Single-cell RNA sequencing identifies eggplant as a regulator of germ cell development in Drosophila.

Drosophila ovarian germline stem cells (GSCs) are a powerful model for stem cell research. In this study, we use single-cell RNA sequencing (scRNA-seq), an RNAi screen and bioinformatic analysis, to identify genes involved in germ cell differentiation, including 34 genes with upregulated expression during early germ cell development and 19 genes that may regulate germ cell differentiation. Among these, a gene we have named eggplant (eggpl) is highly expressed in GSCs and downregulated in early daughter cells. RNAi knockdown of eggpl causes germ cell proliferation and differentiation defects. In flies fed a rich yeast diet, the expression of eggpl is significantly lower and knockdown or knockout of eggpl phenocopies a rich diet. In addition, eggpl knockdown suppresses the reduction in germ cell proliferation caused by inhibition of the insulin effector PI3K. These findings suggest that downregulation of eggpl links nutritional status to germ cell proliferation and differentiation. Collectively, this study provides new insights into the signaling networks that regulate early germ cell development and identifies eggpl as a key player in this process.

Effect of estrogen receptor α on cardiopulmonary adaptation to chronic developmental hypoxia in a rat model.

Humans living at high-altitude (HA) have adapted to this environment by increasing pulmonary vascular and alveolar growth. RNA sequencing data from a novel murine model that mimics this phenotypical response to HA suggested estrogen signaling via estrogen receptor alpha (ERα) may be involved in this adaptation. We hypothesized ERα was a key mediator in the cardiopulmonary adaptation to chronic hypoxia and sought to delineate the mechanistic role ERα contributes to this process by exposing novel loss-of-function ERα mutant (ERαMut) rats to simulated HA. ERα mutant or wild-type (wt) rats were exposed to normoxia or hypoxia starting at conception and continued postnatally until 6 wk of age. Both wt and ERαMut animals born and raised in hypoxia exhibited lower body mass and higher hematocrits, total alveolar volumes (Va), diffusion capacities of carbon monoxide (DLCO), pulmonary arteriole (PA) wall thickness, and Fulton indices than normoxia animals. Right ventricle adaptation was maintained in the setting of hypoxia. Although no major physiologic differences were seen between wt and ERαMut animals at either exposure, ERαMut animals exhibited smaller mean linear intercepts (MLI) and increased PA total and lumen areas. Hypoxia exposure or ERα loss-of-function did not affect lung mRNA abundance of vascular endothelial growth factor, angiopoietin 2, or apelin. Sexual dimorphisms were noted in PA wall thickness and PA lumen area in ERαMut rats. In summary, in room air-exposed rats and rats with peri- and postnatal hypoxia exposure, ERα loss-of-function was associated with decreased alveolar size (primarily driven by hypoxic animals) and increased PA remodeling.NEW & NOTEWORTHY By exposing novel loss-of-function estrogen receptor alpha (Erα) mutant rats to a novel model of human high-altitude exposure, we demonstrate that ERα has subtle but inconsistent effects on endpoints relevant to cardiopulmonary adaptation to chronic hypoxia. Given that we observed some histologic, sex, and genotype differences, further research into cell-specific effects of ERα during hypoxia-induced cardiopulmonary adaptation is warranted.

Expression-environment associations in transcriptomic heat stress responses for a global plant lineage.

The increasing frequency and severity of heatwaves will intensify stress on plants. Given regional variation in heatwave exposure and expected differences in thermal tolerance between species it is unlikely that all plant species will be affected equally by climate change. However, little is currently known about variation in the responses of plants to heat stress, or how those responses differ among closely related species adapted to different environments. Here we quantify the response of 17 Acacia species (175 RNA-seq libraries), from across Australia's diverse biomes, to a multi-day experimental heatwave treatment to identify variation in transcriptomic and physiological responses to heat stress. Genes with known heat response functions showed consistent responses across Acacia species. Up to 10% of all genes and over 100 gene families showed significant clinal variation in the magnitude of their expression plasticity across species. Specifically, gene families linked to the temperature stress response were overrepresented among significant relationships with home range temperature conditions. Gene expression responses seen on the first day of the heatwave were more frequently associated with home range climates, while expression responses by day four were more commonly related to photosystem II acclimation. Comparative transcriptomics on non-model species has the potential to provide key information on stress response plasticity, especially when linked with our understanding of model species. Our study indicates that the pressing challenge to identifying potentially vulnerable species to climate change could be benefited by the further exploration of clinal variation in transcriptome plasticity.

Tecovirimat Resistance in Mpox Patients, United States, 2022-2023.

During the 2022 multinational outbreak of monkeypox virus (MPXV) infection, the antiviral drug tecovirimat (TPOXX; SIGA Technologies, Inc., https://www.siga.com) was deployed in the United States on a large scale for the first time. The MPXV F13L gene homologue encodes the target of tecovirimat, and single amino acid changes in F13 are known to cause resistance to tecovirimat. Genomic sequencing identified 11 mutations previously reported to cause resistance, along with 13 novel mutations. Resistant phenotype was determined using a viral cytopathic effect assay. We tested 124 isolates from 68 patients; 96 isolates from 46 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of tecovirimat treatment, whereas most isolates identified by routine surveillance of patients not treated with tecovirimat remained sensitive. The frequency of resistant viruses remains relatively low (<1%) compared with the total number of patients treated with tecovirimat.

Phylogenomics reveals extreme gene tree discordance in a lineage of dominant trees: hybridization, introgression, and incomplete lineage sorting blur deep evolutionary relationships despite clear species groupings in Eucalyptus subgenus Eudesmia.

Eucalypts are a large and ecologically important group of plants on the Australian continent, and understanding their evolution is important in understanding evolution of the unique Australian flora. Previous phylogenies using plastome DNA, nuclear-ribosomal DNA, or random genome-wide SNPs, have been confounded by limited genetic sampling or by idiosyncratic biological features of the eucalypts, including widespread plastome introgression. Here we present phylogenetic analyses of Eucalyptus subgenus Eudesmia (22 species from western, northern, central and eastern Australia), in the first study to apply a target-capture sequencing approach using custom, eucalypt-specific baits (of 568 genes) to a lineage of Eucalyptus. Multiple accessions of all species were included, and target-capture data were supplemented by separate analyses of plastome genes (average of 63 genes per sample). Analyses revealed a complex evolutionary history likely shaped by incomplete lineage sorting and hybridization. Gene tree discordance generally increased with phylogenetic depth. Species, or groups of species, toward the tips of the tree are mostly supported, and three major clades are identified, but the branching order of these clades cannot be confirmed with confidence. Multiple approaches to filtering the nuclear dataset, by removing genes or samples, could not reduce gene tree conflict or resolve these relationships. Despite inherent complexities in eucalypt evolution, the custom bait kit devised for this research will be a powerful tool for investigating the evolutionary history of eucalypts more broadly.

Wingless promotes EGFR signaling in follicle stem cells to maintain self-renewal.

Adult stem cell niche boundaries must be precisely maintained to facilitate the segregation of stem cell and daughter cell fates. However, the mechanisms that govern this process in epithelial tissues are not fully understood. In this study, we investigated the relationship between two signals, Wnt and EGFR, that are necessary for self-renewal of the epithelial follicle stem cells (FSCs) in the Drosophila ovary, but must be downregulated in cells that have exited the niche to allow for differentiation. We found that Wingless produced by inner germarial sheath (IGS) cells acts over a short distance to activate Wnt signaling in FSCs, and that movement across the FSC niche boundary is limited. In addition, we show that Wnt signaling functions genetically upstream of EGFR signaling by activating the expression of the EGFR ligand, Spitz, and that constitutive activation of EGFR partially rescues the self-renewal defect caused by loss of Wnt signaling. Collectively, our findings support a model in which the Wnt and EGFR pathways operate in a signaling hierarchy to promote FSC self-renewal.

Neighborhood greenness and burden of non-communicable diseases in Sub-Saharan Africa: A multi-country cross-sectional study.

Population growth, demographic transitions and urbanization in sub-Saharan Africa (SSA) will increase non-communicable disease (NCD) burden. We studied the association between neighborhood greenness and NCDs in a multi-country cross-sectional study. Among 1178 participants, in adjusted models, a 0.11 unit NDVI increase was associated with lower BMI (ß: -1.01, 95% CI: -1.35, -0.67), and lower odds of overweight/obesity (aOR: 0.73, 95% CI: 0.62, 0.85), diabetes (aOR: 0.77, 95% CI: 0.62, 0.96), and having ≥3 allostatic load components compared to none (aOR: 0.66, 95% CI: 0.52, 0.85). Except for diabetes, these remained statistically significant after Bonferroni correction. We observed no association between NDVI and hypertension or cholesterol. Our findings are consistent with health benefits of neighborhood greenness reported in other countries, suggesting greening strategies could be considered as part of broader public health interventions for NCDs.

Drosophila anion exchanger 2 is required for proper ovary development and oogenesis.

Understanding how cell fate decisions are regulated is a central question in stem cell biology. Recent studies have demonstrated that intracellular pH (pHi) dynamics contribute to this process. Indeed, the pHi of cells within a tissue is not simply a consequence of chemical reactions in the cytoplasm and other cellular activity, but is actively maintained at a specific setpoint in each cell type. We found previously that the pHi of cells in the follicle stem cell (FSC) lineage in the Drosophila ovary increases progressively during differentiation from an average of 6.8 in the FSCs, to 7.0 in newly produced daughter cells, to 7.3 in more differentiated cells. Two major regulators of pHi in this lineage are Drosophila sodium-proton exchanger 2 (dNhe2) and a previously uncharacterized gene, CG8177, that is homologous to mammalian anion exchanger 2 (AE2). Based on this homology, we named the gene anion exchanger 2 (ae2). Here, we generated null alleles of ae2 and found that homozygous mutant flies are viable but have severe defects in ovary development and adult oogenesis. Specifically, we find that ae2 null flies have smaller ovaries, reduced fertility, and impaired follicle formation. In addition, we find that the follicle formation defect can be suppressed by a decrease in dNhe2 copy number and enhanced by the overexpression of dNhe2, suggesting that this phenotype is due to the dysregulation of pHi. These findings support the emerging idea that pHi dynamics regulate cell fate decisions and our studies provide new genetic tools to investigate the mechanisms by which this occurs.

Bat and Lyssavirus Exposure among Humans in Area that Celebrates Bat Festival, Nigeria, 2010 and 2013.

Using questionnaires and serologic testing, we evaluated bat and lyssavirus exposure among persons in an area of Nigeria that celebrates a bat festival. Bats from festival caves underwent serologic testing for phylogroup II lyssaviruses (Lagos bat virus, Shimoni bat virus, Mokola virus). The enrolled households consisted of 2,112 persons, among whom 213 (10%) were reported to have ever had bat contact (having touched a bat, having been bitten by a bat, or having been scratched by a bat) and 52 (2%) to have ever been bitten by a bat. Of 203 participants with bat contact, 3 (1%) had received rabies vaccination. No participant had neutralizing antibodies to phylogroup II lyssaviruses, but >50% of bats had neutralizing antibodies to these lyssaviruses. Even though we found no evidence of phylogroup II lyssavirus exposure among humans, persons interacting with bats in the area could benefit from practicing bat-related health precautions.

Inactivated Rabies Virus-Based Ebola Vaccine Preserved by Vaporization Is Heat-Stable and Immunogenic Against Ebola and Protects Against Rabies Challenge.

BACKGROUND: Ebola virus (EBOV) is a highly lethal member of the Filoviridae family associated with human hemorrhagic disease. Despite being a sporadic disease, it caused a large outbreak in 2014-2016 in West Africa and another outbreak recently in the Democratic Republic of Congo. Several vaccine candidates are currently in preclinical and clinical studies but none are stable without cold chain storage. METHODS: We used preservation by vaporization (PBV), a novel processing technology to heat-stabilize FiloRab1 (inactivated rabies-based Ebola vaccine), a candidate Ebola vaccine, and stored the vials at temperatures ranging from 4°C to 50°C for 10 days to 12 months. We immunized Syrian hamsters with the best long-term stable FiloRab1 PBV vaccines and challenged them with rabies virus (RABV). RESULTS: Syrian hamsters immunized with FiloRab1 PBV-processed vaccines stored at temperatures of 4°C and 37°C for 6 months, and at 50°C for 2 weeks, seroconverted against both RABV-G and EBOV-GP. Notably, all of the FiloRab1 PBV vaccines proved to be 100% effective in a RABV challenge model. CONCLUSIONS: We successfully demonstrated that the FiloRab1 PBV vaccines are stable and efficacious for up to 6 months when stored at temperatures ranging from 4°C to 37°C and for up to 2 weeks at 50°C.

Humanizing lesbian characters on television: Exploring their characterization and interpersonal relationships.

The present study examined representations of 39 lesbian characters' interpersonal relationships and characterological profiles in 20 "lesbian-centric" television shows from 2008 to 2018. Using a mixed-methods approach, the following variables were analyzed: the quality of lesbian characters' relationships with their parents, children, close friends, and romantic partners; their sense of acceptance from these relationships; their gender presentation and expression; the use of homonegative tropes in targeted programs; portrayals of sexual behaviors; and demographic characteristics. Results indicated that the majority of the lesbian characters were young, cisgender, white, middle-class, and portrayed within various homonegative tropes. Most of the lesbian characters shared positive relationships with their mothers, children, close friends, and romantic partners, but not with their fathers. Qualitative findings evidenced support for the quantitative analyses; however, they revealed that lesbian characters' friendships were not fully developed. The strengths and limitations of this study, and directions for future research are outlined.

Phosphorylated Groucho delays differentiation in the follicle stem cell lineage by providing a molecular memory of EGFR signaling in the niche.

In the epithelial follicle stem cells (FSCs) of the Drosophila ovary, Epidermal Growth Factor Receptor (EGFR) signaling promotes self-renewal, whereas Notch signaling promotes differentiation of the prefollicle cell (pFC) daughters. We have identified two proteins, Six4 and Groucho (Gro), that link the activity of these two pathways to regulate the earliest cell fate decision in the FSC lineage. Our data indicate that Six4 and Gro promote differentiation towards the polar cell fate by promoting Notch pathway activity. This activity of Gro is antagonized by EGFR signaling, which inhibits Gro-dependent repression via p-ERK mediated phosphorylation. We have found that the phosphorylated form of Gro persists in newly formed pFCs, which may delay differentiation and provide these cells with a temporary memory of the EGFR signal. Collectively, these findings demonstrate that phosphorylated Gro labels a transition state in the FSC lineage and describe the interplay between Notch and EGFR signaling that governs the differentiation processes during this period.

Cigarette Smoking Impairs Adipose Stromal Cell Vasculogenic Activity and Abrogates Potency to Ameliorate Ischemia.

Cigarette smoking (CS) adversely affects the physiologic function of endothelial progenitor, hematopoietic stem and progenitor cells. However, the effect of CS on the ability of adipose stem/stromal cells (ASC) to promote vasculogenesis and rescue perfusion in the context of ischemia is unknown. To evaluate this, ASC from nonsmokers (nCS-ASC) and smokers (CS-ASC), and their activity to promote perfusion in hindlimb ischemia models, as well as endothelial cell (EC) survival and vascular morphogenesis in vitro were assessed. While nCS-ASC improved perfusion in ischemic limbs, CS-ASC completely lost this therapeutic effect. In vitro vasculogenesis assays revealed that human CS-ASC and ASC from CS-exposed mice showed compromised support of EC morphogenesis into vascular tubes, and the CS-ASC secretome was less potent in supporting EC survival/proliferation. Comparative secretome analysis revealed that CS-ASC produced lower amounts of hepatocyte growth factor (HGF) and stromal cell-derived growth factor 1 (SDF-1). Conversely, CS-ASC secreted the angiostatic/pro-inflammatory factor Activin A, which was not detected in nCS-ASC conditioned media (CM). Furthermore, higher Activin A levels were measured in EC/CS-ASC cocultures than in EC/nCS-ASC cocultures. CS-ASC also responded to inflammatory cytokines with 5.2-fold increase in Activin A secretion, whereas nCS-ASC showed minimal Activin A induction. Supplementation of EC/CS-ASC cocultures with nCS-ASC CM or with recombinant vascular endothelial growth factor, HGF, or SDF-1 did not rescue vasculogenesis, whereas inhibition of Activin A expression or activity improved network formation up to the level found in EC/nCS-ASC cocultures. In conclusion, ASC of CS individuals manifest compromised in vitro vasculogenic activity as well as in vivo therapeutic activity. Stem Cells 2018;36:856-867.

The cost of diabetic foot ulcers and amputations to the National Health Service in England.

AIM: To estimate the healthcare costs of diabetic foot disease in England. METHODS: Patient-level data sets at a national and local level, and evidence from clinical studies, were used to estimate the annual cost of health care for foot ulceration and amputation in people with diabetes in England in 2014-2015. RESULTS: The cost of health care for ulceration and amputation in diabetes in 2014-2015 is estimated at between £837 million and £962 million; 0.8% to 0.9% of the National Health Service (NHS) budget for England. More than 90% of expenditure was related to ulceration, and 60% was for care in community, outpatient and primary settings. For inpatients, multiple regression analysis suggested that ulceration was associated with a length of stay 8.04 days longer (95% confidence interval 7.65 to 8.42) than that for diabetes admissions without ulceration. CONCLUSIONS: Diabetic foot care accounts for a substantial proportion of healthcare expenditure in England, more than the combined cost of breast, prostate and lung cancers. Much of this expenditure arises through prolonged and severe ulceration. If the NHS were to reduce the prevalence of diabetic foot ulcers in England by one-third, the gross annual saving would be more than £250 million. Diabetic foot ulceration is a large and growing problem globally, and it is likely that there is potential to improve outcomes and reduce expenditure in many countries.

Male Body Image Self-Consciousness During Physical Intimacy (M-BISC): Validating the M-BISC With Gay Men.

INTRODUCTION: An expanding area of research within the realm of body image is its role in human sexual functioning, which denotes people's overall satisfaction with their performance during a specific sexual encounter. Traditionally, studies investigating the association between body image and sexual functioning have focused on women. The Male Body Image Self-Consciousness Scale (M-BISC) was developed to exclusively assess male body image self-consciousness during sexual activity using a sample consisting primarily of heterosexual men. AIM: The purpose of the current study is to evaluate the dimensionality, reliability, and validity of the M-BISC with a sample of gay men. Research suggests that sexual difficulties and body image concerns can overlap and interrelate. Therefore, 2 subscales (erectile difficulties and body embarrassment) from the Gay Male Sexual Difficulties Scale (GMSDS) were used to assess the validity of the scale. METHODS: 1,930 men self-identifying as "exclusively gay" completed an online survey consisting of demographics, the M-BISC, and the GMSDS (erectile difficulties and body embarrassment subscales). MAIN OUTCOME MEASURE: The replicability of the M-BISC factor structure with a gay male sample was determined using an exploratory and confirmatory factor analysis. Additionally, the GMSDS (erectile difficulties and body embarrassment subscales) was used to determine the validity of the M-BISC. RESULTS: Exploratory and confirmatory factor analyses revealed that, following the removal of 3 items, the M-BISC was unidimensional. Scale score reliability for the 14-item M-BISC was good. Finally, as predicted, scores on the M-BISC correlated with scores on the GMSDS (ie, greater sexual difficulties). CLINICAL IMPLICATIONS: The results indicate that assessment scales developed using samples consisting primarily of heterosexual men may not be appropriate for use with gay men in their original form. Thus, limiting the accuracy of the measurement and increasing the risk of misdiagnoses. STRENGTH & LIMITATIONS: Strengths of this study include a large sample of exclusively gay men and the utilization of best-practice statistical analysis for assessing factor structure, validity, and reliability of measures. Limitations include the assumption that the M-BISC should be used in lieu of a novel scale developed exclusively for gay men. Further, the study utilizes an Internet sample consisting primarily of Caucasian gay men. CONCLUSION: Results of the current study illustrate that the M-BISC is a valid tool to measure gay men's body concerns during intimacy. More importantly, it also highlights gay men's elevated body concerns during intimacy and the need to understand the etiology of these apprehensions. Currently, there is a noticeable gap in the literature regarding the cause of gay male body concerns that have potential clinic implications. Kiss MJ, Morrison TG, McDonagh LK. Male Body Image Self-Consciousness During Physical Intimacy (M-BISC): Validating the M-BISC With Gay Men. J Sex Med 2018;16:307-315.

Utilization of Spinal Intra-operative Three-dimensional Navigation by Canadian Surgeons and Trainees: A Population-based Time Trend Study.

BACKGROUND: Computer-assisted navigation (CAN) improves the accuracy of spinal instrumentation in vertebral fractures and degenerative spine disease; however, it is not widely adopted because of lack of training, high capital costs, workflow hindrances, and accuracy concerns. We characterize shifts in the use of spinal CAN over time and across disciplines in a single-payer health system, and assess the impact of intra-operative CAN on trainee proficiency across Canada. METHODS: A prospectively maintained Ontario database of patients undergoing spinal instrumentation from 2005 to 2014 was reviewed retrospectively. Data were collected on treated pathology, spine region, surgical approach, institution type, and surgeon specialty. Trainee proficiency with CAN was assessed using an electronic questionnaire distributed across 15 Canadian orthopedic surgical and neurosurgical programs. RESULTS: In our provincial cohort, 16.8% of instrumented fusions were CAN-guided. Navigation was used more frequently in academic institutions (15.9% vs. 12.3%, p<0.001) and by neurosurgeons than orthopedic surgeons (21.0% vs. 12.4%, p<0.001). Of residents and fellows 34.1% were fully comfortable using spinal CAN, greater for neurosurgical than orthopedic surgical trainees (48.1% vs. 11.8%, p=0.008). The use of CAN increased self-reported proficiency in thoracic instrumentation for all trainees by 11.0% (p=0.036), and in atlantoaxial instrumentation for orthopedic trainees by 18.0% (p=0.014). CONCLUSIONS: Spinal CAN is used most frequently by neurosurgeons and in academic centers. Most spine surgical trainees are not fully comfortable with the use of CAN, but report an increase in technical comfort with CAN guidance particularly for thoracic instrumentation. Increased education in spinal CAN for trainees, particularly at the fellowship stage and, specifically, for orthopedic surgery, may improve adoption.

CONTEXTE: La chirurgie assistée par ordinateur (CAO) permet d'améliorer la précision de l'exploration instrumentale employée dans le cas de fractures vertébrales et de maladies dégénératives de la colonne vertébrale. Cela dit, elle n'a pas encore été adoptée à grande échelle en raison d'un manque de formation, de coûts d'immobilisation considérables, d'obstacles liés à l'organisation du travail et de doutes quant à son exactitude. C'est dans cette perspective que nous voulons décrire, parmi divers champs de pratique, les transformations se rapportant au fil du temps à l'utilisation de la CAO de la colonne vertébral dans le cadre d'un régime de santé universel à payeur unique. Qui plus est, nous voulons aussi évaluer l'impact de la CAO en ce qui a trait aux compétences des stagiaires partout au Canada. MÉTHODES: Pour ce faire, nous avons passé en revue de façon rétrospective une base de données tenue à jour prospectivement au sujet de patients ontariens ayant été soumis de 2005 à 2014 à une exploration instrumentale de la colonne vertébrale. Les données obtenues portaient sur le type de pathologie traitée, sur la région de la colonne vertébrale visée, sur l'approche chirurgicale privilégiée, sur le type d'établissement et sur la spécialité du chirurgien ayant intervenu. Les compétences des stagiaires en matière de CAO ont également été évaluées à l'aide d'un questionnaire en ligne diffusé au sein de 15 programmes canadiens de chirurgie orthopédique et de neurochirurgie. RÉSULTATS: En tout, 16,8 % des fusions instrumentées réalisées au sein de notre cohorte ontarienne l'ont été à l'aide de la technique de la CAO. Cette dernière a été utilisée plus fréquemment dans des établissements d'enseignement universitaire (15,9 % par opposition à 12,3 % pour les autres; p<0,001) mais aussi plus souvent par des neurochirurgiens (21,0 % par opposition à 12,4 % par des chirurgiens orthopédiques; p<0,001). En outre, 34,1 % des résidents et des médecins suivant une formation complémentaire étaient parfaitement à l'aise dans l'utilisation de la CAO de la colonne vertébrale (48,1 % de ceux se spécialisant en neurochirurgie par opposition à 11,8 % de ceux se spécialisant en chirurgie orthopédique; p = 0,008). L'utilisation de la CAO a par ailleurs entraîné une augmentation, auto-déclarée, de 11,0 % de l'aptitude à faire usage de l'exploration instrumentale thoracique chez tous les stagiaires (p = 0,036); dans le cas de l'exploration instrumentale atlanto-axiale, cette augmentation a été de 18,0 % (p = 0,014) chez les stagiaires en chirurgie orthopédique. CONCLUSIONS: La CAO de la colonne vertébrale est employée le plus souvent par les neurochirurgiens dans des établissements d'enseignement universitaire. La plupart des stagiaires en chirurgie de la colonne vertébrale ne sont pas entièrement à l'aise en ce qui concerne l'utilisation de la CAO. Toutefois, ils ont signalé une augmentation de leur aisance à utiliser la CAO et à bénéficier de son assistance, en particulier dans des cas d'exploration instrumentale thoracique. En somme, une plus ample formation en matière de CAO de la colonne vertébrale offerte aux stagiaires, particulièrement à ceux suivant une formation complémentaire et dans le champ de la chirurgie orthopédique, pourrait favoriser son adoption.

Position Statement on Atopic Dermatitis in Sub-Saharan Africa: current status and roadmap.

BACKGROUND: The first International Society of Atopic Dermatitis (ISAD) global meeting dedicated to atopic dermatitis (AD) in Sub-Saharan Africa (SSA) was held in Geneva, Switzerland in April 2019. A total of 30 participants were present at the meeting, including those from 17 SSA countries, representatives of the World Health Organization (WHO), the International Foundation for Dermatology (IFD) (a committee of the International League of Dermatological Societies, ILDS www.ilds.org), the Fondation pour la Dermatite Atopique, as well as specialists in telemedicine, artificial intelligence and therapeutic patient education (TPE). RESULTS: AD is one of the most prevalent chronic inflammatory skin diseases in SSA. Besides neglected tropical diseases (NTDs) with a dermatological presentation, AD requires closer attention from the WHO and national Departments of Health. CONCLUSIONS: A roadmap has been defined with top priorities such as access to essential medicines and devices for AD care, in particular emollients, better education of primary healthcare workers for adequate triage (e.g. better educational materials for skin diseases in pigmented skin generally and AD in particular, especially targeted to Africa), involvement of traditional healers and to a certain extent also patient education, bearing in mind the barriers to effective healthcare faced in SSA countries such as travel distances to health facilities, limited resources and the lack of dermatological expertise. In addition, several initiatives concerning AD research in SSA were discussed and should be implemented in close collaboration with the WHO and assessed at follow-up meetings, in particular, at the next ISAD meeting in Seoul, South Korea and African Society of Dermatology and Venereology (ASDV) meeting in Nairobi, Kenya, both in 2020.

Stress and corticosteroids regulate rat hippocampal mitochondrial DNA gene expression via the glucocorticoid receptor.

Glucocorticoids (GCs) are involved in stress and circadian regulation, and produce many actions via the GC receptor (GR), which is classically understood to function as a nuclear transcription factor. However, the nuclear genome is not the only genome in eukaryotic cells. The mitochondria also contain a small circular genome, the mitochondrial DNA (mtDNA), that encodes 13 polypeptides. Recent work has established that, in the brain and other systems, the GR is translocated from the cytosol to the mitochondria and that stress and corticosteroids have a direct influence on mtDNA transcription and mitochondrial physiology. To determine if stress affects mitochondrially transcribed mRNA (mtRNA) expression, we exposed adult male rats to both acute and chronic immobilization stress and examined mtRNA expression using quantitative RT-PCR. We found that acute stress had a main effect on mtRNA expression and that expression of NADH dehydrogenase 1, 3, and 6 (ND-1, ND-3, ND-6) and ATP synthase 6 (ATP-6) genes was significantly down-regulated. Chronic stress induced a significant up-regulation of ND-6 expression. Adrenalectomy abolished acute stress-induced mtRNA regulation, demonstrating GC dependence. ChIP sequencing of GR showed that corticosterone treatment induced a dose-dependent association of the GR with the control region of the mitochondrial genome. These findings demonstrate GR and stress-dependent transcriptional regulation of the mitochondrial genome in vivo and are consistent with previous work linking stress and GCs with changes in the function of brain mitochondria.