Category: Nevin Manimala

Viruses. 2023 Aug 17;15(8):1757. doi: 10.3390/v15081757.

ABSTRACT

(1) Introduction: Since May 2021, sotrovimab has been available in Italy for early treatment of SARS-CoV-2 infection and to prevent disease progression. However, some in vitro studies have questioned its efficacy on Omicron variants. Therefore, we aim to further investigate the efficacy of sotrovimab in real-life settings. (2) Methods: We conducted a retrospective study collecting medical records of people with SARS-CoV-2 infection evaluated in the infectious diseases units of Sassari, Foggia, and Bari, Italy. We included people with SARS-CoV-2 infection treated with sotrovimab and people who did not receive any treatment in 2022. The primary study outcome was to evaluate the efficacy of sotrovimab in reducing disease progression (defined as the necessity of starting oxygen supplementation) and COVID-19-related death. The secondary outcome was to evaluate the safety of sotrovimab. (3) Results: We included 689 people; of them, 341 were treated with sotrovimab, while 348 did not receive any treatment. Overall, we registered 161 (23.4%) disease progressions and 65 (9.4%) deaths, with a significant difference between treated and not-treated people (p < 0.001). In the multivariate logistic regression, increasing age [OR for ten years increasing age 1.23 (95%CI 1.04-1.45)] was associated with a higher risk of disease progression. In addition, cardiovascular disease [OR 1.69 (1.01-2.80), fever [OR 3.88 (95%CI 2.35-6.38)], and dyspnea [OR 7.24 (95%CI 4.17-12.58)] were associated with an increased risk of disease progression. In contrast, vaccination [OR 0.21 (95%CI 0.12-0.37)] and sotrovimab administration [OR 0.05 (95%CI 0.02-0.11)] were associated with a lower risk of developing severe COVID-19. Regarding mortality, people with older age [OR for ten years increasing age 1.36 (95%CI 1.09-1.69)] had a higher risk of death. In addition, in the multivariate analysis, cardiovascular disease lost statistical significance, while people on chemotherapy for haematological cancer [OR 4.07 (95%CI 1.45-11.4)] and those with dyspnea at diagnosis [OR 3.63 (95%CI 2.02-6.50)] had an increased risk of death. In contrast, vaccination [OR 0.37 (95%CI 0.20-0.68)] and sotrovimab treatment [OR 0.16 (95%CI 0.06-0.42)] were associated with lower risk. Only two adverse events were reported; one person complained of diarrhoea a few hours after sotrovimab administration, and one had an allergic reaction with cutaneous rash and itching. (4) Conclusions: Our study showed that sotrovimab treatment was associated with a reduction of the risk of disease progression and death in SARS-CoV-2-infected people, 70% of whom were over 65 years and a with high vaccination rate, with excellent safety. Therefore, our results reinforce the evidence about the efficacy and safety of sotrovimab during the Omicron era in a real-world setting.

PMID:37632099 | DOI:10.3390/v15081757

Viruses. 2023 Aug 15;15(8):1743. doi: 10.3390/v15081743.

ABSTRACT

Epstein-Barr virus (EBV) is a well-known risk factor for the development of nasopharyngeal carcinoma, Hodgkin’s lymphoma (HL), and Non-Hodgkin’s lymphoma (NHL). People with HIV infection (PWH) are at increased risk for EBV-associated malignancies such as HL and NHL. Nevertheless, there are limited data on the burden of EBV among this population group in Ethiopia. Hence, this study aimed to determine the burden of EBV infection among adult HIV-positive individuals in Ethiopia and assess the determinants of EBV DNA positivity. We conducted a cross-sectional study at the Tikur Anbessa Specialised Hospital from March 2020 to March 2021. Two hundred and sixty individuals were enrolled in this study, including 179 HIV-positive and 81 HIV-negative individuals. A structured questionnaire was used to capture demographic and individual attributes. In addition, the clinical data of patients were also retrieved from clinical records. EBV viral capsid antigen (VCA) IgG antibody was measured by multiplex flow immunoassay, and EBV DNA levels were tested by quantitative real-time polymerase chain reaction (q-PCR) assays targeting the EBNA-1 open reading frame (ORF). Descriptive statistics were conducted to assess each study variable. A multivariable logistic regression model was applied to evaluate the determinants of EBV infection. Statistical significance was determined at a p-value < 0.05. Two hundred and fifty-three (97.7%) study participants were seropositive for the EBV VCA IgG antibody. Disaggregated by HIV status, 99.4% of HIV-positive and 93.8% of HIV-negative participants were EBV seropositive. In this study, 49.7% of HIV-positive and 24.7% of HIV-negative individuals were EBV DNA positive. PWH had a higher risk of EBV DNA positivity at 3.05 times (AOR: 3.05, 95% CI: 1.40-6.67). Moreover, among PWH, those with an HIV viral load greater than 1000 RNA copies/mL (AOR = 5.81, 95% CI = 1.40, 24.13) had a higher likelihood of EBV DNA positivity. The prevalence of EBV among PWH was significantly higher than among HIV-negative individuals. Higher HIV viral loads in PWH were associated with an increased risk of EBV DNA positivity. Since the increases in the viral load of EBV DNA among PWH could be related to the risk of developing EBV-associated cancers, it is necessary for more research on the role of EBV in EBV-associated cancer in this population group to be carried out.

PMID:37632085 | DOI:10.3390/v15081743

Viruses. 2023 Aug 14;15(8):1735. doi: 10.3390/v15081735.

ABSTRACT

HepB LiveTest is a machine learning decision support system developed for the early detection of hepatitis B virus (HBV). However, there is a lack of evidence on its generalisability. In this study, we aimed to externally assess the clinical validity and portability of HepB LiveTest in predicting HBV infection among independent patient cohorts from Nigeria and Australia. The performance of HepB LiveTest was evaluated by constructing receiver operating characteristic curves and estimating the area under the curve. Delong’s method was used to estimate the 95% confidence interval (CI) of the area under the receiver-operating characteristic curve (AUROC). Compared to the Australian cohort, patients in the derivation cohort of HepB LiveTest and the hospital-based Nigerian cohort were younger (mean age, 45.5 years vs. 38.8 years vs. 40.8 years, respectively; p < 0.001) and had a higher incidence of HBV infection (1.9% vs. 69.4% vs. 57.3%). In the hospital-based Nigerian cohort, HepB LiveTest performed optimally with an AUROC of 0.94 (95% CI, 0.91-0.97). The model provided tailored predictions that ensured most cases of HBV infection did not go undetected. However, its discriminatory measure dropped to 0.60 (95% CI, 0.56-0.64) in the Australian cohort. These findings indicate that HepB LiveTest exhibits adequate cross-site transportability and clinical validity in the hospital-based Nigerian patient cohort but shows limited performance in the Australian cohort. Whilst HepB LiveTest holds promise for reducing HBV prevalence in underserved populations, caution is warranted when implementing the model in older populations, particularly in regions with low incidence of HBV infection.

PMID:37632077 | DOI:10.3390/v15081735

Viruses. 2023 Aug 14;15(8):1733. doi: 10.3390/v15081733.

ABSTRACT

We recently reported the isolation and characterization of an anti-SARS-CoV-2 antibody, called IgG-A7, that protects transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from an infection with SARS-CoV-2 Wuhan. We show here that IgG-A7 protected 100% of the transgenic mice infected with Delta (B.1.617.2) and Omicron (B.1.1.529) at doses of 0.5 and 5 mg/kg, respectively. In addition, we studied the pharmacokinetic (PK) profile and toxicology (Tox) of IgG-A7 in CD-1 mice at single doses of 100 and 200 mg/kg. The PK parameters at these high doses were proportional to the doses, with serum half-life of ~10.5 days. IgG-A7 was well tolerated with no signs of toxicity in urine and blood samples, nor in histopathology analyses. Tissue cross-reactivity (TCR) with a panel of mouse and human tissues showed no evidence of IgG-A7 interaction with the tissues of these species, supporting the PK/Tox results and suggesting that, while IgG-A7 has a broad efficacy profile, it is not toxic in humans. Thus, the information generated in the CD-1 mice as a PK/Tox model complemented with the mouse and human TCR, could be of relevance as an alternative to Non-Human Primates (NHPs) in rapidly emerging viral diseases and/or quickly evolving viruses such as SARS-CoV-2.

PMID:37632075 | DOI:10.3390/v15081733

Microbiome. 2023 Aug 26;11(1):191. doi: 10.1186/s40168-023-01612-z.

ABSTRACT

BACKGROUND: Freshwater sediment microbes are crucial decomposers that play a key role in regulating biogeochemical cycles and greenhouse gas emissions. They often exhibit a highly ordered structure along depth profiles. This stratification not only reflects redox effects but also provides valuable insights into historical transitions, as sediments serve as important archives for tracing environmental history. The Anthropocene, a candidate geological epoch, has recently garnered significant attention. However, the human impact on sediment zonation under the cover of natural redox niches remains poorly understood. Dam construction stands as one of the most far-reaching anthropogenic modifications of aquatic ecosystems. Here we attempted to identify the ecological imprint of damming on freshwater sediment microbiome.

RESULTS: We conducted a year-round survey on the sediment profiles of Lake Chaohu, a large shallow lake in China. Through depth-discrete shotgun metagenomics, metataxonomics, and geophysiochemical analyses, we unveiled a unique prokaryotic hierarchy shaped by the interplay of redox regime and historical damming (labeled by the ¹³⁷Cs peak in AD 1963). Dam-induced initial differentiation was further amplified by nitrogen and methane metabolism, forming an abrupt transition governing nitrate-methane metabolic interaction and gaseous methane sequestration depth. Using a random forest algorithm, we identified damming-sensitive taxa that possess distinctive metabolic strategies, including energy-saving mechanisms, unique motility behavior, and deep-environment preferences. Moreover, null model analysis showed that damming altered microbial community assembly, from a selection-oriented deterministic process above to a more stochastic, dispersal-limited one below. Temporal investigation unveiled the rapid transition zone as an ecotone, characterized by high species richness, low community stability, and emergent stochasticity. Path analysis revealed the observed emergent stochasticity primarily came from the high metabolic flexibility, which potentially contributed to both ecological and statistical neutralities.

CONCLUSIONS: We delineate a picture in which dam-induced modifications in nutrient availability and sedimentation rates impact microbial metabolic activities and generate great changes in the community structure, assembly, and stability of the freshwater sediment microbiome. These findings reflect profound ecological and biogeochemical ramifications of human-Earth system interactions and help re-examine the mainstream views on the formation of sediment microbial stratification. Video Abstract.

PMID:37626433 | DOI:10.1186/s40168-023-01612-z

BMC Med. 2023 Aug 25;21(1):323. doi: 10.1186/s12916-023-03032-0.

ABSTRACT

BACKGROUND: Precocious puberty (PP) in girls is traditionally defined as the onset of breast development before the age of 8 years. The specific biomarkers of premature thelarche (PT) and central precocious puberty (CPP) girls are uncertain, and little is known about their metabolic characteristics driven by perfluorinated compounds (PFCs) and clinical phenotype. This study aimed to screen specific biomarkers of PT and CPP and elucidate their underlying pathogenesis. The relationships of clinical phenotype-serum PFCs-metabolic characteristics were also explored to reveal the relationship between PFCs and the occurrence and development of PT and CPP.

METHODS: Nuclear magnetic resonance (NMR)-based cross-metabolomics strategy was performed on serum from 146 PP (including 30 CPP, 40 PT, and 76 unspecified PP) girls and 64 healthy girls (including 36 prepubertal and 28 adolescent). Specific biomarkers were screened by the uni- and multivariate statistical analyses. The relationships between serum PFCs and clinical phenotype were performed by correlation analysis and weighted gene co-expression network analysis to explore the link of clinical phenotype-PFCs-metabolic characteristics in PT and CPP.

RESULTS: The disordered trend of pyruvate and butyrate metabolisms (metabolites mapped as formate, ethanol, and 3-hydroxybutyrate) were shared and kept almost consistent in PT and CPP. Eight and eleven specific biomarkers were screened for PT and CPP, respectively. The area under curve of specific biomarker combination was 0.721 in CPP vs. prepubertal, 0.972 in PT vs. prepubertal, 0.646 in CPP vs. prepubertal integrated adolescent, and 0.822 in PT vs. prepubertal integrated adolescent, respectively. Perfluoro-n-heptanoic acid and perfluoro-n-hexanoic acid were statistically different between PT and CPP. Estradiol and prolactin were significantly correlated with PFCs in CPP and PT. Clinical phenotypes and PFCs drive the metabolic characteristics and cause metabolic disturbances in CPP and PT.

CONCLUSIONS: The elevation of formate, ethanol, and 3-hydroxybutyrate may serve as the early diagnostic indicator for PP in girls. But the stratification of PP still needs to be further determined based on the specific biomarkers. Specific biomarkers of CPP and PT exhibited good sensitivity and can facilitate the classification diagnosis of CPP and PT. PFC exposure is associated with endocrine homeostasis imbalance. PFC exposure and/or endocrine disturbance directly or indirectly drive metabolic changes and form overall metabolic network perturbations in CPP and PT.

PMID:37626398 | DOI:10.1186/s12916-023-03032-0

BMC Psychol. 2023 Aug 25;11(1):245. doi: 10.1186/s40359-023-01249-5.

ABSTRACT

BACKGROUND: Stress-related disorders such as anxiety and depression are highly prevalent and cause a tremendous burden for affected individuals and society. In order to improve prevention strategies, knowledge regarding resilience mechanisms and ways to boost them is highly needed. In the Dynamic Modelling of Resilience – interventional multicenter study (DynaM-INT), we will conduct a large-scale feasibility and preliminary efficacy test for two mobile- and wearable-based just-in-time adaptive interventions (JITAIs), designed to target putative resilience mechanisms. Deep participant phenotyping at baseline serves to identify individual predictors for intervention success in terms of target engagement and stress resilience.

METHODS: DynaM-INT aims to recruit N = 250 healthy but vulnerable young adults in the transition phase between adolescence and adulthood (18-27 years) across five research sites (Berlin, Mainz, Nijmegen, Tel Aviv, and Warsaw). Participants are included if they report at least three negative burdensome past life events and show increased levels of internalizing symptoms while not being affected by any major mental disorder. Participants are characterized in a multimodal baseline phase, which includes neuropsychological tests, neuroimaging, bio-samples, sociodemographic and psychological questionnaires, a video-recorded interview, as well as ecological momentary assessments (EMA) and ecological physiological assessments (EPA). Subsequently, participants are randomly assigned to one of two ecological momentary interventions (EMIs), targeting either positive cognitive reappraisal or reward sensitivity. During the following intervention phase, participants’ stress responses are tracked using EMA and EPA, and JITAIs are triggered if an individually calibrated stress threshold is crossed. In a three-month-long follow-up phase, parts of the baseline characterization phase are repeated. Throughout the entire study, stressor exposure and mental health are regularly monitored to calculate stressor reactivity as a proxy for outcome resilience. The online monitoring questionnaires and the repetition of the baseline questionnaires also serve to assess target engagement.

DISCUSSION: The DynaM-INT study intends to advance the field of resilience research by feasibility-testing two new mechanistically targeted JITAIs that aim at increasing individual stress resilience and identifying predictors for successful intervention response. Determining these predictors is an important step toward future randomized controlled trials to establish the efficacy of these interventions.

PMID:37626397 | DOI:10.1186/s40359-023-01249-5

BMC Musculoskelet Disord. 2023 Aug 25;24(1):678. doi: 10.1186/s12891-023-06827-7.

ABSTRACT

BACKGROUND: The peripatellar fat pads are critical for protective cushioning during movement, and their endocrine function has been shown to affect osteoarthritis. Magnetic resonance imaging (MRI) is frequently used to visualize edema of the peripatellar fat pads due to injury. In this study, we aimed to assess the relationship between peripatellar fat pad edema and patellofemoral maltracking MRI parameters and investigate the association among cases of peripatellar fat pad edema.

METHODS: Age- and sex-matched peripatellar fat pad edema cases were identified and divided into superolateral Hoffa, quadriceps, and prefemoral groups. Images were assessed according to tibial tuberosity lateralization, trochlear dysplasia, patellar alta, patellar tilt, and bisect offset. McNemar’s test or paired t-tests and Spearman’s correlation were used for statistical analysis. Interobserver agreement was assessed with the intraclass correlation coefficient.

RESULTS: Of 1210 MRI scans, 50, 68, and 42 cases were in the superolateral Hoffa, quadriceps, and prefemoral groups, respectively. Subjects with superolateral Hoffa fat pad edema had a lower lateral trochlear inclination (p = 0.028), higher Insall-Salvati (p < 0.001) and modified Insall-Salvati (p = 0.021) ratios, and lower patellotrochlear index (p < 0.001) than controls. The prefemoral group had a lower lateral trochlear inclination (p = 0.014) and higher Insall-Salvati (p < 0.001) and modified Insall-Salvati (p = 0.004) ratios compared with the control group. In contrast, the patellotrochlear index (p = 0.001) was lower. Mean patellar tilt angle (p = 0.019) and mean bisect offset (p = 0.005) were significantly different between cases and controls. The quadriceps group showed no association. Superolateral Hoffa was positively correlated with prefemoral (p < 0.001, r = 0.408) and negatively correlated with quadriceps (p < 0.001, r = -0.500) fat pad edema.

CONCLUSIONS: Superolateral Hoffa and prefemoral fat pad edemas were associated with patellar maltracking parameters. Quadriceps fat pad edema and maltracking parameters were not associated. Superolateral Hoffa fat pad edema was positively correlated with prefemoral and negatively correlated with quadriceps fat pad edema.

PMID:37626375 | DOI:10.1186/s12891-023-06827-7

Infect Dis Poverty. 2023 Aug 25;12(1):79. doi: 10.1186/s40249-023-01125-9.

ABSTRACT

BACKGROUND: The COVID-19 pandemic posed a danger to global public health because of the unprecedented physical, mental, social, and environmental impact affecting quality of life (QoL). The study aimed to find the changes in QoL among COVID-19 recovered individuals and explore the determinants of change more than 1 year after recovery in low-resource settings.

METHODS: COVID-19 patients from all eight divisions of Bangladesh who were confirmed positive by reverse transcription-polymerase chain reaction from June 2020 to November 2020 and who subsequently recovered were followed up twice, once immediately after recovery and again 1 year after the first follow-up. The follow-up study was conducted from November 2021 to January 2022 among 2438 individuals using the World Health Organization Quality of Life Brief Version (WHOQOL-BREF). After excluding 48 deaths, 95 were rejected to participate, 618 were inaccessible, and there were 45 cases of incomplete data. Descriptive statistics, paired-sample analyses, generalized estimating equation (GEE) analysis, and multivariable logistic regression analyses were performed to test the mean difference in participants’ QoL scores between the two interviews.

RESULTS: Most participants (n = 1710, 70.1%) were male, and one-fourth (24.4%) were older than 46. The average physical domain score decreased significantly from baseline to follow-up, and the average scores in psychological, social, and environmental domains increased significantly at follow-up (P < 0.05). By the GEE equation approach, after adjusting for other factors, we found that older age groups (P < 0.001), being female (P < 0.001), having hospital admission during COVID-19 illness (P < 0.001), and having three or more chronic diseases (P < 0.001), were significantly associated with lower physical and psychological QoL scores. Higher age and female sex [adjusted odd ratio (aOR) = 1.3, 95% confidence interval (CI) 1.0-1.6] were associated with reduced social domain scores on multivariable logistic regression analysis. Urban or semi-urban people were 49% less likely (aOR = 0.5, 95% CI 0.4-0.7) and 32% less likely (aOR = 0.7, 95% CI 0.5-0.9) to have a reduced QoL score in the psychological domain and the social domain respectively, than rural people. Higher-income people were more likely to experience a decrease in QoL scores in physical, psychological, social, and environmental domains. Married people were 1.8 times more likely (aOR = 1.8, 95% CI 1.3-2.4) to have a decreased social QoL score. In the second interview, people admitted to hospitals during their COVID-19 infection showed a 1.3 times higher chance (aOR = 1.3, 95% CI 1.1-1.6) of a decreased environmental QoL score. Almost 13% of participants developed one or more chronic diseases between the first and second interviews. Moreover, 7.9% suffered from reinfection by COVID-19 during this 1-year time.

CONCLUSIONS: The present study found that the QoL of COVID-19 recovered people improved 1 year after recovery, particularly in psychological, social, and environmental domains. However, age, sex, the severity of COVID-19, smoking habits, and comorbidities were significantly negatively associated with QoL. Events of reinfection and the emergence of chronic disease were independent determinants of the decline in QoL scores in psychological, social, and physical domains, respectively. Strong policies to prevent and minimize smoking must be implemented in Bangladesh, and we must monitor and manage chronic diseases in people who have recovered from COVID-19.

PMID:37626363 | DOI:10.1186/s40249-023-01125-9

Arch Public Health. 2023 Aug 25;81(1):161. doi: 10.1186/s13690-023-01172-6.

ABSTRACT

BACKGROUND: Cadmium (Cd), lead (Pb), and mercury (Hg) have been shown to exhibit endocrine disrupting properties. Their effects on women’s reproductive health, however, remain elusive. Here, we investigated associations between blood concentrations of Pb, Cd, Hg, and their mixture and infertility and long-term amenorrhea in women aged 20-49 years using the US National Health and Nutrition Examination Survey (NHANES) 2013-2018 cross-sectional survey.

METHODS: A total of 1,990 women were included for the analysis of infertility and 1,919 women for long-term amenorrhea. The methods of log-transformation and use of quartiles were used to analyze blood heavy metal concentrations. Statistical differences in the covariates between the outcome groups were evaluated using a chi-squared test for categorical variables and a t-test for continuous variables. Multiple logistic regression models were used to examine the associations.

RESULTS: The blood concentrations of Pb and heavy metal mixtures were significantly higher in ever-infertile women than pregnant women, but the concentrations of Cd and Hg were comparable. After full adjustment, multiple logistic regression analyses revealed a significant and dose-dependent positive association between blood Pb concentrations and women’s historical infertility, a negative association between Cd and women’s long-term amenorrhea, and no associations between Hg and heavy metal mixture and women’s infertility or long-term amenorrhea.

CONCLUSIONS: Our study suggests that exposure to heavy metals exhibit differential associations with history of infertility and amenorrhea, and Pb may adversely impact women’s reproduction and heighten the risks of infertility and long-term amenorrhea.

PMID:37626359 | DOI:10.1186/s13690-023-01172-6