Tissue biochemical diversity of 20 gooseberry cultivars and the effect of ethylene supplementation on postharvest life

The European gooseberry (Ribes uva-crispa) is still an understudied crop with limited data available on its biochemical profile and postharvest life. A variety of polyphenols were detected in the skin and flesh of 20 gooseberry cvs, representing mainly flavonol glycosides, anthocyanins and flavan-3-ols. In contrast, gooseberry seeds were for the first time characterised by the presence of considerable amounts of hydroxycinnamic acid glycosides tentatively identified by UPLC-QToF/MS. All cvs examined represented a good source of vitamin C while being low in sugar. Furthermore, the postharvest stability of bioactives was explored by supplementation of exogenous ethylene in air at 5 °C. Results suggest a low sensitivity of gooseberries to ethylene. The overall quality of gooseberries remained stable over two weeks, showing potential for extended bioactive life

Alcohol and illicit drug use among young people living with HIV compared to their uninfected peers from the Kenyan coast: prevalence and risk indicators

Background: In sub-Saharan Africa, there is paucity of research on substance use patterns among young people living with HIV (YLWH). To address the gap, we sought to: i) determine the prevalence of substance use, specifically alcohol and illicit drug use, among YLWH compared to their HIV-uninfected peers; ii) investigate the independent association between young people’s HIV infection status and substance use; iii) investigate the risk indicators for substance use among these young people. Methods: Between November 2018 and September 2019, a cross-sectional study was conducted at the Kenyan coast recruiting 819 young people aged 18–24 years (407 HIV-positive). Alcohol and drug use disorders identification tests (AUDIT and DUDIT) were administered via audio computer-assisted self-interview alongside other measures. Logistic regression was used to determine substance use risk indicators. Results: The point prevalence of current substance use was significantly lower among YLWH than HIV-uninfected youths: current alcohol use, 13% vs. 24%, p \u3c 0.01; current illicit drug use, 7% vs. 15%, p \u3c 0.01; current alcohol and illicit drug use comorbidity, 4 vs. 11%, p \u3c 0.01. Past-year prevalence estimates for hazardous substance use were generally low among young people in this setting (\u3c 10%) with no significant group differences observed. Being HIV-positive independently predicted lower odds of current substance use, but not hazardous substance use. There was overlap of some risk indicators for current substance use between young people with and without HIV including male sex, khat use and an experience of multiple negative life events, but risk indicators unique to either group were also identified. Among YLWH, none of the HIV-related factors was significantly associated with current substance use. Conclusions: At the Kenyan coast, substance use is a reality among young people. The frequency of use generally appears to be low among YLWH compared to the HIV-uninfected peers. Substance use prevention initiatives targeting young people, regardless of HIV infection status, are warranted in this setting to avert their potential risk for developing substance use disorders, including dependence. The multifaceted intrapersonal and interpersonal factors that place young people at risk of substance use need to be addressed as part of the substance use awareness and prevention initiatives

Clinical and Genetic Risk Factors for Adverse Metabolic Outcomes in North American Testicular Cancer Survivors

Background: Testicular cancer survivors (TCS) are at significantly increased risk for cardiovascular disease (CVD), with metabolic syndrome (MetS) an established risk factor. No study has addressed clinical and genetic MetS risk factors in North American TCS. Patients and Methods: TCS were aged <55 years at diagnosis and received first-line chemotherapy. Patients underwent physical examination, and had lipid panels, testosterone, and soluble cell adhesion molecule-1 (sICAM-1) evaluated. A single nucleotide polymorphism in rs523349 (5-α-reductase gene, SRD5A2), recently implicated in MetS risk, was genotyped. Using standard criteria, MetS was defined as ≥3 of the following: hypertension, abdominal obesity, hypertriglyceridemia, decreased high-density lipoprotein (HDL) cholesterol level, and diabetes. Matched controls were derived from the National Health and Nutrition Examination Survey. Results: We evaluated 486 TCS (median age, 38.1 years). TCS had a higher prevalence of hypertension versus controls (43.2% vs 30.7%; P<.001) but were less likely to have decreased HDL levels (23.7% vs 34.8%; P<.001) or abdominal obesity (28.2% vs 40.1%; P<.001). Overall MetS frequency was similar in TCS and controls (21.0% vs 22.4%; P=.59), did not differ by treatment (P=.20), and was not related to rs523349 (P=.61). For other CVD risk factors, TCS were significantly more likely to have elevated low-density lipoprotein (LDL) cholesterol levels (17.7% vs 9.3%; P<.001), total cholesterol levels (26.3% vs 11.1%; P<.001), and body mass index ≥25 kg/m2 (75.1% vs 69.1%; P=.04). On multivariate analysis, age at evaluation (P<.001), testosterone level ≤3.0 ng/mL (odds ratio [OR], 2.06; P=.005), and elevated sICAM-1 level (ORhighest vs lowest quartile, 3.58; P=.001) were significantly associated with MetS. Conclusions and Recommendations: Metabolic abnormalities in TCS are characterized by hypertension and increased LDL and total cholesterol levels but lower rates of decreased HDL levels and abdominal obesity, signifying possible shifts in fat distribution and fat metabolism. These changes are accompanied by hypogonadism and inflammation. TCS have a high prevalence of CVD risk factors that may not be entirely captured by standard MetS criteria. Cancer treatment–associated MetS requires further characterization

Neurocognitive outcomes of children exposed to and living with HIV aged 3–5 years in Kilifi, Kenya

IntroductionGlobally, 1.7 million children are living with HIV, with the majority of them residing in sub-Saharan Africa. Due to reduced rates of vertical transmission of HIV, there is an increasing population of children born to HIV-infected mothers who remain uninfected. There is a growing concern around the development of these children in the antiretroviral therapy era. This study examined the neurocognitive outcomes of children who are HIV-exposed infected (CHEI), HIV-exposed uninfected (CHEU) and HIV-unexposed uninfected (CHUU) and explored the relationship between child neurocognitive outcomes and child's biomedical and caregivers’ psychosocial factors.MethodsCHEI, CHUU and CHEU aged 3–5 years and their caregivers were recruited into the study. Neurocognitive outcomes were assessed using a validated battery of assessments. One-way analysis of variance and covariance (ANOVA and ANCOVA) were used to evaluate differences among the three groups by neurocognitive outcomes. Linear regression models were used to investigate the association between child neurocognitive outcomes and biomedical factors (nutritional status, HIV disease staging) and caregivers’ psychosocial factors [symptoms of common mental disorders (CMDs) and parenting behaviour].ResultsThe study included 153 children and their caregivers: 43 (28.1%) CHEI, 52 (34.0%) CHEU and 58 (39.9%) CHUU. ANOVA and ANCOVA revealed a significant difference in cognitive ability mean scores across the child groups. Post hoc analysis indicated that CHEU children had higher cognitive ability mean scores than the CHUU group. Better nutritional status was significantly associated with higher cognitive ability scores (β = 0.68, 95% CI [0.18–1.18], p = 0.008). Higher scores of CMDs were negatively associated with inhibitory control (β = −0.28, 95% CI [−0.53 to 0.02], p = 0.036). While comparing HIV stages 2 and 3, large effect sizes were seen in working memory (0.96, CI [0.08–1.80]) and cognitive ability scores (0.83 CI [0.01–1.63]), indicating those in stage 3 had poor performance.ConclusionsNeurocognitive outcomes were similar across CHEI, CHEU and CHUU, although subtle differences were seen in cognitive ability scores where CHEU had significantly higher cognitive mean scores than the CHUU. Well-designed longitudinal studies are needed to ascertain these findings. Nonetheless, study findings underscore the need for strategies to promote better child nutrition, mental health, and early antiretroviral therapy initiation

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Alternative splicing of the Anopheles gambiae Dscam gene in diverse Plasmodium falciparum infections

Background: In insects, including Anopheles mosquitoes, Dscam (Down syndrome cell adhesion molecule) appears to be involved in phagocytosis of pathogens, and shows pathogen-specific splice-form expression between divergent pathogen (or parasite) types (e.g. between bacteria and Plasmodium or between Plasmodium berghei and Plasmodium falciparum). Here, data are presented from the first study of Dscam expression in response to genetic diversity within a parasite species. Methods: In independent field and laboratory studies, a measure of Dscam splice-form diversity was compared between mosquitoes fed on blood that was free of P. falciparum to mosquitoes exposed to either single or mixed genotype infections of P. falciparum. Results: Significant increases in Anopheles gambiae Dscam (AgDscam) receptor diversity were observed in parasite-exposed mosquitoes, but only weak evidence that AgDscam diversity rises further upon exposure to mixed genotype parasite infections was found. Finally, a cluster of AgDscam exon 4 variants that become especially common during Plasmodium invasion was identified. Conclusions: While the data clearly indicate that AgDscam diversity increases with P. falciparum exposure, they do not suggest that AgDscam diversity rises further in response to increased parasite diversit

Multi-centred mixed-methods PEPFAR HIV care & support public health evaluation: study protocol

BACKGROUND: A public health response is essential to meet the multidimensional needs of patients and families affected by HIV disease in sub-Saharan Africa. In order to appraise current provision of HIV care and support in East Africa, and to provide evidence-based direction to future care programming, and Public Health Evaluation was commissioned by the PEPFAR programme of the US Government. METHODS/DESIGN: This paper described the 2-Phase international mixed methods study protocol utilising longitudinal outcome measurement, surveys, patient and family qualitative interviews and focus groups, staff qualitative interviews, health economics and document analysis. Aim 1) To describe the nature and scope of HIV care and support in two African countries, including the types of facilities available, clients seen, and availability of specific components of care [Study Phase 1]. Aim 2) To determine patient health outcomes over time and principle cost drivers [Study Phase 2]. The study objectives are as follows. 1) To undertake a cross-sectional survey of service configuration and activity by sampling 10% of the facilities being funded by PEPFAR to provide HIV care and support in Kenya and Uganda (Phase 1) in order to describe care currently provided, including pharmacy drug reviews to determine availability and supply of essential drugs in HIV management. 2) To conduct patient focus group discussions at each of these (Phase 1) to determine care received. 3) To undertake a longitudinal prospective study of 1200 patients who are newly diagnosed with HIV or patients with HIV who present with a new problem attending PEPFAR care and support services. Data collection includes self-reported quality of life, core palliative outcomes and components of care received (Phase 2). 4) To conduct qualitative interviews with staff, patients and carers in order to explore and understand service issues and care provision in more depth (Phase 2). 5) To undertake document analysis to appraise the clinical care procedures at each facility (Phase 2). 6) To determine principle cost drivers including staff, overhead and laboratory costs (Phase 2). DISCUSSION: This novel mixed methods protocol will permit transparent presentation of subsequent dataset results publication, and offers a substantive model of protocol design to measure and integrate key activities and outcomes that underpin a public health approach to disease management in a low-income setting

Adaptive Evolution of Staphylococcus aureus during Chronic Endobronchial Infection of a Cystic Fibrosis Patient

The molecular adaptation of Staphylococcus aureus to its host during chronic infection is not well understood. Comparative genome sequencing of 3 S. aureus isolates obtained sequentially over 26 months from the airways of a cystic fibrosis patient, revealed variation in phage content, and genetic polymorphisms in genes which influence antibiotic resistance, and global regulation of virulence. The majority of polymorphisms were isolate-specific suggesting the existence of an heterogeneous infecting population that evolved from a single infecting strain of S. aureus. The genetic variation identified correlated with differences in growth rate, hemolytic activity, and antibiotic sensitivity, implying a profound effect on the ecology of S. aureus. In particular, a high frequency of mutations in loci associated with the alternate transcription factor SigB, were observed. The identification of genes under diversifying selection during long-term infection may inform the design of novel therapeutics for the control of refractory chronic infections

Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects