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Nevin Manimala Statistics

Identification of concealed structural alerts using QSTR modeling for Pseudokirchneriella subcapitata

Aquat Toxicol. 2021 Sep 8;239:105962. doi: 10.1016/j.aquatox.2021.105962. Online ahead of print.

ABSTRACT

In the present work, QSTR modeling was conducted for microalga Pseudokirchneriella subcapitata using a data set of 271 molecules belonging to different types of chemical classes for the prediction of EC50 for 72 hr based assays. The balanced QSTR model encompasses seven easily interpretable molecular descriptors and possesses statistical robustness with high predictive ability. This Genetic Algorithm Multi-linear regression (GA-MLR) model was subjected to internal validation, Y-randomization test, applicability domain analysis, and external validation as per the recommended OECD guidelines. The newly developed model fulfilled the threshold values for more than 20 recommended validation parameters including R2 = 0.72, Q2LOO = 0.70, etc. The developed QSTR model was successful in identifying the type of hybridization or specific type of atoms of previously reported and newer structural alerts. Thus, the model could be useful for data gap filling and expanding mechanistic interpretation of toxicity for different chemicals.

PMID:34525418 | DOI:10.1016/j.aquatox.2021.105962

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Nevin Manimala Statistics

No association between children’s febrile seizures and S100B protein levels: A meta-analysis

Seizure. 2021 Aug 31;92:158-165. doi: 10.1016/j.seizure.2021.08.015. Online ahead of print.

ABSTRACT

BACKGROUND: In recent years, studies have examined the relationship between febrile seizures in children and S100B protein with contradictory results. We systematically evaluated the relationship between children’s febrile seizures and S100B protein levels.

METHODS: We used Stata 11.0 software to conduct a meta-analysis of the included studies published in The China National Knowledge Infrastructure, VIP, Wanfang, Chinese Biology Medicine Disc, PubMed, Web of Science, Cochrane Library, and EMBASE databases as well as clinical trial registries in China, Europe, and the United States.

RESULTS: Six case-control studies were finally included in the meta-analysis. The results of the meta-analysis showed that the serum S100B protein level of children with febrile seizures was 0.72 higher than the serum S100B protein level of healthy children (Z=6.85, 95% CI 0.52∼0.93, P<0.05). There was no difference in the serum S100B protein level between the children with febrile seizures and children with fever but without seizures (Z=0.70, 95% CI -0.20∼0.41, P>0.05).

CONCLUSION: The level of serum S100B protein in children with febrile seizures was higher than that of healthy children and was statistically significant, whereas the increase in children with higher fever without seizures was not statistically significant. Because there was only a difference in serum S100B protein levels between children with febrile seizures and healthy children but not in febrile children without seizures as the strongest confounding factors for the results, febrile seizures do not elevate the level of S100B protein levels any more than fever.

PMID:34525431 | DOI:10.1016/j.seizure.2021.08.015

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The exposome in practice: an exploratory panel study of biomarkers of air pollutant exposure in Chinese people aged 60-69 years (China BAPE Study)

Environ Int. 2021 Sep 12;157:106866. doi: 10.1016/j.envint.2021.106866. Online ahead of print.

ABSTRACT

The exposome overhauls conventional environmental health impact research paradigms and provides a novel methodological framework that comprehensively addresses the complex, highly dynamic interplays of exogenous exposures, endogenous exposures, and modifiable factors in humans. Holistic assessments of the adverse health effects and systematic elucidation of the mechanisms underlying environmental exposures are major scientific challenges with widespread societal implications. However, to date, few studies have comprehensively and simultaneously measured airborne pollutant exposures and explored the associated biomarkers in susceptible healthy elderly subjects, potentially resulting in the suboptimal assessment and management of health risks. To demonstrate the exposome paradigm, we describe the rationale and design of a comprehensive biomarker and biomonitoring panel study to systematically explore the association between individual airborne exposure and adverse health outcomes. We used a combination of personal monitoring for airborne pollutants, extensive human biomonitoring, advanced omics analysis, confounding information, and statistical methods. We established an exploratory panel study of Biomarkers of Air Pollutant Exposure in Chinese people aged 60-69 years (China BAPE), which included 76 healthy residents from a representative community in Jinan City, Shandong Province. During the period between September 2018 and January 2019, we conducted prospective longitudinal monitoring with a 3-day assessment every month. This project: (1) leveraged advanced tools for personal airborne exposure monitoring (external exposures); (2) comprehensively characterized biological samples for exogenous and endogenous compounds (e.g., targeted and untargeted monitoring) and multi-omics scale measurements to explore potential biomarkers and putative toxicity pathways; and (3) systematically evaluated the relationships between personal exposure to air pollutants, and novel biomarkers of exposures and effects using exposome-wide association study approaches. These findings will contribute to our understanding of the mechanisms underlying the adverse health impacts of air pollution exposures and identify potential adverse clinical outcomes that can facilitate the development of effective prevention and targeted intervention techniques.

PMID:34525388 | DOI:10.1016/j.envint.2021.106866

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Nevin Manimala Statistics

Analysis of the impact of COVID-19 on collisions, fatalities and injuries using time series forecasting: The case of Greece

Accid Anal Prev. 2021 Sep 4;162:106391. doi: 10.1016/j.aap.2021.106391. Online ahead of print.

ABSTRACT

The current study aims to investigate the impact of the COVID-19 pandemic on road traffic collisions, fatalities, and injuries using time series analyses. To that aim, a database containing road collisions, fatalities, and slight injuries data from Greece were derived from the Hellenic Statistical Authority (HSA) and covered a ten-year timeframe (from January 2010 to August 2020. The chosen time period contained normal operations, as well as the period of the first COVID-19-induced lockdown period in Greece. Three different Seasonal Autoregressive Integrated Moving Average (SARIMA) time series models were implemented in order to compare the observed measurements to forecasted values that were intended to depict assumed conditions; namely, without the appearance of the COVID-19 pandemic. Modelling results revealed that the total number of road collisions, fatalities, and slightly injured were decreased, mainly due to the sharp traffic volume decrease. However, the percentage reduction of the collision variables and traffic volume were found to be disproportionate, which probably indicates that more collisions occurred with regard to the prevailing traffic volume. An additional finding is that fatalities and slightly injured rates were significantly increased during the lockdown period and the subsequent month. Overall, it can be concluded that a worse performance was identified in terms of road safety. Since subsequent waves of COVID-19 cases and other pandemics may reappear in the future, the outcomes of the current study may be exploited for the improvement of road safety from local authorities and policymakers.

PMID:34525414 | DOI:10.1016/j.aap.2021.106391

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RARG variant predictive of doxorubicin-induced cardiotoxicity identifies a cardioprotective therapy

Cell Stem Cell. 2021 Sep 14:S1934-5909(21)00343-X. doi: 10.1016/j.stem.2021.08.006. Online ahead of print.

ABSTRACT

Doxorubicin is an anthracycline chemotherapy agent effective in treating a wide range of malignancies, but its use is limited by dose-dependent cardiotoxicity. A recent genome-wide association study identified a SNP (rs2229774) in retinoic acid receptor-γ (RARG) as statistically associated with increased risk of anthracycline-induced cardiotoxicity. Here, we show that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from patients with rs2229774 and who suffered doxorubicin-induced cardiotoxicity (DIC) are more sensitive to doxorubicin. We determine that the mechanism of this RARG variant effect is mediated via suppression of topoisomerase 2β (TOP2B) expression and activation of the cardioprotective extracellular regulated kinase (ERK) pathway. We use patient-specific hiPSC-CMs as a drug discovery platform, determining that the RARG agonist CD1530 attenuates DIC, and we confirm this cardioprotective effect in an established in vivo mouse model of DIC. This study provides a rationale for clinical prechemotherapy genetic screening for rs2229774 and a foundation for the clinical use of RARG agonist treatment to protect cancer patients from DIC.

PMID:34525346 | DOI:10.1016/j.stem.2021.08.006

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A Comparison of Clinical Outcomes Between Two Different Models of Surgical Robots in Roux-en-Y Gastric Bypass

J Laparoendosc Adv Surg Tech A. 2021 Sep;31(9):969-977. doi: 10.1089/lap.2021.0477. Epub 2021 Aug 17.

ABSTRACT

Introduction: For the past 20 years, robotic surgical systems have been used for the Roux-en-Y gastric bypass (RYGB). The da Vinci Surgical System (Intuitive Surgical, Inc.) has been one of the most used robotic platforms. This study aims to retrospectively compare the performance of two models of surgical robots. Materials and Methods: A retrospective comparative study was conducted from a prospective database including all patients who underwent robotic RYGB (RRYGB) from 2011 to 2020. Results: Of a total of 277 patients included, 134 were in the RRYGB using the da Vinci S™ (RRYGB-S™) group and 143 were in the RRYGB using the da Vinci Xi™ (RRYGB-Xi™) group. The mean operative time in the RRYGB-S and RRYGB-Xi groups was 154 ± 28 and 151 ± 32 minutes, respectively (P = .510). The was no statistically significant difference in terms of intraoperative complications between the groups with regard to positive blue test, bleeding, and failure of stapler line. The readmission rate was higher in the RRGB-S group (14.1%) than in the RRYGB-Xi group (3.4%) (P = .004), and it was mainly due to major complications (P = .003) including pouch and gastrojejunostomy anastomotic leaks (P = .001). The nonsurgical complications were statistically significantly higher in the RRYGB-S group (7.4%) than in the RRYGB-Xi group (2.1%) (P < .05), as well as the surgical complications were higher in the RRYGB-S group (7.5%) than in the RRYGB-Xi group (0%) (P < .001). The mean percentage of the total weight loss at 1 and 2 years of follow-up did not show any statistically significant difference (P = .547). Conclusions: The higher complication rate in the S surgical system might be correlated with the initial learning curve and stressed the need for proper robotic surgical training and accurate strategies when introducing emerging technologies into the surgical practice.

PMID:34525316 | DOI:10.1089/lap.2021.0477

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Hydrokinetic pancreatic function and insulin secretion are moduled by Cl- uniporter Slc26a9 in mice

Acta Physiol (Oxf). 2021 Sep 15:e13729. doi: 10.1111/apha.13729. Online ahead of print.

ABSTRACT

AIM: Slc26a9 is a member of the Slc26 multifunctional anion transporter family. Polymorphisms in Slc26a9 are associated with an increased incidence of meconium ileus and diabetes in cystic fibrosis patients. We investigated the expression of Slc26a9 in the murine pancreatic ducts, islets and parenchyma, and elucidated its role in pancreatic ductal electrolyte and fluid secretion and endocrine function.

METHODS: Pancreatic Slc26a9 and CFTR mRNA expression, fluid and bicarbonate secretion were assessed in slc26a9-/- mice and their age- and sex-matched wild-type (wt) littermates. Glucose and insulin tolerance tests were performed.

RESULTS: Compared with stomach, the mRNA expression of Slc26a9 was low in pancreatic parenchyma, 20-fold higher in microdissected pancreatic ducts than parenchyma, and very low in islets. CFTR mRNA was ∼ 10fold higher than Slc26a9 mRNA expression in each pancreatic cell type. Significantly reduced pancreatic fluid secretory rates and impaired glucose tolerance were observed in female slc26a9-/- mice, whereas alterations in male mice did not reach statistical significance. No significant difference was observed in peripheral insulin resistance in slc26a9-/- compared to sex- and aged-matched wt controls. In contrast, isolated slc26a9-/- islets in short term culture displayed no difference in insulin content, but a significantly reduced glucose-stimulated insulin secretion compared to age- and sex-matched wt islets, suggesting that the impaired glucose tolerance is a pancreatic defect.

CONCLUSIONS: Deletion of Slc26a9 is associated with a reduction in pancreatic fluid secretion and impaired glucose tolerance in female mice. The results underline the importance of Slc26a9 in pancreatic physiology.

PMID:34525257 | DOI:10.1111/apha.13729

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Does serum TSH level act as a surrogate marker for psychological stress and cardio-metabolic risk among adolescent and young people?

Horm Mol Biol Clin Investig. 2021 Sep 16. doi: 10.1515/hmbci-2021-0021. Online ahead of print.

ABSTRACT

OBJECTIVES: The incidence of metabolic syndrome is increasing even at younger ages. Metabolic syndrome constitutes a group of cardiovascular risk factors that include high cholesterol, triacylglycerol, hyperglycemia, central obesity, etc., which increases the risk of cardiovascular disease, diabetes mellitus, may be even cancer. Indian students enter colleges just after crossing their adolescent age and will be exposed to greater academic stress. Psychological stress or depression is associated with transient change in thyroid hormones level or dysfunction. To explore an association among serum Thyroid Stimulating Hormone (TSH) levels, fT3:fT4 ratio, psychological stress scores, and selected known cardio-metabolic risk markers.

METHODS: Forty first year MBBS students were included. Their demographic, anthropometric variables, and the blood pressure were documented. Serum TSH, fT3, fT4, and salivary cortisol level was quantified. The stress level was assessed using Cohen Perceived Stress Scale Scoring. Data were expressed in mean ± standard deviation. Data (parametric/non-parametric) were compared by Independent unpaired ANOVA or Kruskal Wallis test whichever is appropriate. Spearmen correlation analysis was performed.

RESULTS: Serum TSH and Cohen stress score are negatively correlated (r=-0.152), but serum cortisol showed (r=0.763) a positive correlation. TSH levels and the marks obtained in the summative assessments were negatively correlated and the correlation was not statistically significant.

CONCLUSIONS: The psychological stress is associated with low serum TSH, high cortisol, and poor academic performance in first year MBBS students. Blood pressure, plasma glucose, and anthropometric measures were not associated with the psychological stress.

PMID:34525272 | DOI:10.1515/hmbci-2021-0021

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The Impact of Myasthenia Gravis on Lower Urinary Tract Functions

Int J Clin Pract. 2021 Sep 15:e14873. doi: 10.1111/ijcp.14873. Online ahead of print.

ABSTRACT

AIM: To assess functions of the lower urinary tract (LUT) in patients with myasthenia gravis (MG).

MATERIALS AND METHODS: 36 patients (18 males and 18 females) with MG and 29 healthy controls were enrolled. Participants completed a 3-day voiding diary and responded to questionnaires “Overactive Bladder Symptom Score” (OABSS) and “International Consultation on Incontinence-Short Form” (ICIQ-SF). All patients underwent uroflowmetry and ultrasonography (US). The data were compared based on the onset of disease and serological status.

RESULTS: The most common urinary symptoms were nocturia (80.5%), incontinence (61%), and urgency (47%). OABSS was higher in patients than controls (p= 0.008). Duration of urinary symptoms was longer and nocturia was more common in late-onset MG (LOMG) than in early-onset MG (EOMG) (p= 0.029, p= 0.023). The duration of disease and urinary symptoms statistically increased in ACh-Ab (-) group compared to ACh-Ab (+) group (p= 0.003, p= 0.027). Nighttime urination frequency significantly increased while daytime voided volume (VV) decreased in LOMG compared to EOMG (p= 0.003 and p= 0.01). Residual volume on the US was significantly higher in LOMG than that in EOMG (p= 0.004). The duration of disease was positively correlated with tQmax and daytime urination frequency (p= 0.013, r= 0.48; p= 0.016, r= 0.398). A negative association was found between duration of disease and daytime VV (p= 0.04, r= -0.344).

CONCLUSION: LUT dysfunction may manifest disease in MG, particularly in late-onset forms. The lack of ACh-Ab seemed to prolong the duration of disease and urinary disturbances.

PMID:34525243 | DOI:10.1111/ijcp.14873

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The Reliability and Validity of the Turkish Version of the Post-Dialysis Fatigue Scale

Int J Clin Pract. 2021 Sep 15:e14871. doi: 10.1111/ijcp.14871. Online ahead of print.

ABSTRACT

AIM: Hemodiallysis (HD) commonly leads to post-dialysis fatigue (PDF), and thus worsens the quality of life and the clinical outcomes. The aim of this study was to translate, linguistically validate, and determine the psychometric properties of the “Post-Dialysis Fatigue” Scale for Turkish HD patients.

STUDY DESIGN: A methodological study.

METHODS: The standard lingual translation and validation methods for the initial translation of the PDF Scale and then assessed the psychometric properties of reliability and validity of the translated scale. Visual Analogue Scale (VAS) and Piper Fatigue Scale were used to assess concurrent and construct validity. Also, post-dialysis recovery time was used it as an indirect measurement method for PDF.

RESULTS: A total of 93 patients participated in the study. The Cronbach’s alpha coefficient of PDF was 0.773. There was a statistically significant relationship between the test and retest scores (ICC: 0.973; p < 0.001). PDF Scale was acceptable with 11 items. There was a positive correlation with a statistically significant relationship was present between the PDF scores and Piper Fatigue Scale (r= 0.488; p < 0.001) and VAS score (r= 0.656; p < 0.001). There was a statistically significant positive correlation between the PDF scale and the post-dialysis recovery time (r= 0.270; p= 0.009), CONCLUSION: The study results have shown that the Turkish form of the PDF Scale is a valid and reliable tool in patients undergoing HD treatment. Post-dialysis recovery time may be used as an indirect measurement method to evaluate PDF.

PMID:34525246 | DOI:10.1111/ijcp.14871