Feasibility and acceptability of integrating mass distribution of azithromycin to children 1–11 months into a trachoma mass drug administration campaign to reduce child mortality in Côte d’Ivoire

Evidence suggests that bi-annual mass drug administration (MDA) of single-dose azithromycin to 1–11 month-old children reduces child mortality in high child-mortality settings. Several countries conduct annual MDAs to distribute azithromycin to individuals ages 6 months and older to prevent trachoma infection. This study examined the feasibility and acceptability of reaching 1–11 months-old children during a trachoma MDA in Côte d’Ivoire by extending azithromycin distribution to infants 1–5 months old during the campaign. In November 2020, the study piloted single-dose azithromycin for 1–5 month-olds during a trachoma MDA in one health district. Monitoring data included the number of children reached and occurrences of adverse drug reactions. Feasibility, the extent to which the target population received the intervention (coverage), was assessed through a population-based, household survey with parents/caregivers of eligible children conducted after the MDA. Acceptability was explored through in-depth interviews (IDIs) with parents/caregivers of eligible children, focus group discussions (FGDs) with community drug distributors (CDDs), and IDIs with their supervisors. CDD FGDs and supervisor IDIs also documented implementation challenges and recommendations for scale-up. 1,735 1–5 month-olds received azithromycin during the pilot activity (estimated population coverage of 90.2%). Adverse drug reactions were reported for 1% (n = 18) infants; all were mild and self-limited. The post-MDA coverage survey interviewed 267 parents/caregivers; survey-based intervention coverage was 95.4% of 1–5 month-olds. Qualitative data revealed high intervention acceptability among parents, CDDs, and supervisors. Implementation challenges included the need to weigh babies to calculate dosage for 1–5 month-olds and the need to obtain written informed consent from parents to provide the drug to 1–5 month-olds. CDDs also indicated the need for more information on azithromycin and possible side effects during training. Delivering azithromycin to younger infants appears acceptable to parents and implementers; >90% coverage indicates feasibility to integrate into a trachoma MDA. (Clinicaltrials.gov ID number: NCT04617626)

Defective germline reprogramming rewires the spermatogonial transcriptome.

Defective germline reprogramming in Piwil4 (Miwi2)- and Dnmt3l-deficient mice results in the failure to reestablish transposon silencing, meiotic arrest and progressive loss of spermatogonia. Here we sought to understand the molecular basis for this spermatogonial dysfunction. Through a combination of imaging, conditional genetics and transcriptome analysis, we demonstrate that germ cell elimination in the respective mutants arises as a result of defective de novo genome methylation during reprogramming rather than because of a function for the respective factors within spermatogonia. In both Miwi2-/- and Dnmt3l-/- spermatogonia, the intracisternal-A particle (IAP) family of endogenous retroviruses is derepressed, but, in contrast to meiotic cells, DNA damage is not observed. Instead, we find that unmethylated IAP promoters rewire the spermatogonial transcriptome by driving expression of neighboring genes. Finally, spermatogonial numbers, proliferation and differentiation are altered in Miwi2-/- and Dnmt3l-/- mice. In summary, defective reprogramming deregulates the spermatogonial transcriptome and may underlie spermatogonial dysfunction

Recent advances in understanding hypertension development in sub-Saharan Africa

Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the Human Immunodeficiency Virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions, as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies, and (c) policymakers and health advocates to collectively contribute in creating health-promoting environments in Africa

Sertoli cells maintain leydig cell number and peritubular myoid cell activity in the adult mouse testis

The Sertoli cells are critical regulators of testis differentiation and development. In the adult, however, their known function is restricted largely to maintenance of spermatogenesis. To determine whether the Sertoli cells regulate other aspects of adult testis biology we have used a novel transgenic mouse model in which Amh-Cre induces expression of the receptor for Diphtheria toxin (iDTR) specifically within Sertoli cells. This causes controlled, cell-specific and acute ablation of the Sertoli cell population in the adult animal following Diphtheria toxin injection. Results show that Sertoli cell ablation leads to rapid loss of all germ cell populations. In addition, adult Leydig cell numbers decline by 75% with the remaining cells concentrated around the rete and in the sub-capsular region. In the absence of Sertoli cells, peritubular myoid cell activity is reduced but the cells retain an ability to exclude immune cells from the seminiferous tubules. These data demonstrate that, in addition to support of spermatogenesis, Sertoli cells are required in the adult testis both for retention of the normal adult Leydig cell population and for support of normal peritubular myoid cell function. This has implications for our understanding of male reproductive disorders and wider androgen-related conditions affecting male health

Germ Cell-Specific Targeting of DICER or DGCR8 Reveals a Novel Role for Endo-siRNAs in the Progression of Mammalian Spermatogenesis and Male Fertility

Small non-coding RNAs act as critical regulators of gene expression and are essential for male germ cell development and spermatogenesis. Previously, we showed that germ cell-specific inactivation of Dicer1, an endonuclease essential for the biogenesis of micro-RNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs), led to complete male infertility due to alterations in meiotic progression, increased spermatocyte apoptosis and defects in the maturation of spermatozoa. To dissect the distinct physiological roles of miRNAs and endo-siRNAs in spermatogenesis, we compared the testicular phenotype of mice with Dicer1 or Dgcr8 depletion in male germ cells. Dgcr8 mutant mice, which have a defective miRNA pathway while retaining an intact endo-siRNA pathway, were also infertile and displayed similar defects, although less severe, to Dicer1 mutant mice. These included cumulative defects in meiotic and haploid phases of spermatogenesis, resulting in oligo-, terato-, and azoospermia. In addition, we found by RNA sequencing of purified spermatocytes that inactivation of Dicer1 and the resulting absence of miRNAs affected the fine tuning of protein-coding gene expression by increasing low level gene expression. Overall, these results emphasize the essential role of miRNAs in the progression of spermatogenesis, but also indicate a role for endo-siRNAs in this process

Syndrome néphrotique de l’adulte et autres protéinuries de fort debit [Nephrotic syndrome and other high-level proteinuria]

High level albuminuria and the nephrotic syndrome are pathognomonic of glomerular renal disease and must be distinguished from other high-level proteinuria. Causes of the nephrotic syndrome are numerous and its clinical significance requires diagnostic rigor to propose targeted treatment and prevent possible complications and renal functional decline. A nephrotic syndrome can also be an early expression of potentially severe non-renal medical conditions. It should be considered in any patient with edema, regardless of age and comorbidities

Antibiotiques : quelques considérations pratiques [Antimicrobials : some practical considerations]

Antibiotics are frequently prescribed in hospitalized and in outpatients. We review four important aspects for their daily prescription. In elderly patients, the prescription should take into account changes in the volume of distribution and the usual decline in renal function even in the absence of chronic kidney disease. Particular antibiotics can trigger infection with Clostridium difficile. We discuss actual and novel strategies for its prevention. Renal toxicity of antibiotics includes acute tubular necrosis, interstitial nephritis and crystals obstructing renal tubule, depending on the class of antibiotics. Plasmatic levels of particular antibiotics should be measured either at trough or at peak levels depending of the antibiotic prescribed

Les reins : cibles du réchauffement climatique ? [The kidneys : possible victims of global warming ?]

Over the last decades, an increasing number of cases of chronic and end-stage kidney disease has been observed in Central America and Asia. This kidney disease mainly affects young farmers without classic renal risk factors. The clinical presentation includes a progressive decrease of the glomerular filtration rate, minimal proteinuria and the presence of tubulo-interstitial nephritis at renal biopsy. A close link with global warming is suspected for this disease, called (according to its location) meso-american nephropathy, Sri Lanka nephropathy or chronic kidney disease of unknown etiology. Others have suggested that intake of water contaminated with pesticides may be responsible. This article provides an overview of this new kidney disease. Measures to prevent acute kidney injury during heat waves in Switzerland are also discussed

A Cramér-von Mises test for symmetry of the error distribution in asymptotically stationary stochastic models

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