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Nevin Manimala Statistics

Ensemble Quantitative Read-Across Structure-Activity Relationship Algorithm for Predicting Skin Cytotoxicity

Chem Res Toxicol. 2023 Dec 4. doi: 10.1021/acs.chemrestox.3c00238. Online ahead of print.

ABSTRACT

Read-across (RA) and quantitative structure-activity relationship (QSAR) are two alternative methods commonly used to fill data gaps in chemical registrations. These approaches use physicochemical properties or molecular fingerprints of source substances to predict the properties of unknown substances that have similar chemical structures or physicochemical properties. Research on RA and QSAR is essential to minimize the time, money, and animal testing needed to determine biological properties that are not currently known. This study developed a stacked ensemble quantitative read-across structure-activity relationship algorithm (enQRASAR) for predicting skin irritation toxicity based on negative log cell viability inhibition concentration at 50% (pIC50) against skin keratinocytes as the end point. The goodness-of-fit and predictability of this algorithm were validated using leave-one-out cross-validation and external test data sets. The results obtained were statistically reliable in terms of goodness-of-fit, robustness, and predictability metrics. Additionally, the developed model demonstrated a low prediction error when predicting FDA-approved drugs. These results confirm that the enQRASAR algorithm can be used to predict skin cytotoxicity of chemicals. Therefore, this model was publicly available to further facilitate toxicity predictions of unknown compounds in chemical registrations.

PMID:38047785 | DOI:10.1021/acs.chemrestox.3c00238

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The optimal dose of pain neuroscience education added to an exercise programme for patients with chronic spinal pain: A systematic review and dose-response meta-analysis

Pain. 2023 Nov 30. doi: 10.1097/j.pain.0000000000003126. Online ahead of print.

ABSTRACT

Pain neuroscience education (PNE) has shown promising results in the management of patients with chronic spinal pain (CSP). However, no previous review has determined the optimal dose of PNE added to an exercise programme to achieve clinically relevant improvements. The aim was to determine the dose-response association between PNE added to an exercise programme and improvements in pain intensity and disability in patients with CSP. A systematic search of PubMed/MEDLINE, Embase, Web of Science, Scopus, and the Cochrane Library was conducted from inception to April 19, 2023. The exposure variable (dosage) was the total minutes of PNE. Outcome measures included pain intensity, disability, quality of life, pressure pain thresholds, and central sensitization inventory. Data extraction, risk-of-bias assessment, and certainty of evidence were performed by 2 independent reviewers. The dose-response relationship was assessed using a restricted cubic spline model. Twenty-six randomised controlled trials with 1852 patients were included. Meta-analysis revealed a statistically significant effect in favour of PNE on pain intensity and disability. In addition, a dose of 200 and 150 minutes of PNE added to an exercise programme was estimated to exceed the minimum clinically important difference described in the literature for pain intensity (-2.61 points, 95% CI = -3.12 to -2.10) and disability (-6.84 points, 95% CI = -7.98 to -5.70), respectively. The pooled effect of the isolated exercise was small. These findings may be useful in optimising the most appropriate PNE dose to achieve clinically relevant improvements in patients with CSP.

PMID:38047772 | DOI:10.1097/j.pain.0000000000003126

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Posttraumatic stress disorder and quality of life in patients after open thoracoabdominal aortic repair

Vasa. 2023 Dec 4. doi: 10.1024/0301-1526/a001103. Online ahead of print.

ABSTRACT

Background: Open thoracoabdominal aortic aneurysm (TAAA) repair is often related to significant morbidity and complications like paraplegia or acute kidney injury. Subsequently, prolonged intensive care stay is common. However, there is a lack of research on post-traumatic stress disorder (PTSD) and the perceived quality of life (QOL) in patients undergoing complex aortic procedures, such as open TAAA repair. Therefore, our study aims to determine the prevalence of PTSD and the current QOLin these patients and whether it is associated with demographic factors or complications following open thoracoabdominal aortic repair. Patients and methods: In this retrospective study, a total of 213 adult surviving patients after open thoracoabdominal aortic repair were contacted with two questionnaires one to assess PTSD and another to evaluate current QOL after open thoracoabdominal aortic repair. 61 patients returned one or both the questionnaires, and 59 patients (97%) answered all questions of the 4-item primary care PTSD section of the survey. In addition to the PTSD screening, patients were sent an SF-36 questionnaire to assess their current quality of life. 60 patients answered the SF-36 questionnaire partially or completely (98%). Results: 27% of patients (16/59) screened positive for PTSD. Electronic medical records were matched to all responding patients. Patients who were screened positive for PTSD spent more days in intensive care (OR, 1.073; 95% CI 1.02-1.13; p=0.005), had a higher frequency of tracheotomy (OR, 6.43; 95% CI 1.87-22.06; p=0.004), sepsis (OR, 5.63; 95% CI 1.56-20.33; p=0.014), as well as postoperative paraparesis (OR, 13.23; 95% CI 1.36-129.02; p=0.019). In patients with postoperative complications, a statistically significant decrease in the overall score was observed for certain categories of the SF-36. Conclusions: The prevalence of PTSD is higher, in comparison to the general population’s prevalence, and the quality of life is affected following open thoracoabdominal aortic aneurysm repair, with a significant relation to postoperative complications as well as the length of ICU stay. Further research and screening for PTSD in relation to open TAAA repair is needed to assess its role in patient QOL during follow up.

PMID:38047758 | DOI:10.1024/0301-1526/a001103

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Correlation Between Vitreous Level of Angiogenic Growth Factors and Oxygen Saturation in Retinal Vessels in Diabetic Retinopathy

Invest Ophthalmol Vis Sci. 2023 Dec 1;64(15):4. doi: 10.1167/iovs.64.15.4.

ABSTRACT

PURPOSE: The aim of this study was to investigate whether there is any association between the levels of the angiogenic growth factors and the vascular oxygen saturation in eyes with diabetic retinopathy.

METHODS: The study was designed as a prospective trial. The cohort consisted of 29 diabetic patients with scheduled vitreous procedures (intravitreal injection or pars plana vitrectomy). The control group included 30 patients scheduled for macular surgery (macular hole or epiretinal membrane). Nine patients (four from the diabetic maculopathy [DM] group and five from the control group) were excluded from the study because of unsuccessful vitreous samples. Retinal oximetry was performed several hours before the vitreous procedure was performed, and vitreous samples were obtained during the procedure. The concentrations of VEGF, Serpin F1/pigment epithelium-derived factor (PEDF), and placental growth factor (PlGF) were measured by ELISA.

RESULTS: A negative correlation between level of VEGF and arteriovenous (AV) saturation difference was determined in the DM group (Pearson correlation coefficient r = -0.607; two-tailed test, P = 0.002). Also a negative correlation between level of PlGF and AV saturation difference was determined in the DM group (Pearson correlation coefficient r = -0.521; two-tailed test, P = 0.011) A positive correlation between PlGF level and the vein saturation was not statistically significant (Pearson correlation coefficient r = 0.325; two-tailed test, P = 0.130). We did not find any correlation between vitreous level of PEDF and vascular saturation within the DM group.

CONCLUSIONS: Our findings in diabetic patients suggests a correlation between the intravitreal level of proangiogenic factors and the AV difference measured by retinal oximetry.

PMID:38047739 | DOI:10.1167/iovs.64.15.4

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The incidence and predisposing factors for irritable bowel syndrome following COVID-19: a systematic review and meta-analysis

Eur J Gastroenterol Hepatol. 2023 Nov 30. doi: 10.1097/MEG.0000000000002688. Online ahead of print.

ABSTRACT

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder. Several studies have analyzed the long-term GI symptoms and IBS following coronavirus disease 2019 (COVID-19). The purpose of this study is to evaluate the incidence and predisposing factors for IBS following COVID-19 by a systematic review and meta-analysis.

METHODS: Electronic databases were searched to identify relevant studies. Primary outcomes were the pooled incidence rate of IBS following COVID-19 and the pooled relative risk (RR) for IBS in the COVID-19 group compared to the non-COVID-19 group. Secondary outcomes were the pooled RR and the standardized mean difference (SMD) for predisposing factors in the IBS group compared to the non-IBS group. Heterogeneity was evaluated using Cochran’s Q test and I2 statistics.

RESULTS: Ten studies were included in this study. The pooled incidence rate of IBS in COVID-19 patients was 12%. The pooled incidence rate of IBS-D, IBS-C and IBS-M was 5%, 2% and 1%. The pooled incidence rate of IBS in 6 and 12 months was 10% and 3%. The pooled RR for IBS in COVID-19 patients was 1.23 [95% confidence interval (CI) = 0.50-3.01] compared to non-COVID-19 patients. The pooled RR or SMD for mild, moderate, and severe disease activity, procalcitonin (PCT), depression or anxiety in IBS patients following COVID-19 was 0.94 (95% CI = 0.74-1.21), 1.19 (95% CI = 0.65-2.21), 1.30 (95% CI = 0.63-2.66), 6.73 (95% CI = 6.08-7.38) and 3.21 (95% CI = 1.79-5.75).

CONCLUSION: The incidence of IBS following COVID-19 was 12%. But it was not higher than the general population. We also found some predisposing factors for IBS including depression or anxiety, PCT.

PMID:38047738 | DOI:10.1097/MEG.0000000000002688

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Burnout, moral injury, and suicidal/self-harm ideation among healthcare professionals in Mainland China: Insights from an online survey during the COVID-19 pandemic

Int J Psychiatry Med. 2023 Dec 4:912174231219041. doi: 10.1177/00912174231219041. Online ahead of print.

ABSTRACT

OBJECTIVE: This survey aimed to explore the relationships between burnout, moral injury, and suicidal/self-harm ideation among Chinese health professionals to provide a reference for protecting their mental health.

METHOD: Health professionals were surveyed online using the Maslach Burnout Inventory-Human Services Survey for Medical Personnel, Patient Health Questionnaire-9, and the Moral Injury Symptoms Scale-Health Professional.

RESULTS: In the analysis, 6146 eligible respondents were included in the study. The average participant age was 34.9 ± 8.5 years, and suicidal/self-harm ideation was detected in 2338 participants (38.0%). The prevalence of suicidal/self-harm ideation among those with severe burnout in the dimensions of emotional exhaustion, depersonalisation, and decreased personal accomplishment was significantly higher than those with mild burnout. The prevalence of suicidal/self-harm ideation among those with significant moral injury symptoms was higher than those without moral injury. Unconditional logistic regression analysis showed that those with moderate or severe emotional exhaustion, moderate or severe reduced sense of professional accomplishment and moderate or severe depersonalisation had increased risks of suicidal/self-harm ideation.

CONCLUSIONS: Structural equation modelling demonstrated that burnout significantly mediated the relationship between moral injury and suicidal/self-harm ideation. The proportion of mediation (PM) by burnout was 43.0%. Burnout and moral injury were potential predictors of suicidal/self-harm ideation among health professionals. Both moral injury and burnout had positive and direct effects on suicidal/self-harm ideation, and burnout was a mediator in this relationship among Chinese health professionals. Therefore, to alleviate the moral injury and subsequent burnout of healthcare workers and enhance their mental qualities, active interventions should be developed in the future.

PMID:38047438 | DOI:10.1177/00912174231219041

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Health habits during lockdown for COVID-19 in Spain and its effect on weight

Nutr Hosp. 2023 Nov 16. doi: 10.20960/nh.04740. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: a deterioration of health habits has been found in various studies caused by stressful situations such as mandatory and maintained confinement over time. This study aims to analyze the health habits of the Spanish adult population during confinement due to the COVID-19 pandemic, and the possible impact on their body weight.

METHOD: two thousand eight hundred and thirty-four volunteer subjects participated in the study (69.3 % women). They completed an on-line questionnaire that evaluated their health habits, as well as various sociodemographic variables.

RESULTS: the results show a statistically significant link between the subjects’ body mass index (BMI) and the change in their weight during lockdown (2: 79.303; p: < 0.001). Besides, a statisti-cally significant relationship between the different health habits under analysis was also found, being moderate with respect to the link between eating habits and physical activity (Cramer’s V: .226). A statistically significant relationship was also found between the participants’ weight and the different health habits during lockdown. The effect size of the associations was moderate in relation to the participants’ eating habits (Cramer’s V: .409) and physical activity (Cramer’s V: .292).

CONCLUSIONS: it is suggested the development of prevention programs for long lockdown periods associated with high levels of stress so as to promote a healthy diet, as well as exercise using new technologies and a proper rest, especially in overweight or obese subjects.

PMID:38047424 | DOI:10.20960/nh.04740

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Somatometric alterations and lower APGAR score in indigenous newborns

Nutr Hosp. 2023 Nov 27. doi: 10.20960/nh.04812. Online ahead of print.

ABSTRACT

INTRODUCTION: the indigenous population is vulnerable and there is limited understanding of their somatometric indicators and APGAR score at birth.

AIM: the objective of the study was to explore the association of the condition of indigenous newborn (INB) on somatometric parameters and APGAR score at birth.

METHODS: this study employed an exploratory cross-sectional design, utilizing the registry of newborns (NB) from a private clinic. The APGAR score at one minute after birth, as well as nutritional indicators derived from measurements of weight, height, and perimeters, were taken into consideration. The statistical analysis involved the use of logistic regressions.

RESULTS: the analysis included 7413 NB (1.8 % INB), 52 % were male and 8.1 % were born preterm (gestational age < 37 weeks). In comparison to non-indigenous NB, the INB group showed a higher risk of malnutrition (8 % vs. 6.3 %; p < 0.001), a greater prevalence of excess weight (7.3 % vs. 1.8 %; p < 0.001), smaller head circumference (33.6 cm vs. 34.1 cm; p = 0.017), smaller abdominal circumference (30.9 cm vs. 31.5 cm; p = 0.011), and a higher occurrence of low APGAR scores (< 7) (8.7 % vs. 1.2 %; p < 0.001). Furthermore, the indigenous condition was independently associated with low birth weight (< 2.500 g) (OR, 0.4; 95 % CI, 0.2; 0.9), excess head circumference (OR, 2.7; 95 % CI, 1.5; 4.7), and APGAR score < 7 points (OR, 8.3; 95 % CI, 4.2; 16.5).

CONCLUSIONS: the indigenous condition was associated with factors that have adverse effects on the health of NB, including reduced head circumference and suboptimal performance on the APGAR scale. These results emphasize the importance of improving access to and quality of prenatal healthcare services for indigenous communities.

PMID:38047412 | DOI:10.20960/nh.04812

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Genomic landscape of introgression from the ghost lineage in a gobiid fish uncovers the generality of forces shaping hybrid genomes

Mol Ecol. 2023 Dec 4. doi: 10.1111/mec.17216. Online ahead of print.

ABSTRACT

Extinct lineages can leave legacies in the genomes of extant lineages through ancient introgressive hybridization. The patterns of genomic survival of these extinct lineages provide insight into the role of extinct lineages in current biodiversity. However, our understanding on the genomic landscape of introgression from extinct lineages remains limited due to challenges associated with locating the traces of unsampled ‘ghost’ extinct lineages without ancient genomes. Herein, we conducted population genomic analyses on the East China Sea (ECS) lineage of Chaenogobius annularis, which was suspected to have originated from ghost introgression, with the aim of elucidating its genomic origins and characterizing its landscape of introgression. By combining phylogeographic analysis and demographic modelling, we demonstrated that the ECS lineage originated from ancient hybridization with an extinct ghost lineage. Forward simulations based on the estimated demography indicated that the statistic γ of the HyDe analysis can be used to distinguish the differences in local introgression rates in our data. Consistent with introgression between extant organisms, we found reduced introgression from extinct lineage in regions with low recombination rates and with functional importance, thereby suggesting a role of linked selection that has eliminated the extinct lineage in shaping the hybrid genome. Moreover, we identified enrichment of repetitive elements in regions associated with ghost introgression, which was hitherto little known but was also observed in the re-analysis of published data on introgression between extant organisms. Overall, our findings underscore the unexpected similarities in the characteristics of introgression landscapes across different taxa, even in cases of ghost introgression.

PMID:38047388 | DOI:10.1111/mec.17216

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Evidence of Clinical Efficacy and Pharmacological Mechanisms of Resveratrol in the Treatment of Alzheimer’s Disease

Curr Alzheimer Res. 2023 Dec 1. doi: 10.2174/0115672050272577231120060909. Online ahead of print.

ABSTRACT

BACKGROUND: To evaluate the efficacy and pharmacological mechanisms of resveratrol in Alzheimer’s disease (AD) patients.

METHODS: We conducted a thorough exploration of existing randomized controlled trials concerning the treatment of Alzheimer’s disease patients using resveratrol, utilizing accessible open databases. Quantitative variables were represented as a standardized mean difference (SMD), accompanied by a 95% confidence interval (CI). Additionally, we examined the potential targets and plausible pathways associated with the impact of resveratrol on Alzheimer’s disease using network pharmacology techniques.

RESULTS: Our meta-analysis comprised five trials involving 271 AD patients, of whom 139 received resveratrol treatment and 132 received placebo treatment. Compared with placebo therapy, resveratrol treatment resulted in a significant improvement in Alzheimer’s Disease Cooperative Study- Activities of Daily Living (ADAS-ADL) scores (SMD=0.51; 95% CI, 0.24 to 0.78) and cerebrospinal fluid (CSF) Aβ40 (SMD=0.84; 95% CI, 0.21 to 1.47) and plasma Aβ40 levels (SMD=0.43; 95% CI, 0.07 to 0.79). However, the improvement in the resveratrol-treated group compared with the placebo treatment group on the Mini-Mental State Examination (MMSE) score, CSF Aβ42 and plasma Aβ42 levels, and brain volume was not significant. There were no noteworthy statistical variances in the occurrence of adverse effects noted between the two groups. The outcomes of network pharmacology divulged that the principal enriched interaction pathway between resveratrol and Alzheimer’s disease is primarily concentrated within the PI3K signaling pathways. Resveratrol’s potential key targets for the treatment of AD include MAKP1, HRAS, EGFR, and MAPK2K1.

CONCLUSION: While having a high safety profile, resveratrol has efficacy in AD patients to a certain extent, and more data are required to validate the efficacy of resveratrol for the treatment of AD in the future. Suppression of the PI3K signaling pathways could hold significant importance in the treatment of AD patients using resveratrol.

PMID:38047366 | DOI:10.2174/0115672050272577231120060909