SARS-CoV-2 infection augments species- and age-specific predispositions in cotton rats.

Heterogeneity of COVID-19 manifestations in human population is vast, for reasons unknown. Cotton rats are a clinically relevant small animal model of human respiratory viral infections. Here, we demonstrate for the first time that SARS-CoV-2 infection in cotton rats affects multiple organs and systems, targeting species- and age-specific biological processes. Infection of S. fulviventer, which developed a neutralizing antibody response and were more susceptible to SARS-CoV-2 replication in the upper respiratory tract, was accompanied by hyperplasia of lacrimal drainage-associated lymphoid tissue (LDALT), a first known report of mucosa-associated lymphoid tissue activation at the portal of SARS-CoV-2 entry. Although less permissive to viral replication, S. hispidus showed hyperplasia of bone marrow in the facial bones and increased pulmonary thrombosis in aged males. Augmentation of these features by SARS-CoV-2 infection suggests a virus-induced breach in regulatory mechanisms which could be devastating for people of all ages with underlying conditions and in particular for elderly with a multitude of ongoing disorders.

Correlative outcomes of maternal immunization against RSV in cotton rats.

Maternal anti-respiratory syncytial virus (RSV) antibodies protect neonates from RSV disease throughout first weeks of life. Previous studies of maternal immunization in cotton rats showed that a single immunization during pregnancy of RSV-primed dams with virus-like particles (VLPs) assembled with pre-fusion F protein and the wild type G protein boosted their RSV serum antibody concentration and protected pups early in life against RSV challenge. We extended these findings by evaluating responses to RSV infection in litters from two consecutive pregnancies of immunized dams. Using an RSV-primed population of VLP-vaccinated and unvaccinated dams, we defined correlations between dams' and litters' RSV neutralizing antibodies (NA); between litters' NA and protection; and between litter's NA and their lung expression of selected cytokines, of a first or of a second pregnancy. Lung pathology was also evaluated. We found positive correlation between the NA titers in the dams at delivery and the NA in their first and second litters and negative correlations between the litters' NA and protection from RSV challenge. Vaccination of dams modulated the mRNA expression for IFNγ and IL-6 and lung pathology in the first and in the second litter at different times after birth, even in the absence of detectable NA. Maternal RSV vaccination enhanced the levels of antibodies transferred to offspring and their protection from challenge. Importantly, maternal vaccination also impacted the immunological and inflammatory response of the offspring's lungs well into maturity, and after the antiviral effect of maternally transferred NA waned or was no longer detectable.

Evidence for Interplay Between the Renin-Angiotensin System and Toll-Like Receptor 4 Signaling Pathways in the Induction of Virus-Induced Acute Lung Injury.

Dedication: This article is dedicated to Howard Young, an exceptional scientist who has provided outstanding mentorship to many postbaccalaureates, graduate students, and postdoctoral fellows during his career. Howard has been a colleague to many and was never tired of learning new things. He has brought "thinking out of the box" to the level of an art form and has always provided thoughtful and constructive suggestions to those who have sought his counsel. I am personally greatly indebted to Howard for his guidance in molecular biology over the past 30 years, and hope that we will continue to share a passion for learning and mentoring others for years to come. Thank you, Howard! -Stephanie N. Vogel The SARS-CoV-2 pandemic has led to an unprecedented explosion in studies that have sought to identify key mechanisms that underlie the ravaging aspects of this disease on individuals. SARS-CoV-2 virus gains access to cells by (1) binding of the viral spike (S) protein to cell-associated angiotensin-converting enzyme 2 (ACE2), a key receptor in the renin-angiotensin system (RAS), followed by (2) cleavage of S protein by a cellular serine protease ("S protein priming") to facilitate viral entry. Dysregulation of the RAS system has been implicated in the spectrum of clinical symptoms associated with SARS-CoV-2, including hypercytokinemia, elevated markers of endothelial injury and thrombosis, and both localized and systemic inflammation. However, the underlying mechanisms have yet to be fully delineated.

Women who have undergone female genital mutilation/cutting's perceptions and experiences with healthcare providers in Paris.

Female genital mutilation/cutting (FGM/C) is a health and human rights issue and a dangerous form of gender-based violence. Given migratory flows from the countries in which it is practised, FGM/C concerns a substantial number of women living in Western countries. In this study, we looked at women who had undergone FGM/C experiences with French medical practitioners. We also discussed with them the desirability of screening for, and prevention of, FGM/C in international travel medicine centres. A qualitative approach was used to collect and analyse the data. Focus groups and semi-structured interviews were held with 26 women (24 participants in focus groups and 2 individual interviews). Transcriptions were coded and analysed thematically. All the participants came from sub-Saharan Africa. Their median age was 32.9 years. Persistent silence about FGM/C in the host society following immigration resulted in dissatisfaction with healthcare providers. Participants expected professionals to address the subject of FGM/C, feeling professionals should bring up the subject first so as to put women at ease. International travel medicine centres were discussed by some as a possible means of prevention.

Evolution of protection after maternal immunization for respiratory syncytial virus in cotton rats.

Maternal anti-respiratory syncytial virus (RSV) antibodies acquired by the fetus through the placenta protect neonates from RSV disease through the first weeks of life. In the cotton rat model of RSV infections, we previously reported that immunization of dams during pregnancy with virus-like particles assembled with mutation stabilized pre-fusion F protein as well as the wild type G protein resulted in robust protection of their offspring from RSV challenge. Here we describe the durability of those protective responses in dams, the durability of protection in offspring, and the transfer of that protection to offspring of two consecutive pregnancies without a second boost immunization. We report that four weeks after birth, offspring of the first pregnancy were significantly protected from RSV replication in both lungs and nasal tissues after RSV challenge, but protection was reduced in pups at 6 weeks after birth. However, the overall protection of offspring of the second pregnancy was considerably reduced, even at four weeks of age. This drop in protection occurred even though the levels of total anti-pre-F IgG and neutralizing antibody titers in dams remained at similar, high levels before and after the second pregnancy. The results are consistent with an evolution of antibody properties in dams to populations less efficiently transferred to offspring or the less efficient transfer of antibodies in elderly dams.

Orbital migration of schistosome eggs: a case report.

BACKGROUND: Ocular damage, including damage to the conjunctiva, lacrimal gland, eyelids, and orbit, caused by Schistosoma haematobium is sporadic. We report a clinical case of orbital migration of schistosome eggs. CASE PRESENTATION: A 14-year-old boy of Malian nationality presented with a painless swelling of the upper right eyelid, which had been gradually increasing for approximately 3 months. Visual acuity was logMAR 0.10 and 0.00 in the right and left eye, respectively. External examination revealed a right palpebral mass, pushing the globe slightly downward and inward. Computed tomography revealed a mass of the right lacrimal gland. Total excision of the mass was performed by transpalpebral orbitotomy. Pathological examination revealed an inflammatory granulomatous infiltrate of the lacrimal gland consisting of lymphocytes, eosinophils, giant cells, epithelioid cell, histiocytes and calcified Schistosoma eggs with terminal spine. Urine examination revealed eggs of S. haematobium. Praziquantel 40 mg/kg was administered to the patient. The hematuria stopped after 1 week. After 3 years of follow-up, no recurrence was noted. CONCLUSIONS: The bilharzian granuloma of the lacrimal gland is an ectopic site of the parasite. In this case, the granuloma was cured by surgical excision followed by a course of Praziquantel.

A systematic review and meta-analysis of the consequences of female genital mutilation on maternal and perinatal health outcomes in European and African countries.

INTRODUCTION: Key knowledge gaps remain to improve reproductive health outcomes for millions of women living with female genital mutilation (FGM). We aimed to update previous reviews and quantify more rigorously maternal and perinatal complications related to FGM across different settings. METHODS: In this systematic review and meta-analysis, we searched 15 electronic databases for studies published between 1 August 1995 and 15 March 2020, reporting on maternal and perinatal complications related to FGM. We included studies comparing women with and without FGM while accounting for confounders. Pooled relative risks (RR) were calculated, using fixed-effects and random-effects models, for a range of maternal and perinatal outcomes, adjusting for individual characteristics and according to delivery settings and study design. RESULTS: We identified 106 unique references, assessed 72 full-text articles and included 11 studies. We found non-significant elevated risks of instrumental delivery, caesarean delivery, episiotomy, postpartum haemorrhage, perineal laceration, low Apgar score and miscarriage/stillbirth related to FGM. Heterogeneity was present for most outcomes when combining all studies but reduced in subgroup analyses. The risk of caesarean delivery was increased among primiparous women (1.79, 95% CI 1.04 to 3.07) such as the risk of episiotomy in European specialised settings for women with FGM (1.88, 1.14 to 3.09). In Africa, subgroup analyses revealed elevated risks of postpartum haemorrhage (2.59, 1.28 to 5.25). The most common reported type was FGM II. However, few studies provided stratified analyses by type of FGM, which did not allow an assessment of the impact of the severity of typology on studied outcomes. CONCLUSION: This review suggests maternal and perinatal morbidity related to FGM vary by study design, context and by subgroup of women. Our study also draws attention to the complications that may extend to the postpartum period. This work contributes to shaping a reference framework for future research and clinical guidelines.

Head and neck cancer and occupational exposure to leather dust: results from the ICARE study, a French case-control study.

BACKGROUND: Leather dust is an established carcinogen of the sinonasal cavities; however, evidence is lacking regarding its association with other head and neck cancers (HNC). To date, few studies have been conducted on the association between occupational leather dust exposure and the risk of oral, pharyngeal, and laryngeal cancers. The objective of this study was to investigate the association between the risk of HNC and occupational exposure to leather dust. METHODS: Lifestyle habits and occupational history were collected for 2161 patients with squamous cell carcinoma of oral cavity, pharynx, and larynx, and 3555 controls, using a standardized questionnaire. Occupational exposure to leather dust was assessed using a job-exposure matrix. Odds ratios (OR) and 95% confidence intervals (CI) for HNC globally and by subsite were estimated using multivariate unconditional, and polytomous logistic regressions, respectively. RESULTS: Cumulative lifetime exposure to leather dust < 6 mg/m3-years was associated with an increased risk of laryngeal cancer (OR = 2.26, 95% CI: 1.07-4.76); higher levels were not related to elevated risks of HNC. Some tasks performed and the use of some glues were associated with elevated, although non-significant, risks of HNC. No dose-response relationships were observed. CONCLUSION: Our study did not provide enough evidence for an increased risk of HNC related to occupational exposure to leather dust. Further studies are needed to understand the risks of specific tasks in the leather industry.

[Retinoblastoma: inventory in Mali and program to develop early diagnosis, treatments and rehabilitation]. / Le rétinoblastome: état des lieux au Mali et programme d'aide au diagnostic précoce, aux traitements et à la réhabilitation.

Retinoblastoma (RB) is a rare embryonic tumour that represents 1/16,000 births in France. In Mali, a study showed the characteristics of a hospital series of cases seen in Bamako in the Pediatric Oncology Unit of Gabriel Touré Teaching Hospital and in the Tropical Ophthalmology Institute of Africa (IOTA) between January 2005 and June 2007. Median age was 4 years versus 2 years in France for unilateral disease. Near two third of children with RB had extra-ocular extension at diagnosis, which is now exceptional in France. Only 11% were bilateral versus 35% in France. Cure rate was around 50%, but it is estimated only on the cases arriving in Bamako and with at least 20% lost of follow-up. Cure rate is over 95% in France within an exhaustive register. RB appears as an exemplary tumor and rapid improvements could be obtained in low-income countries with relatively limited means. This is why, the Alliance mondiale contre le cancer (AMCC), the Institut Curie in Paris, which is the reference center in France for RB, and teams in Bamako were proposing a program to help the development of early diagnosis, treatments, including eye preservation, and rehabilitation of children with RB in sub-Saharan Africa in collaboration with the Groupe franco-africain d'oncologie pédiatrique (GFAOP). The official launching of this program was held in Bamako November 4, 2011 for Mali and the surrounding regions. After this first experience, this program is now implemented in other countries.