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Introduction: Community acquired pneumonia (CAP) is a prevalent low respiratory infection. Diagnosis is based on clinical symptoms, radiologic evidence and culture. Biomarkers such as IL6, CRP and procalcitonin are helpful in diagnosis. Procalcitonin is a soluble biomarker in serum that increase in systemic inflammation and bacterial infections. People with normal procalcitonin have low risk to infect pneumonia. Patient with CAP have more oxidative stress than normal people. Studies show that receiving vitamin C can reduce incidence of pneumonia. The present study was designed to evaluate the effect of vitamin C supplement on procalcitonin biomarker in patient with CAP. Methods: Patients with CAP who passed inclusion and exclusion criteria after obtaining informed consent, were assigned randomly in two groups of drug and placebo. The drug group received vitamin C (1000 mg/d) daily and medications that physician prescribed for treating CAP for 10 days and placebo group received placebo and medications that physician prescribed. The serum level of procalcitonin was measured at the beginning of the study and after 10 days of intervention. Results: 35 patients finished the study. Serum level of procalcitonin on the first and tenth day did not show any significant difference between drug and placebo groups. Conclusions: To clarify the relationship between the effects of vitamin C on procalcitonin in CAP, a larger sample size is required. [ABSTRACT FROM AUTHOR]

Misfolding of the cellular PrP (PrPc) protein causes prion disease, leading to neurodegenerative disorders in numerous mammalian species, including goats. A lack of PrPc induces complete resistance to prion disease. The aim of this work was to engineer Alpine goats carrying knockout (KO) alleles of PRNP, the PrPc-encoding gene, using CRISPR/Cas9-ribonucleoproteins and single-stranded donor oligonucleotides. The targeted region preceded the PRNPTer mutation previously described in Norwegian goats. Genome editors were injected under the zona pellucida prior to the electroporation of 565 Alpine goat embryos/oocytes. A total of 122 two-cell-stage embryos were transferred to 46 hormonally synchronized recipient goats. Six of the goats remained pregnant and naturally gave birth to 10 offspring. Among the 10 newborns, eight founder animals carrying PRNP genome-edited alleles were obtained. Eight different mutated alleles were observed, including five inducing KO mutations. Three founders carried only genome-edited alleles and were phenotypically indistinguishable from their wild-type counterparts. Among them, one male carrying a one base pair insertion leading to a KO allele is currently used to rapidly extend a PRNP-KO line of Alpine goats for future characterization. In addition to KO alleles, a PRNPdel6 genetic variant has been identified in one-third of founder animals. This new variant will be tested for its potential properties with respect to prion disease. Future studies will also evaluate the effects of genetic background on other characters associated with PRNP KO, as previously described in the Norwegian breed or other species. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammation biomarkers have been widely shown to be associated with infection. This study aimed to construct a nomogram based on systemic inflammation biomarkers and traditional prognostic factors to assess the risk of surgical site infection (SSI) after hip fracture in the elderly. Methods: Data were retrospectively collected from patients over 60 with acute hip fractures who underwent surgery and were followed for more than 12 months between June 2017 and June 2022 at a tertiary referral hospital. Biomarkers were calculated from peripheral venous blood collected on admission. The Centers for Disease Control and Prevention (CDC) definition of SSI was applied, with SSI identified through medical and pathogen culture records during hospitalization and routine postoperative telephone follow-ups. Multivariable logistic regression identified independent risk factors for SSI and developed predictive nomograms. Model stability was validated using an external set of patients treated from July 2022 to June 2023. Results: A total of 1430 patients were included in model development, with 41 cases (2.87%) of superficial SSI and 6 cases (0.42%) of deep SSI. Multivariable analysis identified traditional prognostic factors older age (OR = 1.08, 95% CI 1.04–1.12), ASA class III-IV (OR = 2.46, 95% CI 1.32–4.56), surgical delay ≥ 6 days (OR = 3.59, 95% CI 1.36–9.47), surgical duration > 180 min (OR = 2.72, 95% CI 1.17–6.35), and systemic inflammation biomarkers Platelet-to-lymphocyte ratio (PAR) ≥ 6.6 (OR = 2.25, 95% CI 1.17–4.33) and Systemic Immune-Inflammation Index (SII) ≥ 541.1 (OR = 2.24, 95% CI 1.14–4.40) as independent predictors of SSI. Model's stability was proved by internal validation, and external validation with 307 patients, and an online dynamic nomogram (https://brooklyn99.shinyapps.io/DynNomapp/) was generated. Conclusions: This study combined systemic inflammatory biomarkers and developed an online dynamic nomogram to predict SSI in elderly hip fracture patients, which could be used to guide early screening of patients with high risk of SSI and provide a reference tool for perioperative management. [ABSTRACT FROM AUTHOR]

Background: Patellar fractures are a common knee injury among elderly patients, with a high risk of developing surgical site infections (SSI) postoperatively, which severely affects patient prognosis and quality of life. Elderly patients are more susceptible to SSI due to various factors such as decreased immune function and chronic diseases. Therefore, identifying the risk factors for SSI is of great clinical significance for prevention. Objective: This study aims to analyze the risk factors for postoperative SSI in elderly patients with patellar fractures, providing a basis for developing more effective clinical prevention and treatment strategies. Methods: This retrospective study collected data from 856 elderly patients who underwent patellar fracture surgery at Baoding First Central Hospital between January 2017 and December 2023. Patients were divided into SSI and non-SSI groups based on the occurrence of SSI, and their demographic data, comorbidities, and laboratory results were analyzed. Logistic regression was used to identify independent risk factors for SSI, and ROC curve analysis was conducted to determine the optimal cutoff point for predictive indicators. Results: The incidence of SSI was found to be 2.1%. Univariate analysis showed that BMI, surgical delay, diabetes, hematocrit (HCT), and albumin (ALB) were significantly associated with SSI. Logistic regression analysis further confirmed that BMI (p = 0.043), surgical delay (p = 0.000), HCT (p = 0.038), ALB (p = 0.015), and diabetes (p = 0.022) were independent risk factors for SSI. ROC curve analysis indicated that the optimal cutoff points for BMI, HCT, and ALB were 25.39 kg/m2, 35.62%, and 39.3 g/L, respectively, with an AUC of 0.794 for the combined predictive indicators. Conclusion: High BMI, surgical delay, diabetes, low HCT, and low ALB are independent risk factors for postoperative SSI in elderly patients with patellar fractures. Preoperative management targeting these high-risk factors, such as optimizing patient weight, controlling diabetes, and improving nutritional status, can effectively reduce the incidence of SSI and improve postoperative outcomes. Future multicenter studies may further validate these findings and provide additional prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Falls are a common problem experienced by people living with HIV yet predictive models specific to this population remain underdeveloped. We aimed to identify, assess and stratify the predictive strength of various physiological, behavioral, and HIV-specific factors associated with falls among people living with HIV and inform a predictive model for fall prevention. Methods: Systematic review and meta-analysis were conducted to explore predictors of falls in people living with HIV. Data was sourced, screened, extracted, and analyzed by two independent reviewers from eight databases up to January 2nd, 2024, following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocol. Evidence quality and bias were assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and the Mixed Method Appraisal Tool (MMAT), respectively. Pooled odds ratios (OR) with 95% confidence intervals (CI) were computed using random-effects models to establish associations between predictors and falls risk. We applied established criteria (Bradford Hill's criteria, Rothman's and Nweke's viewpoints) to stratify risk factors and create a weighted predictive algorithm. Results: This review included 12 studies on falls/balance dysfunction in 117,638 participants (54,513 people living with HIV), with varying ages (45–50 years), sample sizes (32 − 26,373), study durations (6 months to 15 years), disease stages (CD4 + counts 347.2 cells/mm³ to ≥ 500 cells/µL) and fall definitions (self-reported histories to real-time reporting). Some predictors of falls in people living with HIV including depression, cannabis use, cognitive impairment/neurocognitive adverse effects (NCAE), hypertension, and stavudine—showed perfect risk responsiveness (Ri = 1), indicating their strong association with falls. Notably, cannabis use demonstrated the highest risk weight (Rw = 3.0, p < 0.05, 95%CI:1.51–5.82), followed by NCAE (Rw = 2.3, p < 0.05, 95%CI:1.66–3.21) and frailty with a broad confidence interval (Rw = 2.2, p < 0.05, 95%CI:0.73–14.40). Other significant predictors included hypertension (Rw = 1.8, p < 0.05, 95%CI:1.33–2.33), depression (Rw = 1.6, p < 0.05, 95%CI:1.22–2.18), stavudine use (Rw = 1.5, p < 0.05, 95%CI: 0.95–2.25), neuropathy (Rw = 1.3, p < 0.05, 95%CI:1.26–2.11), and polypharmacy (Rw = 1.2, p < 0.05, 95%CI:1.16–1.96). The fall risk threshold score was 12.8, representing the 76th percentile of the specific and sufficient risk weight. Conclusion: Our meta-analysis identifies predictors of falls in people living with HIV, emphasizing physiological, behavioral, and HIV-specific factors. Integrating these into clinical practice could mitigate falls-related sequelae. We propose a novel approach to falls risk prediction using a novel clinical index, resulting in a HIV-specific falls risk assessment tool. Trial registration: The study protocol is registered with PROSPERO ID: CRD42023453556. [ABSTRACT FROM AUTHOR]

Mathematical models are established tools to assist in outbreak response. They help characterise complex patterns in disease spread, simulate control options to assist public health authorities in decision-making, and longer-term operational and financial planning. In the context of vaccine-preventable diseases (VPDs), vaccines are one of the most-cost effective outbreak response interventions, with the potential to avert significant morbidity and mortality through timely delivery. Models can contribute to the design of vaccine response by investigating the importance of timeliness, identifying high-risk areas, prioritising the use of limited vaccine supply, highlighting surveillance gaps and reporting, and determining the short- and long-term benefits. In this review, we examine how models have been used to inform vaccine response for 10 VPDs, and provide additional insights into the challenges of outbreak response modelling, such as data gaps, key vaccine-specific considerations, and communication between modellers and stakeholders. We illustrate that while models are key to policy-oriented outbreak vaccine response, they can only be as good as the surveillance data that inform them. [ABSTRACT FROM AUTHOR]

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) has been a major cause of significant morbidity and mortality. Acute kidney injury (AKI) has been seen in COVID-19-infected subjects, and it has frequently resulted in an abnormal estimated glomerular filtration rate. Colchicine, an immunomodulatory drug, was used in several studies in the early stages of the pandemic. Colchicine has been shown to prevent the development of renal failure in patients with Familial Mediterranean Fever (FMF). It has also been reported to reduce fibrosis, which plays a role in chronic kidney disease. We, therefore, aimed to investigate whether using Colchicine, in addition to standard care, was associated with better renal function in patients with severe COVID-19 infection. Methods: This retrospective cohort study comprised 118 out of 605 hospitalized COVID-19 subjects. Some of the subjects (n = 50) received oral Colchicine plus standard care, called the Col (+) group. The others (n = 68) received only the standard care, called the Col (-) group. The estimated glomerular filtration rate (eGFR) and other laboratory findings, including lymphocytes, D-dimer, and CRP, were analyzed. Results: The D-dimer and serum creatine levels were significantly reduced in both groups. The number of lymphocytes showed a significant increase in both groups at discharge. The level of C-reactive protein (CRP) was significantly higher in the Col (+) group than in the Col (-) group at admission. The reduction of SCr was considerably higher in the Col (+) group than in the Col (-) group. Similarly, the improvement of eGFR was higher in the Col (+) group than in the Col (-) group at discharge and 6–12 mounts follow-up. Conclusion: Our findings indicated the use of Colchicine plus standard care was associated with improved renal function in hospitalized patients with severe COVID-19 infection. [ABSTRACT FROM AUTHOR]

Background: Surgical site infections (SSIs) are one of the most common healthcare-associated infections and preventable complication of surgical procedure; continue to threaten public health with significant effects on the patients and health care human and financial resources. Therefore, this study aimed to determine the incidence of SSIs, risk factors and common microorganisms associated with SSI and assess the practice of antimicrobial use in women following Caesarean Section (CS) at Queen Elizabeth Central Hospital (QECH). Methods: This was a hospital-based quantitative prospective study design involving pregnant women who underwent a CS between February, 2023 and July, 2023 at QECH with 30 day-follow-ups. Wound specimens (wound swabs) were collected from all infected CS wounds and processed at QECH main laboratory, and susceptibility testing was conducted using the Kirby-Bauer disk diffusion method with results reported only as susceptible, intermediate, or resistant and the collected data was analyzed using Stata. Results: The overall cumulative incidence of SSI recorded at QECH during the study period was 9.61% (20 cases out of 208). Of these, 19 (95%) of them reported superficial SSI following CS. The mean age was 26.1 years with a standard deviation of 6.2. All pregnant women who underwent for CS received antibiotic prophylaxis. This study revealed that 138 (66.35%) patients received both preoperative antibiotics (ceftriaxone) and post-CS antibiotics without knowing the specific bacterial organism isolated. This study revealed that ruptured membrane had twice the incidence of SSIs compared to intact membrane (χ2 = 2.0922), though not statistically significant. The majority of patients with SSIs (n = 12, 60%) were readmitted and 5 (25%) out of 20 with SSIs had antimicrobial resistance following susceptibility testing. Staphylococcus aureus was the most common organism (3, 60%) and other bacterial isolates included were Enterobacteriaceae and Acinetobacter baumanni. Conclusion: The incidence of SSIs and inappropriate antimicrobial use following CS remains a challenge at QECH. Therefore, due to increased number of SSIs following CS with relative emergence of AMR ensure intensive infection prevention and control practices, establishing AMS program and routine surveillance of SSIs at QECH. [ABSTRACT FROM AUTHOR]

Background: Schistosoma japonicum infection causes hepatic fibrosis, a primary cause of morbidity and mortality associated with the disease, and effective treatments are still lacking. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenic process of various tissue fibroses. However, the role of lncRNAs in schistosomiasis hepatic fibrosis (HF) is poorly understood. Understanding the role of lncRNAs in schistosomiasis HF will enhance knowledge of disease processes and aid in the discovery of therapeutic targets and diagnostic biomarkers. Methods: Differentially expressed lncRNA profiles in primary hepatic stellate cells (HSCs) of mice infected with S. japonicum were identified using high-throughput lncRNA sequencing. Primary HSCs were isolated from infected mice using collagenase digestion and density-gradient centrifugation, cultured in DMEM with 10% fetal bovine serum. Dual-luciferase reporter assays, nuclear cytoplasm fractionation and RIP assays were employed to assess the relationship between Malat1 and miRNA-96. Malat1 lentivirus and ASO-Malat1 were constructed for forced expression and downregulated expression of Malat1. The Malat1-KO mouse was constructed by CRISPR/Cas9 technology. Pathological features of the liver were evaluated by hematoxylin-eosin (HE), Masson's trichrome staining and immunohistochemistry (IHC). The expression levels of fibrosis-related genes were determined by quantitative real-time PCR (qRT-PCR) and Western blot. Results: A total of 1561 differentially expressed lncRNAs were identified between infected and uninfected primary HSCs. Among the top altered lncRNAs, the downregulated Malat1 was observed in infected HSCs and verified by qPCR. Treatment of infected mice with praziquantel (PZQ) significantly increased the Malat1 expression. Elevated Malat1 expression in infected primary HSC reduced the expressions of profibrogenic genes, whereas Malat1 knockdown had the opposite effect. Moreover, Malat1 was found to interact with miR-96, a profibrotic miRNA, by targeting Smad7. Forced Malat1 expression reduced miR-96 levels in infected primary HSCs, attenuating fibrogenesis and showing negative correlation between Malat1 expression and the expression levels of miR-96 and profibrogenic genes α-SMA and Col1α1. Notably, in Malat1-KO mice, knockout of Malat1 aggravates schistosomiasis HF, while restored Malat1 expression in the infected HSCs reduced the expression of profibrogenic genes. Conclusions: We demonstrate that lncRNA is involved in regulation of schistosomiasis HF. Elevated lncRNA Malat1 expression in infected HSCs reduces fibrosis via the Malat1/miR-96/Smad7 pathway, thus providing a novel therapeutic target for schistosomiasis HF. Furthermore, Malat1 expression is sensitive to PZQ treatment, thus offering a potential biomarker for assessing the response to chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a neglected tropical disease that affects over 250 million people, predominantly in impoverished communities, including those in Ethiopia. However, there is currently no available national data regarding its prevalence in Ethiopia or its potential association with anemia. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-2020) guideline was followed in our study. A comprehensive search strategy was conducted using international databases (PUB Med, Embase, Scopus, and Science Direct) and websites (Google Scholar and Google) from their date of inception to April 22, 2024. The quality of the retrieved studies was assessed using an adapted version of the Newcastle–Ottawa Scale. Publication bias and statistical heterogeneity were statistically assessed. A random effects model was applied, and all analysis was performed with STATA 17 statistical software. Result: The prevalence of schistosomiasis was assessed in twelve studies with 5747 participants. S. mansoni was studied in 11 research papers, while S. hematobium was assessed in one study. Using a random effect model due to high heterogeneity (I2 = 98.46%; P < 0.001), the overall pooled prevalence of schistosomiasis in Ethiopia was 22% (95% CI: 14.3, 29.6). The prevalence of schistosomiasis was about two and a half times higher in rural settings (23%) (95% CI: 15, 31) than in urban areas (10%) (95% CI: 3, 17). The burden of schistosomiasis was 23% between 2020 and 2024, compared to 16% from 2015–2019, with a higher prevalence among pediatric age groups (22%) versus 14% in mixed pediatric and adult age groups. The magnitude of schistosomiasis for good and very good-quality papers was 22% and 17%, respectively. In all the subgroup analyses, there was considerable statistically significant heterogeneity. No study was found to evaluate the association of schistosomiasis with anemia. Conclusion: The study reveals Ethiopia's higher schistosomiasis prevalence. Rural areas have a high burden of schistosomiasis. No eligible study was found to evaluate the association of schistosomiasis with anemia. Therefore, prevention and control measures should focus on rural settings. Trial registration: The registration number at PROSPERO is CRD42024538522. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is a new update on the resistance profile, Macrolide–Lincosamide–Streptogramin B resistance mechanisms and biofilm formation in the Staphylococcus aureus isolated from health care workers (HCWs) nasal carriage at a children's teaching hospital in Babol (Northern Iran). Results: A total of 143 non-repetitive nasal swab samples were collected from volunteers, where 53.8% (n; 77/143) were HCWs, 33.6% (n; 48/143) medical students, and 12.6% (n; 18/143) resident students. The prevalence of nasal carriers of S. aureus was 22.4% (n; 32/143), among them, 40.6% (n; 13/32) were identified as methicillin-resistant Staphylococcus aureus (MRSA(carriers. Antimicrobial susceptibility testing showed that erythromycin (68.8%, n; 22/32) and ciprofloxacin (15.6%, n; 5/32) had the highest and lowest resistance rate, respectively. The frequency of resistance genes in the strains was as follows; ermC (n; 17/32, 53.1%), ermA (n; 11/32, 34.4%), ermB (n; 6/32, 18.7%), ereA (n; 3/32, 9.4%). Moreover, 50.0% (n; 16/32), 28.1% (n; 9/32) and 21.8% (n; 7/32) of isolates were strongly, weakly and moderately biofilm producer, respectively. Macrolides-lincosamides-streptogramins B (MLSB) antibiotic resistance among S. aureus isolates from HCWs nasal carriage have found significant prevalence rates throughout the globe. It is crucial to remember that the development of biofilms and MLS B antibiotic resistance are both dynamic processes. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the prevalence of and factors associated with needle stick and sharps injuries (NSSIs) among health-care workers (HCWs) in a tertiary hospital in China. Materials and methods: This retrospective survey was conducted with 562 HCWs at a tertiary hospital in China in July 2023. Information was collected using a self-designed questionnaire, and all enrolled members were required to fill in the demographic characteristics, occurrence of NSSIs and other associated factors in the past year. Logistic analysis was used to identify variables associated with NSSIs. Results: The proportion of participants with at least one injury within the year preceding the investigation was 21.2%. Male (AOR = 2.116 [1.265, 3.538]), working hours per week > 40 (AOR = 1.718 [1.056,2.796]), rarely checking blood-borne infections before invasive operations (AOR = 2.219 [1.303,3.782]) were significantly associated with NSSIs. Conclusion: The prevalence of NSSIs was not low in the survey area, especially in male, individuals with longer working hours, and rarely checking blood-borne infections before invasive operations. Therefore, it is necessary to promote educational programs to enhance awareness of standard prevention measures, especially for key populations, and reduce heavy workloads to decrease the occurrence of such injuries. [ABSTRACT FROM AUTHOR]

Background: Herpes zoster (HZ), commonly known as "shingles," may contribute to cognitive decline through mechanisms such as neuroinflammation or direct neuronal injury. However, evidence on the longitudinal association between HZ and cognitive decline is conflicting and whether the risk differs by APOE ε4-carrier status has not been studied; prospective cohort studies on the association between HZ vaccination and cognitive decline are also lacking. Methods: We included 149,327 participants from three large cohorts—the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS)—to prospectively examine the association between HZ and subsequent subjective cognitive decline (SCD). Poisson regression was used to estimate the multivariable-adjusted relative risk (MVRR) of a 3-unit increment in SCD score according to years since HZ compared with participants with no history of HZ. Results: Compared with individuals with no history of HZ, the MVRR (95% CI) of a 3-unit increment in SCD score was significantly and independently higher among individuals with a history of HZ, but the duration of time since HZ when the elevated risk of SCD was statistically significant differed among the cohorts. In NHS, HZ was associated with higher long-term risk of SCD; compared with individuals with no history of HZ, the MVRR (95% CI) of a 3-unit increment in SCD score was 1.14 (1.01, 1.32) for ≥ 13 years since HZ. In NHS II, HZ was associated with higher risk of SCD in both the short-term [MVRR 1.34 (1.18, 1.53) for 1–4 years] and long-term [MVRR 1.20 (1.08, 1.34) for ≥ 13 years since HZ]. In HPFS, an elevated risk of SCD was suggested across all time points. Among the subset of participants with information on APOE ε4, there was a suggestion that the association differed by APOE ε4 carrier status, but the results were not consistent between women and men. Among the subset of women with information on HZ vaccination, there was a suggestion that the long-term risk of SCD may be greater among women who were not vaccinated against HZ. Conclusions: Data from three large independent cohorts of women and men showed that HZ was associated with higher long-term risk of SCD, and the risk may differ by APOE ε4-carrier status. [ABSTRACT FROM AUTHOR]

Chronic wasting disease (CWD), a prion disease affecting cervids, has been known in North America (NA) since the 1960s and emerged in Norway in 2016. Surveillance and studies have revealed that there are different forms of CWD in Fennoscandia: contagious CWD in Norwegian reindeer and sporadic CWD in moose and red deer. Experimental studies have demonstrated that NA CWD prions can infect various species, but thus far, there have been no reports of natural transmission to non-cervid species. In vitro and laboratory animal studies of the Norwegian CWD strains suggest that these strains are different from the NA strains. In this work, we describe the intracerebral transmission of reindeer CWD to six scrapie-susceptible sheep. Detection methods included immunohistochemistry (IHC), western blot (WB), enzyme-linked immunosorbent assay (ELISA), real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA). In the brain, grey matter vacuolation was limited, while all sheep exhibited vacuolation of the white matter. IHC and WB conventional detection techniques failed to detect prions; however, positive seeding activity with the RT-QuIC and PMCA amplification techniques was observed in the central nervous system of all but one sheep. Prions were robustly amplified in the lymph nodes of all animals, mainly by RT-QuIC. Additionally, two lymph nodes were positive by WB, and one was positive by ELISA. These findings suggest that sheep can propagate reindeer CWD prions after intracerebral inoculation, resulting in an unusual disease phenotype and prion distribution with a low amount of detectable prions. [ABSTRACT FROM AUTHOR]

Candida auris (C. auris) is a yeast that has caused several outbreaks in the last decade. Cell wall chitin plays a primary role in the antifungal resistance of C. auris. Herein, we investigated the potential of chitinase immobilized with UiO-66 to act as a potent antifungal agent against C. auris. Chitinase was produced from Talaromyces varians SSW3 in a yield of 8.97 U/g dry substrate (ds). The yield was statistically enhanced to 120.41 U/g ds by using Plackett–Burman and Box–Behnken design. We synthesized a UiO-66 framework that was characterized by SEM, TEM, XRD, FTIR, a particle size analyzer, and a zeta sizer. The produced framework had a size of 70.42 ± 8.43 nm with a uniform cubic shape and smooth surface. The produced chitinase was immobilized on UiO-66 with an immobilization yield of 65% achieved after a 6 h loading period. The immobilization of UiO-66 increased the enzyme activity and stability, as indicated by the obtained Kd and T1/2 values. Furthermore, the hydrolytic activity of chitinase was enhanced after immobilization on UiO-66, with an increase in the Vmax and a decrease in the Km of 2- and 38-fold, respectively. Interestingly, the antifungal activity of the produced chitinase was boosted against C. auris by loading the enzyme on UiO-66, with an MIC50 of 0.89 ± 0.056 U/mL, compared to 5.582 ± 0.57 U/mL for the free enzyme. This study offers a novel promising alternative approach to combat the new emerging pathogen C. auris. [ABSTRACT FROM AUTHOR]

Background: Oncomelania hupensis is the exclusive intermediate host of Schistosoma japonicum in China. Snail control is an essential component of schistosomiasis elimination programme. With 70 years of continuous efforts, the range of O. hupensis had reduced significantly, but slowed down in last decades. A large number of levees against flooding were constructed along Yangtze River and its affiliated lakes in the middle and lower reaches, which influenced the hydrology and ecology in the alluvial plains. The purpose of this study was to assess the impact of levees on the distribution of O. hupensis in the middle and lower reaches of the Yangtze River. Methods: The snail habitats were digitalised by hand-held GPS system. The years for discovery and elimination of snail habitats were extracted from historical records. The accumulated snail-infested range for each habitat was calculated on the basis of annual reports. The current distribution of O. hupensis was determined by systematic and environmental sampling. The geographical distribution of levees was obtained from satellite imagery. To assess the impact of levees, the data pertaining to O. hupensis were divided into two parts: inside and outside the Yangtze River. Joinpoint regression was utilised to divide the study time span and further characterise the regression in each period. The 5-year-period moving averages of eliminated area infested by snails were calculated for the habitats inside and outside Yangtze River. The moving routes of corresponding geographical median centres were simulated in ArcGIS. Hotspot analysis was used to determine the areas with statistical significance clustering of O. hupensis density. Results: Three periods were identified according to Joinpoint regression both inside and outside Yangtze River. The area infested by O. hupensis increased in the first two periods. It decreased rapidly outside Yangtze River year over year after 1970, while that inside the Yangtze River did not change significantly. Furthermore, the latter was significantly higher than the former. It was observed that the present density of O. hupensis inside Yangtze River was lower than outside the Yangtze River. The median centre for eliminated ranges inside Yangtze River wavered between the east (lower reach) and the west (middle reach). In contrast, the median centre for eliminated ranges continuously moved from the east to the west. Conclusions: Our findings indicated that the levees had a considerable negative impact on the distribution of O. hupensis outside Yangtze River. Some hotspots observed in the irrigation areas need a sluice system at the inlet of branch for snail control. The major distribution of O. hupensis located in Hubei might be caused by severe waterlogging. The intensive surveillance should be implemented there. The biggest two freshwater lakes, the major endemic regions historically, were identified as cold spots. The long-term impact of Three Gorges Dam on the distribution of O. hupensis in the lakes should be monitored and evaluated. [ABSTRACT FROM AUTHOR]

Background: The incidence of hospital-acquired infections in extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide and is frequently associated with an increase in mortality and morbidity rates. The aim of this study was to characterize clinical XDR-PA isolates recovered during six months at three different hospitals in Egypt. Results: Seventy hospital-acquired clinical isolates of P. aeruginosa were classified into multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR), according to their antimicrobial resistance profile. In addition, the possession of genes associated with mobile genetic elements and genes encoding antimicrobial resistance determinants among isolates were detected using polymerase chain reaction. As a result, a significant percentage of the isolates (75.7%) were XDR, while 18.5% were MDR, however only 5.7% of the isolates were non-MDR. The phenotypic detection of carbapenemases, extended-spectrum β-lactamases (ESBLs) and metallo β-lactamase (MBL) enzymes showed that 73.6% of XDR-PA isolates were carbapenemases producers, whereas 75.5% and 88.7% of XDR-PA isolates produced ESBLs and MBL respectively. In addition, PCR screening showed that oxa gene was the most frequently detected gene of carbapenemases (91.4%), while aac(6ʹ)-lb gene was mostly detected (84.3%) among the screened aminoglycosides-resistance genes. Furthermore, the molecular detection of the colistin resistance gene showed that 12.9% of isolates harbored mcr-1 gene. Concerning mobile genetic element markers (intI, traA, tnp513, and merA), intI was the highest detected gene as it was amplified in 67 isolates (95.7%). Finally, phylogenetic and molecular typing of the isolates via ERIC-PCR analysis revealed 10 different ERIC fingerprints. Conclusion: The present study revealed a high prevalence of XDR-PA in hospital settings which were resistant to a variety of antibiotics due to several mechanisms. In addition, 98% of the XDR-PA clinical isolates contained at least one gene associated with movable genetic elements, which could have aided the evolution of these XDR-PA strains. To reduce spread of drug resistance, judicious use of antimicrobial agents and strict infection control measures are therefore essential. [ABSTRACT FROM AUTHOR]

Background: In the last two decades, a significant increase in the number of Clostridioides difficile infection (CDI) cases has been observed. It is understandable to attempt to determine the factors that can predict the severity of the course of the infection and identify patients at risk of death. This study aimed to analyze the factors affecting the incidence and mortality of CDI in inpatient treatment at the University Clinical Hospital in Wrocław in 2016–2018. Methods: Statistical analysis of data obtained from patients' medical records was performed. Only patients with symptoms of infection and infection confirmed by laboratory tests were enrolled in the study. When analyzing the number of deaths, only adult patients who died in hospital wards were included. The quantitative data including laboratory tests, used antibiotics and Nutritional Risk Screening (NRS) were assessed. Also, the qualitative data such as sex, year of hospitalization, occurrence of diarrhoea on admission to the hospital, presence of additional diseases, as wee ad the use of antibacterial drugs or proton pump blockers and ranitidine during hospitalization were analyzed. Results: A total of 319 adult CDI patients (178 women and 141 men) were enrolled of which 80 people died (50 women and 30 men). The mean age of the patients was 72.08 ± 16.74 years. Over the entire period studied, the morbidity was 174 cases per 100,000 hospitalizations while mortality was 25.08%. The group of deceased patients was characterized by: older age (by 9.24 years), longer duration of hospitalization (by 10 days), reduced albumin levels (Rho = -0.235, p < 0.001), higher urea levels, use of more antibiotics, higher risk of malnutrition in NRS (Rho = 0.219, p < 0.001), higher incidence of sepsis, heart failure, stroke, hypothyroidism. Pneumonia was diagnosed twice as often. It was also shown that deceased patients were significantly more likely to take penicillin and fluoroquinolones. Conclusions: In this study, the morbidity was lower, but mortality was higher compared to similar hospitals in Poland. CDI patients were characterized by older age, multimorbidity, extended hospitalization, and the use of broad-spectrum antibiotics. Risk factors for death included advanced age, prolonged hospital stays, lower albumin, higher urea, malnutrition, and comorbidities like heart failure, stroke, pneumonia, sepsis, and hypothyroidism. Increased antibiotic use, particularly penicillin and fluoroquinolones, was associated with a higher mortality risk. [ABSTRACT FROM AUTHOR]

Background: Detection of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) in humans is important to prevent transmission. However, the most optimal culture method to detect CR-PA is unknown. This systematic review aims to determine which culture method is most sensitive and which culture methods are used to detect CR-PA in humans. Second, to establish the most feasible culture method taking into account the turnaround time (TAT), and third, to provide an overview of the sampling sites used to detect carriage. Methods: We systematically searched the electronic databases Embase, Medline Ovid, Cochrane, Scopus, CINAHL, and Web of Science until January 27, 2023. All diagnostic accuracy studies comparing two or more culture methods to detect CR-PA and recent outbreak or surveillance reports on CR-PA carriage or infection in humans, which describe culture methods and their results, were eligible for inclusion. We used QUADAS-2 guideline for diagnostic accuracy studies and the STROBE or ORION guideline for outbreak-surveillance studies to assess the risk of bias. Results: Six diagnostic accuracy studies were included. An enrichment broth was found to increase the detection of CR-PA. Using an enrichment broth extended the TAT by 18–24 h, yet selective media could reduce the TAT by 24 h compared to routine media. In total, 124 outbreak-surveillance studies were included, of which 17 studies with surveillance samples and 116 studies with clinical samples. In outbreak-surveillance studies with surveillance samples, perianal, rectal swabs or stools were the most common sampling site/specimen (13/17, 76%). A large variety was observed in whether and which kind of enrichment broth and selective media were used. Conclusions: We found a benefit of using an enrichment step prior to inoculation of the material onto selective media for the detection of CR-PA. More research is needed to determine the most sensitive sampling site and culture method. Trail registration: This study was registered in the PROSPERO International prospective register of systematic reviews (registration number: CRD42020207390, http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42020207390). [ABSTRACT FROM AUTHOR]

Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients' safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts' opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery. [ABSTRACT FROM AUTHOR]

Background: The Catalan Cancer Plan (CCP) undertakes periodic audits of cancer treatment outcomes, including organ/space surgical site infections (O/S-SSI) rates, while the Catalan Healthcare-associated Infections Surveillance Programme (VINCat) carries out standardized prospective surveillance of surgical site infections (SSI) in colorectal surgery. This cohort study aimed to assess the concordance between these two monitoring systems for O/S-SSI following primary rectal cancer surgery. Methods: The study compared O/S-SSI incidence data from CCP clinical audits versus the VINCat Programme in patients undergoing surgery for primary rectal cancer, in 2011-12 and 2015-16, in publicly funded centres in Spain. The main outcome variable was the incidence of O/S-SSI in the first 30 days after surgery. Concordance between the two registers was analysed using Cohen's kappa. Discordant cases were reviewed by an expert, and the main reasons for discrepancies evaluated. Results: Pooling data from both databases generated a sample of 2867 patients. Of these, O/S-SSI was detected in 414 patients—235 were common to both registry systems, with satisfactory concordance (κ = 0.69, 95% confidence interval 0.65–0.73). The rate of discordance from the CCP (positive cases in VINCat and negative in CCP) was 2.7%, and from VINCat (positive in CCP and negative in VINCat) was 3.6%. External review confirmed O/S-SSI in 66.2% of the cases in the CCP registry and 52.9% in VINCat. Conclusions: This type of synergy shows the potential of pooling data from two different information sources with a satisfactory level of agreement as a means to improving O/S-SSI detection. ClinicalTrials.gov Identifier: NCT06104579. Registered 30 November 2023. [ABSTRACT FROM AUTHOR]

The first case of CWD in a Norwegian red deer was detected by a routine ELISA test and confirmed by western blotting and immunohistochemistry in the brain stem of the animal. Two different western blotting tests were conducted independently in two different laboratories, showing that the red deer glycoprofile was different from the Norwegian CWD reindeer and CWD moose and from North American CWD. The isolate showed nevertheless features similar to the classical BSE (BSE-C) strain. Furthermore, BSE-C could not be excluded based on the PrPSc immunohistochemistry staining in the brainstem and the absence of detectable PrPSc in the lymphoid tissues. Because of the known ability of BSE-C to cross species barriers as well as its zoonotic potential, the CWD red deer isolate was submitted to the EURL Strain Typing Expert Group (STEG) as a BSE-C suspect for further investigation. In addition, different strain typing in vivo and in vitro strategies aiming at identifying the BSE-C strain in the red deer isolate were performed independently in three research groups and BSE-C was not found in it. These results suggest that the Norwegian CWD red deer case was infected with a previously unknown CWD type and further investigation is needed to determine the characteristics of this potential new CWD strain. [ABSTRACT FROM AUTHOR]

Background: The management of pandemics with highly infectious diseases in modern urban habitats depends largely on the maintenance of public services. Understanding the factors that influence municipal employees' willingness to come to work during a pandemic is therefore a basic requirement for adequate public health preparedness. In this study the extended parallel process model (EPPM) is applied to investigate how the readiness of municipal employees to report to work during an influenza pandemic (IP) is affected by individual attitudes and environmental conditions.Methods: 1.566 employees of a major German city participated in a cross-sectional online survey. The questions of the survey covered the dimensions of risk perception, role competence, self-efficacy, role importance, sense of duty, and willingness to report to work in the case of an IP. Data were analysed by means of path analyses.Results: Data suggest that up to 20% of the public service workers were not willing to come to work during an IP. Willingness to report to work was increased by the perception of a high working role competence, a high assessment of role importance, high self-efficacy expectations, and a high sense of duty. Negative effects on willingness to report to work were identified as the perception of a high risk to become infected at work and the perceived risk to infect family members. The decomposition of direct and indirect effects provided important insights into the interrelationships between model variables.Conclusions: Measures to increase municipal workers' willingness to report to work in case of an infectious pandemic should include communication strategies to inform employees clearly about their particular tasks during such critical events and training exercises to increase their confidence in their competences and skills to fulfil these tasks. [ABSTRACT FROM AUTHOR]

Background: Mother-to-child transmission is the primary cause of HIV cases among children. Antiretroviral therapy (ART) plays a critical role in preventing mother-to-child transmission and reducing HIV progression, morbidity, and mortality among mothers. However, after more than two decades of ART during pregnancy, the comparative effectiveness and safety of ART medications during pregnancy are unclear, and existing evidence is contradictory. This study aimed to assess the effectiveness and safety of different ART regimens among pregnant women living with HIV at preconception or during pregnancy. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science. We included randomized trials that enrolled pregnant women living with HIV and randomized them to receive ART for at least four weeks. Pairs of reviewers independently completed screening for eligible studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool. Our outcomes of interest included low birth weight, stillbirth, preterm birth, mother-to-child transmission of HIV, neonatal death, and congenital anomalies. Network meta-analysis was performed using a random-effects frequentist model, and the certainty of evidence was evaluated using the GRADE approach. Results: We found 14 eligible randomized trials enrolling 9,561 pregnant women. The median duration of ART uptake ranged from 6.0 to 17.4 weeks. No treatment was statistically better than a placebo in reducing the rate of neonatal mortality, stillbirth, congenital defects, preterm birth, or low birth weight deliveries. Compared to placebo, zidovudine (ZDV)/lamivudine (3TC) and ZDV monotherapy likely reduce mother-to-child transmission (odds ratio (OR): 0.13; 95% CI: 0.05 to 0.31, high-certainty; and OR: 0.50; 95% CI: 0.33 to 0.74, moderate-certainty). Moderate-certainty evidence suggested that ZDV/3TC was associated with decreased odds of stillbirth (OR: 0.47; 95% CI: 0.09 to 2.60). Conclusions: Our analysis provides high- to moderate-certainty evidence that ZDV/3TC and ZDV are more effective in reducing the odds of mother-to-child transmission, with ZDV/3TC also demonstrating decreased odds of stillbirth. Notably, our findings suggest an elevated odds of stillbirth and preterm birth associated with all other ART regimens. [ABSTRACT FROM AUTHOR]

Background Emerging evidence has suggested significant associations between ambient air pollution and changes in hemoglobin levels or anemia in specific vulnerable groups, but few studies have assessed this relationship in the general population. This study aimed to evaluate the association between long-term exposure to air pollution and hemoglobin concentrations or anemia in general adults in South Korea. Methods A total of 69,830 Korean adults from a large-scale nationwide survey were selected for our final analysis. Air pollutants included particulate matter with an aerodynamic diameter less than or equal to 10 micrometers (PM10), particulate matter with an aerodynamic diameter less than or equal to 2.5 micrometers, nitrogen dioxide, sulfur dioxide (SO2), and carbon monoxide (CO). We measured the serum hemoglobin concentration to assess anemia for each participant. Results In the fully adjusted model, exposure levels to PM10, SO2, and CO for one and two years were significantly associated with decreased hemoglobin concentrations (all p<0.05), with effects ranging from 0.15 to 0.62% per increase in interquartile range (IQR) for each air pollutant. We also showed a significant association of annual exposure to PM10 with anemia (p=0.0426); the odds ratio (OR) [95% confidence interval (CI)] for anemia per each increase in IQR in PM10 was estimated to be 1.039 (1.001–1.079). This association was also found in the 2-year duration of exposure (OR=1.046; 95% CI=1.009–1.083; adjusted Model 2). In addition, CO exposure during two years was closely related to anemia (OR=1.046; 95% CI=1.004–1.091; adjusted Model 2). Conclusions This study provides the first evidence that long-term exposure to air pollution, especially PM10, is significantly associated with reduced hemoglobin levels and anemia in the general adult population. [ABSTRACT FROM AUTHOR]

Introduction: Infections caused by Stenotrophomonas maltophilia are clinically important due to its intrinsic resistance to a broad range of antibiotics. Therefore, selecting the most appropriate antibiotic to treat S. maltophilia infection is a major challenge. Aim: The current meta-analysis aimed to investigate the global prevalence of antibiotic resistance among S. maltophilia isolates to the develop more effective therapeutic strategies. Method: A systematic literature search was performed using the appropriate search syntax after searching Pubmed, Embase, Web of Science and Scopus databases (May 2023). Statistical analysis was performed using Pooled and the random effects model in R and the metafor package. A total of 11,438 articles were retrieved. After a thorough evaluation, 289 studies were finally eligible for inclusion in this systematic review and meta-analysis. Result: Present analysis indicated that the highest incidences of resistance were associated with doripenem (97%), cefoxitin (96%), imipenem and cefuroxime (95%), ampicillin (94%), ceftriaxone (92%), aztreonam (91%) and meropenem (90%) which resistance to Carbapenems is intrinsic. The lowest resistance rates were documented for minocycline (3%), cefiderocol (4%). The global resistance rate to TMP-SMX remained constant in two periods before and after 2010 (14.4% vs. 14.6%). A significant increase in resistance to tigecycline and ceftolozane/tazobactam was observed before and after 2010. Conclusions: Minocycline and cefiderocol can be considered the preferred treatment options due to low resistance rates, although regional differences in resistance rates to other antibiotics should be considered. The low global prevalence of resistance to TMP-SMX as a first-line treatment for S. maltophilia suggests that it remains an effective treatment option. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a disease primarily caused by eggs laid by pathogens called schistosomes. Among the schistosome species infecting humans, Schistosoma japonicum possesses the largest fecundity; each adult female produces an average of 3500 eggs per day. The lack of proper culture conditions supporting continuous oviposition in vitro has precluded detailed investigation of mechanisms regulating sexual maturation and egg production in Schistosoma japonicum. Methods: We optimized in vitro culture conditions by replacing reagents that are part of the classical ABC169 medium. Fast Blue BB staining and 4′,6-diamidino-2-phenylindole (DAPI) labeling were applied to observe the sexual development status of the females. In vitro RNA interference (RNAi) technology was used to validate the capability of the modified medium. The detection of male β-alanyl-tryptamine (BATT) was conducted using liquid chromatography–mass spectrometry (LC–MS). Results: Both m-AB169 (1640) and AB169 (1640) media are capable of facilitating the sexual development of paired virgin female S. japonicum, as well as sustaining the mature reproductive organs and egg production of adult S. japonicum for at least 22 days in vitro. M-AB169 (1640) provided a more stable condition for supporting the sexual maturity of female S. japonicum, as evidenced by the consistent initiation of egg production compared with AB169 (1640). Through a comparative analysis of S. japonicum and S. mansoni in diverse media, we demonstrated that these closely related species display distinct demands for their sexual development and egg production, suggesting a potential influence of nutritional factors on the observed variations in host ranges among different schistosome species. Importantly, we successfully identified the presence of the pheromone β-alanyl-tryptamine (BATT) in S. japonicum, previously identified in S. mansoni, highlighting its conserved role in schistosome reproductive development. Through the employment of double-stranded RNA (dsRNA) treatment to silence two genes that are involved in either the male (gli1, glioma-associated oncogene homolog 1) or female (vf1, vitellogenic factor 1) side in male-induced female reproductive development of S. mansoni, we confirmed that the combination of m-AB169 (1640) and RNAi technology has the capacity to facilitate in vitro studies of S. japonicum's reproductive and oviposition processes. Conclusions: We developed a novel medium, m-AB169 (1640), that not only maintains the mature reproductive organs and continuous oviposition of adult female Schistosoma japonicum for up to 22 days but also supports the reproductive development and subsequent egg-laying of virgin females after pairing with male worms. This study provides a valuable in vitro platform for functional studies of the mechanisms underlying the fascinating biology of the female sexual development and egg production of S. japonicum, which may accelerate the development of new strategies targeting schistosome egg production. [ABSTRACT FROM AUTHOR]

Background: Surveillance programs are a key element of interventions aiming to reduce rates of surgical site infections (SSIs). The aim of this study was to evaluate rates and trends of SSIs following hip arthroplasty and colon surgery procedures in Piedmont, a region in North-western Italy, from 2010 to 2019. Further, we aimed to assess the burden of SSIs in terms of Disability-Adjusted Life-Years (DALYs). Methods: A prospective cohort study was conducted among 42 hospitals participating in the surveillance system. Procedure-specific SSI rates were calculated and the 2010 - 2019 trend was evaluated using Spearman's Rho test. Patients were stratified according to age, sex and infection risk index according to life expectancy in order to calculate DALYs, using a modified version of the ECDC's BCoDE toolkit: disease models for both procedure types were adapted to incorporate long-term disability associated with SSIs. Results: Overall, 20,356 hip arthroplasty and 11,011 colon surgery procedures were monitored over 10 years and were included in our analyses. Hip arthroplasty and colon surgery cumulative SSIs rates were 1.5% and 8% respectively. Using the Spearman's Rho test, we evaluated a significant downward trend from 2010 to 2019 for colon surgery interventions (Rs − 0.7, p < 0.05), while there was no difference for hip arthroplasty. (Rs − 0.04, p > 0.05). Regarding disease burden, a total of 955.3 (95%CI 837.7–1102.98) and 208.65 (95%CI 180.87–240.90) DALYs were calculated for SSIs following hip arthroplasty, whilst 76.58 (95%CI 67.15–90.71) and 38.62 (95% CI 33.09–45.36) DALYs for SSIs in colon surgery, in 2010 and 2019, respectively. Conclusions: The significant decrease both in terms of incidence and DALYs found in this study for colon surgery and the stability for hip arthroplasty support the role of surveillance networks in improving quality of care. Despite the smaller SSI rate, the burden associated with SSIs following hip arthroplasty was higher, which is important to consider in light of the aging population in Italy. [ABSTRACT FROM AUTHOR]

Background: CD40, encoded by TNFRSF5, participates in the survival of B cells, process of antigen presentation and generation of CD8+ T cell memory. It also has an important effect on HCV antiviral immune response. This study aims to investigate whether TNFRSF5 gene polymorphisms are associated with HCV infection outcomes among Chinese population.Methods: Three single nucleotide polymorphism (SNPs) (rs1535045, rs1883832, rs4810485) on TNFRSF5 were genotyped by TaqMan assay among Chinese population, including 1513 uninfected subjects, 496 spontaneous viral clearance subjects and 768 persistent HCV-infected subjects. Logistic analysis was used to compare these SNPs among different groups in this cross-sectional study. Functional annotations of the identified SNPs were further evaluated by bioinformatics analysis.Results: After adjusted by age, gender and routes of infection, the results of logistic analysis indicated that individuals carrying rs1535045 T allele had a higher risk to infect HCV compared with C allele (in recessive model, adjusted OR = 1.368, 95%CI = 1.070-1.749, P = 0.012). Subjects carried rs1535045 TT genotype were more likely to infect HCV than wild CC genotype (adjusted OR = 1.397, 95%CI = 1.078-1.809, P = 0.011). For rs1883832, T allele was significantly associated with an increased risk of HCV infection (in recessive model, adjusted OR = 1.337, 95%CI = 1.069-1.673, P = 0.011). Subjects with TT genotype had more possibility to infect HCV (adjusted OR = 1.351, 95%CI = 1.060-1.702, P = 0.015). In the stratified analysis, rs1535045 and rs1883832 were remained in various subgroups and the heterogeneity test showed no pronounced heterogeneity in any pairwise comparison (all P > 0.05). In addition, the results of the cumulative effects showed a tendency of that the more risk alleles (rs1535045 T and rs1883832 T) subjects carried, the more possibility of HCV infection exhibited (P<0.001). In haplotype analyses, compared with the CC haplotype, CT, TC and TT was correlated with an increased risk to infect HCV (P = 0.029, P = 0.047 and P<0.001, respectively).Conclusions: In conclusion, CD40 polymorphisms were significantly associated with the susceptibility to HCV among Chinese populations. [ABSTRACT FROM AUTHOR]

Background: Despite the functions of TLRs in the parasitic infections have been extensively reported, few studies have addressed the role of TLR3 in the immune response to Schistosoma japonicum infections. The aim of this study was to investigate the properties of TLR3 in the liver of C57BL/6 mice infected by S. japonicum. Methods: The production of TLR3+ cells in CD4+T cells (CD4+CD3+), CD8+T cells (CD8+CD3+), γδT cells (γδTCR+CD3+), NKT cells (NK1.1+CD3+), B cells (CD19+CD3−), NK (NK1.1−CD3+) cells, MDSC (CD11b+Gr1+), macrophages (CD11b+F4/80+), DCs (CD11c+CD11b+) and neutrophils (CD11b+ Ly6g+) were assessed by flow cytometry. Sections of the liver were examined by haematoxylin and eosin staining in order to measure the area of granulomas. Hematological parameters including white blood cell (WBC), red blood cell (RBC), platelet (PLT) and hemoglobin (HGB) were analyzed. The levels of ALT and AST in the serum were measured using biochemical kits. The relative titers of anti-SEA IgG and anti-SEA IgM in the serum were measured by enzyme-linked immunosorbent assay (ELISA). CD25, CD69, CD314 and CD94 molecules were detected by flow cytometry. Results: Flow cytometry results showed that the expression of TLR3 increased significantly after S. japonicum infection (P < 0.05). Hepatic myeloid and lymphoid cells could express TLR3, and the percentages of TLR3-expressing MDSC, macrophages and neutrophils were increased after infection. Knocking out TLR3 ameliorated the damage and decreased infiltration of inflammatory cells in infected C57BL/6 mouse livers.,The number of WBC was significantly reduced in TLR3 KO-infected mice compared to WT-infected mice (P < 0.01), but the levels of RBC, platelet and HGB were significantly increased in KO infected mice. Moreover, the relative titers of anti-SEA IgG and anti-SEA IgM in the serum of infected KO mice were statistically decreased compared with the infected WT mice. We also compared the activation-associated molecules expression between S.japonicum-infected WT and TLR3 KO mice. Conclusions: Taken together, our data indicated that TLR3 played potential roles in the context of S. japonicum infection and it may accelerate the progression of S. japonicum-associated liver pathology. [ABSTRACT FROM AUTHOR]

Backgrounds: Remdesivir (RDV) is an antiviral agent approved for the treatment of coronavirus disease 2019 (COVID-19); however, is not recommended for patients with renal impairment. Due to limitations associated with prospective clinical trials, real-world data on the safety and efficacy of RDV in patients with renal impairment are necessary. Methods: Propensity score-matched (PSM) retrospective analysis was conducted between March 2020 and September 2022 in COVID-19 patients with an eGFR < 30 mL/min in four Korean hospitals. The RDV treatment group was matched to the untreated control group. The safety and clinical outcomes in patients who received RDV were analyzed. Results: A total of 564 patients were enrolled; 229 patients received RDV either for treatment or prophylaxis. On day 5, no difference in nephrotoxicity was observed between the two groups, and liver enzyme levels were within the normal range. In multivariate analysis for new dialysis, RDV treatment was not a risk factor for new dialysis. Among the 564 patients, 417 were indicated for a 5-day course of RDV treatment and 211 patients were treated with RDV. After PSM, no differences in the clinical outcomes were observed between the two groups. Conclusion: RDV use in COVID-19 patients with renal impairment did not result in significant nephrotoxicity or hepatotoxicity. [ABSTRACT FROM AUTHOR]

Background: Schistosoma mekongi is a human blood fluke causing schistosomiasis that threatens approximately 1.5 million humans in the world. Nonetheless, the limited available S. mekongi genomic resources have hindered understanding of its biology and parasite-host interactions for disease management and pathogen control. The aim of our study was to integrate multiple technologies to construct a high-quality chromosome-level assembly of the S. mekongi genome. Methods: The reference genome for S. mekongi was generated through integrating Illumina, PacBio sequencing, 10 × Genomics linked-read sequencing, and high-throughput chromosome conformation capture (Hi-C) methods. In this study, we conducted de novo assembly, alignment, and gene prediction to assemble and annotate the genome. Comparative genomics allowed us to compare genomes across different species, shedding light on conserved regions and evolutionary relationships. Additionally, our transcriptomic analysis focused on genes associated with parasite-snail interactions in S. mekongi infection. We employed gene ontology (GO) enrichment analysis for functional annotation of these genes. Results: In the present study, the S. mekongi genome was both assembled into 8 pseudochromosomes with a length of 404 Mb, with contig N50 and scaffold N50 lengths of 1168 kb and 46,759 kb, respectively. We detected that 43% of the genome consists of repeat sequences and predicted 9103 protein-coding genes. We also focused on proteases, particularly leishmanolysin-like metalloproteases (M8), which are crucial in the invasion of hosts by 12 flatworm species. Through phylogenetic analysis, it was discovered that the M8 gene exhibits lineage-specific amplification among the genus Schistosoma. Lineage-specific expansion of M8 was observed in blood flukes. Additionally, the results of the RNA-seq revealed that a mass of genes related to metabolic and biosynthetic processes were up-regulated, which might be beneficial for cercaria production. Conclusions: This study delivers a high-quality, chromosome-scale reference genome of S. mekongi, enhancing our understanding of the divergence and evolution of Schistosoma. The molecular research conducted here also plays a pivotal role in drug discovery and vaccine development. Furthermore, our work greatly advances the understanding of host-parasite interactions, providing crucial insights for schistosomiasis intervention strategies. [ABSTRACT FROM AUTHOR]

Background: Oral nucleoside (acid) analogues (NAs) are recommended for patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV-ACLF). The efficacy and safety of tenofovir (TDF) and entecavir (ETV) in these patients remain unclear. Methods: A comprehensive literature search in PubMed, Web of Science, The Cochrane Library, and Embase database was conducted to select studies published before December 2022 on TDF or ETV for HBV-ACLF. The primary outcomes were survival rates at 4, 12, and 48 weeks. Secondary outcomes were virologic and biochemical responses, serum antigen conversion, liver function score, and safety. Results: Four prospective and one retrospective cohort studies were selected. The overall analysis showed comparable survival rates at 4, 12, and 48 weeks for all patients receiving TDF or ETV (4-week: RR = 1.17, 95% CI: 0.90–1.51, p = 0.24; 12-week: RR = 1.00, 95% CI: 0.88–1.13, p = 0.94; 48-week: RR = 0.96, 95% CI: 0.58–1.57, p = 0.86). Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score at 12 weeks were comparable in both groups but lower than baseline (CTP: SMD = -0.75, 95% CI:-2.81–1.30, p = 0.47; MELD: SMD = -1.10, 95% CI:-2.29–0.08, p = 0.07). At 48 weeks, estimated glomerular filtration rate (eGFR) levels were found to decrease to different degrees from baseline in both the TDF and ETV groups, and the decrease was greater in the TDF group than in the ETV group. No significant differences were found in biochemical, virologic response, and serum antigen conversion between the two groups during the observation period. Conclusion: TDF treatment of HBV-ACLF is similar to ETV in improving survival, liver function, and virologic response but the effects on renal function in two groups in the long term remain unclear. More and larger long-term clinical trials are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Citrobacter koseri (C. koseri) is a Gram-negative, motile, non-spore-forming facultative anaerobic bacillus belonging to the Enterobacteriaceae family. C. koseri typically utilizes citrate as the sole carbon source and constitutes part of the normal gastrointestinal flora in humans and animals. As an opportunistic pathogen, C. koseri infections are mainly observed in neonates, elderly individuals, and immunocompromised hosts. C. koseri has been one of the main etiological agents of neonatal meningitis and cerebral abscess. In recent years, an increasing number of cases have been reported in adults with severe infections caused by C. koseri. Here, we report for the first time a clinical case of concurrent C. koseri intra-abdominal infection in a patient with severe asthma and provide a brief review of the relevant literature. With this report, we hope to increase awareness and alertness among clinicians to the possibility of concurrent infection of gut commensal bacteria in asthmatic patients requiring long-term oral corticosteroid administration. [ABSTRACT FROM AUTHOR]

Prion diseases, including chronic wasting disease (CWD) in cervids, are fatal neurodegenerative disorders caused by the misfolding of cellular prion proteins. CWD is known to spread among captive and free-ranging deer in North America. In 2016, an outbreak of contagious CWD was detected among wild reindeer in Norway, marking the first occurrence of the disease in Europe. Additionally, new sporadic forms of CWD have been discovered in red deer in Norway and moose in Fennoscandia. We used serial protein misfolding cyclic amplification to study the ability of Norwegian prion isolates from reindeer, red deer, and moose (two isolates), as well as experimental classical scrapie from sheep, to convert a panel of 16 brain homogenates (substrates) from six different species with various prion protein genotypes. The reindeer CWD isolate successfully converted substrates from all species except goats. The red deer isolate failed to convert sheep and goat substrates but exhibited amplification in all cervid substrates. The two moose isolates demonstrated lower conversion efficacies. The wild type isolate propagated in all moose substrates and in the wild type red deer substrate, while the other isolate only converted two of the moose substrates. The experimental classical scrapie isolate was successfully propagated in substrates from all species tested. Thus, reindeer CWD and classical sheep scrapie isolates were similarly propagated in substrates from different species, suggesting the potential for spillover of these contagious diseases. Furthermore, the roe deer substrate supported conversion of three isolates suggesting that this species may be vulnerable to prion disease. [ABSTRACT FROM AUTHOR]

Background: Rifampicin plays a key role in the management of prosthetic joint infections (PJIs), however, the emergence of rifampicin resistance is associated with less favourable clinical outcomes. The purpose of this study was to investigate the impact of rifampicin resistance and other patient-related factors on recovery rates among patients with PJI undergoing debridement, antibiotics and implant retention (DAIR). Methods: We reviewed medical records and microbiology reports of 67 patients (37 males and 30 females) undergoing DAIR due to PJI between 2014 and 2021. Patient-related factors, co-morbidities and microbiological reports were collected and reviewed. Forty-four patients had hip, 21 had knee, 1 had shoulder and 1 had elbow joint infection. Obtained data were statistically analysed with a logistic regression model. Results: Rifampicin-sensitive organism was isolated in 47 cases. Recovery rate was 72.3% in the sensitive and 76.9% in the resistant group. We found no significant effect of rifampicin resistance on the probability of recovery. Age and diabetes mellitus showed negative clinical impact on recovery. Staphylococcus aureus and coagulase-negative Staphylococci were predominant in the rifampicin-sensitive (66.6% of the isolates) and Gram-negative rods in the resistant group (65.2%). Conclusions: Based on our results, higher age and diabetes mellitus may have a clinically relevant negative impact on clinical outcome, however, this effect was not statistically significant. This may be due to the limited number of patients included in this study. We observed no clinically relevant effect of rifampicin-resistance, sex and body mass index (BMI) on recovery rates among patients undergoing DAIR due to PJI. [ABSTRACT FROM AUTHOR]

Background: Using pigs as organ donors has advanced xenotransplantation to the point that it is almost ready for clinical use. However, there is still a zoonotic risk associated with xenotransplantation, and the potential transmission of porcine endogenous retroviruses needs to be surveyed. Despite significant attempts to eliminate this risk, by the selection of PERV-C free pigs with low expression of PERV-A, -B, and by the genome-wide inactivation of PERV using CRISPR/Cas9, the impact of superinfection resistance (SIR) was not investigated. SIR is a viral trait that prevents reinfection (superinfection). For PERV, the underlying mechanism is unclear, whether and how cells, that harbor functional PERV, are protected. Using PERV-C(5683) as a reference virus, we investigated SIR in a newly developed in vitro model to pursue the mechanism and confirm its protective effect. Results: We developed three PERV-C constructs on the basis of PERV-C(5683), each of which carries a hemagglutinin tag (HA-tag) at a different position of the envelope gene (SP-HA, HA-VRA, and RPep-HA), to distinguish between primary infection and superinfection. The newly generated PERV-C(5683)-HA viruses were characterized while quantifying the viral RNA, reverse transcriptase activity, protein expression analysis, and infection studies. It was demonstrated that SP-HA and RPep-HA were comparable to PERV-C(5683), whereas HA-VRA was not replication competent. SP-HA and RPep-HA were chosen to challenge PERV-C(5683)-positive ST-IOWA cells demonstrating that PERV-C-HA viruses are not able to superinfect those cells. They do not integrate into the genome and are not expressed. Conclusions: The mechanism of SIR applies to PERV-C. The production of PERV-C particles serves as a defense mechanism from superinfection with exogenous PERV-C. It was demonstrated by newly generated PERV-C(5683)-HA clones that might be used as a cutting-edge tool. The HA-tagging of PERV-C is novel, providing a blueprint for the tagging of other human tropic PERV viruses. The tagged viruses are suitable for additional in vitro and in vivo infection studies and will contribute, to basic research on viral invasion and pathogenesis. It will maintain the virus safety of XTx. [ABSTRACT FROM AUTHOR]

Background: Candida auris is an emerging yeast pathogen that can cause invasive infections, particularly candidemia, in healthcare settings. Candida auris is characterized by resistance to multiple classes of antifungal drugs and high mortality. Objective: To describe the risk factors, clinical characteristics, antifungal susceptibility pattern and outcomes of Candida auris blood stream infection. Methods: We conducted a retrospective review of electronic medical records of C. auris fungemia cases in the facilities under Hamad Medical corporation, Qatar from 1/11/2018 to 31/7/2021. Demographic data, risk factors, antibiogram and 30-day outcome are described. Results: We identified 36 patients with C. auris fungemia. Most of the patients were in intensive care unit following severe COVID-19 pneumonia and had received steroids and broad-spectrum antibiotics. Most cases were central line related. Over 90% of isolates were non-susceptible to fluconazole, while amphotericin B resistance reached 85%. Factors associated with high mortality included initial SOFA score of 9 or above and absence of source control. Conclusion: Our study reveals a concerning 41.6% mortality rate within 30 days of C. auris candidemia. Furthermore, the prevalence of amphotericin B resistance in Qatar exceeds what has been reported in the literature necessitating further exploration. Echinocandins retains nearly 100% susceptibility and should be prioritized as the treatment of choice. These findings emphasize the need for vigilant monitoring and appropriate management strategies to combat C. auris infections and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: This study conducted a survey of men who have sex with men (MSM) in Maanshan City of Anhui Province to assess the risk behaviors related to human immunodeficiency virus (HIV) infection. Methods: A cross-sectional survey was conducted from June 2016 to June 2019. The MSM were recruited by a peer-driven sampling method. A face-to-face interview with anonymous questionnaire was used for data collection. The information collected by the survey was summarized and epidemiology described the basic characteristics of MSM, and then the related factors were statistically analyzed. Results: A total of 934 MSM were recruited with a average age was 30.5 (SD = 8.90) years old, including 816 (87.4%) HIV negative participants and 118 (12.6%) HIV positive ones. This study showed that freelancer (OR = 4.02, 95% CI: 1.96–8.23), scope of sexual partners distribution (OR = 1.78, 95% CI: 1.36–2.33), number of male sexual partners (OR = 2.11, 95% CI: 1.47–3.02), role of anal sex with men was receptive (OR = 2.54, 95% CI: 1.25–5.13) and versatile (OR = 2.34, 95% CI: 1.31–4.19) and non-steady sex partners (OR = 2.14, 95% CI: 1.56–2.93) were risk factors for HIV infection, while monthly income (OR = 0.68, 95% CI: 0.57–0.82), education level (OR = 0.79, 95% CI: 0.66–0.95), frequency of condom use (OR = 0.53, 95% CI: 0.35–0.81) and number of oral sex partners (OR = 0.35, 95% CI: 0.24–0.51) in the past 6 months were protective factors for HIV infection. Conclusion: Risk behaviors were common in MSM, and urgent need for targeted and comprehensive interventions to reduce risky sexual behaviour and to prevent HIV infection in MSM. [ABSTRACT FROM AUTHOR]

Background: In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged with a high transmissibility rate and resulted in numerous negative impacts on global life. Preventive measures such as face masks, social distancing, and vaccination helped control the pandemic. Nonetheless, the emergence of SARS-CoV-2 variants, such as Omega and Delta, as well as coronavirus disease 2019 (COVID-19) reinfection, raise additional concerns. Therefore, this study aimed to determine the overall prevalence of reinfection on global and regional scales. Methods: A systematic search was conducted across three databases, PubMed, Scopus, and ProQuest Central, including all articles pertaining to COVID-19 reinfection without language restriction. After critical appraisal and qualitative synthesis of the identified relevant articles, a meta-analysis considering random effects was used to pool the studies. Results: We included 52 studies conducted between 2019 and 2022, with a total sample size of 3,623,655 patients. The overall prevalence of COVID-19 reinfection was 4.2% (95% confidence interval [CI]: 3.7–4.8%; n = 52), with high heterogeneity between studies. Africa had the highest prevalence of 4.7% (95% CI: 1.9–7.5%; n = 3), whereas Oceania and America had lower estimates of 0.3% (95% CI: 0.2–0.4%; n = 1) and 1% (95% CI: 0.8–1.3%; n = 7), respectively. The prevalence of reinfection in Europe and Asia was 1.2% (95% CI: 0.8–1.5%; n = 8) and 3.8% (95% CI: 3.4–4.3%; n = 43), respectively. Studies that used a combined type of specimen had the highest prevalence of 7.6% (95% CI: 5.8–9.5%; n = 15) compared with those that used oropharyngeal or nasopharyngeal swabs only that had lower estimates of 6.7% (95% CI: 4.8–8.5%; n = 8), and 3.4% (95% CI: 2.8–4.0%; n = 12) respectively. Conclusion: COVID-19 reinfection occurs with varying prevalence worldwide, with the highest occurring in Africa. Therefore, preventive measures, including vaccination, should be emphasized to ensure control of the pandemic. [ABSTRACT FROM AUTHOR]

Background: The prevalence of Human Papillomavirus (HPV) infection in the general population is widely known, however, there are still few studies related to this infection in minority groups, Thus, the objective is to analyze the frequency of human papillomavirus and associated factors in quilombola and gypsy women. Methods: Cross-sectional research with 145 quilombola and gypsy women from Caxias, Maranhão. Two Pap smear collections were performed and a questionnaire with 46 questions was applied between January, 2020 and March, 2021. Descriptive analysis and Odds Ratio with 95% confidence interval were performed. The research was approved by the ethics committee. Results: There were 09 cases of atypia. The frequency of human papillomavirus was 41.37%, with a higher risk in quilombolas 55 (91.70%). Multiple infections were prevalent (53%) with high-risk genotypes 21 (35%). Types 16 and 18 together accounted for 42.85% of cases. Conclusions: The frequency of human papillomavirus infection was higher than those recorded in the Northeast and Brazil, and therefore type 16 predominated. Due to limitations, the virus lineages and sublineages were not evaluated. Quilombola women had a higher rate of infection than gypsies. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a major neglected tropical disease that affects up to 250 million individuals worldwide. The diagnosis of human schistosomiasis is mainly based on the microscopic detection of the parasite's eggs in the feces (i.e., for Schistosoma mansoni or Schistosoma japonicum) or urine (i.e., for Schistosoma haematobium) samples. However, these techniques have limited sensitivity, and microscopic expertise is waning outside endemic areas. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) has become the gold standard diagnostic method for the identification of bacteria and fungi in many microbiological laboratories. Preliminary studies have recently shown promising results for parasite identification using this method. The aims of this study were to develop and validate a species-specific database for adult Schistosoma identification, and to evaluate the effects of different storage solutions (ethanol and RNAlater) on spectra profiles. Methods: Adult worms (males and females) of S. mansoni and S. japonicum were obtained from experimentally infected mice. Species identification was carried out morphologically and by cytochrome oxidase 1 gene sequencing. Reference protein spectra for the creation of an in-house MALDI-TOF MS database were generated, and the database evaluated using new samples. We employed unsupervised (principal component analysis) and supervised (support vector machine, k-nearest neighbor, Random Forest, and partial least squares discriminant analysis) machine learning algorithms for the identification and differentiation of the Schistosoma species. Results: All the spectra were correctly identified by internal validation. For external validation, 58 new Schistosoma samples were analyzed, of which 100% (58/58) were correctly identified to genus level (log score values ≥ 1.7) and 81% (47/58) were reliably identified to species level (log score values ≥ 2). The spectra profiles showed some differences depending on the storage solution used. All the machine learning algorithms classified the samples correctly. Conclusions: MALDI-TOF MS can reliably distinguish adult S. mansoni from S. japonicum. [ABSTRACT FROM AUTHOR]

Background: Sternal wound infection (SWI) post cardiac surgery remains an important cause of extra morbidity, mortality and cost. The objective was to identify risk factors for SWI in a cardiac centre in Eastern Saudi Arabia as part of the investigation into Surveillance variance in the local rates of SWI. Methods: We included cases and controls from a cross section of patients who underwent major cardiac surgery between 2017 and 2020 matched for age, sex and time of surgery. An explanatory logistic regression model was fitted to estimate the risk factors. Results: N = 204 (51 cases and 153 controls matching ratio 1:3, from a source population of 985 patients). factors significantly associated with SWI in the final multivariate model: hospital stay OR (1.05, Cl 1.01–1.10), Graft Conduit BIMA versus No Graft OR (10.94, Cl 1.60–74.63), transfusion of both packed cells plus other blood products versus no transfusion OR (3.53, Cl 93–13.44), HbA1c OR (1.09 Cl 0.84–1.41), BMI OR (1.25, Cl 1.04–1.50), perioperative blood glucose OR (1.02, Cl 1.004–1.03), surgery time OR (1.19, Cl 1.00–1.58). Conclusions: The diverse aetiology, cross-disciplinary nature of SWI prevention, and despite improved prevention and control practices, including related care bundles with their proven value, SWI remain a serious challenge in cardiac surgery. Multidisciplinary consensus guidelines are well overdue. [ABSTRACT FROM AUTHOR]

Background: Periprosthetic joint infection (PJI) following total knee arthroplasty (TKA) is a severe complication in terms of disability, morbidity, and cost. We performed a study to investigate whether early PJI (within 90 days of primary TKA) is associated with increased mortality. Secondary aims were to compare mortality rates over time and between surgical treatment methods. Methods: Patients with suspected PJI were identified by linkage of the Swedish Knee Arthroplasty Register (SKAR) and the Swedish Prescribed Drug Register (SPDR) in 2007–2008 and 2012–2013. Medical records of patients receiving more than 4 weeks of continuous antibiotic therapy were subsequently reviewed to verify the PJI diagnosis. Information on mortality was obtained through the SKAR which is updated daily from the tax agency and patients with PJI were compared to patients without PJI. Results: Four hundred sixty-six patients were diagnosed with PJI within 90 days and compared to 40,362 patients without PJI. Mortality rates were significantly higher for PJI patients in both short- and long term: 2.6% vs. 0.8% at 1 year, 4.9% vs. 1.9% at 2 years, 15.7% vs. 7.1% at 5 years, and 38% vs. 21.4% at 10 years. The difference in mortality rate remained after adjusting for sex, age, diagnosis, and time period for surgery with Hazard Ratio 1.8 (95% CI:1.6–2.1). Mortality rates did not differ between time periods, and we found no correlation to surgical treatment. Conclusion: Patients with early PJI after primary TKA have an increased mortality rate compared to TKA patients without PJI. Improvements in surgical treatment strategy has not resulted in better survival. Long term difference in mortality rates indicates that PJI is not the sole reason for mortality suggesting a general frailty in PJI patients. [ABSTRACT FROM AUTHOR]

Background: In the past decade, Brazil has significantly reduced the prevalence of schistosomiasis through a combined effort of early treatment of infected people, expansion of basic sanitation infrastructure and educational measures. Despite these efforts, in some areas, prevalence of schistosomiasis exceeds 20% of the school population, who lack knowledge of the risks of the disease. Action can be taken in schools to empower this population about their health condition. This paper describes the role of the teacher as a multiplier of knowledge about schistosomiasis and proposes two different approaches to training these teachers.Methods: This study used mixed methods to evaluate training of teachers and educational intervention with those teachers' pupils. Two training courses, each with 40 h of face-to-face activity, were offered to 19 teachers, using two different but complementary approaches, based on theoretical references and specific educational strategies: Critical Pedagogical Approach (Training Course I, held in 2013) and Creative Play Approach (Training Course II, held in 2014).The courses included classroom activities, laboratory and field work. After the training, the teachers conducted activities on schistosomiasis with their pupils. These activities involved constructing educational materials and cultural productions. The pupils' knowledge about the disease was evaluated before the activities and 12 months later. The teachers' acceptance and perceptions were assessed through structured interviews and subsequent thematic analysis. The Shistosoma mansoni infection status of teachers and their students was also assessed using the Kato Katz stool test.Results: The parasitological study showed 31.6% of the teachers and 21.4% of the pupils to be positive for S. mansoni. The teachers' knowledge of important aspects of schistosomiasis transmission and prevention was fragmented and incorrect prior to the training. The teachers' knowledge changed significantly after the training and they were strongly accepting of the pedagogical methods used during the training. The level of their pupils' knowledge about the disease had increased significantly (p < 0.05). However, pupils responded that, even after the educational activities, they still had contact with the city's contaminated waters (p > 0.05).Conclusions: The results of this study underline the importance of schools and teachers as partners in controlling and eliminating schistosomiasis. Teacher training on the disease significantly increases their pupils' knowledge, reflecting empowerment with regard to local health conditions. [ABSTRACT FROM AUTHOR]

Background: Heat shock proteins (HSPs) are evolutionarily conserved proteins, produced by cells in response to hostile environmental conditions, that are vital to organism homeostasis. Here, we undertook the first detailed molecular bioinformatic analysis of these important proteins and mapped their tissue expression in the human parasitic blood fluke, Schistosoma mansoni, one of the causative agents of the neglected tropical disease human schistosomiasis. Methods: Using bioinformatic tools we classified and phylogenetically analysed HSP family members in schistosomes, and performed transcriptomic, phosphoproteomic, and interactomic analysis of the S. mansoni HSPs. In addition, S. mansoni HSP protein expression was mapped in intact parasites using immunofluorescence. Results: Fifty-five HSPs were identified in S. mansoni across five HSP families; high conservation of HSP sequences were apparent across S. mansoni, Schistosoma haematobium and Schistosoma japonicum, with S. haematobium HSPs showing greater similarity to S. mansoni than those of S. japonicum. For S. mansoni, differential HSP gene expression was evident across the various parasite life stages, supporting varying roles for the HSPs in the different stages, and suggesting that they might confer some degree of protection during life stage transitions. Protein expression patterns of HSPs were visualised in intact S. mansoni cercariae, 3 h and 24 h somules, and adult male and female worms, revealing HSPs in the tegument, cephalic ganglia, tubercles, testes, ovaries as well as other important organs. Analysis of putative HSP protein-protein associations highlighted proteins that are involved in transcription, modification, stability, and ubiquitination; functional enrichment analysis revealed functions for HSP networks in S. mansoni including protein export for HSP 40/70, and FOXO/mTOR signalling for HSP90 networks. Finally, a total of 76 phosphorylation sites were discovered within 17 of the 55 HSPs, with 30 phosphorylation sites being conserved with those of human HSPs, highlighting their likely core functional significance. Conclusions: This analysis highlights the fascinating biology of S. mansoni HSPs and their likely importance to schistosome function, offering a valuable and novel framework for future physiological investigations into the roles of HSPs in schistosomes, particularly in the context of survival in the host and with the aim of developing novel anti-schistosome therapeutics. [ABSTRACT FROM AUTHOR]

Background: Prediction models for poor patient-reported surgical outcomes after total hip replacement (THR) and total knee replacement (TKR) may provide a method for improving appropriate surgical care for hip and knee osteoarthritis. There are concerns about methodological issues and the risk of bias of studies producing prediction models. A critical evaluation of the methodological quality of prediction modelling studies in THR and TKR is needed to ensure their clinical usefulness. This systematic review aims to (1) evaluate and report the quality of risk stratification and prediction modelling studies that predict patient-reported outcomes after THR and TKR; (2) identify areas of methodological deficit and provide recommendations for future research; and (3) synthesise the evidence on prediction models associated with post-operative patient-reported outcomes after THR and TKR surgeries. Methods: MEDLINE, EMBASE, and CINAHL electronic databases will be searched to identify relevant studies. Title and abstract and full-text screening will be performed by two independent reviewers. We will include (1) prediction model development studies without external validation; (2) prediction model development studies with external validation of independent data; (3) external model validation studies; and (4) studies updating a previously developed prediction model. Data extraction spreadsheets will be developed based on the CHARMS checklist and TRIPOD statement and piloted on two relevant studies. Study quality and risk of bias will be assessed using the PROBAST tool. Prediction models will be summarised qualitatively. Meta-analyses on the predictive performance of included models will be conducted if appropriate. A narrative review will be used to synthesis the evidence if there are insufficient data to perform meta-analyses. Discussion: This systematic review will evaluate the methodological quality and usefulness of prediction models for poor outcomes after THR or TKR. This information is essential to provide evidence-based healthcare for end-stage hip and knee osteoarthritis. Findings of this review will contribute to the identification of key areas for improvement in conducting prognostic research in this field and facilitate the progress in evidence-based tailored treatments for hip and knee osteoarthritis. Systematic review registration: PROSPERO registration number CRD42021271828. [ABSTRACT FROM AUTHOR]

Background: The Internet has become an important virtual venue for men who have sex with men to seek sexual partners, with a high potential threat to spread sexually transmitted infections (STIs). However, the online sex-seeking use and its risk causing STIs spread remain unclear among heterosexual men. We conducted a cross-sectional study to investigate the use of online sex-seeking venues and the related risky sex activities (e.g. condomless sex, quick sex) in STIs clinics in Guangdong, China.Methods: These STIs clinics were involved in the Guangdong governmental sentinel network and we recruited heterosexual men (age >  = 18) between March and August 2018. Multivariable logistic regression models were used to identify the factors associated with online sex-seeking use and risky sex activities with online sex partners.Results: 191 of 2,154 participants (8.9%) ever sought sex online. Among users,16.8% met their partners in-person within 24 h, 31.4% engaged in condomless sex with their last online partner. Online sex-seeking was positively associated with a) Ever been diagnosed with STIs (aOR = 3.0, 95%CI:2.0-4.6), and b) Had casual sex in the last three months (aOR = 3.3, 95%CI 2.4-4.6). Condomless sex with the last online partner was negatively associated with the correct answer of "Having only one partner can reduce the risk to infect HIV" (aOR = 0.3, 95%CI:0.1-0.8).Conclusion: In China, online sex-seeking and its related risky sexual activities are not rare among heterosexual men. Future prevention strategies to reduce STIs incidence should especially target heterosexual men engaging in online sex-seeking. [ABSTRACT FROM AUTHOR]

Background: Coinfection with hepatitis C virus (HCV) is common in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients due to shared routes of transmission. We aimed to investigate the characteristics of HCV subgenotypes among HIV/HCV-coinfected patients in Guangdong and explore the molecular transmission networks and related risk factors for HCV strains. Methods: Plasma samples were obtained from 356 HIV/HCV-coinfected patients for HCV NS5B region sequencing. A neighbor-joining phylogenetic tree was constructed to affirm HCV subgenotypes. The transmission networks based on maximum likelihood phylogenetic tree were determined by Cluster Picker, and visualized using Cytoscape 3.2.1. Results: A total of 302 HCV NS5B sequences were successfully amplified and sequenced from the 356 plasma samples. A neighbor-joining phylogenetic tree based on the 302 NS5B sequences revealed the profile of HCV subgenotypes circulating among HIV/HCV coinfection patients in Guangdong. Two predominant strains were found to be 6a (58.28%, 176/302) and 1b (18.54%, 56/302), followed by 3a (10.93%, 33/302), 3b (6.95%, 21/302), 1a (3.64%, 11/302), 2a (0.99%, 3/302) and 6n (0.66%, 2/302). A molecular transmission network of five major HCV genotypes was constructed, with a clustering rate of 44.04%. The clustering rates of subgenotypes 1a, 3a, 3b, 1b, and 6a were 18.18% (2/11), 42.42%, 52.38%, 48.21%, and 44.89%, respectively. Multivariate logistic regression analysis showed no significant effects from sex, age, transmission route, geographical region, baseline CD4 + T cell count or subgenotype (P > 0.05), except marital status. Married or cohabiting people (compared with unmarried people) had more difficulty forming transmission networks. Conclusions: In summary, this study, based on HCV NS5B subgenotypes, revealed the HCV subtype diversity and distribution among HIV/HCV-coinfected patients in Guangdong. Marital status inclined to be the factor influencing HCV transmission networks formation. [ABSTRACT FROM AUTHOR]

Background: Comparative effectiveness research (CER) using observational databases has been suggested to obtain personalized evidence of treatment effectiveness. Inferential difficulties remain using traditional CER approaches especially related to designating patients to reference classes a priori. A novel Instrumental Variable Causal Forest Algorithm (IV-CFA) has the potential to provide personalized evidence using observational data without designating reference classes a priori, but the consistency of the evidence when varying key algorithm parameters remains unclear. We investigated the consistency of IV-CFA estimates through application to a database of Medicare beneficiaries with proximal humerus fractures (PHFs) that previously revealed heterogeneity in the effects of early surgery using instrumental variable estimators.Methods: IV-CFA was used to estimate patient-specific early surgery effects on both beneficial and detrimental outcomes using different combinations of algorithm parameters and estimate variation was assessed for a population of 72,751 fee-for-service Medicare beneficiaries with PHFs in 2011. Classification and regression trees (CART) were applied to these estimates to create ex-post reference classes and the consistency of these classes were assessed. Two-stage least squares (2SLS) estimators were applied to representative ex-post reference classes to scrutinize the estimates relative to known 2SLS properties.Results: IV-CFA uncovered substantial early surgery effect heterogeneity across PHF patients, but estimates for individual patients varied with algorithm parameters. CART applied to these estimates revealed ex-post reference classes consistent across algorithm parameters. 2SLS estimates showed that ex-post reference classes containing older, frailer patients with more comorbidities, and lower utilizers of healthcare were less likely to benefit and more likely to have detriments from higher rates of early surgery.Conclusions: IV-CFA provides an illuminating method to uncover ex-post reference classes of patients based on treatment effects using observational data with a strong instrumental variable. Interpretation of treatment effect estimates within each ex-post reference class using traditional CER methods remains conditional on the extent of measured information in the data. [ABSTRACT FROM AUTHOR]