, belongs to the taxonomic class of Actinobacteria. We identified A. massiliense as a cohabitant of urethral catheter biofilms (CB). The CBs also harbored common uropathogens such as Proteus mirabilis and Aerococcus urinae, supporting the notion that A. massiliense is adapted to a life style in polymicrobial biofilms. We isolated a strain from an agar colony derived from a clinical sample. Using 16S rRNA gene sequencing and shotgun proteomics, we identified and characterized A. massiliense, comparing the isolate grown in vitro and four clinical ‘in vivo’ samples. Based on abundances of proteins in the in vivo milieu, we assessed their functions related to nutrient import and responses to hostile host conditions characterized by neutrophil infiltration. Two putative subtilisin-like proteases and a heme/oligopeptide transporter were highly expressed in vivo and are perhaps important for survival in the host milieu. The uptake of xylose/glucuronate and oligopeptides apparently enables feeding metabolites into mixed acid fermentation and peptidolysis pathways, respectively, to generate energy. A putative polyketide synthase which may generate a secondary metabolite interacting with either the host or co-colonizing microbes was identified. The enzyme may contribute to A. massiliense persistence in CBs.

In contrast to previous incursions of highly pathogenic H5 viruses, H5N8 clade 2.3.4.4b caused numerous lethal infections in white-tailed sea eagles (Haliaeetus albicilla) in Germany during the winter 2016/2017. Until April 2017, 17 HPAIV H5N8-positive white-tailed sea eagles had been detected (three alive and 14 dead). Mainly young eagles died (before reaching the adult plumage at 5 years), often with severe neurological symptoms, where histopathology revealed mild to moderate, oligo- to multifocal necrotizing polioencephalitis. Lethal lead (Pb) concentrations, proven as main mortality factor of the sea eagles could be ruled out since values measured in liver or kidney tissue were all within background levels (< 1 ppm). Since the fall of 2016, the epizootic of HPAIV H5 clade 2.3.4.4b reportedly induced, for the first time, fatal disease in European white-tailed see eagles. The virus strain may become a new threat to a highly protected species across its distribution range in Eurasia. Positive cloacal swaps have proven that the eagles can spread the virus with their faeces.

Human microbiome data from genomic sequencing technologies is fast accumulating, giving us insights into bacterial taxa that contribute to health and disease. Predictive modeling of such microbiota count data for classification of human infection from parasitic worms such as helminths can help in detection and management across global populations. Real-world datasets of microbiome experiments are typically sparse containing hundreds of measurements for bacterial species, of which only a few are detected in the bio-specimens that are analyzed. This feature of microbiome data produces the challenge of needing more observations for accurate predictive modeling and has been dealt with previously using different methods of feature reduction. To our knowledge, integrative methods such as transfer learning has not been explored in the microbiome domain yet, as a way to deal with data sparsity by incorporating knowledge of different but related datasets. One way of incorporating this knowledge is by using a meaningful mapping among features of these datasets. In this paper, we claim that this mapping would exist among members of each individual cluster grouped based on phylogenetic dependency among taxa and their association to the phenotype. We validate our claim by showing that models incorporating associations in such a grouped feature space result in no performance deterioration for the given classification task. In this paper, we test our hypothesis using classification models that detect helminth infection in microbiota of human fecal samples obtained from Indonesia and Liberia countries. In our experiments, we first learn binary classifiers for helminth infection detection by using Naive Bayes, Support Vector Machines, Multilayer Perceptrons, and Random Forest methods. In the next step, we add taxonomic modeling using the SMART-scan module to group the data, and learn classifiers using the same four methods, to test the validity of the achieved groupings. We observed a 6% to 23% and 7% to 26% performance improvement based on the Area Under ROC Curve (AUC) and Balanced Accuracy(Bacc) measures, respectively, over 10 runs of 10-fold cross-validation. These results show that using phylogenetic dependency for grouping our microbiota data actually results in a noticeable improvement in classification performance for helminth infection detection. These promising results from this feasibility study demonstrate that methods such as SMART-scan can be utilized in the future for knowledge transfer from different but related microbiome datasets by phylogenetically-related functional mapping, to enable novel integrative biomarker discovery.