Effect of Tetracycline on Late-stage African trypanosomiasis in Rats

The effect of tetracycline on late stage African trypanosomiasis was examined in an in vivo experiment using rats infected with Trypanosoma brucei brucei. Infected rats were treated on the 5th day of infection with 10mg/kg and 20mg/kg rat weight of tetracycline and tetracycline hydrochloride. Tetracycline at 10mg/kg extended the life-span of infected rats from 6 days to 11 days, but with 20mg/kg the rats died on day 6. Tetracycline–HCl at 10 and 20mg/kg extended the lifespan to 9 and 12 days respectively. The trypanocidal effect of tetracycline on late stage trypanosomiasis is probably due to its ability to penetrate the blood brain barrier and its probable role in inhibiting ribonucleotide reductase through iron chelation. We suggest that tetracycline-HCl and low concentrations of tetracycline can be used in the clinical management of African Trypanosomiasis.Key words: African trypanosomiasis, Tetracycline, Late Stag

Demographic attributes of COVID-19 patients in an Infectious Disease Center of Nigeria

Background: As part of our contribution to the growing pool of knowledge on the prevention and control of the COVID-19 pandemic, this study describes the demographic features of patients with COVID-19 hospitalized at Infectious Disease Center (IDC), Olodo, Ibadan, Oyo State, Nigeria.Methodology: This was a descriptive cross-sectional study of COVID-19 patients whose data were collected during admission between April 27, 2020 and June 20, 2020. SARS-CoV-2 infection was diagnosed on nasopharyngeal specimen using a real-time reverse transcription–polymerase chain reaction (rRT-PCR) assay. Data were analysed using the Statistical Package for Social Sciences (SPSS Inc., USA) version 20.0Results: Among 131 patients, 58% were between age 18 and 35 years, 48.1% were employees of private establishments, and 64.1% were males. High proportion (84.3%) of the patients spent less than 14 days on admission. As at June 20, 2020, the overall COVID-19 mortality in the IDC was 0.0%.Conclusion: This study concluded that COVID-19 was common among male Nigerians, those working in private establishments, and those aged 18-35 years. Future researches on COVID-19 in Nigeria must put gender and age into consideration. Keywords: SARS-COV2; COVID-19; age; gender; occupation French Title: Attributs démographiques des patients atteints de COVID-19dans un centre de maladies infectieuses du Nigéria Contexte: Dans le cadre de notre contribution au pool croissant de connaissances sur la prévention et le contrôle de la pandémie COVID-19, cette étude décrit les caractéristiques démographiques des patients atteints de COVID19 hospitalisés au Centre des maladies infectieuses (IDC), Olodo, Ibadan, État d'Oyo, Nigéria. Méthodologie: Il s'agissait d'une étude transversale descriptive de patients atteints de COVID-19 dont lesdonnées ont été collectées lors de l'admission entre le 27 avril 2020 et le 20 juin 2020. L'infection par le  SRASCoV-2 a été diagnostiquée sur un échantillon nasopharyngé à l'aide d'une transcription inverse en temps réel–Test de réaction en chaîne par polymérase (rRT-PCR). Les données ont été analysées à l'aide du StatisticalPackage for Social Sciences (SPSS Inc., USA) version 20.0 Résultats: Parmi 131 patients, 58% avaient entre 18 et 35 ans, 48,1% étaient des employés d'établissementsprivés et 64,1% étaient des hommes. Une forte proportion (84,3%) des patients ont passé moins de 14 jours àl'admission. Au 20 juin 2020, la mortalité globale par COVID-19 dans l'IDC était de 0,0%. Conclusion: Cette étude a conclu que le COVID-19 était courant chez les hommes Nigérians, ceux travaillantdans des établissements privés et ceux âgés de 18 à 35 ans. Les futures recherches sur le COVID-19 au Nigériadoivent prendre en compte le sexe et l'âge. Mots clés: SRAS-COV2; COVID-19; âge; le sexe; occupatio

Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits

The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Throug

A compendium of multi-omics data illuminating host responses to lethal human virus infections

Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses. For comparison, we have included transcriptomics datasets from cells treated with type I and type II human interferon. Raw multi-omics data and metadata were deposited in public repositories, and we provide a central location linking the raw data with experimental metadata and ready-to-use, quality-controlled, statistically processed multi-omics datasets not previously available in any public repository. This compendium of infection-induced host response data for reuse will be useful for those endeavouring to understand viral disease pathophysiology and network biology

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Star clusters near and far; tracing star formation across cosmic time

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s11214-020-00690-x.Star clusters are fundamental units of stellar feedback and unique tracers of their host galactic properties. In this review, we will first focus on their constituents, i.e.\ detailed insight into their stellar populations and their surrounding ionised, warm, neutral, and molecular gas. We, then, move beyond the Local Group to review star cluster populations at various evolutionary stages, and in diverse galactic environmental conditions accessible in the local Universe. At high redshift, where conditions for cluster formation and evolution are more extreme, we are only able to observe the integrated light of a handful of objects that we believe will become globular clusters. We therefore discuss how numerical and analytical methods, informed by the observed properties of cluster populations in the local Universe, are used to develop sophisticated simulations potentially capable of disentangling the genetic map of galaxy formation and assembly that is carried by globular cluster populations.Peer reviewedFinal Accepted Versio

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Association of variants in the SPTLC1 gene with juvenile amyotrophic lateral sclerosis

IMPORTANCE Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.OBJECTIVE To identify the genetic variants associated with juvenile ALS.DESIGN, SETTING, AND PARTICIPANTS In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.MAIN OUTCOMES AND MEASURES De novo variants present only in the index case and not in unaffected family members.RESULTS Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p. Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.CONCLUSIONS AND RELEVANCE These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.Genetics of disease, diagnosis and treatmen

K-Shell photodetachment of Li−: Experiment and theory

We have measured the first and second moments of the hadronic mass-squared distribution in B→Xclv, for Plepton>1.5 GeV/c. We find(MX 2−MD −2)= 0.251 ± 0.66 GeV2,((MX 2−MX 2)2)=0.576 ± 0.170 GeV4, where M¯ Dis the spin-averaged D meson mass. From that first moment and the first moment of the photon energy spectrum in b→s γ, we find the heavy quark effective theory parameter λ1(in the modified minimal subtraction renormalization scheme, to order 1/MB 3and γ0αs 2) to be −0.24±0.11GeV2. Using these first moments and the B semileptonic width, and assuming parton-hadron duality, we obtain|Vcb|=0.0404±0.0013