Categories
Nevin Manimala Statistics

Efficacy, Pharmacokinetics, and Toxicity Profiles of a Broad Anti-SARS-CoV-2 Neutralizing Antibody

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

Categories
Nevin Manimala Statistics

Anthropogenic activities mediate stratification and stability of microbial communities in freshwater sediments

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

Categories
Nevin Manimala Statistics

Metabolic characteristics and pathogenesis of precocious puberty in girls: the role of perfluorinated compounds

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

Categories
Nevin Manimala Statistics

Investigating two mobile just-in-time adaptive interventions to foster psychological resilience: research protocol of the DynaM-INT study

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

Categories
Nevin Manimala Statistics

Association among peripatellar fat pad edema and related patellofemoral maltracking parameters: a case-control magnetic resonance imaging study

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

Categories
Nevin Manimala Statistics

Quality of life of COVID-19 recovered patients: a 1-year follow-up study from Bangladesh

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

Categories
Nevin Manimala Statistics

Associations between exposure to cadmium, lead, mercury and mixtures and women’s infertility and long-term amenorrhea

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

Categories
Nevin Manimala Statistics

Using the Health Belief Model to assess COVID-19 perceptions and behaviours among a group of Egyptian adults: a cross-sectional study

BMC Public Health. 2023 Aug 25;23(1):1624. doi: 10.1186/s12889-023-16513-x.

ABSTRACT

BACKGROUND: It is crucial to study the public’s perceptions and behaviour during a pandemic as this will be the driving force for practicing recommended precautions. The current study aimed to identify perceptions of a group of Egyptian adults to COVID-19 using the Health Belief Model (HBM), to measure self-reported practice of preventive behaviours and to identify influencing factors.

METHODS: Cross sectional study was used, including Egyptian adults aged 18 + years. A structured anonymous online questionnaire was used including: a demographic section, the modified MERS- CoV Health Belief Model scale after addition of questions related to COVID-19 and questions on preventive behaviours to COVID-19.

RESULTS: Of the 532 study participants, 28.6% were males, age ranges (18 to 74 years). There was a statistically significant positive correlation between total practice score and all COVID-19 Health Belief Model constructs total scores except for perceived barriers score showing negative correlation (P value < 0.05). Linear regression analysis showed that older age, male gender and living inside Cairo were associated with lower practice score (P value < 0.01).

CONCLUSIONS: Increased perceived susceptibility, perceived benefits, cues to action and perceived self-efficacy scores were associated with higher practice score in the current study. Additionally, results revealed that social media and websites can play an important role in shaping risk perception in the community. Stressing risk perception and efficacy beliefs prevention message can drive people to practice preventive behaviors.

PMID:37626356 | DOI:10.1186/s12889-023-16513-x

Categories
Nevin Manimala Statistics

Anomaly prediction of CT equipment based on IoMT data

BMC Med Inform Decis Mak. 2023 Aug 25;23(1):166. doi: 10.1186/s12911-023-02267-4.

ABSTRACT

BACKGROUND: Large-scale medical equipment, which is extensively implemented in medical services, is of vital importance for diagnosis but vulnerable to various anomalies and failures. Most hospitals that conduct regular maintenance have been suffering from medical equipment-related incidents for years. Currently, the Internet of Medical Things (IoMT) has emerged as a crucial tool in monitoring the real-time status of the medical equipment. In this paper, we develop an IoMT system of Computed Tomography (CT) equipment in the West China Hospital, Sichuan University and collected the system status time-series data. Novel multivariate time-series classification models and frameworks are proposed to predict the anomalies of CT equipment. The important features that are closely related to the equipment anomalies are identified with the model.

METHODS: We extracted the real-time CT equipment status time-series data of 11 equipment between May 19, 2020 and May 19, 2021 from the IoMT, which includes the equipment oil temperature, anode voltage, etc. The arcs are identified as labels of anomalies due to their relationship with decreased imaging quality and CT equipment failures. To improve prediction accuracy, the statistics and transformations of the raw historical time-series data segment in the sliding time window are used to construct new features. Due to the particularity of time-series data, two frameworks are proposed for splitting the training and test sets. Then the Decision Tree, Support Vector Machine, Logistic Regression, Naive Bayesian, and K-Nearest Neighbor classification models are used to classify the system status. We also compare our model to state-of-the-art models.

RESULTS: The results show that the anomaly prediction accuracy and recall of our method are 79% and 77%, respectively. The oil temperature and anode voltage are identified as the decisive features that may lead to anomalies. The proposed model outperforms the others when predicting the anomalies of the CT equipment based on our dataset.

CONCLUSIONS: The proposed method could predict the state of CT equipment and be used as a reference for practical maintenance, where unexpected anomalies of medical equipment could be reduced. It also brings new insights into how to handle non-uniform and imbalanced time series data in practical cases.

PMID:37626352 | DOI:10.1186/s12911-023-02267-4

Categories
Nevin Manimala Statistics

Sex-specific prevalence, awareness, treatment and control of hypertension in adults in India: a study for developing sex-specific public policy from the longitudinal ageing study in India (LASI) data 2017-2018

J Health Popul Nutr. 2023 Aug 25;42(1):85. doi: 10.1186/s41043-023-00404-3.

ABSTRACT

BACKGROUND AND OBJECTIVE: Hypertension is a key risk factor for cardiovascular disease and the leading cause of mortality among Indian adults. The difference in health status between men and women is becoming a great burden in itself worldwide. This study aimed to examine the differences between men and women in the prevalence, awareness, treatment, and control of hypertension and related risk factors among people aged 45 and older in India using data from the Longitudinal Ageing Study in India in 2017-2018.

METHODS: Descriptive statistics were presented separately for males and females. Multivariable logistic regression was used to analyze the socio-demographic, lifestyle behaviours, and biological factors associated with the prevalence of hypertension. All statistical analyses were conducted using Stata Version 16.0 statistical software. The study of the data was conducted using survey weights available in the LASI datasets.

KEY FINDINGS: Overall, the study found that 45.1% of the study population had hypertension, with 26.9% self-reporting their condition and 30% having hypertension at the time of measurement. Approximately 41% of males and 59% of females had hypertension. The self-reported hypertension of men was found to differ significantly from measured hypertension by 8.7%, while in women the difference was only 1.2%. Diabetes was found to increase the odds of having hypertension in both males (OR = 3.65, 95% CI (3.37-3.97)) and females (OR = 3.46, 95% CI (3.21-3.74)).

CONCLUSION: The difference between self-reported and measured hypertension in men and women is contributing to sex-gender and health inequalities that must be addressed. For adult females with hypertension, it is important to prioritize obesity, education level, physical activity, and regular clinic visits to manage chronic conditions. Based on our findings, policy recommendations can be made to focus on increasing women’s literacy, promoting men’s screening for hypertension, banning tobacco and alcohol sales, and organizing hypertension awareness campaigns specifically for men and in rural areas.

PMID:37626344 | DOI:10.1186/s41043-023-00404-3