Efficacy and safety of emodepside compared with albendazole in adolescents and adults with hookworm infection in Pemba Island, Tanzania: a double-blind, superiority, phase 2b, randomised controlled trial.

BACKGROUND: Human hookworm is a cause of enormous global morbidity. Current treatments have insufficient efficacy and their extensive and indiscriminate distribution could also result in drug resistance. Therefore, we tested the efficacy and safety of emodepside, a strong anthelmintic candidate that is currently undergoing clinical development for onchocerciasis and soil-transmitted helminth infections. METHODS: We conducted a double-blind, superiority, phase 2b, randomised controlled clinical trial comparing emodepside and albendazole. Participants in the emodepside group received six 5 mg tablets of emodepside (totalling 30 mg) and one placebo; participants in the albendazole group received one 400 mg tablet of albendazole and six placebos. Participants were recruited from four endemic villages and three secondary schools in Pemba Island, Tanzania. Participants aged 12-60 years were eligible for treatment if they were positive for hookworm infection, and they had 48 or more eggs per gram from four Kato-Katz thick smears and at least two slides had more than one hookworm egg present. Participants' treatment allocation was stratified by infection intensity and efficacy was measured by cure rate: participants who were hookworm positive and became hookworm negative after treatment. Adverse events were reported at 3 h, 24 h, 48 h, and 14-21 days post-treatment. The trial is registered at ClinicalTrials.gov, NCT05538767. FINDINGS: From Sept 15 to Nov 8, 2022, and from Feb 15 to March 15, 2023, 1609 individuals were screened for hookworm. Of these, 293 individuals were treated: 147 with albendazole and 146 with emodepside. Emodepside demonstrated superiority, with an observed cure rate against hookworm of 96·6%, which was significantly higher compared with albendazole (cure rate 81·2%, odds ratio 0·14, 95% CI 0·04-0·35; p=0·0001). The most common adverse event in the emodepside treatment group was vision blur at 3 h after treatment (57 [39%] of 146). Other common adverse events were vision blur at 24 h after treatment (55 [38%]), and headache and dizziness at 3 h after treatment (55 [38%] for headache and 43 [30%] for dizziness). In the emodepside treatment group, 298 (93%) of the 319 adverse events were mild. The most commonly reported adverse events in the albendazole treatment group were headache and dizziness at 3 h after treatment (27 [18%] of 147 for headache and 14 [10%] for dizziness). No serious adverse events were reported. INTERPRETATION: This phase 2b clinical trial confirms the high efficacy of emodepside against hookworm infections, solidifying emodepside as a promising anthelmintic candidate. However, although the observed safety events were generally mild in severity, considerations must be made to balance the strong efficacy outcomes with the increased frequency of adverse events compared with albendazole. FUNDING: European Research Council.

Test-treat-track-test-treat (5T) approach for Schistosoma haematobium elimination on Pemba Island, Tanzania.

BACKGROUND: After decades of praziquantel mass drug administration (MDA), several countries approach schistosomiasis elimination. Continuing MDA in largely uninfected populations no longer seems justified. Alternative interventions to maintain the gains or accelerate interruption of transmission are needed. We report results, strengths, and shortcomings of novel test-treat-track-test-treat (5T) interventions in low Schistosoma haematobium prevalence areas on Pemba, Tanzania. METHODS: School- and household-based surveys were conducted in 2021 and 2022 to monitor the S. haematobium and microhematuria prevalence and assess the impact of interventions. In 2021, 5T interventions were implemented in 15 low-prevalence areas and included: (i) testing schoolchildren in primary and Islamic schools for microhematuria as a proxy for S. haematobium, (ii) treating positive children, (iii) tracking them to their households and to water bodies they frequented, (iv) testing individuals at households and water bodies, and (v) treating positive individuals. Additionally, test-and-treat interventions were implemented in the 22 health facilities of the study area. RESULTS: The S. haematobium prevalence in the school-based survey in 15 low-prevalence implementation units was 0.5% (7/1560) in 2021 and 0.4% (6/1645) in 2022. In the household-based survey, 0.5% (14/2975) and 0.7% (19/2920) of participants were infected with S. haematobium in 2021 and 2022, respectively. The microhematuria prevalence, excluding trace results, in the school-based survey was 1.4% (21/1560) in 2021 and 1.5% (24/1645) in 2022. In the household-based survey, it was 3.3% (98/2975) in 2021 and 5.4% (159/2920) in 2022. During the 5T interventions, the microhaematuria prevalence was 3.8% (140/3700) and 5.8% (34/594) in children in primary and Islamic schools, respectively, 17.1% (44/258) in household members, and 16.7% (10/60) in people at water bodies. In health facilities, 19.8% (70/354) of patients tested microhematuria-positive. CONCLUSIONS: The targeted 5T interventions maintained the very low S. haematobium prevalence and proved straightforward and feasible to identify and treat many of the few S. haematobium-infected individuals. Future research will show whether 5T interventions can maintain gains in the longer-term and expedite elimination. TRIAL REGISTRATION: ISRCTN, ISCRCTN91431493. Registered 11 February 2020, https://www.isrctn.com/ISRCTN91431493 .

Effectiveness of Gabapentin as a Benzodiazepine-Sparing Agent in Alcohol Withdrawal Syndrome.

Background and Objectives: Gabapentin has shown promise as a potential agent for the treatment of alcohol withdrawal syndrome. We aimed to evaluate the effectiveness of gabapentin as a benzodiazepine-sparing agent in patients undergoing alcohol withdrawal treatment in all the hospitals of a large tertiary healthcare system. Materials and Methods: Medical records of patients admitted to the hospital for alcohol withdrawal management between 1 January 2020 and 31 August 2022 were reviewed. Patients were divided into two cohorts: benzodiazepine-only treatment who received benzodiazepines as the primary pharmacotherapy and gabapentin adjunctive treatment who received gabapentin in addition to benzodiazepines. The outcomes assessed included the total benzodiazepine dosage administered during the treatment and the length of hospital stay. The statistical models were calibrated to account for various factors. Results: A total of 4364 patients were included in the final analysis. Among these, 79 patients (1.8%) received gabapentin in addition to benzodiazepines, and 4285 patients (98.2%) received benzodiazepines only. Patients administered gabapentin required significantly lower average cumulative benzodiazepine dosages, approximately 17.9% less, compared to those not receiving gabapentin (median 2 mg vs. 4 mg of lorazepam equivalent dose (p < 0.01)). However, there were no significant differences in outcomes between the two groups. Conclusions: Our findings demonstrate that using gabapentin with benzodiazepine was associated with a reduction in the cumulative benzodiazepine dosage for alcohol withdrawal. Considering gabapentin as an adjunctive therapy holds promise for patients with comorbidities who could benefit from reducing benzodiazepine dose. This strategy warrants further investigation.

High rates of placental inflammation among samples collected by the Multi-Omics for Mothers and Infants consortium.

BACKGROUND: The Multi-Omics for Mothers and Infants consortium aims to improve birth outcomes. Preterm birth is a major obstetrical complication globally and causes significant infant and childhood morbidity and mortality. OBJECTIVE: We analyzed placental samples (basal plate, placenta or chorionic villi, and the chorionic plate) collected by the 5 Multi-Omics for Mothers and Infants sites, namely The Alliance for Maternal and Newborn Health Improvement Bangladesh, The Alliance for Maternal and Newborn Health Improvement Pakistan, The Alliance for Maternal and Newborn Health Improvement Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth Bangladesh, and The Global Alliance to Prevent Prematurity and Stillbirth Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. STUDY DESIGN: The teams provided biopsies from 166 singleton preterm (<37 weeks' gestation) and 175 term (≥37 weeks' gestation) deliveries. The samples were fixed in formalin and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphologic analyses. Other placental biopsies (n=35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. RESULTS: The morphologic analyses revealed a surprisingly high rate of inflammation that involved the basal plate, placenta or chorionic villi, and the chorionic plate. The rate of inflammation in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs in the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes that were differentially expressed between placentas from preterm vs those from term births (123 upregulated, 144 downregulated). Mapping the differentially expressed genes onto single-cell RNA sequencing data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathologic findings, gene ontology analyses highlighted the presence of leukocyte infiltration or activation and inflammatory responses in both the fetal and maternal compartments. CONCLUSION: The relationship between placental inflammation and preterm birth is appreciated in developed countries. In this study, we showed that this link also exists in developing geographies. In addition, among the participating sites, we found geographic- and population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Identify risk factors for perioperative outcomes in Intracorporeal Urinary Diversion and Extracorporeal Urinary Diversion with Robotic Cystectomy

ABSTRACT Introduction: The increasing adoption of robotic-assisted cystectomy with intracorporeal urinary diversion (ICUD), despite its complexity, prompts a detailed comparison with extracorporeal urinary diversion (ECUD). Our study at a single institution investigates perioperative outcomes and identifies risk factors impacting the success of these surgical approaches. Methods: In this retrospective analysis, 174 patients who underwent robotic-assisted cystectomy at the University of Louisville from June 2016 to August 2021 were reviewed. The cohort was divided into two groups based on the urinary diversion method: 30 patients underwent ECUD and 144 underwent ICUD. Data on demographics, complication rates, length of hospital stay, and readmission rates were meticulously collected and analyzed. Results: Operative times were comparable between the ICUD and ECUD groups. However, the ICUD group had a significantly lower intraoperative transfusion rate (0.5 vs. 1.0, p=0.02) and shorter hospital stay (7.8 vs. 12.3 days, p<0.001). Factors such as male sex, smoking history, diabetes mellitus, intravesical therapy, higher ASA, and ACCI scores were associated with increased Clavien-Dindo Grade 3 or higher complications. Age over 70 was the sole factor linked to a higher 90-day readmission rate, with no specific characteristics influencing the 30-day rate. Conclusion: Robotic cystectomy with ICUD results in shorter hospitalizations and lower intraoperative transfusion rates compared to ECUD, without differences in operative time, high-grade postoperative complications, or readmission rates. These findings can inform clinical decision-making, highlighting ICUD as a potentially more favorable option in appropriate settings.

Identify risk factors for perioperative outcomes in Intracorporeal Urinary Diversion and Extracorporeal Urinary Diversion with Robotic Cystectomy.

INTRODUCTION: The increasing adoption of robotic-assisted cystectomy with intracorporeal urinary diversion (ICUD), despite its complexity, prompts a detailed comparison with extracorporeal urinary diversion (ECUD). Our study at a single institution investigates perioperative outcomes and identifies risk factors impacting the success of these surgical approaches. METHODS: In this retrospective analysis, 174 patients who underwent robotic-assisted cystectomy at the University of Louisville from June 2016 to August 2021 were reviewed. The cohort was divided into two groups based on the urinary diversion method: 30 patients underwent ECUD and 144 underwent ICUD. Data on demographics, complication rates, length of hospital stay, and readmission rates were meticulously collected and analyzed. RESULTS: Operative times were comparable between the ICUD and ECUD groups. However, the ICUD group had a significantly lower intraoperative transfusion rate (0.5 vs. 1.0, p=0.02) and shorter hospital stay (7.8 vs. 12.3 days, p<0.001). Factors such as male sex, smoking history, diabetes mellitus, intravesical therapy, higher ASA, and ACCI scores were associated with increased Clavien-Dindo Grade 3 or higher complications. Age over 70 was the sole factor linked to a higher 90-day readmission rate, with no specific characteristics influencing the 30-day rate. CONCLUSION: Robotic cystectomy with ICUD results in shorter hospitalizations and lower intraoperative transfusion rates compared to ECUD, without differences in operative time, high-grade postoperative complications, or readmission rates. These findings can inform clinical decision-making, highlighting ICUD as a potentially more favorable option in appropriate settings.

Management of an obstructing calculus in an anticoagulated patient with a ureteral hernia.

Introduction: Ureteral hernias are a rare urologic occurrence and can complicate otherwise straightforward management of commonly encountered urologic emergencies. Methods: We review the incidence and identification of ureteroinguinal hernias and present a novel and easily reproducible technique using a modified bander stent to decompress the upper tracts. Results: The technique allowed for decompression of the upper tract secondary to an obstructing stone in a ureteral hernia. No complications were documented. Conclusion: We propose a novel and easily reproducible technique to allow for emergent upper tract decompression in patients with ureteral hernias who are not candidates for percutaneous access.

Early to mid-pregnancy HbA1c levels and its association with adverse pregnancy outcomes in three low middle-income countries in Asia and Sub-Saharan Africa.

BACKGROUND: Hyperglycemia during pregnancy leads to adverse maternal and fetal outcomes. Thus, strict monitoring of blood glucose levels is warranted. This study aims to determine the association of early to mid-pregnancy HbA1c levels with the development of pregnancy complications in women from three countries in South Asia and Sub-Saharan Africa. METHODS: We performed a secondary analysis of the AMANHI (Alliance for Maternal and Newborn Health Improvement) cohort, which enrolled 10,001 pregnant women between May 2014 and June 2018 across Sylhet-Bangladesh, Karachi-Pakistan, and Pemba Island-Tanzania. HbA1c assays were performed at enrollment (8 to < 20 gestational weeks), and epidemiological data were collected during 2-3 monthly household visits. The women were followed-up till the postpartum period to determine the pregnancy outcomes. Multivariable logistic regression models assessed the association between elevated HbA1c levels and adverse events while controlling for potential confounders. RESULTS: A total of 9,510 pregnant women were included in the analysis. The mean HbA1c level at enrollment was found to be the highest in Bangladesh (5.31 ± 0.37), followed by Tanzania (5.22 ± 0.49) and then Pakistan (5.07 ± 0.58). We report 339 stillbirths and 9,039 live births. Among the live births were 892 preterm births, 892 deliveries via cesarean section, and 532 LGA babies. In the multivariate pooled analysis, maternal HbA1c levels of ≥ 6.5 were associated with increased risks of stillbirths (aRR = 6.3, 95% CI = 3.4,11.6); preterm births (aRR = 3.5, 95% CI = 1.8-6.7); and Large for Gestational Age (aRR = 5.5, 95% CI = 2.9-10.6). CONCLUSION: Maternal HbA1c level is an independent risk factor for predicting adverse pregnancy outcomes such as stillbirth, preterm birth, and LGA among women in South Asia and Sub-Saharan Africa. These groups may benefit from early interventional strategies.

Technique and outcomes of robotic-assisted retroperitoneal radical nephrectomy.

Background: Robotic retroperitoneal partial nephrectomy (rRPN) has numerous advantages over transperitoneal surgery, including direct access to the renal hilum and posterior tumors, and avoidance of the peritoneal cavity in patients with a hostile abdomen. Although the use of the retroperitoneal approach has increased over the last decade, there is little literature on robotic retroperitoneal radical nephrectomy (rRRN), which has similar benefits over the transperitoneal approach. The aim of this study was to describe our technique for robotic retroperitoneal nephrectomy (rRN) and assess its feasibility and outcomes at a high-volume center. Methods: A retrospective review of patients who underwent some form of rRN [rRRN, robotic retroperitoneal simple nephrectomy (rRSN), or robotic retroperitoneal nephroureterectomy (rRNU)] at a single institution between 2013 and 2023. Patient characteristics, operative data, and postoperative complication rates were assessed. The technique for rRN was detailed. Results: A total of 13 renal units in 12 patients were included for analysis (7 rRRN, 5 rRSN, 1 rRNU). Median patient age was 64.0 years, and median body mass index (BMI) was 36.0 kg/m2. Indications for retroperitoneal surgery were prior abdominal surgery in all patients, including three with bowel diversions, super morbid central obesity in two patients, and a large ventral hernia in one patient. Median operative time was 213 minutes and median estimated blood loss (EBL) was 85 cc. Median postoperative length of stay (LOS) was 3 days, and only one patient experienced a Clavien-Dindo grade ≥3 complication within 90 days of surgery. Conclusions: The retroperitoneal approach for robotic-assisted nephrectomy is feasible and associated with similar outcomes as the transperitoneal approach. This approach may prove beneficial in select patients with significant prior abdominal surgery including those who are morbidly obese.

Identification of Medication-Related Risks in Bariatric Surgery Patients by Performing Structured Medication Reviews.

PURPOSE: More medication-related issues are seen with the growing demand for bariatric surgery, because of possible altered pharmacokinetics after surgery. Collaboration with a pharmacist could improve the short- and long-term safety and efficacy of pharmacotherapy in patients undergoing bariatric surgery. The aim of this study was to evaluate the impact of a structured medication review to identify medication-related risks before bariatric surgery. MATERIALS AND METHODS: The impact on pharmacy-led interventions of introducing a structured medication review was evaluated in a historically controlled study. In the retrospective part, we evaluated patient characteristics, medication use, and number of pre-surgery consultations with a pharmacist before the introduction of medication reviews. A flowchart was developed to detect the use of medicines with risks associated with bariatric surgery. In the prospective part, we evaluated pharmacy-led interventions after the introduction of structured medication reviews using the flowchart. Outcome effectiveness was measured through the number of pre-surgery pharmacy-led interventions. RESULTS: Before using the flowchart for screening on risk medicines, 40 (2.6%) pharmacy-led interventions were identified in 1536 patients. In the prospective group, 195 patients were included and 88 (45%) interventions were identified (p < 0.001). CONCLUSION: A structured medication review before bariatric surgery significantly increased the number of pharmacy-led interventions in bariatric surgery patients. This procedure will shift interventions to pre-surgery instead of post-surgery, contributing to the optimization of pharmacotherapy at an early stage.

Immediate gemcitabine bladder instillation following bladder closure during robotic-assisted radical nephroureterectomy: a multi-institutional report of feasibility and initial outcomes.

Background: Bladder recurrence after radical nephroureterectomy (RNU) is common and randomized data supports utilization of prophylactic intravesical mitomycin to reduce recurrence. Recently, gemcitabine has been shown to be safe and effective at reducing recurrence following transurethral resection of bladder tumors. We sought to evaluate the safety and efficacy of a single, intraoperative gemcitabine instillation immediately following bladder cuff closure during RNU, and to compare outcomes with non-gemcitabine intravesical chemotherapy agents. Methods: We retrospectively reviewed all patients from two high volume centers who underwent robotic-assisted RNU between 2016-2020 and received either 2 g intravesical gemcitabine immediately following bladder cuff closure or non-gemcitabine intravesical chemotherapies [40 mg mitomycin C (MMC) or 50 mg doxorubicin] at the beginning of the procedure. Clinicopathologic factors were compared between cohorts. Bladder recurrence rates were evaluated using the Kaplan-Meier method and log-rank test. Results: During RNU, 24 patients received gemcitabine and 31 patients received non-gemcitabine chemotherapy. In total, 35% (19/55) of patients experienced a bladder cancer recurrence. There was no significant difference in estimated bladder recurrence-free survival (bRFS) between gemcitabine and non-gemcitabine patient cohorts (P=0.64). By 12 months post-surgery, 25% of patients had experienced bladder recurrence. The estimated 1-year bladder RFS survival was 73% for gemcitabine and 76% for non-gemcitabine chemotherapy. Overall survival and cancer-specific survival did not differ between cohorts. No adverse events potentially attributable to the use of gemcitabine were noted within 30 days postoperatively. Conclusions: Gemcitabine instilled immediately following bladder cuff closure during RNU has similar bRFS rates compared to established chemotherapy agents instilled at the start of surgery.

The long road to schistosomiasis elimination in Zanzibar: A systematic review covering 100 years of research, interventions and control milestones.

Zanzibar is among the few places in sub-Saharan Africa where interruption of Schistosoma transmission seems an achievable goal. Our systematic review identifies and discusses milestones in schistosomiasis research, control and elimination efforts in Zanzibar over the past 100 years. The search in online databases, libraries, and the World Health Organization Archives revealed 153 records published between May 1928 and August 2022. The content of records was summarised to highlight the pivotal work leading towards urogenital schistosomiasis elimination and remaining research gaps. The greatest achievement following 100 years of schistosomiasis interventions and research is undoubtedly the improved health of Zanzibaris, exemplified by the reduction in Schistosoma haematobium prevalence from>50% historically down to<5% in 2020, and the absence of severe morbidities. Experiences from Zanzibar have contributed to global schistosomiasis guidelines, whilst also revealing challenges that impede progression towards elimination. Challenges include: transmission heterogeneity requiring micro-targeting of interventions, post-treatment recrudescence of infections in transmission hotspots, biological complexity of intermediate host snails, emergence of livestock Schistosoma species complicating surveillance whilst creating the risk for interspecies hybridisation, insufficient diagnostics performance for light intensity infections and female genital schistosomiasis, and a lack of acceptable sanitary alternatives to freshwater bodies. Our analysis of the past revealed that much can be achieved in the future with practical implementation of integrated interventions, alongside operational research. With continuing national and international commitments, interruption of S. haematobium transmission across both islands is within reach by 2030, signposting the future demise of urogenital schistosomiasis across other parts of sub-Saharan Africa.

Comparative predictive power of serum vs plasma proteomic signatures in feto-maternal medicine.

BACKGROUND: Blood proteins are frequently measured in serum or plasma, because they provide a wealth of information. Differences in the ex vivo processing of serum and plasma raise concerns that proteomic health and disease signatures derived from serum or plasma differ in content and quality. However, little is known about their respective power to predict feto-maternal health outcomes. Predictive power is a sentinel characteristic to determine the clinical use of biosignatures. OBJECTIVE: This study aimed to compare the power of serum and plasma proteomic signatures to predict a physiological pregnancy outcome. STUDY DESIGN: Paired serum and plasma samples from 73 women were obtained from biorepositories of a multinational prospective cohort study on pregnancy outcomes. Gestational age at the time of sampling was the predicted outcome, because the proteomic signatures have been validated for such a prediction. Multivariate and cross-validated models were independently derived for serum and plasma proteins. RESULTS: A total of 1116 proteins were measured in 88 paired samples from 73 women with a highly multiplexed platform using proximity extension technology (Olink Proteomics Inc, Watertown, MA). The plasma proteomic signature showed a higher predictive power (R=0.64; confidence interval, 0.42-0.79; P=3.5×10-6) than the serum signature (R=0.45; confidence interval, 0.18-0.66; P=2.2×10-3). The serum signature was validated in plasma with a similar predictive power (R=0.58; confidence interval, 0.34-0.75; P=4.8×10-5), whereas the plasma signature was validated in serum with reduced predictive power (R=0.53; confidence interval, 0.27-0.72; P=2.6×10-4). Signature proteins largely overlapped in the serum and plasma, but the strength of association with gestational age was weaker for serum proteins. CONCLUSION: Findings suggest that serum proteomics are less informative than plasma proteomics. They are compatible with the view that the partial ex-vivo degradation and modification of serum proteins during sample processing are an underlying reason. The rationale for collecting and analyzing serum and plasma samples should be carefully considered when deriving proteomic biosignatures to ascertain that specimens of the highest scientific and clinical yield are processed. Findings suggest that plasma is the preferred matrix.

First principles and mean field study on the magnetocaloric effect of YFe3 and HoFe3 compounds.

In this work, the magnetothermal characteristics and magnetocaloric effect in YFe3 and HoFe3 compounds are calculated as function of temperature and magnetic field. These properties were investigated using the two-sublattice mean field model and the first-principles DFT calculation using the WIEN2k code. The two-sublattice model of the mean-field theory was used to calculate the temperature and field-dependences of magnetization, magnetic heat capacity, magnetic entropy, and the isothermal change in entropy ∆Sm. We used the WIEN2k code to determine the elastic constants and, subsequently, the bulk and shear moduli, the Debye temperature, and the density-of-states at Ef. According to the Hill prediction, YFe3 has bulk and shear moduli of roughly 99.3 and 101.2 GPa respectively. The Debye temperature is ≈ 500 K, and the average sound speed is ≈ 4167 m/s. In fields up to 60 kOe and at temperatures up to and above the Curie point for both substances, the trapezoidal method was used to determine ∆Sm. For instance, the highest ∆Sm values for YFe3 and HoFe3 in 30 kOe are approximately 0.8 and 0.12 J/mol. K, respectively. For the Y and Ho systems, respectively, the adiabatic temperature change in a 3 T field decreases at a rate of around 1.3 and 0.4 K/T. The ferro (or ferrimagnetic) to paramagnetic phase change in these two compounds, as indicated by the temperature and field dependences of the magnetothermal and magnetocaloric properties, ∆Sm and ∆Tad, is a second-order phase transition. The Arrott plots and the universal curve for YFe3 were also calculated and their features give an additional support to the second order nature of the phase transition.

Molecular dynamics simulation of phosphatidylcholine membrane in low ionic strengths of sodium chloride.

The one-microsecond molecular dynamics simulations of a membrane-protein complex investigate the influence of the aqueous sodium chloride solutions on the structure and dynamics of a palmitoyl-oleoyl-phosphatidylcholine bilayer membrane. The simulations were performed on five different concentrations (40, 150, 200, 300, and 400 mM) in addition to a salt-free system by using the charmm36 force field for all atoms. Four biophysical parameters, (membrane thicknesses of annular and bulk lipids, and the area per lipid of both leaflets), were computed separately. Nevertheless, the area per lipid was expressed by using the Voronoi algorithm. All time-independent analyses were carried out for the last 400 ns trajectories. Different concentrations revealed dissimilar membrane dynamics before equilibration. The biophysical properties of the membrane (thickness, area-per-lipid, and order parameter) have non-significant changes with increasing ionic strength, however, the 150 mM system had exceptional behavior. Sodium cations were dynamically penetrating the membrane forming weak coordinate bonds with single or multiple lipids. Nevertheless, the binding constant was unaffected by the cation concentration. The electrostatic and Van der Waals energies of lipid-lipid interactions were influenced by the ionic strength. On the other hand, the Fast Fourier Transform was performed to figure out the dynamics at the membrane-protein interface. The nonbonding energies of membrane-protein interactions and order parameters explained the differences in the synchronization pattern. All results were consensus with experimental and theoretical works.Communicated by Ramaswamy H. Sarma.

Relation between Vitamin B12 Levels and Smell Affection in COVID-19 Patients

Abstract Introduction Olfactory and gustative alterations are frequent in the initial stages of the COVID-19 infection. Vitamin B12 deficiency has been linked to olfactory dysfunction. Objective The present study aimed to assess the relationship between vitamin B12 levels and smell affection in COVID-19 patients. Methods The present study included 201 laboratory-confirmed COVID-19 patients. Smell affection was assessed using self-rated olfactory function. Serum vitamin B12 levels were assessed using commercial enzyme-linked immunosorbent assay (ELISA) kits. Results According to the smell function assessment, the patients were classified into three categories: normal osmesis (n = 77), hyposmia (n = 49), and anosmia (n = 75) (►Fig. 1). Four weeks later, 195 patients (97.0%) had their normal smell function restored. The remainder 6 patients included 4 anosmic and 2 hyposmic patients. Patients with hyposmia or anosmia had significantly lower vitamin B12 levels when compared with patients with normal osmesis (median [IQR]: 363.0 [198.0-539.0] versus 337.0 [175.0-467.0] and 491.0 [364.5-584.5] pg/ml, respectively, p < 0.001). Conclusion Vitamin B12 appears to have some contribution to smell affection in patients with COVID-19 infection.

Relation between Vitamin B12 Levels and Smell Affection in COVID-19 Patients.

Introduction Olfactory and gustative alterations are frequent in the initial stages of the COVID-19 infection. Vitamin B12 deficiency has been linked to olfactory dysfunction. Objective The present study aimed to assess the relationship between vitamin B12 levels and smell affection in COVID-19 patients. Methods The present study included 201 laboratory-confirmed COVID-19 patients. Smell affection was assessed using self-rated olfactory function. Serum vitamin B12 levels were assessed using commercial enzyme-linked immunosorbent assay (ELISA) kits. Results According to the smell function assessment, the patients were classified into three categories: normal osmesis ( n = 77), hyposmia ( n = 49), and anosmia ( n = 75) ( Fig. 1 ). Four weeks later, 195 patients (97.0%) had their normal smell function restored. The remainder 6 patients included 4 anosmic and 2 hyposmic patients. Patients with hyposmia or anosmia had significantly lower vitamin B12 levels when compared with patients with normal osmesis (median [IQR]: 363.0 [198.0-539.0] versus 337.0 [175.0-467.0] and 491.0 [364.5-584.5] pg/ml, respectively, p < 0.001). Conclusion Vitamin B12 appears to have some contribution to smell affection in patients with COVID-19 infection.

Genomic epidemiology of SARS-CoV-2 within households in coastal Kenya: a case ascertained cohort study

BackgroundAnalysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequence data from household infections should aid its detailed epidemiological understanding. Using viral genomic sequence data, we investigated household SARS-CoV-2 transmission and evolution in coastal Kenya households. MethodsWe conducted a case-ascertained cohort study between December 2020 and February 2022 whereby 573 members of 158 households were prospectively monitored for SARS-CoV-2 infection. Households were invited to participate if a member tested SARS-CoV-2 positive or was a contact of a confirmed case. Follow-up visits collected a nasopharyngeal/oropharyngeal (NP/OP) swab on days 1, 4 and 7 for RT-PCR diagnosis. If any of these were positive, further swabs were collected on days 10, 14, 21 and 28. Positive samples with an RT-PCR cycle threshold of <33.0 were subjected to whole genome sequencing followed by phylogenetic analysis. Ancestral state reconstruction was used to determine if multiple viruses had entered households. ResultsOf 2,091 NP/OP swabs that were collected, 375 (17.9%) tested SARS-CoV-2 positive. Viral genome sequences (>80% coverage) were obtained from 208 (55%) positive samples obtained from 61 study households. These genomes fell within 11 Pango lineages and four variants of concern (Alpha, Beta, Delta and Omicron). We estimated 163 putative transmission events involving members of the sequenced households, 40 (25%) of which were intra-household transmission events while 123 (75%) were infections that likely occurred outside the households. Multiple virus introductions (up-to-5) were observed in 28 (47%) households with the 1-month follow-up period. ConclusionsWe show that a considerable proportion of SARS-CoV-2 infections in coastal Kenya occurred outside the household setting. Multiple virus introductions frequently occurred into households within the same infection wave in contrast to observations from high income settings, where single introduction appears to be the norm. Our findings suggests that control of SARS-CoV-2 transmission by household member isolation may be impractical in this setting.

Fine-scale-mapping of Schistosoma haematobium infections at the school and community levels and intermediate host snail abundance in the north of Pemba Island: baseline cross-sectional survey findings before the onset of a 3-year intervention study.

BACKGROUND: Schistosomiasis elimination has gained renewed priority in the WHO guidance documents published in 2020 and 2022. The SchistoBreak project, implemented in Pemba, Tanzania between 2020 and 2024, aims to assess new tools and strategies for shifting from elimination as a public health problem towards interruption of transmission. Here we report our baseline findings and discuss implications for future interventions. METHODS: In 2020, human water contact sites (HWCSs) in the study area were geolocated and snail surveys were conducted. A parasitological and questionnaire cross-sectional baseline survey was implemented in 20 communities and their 16 primary schools between November 2020 and February 2021. Urine samples were collected at the school and household levels from individuals aged ≥ 4 years. Schistosoma haematobium infection was detected by urine filtration microscopy. Snail, parasitological and questionnaire-derived data were analyzed descriptively, spatially and with generalized estimated equation models. RESULTS: The intermediate host snail Bulinus globosus was detected in 19.8% (33/167) of HWCSs. The overall S. haematobium prevalence was 1.2% (26/2196) in school-aged children and 0.8% (31/3893) in community members, with 0.2% (4/2196) and 0.1% (3/3893) heavy-intensity infections, respectively. Children who studied < 1 km away from HWCSs with B. globosus had significantly higher odds for a S. haematobium infection than those attending a school located > 2 km away (odds ratio [OR]: 5.0; 95% confidence interval [CI]: 2.3-11.1). Individuals living in a house located < 1 km away from HWCSs with B. globosus had higher odds than those residing in > 2 km distance (OR: 18.0; 95% CI: 2.9-111.0). Self-reported praziquantel treatment coverage was 83.2% (2015/2423) in schoolchildren in the mass drug administration (MDA) conducted in August 2020. Coverage among adult community members was 59.9% (574/958), but only 34.8% (333/958) took praziquantel correctly. CONCLUSIONS: While the S. haematobium prevalence is very low in Pemba, there are many HWCSs with B. globosus situated close to schools or houses that pose a considerable risk of recrudescence. To maintain and accelerate the progress towards interruption of transmission, targeted and cost-effective interventions that are accepted by the community are needed; for example, snail control plus focal MDA, or test-and-treat in schools and households near infested waterbodies.

Forecasting the Potential Effects of Climate Change on Malaria in the Lake Victoria Basin Using Regionalized Climate Projections.

BACKGROUND: Malaria epidemics are increasing in East Africa since the 1980s, coincident with rising temperature and widening climate variability. A projected 1-3.5 °C rise in average global temperatures by 2100 could exacerbate the epidemics by modifying disease transmission thresholds. Future malaria scenarios for the Lake Victoria Basin (LVB) are quantified for projected climate scenarios spanning 2006-2100. METHODS: Regression relationships are established between historical (1995-2010) clinical malaria and anaemia cases and rainfall and temperature for four East African malaria hotspots. The vector autoregressive moving average processes model, VARMAX (p,q,s), is then used to forecast malaria and anaemia responses to rainfall and temperatures projected with an ensemble of eight General Circulation Models (GCMs) for climate change scenarios defined by three Representative Concentration Pathways (RCPs 2.6, 4.5 and 8.5). RESULTS: Maximum temperatures in the long rainy (March-May) and dry (June-September) seasons will likely increase by over 2.0 °C by 2070, relative to 1971-2000, under RCPs 4.5 and 8.5. Minimum temperatures (June-September) will likely increase by over 1.5-3.0 °C under RCPs 2.6, 4.5 and 8.5. The short rains (OND) will likely increase more than the long rains (MAM) by the 2050s and 2070s under RCPs 4.5 and 8.5. Historical malaria cases are positively and linearly related to the 3-6-month running means of monthly rainfall and maximum temperature. Marked variation characterizes the patterns projected for each of the three scenarios across the eight General Circulation Models, reaffirming the importance of using an ensemble of models for projections. CONCLUSIONS: The short rains (OND), wet season (MAM) temperatures and clinical malaria cases will likely increase in the Lake Victoria Basin. Climate change adaptation and mitigation strategies, including malaria control interventions could reduce the projected epidemics and cases. Interventions should reduce emerging risks, human vulnerability and environmental suitability for malaria transmission.