Enhanced tuberculosis diagnosis with computer-aided chest X-ray and urine LAM in adults with HIV admitted to hospital (CASTLE study): A cluster randomised trial.

BACKGROUND: People with HIV (PHIV) admitted to hospital have high mortality, with tuberculosis (TB) being the major cause of death. Systematic use of new TB diagnostics could improve TB diagnosis and might improve outcomes. METHODS: We conducted a cluster randomised trial among adult PHIV admitted to Zomba Central Hospital, Malawi. Admission-days were randomly assigned to: enhanced TB diagnostics using urine lipoarabinomannan (LAM) antigen tests (SILVAMP-LAM, Fujifilm, Japan and Determine-LAM, Alere/Abbot, USA), digital chest X-ray with computer aided diagnosis (dCXR-CAD, CAD4TBv6, Delft, Netherlands), plus usual care ("enhanced TB diagnostics"); or usual care alone ("usual care"). The primary outcome was TB treatment initiation during admission. Secondary outcomes were 56-day mortality, TB diagnosis within 24-hours, and undiagnosed TB at discharge, ascertained by culture of one admission sputum sample. FINDINGS: Between 2 September 2020 and 15 February 2022, we recruited 419 people. Four people were excluded post-recruitment, leaving 415 adults recruited during 207 randomly assigned admission-days in modified intention-to-treat analysis. At admission, 90.8% (377/415) were taking antiretroviral therapy (ART) with median (IQR) CD4 cell count 240 cells/mm3. In the enhanced diagnostic arm, median CAD4TBv6 score was 60 (IQR: 51-71), 4.4% (9/207) had SILVAMP-LAM-positive and 14.4% (29/201) had Determine-LAM positive urine with three samples positive by both urine tests. TB treatment was initiated in 46/208 (22%) in enhanced TB diagnostics arm and 24/207 (12%) in usual care arm (risk ratio [RR] 1.92, 95% CI 1.20-3.08). There was no difference in mortality by 56 days (enhanced TB diagnosis: 54/208, 26%; usual care: 52/207, 25%; hazard ratio 1.05, 95% CI 0.72-1.53); TB treatment initiation within 24 hours (enhanced TB diagnosis: 8/207, 3.9%; usual care: 5/208, 2.4%; RR 1.61, 95% CI 0.53-4.71); or undiagnosed microbiological-confirmed TB at discharge (enhanced TB diagnosis, 0/207 (0.0%), usual care arm 2/208 (1.0%) (p = 0.50). INTERPRETATION: Urine SILVAMP-LAM/Determine-LAM plus dCXR-CAD diagnostics identified more hospitalised PHIV with TB than usual care. The increase in TB treatment appeared mainly due to greater use of Determine-LAM, rather than SILVAMP-LAM or dCXR-CAD. Poor concordance between Determine-LAM and SILVAMP-LAM urine tests requires further investigation. Inpatient mortality for adults with HIV remains unacceptability high.

The kinesin KIF4 mediates HBV/HDV entry through the regulation of surface NTCP localization and can be targeted by RXR agonists in vitro.

Intracellular transport via microtubule-based dynein and kinesin family motors plays a key role in viral reproduction and transmission. We show here that Kinesin Family Member 4 (KIF4) plays an important role in HBV/HDV infection. We intended to explore host factors impacting the HBV life cycle that can be therapeutically addressed using siRNA library transfection and HBV/NLuc (HBV/NL) reporter virus infection in HepG2-hNTCP cells. KIF4 silencing resulted in a 3-fold reduction in luciferase activity following HBV/NL infection. KIF4 knockdown suppressed both HBV and HDV infection. Transient KIF4 depletion reduced surface and raised intracellular NTCP (HBV/HDV entry receptor) levels, according to both cellular fractionation and immunofluorescence analysis (IF). Overexpression of wild-type KIF4 but not ATPase-null KIF4 mutant regained the surface localization of NTCP and significantly restored HBV permissiveness in these cells. IF revealed KIF4 and NTCP colocalization across microtubule filaments, and a co-immunoprecipitation study revealed that KIF4 interacts with NTCP. KIF4 expression is regulated by FOXM1. Interestingly, we discovered that RXR agonists (Bexarotene, and Alitretinoin) down-regulated KIF4 expression via FOXM1-mediated suppression, resulting in a substantial decrease in HBV-Pre-S1 protein attachment to HepG2-hNTCP cell surface and subsequent HBV infection in both HepG2-hNTCP and primary human hepatocyte (PXB) (Bexarotene, IC50 1.89 ± 0.98 µM) cultures. Overall, our findings show that human KIF4 is a critical regulator of NTCP surface transport and localization, which is required for NTCP to function as a receptor for HBV/HDV entry. Furthermore, small molecules that suppress or alleviate KIF4 expression would be potential antiviral candidates targeting HBV and HDV entry.

Biochemical implication of acetylcholine, histamine, IL-18, and interferon-alpha as diagnostic biomarkers in hepatitis C virus, coronavirus disease 2019, and dual hepatitis C virus-coronavirus disease 2019 patients.

Globally, hepatitis C virus (HCV) and coronavirus disease 2019 (COVID-19) are the most common causes of death due to the lack of early predictive and diagnostic tools. Therefore, research for a new biomarker is crucial. Inflammatory biomarkers are critical central players in the pathogenesis of viral infections. IL-18, produced by macrophages in early viral infections, triggers inflammatory biomarkers and interferon production, crucial for viral host defense. Finding out IL-18 function can help understand COVID-19 pathophysiology and predict disease prognosis. Histamine and its receptors regulate allergic lung responses, with H1 receptor inhibition potentially reducing inflammation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. angiotensin-converting enzyme 2 (ACE-2) receptors on cholangiocytes suggest liver involvement in SARS-CoV-2 infection. The current study presents the potential impact of circulating acetylcholine, histamine, IL-18, and interferon-Alpha as diagnostic tools in HCV, COVID-19, and dual HCV-COVID-19 pathogenesis. The current study was a prospective cross-section conducted on 188 participants classified into the following four groups: Group 1 COVID-19 (n = 47), Group 2 HCV (n = 47), and Group 3 HCV-COVID-19 patients (n = 47), besides the healthy control Group 4 (n = 47). The levels of acetylcholine, histamine, IL-18, and interferon-alpha were assayed using the ELISA method. Liver and kidney functions within all groups showed a marked alteration compared to the healthy control group. Our statistical analysis found that individuals with dual infection with HCV-COVID-19 had high ferritin levels compared to other biomarkers while those with COVID-19 infection had high levels of D-Dimer. The histamine, acetylcholine, and IL-18 biomarkers in both COVID-19 and dual HCV-COVID-19 groups have shown discriminatory power, making them potential diagnostic tests for infection. These three biomarkers showed satisfactory performance in identifying HCV infection. The IFN-Alpha test performed well in the HCV-COVID-19 group and was fair in the COVID-19 group, but it had little discriminative value in the HCV group. Moreover, our findings highlighted the pivotal role of acetylcholine, histamine, IL-18, and interferon-Alpha in HCV, COVID-19, and dual HCV-COVID-19 infection. Circulating levels of acetylcholine, histamine, IL-18, and interferon-Alpha can be potential early indicators for HCV, COVID-19, and dual HCV-COVID-19 infection. We acknowledge that further large multicenter experimental studies are needed to further investigate the role biomarkers play in influencing the likelihood of infection to confirm and extend our observations and to better understand and ultimately prevent or treat these diseases.

Nanoassemblies of Chitosan-Based Polyelectrolyte Complexes as Nucleic Acid Delivery Systems.

Nucleic acid delivery requires vectorization for protection from nucleases, preventing clearance by the reticuloendothelial system, and targeting to allow cellular uptake. Nanovectors meeting the above specifications should be safe for the patient, simple to manufacture, and display long-term stability. Our nanovectors were obtained via the green process of polyelectrolyte complexation, carried out at 25 °C in water at a low shear rate using chitosan (a polycationic biocompatible polysaccharide of specific molar mass and acetylation degree) and dextran sulfate as a polyanionic biocompatible polysaccharide. These complexes formed nanoassemblies of primary nanoparticles (20-35 nm) and maintained their colloidal stability for over 1 year at 25 °C. They could be steam sterilized, and a model nucleic acid could be either encapsulated or surface adsorbed. A targeting agent was finally bound to their surface. This work serves as a proof of concept of the suitability of chitosan-based polyelectrolyte complexes as nanovectors by sequential multilayered adsorption of various biomacromolecules.

Postoperative infectious complications worsen oncologic outcomes following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreaticoduodenectomy (PD) remains the only curative option for patients with pancreatic adenocarcinoma (PDAC). Infectious complications (IC) can negatively impact patient outcomes and delay adjuvant therapy in most patients. This study aims to determine IC effect on overall survival (OS) following PD for PDAC. STUDY DESIGN: Patients who underwent PD for PDAC between 2010 and 2020 were identified from a single institutional database. Patients were categorized into two groups based on whether they experienced IC or not. The relationship between postoperative IC and OS was investigated using Kaplan-Meier and Cox-regression multivariate analysis. RESULTS: Among 655 patients who underwent PD for PDAC, 197 (30%) experienced a postoperative IC. Superficial wound infection was the most common type of infectious complication (n = 125, 63.4%). Patients with IC had significantly more minor complications (Clavien-Dindo [CD] < 3; [59.4% vs. 40.2%, p < 0.001]), major complications (CD ≥ 3; [37.6% vs. 18.8%, p < 0.001]), prolonged LOS (47.2% vs 20.3%, p < 0.001), biochemical leak (6.1% vs. 2.8%, p = 0.046), postoperative bleeding (4.1% vs. 1.3%, p = 0.026) and reoperation (9.6% vs. 2.2%, p < 0.001). Time to adjuvant chemotherapy was delayed in patients with IC versus those without (10 vs. 8 weeks, p < 0.001). Median OS for patients who experienced no complication, noninfectious complication, and infectious complication was 33.3 months, 29.06 months, and 27.58 months respectively (p = 0.023). On multivariate analysis, postoperative IC were an independent predictor of worse OS (HR 1.32, p = 0.049). CONCLUSIONS: IC following PD for PDAC independently predict worse oncologic outcomes. Thus, efforts to prevent and manage IC should be a priority in the care of patients undergoing PD for PDAC.

The aetiology and antimicrobial resistance of bacterial maternal infections in Sub-Saharan Africa-a systematic review and meta-analysis.

BACKGROUND: Understanding the aetiological organisms causing maternal infections is crucial to inform antibiotic treatment guidelines, but such data are scarce from Sub-Saharan Africa (SSA). We performed this systematic review and meta-analysis to address this gap. METHODS: Microbiologically confirmed maternal infection data were collected from PubMed, Embase, and African Journals online databases. The search strategy combined terms related to bacterial infection, pregnancy, postnatal period, observational studies, SSA. Exclusion criteria included colonization, asymptomatic infection, and screening studies. Pooled proportions for bacterial isolates and antimicrobial resistance (AMR) were calculated. Quality and completeness of reporting were assessed using the Newcastle-Ottawa and STROBE checklists. FINDINGS: We included 14 papers comprising data from 2,575 women from four sources (blood, urine, surgical wound and endocervical). Mixed-growth was commonly reported at 17% (95% CI: 12%-23%), E. coli from 11%(CI:10%-12%), S. aureus from 5%(CI: 5%-6%), Klebsiella spp. at 5%(CI: 4%- 5%) and Streptococcus spp. at 2%(CI: 1%-2%). We observed intra-sample and inter-sample heterogeneity between 88-92% in all meta-analyses. AMR rates were between 19% -77%, the highest with first-line beta-lactam antibiotics. Convenience sampling, and limited reporting of laboratory techniques were areas of concern. INTERPRETATION: We provide a comprehensive summary of microbial aetiology of maternal infections in SSA and demonstrate the paucity of data available for this region. We flag the need to review the current local and international empirical treatment guidelines for maternal bacterial infections in SSA because there is high prevalence of AMR among common causative bacteria. FUNDING: This research was supported by the NIHR-Professorship/NIHR300808 and the Wellcome-Strategic-award /206545/Z/17/Z. TRIAL REGISTRATION: Prospero ID CRD42021238515.

Deliveries in Lebanon, the Country with the Highest Refugee Density in the World: A Descriptive Review.

PURPOSE: The aim of this study is to analyze obstetrical and reproductive health parameters in Lebanon from 2015 until 2018 in the setting of the Syrian refugee influx in order to evaluate potential risks and provide a management plan to improve outcomes. DESCRIPTION: Data from the Lebanese Ministry of Public Health (LMPH) on all obstetrical deliveries that occurred in Lebanon between 2015 and 2018 was screened and analyzed. Number and mode of delivery as well as maternal and neonatal outcomes were included. Joinpoint regression analysis was used for trends of selected parameters. Independent two-sample t-tests were used for comparisons. ASSESSMENT: Women of non-Lebanese nationality residing in Lebanon had a significantly greater number of total deliveries (p-value < 0.001), vaginal deliveries (p-value = 0.002), cesarean sections (p-value = 0.02). When looking at delivery trends from 2015 to 2018, Lebanese women had a significant decrease in total number of deliveries (p-value < 0.001) and vaginal deliveries (p-value < 0.001). CONCLUSION: Total number of deliveries and cesarean sections is on the rise in Lebanon. Cesarean section practice should be audited by the LMPH and the Lebanese Order of Physicians (LOP). Local and international agencies should prioritize the implementation and management of family planning facilities in refugee hosting countries.

Efficiency of natural oils as alternative adjuvants to mineral oils in inactivated avian influenza vaccine formulation.

1. The effectiveness of inactivated vaccines depends on selecting the suitable adjuvant for vaccine formulation. The potency of vaccines with low antigen content can be improved with the appropriate adjuvant. This could allow production of more doses and lower the production cost.2. This study evaluated the efficiency of vaccines prepared using oil extracted from natural sources including argan oil, almond oil, sesame seed oil, pumpkin oil, cactus oil and black seed oil as alternative adjuvants for improving the protection capacity of inactivated influenza virus vaccine as compared to commonly used mineral oils.3. Each vaccine formulation was evaluated for stability, safety and immunogenicity in chickens, as well as for reducing the viral shedding after challenge infection.4. The cactus, sesame and pumpkin seed oil-based vaccines were found to be potent and successfully induced the production of humoral immunity in vaccinated chickens.

THE EFFECT OF NUTRITIONAL GENOMICS ON CARDIOVASCULAR SYSTEM.

The idea that obesity and cardiovascular diseases together are considered for a sizable share of adult global morbidity and mortality is supported by epidemiological data. They have intricate systems in which environmental and genetic variables interact, including nutrition. As an environmental component, nutrition has a major and well-known role in managing health and preventing obesity and disorders connected to obesity, such as cardiovascular disease (CVD). Nonetheless, people with the same food pattern but obese exhibit a notable difference in CVD. This variance might be explained by the various genetic polymorphisms which gave rise to the field of nutrigenetics. The discipline known as nutritional genomics, or nutrigenetics, examines and describes gene variants linked to varying reactions to particular nutrients and links these variations to various disorders, including obesity-related cardiovascular disease (CVD). Therefore, tailored nutrition advice depending on a person's genetic background could enhance the results of a particular dietary intervention and offer a novel dietary technique to enhance health by lowering obesity and cardiovascular disease. With these suppositions, it seems reasonable to assume that understanding food and gene interactions will provide more targeted and efficacious dietary treatments in preventing obesity and CVD by nutrigenetics-based personalized nutrition. In addition to elucidating the connection between diet and gene expression and the major nutrition-related genes involved in obesity and CVD, this research seeks to provide a concise summary of the greater significant genes linked to obesity and CVD.

Robotic Pancreaticoduodenectomy: Increased Adoption and Improved Outcomes: Is Laparoscopy Still Justified?

OBJECTIVE: To compare the rate of postoperative 30-day complications between laparoscopic pancreaticoduodenectomy (LPD) and robotic pancreaticoduodenectomy (RPD). BACKGROUND: Previous studies suggest that minimally invasive pancreaticoduodenectomy (MI-PD)-either LPD or RPD-is noninferior to open pancreaticoduodenectomy in terms of operative outcomes. However, a direct comparison of the two minimally invasive approaches has not been rigorously performed. METHODS: Patients who underwent MI-PD were abstracted from the 2014 to 2019 pancreas-targeted American College of Surgeons National Sample Quality Improvement Program (ACS NSQIP) dataset. Optimal outcome was defined as absence of postoperative mortality, serious complication, percutaneous drainage, reoperation, and prolonged length of stay (75th percentile, 11 days) with no readmission. Multivariable logistic regression models were used to compare optimal outcome of RPD and LPD. RESULTS: A total of 1540 MI-PDs were identified between 2014 and 2019, of which 885 (57%) were RPD and 655 (43%) were LPD. The rate of RPD cases/year significantly increased from 2.4% to 8.4% ( P =0.008) from 2014 to 2019, while LPD remained unchanged. Similarly, the rate of optimal outcome for RPD increased during the study period from 48.2% to 57.8% ( P <0.001) but significantly decreased for LPD (53.5% to 44.9%, P <0.001). During 2018-2019, RPD outcomes surpassed LPD for any complication [odds ratio (OR)=0.58, P =0.004], serious complications (OR=0.61, P =0.011), and optimal outcome (OR=1.78, P =0.001). CONCLUSIONS: RPD adoption increased compared with LPD and was associated with decreased overall complications, serious complications, and increased optimal outcome compared with LPD in 2018-2019.

Obesity Is Associated With Increased Risk for Adverse Postoperative Outcomes After Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: Conflicting reports exist about the effect obesity has on adverse postoperative surgical outcomes after distal pancreatectomy (DP). The aim of this study is to explore the role of obesity in terms of morbidity and pancreas-specific complications following DP for pancreatic ductal adenocarcinoma (PDAC). METHODS: All patients who underwent DP at a single institution over 10 y were analyzed (2009-2020). Patients were categorized as nonobese (body mass index [BMI] < 30 kg/m2) and obese (BMI ≥ 30 kg/m2). Independent predictors of adverse postoperative outcomes were calculated using multivariate logistic regression models. Overall survival was assessed using Kaplan-Meier survival analysis. RESULTS: Of the 178 patients included, 58 (32.5%) were obese. Clinically relevant postoperative pancreatic fistula (CR-POPF) formation rate was significantly higher in the obese group (20.6% versus 7.5%, P value = 0.011). We did not identify any significant difference between obese and nonobese patients in median overall survival (30.2 mon versus 28.9 mon, P value = 0.811). On multivariate binary logistic regression analysis, BMI ≥ 30 was an independent predictor of morbidity (any complication) and CR-POPF formation after DP for PDAC. CONCLUSIONS: Obesity is associated with a significantly increased risk for CR-POPF in patients undergoing DP for PDAC. Obesity should be considered as a variable in fistula risk calculators for DP.

Occupational risk factors and exposure-response relationships for airway disease among health workers exposed to cleaning agents in tertiary hospitals.

OBJECTIVES: This study investigated occupational risk factors and exposure-response relationships for airway disease among health workers (HWs) exposed to cleaning agents in two tertiary hospitals in South Africa and Tanzania. METHODS: In this cross-sectional study, 697 participants completed questionnaire interviews while 654 underwent fractional exhaled nitric oxide (FeNO) testing. Asthma Symptom Score (ASS) was computed based on the sum of answers to five questions on asthma-related symptoms in the past 12 months. For exposure-response analyses, cleaning agent-related self-reported exposure variables were categorised into three levels (cleaning product not used; use of a cleaning product for up to 99 min per week and use of a cleaning product for ≥100 min per week). RESULTS: Asthma-related outcomes (ASS and FeNO) demonstrated positive associations with medical instrument cleaning agents (orthophthalaldehyde and enzymatic cleaners) and tasks (instruments precleaning and changing sterilisation solutions) as well as patient care activities (disinfection prior to procedures and disinfecting wounds). A particularly pronounced dose-response relationship was observed between work-related ocular-nasal symptoms and medical instrument cleaning agents (orthophthalaldehyde, glutaraldehyde, enzymatic cleaners, alcohols and bleach) (OR range: 2.37-4.56) and tasks (OR range: 2.92-4.44). A strong association was also observed between ASS and use of sprays for fixed surface cleaning (mean ratio 2.81; 95% CI 1.41 to 5.59). CONCLUSIONS: Specific agents for medical instrument disinfection for example, orthophthalaldehyde and enzymatic cleaners, patient care activities and use of sprays are important occupational risk factors for airway disease among HWs.

Prevalence of work-related skin symptoms and associated factors among tertiary hospital workers exposed to cleaning agents in Southern Africa.

INTRODUCTION: Working with cleaning products is associated with occupational contact dermatitis in health workers (HWs), but information on predictors for these outcomes is limited. OBJECTIVES: This study investigated the prevalence of work-related skin symptoms (WRSS) and associated factors in HWs exposed to cleaning agents in two Southern African tertiary hospitals. METHODS: A cross-sectional study of 697 HWs used an interviewer-administered questionnaire and assessed for atopy using Phadiatop. RESULTS: HWs' median age was 42 years, 77.0% were female and 42.5% were atopic. The prevalence of WRSS in the last 12 months was 14.8%, 12.3% had probable contact dermatitis (PCD) and 3.2% had probable contact urticaria (PCU). Technicians (ORadj 3.91) and tasks involving cleaning and disinfection of skin wounds (ORadj 1.98) were associated with WRSS in the past year. Factors associated with PCD included sterilizing instruments, disinfecting skin before procedures and use of wound adhesives. Factors associated with PCU included specimen preparation using formalin, medical instrument sterilization tasks, and skin/wound cleaning and disinfection. Appropriate glove use when performing patients' skin/wound care was protective against WRSS. CONCLUSIONS: Tasks involving cleaning and disinfecting patients' skin and wounds were associated with WRSS in HWs, especially when performed without gloves.

Efficacy of in ovo delivered resveratrol (Trans 3, 4, 5-trihydroxystilbene) on growth, carcass weights, and blood metabolites of broiler chicks.

This research aimed to determine the impact of in ovo resveratrol (RV) (Trans.3, 4, 5-trihydroxystilbene) injection on performance, carcass weights, and blood constituents in Cobb chicks. A total of 300 fertile broiler breeder eggs were divided into five treatments as 60 eggs in each group, with 6 replicates (10 eggs each). The groups were as follows: (1) negative control (without additive), (2) positive control (saline injection), (3) 1.5 mg RV, 4) 3.0 mg RV, and (5) 4.5 mg in ovo RV injections. Significant changes were found in the amount of forage consumed per day, and the feed conversion ratio between treatment groups. RV injection significantly altered the parameters of the complete lipid profile, including total cholesterol, triglycerides, low-density lipoproteins, and very low-density lipoproteins, in plasma. RV injection significantly affected blood biochemical parameters, including total protein, albumin, and globulin in broiler chicken plasma. Liver and kidney functions were influenced by the injection of RV eggs into broiler chickens. The antioxidant enzymes also changed significantly after RV injection. Moreover, in egg injection from RV the immunogenicity (IgG and IgM) in broiler chickens were significantly altered. In conclusion, in ovo injection with RV significantly improved liver and kidney functions, antioxidant activity, and immune function in Cobb broilers.

Exploitation of Sugarcane Bagasse and Environmentally Sustainable Production, Purification, Characterization, and Application of Lovastatin by Aspergillus terreus AUMC 15760 under Solid-State Conditions.

Using the internal transcribed spacer (ITS) region for identification, three strains of Aspergillus terreus were identified and designated AUMC 15760, AUMC 15762, and AUMC 15763 for the Assiut University Mycological Centre culture collection. The ability of the three strains to manufacture lovastatin in solid-state fermentation (SSF) using wheat bran was assessed using gas chromatography-mass spectroscopy (GC-MS). The most potent strain was strain AUMC 15760, which was chosen to ferment nine types of lignocellulosic waste (barley bran, bean hay, date palm leaves, flax seeds, orange peels, rice straw, soy bean, sugarcane bagasse, and wheat bran), with sugarcane bagasse turning out to be the best substrate. After 10 days at pH 6.0 at 25 °C using sodium nitrate as the nitrogen source and a moisture content of 70%, the lovastatin output reached its maximum quantity (18.2 mg/g substrate). The medication was produced in lactone form as a white powder in its purest form using column chromatography. In-depth spectroscopy examination, including 1H, 13C-NMR, HR-ESI-MS, optical density, and LC-MS/MS analysis, as well as a comparison of the physical and spectroscopic data with published data, were used to identify the medication. At an IC50 of 69.536 ± 5.73 µM, the purified lovastatin displayed DPPH activity. Staphylococcus aureus and Staphylococcus epidermidis had MICs of 1.25 mg/mL, whereas Candida albicans and Candida glabrata had MICs of 2.5 mg/mL and 5.0 mg/mL, respectively, against pure lovastatin. As a component of sustainable development, this study offers a green (environmentally friendly) method for using sugarcane bagasse waste to produce valuable chemicals and value-added commodities.

Adenovirus type D and type E infection in broiler chickens: the effect on CD4 and CD8 T cell response, cytokines expression and their immunopathology.

1. A total of 150-day-old chicks were divided into three groups of 50 birds (G1-G3); G1 and G2 were orally inoculated at 1-day old with 0.5 ml of 107 TCID50/ml FAdV-D serotype 2 (MT386509.1) and FAdV-E serotype 8a (MW847902), respectively, and G3 was blank control group.2. Cell-mediated immune response was evaluated by detection of CD4, CD8 T lymphocytes and the mRNA expression of IL6 and IL8 in the chicken spleen using q-PCR. Additionally, immunopathology was performed at 3, 5 and 7 day post infection (dpi) and weekly until the end of the experiment.3. Results revealed that transcription of inflammatory cytokines (IL6, IL8) was up regulated in the spleen of FAdV type D and type E infected chickens at various time points relative to the control group. A marked decrease in the number of CD4 and CD8 T lymphocytes at 5 and 7 dpi in G1 of chickens infected with FAdV type D. Whereas, in chickens infected with FAdV type E, the CD4 and CD8 T lymphocytes were markedly decreased at 7 dpi.4. In contrast, there were no significant differences in humoral immune responses against NDV vaccine in (G1 and G2) at different intervals post-vaccination compared to the control group. The histopathology of the bursa, thymus, and spleen in the infected groups showed lymphocytolysis with severe reticular cells hyperplasia and lymphoid depletion.5. In conclusion, fowl adenovirus types D and E have an immunosuppressive effect in broilers which may be considered one of the main causes of the continuous co-infections with other viruses reported in the field during the last 10 years.

The use of angiotensin system inhibitors correlates with longer survival in resected pancreatic adenocarcinoma patients.

BACKGROUND: Activities and inhibition of the Renin-Angiotensin-Aldosterone System (RAAS) may affect the survival of resected pancreatic ductal adenocarcinoma (PDAC) patients METHOD: A single-institution retrospective analysis of resected PDAC patients between 2010 and 2019. To estimate the effect of angiotensin system inhibitors (ASIs) on patient survival, we performed Kaplan Meier analysis, Cox Proportional Hazards model, Propensity Score Matching (PSM), and inverse probability weighting (IPW) analysis. RESULTS: 742 patients were included in the analysis. The average age was 67.0 years, with a median follow-up of 24.1 months. The use of ASI was associated with significantly longer overall survival in univariate (p = 0.004) and multivariable (HR = 0.70 [0.56-0.88],p = 0.003) adjusted analysis. In a propensity score-matched cohort of 400 patients, ASI use was again associated with longer overall survival (p = 0.039). Lastly, inverse probability weighting (IPW) analysis suggested that the use of ASI was associated with an average treatment effect on the treated (ATT) of HR = 0.68 [0.53-0.86],p = 0.002) for overall survival. CONCLUSION: In this single-institution retrospective study focusing on resected PDAC patients, the use of ASI was associated with longer overall survival in multiple statistical models. Prospective clinical trials are needed before routine clinical implementation of ASI as an adjuvant to existing therapy can be recommended.

MafF Is an Antiviral Host Factor That Suppresses Transcription from Hepatitis B Virus Core Promoter.

Hepatitis B virus (HBV) is a stealth virus that exhibits only minimal induction of the interferon system, which is required for both innate and adaptive immune responses. However, 90% of acutely infected adults can clear the virus, suggesting the presence of additional mechanisms that facilitate viral clearance. Here, we report that Maf bZIP transcription factor F (MafF) promotes host defense against infection with HBV. Using a small interfering RNA (siRNA) library and an HBV/NanoLuc (NL) reporter virus, we screened to identify anti-HBV host factors. Our data showed that silencing of MafF led to a 6-fold increase in luciferase activity after HBV/NL infection. Overexpression of MafF reduced HBV core promoter transcriptional activity, which was relieved upon mutation of the putative MafF binding region. Loss of MafF expression through CRISPR/Cas9 editing (in HepG2-hNTCP-C4 cells) or siRNA silencing (in primary hepatocytes [PXB cells]) induced HBV core RNA and HBV pregenomic RNA (pgRNA) levels, respectively, after HBV infection. MafF physically binds to the HBV core promoter and competitively inhibits HNF-4α binding to an overlapping sequence in the HBV enhancer II sequence (EnhII), as seen by chromatin immunoprecipitation (ChIP) analysis. MafF expression was induced by interleukin-1ß (IL-1ß) or tumor necrosis factor alpha (TNF-α) treatment in both HepG2 and PXB cells, in an NF-κB-dependent manner. Consistently, MafF expression levels were significantly enhanced and positively correlated with the levels of these cytokines in patients with chronic HBV infection, especially in the immune clearance phase. IMPORTANCE HBV is a leading cause of chronic liver diseases, infecting about 250 million people worldwide. HBV has developed strategies to escape interferon-dependent innate immune responses. Therefore, the identification of other anti-HBV mechanisms is important for understanding HBV pathogenesis and developing anti-HBV strategies. MafF was shown to suppress transcription from the HBV core promoter, leading to significant suppression of the HBV life cycle. Furthermore, MafF expression was induced in chronic HBV patients and in primary human hepatocytes (PXB cells). This induction correlated with the levels of inflammatory cytokines (IL-1ß and TNF-α). These data suggest that the induction of MafF contributes to the host's antiviral defense by suppressing transcription from selected viral promoters. Our data shed light on a novel role for MafF as an anti-HBV host restriction factor.

Prevalence and risk factors for non-collision injuries among bus commuters in Dar es Salaam, Tanzania.

BACKGROUND: Migration of people from rural to urban areas has led to the increase in demand for transportation services in the cities. However, authorities have failed to cope with this problem in a consistently manner. This has led to the increase in non-collision injuries among commuters. This study aimed at investigating the prevalence and risk factors for non-collision injuries among commuters using public transport in Dar es Salaam, Tanzania. METHODS: A cross sectional study was conducted in Dar es Salaam involving 290 commuters from 7 bus routes travelling to and from the city centre using public transport which are privately owned and commonly known as "daladala". Stratified random sampling was used to sample buses based on the passenger carrying capacity (i.e. 15-24, 25-34 and 35-45 passengers). Systematic random sampling was used to get a total of three commuters from each bus for the interview. RESULTS: Lifetime prevalence of non-collision injuries was 71%, while these rates were 70 and 39% in the last 12 and 6 months, respectively. Commuters aged between 18 and 28 years experienced non-collision injuries the most (56%) in the last 12 months. Most non-collision injuries occurred on weekdays in the evening from 5:00 pm to 10:00 pm. Strong association was observed between the occurrence of non-collision injuries and commuting time between 5:00 pm to 10:00 pm (adjusted OR = 9.24; 95% CI: 2.68-19.54); boarding and disembarking (adjusted OR = 9.21; 95% CI: 3.77-25.11) and scrambling during boarding (adjusted OR = 5.03; 95% CI: 2.51-21.32). The lower limbs (adjusted OR = 8.64; 95% CI: 2.72-21.76) and the upper limbs (adjusted OR = 13.55; 95% CI: 5.32-33.21) were the most affected body parts. CONCLUSIONS: This study has demonstrated high prevalence of non-collision injuries among commuters using public transport in Dar es Salaam. Travelling in the evening between 5:00 pm to 10:00 pm on the weekdays, boarding and disembarking especially when scrambling for the bus during boarding, overcrowding in the bus especially when the bus is already full with no seats available are the major risk factors for non-collision injuries.

Work-related allergy and asthma associated with cleaning agents in health workers in Southern African tertiary hospitals.

BACKGROUND: Health workers (HWs) are exposed to diverse cleaning agents in large hospitals. This study determined the prevalence of work-related symptoms, allergic sensitization, and lung function abnormalities in HWs of two tertiary hospitals in Southern Africa. METHODS: A cross-sectional study of 699 HWs (South Africa: SAH, n = 346; Tanzania: TAH, n = 353) was conducted. Health outcomes were assessed using a standardized ECRHS questionnaire, immunological tests (specific IgE antibody to common aero-allergens and to occupational allergens: natural rubber latex [NRL]  Hev b5 and Hev b6.02, chlorhexidine, and ortho-phthalaldehyde [OPA]), spirometry [pre-and post- bronchodilator], methacholine challenge, and fractional exhaled nitric oxide (FeNO). RESULTS: A large proportion of participants (78%) were women. Median age was 42 years, with 76% nurses, 12% cleaners, and 5% administrative workers. Current smoking was more common in SAHWs (12%) than TAHWs (1%). The overall prevalence of doctor-diagnosed asthma was 7%. Atopy was present in 43% of HWs, while 4% were sensitized to OPA, 2% to NRL, and 1% to chlorhexidine. Prevalence of work-related ocular-nasal symptoms (16%) was higher than skin (12%) and chest (7%) symptoms. TAHWs had significantly lower mean lung volumes, higher degrees of significant airflow obstruction and impaired lung function. The prevalence of bronchial hyperresponsiveness in SAHWs (14%) was high. Overall, 23% of HWs had abnormal FeNO; 6% having high (>50 ppb) levels. FeNO was positively associated with sensitization to occupational allergens, primarily OPA and NRL. CONCLUSIONS: HWs from both hospitals had similar prevalence of work-related respiratory symptoms. Sensitization to OPA and NRL appears to be contributing to allergic airway inflammation in these HWs.