Transmission risk of respiratory viruses in natural and mechanical ventilation environments: implications for SARS-CoV-2 transmission in Africa.

Respiratory viruses can be transmitted through contact, droplet and airborne routes. Viruses that are not naturally airborne may be aerosolised during medical procedures and transmitted to healthcare workers. Most resource-limited healthcare settings lack complex air handling systems to filter air and create pressure gradients that are necessary for minimising viral transmission. This review explores the association between ventilation and the transmission of respiratory viruses like SAR-CoV-2. When used appropriately, both natural and mechanical ventilation can decrease the concentration of viral aerosols, thereby reducing transmission. Although mechanical ventilation systems are more efficient, installation and maintenance costs limit their use in resource-limited settings, whereas the prevailing climate conditions make natural ventilation less desirable. Cost-effective hybrid systems of natural and mechanical ventilation may overcome these limitations

Prevalence of Epilepsy, Human Cysticercosis, and Porcine Cysticercosis in Western Kenya

Cysticercosis is the leading cause of acquired epilepsy worldwide and has been shown to be highly prevalent in pig populations in western Kenya. We conducted a community-based door-to-door survey in a region of western Kenya with a high proportion of pig-keeping households. Persons with epilepsy (PWE) were determined using a screening questionnaire followed by a neurologist evaluation. Cysticercosis serum apDia antigen ELISAs and Western blot for LLGP and rT24h antigen were performed on all PWE and 2% of screen-negative patients. All PWE or people with positive apDia underwent contrast-enhanced brain computed tomography (CT). Of a sample of 810 village residents, 660 (81%) were present in the homestead, of whom 648 (98%) participated. Of these, 17 were confirmed to have lifetime epilepsy, an estimated crude prevalence of 2.6%. No humans with (N = 17) or without (N = 12) epilepsy had serological evidence of cysticercosis infection. Fourteen PWE and one individual with borderline positive apDia antigen ELISA underwent brain CT; none had radiographic findings consistent with neurocysticercosis. Nearly 30% of households kept pigs, with 69% always tethered in both wet and dry seasons. More than 8% (6/72) of pigs had palpable lingual cysts; these pigs all originated from homesteads with latrines, one-third of which were free-ranging at least some of the time. Epilepsy prevalence in our study was greater than the national prevalence, but we found no individuals with epilepsy attributable to cysticercosis. Additional studies are required to identify causes of epilepsy, human and porcine cysticercosis, the role of spatial clustering, and protective factors like host-pathogen immunity

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Steroidogenic Enzymes and Stem Cell Markers Are Upregulated during Androgen Deprivation in Prostate Cancer

Considerable levels of testosterone and dihydrotestosterone (DHT) are found in prostate cancer (PCa) tissue after androgen deprivation therapy. Treatment of surviving cancer-initiating cells and the ability to metabolize steroids from precursors may be the keystones for the appearance of recurrent tumors. To study this hypothesis, we assessed the expression of several steroidogenic enzymes and stem cell markers in clinical PCa samples and cell cultures during androgen depletion. Gene expression profiles were determined by microarray or qRT-PCR. In addition, we measured cell viability and analyzed stem cell marker expression in DuCaP cells by immunocytochemistry. Seventy patient samples from different stages of PCa, and the PCa cell line DuCaP were included in this study. The androgen receptor (AR) and enzymes (AKR1C3, HSD17B2, HSD17B3, UGT2B15 and UGT2B17 ) that are involved in the metabolism of adrenal steroids were upregulated in castration resistant prostate cancer (CRPC). In vitro, some DuCaP cells survived androgen depletion, and eventually gave rise to a culture adapted to these conditions. During and after this transition, most of the steroidogenic enzymes were upregulated. These cells also are enriched with stem/progenitor cell markers cytokeratin 5 (CK5) and ATP-binding cassette sub-family G member 2 (ABCG2). Similarly, putative stem/progenitor cell markers CK5, c-Kit, nestin, CD44, c-met, ALDH1A1, α2-integrin, CD133, ABCG2, CXCR4 and POU5F1 were upregulated in clinical CRPC. The upregulation of steroidogenic enzymes and stem cell markers in recurrent tumors suggests that cancer initiating cells can expand by adaptation to their T/DHT deprived environment. Therapies targeting the metabolism of adrenal steroids by the tumor may prove effective in preventing tumor regrowth

Burden of neurological and neurocognitive impairment in pediatric sickle cell anemia in Uganda (BRAIN SAFE): a cross-sectional study

Background Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Detailed evaluations in sub-Saharan Africa are limited. Methods We aimed to establish the frequency and types of pediatric brain injury in a cross-sectional study at a large SCA clinic in Kampala, Uganda in a randomly selected sample of 265 patients with HbSS ages 1–12 years. Brain injury was defined as one or more abnormality on standardized testing: neurocognitive impairment using an age-appropriate test battery, prior stroke by examination or transcranial Doppler (TCD) velocities associated with stroke risk in children with SCA (cerebral arterial time averaged mean maximum velocity ≥ 170 cm/second). Results Mean age was 5.5 ± 2.9 years; 52.3% were male. Mean hemoglobin was 7.3 ± 1.01 g/dl; 76.4% had hemoglobin < 8.0 g/dl. Using established international standards, 14.7% were malnourished, and was more common in children ages 5–12. Overall, 57 (21.5%) subjects had one to three abnormal primary testing. Neurocognitive dysfunction was found in 27, while prior stroke was detected in 15 (5.7%). The most frequent abnormality was elevated TCD velocity 43 (18.1%), of which five (2.1%) were in the highest velocity range of abnormal. Only impaired neurocognitive dysfunction increased with age (OR 1.44, 95%CI 1.23–1.68), p < 0.001). In univariate models, malnutrition defined as wasting (weight-for-height ≤ −2SD), but not sex or hemoglobin, was modestly related to elevated TCD (OR 1.37, 95%CI 1.01–1.86, p = 0.04). In adjusted models, neurocognitive dysfunction was strongly related to prior stroke (OR 6.88, 95%CI 1.95–24.3, p = .003) and to abnormal TCD (OR 4.37, 95%CI 1.30, p = 0.02). In a subset of 81 subjects who were enriched for other abnormal results, magnetic resonance imaging and angiography (MRI/MRA) detected infarcts and/or arterial stenosis in 52%. Thirteen subjects (25%) with abnormal imaging had no other abnormalities detected. Conclusions The high frequency of neurocognitive impairment or other abnormal results describes a large burden of pediatric SCA brain disease in Uganda. Evaluation by any single modality would have underestimated the impact of SCA. Testing the impact of hydroxyurea or other available disease-modifying interventions for reducing or preventing SCA brain effects is warranted

Brain Malformations Associated With Knobloch Syndrome-Review of Literature, Expanding Clinical Spectrum, and Identification of Novel Mutations

BACKGROUND: Knobloch syndrome is a rare, autosomal recessive, developmental disorder characterized by stereotyped ocular abnormalities with or without occipital skull deformities (encephalocele, bone defects, and cutis aplasia). Although there is clear heterogeneity in clinical presentation, central nervous system malformations, aside from the characteristic encephalocele, have not typically been considered a component of the disease phenotype. METHODS: Four patients originally presented for genetic evaluation of symptomatic structural brain malformations. Whole-genome genotyping, whole-exome sequencing, and confirmatory Sanger sequencing were performed. Using immunohistochemical analysis, we investigated the protein expression pattern of COL18A1 in the mid-fetal and adult human cerebral cortex and then analyzed the spatial and temporal changes in the expression pattern of COL18A1 during human cortical development using the Human Brain Transcriptome database. RESULTS: We identified two novel homozygous deleterious frame-shift mutations in the COL18A1 gene. On further investigation of these patients and their families, we found that many exhibited certain characteristics of Knobloch syndrome, including pronounced ocular defects. Our data strongly support an important role for COL18A1 in brain development, and this report contributes to an enhanced characterization of the brain malformations that can result from deficiencies of collagen XVIII. CONCLUSIONS: This case series highlights the diagnostic power and clinical utility of whole-exome sequencing technology allowing clinicians and physician scientists to better understand the pathophysiology and presentations of rare diseases. We suggest that patients who are clinically diagnosed with Knobloch syndrome and/or found to have COL18A1. mutations via genetic screening should be investigated for potential structural brain abnormalities even in the absence of an encephalocele