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Background: Malaria is a significant health challenge in Sierra Leone, particularly affecting pregnant women and children under five years of age. Despite efforts to reduce malaria cases, its prevalence remains high. The Sierra Leone National Malaria Elimination Strategic Plan (NMESP) 2021-2025 aims to reduce the malaria burden significantly through universal access to Insecticide Treated Nets (ITNs)., Objective: This study evaluates the knowledge and utilization of ITNs for malaria control in the Moyamba and Bo districts of Sierra Leone (at the Njala University's Main Campus in Moyamba District and Towama Location on Bo Campus in Bo District). It assesses awareness levels, factors associated with ITN use, and the effectiveness of current campaign strategies., Methods: A cross-sectional survey was conducted from July to September 2023, involving 742 participants from the Moyamba and Bo districts. Data were collected using a pretested interview guide covering ITN ownership, usage, and challenges. Descriptive statistics and Pearson's Chi-squared test were used for data analysis., Results: Of the respondents, 84.8% received training on ITN usage, primarily from health workers (46.1%). Most participants (94.7%) understood that ITNs provide protection against mosquitoes, and 84.5% believed in their effectiveness in preventing malaria. Sociodemographic factors like age, sex, education, marital status, and sources of information were significantly associated with ITN knowledge and utilization. Moreover, health workers' campaigns and interpersonal networks (community leaders, plus family and friends) play crucial roles in promoting ITN utilization, while mass media campaigns alone may not suffice. However, 48.2% of the participants found current ITN campaign strategies effective., Conclusion: While awareness and ownership of ITNs are high in the Moyamba and Bo districts, utilization is hindered by various factors, including availability and alternative uses. Enhanced campaign strategies and increased ITN distribution are necessary to improve usage and reduce malaria incidence., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted following the Declaration of Helsinki. A written consent was read to all participants about the nature and purpose of the research survey. We sought ethical approval from the Directorate of Research and Development of Njala University. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Subcutaneous (SC) administration of antibiotics is a practical alternative to IV administration. Cefazolin is widely used for skin and soft tissue infections and other complex infections by IV administration., Methods: In this prospective, cross-over self-controlled study, a single dose of SC cefazolin was administered to 15 stable inpatients established on IV cefazolin as part of their management plan. The equivalent dose of cefazolin was diluted in 50 mL of normal saline via gravity feed over 30 min. Venous blood samples were collected at baseline and 0.5, 1, 2, 4 and 8 h following both the SC and IV doses. Antibiotic concentrations were measured using UPLC-MS/MS. Pharmacokinetic data were analysed using a non-linear mixed-effects modelling approach. Pain scores and infusion site reactions (oedema/erythema) were evaluated., Results: SC cefazolin was well tolerated. The bioavailability of SC administration was 74.8% (95% CI 66.7%-81.7%). Slower absorption from SC tissue was associated with a BMI of ≥30. Lower peak, and higher trough concentrations were observed with SC administration. Although lower bioavailability was observed with SC administration, the PTA for unbound drug concentrations greater than the MIC for more than 90% of the time between doses was higher for SC compared with IV administration at MICs between 0.25 and 4 mg/L. Simulated SC doses of 3 g twice daily had similar PTA to standard IV dosing of 2 g three times daily. A simulated 6 g continuous 24 h infusion of SC cefazolin had a favourable pharmacokinetic profile., Conclusion: SC cefazolin appears to be well tolerated, with an improved pharmacokinetic profile compared with IV administration. Either 3 g twice daily, or 6 g as a 24 h SC infusion could be considered for future evaluation., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Introduction: Selenium (Se), a trace element found in soil and groundwater, is necessary for many biological functions, including cerebrovascular health, through selenoprotein formation. However, high concentrations may be harmful. American Indians face elevated cerebrovascular disease rates, which may be associated with other trace elements, such as Se. This cohort study evaluates associations of Se levels with brain health in older American Indians., Methods: The Strong Heart Study is a longitudinal cohort of American Indians, with comprehensive medical assessments, including trace element exposure assessment. Urinary Se measurements, brain MRIs, and neuropsychological testing were available for 728 participants aged 65-95 at the time of brain MRI. We evaluated associations of urinary Se (divided by urinary creatinine to account for urine dilution) with MRI and neuropsychological tests and adjusted for potential confounders using linear regression models., Results: Increased urinary Se was significantly associated with abnormal sulcal atrophy, ventricular widening, and increased white matter hyperintensity volume but not independent of sociodemographic factors and common vascular co-morbidities. Increased urinary Se was also significantly and independently associated with decreased performance in verbal fluency and processing speed, independent of sociodemographics, vascular co-morbidities, depression, and traumatic brain injury., Discussion: These findings suggest urinary Se levels, particularly those above 50-60 μg Se/g creatinine, are associated with adverse structural brain findings on imaging and diminished cognitive health in older American Indians. This epidemiologic evidence may be useful for public health professionals in evaluating environmental risk, especially within the context of vulnerable populations and high Se intake., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Subcutaneous delivery of antibiotics is a practical alternative to IV administration. Meropenem is commonly used to treat infections caused by resistant Gram-negative organisms., Methods: This was a prospective, crossover self-controlled study in 11 stable inpatients established on meropenem. Participants received a single dose of subcutaneous meropenem, in 50 mL normal saline via gravity feed. Venous blood sampling was performed at baseline, 0.5, 1, 2, 4 and 8 h following the subcutaneous and IV doses. Antibiotic concentrations were measured using UPLC-MS/MS. Pharmacokinetic data were analysed using a non-linear mixed-effects modelling approach. Pain scores and infusion site reactions (oedema/erythema) were assessed., Results: Subcutaneous meropenem was well tolerated. The bioavailability of subcutaneous administration was 81.5% (95% CI 71.6%-93.2%). Increasing BMI was associated with slower absorption from subcutaneous tissue. Compared with IV, subcutaneous administration resulted in lower peak and higher trough concentrations. Despite the lower bioavailability observed, the PTA for free drug concentrations greater than the MIC for more than 40% of the time between doses was higher for subcutaneous than IV administration at MIC values between 0.03 and 8 mg/L. Simulated subcutaneous doses of 1.5 g twice daily, or 3 g continuous 24 h infusion had improved PTA relative to standard IV dosing of 1 g three times daily., Conclusions: Subcutaneous meropenem appears to be well tolerated and has a favourable pharmacokinetic profile. Either 1.5 g twice daily or 3 g as a 24 h subcutaneous infusion could be considered for future evaluation., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Attenuated total reflection (ATR) Fourier transform infrared spectroscopy (FT-IR) is used to characterize a vast array of materials at the molecular level in various industry types. Here we compare the performance of a portable spectrometer with a novel three-bounce-two-pass (3B2P) ATR scanning interface to the same device with a standard one-bounce (1B) ATR, and to a benchtop spectrometer with a 10-bounce (10B) ATR, in ideal sample-interface conditions and an applied dermatological study setting. In both application settings, the benchtop 10B ATR interface showed the highest signal-to-noise ratio (SNR), however, the novel 3B2P produced a six-fold increase in the sensitivity of the portable spectrometer when analyzing isopropanol and showed the greatest consistency of SNR of all devices when analyzing isopropanol and in vivo skin samples. Spectral data were sourced from a recently undertaken dermatological study involving a cohort of 180 healthy, full-term babies, using both 1B and 3B2P interfaces. Use of the 3B2P interface resulted in a 55% greater successful high-quality spectrum collection rate, compared to the 1B, and showed significantly superior SNR at both observed study time points, i.e., birth (1B: 68.37; 3B2P: 77.37), and at four weeks (1B: 74.53; 3B2P: 80.22). The utility of ATR FT-IR spectrometers as a dermatological clinical tool was also exemplified here, by quantifying the moisture level of newborn skin. By gathering rich spectroscopic data on the molecular structure of the skin, this technique holds great promise for the quantification of skin disease-specific biomarkers., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Sierra Leone faces a significant challenge in addressing HIV/AIDS, particularly among adolescent girls and young women. This age group is considered highly vulnerable due to biological factors and social inequalities. Understanding the prevalence of HIV testing in this demographic is crucial for designing effective prevention and treatment strategies. This study investigated the spatial distribution of HIV testing and its associated factors among adolescent girls and young women in Sierra Leone., Methods: Data from the 2019 Sierra Leone Demographic and Health Survey was used for the study. The sample comprised 6,062 adolescent girls and young women between the ages of 15 and 24. Spatial autocorrelation and Moran's I statistic were employed to analyze the spatial distribution of HIV testing. An analysis utilising mixed-effect multilevel binary logistic regression was performed to determine the factors associated with HIV testing. The findings were presented as adjusted odds ratios (aOR) and a 95% confidence interval (CI)., Results: The national prevalence of HIV testing among adolescents and young women in Sierra Leone was 42.1% [40.3,43.9]. Kailahun, Kambia, Tonkolil, some parts of the Western rural area, and Bonthe districts were found to be statistically significant hotspot for HIV testing. Whereas, Karene, Falaba, Bo, kenema, and some parts of Pujuhun were statistically cold spot districts. Adolescent girls and young women aged 20-24 [aOR = 1.63, 95% CI = 1.29, 2.07] had higher odds of HIV testing than those aged 15-19. Those with secondary/higher education [aOR = 1.87, 95% CI = 1.40, 2.51] had higher odds of HIV testing than those with no education. The odds of HIV testing was higher among adolescent girls and young women who use the Internet [aOR = 1.75, 95% CI = 1.32, 2.33] than those who did not use internet. Adolescent girls and young women with one [aOR = 16.56, 95% CI = 12.31, 22.29] and two or more parity [aOR = 16.37, 95% CI = 10.86, 24.68] had higher odds of HIV testing than those with no parity. The likelihood of HIV testing was higher among adolescent girls and young women who had sex below 18 [aOR = 4.54, 95% CI = 3.25, 6.34] and those who had sex at 18+ [aOR = 5.70, 95% CI = 3.84, 8.45] compared to those who had never had sex. Adolescent girls and young women who visited health facilities in the past 12 months [aOR = 1.82, 95% CI = 1.46, 2.26] had higher odds of HIV testing than those who did not., Conclusion: Despite some positive trends, HIV testing rates among adolescent girls and young women in Sierra Leone remain moderate. Spatial autocorrelation analysis consistently revealed hotspots and cold spots for HIV testing, with Kailahun, Kambia, Tonkolil, some parts of the Western rural area, and Bonthe districts remaining persistent hotspots. Age, education, internet use, sexual history, parity, and healthcare access are significant factors influencing testing behaviour. To improve testing rates, the government and policymakers should prioritize educational campaigns, expand internet access, integrate HIV testing into routine healthcare, and address stigma associated with HIV., (© 2024. The Author(s).)

Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful nodules, abscesses and purulent secretions in intertriginous regions. Intense pruritus frequently accompanies HS lesions, adding further discomfort for patients. While Th17 pathway activation is implicated in HS pathogenesis, disease mechanisms are still not fully understood, and therapeutics are lacking. Previous reports raise a potential role for eosinophils in HS, showing a strong association of eosinophil levels with disease severity. To investigate eosinophils in HS, we recruited patients and matched healthy controls and then performed flow-cytometry studies, eosinophil stimulation assays, and lesional skin staining for eosinophils. We found that HS patients reported similar levels of pain and itch. Compared to matched controls, HS blood exhibited decreased mature eosinophils and increased numbers of immature eosinophils, coupled with a significant increase in dermal eosinophilic infiltrates. Additionally, IL-17RA + eosinophils were highly and significantly correlated with multiple HS-related clinical scores. In both stimulated and unstimulated conditions, HS eosinophils showed an inflammatory phenotype versus controls, including an increase in costimulatory T- and B-cell markers (e.g. CD5 and CD40) following all stimulations (TNFα/IL-17A/IL-17F). These findings highlight the significance of pruritus in HS and suggest a higher turnover of eosinophils in HS blood, potentially due to the consumption of eosinophils in skin lesions. Our data delineate the features and functions of eosinophils in HS and suggest that eosinophils participate in disease pathogenesis, advancing Th17-related inflammation. Further studies are needed to investigate eosinophils' response to current HS treatments and their potential as a therapeutic target in the disease., (© 2024 The Author(s). Experimental Dermatology published by John Wiley & Sons Ltd.)

Background: Advanced HIV disease (AHD) in young people living with HIV (PLHIV) is an increasingly pressing public health issue in sub-Saharan Africa. Despite global progress in early HIV testing and reducing HIV-related deaths, many youths experience increased rates of HIV disease progression in sub-Saharan Africa. This study describes the burden, clinical manifestations, and factors for disease progression among young PLHIV aged 15 - 24 years seeking medical services at a major public hospital in Sierra Leone., Methods: We performed a cross-sectional analysis of routinely collected data for PLHIV patients aged 15 to 24 seen at Connaught Hospital in Sierra Leone between September 2022 and March 2023. We estimated the proportion of AHD in young PLHIV and performed logistic regression modelling to explore predictors of AHD. The statistical significance level was set at 0.05 for all statistical tests., Results: Of the 581 PLHIV that were reported, 238 (40.9%) were between the ages of 15 and 24 years, with a median age of 22 (20-24), and 151 (63.5%) were females. On review, 178 (74.8%) has initiated antiretroviral therapy regimen (ART); 117 (65.7%) were actively on ART for ≤ 6 months, while 114 (64%) had interruptions with their ART treatment. The overall prevalence of AHD was 41.6% (99/238); 46.7% (35/68) of young PLHIV at the HIV clinic, and 39.3% (64/163) of admission. Sex-Female (OR, 0.51; 95% CI, 0.28-0.94; p = 0.030), and Tertiary Education level (OR, 0.27; 95% CI, 0.10 - 0.78; p = 0.015) have significantly lower odds of AHD in the entire study population. While for inpatients, Age (young Adults) of PLHIV (OR, 1.23; 95% CI, 1.00-1.52; p = 0.047) had 1.23 times the odds of AHD compared to adolescents, and being female (OR, 0.27; 95% CI, 0.08-0.84; p = 0.024), Overweight-Body mass index (OR, 0.10; 95% CI, 0.01-0.77; p = 0.028), Tertiary Education level (OR, 0.08; 95% CI, 0.01-0.52; p = 0.008) have significantly lower odds of AHD. Common conditions reported for the AHD group in the medical wards are tuberculosis (13.58%), hepatitis B (6.13%), Kaposi sarcoma (3.07%), and oesophagal candidiasis (2.45%)., Conclusion: We reported a high prevalence of advanced HIV among young patients in a tertiary Hospital in Sierra Leone. One in two young PLHIV aged 15 to 24 years reported AHD, emphasizing the need to strengthen public health measures that address access to and retention of HIV services., (© 2024. The Author(s).)

Hidradenitis Suppurativa (HS) is a chronic autoinflammatory skin disease with activated keratinocytes, tunnel formation and a complex immune infiltrate in tissue. The HS microbiome is polymicrobial with an abundance of commensal gram-positive facultative (GPs) Staphylococcus species and gram-negative anaerobic (GNA) bacteria like Prevotella, Fusobacterium and Porphyromonas with increasing predominance of GNAs with disease severity. We sought to define the keratinocyte response to bacteria commonly isolated from HS lesions to probe pathogenic relationships between HS and the microbiome. Type strains of Prevotella nigrescens, Prevotella melaninogenica, Prevotella intermedia, Prevotella asaccharolytica, Fusobacterium nucleatum, as well as Staphylococcus aureus and the normal skin commensal Staphylococcus epidermidis were heat-killed and co-incubated with normal human keratinocytes. RNA was collected and analysed using RNAseq and RT-qPCR. The supernatant was collected from cell culture for protein quantification. Transcriptomic profiles between HS clinical samples and stimulated keratinocytes were compared. Co-staining of patient HS frozen sections was used to localize bacteria in lesions. A mouse intradermal injection model was used to investigate early immune recruitment. TLR4 and JAK inhibitors were used to investigate mechanistic avenues of bacterial response inhibition. GNAs, especially F. nucleatum, stimulated vastly higher CXCL8, IL17C, CCL20, IL6, TNF and IL36γ transcription in normal skin keratinocytes than the GPs S. epidermidis and S. aureus. Using RNAseq, we found that F. nucleatum (and Prevotella) strongly induced the IL-17 pathway in keratinocytes and overlapped with transcriptome profiles of HS patient clinical samples. Bacteria were juxtaposed to activated keratinocytes in vivo, and F. nucleatum strongly recruited murine neutrophil and macrophage migration. Both the TLR4 and pan-JAK inhibitors reduced cytokine production. Detailed transcriptomic profiling of healthy skin keratinocytes exposed to GNAs prevalent in HS revealed a potent, extensive inflammatory response vastly stronger than GPs. GNAs stimulated HS-relevant genes, including many genes in the IL-17 response pathway, and were significantly associated with HS tissue transcriptomes. The close association of activated keratinocytes with bacteria in HS lesions and innate infiltration in murine skin cemented GNA pathogenic potential. These novel mechanistic insights could drive future targeted therapies., (© 2024 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Background: Atopic dermatitis (AD) is characterized by skin barrier defects that are often measured by biophysical tools that observe the functional properties of the stratum corneum (SC)., Objectives: To employ in vivo infrared spectroscopy alongside biophysical measurements to analyse changes in the chemical composition of the SC in relation to AD severity., Methods: We conducted an observational cross-sectional cohort study where attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy measurements were collected on the forearm alongside surface pH, capacitance, erythema and transepidermal water loss (TEWL), combined with tape stripping, in a cohort of 75 participants (55 patients with AD stratified by phenotypic severity and 20 healthy controls). Common FLG variant alleles were genotyped., Results: Reduced hydration, elevated TEWL and redness were all associated with greater AD severity. Spectral analysis showed a reduction in 1465 cm-1 (full width half maximum) and 1340 cm-1 peak areas, indicative of less orthorhombic lipid ordering and reduced carboxylate functional groups, which correlated with clinical severity (lipid structure r = -0.59, carboxylate peak area r = -0.50)., Conclusions: ATR-FTIR spectroscopy is a suitable tool for the characterization of structural skin barrier defects in AD and has potential as a clinical tool for directing individual treatment based on chemical structural deficiencies., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Acoustic telemetry has become a fundamental tool to monitor the movement of aquatic species. Advances in technology, in particular the development of batteries with lives of > 10 years, have increased our ability to track the long-term movement patterns of many species. However, logistics and financial constraints often dictate the locations and deployment duration of acoustic receivers. Consequently, there is often a compromise between optimal array design and affordability. Such constraints can hinder the ability to track marine animals over large spatial and temporal scales. Continental-scale receiver networks have increased the ability to study large-scale movements, but significant gaps in coverage often remain., Methods: Since 2007, the Integrated Marine Observing System's Animal Tracking Facility (IMOS ATF) has maintained permanent receiver installations on the eastern Australian seaboard. In this study, we present the recent enhancement of the IMOS ATF acoustic tracking infrastructure in Queensland to collect data on large-scale movements of marine species in the northeast extent of the national array. Securing a relatively small initial investment for expanding receiver deployment and tagging activities in Queensland served as a catalyst, bringing together a diverse group of stakeholders (research institutes, universities, government departments, port corporations, industries, Indigenous ranger groups and tourism operators) to create an extensive collaborative network that could sustain the extended receiver coverage into the future. To fill gaps between existing installations and maximise the monitoring footprint, the new initiative has an atypical design, deploying many single receivers spread across 2,100 km of Queensland waters., Results: The approach revealed previously unknown broad-scale movements for some species and highlights that clusters of receivers are not always required to enhance data collection. However, array designs using predominantly single receiver deployments are more vulnerable to data gaps when receivers are lost or fail, and therefore "redundancy" is a critical consideration when designing this type of array., Conclusion: Initial results suggest that our array enhancement, if sustained over many years, will uncover a range of previously unknown movements that will assist in addressing ecological, fisheries, and conservation questions for multiple species., (© 2024. The Author(s).)

Background: Hidradenitis suppurativa (HS) has a high unmet need for better treatments. Biopsies are considered the gold standard for studying molecular alterations in skin. A reproducible, minimally invasive approach is needed for longitudinal monitoring in trials and in pediatric populations., Objective: To determine whether skin tape strips can detect molecular alterations in HS and identify biomarkers of disease activity., Methods: We performed RNA sequencing on tape strips collected from lesional and healthy-appearing (nonlesional) HS skin (n = 22) and healthy controls (n = 21). We correlated the expression of skin biomarkers between tape strips and a previously published gene-signature of HS biopsies., Results: Tape strips detected upregulation of known HS biomarkers (eg, Interleukin[IL]-17A) in nonlesional and/or lesional skin and also identified novel clinically actionable targets, including OX40 and JAK3. The expression of Th17 and tumor necrosis factor-α pathways were highly correlated between tape strips and biopsies. HS clinical severity was significantly associated with expression of biomarkers (eg tumor necrosis factor-α , IL-17 A/F, OX40, JAK1-3, IL-4R) in HS lesional and/or nonlesional skin., Limitations: Sample size. Tape stripping is limited in depth., Conclusion: This study validates tape strips as a minimally-invasive approach to identify cutaneous biomarkers in HS. This provides a novel avenue for monitoring treatment efficacy and a potential step toward individualized therapy in HS., Competing Interests: Conflicts of interest KN, HH, MM, EA, MK, MM, DGS, SB, SCW, SG, JCR have no conflicts to disclose. SK is an employee of Mount Sinai and a consultant for AbbVie, Eli Lilly, Glenmark, Ichnos Sciences, Janssen, and Novartis. She serves on the Advisory Boards for Eli Lilly, Glenmark, Ichnos Sciences, Janssen, Abbvie, Argenx, Regeneron-Sanofi, Novartis, and UCB. She has received research funds from Pfizer, AbbVie, BMS, Incyte, Galderma and Acelyrin, and speaker bureau for AbbVie, Regeneron-Sanofi, Lilly, UCB, Janssen, Arcutis and Leo. ABG has received honoraria as an advisory board member and consultant for Amgen, AnaptypsBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dice Therapeutics, Eli Lilly, Janssen, Novartis, Sanofi, UCB, and Xbiotech and has received research/educational grants from AnaptypsBio, Moonlake Immunotherapeutics AG, Novartis, Bristol-Myers Squibb, and UCB Pharma (all paid to Mount Sinai School of Medicine). JGK has acted as a consultant for and/or received honoraria from AbbVie, Aclaris, Allergan, Almirall, Amgen, Arena, Aristea, Asana, Aurigene, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Escalier, Galapagos, Janssen, Lilly, MoonLake Immunotherapeutics, Nimbus, Novartis, Pfizer, Sanofi, Sienna Biopharmaceuticals, Sun Pharma, Target-Derm, UCB, Valeant, and Ventyx. James Krueger has received grant support (to The Rockefeller University) from AbbVie, Akros, Allergan, Amgen, Avillion, Biogen, Botanix, Boehringer Ingelheim, Bristol-Myers Squibb, Exicure, Innovaderm, Incyte, Janssen, Kyowa Kirin, Lilly, Nimbus Lackshmi, Novan, Novartis, PAREXEL, Pfizer, Regeneron, UCB, and Vitae Pharmaceuticals. EGY has served as a consultant for AbbVie, Amgen, Allergan, Asana Bioscience, Celgene, Concert, Dermira, DS Biopharma, Escalier, Galderma, Glenmark, Kyowa Kirin, LEO Pharmaceuticals, Lilly, Mitsubishi Tanabe, Novartis, Pfizer, Regeneron, Sanofi, and Union Therapeutics; a member of advisory boards of Allergan, Asana Bioscience, Celgene, DBV, Dermavant, Dermira, Escalier, Galderma, Glenmark, Kyowa Kirin, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron, and Sanofi; and a recipient of research grants from AbbVie, AnaptysBio, AntibioTx, Asana Bioscience, Boehringer-Ingelheim, Celgene, DBV, Dermavant, DS Biopharma, Galderma, Glenmark, Innovaderm, Janssen Biotech, Kiniksa Pharma, LEO Pharmaceuticals, Lilly, Medimmune, Sienna Biopharmaceuticals, Novan, Novartis, Ralexar, Regeneron, Pfizer, UCB, and Union Therapeutics., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Tumour survival and growth are reliant on angiogenesis, the formation of new blood vessels, to facilitate nutrient and waste exchange and, importantly, provide a route for metastasis from a primary to a secondary site. Whilst current models can ensure the transport and exchange of nutrients and waste via diffusion over distances greater than 200 μm, many lack sufficient vasculature capable of recapitulating the tumour microenvironment and, thus, metastasis. In this study, we utilise gelatin-containing polymerised high internal phase emulsion (polyHIPE) templated polycaprolactone-methacrylate (PCL-M) scaffolds to fabricate a composite material to support the 3D culture of MDA-MB-231 breast cancer cells and vascular ingrowth. Firstly, we investigated the effect of gelatin within the scaffolds on the mechanical and chemical properties using compression testing and FTIR spectroscopy, respectively. Initial in vitro assessment of cell metabolic activity and vascular endothelial growth factor expression demonstrated that gelatin-containing PCL-M polyHIPEs are capable of supporting 3D breast cancer cell growth. We then utilised the chick chorioallantoic membrane (CAM) assay to assess the angiogenic potential of cell-seeded gelatin-containing PCL-M polyHIPEs, and vascular ingrowth within cell-seeded, surfactant and gelatin-containing scaffolds was investigated via histological staining. Overall, our study proposes a promising composite material to fabricate a substrate to support the 3D culture of cancer cells and vascular ingrowth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jackson, Doyle, Khan, Williams, Aldemir Dikici, Barajas Ledesma, Bryant, English, Green and Claeyssens.)

Melanoma accounts for the majority of skin cancer-related mortality, highlighting the need to better understand melanoma initiation and progression. In-depth molecular analysis of neoplastic melanocytes in whole tissue biopsies may be diluted by inflammatory infiltration, which may obscure gene signatures specific to neoplastic cells. Thus, a method is needed to precisely uncover molecular changes specific to tumor cells from a limited sample of primary melanomas. Here, we performed laser capture microdissection (LCM) and gene expression profiling of patient-derived frozen sections of pigmented lesions and primary cutaneous melanoma. Compared to bulk tissue analysis, analysis of LCM-derived samples identified 9528 additional differentially expressed genes (DEGs) including melanocyte-specific genes like PMEL and TYR, with enriched of pathways related to cell proliferation. LCM methodology also identified potentially targetable kinases specific to melanoma cells that were not detected by bulk tissue analysis. Taken together, our data demonstrate that there are marked differences in gene expression profiles depending on the method of sample isolation. We found that LCM captured higher expression of melanoma-related genes while whole tissue biopsy identified a wider range of inflammatory markers. Taken together, our data demonstrate that LCM is a valid approach to identify melanoma-specific changes using a relatively small amount of primary patient-derived melanoma sample., (© 2023 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

Adolescent bullying victimization is recognized as a public health and mental health problem in many countries. However, data on bullying victimization's prevalence and risk factors is scarce in sub-Saharan Africa Sierra Leone. This research aimed to determine bullying victimization prevalence and its associated factors among Sierra Leonean school-going adolescents. The Sierra Leone 2017 Global School-based Health Survey (GSHS) dataset was analyzed. The outcome variable was the respondent's self-report of bullying victimization ("How many days in the previous 30 days were you bullied?"). Descriptive, Pearson chi-square and binary logistic regression analyses were conducted. The regression analysis yielded adjusted odds ratios (aOR) with 95% confidence intervals (CIs) and a significance level of p 0.05. Bullying victimization was prevalent among 48.7% of the in-school adolescents. Adolescents who drank alcohol [aOR = 2.48, 95% CI = 1.50-4.10], who reported feelings of loneliness [aOR = 1.51, 95% CI = 1.07-2.14] and who had attempted suicide [aOR = 1.72, 95% CI = 1.03-2.87] were also more likely to be bullied. Also, school truancy [aOR = 1.53, 95% CI = 1.24-1.88] among teenagers was associated with an increased risk of being bullied. Our findings suggest that bullying is a widespread problem among Sierra Leonean school-aged youth, and alcohol drinking, loneliness, suicide attempt and school truancy are potential risk factors. In light of the aforementioned causes of bullying in schools, policymakers and school administrators in Sierra Leone need to develop and execute anti-bullying policies and initiatives that target the underlying risk factors of bullying among teenagers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Osborne et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Advanced HIV in young people living with HIV is an increasingly pressing public health issue in sub-Saharan Africa. Despite global progress in early HIV testing and reducing HIV-related deaths, many young people with HIV continue to experience HIV disease progression in sub-Saharan Africa. This study provides an overview of the prevalence, clinical manifestations, and factors associated with advanced HIV in young people seeking medical services in a major hospital in Sierra Leone., Methods: We used a cross-sectional design to collect data from HIV patients aged 15 to 24 years at a major hospital in Sierra Leone between September 2022 and March 2023. Advanced HIV was defined as (i) CD4+ below 200 cells/mm3 or (ii) WHO clinical stage 3 or 4. Logistic regression models determined the association between observable independent characteristics and advanced HIV. The statistical significance level was set at 0.05 for all statistical tests., Results: About 40% (231/574) of patients were recruited; 70.6% (163/231) were inpatients, and 29.4% (68/231) were outpatients. The mean age was approximately 21.6 years (SD ±2.43). The overall prevalence of advanced HIV was 42.9% (99/231), 51.5% (35/68) of outpatients, and 39.3% (64/163) of inpatients. Age of inpatients (OR, 1.23; 95% CI, 1.00-1.52; p= 0.047) was associated with a higher risk. Female sex (OR, 0.51; 95% CI, 0.28-0.94; p= 0.030), higher education (OR, 0.27; 95% CI, 0.10 - 0.78; p= 0.015), and Body Mass (OR, 0.10; 95% CI, 0.01-0.77; p= 0.028) were at lower risk of advance HIV. Common conditions diagnosed in this population are tuberculosis (13.58%), hepatitis B (6.13%), Kaposi sarcoma (3.07%), and esophageal candidiasis (2.45%)., Conclusion: We reported a high prevalence of advanced HIV among young patients in a referral Hospital in Sierra Leone. This emphasises the need to strengthen public health measures and policies that address challenges of access to HIV services.

Purpose of Review: Organosulfur compounds are intentionally added to natural gas as malodorants with the intent of short-term nasal inhalation to aid in leak detection. Regulatory exposure limits have not been established for all commonly used natural gas odorants, and recent community-level exposure events and growing evidence of indoor natural gas leakage have raised concerns associated with natural gas odorant exposures. We conducted a scoping review of peer-reviewed scientific publications on human exposures and animal toxicological studies of natural gas odorants to assess toxicological profiles, exposure potential, health effects and regulatory guidelines associated with commonly used natural gas odorants., Recent Findings: We identified only 22 studies which met inclusion criteria for full review. Overall, there is limited evidence of both transient nonspecific health symptoms and clinically diagnosed causative neurotoxic effects associated with prolonged odorant exposures. Across seven community-level exposure events and two occupational case reports, consistent symptom patterns included: headache, ocular irritation, nose and throat irritation, respiratory complaints such as shortness of breath and asthma attacks, and skin irritation and rash. Of these, respiratory inflammation and asthma exacerbations are the most debilitating, whereas the high prevalence of ocular and dermatologic symptoms suggest a non-inhalation route of exposure. The limited evidence available raises the possibility that organosulfur odorants may pose health risks at exposures much lower than presently understood, though additional dose-response studies are needed to disentangle specific toxicologic effects from nonspecific responses to noxious organosulfur odors. Numerous recommendations are provided including more transparent and prescriptive natural gas odorant use practices., (© 2023. The Author(s).)

Background: Bats are considered wildlife species of public health concern, as they are known to host various pathogenic agents, and their interactions with humans are potential routes of pathogen spillover. A high level of knowledge on Bat-borne Zoonotic Diseases (BZD), their causative agents, signs, symptoms, mode and pattern of transmission, health attitudes, and practices towards the disorders are vital parameters in handling them. This study aimed to look into BZD knowledge, public attitudes, and behaviour., Methods:  We surveyed the 14 chiefdoms of Moyamba district. A total of 421 participants were randomly sampled using closed-ended questionnaire. Simple linear regression analysis was used to determine the effects of gender, age, education, and livelihood opportunities on BZD knowledge (at 95% confidence interval and alpha value = 0.05). The findings were analysed and correlated with a scientific and public health perspective to assess the breadth of knowledge and awareness of BZD among the people of Moyamba district., Results: The findings from the study show a low level of knowledge on BZD among the people of the Moyamba district, with only 119 (28.3%) individuals that had some knowledge about BZD. Of those that knew about BZD, 94 (79.0%) had very little knowledge, 24 (20.2%) had a fair amount, and 1 (0.8%) had a great deal of knowledge about BZD. The primary mode of knowledge dissemination was through social media platforms., Conclusion: The level of knowledge about BZD is also very low. As a result of these findings, policymakers, health professionals, and environmental educators will be compelled to develop strategies to reduce the risk of BZD transmission in Sierra Leone's population., Competing Interests: The authors declare that they have no competing interests., (© 2023 Williams et al.)

According to the latest World Drug Report, released by the United Nations Office on Drugs and Crime (UNODC), drug use is up 30% over the past decade and there are more drugs, and more types of drugs, than ever. Herein we use Fourier Transform Infrared Spectroscopy (FTIR) for the rapid ID of narcotics in a range of concentrations - from pure forms (as it is likely to be smuggled & transported) to street forms, often mixed with conventional cutting agents. Using FTIR, 75% of "street sample" narcotics were rapidly identified, and the effects of cutting agents on identification (ID) were also investigated. The limit of detection of MDMA was assessed, with a correct ID shown from 25% w/v. Concentration was correlated with Hit Quality Index, showing the capability of FTIR use in concentration estimation.

Accurate and robust estimation of joint kinematics via surface electromyogram (sEMG) signals provides a human-machine interaction (HMI)-based method that can be used to adequately control rehabilitation robots while performing complex movements, such as running, for motor function restoration in affected individuals. To this end, this paper proposes a deep learning-based model (AM-BiLSTM) that integrates a bidirectional long short-term memory (BiLSTM) network and an attention mechanism (AM) for robust estimation of joint kinematics. The proposed model was appraised using knee joint kinematic and sEMG signals collected from fourteen subjects who performed running at the speed of 2 m/s. The proposed model's generalizability was tested for both within- and cross-subject scenarios and compared with long short-term memory (LSTM) and multi-layer perceptron (MLP) networks in terms of normalized root-mean-square error and correlation coefficient metrics. Based on the statistical tests, the proposed AM-BiLSTM model significantly outperformed the LSTM and MLP methods in both within- and cross-subject scenarios (p<0.05) and achieved state-of-the-art performance.Clinical Relevance- The promising results of this study suggest that the AM-BiLSTM model has the potential for continuous cross-subject estimation of lower limb kinematics during running, which can be used to control sEMG-driven exoskeleton robots oriented towards rehabilitation training.

Detailed within is an attempt to implement a real-time radar signal classification system to monitor and count bee activity at the hive entry. There is interest in keeping records of the productivity of honeybees. Activity at the entrance can be a good measure of overall health and capacity, and a radar-based approach could be cheap, low power, and versatile, beyond other techniques. Fully automated systems would enable simultaneous, large-scale capturing of bee activity patterns from multiple hives, providing vital data for ecological research and business practice improvement. Data from a Doppler radar were gathered from managed beehives on a farm. Recordings were split into 0.4 s windows, and Log Area Ratios (LARs) were computed from the data. Support vector machine models were trained to recognize flight behavior from the LARs, using visual confirmation recorded by a camera. Spectrogram deep learning was also investigated using the same data. Once complete, this process would allow for removing the camera and accurately counting the events by radar-based machine learning alone. Challenging signals from more complex bee flights hindered progress. System accuracy of 70% was achieved, but clutter impacted the overall results requiring intelligent filtering to remove environmental effects from the data.

Permeable phylogeographic barriers characterize the vast open ocean, boosting gene flow and counteracting population differentiation and speciation of widely distributed and migratory species. However, many widely distributed species consists of distinct populations throughout their distribution, evidencing that our understanding of how the marine environment triggers population and species divergence are insufficient. The sailfish is a circumtropical and highly migratory billfish that inhabits warm and productive areas. Despite its ecological and socioeconomic importance as a predator and fishery resource, the species is threatened by overfishing, requiring innovative approaches to improve their management and conservation status. Thus, we presented a novel high-quality reference genome for the species and applied a seascape genomics approach to understand how marine environmental features may promote local adaptation and how it affects gene flow between populations. We delimit two populations between the Atlantic and Indo-Western Pacific oceans and detect outlier loci correlated with sea surface temperature, salinity, oxygen, and chlorophyll concentrations. However, the most significant explanatory factor that explains the differences between populations was isolation by distance. Despite recent population drops, the sailfish populations are not inbred. For billfishes in general, genome-wide heterozygosity was found to be relatively low compared to other marine fishes, evidencing the need to counteract overfishing effects. In addition, in a climate change scenario, management agencies must implement state-of-the-art sequencing methods, consider our findings in their management plans, and monitor genome-wide heterozygosity over time to improve sustainable fisheries and the long-term viability of its populations., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Background: More than 4 billion doses of the Coronavirus disease (COVID-19) vaccine have been administered worldwide but the relationship between the different vaccines and the development of renal disease is unknown. We present a case of tubulointerstitial nephritis following administration of the Oxford-AstraZeneca COVID-19 vaccine., Case Presentation: A previously fit and well 51-year-old female presented on 27th May 2021 with a one-month history of weight loss, fatigue, nausea, and a metallic taste. She had an acute kidney injury with a creatinine of 484 umol/L. She was on no regular medications and denied taking any over-the-counter or alternative medicines. She had received her first dose of the Oxford-AstraZeneca vaccine on 23rd March 2021 and her second dose on 20th May 2021. A renal biopsy was performed the following day. The 19 glomeruli appeared normal to light microscopy but the tubulointerstitial compartment contained a dense inflammatory infiltrate including many eosinophils. There was widespread acute tubular injury with tubulitis, but no established or longstanding atrophy. A diagnosis was made of an acute tubulointerstitial nephritis. She was commenced on oral prednisolone and her renal function improved. She did not require renal replacement therapy at any time., Conclusions: To our knowledge, this was the first described case of acute tubulointerstitial nephritis following administration of the Oxford-AstraZeneca COVID-19 vaccine, although a number of cases have emerged more recently. In our case the patient was very fit and well, had no previous past medical history and had not taken any recent prescribed, over-the-counter or alternative medications. The absence of these provoking factors in our case makes the vaccine the most likely explanation for the development of tubulointerstitial nephritis although the pathophysiology behind this remains unknown. Given the unprecedented number of vaccinations being delivered around the world, nephrologists should be aware of this possible link although more research into the topic is required., (© 2023. The Author(s).)

Background: Psilocybin is being studied for use in treatment-resistant depression., Methods: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits)., Results: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups., Conclusions: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.)., (Copyright © 2022 Massachusetts Medical Society.)

Sodium-glucose co-transporter-2 inhibitors are increasingly prescribed for patients with type 2 diabetes. Their use has been associated with life-threatening diabetic ketoacidosis. The risk is increased during times of fasting and intercurrent medical illness, which are common in the perioperative period. Diagnosis can be difficult, so perioperative clinicians must be familiar with preventing and recognising such complications.

We examined the characteristics of pro-calcitonin (PCT) in hospitalized COVID-19 patients (cohort 1) and clinical outcomes of antibiotic use stratified by PCT in non-critically ill patients without bacterial co-infection (cohort 2). Retrospective reviews were performed in adult, hospitalized COVID-19 patients during March-May 2020. For cohort 1, we excluded hospital transfers, renal disease and extra-pulmonary infection without isolated pathogen(s). For cohort 2, we further excluded microbiologically confirmed infection, 'do not resuscitate ± do not intubate' status, and intensive care unit (ICU). For cohort 1, PCT was compared between absent/low-suspicion and proven bacterial co-infections. Factors associated with elevated PCT and sensitivity/specificity/PPV/NPV of PCT cutoffs for identifying bacterial co-infections were explored. For cohort 2, clinical outcomes including mechanical ventilation within 5 days (MV5) were compared between the antibiotic and non-antibiotic groups stratified by PCT ≥ 0.25 µg/L. Nine hundred and twenty four non-ICU and 103 ICU patients were included (cohort 1). The median PCT was higher in proven vs. absent/low-suspicion of bacterial co-infection. Elevated PCT was significantly associated with proven bacterial co-infection, ICU status and oxygen requirement. For PCT ≥ 0.25 µg/L, sensitivity/specificity/PPV/NPV were 69/65/6.5/98% (non-ICU) and 75/33/8.6/94% (ICU). For cohort 2, 756/1305 (58%) patients were included. Baseline characteristics were balanced between the antibiotic and non-antibiotic groups except PCT ≥ 0.25 µg/L (antibiotic:non-antibiotic = 59%:24%) and tocilizumab use (antibiotic:non-antibiotic = 5%:2%). 23% (PCT < 0.25 µg/L) and 58% (PCT ≥ 0.25 µg/L) received antibiotics. Antibiotic group had significantly higher rates of MV5. COVID-19 severity inferred from ICU status and oxygen requirement as well as the presence of bacterial co-infections were associated with elevated PCT. PCT showed poor PPV and high NPV for proven bacterial co-infections. The use of antibiotics did not show improved clinical outcomes in COVID-19 patients with PCT ≥ 0.25 µg/L outside of ICU when bacterial co-infections are of low suspicion., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Background: Hidradenitis suppurativa (HS) is an inflammatory skin disease with dysregulation of the interleukin (IL)-17 axis. Recently, we reported the clinical benefit of brodalumab, a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody, in moderate-to-severe HS., Objectives: To characterize the molecular response to brodalumab in HS skin and serum, and to identify biomarkers of treatment response., Methods: Ten participants, who received brodalumab 210 mg /1·5 mL subcutaneously at weeks 0, 1, 2, 4 and every 2 weeks thereafter, were included in this molecular profiling study (NCT03960268). RNA sequencing and immunohistochemistry of nonlesional, perilesional and lesional HS skin biopsies, and Olink high-throughput proteomics of serum at baseline, weeks 4 and 12 were assessed., Results: At week 12, brodalumab led to a decrease of overall inflammation, and improvement of psoriasis-, keratinocyte- and neutrophil-related pathways. Despite perilesional and lesional skin exhibiting no differentially expressed genes at baseline, treatment response was best assessed in perilesional skin. In serum, brodalumab treatment decreased pathways involved in neutrophil inflammation. Patients with higher baseline expression of neutrophil-associated lipocalin-2 (LCN2) in the skin or IL-17A in the serum demonstrated greater decreases of HS-related inflammatory cytokines as measured in skin biopsies at week 12., Conclusions: IL-17RA inhibition by brodalumab decreases several pathogenic inflammatory axes in HS. Perilesional skin provides a valid and robust assessment of treatment response. Expression of LCN2 in skin or IL-17A in serum may be used as biomarkers to stratify patients that may have a superior molecular response to brodalumab., (© 2022 British Association of Dermatologists.)

Introduction: The emergence of the novel severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) rapidly evolved into a worldwide pandemic of Coronavirus Disease 2019 (COVID-19). The pandemic had a major operational impact upon the US military, requiring interventions to mitigate transmission risk resulting in DoD-wide disruption of daily operations, restriction of movement, and delays in training. Development of a rapid mobile COVID-19 testing strategy was pursued as a means to allow service members to complete critical missions in select settings. In this report, we describe the first of its kind mobile medical laboratory (MML) that allowed for testing of approximately 4,000 soldiers of the 1/34th Armored Brigade Combat Team (1/34th ABCT), 34th Infantry Division, prior to deployment for validation exercises to the National Training Center, Fort Irwin, CA. We describe the utilizing of the MML, COVID-19 testing workflow, clinical symptom data/cycle threshold (Ct) data from positive patients, and outcomes from this testing mission.

Informed decisions about one's sexual and reproductive health can be made through family planning. Women of reproductive age in rural Sierra Leone's Western area were asked to participate in a survey to determine their attitudes and knowledge toward family planning and the use of contraceptives. A descriptive cross-sectional study survey was conducted in the Western Area Rural of Sierra Leone. Females in the range of 15 to 49 years old were included in the study. The research was conducted from November 2021 to December 2021. Using a pre-designed and pretested questionnaire, 180 women were assessed for their knowledge, attitudes, and practices regarding family planning. According to the study, all participants knew about family planning, but only 68.3% had used contraceptives. There were more than half who learned about it from the media. The study found that 95% of participants had a positive attitude towards contraceptives. Most commonly, contraceptives used were oral pills (31.6), injections (21.1%), implants (19.1%), lactational amenorrhea (13.8%), condoms (8.8%), and intrauterine devices (5%). In our study, the most common reasons given by participants for not using contraceptives were; not willing to disclose 52.6%, a desire for a child 19.2%, fear of side effects 15.7%, currently pregnant 8.7%, and against religious beliefs 3.5%. The study shows that even if people are aware and educated about contraceptives, they may not use them. Educating and motivating people and improving access to family planning services are still necessary to improve the effectiveness and appropriateness of contraceptive use and halt the population growth trend.

Background: The skin of patients with atopic dermatitis is characterized by abnormal stratum corneum lipid levels. Consequently, the lamellar matrices are disrupted and skin barrier function is diminished, increasing skin sensitivity to irritants and allergens., Objectives: To determine whether a cream containing ceramides, triglycerides and cholesterol in a multivesicular emulsion can reinforce the skin barrier and protect against skin irritation., Methods: A randomized observer-blind intrapatient-controlled study in 34 adults with dry, eczema-prone skin was conducted. Each participant underwent 4 weeks of treatment with the test cream on one forearm and lower leg and a reference emollient cream on the other. Skin properties were determined before and after treatment. Lipid structure was assessed by Fourier-transform infrared spectroscopy using a novel interface., Results: Skin barrier integrity was greater at sites treated with the test cream [effect size for area under the transepidermal water loss curve -162, 95% confidence interval (CI) -206 to -118]. Skin sensitivity to sodium lauryl sulfate was reduced (-0·5 points visual redness, 97·57% CI -1·00 to -0·25), as was transepidermal water loss (-15·3 g m -2 h -1 , 95% CI -20·3 to -10·4) compared with the reference. Sites treated with the test cream displayed enhanced lipid chain ordering, which was significantly associated with skin barrier integrity (r = 0·61). Compared with the reference, treatment with the test cream increased hydration (8·61 capacitance units, 95% CI 6·61-10·6) and decreased signs of dryness., Conclusions: The test cream facilitates skin barrier restoration and protects the skin from dryness and irritation. Compared with a commonly prescribed emollient in the UK, the test cream is highly suited to the management of dry, sensitive skin., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Surface myoelectric pattern recognition (sMPR) based control strategy is a popularly adopted scheme for multifunctional upper limb prostheses. Meanwhile, above-elbow amputees (transhumeral: TH) usually have limited residual arm muscles, that mostly hinder the provision of requisite signals necessary for physiologically appropriate sMPR control. Hence, the need to maximally explore the limited signals to realize adequate sMPR control scheme in practical settings. This study proposes an effective signal denoising method driven by Multi-scale Local Polynomial Transform (MLPT) concept that can improve the signal quality, thus allowing adequate decoding of TH amputees' motion intent from high-density electromyogram (HD-sEMG) signals. The proposed method's performance was systematically investigated with HD-sEMG signals obtained from TH amputees that performed multiple classes of targeted upper limb movement tasks, and compared with two common signal denoising methods based on wavelet transform. The obtained results show that the proposed MLPT method outperformed both existing methods for motion tasks decoding with over 13.0% increment in accuracy across subjects. The possibility of generating distinct and repeatable myoelectric contraction patterns using the MLPT based denoised HDs-EMG recordings was investigated. The obtained results proved that the MLPT method can better denoise and aid the reconstruction of myoelectric signal patterns of the amputees. Therefore, this suggest the potential of the MLPT method in characterizing high-level upper limb amputees' muscle activation patterns in the context of sMPR prostheses control scheme.

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory skin disease with still largely unknown pathogenesis. While infectious organisms have been identified in lesions of the disease since the 1980s, questions remain over the role that bacteria and microbiome play. Recent studies using 16S ribosomal RNA gene sequencing and larger culture-based studies have begun to paint a clearer picture of the microbial world of HS. With this systematic review, we summarize all the work that has been done to date in HS bacteriology, analyse potential pitfalls and limitations of the current studies, and address future directions of investigation. This systematic review attempted to collate and analyse all bacteriology studies done to date. This review was prospectively registered with PROSPERO (1670769) performed in line with the PRISMA checklist. Twenty two studies were identified comprising 862 individual HS patients for culture studies and 206 HS patients for 16S rRNA gene sequencing studies. Methodology tended to be varied, with different sampling, culturing and sequencing methods as well as amount of analysis and stratification of patients. Bacteria identified as elevated in HS lesions in sequencing studies as well as grown from HS lesions in culture studies are identified and discussed. These primarily included the anerobic Gram-negative bacilli Prevotella, Porphyromonas and Fusibacterium, the Gram-positive bacilli Corynebacterium, and the Gram-positive cocci Staphylococcus, Streptococcus and Parvimonas. Potential interactions, as well as work in other disease models with related bacteria are also discussed. Areas of further investigation include in vitro studies of interactions between bacteria and keratinocytes, gut and oral microbiome studies and deep sequencing studies for virulence and phage factors., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The pathophysiology of adverse events following programmed cell death protein 1 (PD-1) blockade, including tuberculosis (TB) and autoimmunity, remains poorly characterized. We studied a patient with inherited PD-1 deficiency and TB who died of pulmonary autoimmunity. The patient's leukocytes did not express PD-1 or respond to PD-1-mediated suppression. The patient's lymphocytes produced only small amounts of interferon (IFN)-γ upon mycobacterial stimuli, similarly to patients with inborn errors of IFN-γ production who are vulnerable to TB. This phenotype resulted from a combined depletion of Vδ2 + γδ T, mucosal-associated invariant T and CD56 bright natural killer lymphocytes and dysfunction of other T lymphocyte subsets. Moreover, the patient displayed hepatosplenomegaly and an expansion of total, activated and RORγT + CD4 - CD8 - double-negative αβ T cells, similar to patients with STAT3 gain-of-function mutations who display lymphoproliferative autoimmunity. This phenotype resulted from excessive amounts of STAT3-activating cytokines interleukin (IL)-6 and IL-23 produced by activated T lymphocytes and monocytes, and the STAT3-dependent expression of RORγT by activated T lymphocytes. Our work highlights the indispensable role of human PD-1 in governing both antimycobacterial immunity and self-tolerance, while identifying potentially actionable molecular targets for the diagnostic and therapeutic management of TB and autoimmunity in patients on PD-1 blockade., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Anecdotal reports from fishers in Southeast Queensland, Australia suggest that shark depredation is a significant issue, however little is known about which species are responsible for depredating catches. This research aimed to identify depredating species in Southeast Queensland line based fisheries, by undertaking a genetic analysis of depredated samples collected by commercial, charter and recreational fishers. The genetic analysis successfully identified ten depredating sharks, all from the genus Carcharhinus (19.2% success). The species identified using mitochondrial DNA included five C. leucas (bull sharks), two C. plumbeus (sandbar sharks), one C. amboinensis (pigeye shark), one C. brevipinna (spinner shark) and one unconfirmed C. plumbeus/C. altimus (bignose shark). While many species of Carcharhinus have been found to depredate catches in Australia, C. leucas has not been highlighted until this research as a potential problematic species. The optimised protocol allowed for the confident identification of shark species responsible for depredation in fisheries using frozen fish samples donated by fishers.

Background: The Ottawa subarachnoid haemorrhage (SAH) rule and the Emerald SAH rule are clinical decision tools to aid in the decision for computed tomography (CT) of the head in patients attending an emergency department (ED) with acute non-traumatic headache. The objective of this study was to analyse the performance of these rules in a contemporary UK cohort., Methods: We performed a retrospective external validation study. Patients undergoing CT of the head for the evaluation and treatment of non-traumatic headaches over a 6-month period in the ED at two tertiary centres were assessed. Each patient's Ottawa rule and Emerald rule were calculated and compared with their final diagnosis., Results: The cohort consisted of 366 patients and there were 16 cases of SAH (based on CT findings or the presence of xanthochromia in cerebrospinal fluid). The Ottawa rule identified 288 patients requiring CT of the head. The sensitivity of the Ottawa rule was 100% (95% confidence interval (CI) 71-100%) and the specificity was 22% (95% CI 18-27%). The Emerald rule identified 267 patients who required CT, and achieved a sensitivity of 81% (95% CI 54-96%) and a specificity of 27% (95% CI 23-32%)., Conclusions: The Ottawa SAH rule correctly identified all patients with SAH in this contemporary cohort. The Emerald rule did not perform as well in this cohort and is unsuitable for clinical use. The Ottawa rule is a useful tool to aid in the decision for CT of the head in patients presenting with acute non-traumatic headache to the ED., (© Royal College of Physicians 2021. All rights reserved.)

PNU-159682 is a highly potent secondary metabolite of nemorubicin belonging to the anthracycline class of natural products. Due to its extremely high potency and only partially understood mechanism of action, it was deemed an interesting starting point for the development of a new suite of linker drugs for antibody drug conjugates (ADCs). Structure activity relationships were explored on the small molecule which led to six linker drugs being developed for conjugation to antibodies. Herein we describe the synthesis of novel PNU-159682 derivatives and the subsequent linker drugs as well as the corresponding biological evaluations of the small molecules and ADCs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The purpose of this education innovation was to facilitate office hour (OH) instruction for student nurse athletes due to training schedules and off-campus travel. Effective integration of technology, learning theory, and multimedia resources provide strategies to enhance student athlete access to faculty OH and associated learning opportunities. Explain Everything™ software, a digital interactive whiteboard space, enables students and faculty to collaborate and learn across distance. This innovative approach enriches learning, ensuring OH access among student athletes.

Background: The spread of SARS-CoV-2 and the COVID-19 pandemic have caused significant morbidity and mortality worldwide. The clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 and HIV co-infection remain uncertain., Methods: We conducted a matched retrospective cohort study of adults hospitalized with a COVID-19 illness in New York City between March 3, 2020, and May 15, 2020. We matched 30 people with HIV (PWH) with 90 control group patients without HIV based on age, sex, and race/ethnicity. Using electronic health record data, we compared demographic characteristics, clinical characteristics, and clinical outcomes between PWH and control patients., Results: In our study, the median age (interquartile range) was 60.5 (56.6-70.0) years, 20% were female, 30% were black, 27% were white, and 24% were of Hispanic/Latino/ethnicity. There were no significant differences between PWH and control patients in presenting symptoms, duration of symptoms before hospitalization, laboratory markers, or radiographic findings on chest x-ray. More patients without HIV required a higher level of supplemental oxygen on presentation than PWH. There were no differences in the need for invasive mechanical ventilation during hospitalization, length of stay, or in-hospital mortality., Conclusions: The clinical manifestations and outcomes of COVID-19 among patients with SARS-CoV-2 and HIV co-infection were not significantly different than patients without HIV co-infection. However, PWH were hospitalized with less severe hypoxemia, a finding that warrants further investigation., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

In the era of highly active antiretroviral therapy (HAART), disseminated Kaposi sarcoma (KS) has become much rarer in the USA. We report a case of a 34-year-old man with KS of the skin, oropharynx, lung and rectum. Within the same lung nodule, we discovered significant burden of colesional Cryptococcus neoformans, in the context of a positive asymptomatic cryptococcal antigenemia, which was a previously unreported occurrence. The gold standard of treatment for KS continues to be HAART. The role of chemotherapy is still controversial. In addition, a cryptococcal antigen screen-and-treat approach with fluconazole is still not routinely recommended in the USA to prevent serious meningeal disease despite recent studies showing efficacy and applicability. We discuss both issues here and the outcome of our patient. We also present the patient's own unique perspective in dealing with the ramifications of these diagnoses., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Marburg virus (MARV) causes sporadic outbreaks of severe Marburg virus disease (MVD). Most MVD outbreaks originated in East Africa and field studies in East Africa, South Africa, Zambia, and Gabon identified the Egyptian rousette bat (ERB; Rousettus aegyptiacus) as a natural reservoir. However, the largest recorded MVD outbreak with the highest case-fatality ratio happened in 2005 in Angola, where direct spillover from bats was not  shown. Here, collaborative studies by the Centers for Disease Control and Prevention, Njala University, University of California, Davis USAID-PREDICT, and the University of Makeni identify MARV circulating in ERBs in Sierra Leone. PCR, antibody and virus isolation data from 1755 bats of 42 species shows active MARV infection in approximately 2.5% of ERBs. Phylogenetic analysis identifies MARVs that are similar to the Angola strain. These results provide evidence of MARV circulation in West Africa and demonstrate the value of pathogen surveillance to identify previously undetected threats.

The genome of the archaeon Pyrobaculum aerophilum (T opt  ~ 100 °C) contains an operon (PAE2859-2861) encoding a putative pyranopterin-containing oxidoreductase of unknown function and metal content. These genes (with one gene modified to encode a His-affinity tag) were inserted into the fermentative anaerobic archaeon, Pyrococcus furiosus (T opt  ~ 100 °C). Dye-linked assays of cytoplasmic extracts from recombinant P. furiosus show that the P. aerophilum enzyme is a thiosulfate reductase (Tsr) and reduces thiosulfate but not polysulfide. The enzyme (Tsr-Mo) from molybdenum-grown cells contains Mo (Mo:W = 9:1) while the enzyme (Tsr-W) from tungsten-grown cells contains mainly W (Mo:W = 1:6). Purified Tsr-Mo has over ten times the activity (V max  = 1580 vs. 141 µmol min -1 mg -1 ) and twice the affinity for thiosulfate (K m  = ~ 100 vs. ~ 200 μM) than Tsr-W and is reduced at a lower potential (E peak  = - 255 vs - 402 mV). Tsr-Mo and Tsr-W proteins are heterodimers lacking the membrane anchor subunit (PAE2861). Recombinant P. furiosus expressing P. aerophilum Tsr could not use thiosulfate as a terminal electron acceptor. P. furiosus contains five pyranopterin-containing enzymes, all of which utilize W. P. aerophilum Tsr-Mo is the first example of an active Mo-containing enzyme produced in P. furiosus.

Background: Optimal follow-up (FU) strategy to detect potentially curable (PC) recurrences after treatment of localised clear cell renal cell carcinoma (ccRCC) is unclear. This study retrospectively analysed a large international database to determine recurrence patterns and overall survival (OS), as part of a wider project to issue recommendations on FU protocols., Objective: To analyse associations between RCC recurrences in patients with ccRCC, their risk group stratifications, treatments, and subsequent outcomes., Design, Setting, and Participants: Nonmetastatic ccRCC patients treated with curative intent between 1 January 2006 and 31 December 2011, with at least 4 yr of FU, were included. Patient, tumour and recurrence characteristics, Leibovich score, and management and survival data were recorded. Isolated local, solitary, and oligometastatic (three or fewer lesions at a single site) recurrences were considered PC, while all others were probably incurable (PI)., Intervention: Primarily curative surgical treatment of ccRCC while at recurrence detection metastasectomy, systemic therapy, best supportive care, or observation., Outcome Measurements and Statistical Analysis: Incidence, time to recurrence (TTR), and OS were measured. Competing risk analysis, Kaplan-Meier, and Cox regression models were used., Results and Limitation: Of 1265 patients with ccRCC, 286 had a recurrence, with 131 being PC and 155 PI. Five-year cumulative risks of recurrence for low- (n=53), intermediate- (n=105), and high-risk (n=128) patients were, respectively, 7.2%, 23.2%, and 61.6%, of whom 52.8%, 37.1%, and 30.5% were PC, respectively. Median TTR was 25.0 for PC patients versus 17.3 mo for PI patients (p=0.004). Median OS was longer in PC compared with that in PI patients (p<0.001). Competing risk analysis showed highest risk of ccRCC-related death in younger and high-risk patients. Limitations were no data on comorbidities, retrospective cohort, and insufficient data excluding 12% of cohort., Conclusions: Low-risk group recurrences are rare and develop later. Treatment of recurrences with curative intent is disappointing, especially in high-risk patients. An age- and risk score-dependent FU approach is suggested., Patient Summary: We analysed data from eight European countries, and found that the incidence of the kidney cancer recurrence and patient survival correlated with clinical factors known to predict cancer recurrence reliably and age. We conclude that these factors should be used to design follow-up strategies., (Copyright © 2018 European Association of Urology. All rights reserved.)

Background: Spatially accurate population data are critical for determining health impacts from many known risk factors. However, the utility of the increasing spatial resolution of disease mapping and environmental exposures is limited by the lack of receptor population data at similar sub-census block spatial scales., Methods: Here we apply an innovative method (Population Allocation by Occupied Domicile Estimation - ABODE) to disaggregate U.S. Census populations by allocating an average person per household to geospatially-identified residential housing units (RHU). We considered two possible sources of RHU location data: address point locations and building footprint centroids. We compared the performance of ABODE with the common proportional population allocation (PPA) method for estimating the nighttime residential populations within 200 m radii and setback areas (100 - 300 ft) around active underground natural gas storage (UGS) wells (n = 9834) in six U.S. states., Results: Address location data generally outperformed building footprint data in predicting total counts of census residential housing units, with correlations ranging from 0.67 to 0.81 at the census block level. Using residentially-sited addresses only, ABODE estimated upwards of 20,000 physical households with between 48,126 and 53,250 people living within 200 m of active UGS wells - likely encompassing the size of a proposed UGS Wellhead Safety Zone. Across the 9834 active wells assessed, ABODE estimated between 5074 and 10,198 more people living in these areas compare to PPA, and the difference was significant at the individual well level (p = < 0.0001). By either population estimation method, OH exhibits a substantial degree of hyperlocal land use conflict between populations and UGS wells - more so than other states assessed. In some rare cases, population estimates differed by more than 100 people for the small 200 m 2 well-areas. ABODE's explicit accounting of physical households confirmed over 50% of PPA predictions as false positives indicated by non-zero predictions in areas absent physical RHUs., Conclusions: Compared to PPA - in allocating identical population data at sub-census block spatial scales -ABODE provides a more precise population at risk (PAR) estimate with higher confidence estimates of populations at greatest risk. 65% of UGS wells occupy residential urban and suburban areas indicating the unique land use conflicts presented by UGS systems that likely continue to experience population encroachment. Overall, ABODE confirms tens of thousands of homes and residents are likely located within the proposed UGS Wellhead Safety Zone - and in some cases within state's oil and gas well surface setback distances - of active UGS wells.

Objective: Modality and frequency of image-based renal cell carcinoma (R.C.C.) follow-up strategies are based on risk of recurrence. Using the R.E.C.U.R.-database, frequency of imaging was studied in regard to prognostic risk groups. Furthermore, it was investigated whether imaging modality utilized in contemporary follow-up were associated with outcome after detection of recurrence. Moreover, outcome was compared based on whether the assessment of potential curability was a pre-defined set of criteria's (per-protocol) or stated by the investigator. Materials and methods: Consecutive non-metastatic R.C.C. patients ( n  = 1,612) treated with curative intent at 12 institutes across eight European countries between 2006 and 2011 were included. Leibovich or U.I.S.S. risk group, recurrence characteristics, imaging modality, frequency and survival were recorded. Primary endpoints were overall survival (O.S.) after detection of recurrence and frequency of features associated with favourable outcome (non-symptomatic recurrences and detection within the follow-up-programme). Results: Recurrence occurred in 336 patients. Within low, intermediate and high risk for recurrence groups, the frequency of follow-up imaging was highest in the early phase of follow-up and decreased significantly over time ( p  < 0.001). However, neither the image modality for detection nor ≥ 50% cross-sectional imaging during follow-up were associated with improved O.S. after recurrence. Differences between per protocol and investigator based assessment of curability did not translate into differences in O.S. Conclusions: As expected, the frequency of imaging was highest during early follow-up. Cross-sectional imaging use for detection of recurrences following surgery for localized R.C.C. did not improve O.S. post-recurrence. Prospective studies are needed to determine the value of imaging in follow-up.

We investigated whether commercially landed black marlin Istiompax indica were being misidentified by fisheries observers operating throughout the Pacific Ocean. Of 83 samples reported by observers as I. indica, 77% were genetically identified to be blue marlin Makaira nigricans and 2% to be striped marlin Kajikia audax. The high rate of misidentification by observers places considerable uncertainty over historic catch ratios of Indo-Pacific marlin and stock assessments relying on the validity of these data., (© 2018 The Fisheries Society of the British Isles.)