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.

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.

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 .

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.

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.

Comparison of blood lead levels between battery recycling workers and controls in Northern Nigeria.

About 80% of the global lead production is consumed by the battery industry. As old batteries are increasingly being recycled without adequate recourse to safety and protection in many developing countries, there is well-documented evidence of lead poisoning among the workers. This study compared blood lead levels (BLL) of battery recycling workers (BRW) with controls in Northern Nigeria. This cross-sectional study assessed the BLL of BRW (self-employed informal workers, n = 98) and controls (healthcare workers, n = 98). Respondents were selected using systematic random sampling from the lists of BRW and healthcare workers. All respondents in the two groups were males, matched for age (27.81 ± 7.2, 27.67 ± 7.0 years; p = 0.890). The mean BLL was significantly higher (p < 0.001) among the BRW compared to the controls (40.17 ± 4.2 and 3.61 ± 0.4 µg/dL, respectively), with 78.1% of the BRW having elevated BLL (≥20.0 µg/dL) and none (0.0%) of the controls having elevated BLL. Logistic regression shows none of the variables was an independent predictor of BLL in this study, implying battery reclamation as the main source of lead. Federal and state government policies should ban informal battery recycling and emphasize on plants through national collection system to consolidate used batteries only to smelters that meet minimum regulatory requirements.

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.

Direct maternal morbidity and the risk of pregnancy-related deaths, stillbirths, and neonatal deaths in South Asia and sub-Saharan Africa: A population-based prospective cohort study in 8 countries.

BACKGROUND: Maternal morbidity occurs several times more frequently than mortality, yet data on morbidity burden and its effect on maternal, foetal, and newborn outcomes are limited in low- and middle-income countries. We aimed to generate prospective, reliable population-based data on the burden of major direct maternal morbidities in the antenatal, intrapartum, and postnatal periods and its association with maternal, foetal, and neonatal death in South Asia and sub-Saharan Africa. METHODS AND FINDINGS: This is a prospective cohort study, conducted in 9 research sites in 8 countries of South Asia and sub-Saharan Africa. We conducted population-based surveillance of women of reproductive age (15 to 49 years) to identify pregnancies. Pregnant women who gave consent were include in the study and followed up to birth and 42 days postpartum from 2012 to 2015. We used standard operating procedures, data collection tools, and training to harmonise study implementation across sites. Three home visits during pregnancy and 2 home visits after birth were conducted to collect maternal morbidity information and maternal, foetal, and newborn outcomes. We measured blood pressure and proteinuria to define hypertensive disorders of pregnancy and woman's self-report to identify obstetric haemorrhage, pregnancy-related infection, and prolonged or obstructed labour. Enrolled women whose pregnancy lasted at least 28 weeks or those who died during pregnancy were included in the analysis. We used meta-analysis to combine site-specific estimates of burden, and regression analysis combining all data from all sites to examine associations between the maternal morbidities and adverse outcomes. Among approximately 735,000 women of reproductive age in the study population, and 133,238 pregnancies during the study period, only 1.6% refused consent. Of these, 114,927 pregnancies had morbidity data collected at least once in both antenatal and in postnatal period, and 114,050 of them were included in the analysis. Overall, 32.7% of included pregnancies had at least one major direct maternal morbidity; South Asia had almost double the burden compared to sub-Saharan Africa (43.9%, 95% CI 27.8% to 60.0% in South Asia; 23.7%, 95% CI 19.8% to 27.6% in sub-Saharan Africa). Antepartum haemorrhage was reported in 2.2% (95% CI 1.5% to 2.9%) pregnancies and severe postpartum in 1.7% (95% CI 1.2% to 2.2%) pregnancies. Preeclampsia or eclampsia was reported in 1.4% (95% CI 0.9% to 2.0%) pregnancies, and gestational hypertension alone was reported in 7.4% (95% CI 4.6% to 10.1%) pregnancies. Prolonged or obstructed labour was reported in about 11.1% (95% CI 5.4% to 16.8%) pregnancies. Clinical features of late third trimester antepartum infection were present in 9.1% (95% CI 5.6% to 12.6%) pregnancies and those of postpartum infection in 8.6% (95% CI 4.4% to 12.8%) pregnancies. There were 187 pregnancy-related deaths per 100,000 births, 27 stillbirths per 1,000 births, and 28 neonatal deaths per 1,000 live births with variation by country and region. Direct maternal morbidities were associated with each of these outcomes. CONCLUSIONS: Our findings imply that health programmes in sub-Saharan Africa and South Asia must intensify their efforts to identify and treat maternal morbidities, which affected about one-third of all pregnancies and to prevent associated maternal and neonatal deaths and stillbirths. TRIAL REGISTRATION: The study is not a clinical trial.

Novel tools and strategies for breaking schistosomiasis transmission: study protocol for an intervention study.

BACKGROUND: Global elimination of schistosomiasis as a public health problem is set as target in the new World Health Organization's Neglected Tropical Diseases Roadmap for 2030. Due to a long history of interventions, the Zanzibar islands of Tanzania have reached this goal since 2017. However, challenges occur on the last mile towards interruption of transmission. Our study will investigate new tools and strategies for breaking schistosomiasis transmission. METHODS: The study is designed as an intervention study, documented through repeated cross-sectional surveys (2020-2024). The primary endpoint will be the sensitivity of a surveillance-response approach to detect and react to outbreaks of urogenital schistosomiasis over three years of implementation. The surveys and multi-disciplinary interventions will be implemented in 20 communities in the north of Pemba island. In low-prevalence areas, surveillance-response will consist of active, passive and reactive case detection, treatment of positive individuals, and focal snail control. In hotspot areas, mass drug administration, snail control and behaviour change interventions will be implemented. Parasitological cross-sectional surveys in 20 communities and their main primary schools will serve to adapt the intervention approach annually and to monitor the performance of the surveillance-response approach and impact of interventions. Schistosoma haematobium infections will be diagnosed using reagent strips and urine filtration microscopy, and by exploring novel point-of-care diagnostic tests. DISCUSSION: Our study will shed light on the field applicability and performance of novel adaptive intervention strategies, and standard and new diagnostic tools for schistosomiasis elimination. The evidence and experiences generated by micro-mapping of S. haematobium infections at community level, micro-targeting of new adaptive intervention approaches, and application of novel diagnostic tools can guide future strategic plans for schistosomiasis elimination in Zanzibar and inform other countries aiming for interruption of transmission. Trial registration ISRCTN, ISCRCTN91431493. Registered 11 February 2020, https://www.isrctn.com/ISRCTN91431493.

Machine learning guided postnatal gestational age assessment using new-born screening metabolomic data in South Asia and sub-Saharan Africa.

BACKGROUND: Babies born early and/or small for gestational age in Low and Middle-income countries (LMICs) contribute substantially to global neonatal and infant mortality. Tracking this metric is critical at a population level for informed policy, advocacy, resources allocation and program evaluation and at an individual level for targeted care. Early prenatal ultrasound examination is not available in these settings, gestational age (GA) is estimated using new-born assessment, last menstrual period (LMP) recalls and birth weight, which are unreliable. Algorithms in developed settings, using metabolic screen data, provided GA estimates within 1-2 weeks of ultrasonography-based GA. We sought to leverage machine learning algorithms to improve accuracy and applicability of this approach to LMICs settings. METHODS: This study uses data from AMANHI-ACT, a prospective pregnancy cohorts in Asia and Africa where early pregnancy ultrasonography estimated GA and birth weight are available and metabolite screening data in a subset of 1318 new-borns were also available. We utilized this opportunity to develop machine learning (ML) algorithms. Random Forest Regressor was used where data was randomly split into model-building and model-testing dataset. Mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate performance. Bootstrap procedures were used to estimate confidence intervals (CI) for RMSE and MAE. For pre-term birth identification ROC analysis with bootstrap and exact estimation of CI for area under curve (AUC) were performed. RESULTS: Overall model estimated GA had MAE of 5.2 days (95% CI 4.6-6.8), which was similar to performance in SGA, MAE 5.3 days (95% CI 4.6-6.2). GA was correctly estimated to within 1 week for 85.21% (95% CI 72.31-94.65). For preterm birth classification, AUC in ROC analysis was 98.1% (95% CI 96.0-99.0; p < 0.001). This model performed better than Iowa regression, AUC Difference 14.4% (95% CI 5-23.7; p = 0.002). CONCLUSIONS: Machine learning algorithms and models applied to metabolomic gestational age dating offer a ladder of opportunity for providing accurate population-level gestational age estimates in LMICs settings. These findings also point to an opportunity for investigation of region-specific models, more focused feasible analyte models, and broad untargeted metabolome investigation.

Randomized Controlled Trial on Autologous Platelet-Rich Plasma Versus Saline Dressing in Treatment of Non-healing Diabetic Foot Ulcers.

BACKGROUND: This randomized clinical trial was conducted to assess the role of platelet-rich plasma (PRP) gel as a treatment of clean non-healing diabetic foot ulcer (DFU) in comparison with regular dressing with saline as a control. METHODS: Patients with DFU were randomly assigned to one of two equal groups: group I received dressing with PRP gel and group II received regular saline dressing. The main outcomes of the study were percent reduction in the dimensions of the DFU, healing of DFU, and complications at 20 weeks of follow-up. RESULTS: Twenty-four patients were included to the study. The mean age of patients was 55.2 ± 6.4 years. Only three (25%) patients in group I achieved complete healing versus none of group II patients. In total, 8.3% of group I and 41.6% of group II patients did not show any response to treatment. The percent of reduction in the longitudinal and horizontal dimensions of the DFU was significantly greater in group I than group II (43.2% vs 4.1%) and (42.3% vs 8.2%), respectively. The time required to maximum healing was significantly shorter in group I than group II (6.3 ± 2.1 vs 10.4 ± 1.7 weeks, P < 0.0001). CONCLUSION: The use of PRP gel as a dressing for chronic DFU resulted in a more significant reduction in the size of the ulcer when compared to regular saline dressing. Also the time to reach the point of maximal possible healing with the least wound dimensions was significantly shorter when using PRP as a dressing protocol.

Development of a Molecular Snail Xenomonitoring Assay to Detect Schistosoma haematobium and Schistosoma bovis Infections in their Bulinus Snail Hosts.

Schistosomiasis, a neglected tropical disease of medical and veterinary importance, transmitted through specific freshwater snail intermediate hosts, is targeted for elimination in several endemic regions in sub-Saharan Africa. Multi-disciplinary methods are required for both human and environmental diagnostics to certify schistosomiasis elimination when eventually reached. Molecular xenomonitoring protocols, a DNA-based detection method for screening disease vectors, have been developed and trialed for parasites transmitted by hematophagous insects, such as filarial worms and trypanosomes, yet few have been extensively trialed or proven reliable for the intermediate host snails transmitting schistosomes. Here, previously published universal and Schistosoma-specific internal transcribed spacer (ITS) rDNA primers were adapted into a triplex PCR primer assay that allowed for simple, robust, and rapid detection of Schistosoma haematobium and Schistosoma bovis in Bulinus snails. We showed this two-step protocol could sensitively detect DNA of a single larval schistosome from experimentally infected snails and demonstrate its functionality for detecting S. haematobium infections in wild-caught snails from Zanzibar. Such surveillance tools are a necessity for succeeding in and certifying the 2030 control and elimination goals set by the World Health Organization.

Radical Approaches During Unusual Circumstances: Intellectual Property Regulation and the COVID-19 Dilemma.

The current outbreak of COVID-19 pandemic traces its roots back many decades and is worsened by a number of ill-conceived strategies and policies. The current patent protection regime and its suitability in dealing with the current COVID-19 pandemic need to be questioned. Strengthened intellectual property protection manifested by the rise of TRIPS-Plus standards is having a negative impact on the affordability and accessibility of medicines. Dealing with the current pandemic urgently demands serious reform and collective efforts.

Outcome of Modified Park's Technique for Treatment of Complex Anal Fistula.

BACKGROUND: Treatment of complex anal fistula (CAF) can be associated with high rates of recurrence and fecal incontinence (FI). Park suggested drainage of the affected intersphincteric anal gland for treatment of cryptoglandular anal fistula; however, recurrence after this technique was high. We modified the original Park's technique by extending the internal sphincterotomy to ensure adequate drainage of the intersphincteric space. The aim of this study was to evaluate the incidence of recurrence and FI after modified Park's technique in treatment of CAF. METHODS: Adult patients of both genders with CAF were evaluated before undergoing modified Park's technique with Wexner continence score, clinical examination, and endoanal ultrasonography or MRI. Postoperatively, patients were examined every 2 wk until complete wound healing. The continence state was evaluated with Wexner continence score, and quality of life was assessed before surgery and at 6 mo postoperatively by Short Form-36 questionnaire. RESULTS: Thirty-two patients (27 male) of a mean age of 38 y were included. Median follow-up was 12 mo. Two patients (6.25%) experienced recurrence and 5 (15.6%) developed complications. One patient (3.1%) developed new-onset FI postoperatively. Twenty-eight (87.5%) patients were completely satisfied with the procedure. Quality of life showed significant improvement at 6 mo postoperatively. CONCLUSIONS: The modified Park's technique is a promising procedure for the treatment of CAF with low recurrence and FI rates, and improved quality of life.

The Impact of 5α-Reductase Inhibitor Use for Male Pattern Hair Loss on Men's Health.

PURPOSE OF REVIEW: Male pattern hair loss, mediated by dihydrotestosterone, is a common hair loss disorder, affecting over 50% of men over the age of 50. The 5-α reductase inhibitors, finasteride and dutasteride, are Food and Drug Administration-approved drugs for the treatment of this disorder. Several recent studies have reported adverse sexual and spermatogenic events among young men using 5-α reductase inhibitors, such as erectile dysfunction, decreased ejaculate volume, decreased libido, and infertility. In this review, we summarize and analyze the literature regarding the efficacy and safety of these medications, with an overall focus on men's health. RECENT FINDINGS: Finasteride for the treatment of male pattern hair loss was considered safe according to many previous clinical trials. However, these trials have been recently criticized for inadequate safety reporting. Comprehensive review of the current literature reveals that there is a disproportionately high number of men with 5-α reductase inhibitor-associated sexual dysfunction and infertility. Although uncommon, the use of 5-α reductase inhibitors is associated with serious and persistent sexual and reproductive side effects, such as erectile dysfunction, decreased ejaculate volume, decreased libido, and infertility.

Isolation of the major chiral compounds from Bubonium graveolens essential oil by HPLC and absolute configuration determination by VCD.

The chirality issues in the essential oils (EOs) of leaves and flowers from Bubonium graveolens were addressed by chiral high-performance liquid chromatography (HPLC) with polarimetric detection and vibrational circular dichroism (VCD). The chemical compositions of the crude oils of three samples were established by gas chromatography / mass spectrometry (GC/MS). The well-known cis-chrysanthenyl acetate (1), oxocyclonerolidol (2), and the recently disclosed cis-acetyloxychrysanthenyl acetate (3), the three major chiral compounds, were isolated by preparative HPLC. The naturally occurring oxocycloneroledol (2), mostly found in the leaf oil (49.4-55.6%), presents a (+) sign in the mobile phase during HPLC on a chiral stationary phase (CSP) with a Jasco polarimetric detection. The naturally occurring cis-chrysanthenyl acetate (1) and cis-acetyloxychrysanthenyl acetate (3), mostly found in the flower EO (35.9-74.9% and 10.0-34.3%, respectively), both present a (-) sign. HPLC on a CSP with polarimetric detection is an unprecedented approach to readily differentiate the flower and leaf EOs according to their chiral signature. The comparison of the experimental and calculated VCD spectra of pure isolated 1, 2, and 3 provided their absolute configuration as being (1S,5R,6S)-(-)-2,7,7-trimethylbicyclo[3.1.1]hept-2-en-6-yl acetate 1, (2R,6R)-(+)-6-ethenyl-2,6-dimethyl-2-(4-methylpent-3-en-1-yl)dihydro-2H-pyran-3(4H)-one) 2 and (1S,5R,6R,7S)-(-)-7-(acetyloxy)-2,6-dimethylbicyclo[3.1.1]hept-2-en-6-yl]methyl acetate 3. Compounds 1, 2, and 3 were already known in B. graveolens but this is the first report of the absolute configuration of (+)-2 and (-)-3. The VCD chiral signatures of the crude oils were also recorded.

Update on the Diagnosis and Management of Renal Angiomyolipoma.

PURPOSE: Advances in minimally invasive therapies and novel targeted chemotherapeutics have provided a breadth of options for the management of renal masses. Management of renal angiomyolipoma has not been reviewed in a comprehensive fashion in more than a decade. We provide an updated review of the current diagnosis and management strategies for renal angiomyolipoma. MATERIALS AND METHODS: We conducted a PubMed(®) search of all available literature for renal or kidney angiomyolipoma. Further sources were identified in the reference lists of identified articles. We specifically reviewed case series of partial nephrectomy, selective arterial embolization and ablative therapies as well as trials of mTOR inhibitors for angiomyolipoma from 1999 to 2014. RESULTS: Renal angiomyolipoma is an uncommon benign renal tumor. Although associated with tuberous sclerosis complex, these tumors occur sporadically. Risk of life threatening hemorrhage is the main clinical concern. Due to the fat content, angiomyolipomas are generally readily identifiable on computerized tomography and magnetic resonance imaging. However, fat poor angiomyolipoma can present a diagnostic challenge. Novel research suggests that various strategies using magnetic resonance imaging, including chemical shift magnetic resonance imaging, have the potential to differentiate fat poor angiomyolipoma from renal cell carcinoma. Active surveillance is the accepted management for small asymptomatic masses. Generally, symptomatic masses and masses greater than 4 cm should be treated. However, other relative indications may apply. Options for treatment have traditionally included radical and partial nephrectomy, selective arterial embolization and ablative therapies, including cryoablation and radio frequency ablation, all of which we review and update. We also review recent advances in the medical treatment of patients with tuberous sclerosis complex associated angiomyolipomas with mTOR inhibitors. Specifically trials of everolimus for patients with tuberous sclerosis complex suggest that this agent may be safe and effective in treating angiomyolipoma tumor burden. A schema for the suggested management of renal angiomyolipoma is provided. CONCLUSIONS: Appropriately selected cases of renal angiomyolipoma can be managed by active surveillance. For those patients requiring treatment nephron sparing approaches, including partial nephrectomy and selective arterial embolization, are preferred options. For those with tuberous sclerosis complex mTOR inhibitors may represent a viable approach to control tumor burden while conserving renal parenchyma.

Zoonosis emergence linked to agricultural intensification and environmental change.

A systematic review was conducted by a multidisciplinary team to analyze qualitatively best available scientific evidence on the effect of agricultural intensification and environmental changes on the risk of zoonoses for which there are epidemiological interactions between wildlife and livestock. The study found several examples in which agricultural intensification and/or environmental change were associated with an increased risk of zoonotic disease emergence, driven by the impact of an expanding human population and changing human behavior on the environment. We conclude that the rate of future zoonotic disease emergence or reemergence will be closely linked to the evolution of the agriculture-environment nexus. However, available research inadequately addresses the complexity and interrelatedness of environmental, biological, economic, and social dimensions of zoonotic pathogen emergence, which significantly limits our ability to predict, prevent, and respond to zoonotic disease emergence.

Artemisia arborescens Essential Oil Composition, Enantiomeric Distribution, and Antimicrobial Activity from Different Wild Populations from the Mediterranean Area.

Aerial parts of Artemisia arborescens were collected from different sites of the Mediterranean area (southwestern Algeria and southern Italy) and the chemical composition of their essential oil (EO) extracted by hydrodistillation was studied by both gas chromatography (GC) equipped with an enantioselective capillary column and GC/mass spectrometry (GC/MS). The EOs obtained were tested against several Listeria monocytogenes strains. Using GC and GC/MS, 41 compounds were identified, accounting for 96.0 - 98.8% of the total EO. All EOs showed a similar terpene profile, which was rich in chamazulene, ß-thujone, and camphor. However, the concentration of such compounds varied among the EOs. A. arborescens EO inhibited up to 83.3% of the L. monocytogenes strains, but the inhibitory spectrum varied among the EOs, with those from Algeria showing a higher inhibition degree than the Italian EOs. Such effect likely depended on the ketone (ß-thujone + camphor) content of the EO. The differences in the EO composition support the hypothesis that A. arborescens has at least two different chemotypes: a ß-thujone and a chamazulene type. The EO inhibitory spectrum indicates the A. arborescens EO as a valuable option in the control of the food-borne pathogens.

Improving performance of the Tariff Method for assigning causes of death to verbal autopsies.

BACKGROUND: Reliable data on the distribution of causes of death (COD) in a population are fundamental to good public health practice. In the absence of comprehensive medical certification of deaths, the only feasible way to collect essential mortality data is verbal autopsy (VA). The Tariff Method was developed by the Population Health Metrics Research Consortium (PHMRC) to ascertain COD from VA information. Given its potential for improving information about COD, there is interest in refining the method. We describe the further development of the Tariff Method. METHODS: This study uses data from the PHMRC and the National Health and Medical Research Council (NHMRC) of Australia studies. Gold standard clinical diagnostic criteria for hospital deaths were specified for a target cause list. VAs were collected from families using the PHMRC verbal autopsy instrument including health care experience (HCE). The original Tariff Method (Tariff 1.0) was trained using the validated PHMRC database for which VAs had been collected for deaths with hospital records fulfilling the gold standard criteria (validated VAs). In this study, the performance of Tariff 1.0 was tested using VAs from household surveys (community VAs) collected for the PHMRC and NHMRC studies. We then corrected the model to account for the previous observed biases of the model, and Tariff 2.0 was developed. The performance of Tariff 2.0 was measured at individual and population levels using the validated PHMRC database. RESULTS: For median chance-corrected concordance (CCC) and mean cause-specific mortality fraction (CSMF) accuracy, and for each of three modules with and without HCE, Tariff 2.0 performs significantly better than the Tariff 1.0, especially in children and neonates. Improvement in CSMF accuracy with HCE was 2.5%, 7.4%, and 14.9% for adults, children, and neonates, respectively, and for median CCC with HCE it was 6.0%, 13.5%, and 21.2%, respectively. Similar levels of improvement are seen in analyses without HCE. CONCLUSIONS: Tariff 2.0 addresses the main shortcomings of the application of the Tariff Method to analyze data from VAs in community settings. It provides an estimation of COD from VAs with better performance at the individual and population level than the previous version of this method, and it is publicly available for use.