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Nevin Manimala Statistics

Investigation of crocin’s protective effect on cyclophosphamide-induced hypothalamic-pituitary-gonadal axis defects in adult female rats

Women Health. 2023 Nov 28:1-9. doi: 10.1080/03630242.2023.2286264. Online ahead of print.

ABSTRACT

Cyclophosphamide is a drug used in chemotherapy. However, it has side effects, including changes in reproductive system functioning. Some herbal compounds can reduce the harmful effects of cyclophosphamide. This study aims to investigate the protective role of crocin against changes caused by Cyclophosphamide in ovarian tissue through changes in the expression of genes involved in the hypothalamic-pituitary-gonadal axis. This experimental study was performed on 24 adult female Wistar rats. Mice were divided into four groups (normal saline, 30 mg/kg cyclophosphamide, 100 mg/kg crocin and 30 mg/kg cyclophosphamide, and 200 mg/kg crocin and 30 mg/kg cyclophosphamide). At the end of the treatment period, the hypothalamus and ovaries were also removed to evaluate ob-Rb, ob-Ra, and NPY genes expression using real-time PCR and histological changes in the ovaries. Data were analyzed by SPSS statistical software. The expression of genes, number of follicles, and follicle diameter significantly decreased in the cyclophosphamide-treated groups compared with the control group. In the crocin and cyclophosphamide-treated groups, drug-induced reproductive complications were mitigated. The current findings indicate that by increasing the expression of genes ob-Rb, ob-Ra, and NPY, crocin could modulate the harmful effects of cyclophosphamide.

PMID:38014433 | DOI:10.1080/03630242.2023.2286264

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Early Serial Echocardiographic and Ultrasonographic Findings in Critically Ill Patients With COVID-19

CHEST Crit Care. 2023 Jun;1(1):100002. doi: 10.1016/j.chstcc.2023.100002. Epub 2023 Mar 22.

ABSTRACT

BACKGROUND: Cardiac function of critically ill patients with COVID-19 generally has been reported from clinically obtained data. Echocardiographic deformation imaging can identify ventricular dysfunction missed by traditional echocardiographic assessment.

RESEARCH QUESTION: What is the prevalence of ventricular dysfunction and what are its implications for the natural history of critical COVID-19?

STUDY DESIGN AND METHODS: This is a multicenter prospective cohort of critically ill patients with COVID-19. We performed serial echocardiography and lower extremity vascular ultrasound on hospitalization days 1, 3, and 8. We defined left ventricular (LV) dysfunction as the absolute value of longitudinal strain of < 17% or left ventricle ejection fraction (LVEF) of < 50%. Primary clinical outcome was inpatient survival.

RESULTS: We enrolled 110 patients. Thirty-nine (35.5%) died before hospital discharge. LV dysfunction was present at admission in 38 patients (34.5%) and in 21 patients (36.2%) on day 8 (P = .59). Median baseline LVEF was 62% (interquartile range [IQR], 52%-69%), whereas median absolute value of baseline LV strain was 16% (IQR, 14%-19%). Survivors and nonsurvivors did not differ statistically significantly with respect to day 1 LV strain (17.9% vs 14.4%; P = .12) or day 1 LVEF (60.5% vs 65%; P = .06). Nonsurvivors showed worse day 1 right ventricle (RV) strain than survivors (16.3% vs 21.2%; P = .04).

INTERPRETATION: Among patients with critical COVID-19, LV and RV dysfunction is common, frequently identified only through deformation imaging, and early (day 1) RV dysfunction may be associated with clinical outcome.

PMID:38014378 | PMC:PMC10030437 | DOI:10.1016/j.chstcc.2023.100002

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Machine learning-based prediction of COVID-19 mortality using immunological and metabolic biomarkers

BMC Digit Health. 2023;1(1):6. doi: 10.1186/s44247-022-00001-0. Epub 2023 Feb 3.

ABSTRACT

COVID-19 mortality prediction Background COVID-19 has become a major global public health problem, despite prevention and efforts. The daily number of COVID-19 cases rapidly increases, and the time and financial costs associated with testing procedure are burdensome. Method To overcome this, we aim to identify immunological and metabolic biomarkers to predict COVID-19 mortality using a machine learning model. We included inpatients from Hong Kong’s public hospitals between January 1, and September 30, 2020, who were diagnosed with COVID-19 using RT-PCR. We developed three machine learning models to predict the mortality of COVID-19 patients based on data in their electronic medical records. We performed statistical analysis to compare the trained machine learning models which are Deep Neural Networks (DNN), Random Forest Classifier (RF) and Support Vector Machine (SVM) using data from a cohort of 5,059 patients (median age = 46 years; 49.3% male) who had tested positive for COVID-19 based on electronic health records and data from 532,427 patients as controls. Result We identified top 20 immunological and metabolic biomarkers that can accurately predict the risk of mortality from COVID-19 with ROC-AUC of 0.98 (95% CI 0.96-0.98). Of the three models used, our result demonstrate that the random forest (RF) model achieved the most accurate prediction of mortality among COVID-19 patients with age, glomerular filtration, albumin, urea, procalcitonin, c-reactive protein, oxygen, bicarbonate, carbon dioxide, ferritin, glucose, erythrocytes, creatinine, lymphocytes, PH of blood and leukocytes among the most important biomarkers identified. A cohort from Kwong Wah Hospital (131 patients) was used for model validation with ROC-AUC of 0.90 (95% CI 0.84-0.92). Conclusion We recommend physicians closely monitor hematological, coagulation, cardiac, hepatic, renal and inflammatory factors for potential progression to severe conditions among COVID-19 patients. To the best of our knowledge, no previous research has identified important immunological and metabolic biomarkers to the extent demonstrated in our study.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s44247-022-00001-0.

PMID:38014372 | PMC:PMC9896457 | DOI:10.1186/s44247-022-00001-0

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Differential responses of primary neuron-secreted MCP-1 and IL-9 to type 2 diabetes and Alzheimer’s disease-associated metabolites

bioRxiv. 2023 Nov 17:2023.11.17.567595. doi: 10.1101/2023.11.17.567595. Preprint.

ABSTRACT

Type 2 diabetes (T2D) is implicated as a risk factor for Alzheimer’s disease (AD), the most common form of dementia. In this work, we investigated neuroinflammatory responses of primary neurons to potentially circulating, blood-brain barrier (BBB) permeable metabolites associated with AD, T2D, or both. We identified nine metabolites associated with protective or detrimental properties of AD and T2D in literature (lauric acid, asparagine, fructose, arachidonic acid, aminoadipic acid, sorbitol, retinol, tryptophan, niacinamide) and stimulated primary mouse neuron cultures with each metabolite before quantifying cytokine secretion via Luminex. We employed unsupervised clustering, inferential statistics, and partial least squares discriminant analysis to identify relationships between cytokine concentration and disease-associations of metabolites. We identified MCP-1, a cytokine associated with monocyte recruitment, as differentially abundant between neurons stimulated by metabolites associated with protective and detrimental properties of AD and T2D. We also identified IL-9, a cytokine that promotes mast cell growth, to be differentially associated with T2D. Indeed, cytokines, such as MCP-1 and IL-9, released from neurons in response to BBB-permeable metabolites associated with T2D may contribute to AD development by downstream effects of neuroinflammation.

PMID:38014333 | PMC:PMC10680853 | DOI:10.1101/2023.11.17.567595

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Genomic Insights into the Shared and Distinct Genetic Architecture of Cognitive Function and Schizophrenia

medRxiv. 2023 Nov 14:2023.11.13.23298348. doi: 10.1101/2023.11.13.23298348. Preprint.

ABSTRACT

Cognitive impairment is a major determinant of functional outcomes in schizophrenia, and efforts to understand the biological basis of cognitive dysfunction in the disorder are ongoing. Previous studies have suggested genetic overlap between global cognitive ability and schizophrenia, but further work is needed to delineate the shared genetic architecture. Here, we apply genomic structural equation modelling to identify latent cognitive factors capturing genetic liabilities to 12 cognitive traits measured in the UK Biobank (UKB). We explore the overlap between latent cognitive factors, schizophrenia, and schizophrenia symptom dimensions using a complementary set of statistical approaches, applied to data from the latest schizophrenia genome-wide association study (Ncase = 53,386, Ncontrol = 77,258) and the Thematically Organised Psychosis study (Ncase = 306, Ncontrol = 1060). We identified three broad factors (visuo-spatial, verbal analytic and decision/reaction time) that underly the genetic correlations between the UKB cognitive tests. Global genetic correlations showed a significant but moderate negative genetic correlation between each cognitive factor and schizophrenia. Local genetic correlations implicated unique genomic regions underlying the overlap between schizophrenia and each cognitive factor. We found evidence of substantial polygenic overlap between each cognitive factor and schizophrenia but show that most loci shared between the latent cognitive factors and schizophrenia have unique patterns of association with the cognitive factors. Biological annotation of the shared loci implicated gene-sets related to neurodevelopment and neuronal function. Lastly, we find that the common genetic determinants of the latent cognitive factors are not predictive of schizophrenia symptom dimensions. Overall, these findings inform our understanding of cognitive function in schizophrenia by demonstrating important differences in the shared genetic architecture of schizophrenia and cognitive abilities.

PMID:38014326 | PMC:PMC10680895 | DOI:10.1101/2023.11.13.23298348

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Cingulate cortex facilitates auditory perception under challenging listening conditions

bioRxiv. 2023 Nov 14:2023.11.10.566668. doi: 10.1101/2023.11.10.566668. Preprint.

ABSTRACT

We often exert greater cognitive resources (i.e., listening effort) to understand speech under challenging acoustic conditions. This mechanism can be overwhelmed in those with hearing loss, resulting in cognitive fatigue in adults, and potentially impeding language acquisition in children. However, the neural mechanisms that support listening effort are uncertain. Evidence from human studies suggest that the cingulate cortex is engaged under difficult listening conditions, and may exert top-down modulation of the auditory cortex (AC). Here, we asked whether the gerbil cingulate cortex (Cg) sends anatomical projections to the AC that facilitate perceptual performance. To model challenging listening conditions, we used a sound discrimination task in which stimulus parameters were presented in either ‘Easy’ or ‘Hard’ blocks (i.e., long or short stimulus duration, respectively). Gerbils achieved statistically identical psychometric performance in Easy and Hard blocks. Anatomical tracing experiments revealed a strong, descending projection from layer 2/3 of the Cg1 subregion of the cingulate cortex to superficial and deep layers of primary and dorsal AC. To determine whether Cg improves task performance under challenging conditions, we bilaterally infused muscimol to inactivate Cg1, and found that psychometric thresholds were degraded for only Hard blocks. To test whether the Cg-to-AC projection facilitates task performance, we chemogenetically inactivated these inputs and found that performance was only degraded during Hard blocks. Taken together, the results reveal a descending cortical pathway that facilitates perceptual performance during challenging listening conditions.

SIGNIFICANCE STATEMENT: Sensory perception often occurs under challenging conditions, such a noisy background or dim environment, yet stimulus sensitivity can remain unaffected. One hypothesis is that cognitive resources are recruited to the task, thereby facilitating perceptual performance. Here, we identify a top-down cortical circuit, from cingulate to auditory cortex in the gerbils, that supports auditory perceptual performance under challenging listening conditions. This pathway is a plausible circuit that supports effortful listening, and may be degraded by hearing loss.

PMID:38014324 | PMC:PMC10680599 | DOI:10.1101/2023.11.10.566668

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Physical and mental health of informal caregivers before and during the COVID-19 pandemic in the United States

BMC Public Health. 2023 Nov 27;23(1):2349. doi: 10.1186/s12889-023-17164-8.

ABSTRACT

BACKGROUND: Informal caregiving, a common form of social support, can be a chronic stressor with health consequences for caregivers. It is unclear how varying restrictions during the COVID-19 pandemic affected caregivers’ physical and mental health. This study explores pre-post March 2020 differences in reported days of poor physical and mental health among informal caregivers.

METHODS: Data from the 2019/2020 Behavioral Risk Factor Surveillance System survey were used to match, via propensity scores, informal caregivers who provided care during COVID-19 restrictions to those who provided care before the pandemic. Negative binomial weighted regression models estimated incidence rate ratios (IRRs) and differences by demographics of reporting days of poor physical and mental health. A sensitivity analysis including multiple imputation was also performed.

RESULTS: The sample included 9,240 informal caregivers, of whom 861 provided care during the COVID-19 pandemic. The incidence rate for days of poor physical health was 26% lower (p = 0.001) for those who provided care during the COVID-19 pandemic, though the incidence rates for days of poor mental health were not statistically different between groups. Informal caregivers with low educational attainment experienced significantly higher IRRs for days of poor physical and mental health. Younger informal caregivers had a significantly lower IRR for days of poor physical health, but higher IRR for days of poor mental health.

CONCLUSIONS: This study contends that the physical and mental health burden associated with informal caregiving in a period of great uncertainty may be heightened among certain populations. Policymakers should consider expanding access to resources through institutional mechanisms for informal caregivers, who may be likely to incur a higher physical and mental health burden during public health emergencies, especially those identified as higher risk.

PMID:38012592 | DOI:10.1186/s12889-023-17164-8

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Knowledge, attitude and practice of physical exercises among pregnant women attending prenatal care clinics of public health institutions in Hawassa city, Sidama, Ethiopia, in 2021: descriptive cross-sectional study

BMC Womens Health. 2023 Nov 27;23(1):630. doi: 10.1186/s12905-023-02756-8.

ABSTRACT

BACKGROUND: Participating in physical exercise enhances the physical and mental health of pregnant women. Preventing excessive weight gain, decreasing gestational hypertension, reducing back pain and labor complications are some of the main benefits of physical exercise during pregnancy and childbirth. Scrutinizing factors associated with sedentary life style among women during pregnancy could aid to design effective strategies to tackle the problem. Despite its benefit, little is explored about knowledge, attitude and practice of physical exercise among pregnant women in the study setting.

OBJECTIVE: To assess prevalence of knowledge, attitude and practice of physical exercise among pregnant women who visit antenatal care at public health facilities of Hawassa town, Ethiopia, in 2023.

METHODS: Facility based survey was conducted from November-December, in 2021. Data were collected using interview administered and structured questionnaire. Data were cleaned, coded and entered using Epi-data 4.6 and exported into SPSS 25 for analysis. Descriptive statistics was done using frequency count, percentage and mean values of variables. Finally, findings are presented using text, tables and charts.

RESULTS: All of the study subjects completed interview making a response rate of 100% in this study. The mean adequate knowledge score was 42.2%. Positive attitude towards physical exercise during pregnancy was accounted as 63.7% and proportion of good practice of physical exercise was as 35.8%. Regarding practice of exercise, most (95.9%) of the subjects walk, however; only 11(8.9%) women perform pelvic floor exercise were the highest and least practiced physical exercise. Concerning knowledge of exercise, prevent excess weight 72.1% and increasing energy 53.2% were the commonly known benefits of physical exercise. Breathing difficulty (41.3%), chest pain (39.8%) and premature labor (34.0%) were the predominant perceptions of contra-indication of physical exercise during pregnancy.

CONCLUSIONS: In conclusion, the proportion of knowledge, attitude and practice of antenatal exercise is found to be sub-optimum in the study area. Therefore, health education should be enhanced about the benefit of physical exercise during pregnancy.

PMID:38012589 | DOI:10.1186/s12905-023-02756-8

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Evaluating the effect of a 12-month youth advisory group on adolescent’s leadership skills and perceptions related to chronic disease prevention research: a mixed-methods study

BMC Public Health. 2023 Nov 27;23(1):2344. doi: 10.1186/s12889-023-17283-2.

ABSTRACT

BACKGROUND: Youth Advisory Groups (YAGs) represent a promising method to engage adolescents in research of relevance to them and their peers. However, YAGs are rarely implemented or evaluated in chronic disease prevention research. The aims of this study were firstly, to evaluate the effect of participation in a 12-month YAG on adolescents’ leadership skills and perceptions related to chronic disease prevention research and secondly, to evaluate the process of establishing and facilitating a 12-month YAG and identify barriers and enablers to establishment and facilitation.

METHODS: This study was a 12-month pre-post study. Eligible participants were adolescents (13-18-years) and current members of an established YAG. Data collection involved online surveys and semi-structured interviews at baseline, six-months and 12-months follow-up. Participatory outcomes such as self-efficacy, leadership skills, and collective participation were derived from Youth Participatory Action Research Principles (YPAR), and the Lansdown-UNICEF conceptual framework for measuring outcomes of adolescent participation. Process evaluation data were captured via meeting minutes, Slack metrics and researcher logs. Quantitative data was analysed using descriptive statistics and qualitative data was thematically analysed using a reflexive thematic analysis approach.

RESULTS: Thirteen (13/16) YAG youth advisors consented to participate in the evaluation study (mean age 16.0 years, SD 1.3; 62% (8/13) identified as female). Survey data assessing participatory outcomes found an increase in leadership and life skills scores over 12-months (+ 8.90 points). Semi-structured interview data collected over the 12-month term revealed three key themes namely: influence, empowerment, and contribution. Comparison of pre-post themes determined a positive trend at follow-ups, demonstrating improved participatory outcomes. Process indicators revealed that at 12-month follow-up the YAG was implemented as planned. Semi-structured interview data determined barriers to YAG facilitation included time and limited face-to-face components, while enablers to YAG facilitation included flexibility, accessible delivery methods, and a supportive adult facilitator.

CONCLUSION: This study found that a YAG fostered positive participatory outcomes and unique opportunities for youth participants. A successful YAG based on YPAR principles requires researchers to ensure YAG establishment and facilitation is an iterative process. Taking into consideration important barriers and enablers to YAG facilitation ensures adolescent engagement in a YAG is both meaningful and impactful.

PMID:38012583 | DOI:10.1186/s12889-023-17283-2

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Repeated intravenous thrombolysis in recurrent ischemic stroke within 3 months: a systematic review

BMC Neurol. 2023 Nov 27;23(1):422. doi: 10.1186/s12883-023-03472-4.

ABSTRACT

BACKGROUND: Repeated intravenous thrombolysis (RIVT) within 3 months is an off-guideline therapy, however, may be an effective and safe way to treat early recurrent ischemic stroke. This study was conducted to assess the potential influencing factors on the efficacy and safety of RIVT in recurrent ischemic stroke within 3 months and to explore the strategy of RIVT within 3 months.

METHODS: PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang Database were searched for cases of RIVT in recurrent ischemic stroke within 3 months up to February 1, 2023. Clinical characteristics were compared and analyzed between the good-outcome and poor-outcome groups and between the symptomatic intracranial hemorrhage (sICH) and non-sICH groups respectively.

RESULTS: A total of 16 studies including 24 cases of RIVT within 3 months were retrospectively analyzed in the present study. The patients’ ages ranged from 42 to 87 years (median 73.5 years) and the intervals between thrombolysis were from 0.25 to 90 days (median 9.5 days). Comparing the clinical characteristics between the good-outcome group and the poor-outcome group, no statistically significant differences were found (P > 0.05), but the differences in baseline National Institutes of Health stroke scale (NIHSS) score of the recurrent stroke (P = 0.056) and good outcome after the previous IVT (P = 0.054) nearly reached statistical significance. Comparing the data between the non-sICH group and the sICH group, statistically significant differences were found in terms of the proportion of cardiogenic embolism (P = 0.036), baseline NIHSS score in the recurrent stroke (P = 0.007) and the interval between thrombolysis (P = 0.041), but no significant difference was found by regression analysis.

CONCLUSION: In patients with recurrent ischemic stroke within 3 months, those with a good outcome after the previous IVT and a low baseline NIHSS score in the recurrent stroke may be considered for RIVT, whereas those with a high baseline NIHSS score, a short interval between thrombolysis, and cardiogenic embolism may suffer a higher risk of sICH. Due to sample size and publication bias, more studies with larger sample sizes and more rigorous designs are needed to confirm this conclusion.

PMID:38012577 | DOI:10.1186/s12883-023-03472-4