Category: Nevin Manimala

Sleep Breath. 2023 Feb 28. doi: 10.1007/s11325-023-02797-1. Online ahead of print.

ABSTRACT

BACKGROUND: No study has examined the psychometric properties of the sleep condition indicator (SCI) for screening poststroke insomnia in the Indonesian population. We aimed to develop the Indonesian version of the sleep condition indicator (ISCI) and to examine its psychometric properties for screening adult patients in late sub-acute and chronic periods after stroke.

METHODS: This was a cross-sectional study with two stages. In the first stage, the English version of the SCI was translated into the ISCI using standard procedures. The psychometric properties of the ISCI were tested in the second stage. Internal consistency and test-retest reliability of ISCI were used to evaluate reliability. A confirmatory factor analysis (CFA) was performed to test construct validity. To test concurrent and convergent validity, the Indonesian version of the insomnia severity index (ISI-INA), generalized anxiety disorder questionnaire (IGAD-7), and patient health questionnaire (IPHQ-9) were used. A receiver operating characteristic (ROC) analysis was conducted to calculate the optimal cutoff score of the ISCI on the basis of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for insomnia.

RESULTS: A total of 160 adults with a diagnosis of stroke for more than 3 months were included (median age of 58.5 years, 31% met the DSM-5 criteria for insomnia). The ISCI had a satisfactory Cronbach’s alpha of 0.89 and test-retest reliability of 0.78. The CFA revealed that the ISCI exhibited a satisfactory model fit and was associated with the ISI-INA, IGAD-7, and IPHQ-9 (r = -0.81, -0.32, and -0.52, respectively; all P < .001). The ROC test revealed that the optimal cutoff point of ≤23 yielded the highest sensitivity (94%) and specificity (97%).

CONCLUSION: The study results revealed that the 8-item ISCI is a reliable and valid screening tool for detecting insomnia symptoms according to the DSM-5 criteria in the chronic period after stroke.

PMID:36854859 | DOI:10.1007/s11325-023-02797-1

Endocrine. 2023 Mar 1. doi: 10.1007/s12020-023-03334-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Breast cancer is a leading cause of cancer morbidity and mortality in females. Decreased availability of Vitamin D within breast cells, contributed by deficiency of serum Vitamin D and polymorphisms of Vitamin D receptor genes are possible risk factors for breast cancer.

OBJECTIVES: To study the association of FokI polymorphism of the Vitamin D Receptor gene with breast cancer in females and to study the levels of Vitamin D in breast cancer patients.

MATERIALS AND METHODS: VDR gene FokI genotyping was done by PCR-RFLP method and levels of serum Vitamin D were estimated by ELISA. Statistical analysis was done with SPSS v.21.

RESULTS: Serum Vitamin D was significantly lower in newly diagnosed breast cancer patients than in healthy controls (P = 0.016). Females with serum Vitamin D levels in the highest quartile have a lesser risk of breast cancer than those with serum Vitamin D levels in the lowest quartile (O. R = 2.4421, C.I = 1.09-5.45, P = 0.029). The risk of developing breast cancer is higher in women with the polymorphic T allele for VDR FokI genotype (CT/TT) than those homozygous for the wild C allele (CC). (O.R. = 4.295, C.I. = 2.2110-8.3451, p-value = <0.0001). Levels of serum Vitamin D were significantly higher (p < 0.001) in ER + patients and significantly low in those presenting with higher stages of cancer (p = 0.009).

CONCLUSIONS: FokI polymorphism of VDR gene and low circulating Vitamin D levels increase the risk of developing breast cancer in North Indian females. Serum Vitamin D can be used as a prognostic factor.

PMID:36854857 | DOI:10.1007/s12020-023-03334-6

Funct Integr Genomics. 2023 Feb 28;23(1):70. doi: 10.1007/s10142-023-00995-4.

ABSTRACT

Body dysmorphic disorder (BDD) is a disorder associated with depression and eating disorders. It often arises from minor defects in appearance or an individual imagining that he or she is defective. However, the mechanisms causing BDD remain unclear, and its pathogenesis and adjuvant treatment methods still need to be explored. Here, we employed a liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach to identify key metabolic differences in BDD versus healthy patients. We obtained plasma samples from two independent cohorts (including eight BDD patients and eight healthy control patients). Raw data were analyzed using Compound Discoverer to determine peak alignment, retention time correction, and extraction of peak areas. Metabolite structure identification was also obtained using Compound Discoverer by of accurate mass matching (< 10 ppm) and secondary spectral matching queries of compound databases. Next, multidimensional statistical analyses were performed using the ropls R package. These analyses included: unsupervised principal component analysis, supervised partial Least-Squares Discriminant Analysis, and orthogonal partial Least-Squares Discriminant Analysis. We then identified the most promising metabolic signatures associated with BDD across all metabolomic datasets. Principal component analysis showed changes in small-molecule metabolites in patients, and we also found significant differences in metabolite abundance between the BDD and normal groups. Our findings suggest that the occurrence of BDD may be related to metabolites participating in the following KEGG pathways: ABC transporters, purine metabolism, glycine, serine and threonine metabolism, pyrimidine, pyrimidine metabolism, biosynthesis of 12-, 14-, and 16-membered macrolides, microbial metabolism in diverse environments, biosynthesis of secondary metabolites, and caffeine and insect hormone biosynthesis.

PMID:36854840 | DOI:10.1007/s10142-023-00995-4

Reprod Sci. 2023 Feb 28. doi: 10.1007/s43032-023-01201-3. Online ahead of print.

ABSTRACT

The role of MTHFR C677T polymorphism in repeated pregnancy loss (RPL) among different populations has been studied with inconsistent results. The study objective was to determine the association between MTHFR C677T polymorphisms and RPL among Arab women. The review included all the available studies investigating the association between MTHFR C677T polymorphism and RPL from 2000 until now. The searched database included Cochrane, Trip, EMBASE, and Google Scholar. Two authors independently reviewed the searched articles for eligibility, judged their risk of bias, and extracted the characteristics of the studies. Review Manager 5.3 program was used for data analysis using odds ratio (OR) at a 95% confidence interval (CI). The study revealed a statistically significant difference between cases and controls regarding combined MTHFR C677T polymorphisms (OR = 1.50, 95% CI = 1.15-1.96), MTHFR C677T heterozygous (OR = 1.41, 95% CI = 1.08-1.83), and MTHFR C677T homozygous (OR = 4.19, 95% CI = 1.87-9.39). Considerable significant heterogeneity was recorded in the three analyses (P < 0.05). The review supported the hypothesis that MTHFR C677T mutation is considered a significant risk factor for RPL among Arab women.

PMID:36854824 | DOI:10.1007/s43032-023-01201-3

Biometrics. 2023 Feb 28. doi: 10.1111/biom.13848. Online ahead of print.

ABSTRACT

False discovery rate (FDR) controlling procedures provide important statistical guarantees for replicability in signal identification based on multiple hypotheses testing. In many fields of study, FDR controlling procedures are used in high-dimensional (HD) analyses to discover features that are truly associated with the outcome. In some recent applications, data on the same set of candidate features are independently collected in multiple different studies. For example, gene expression data are collected at different facilities and with different cohorts, to identify the genetic biomarkers of multiple types of cancers. These studies provide us with opportunities to identify signals by considering information from different sources (with potential heterogeneity) jointly. This paper is about how to provide FDR control guarantees for the tests of union null hypotheses of conditional independence. We present a knockoff-based variable selection method (Simultaneous knockoffs) to identify mutual signals from multiple independent data sets, providing exact FDR control guarantees under finite sample settings. This method can work with very general model settings and test statistics. We demonstrate the performance of this method with extensive numerical studies and two real data examples. This article is protected by copyright. All rights reserved.

PMID:36854821 | DOI:10.1111/biom.13848

Eur Arch Otorhinolaryngol. 2023 Feb 28. doi: 10.1007/s00405-023-07891-4. Online ahead of print.

ABSTRACT

PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) is a renal disease with genetic transmisson. Mutations in the PKD1 and PKD2 genes, which encode integral membrane proteins of the cilia of primary renal tubule epithelial cells, are seen in ADPKD. The aim of this study was to evaluate the sinonasal epithelium, which is epithelium with cilia, by measuring the nasal mucociliary clearance time, and to investigate the effect of ADPKD on nasal mucociliary clearance.

METHODS: The study included 34 patients, selected from patients followed up in the Nephrology Clinic, and 34 age and gender-matched control group subjects. The nasal mucociliary clearance time (NMCT) was measured with the saccharin test.

RESULTS: The mean age of the study subjects was 47.15 ± 14.16 years in the patient group and 47.65 ± 13.85 years in the control group. The eGFR rate was determined as mean 72.06 ± 34.26 mL/min in the patient group and 99.79 ± 17.22 mL/min in the control group (p < 0.001). The NMCT was determined to be statistically significantly longer in the patient group (903.6 ± 487.8 s) than in the control group (580 ± 259 s) (p = 0.006).

CONCLUSIONS: The study results showed that the NMCT was statistically significantly longer in patients with ADPKD compared to the control group, but in the linear regression analysis results, no correlation was determined between eGFR and NMCT.

PMID:36854810 | DOI:10.1007/s00405-023-07891-4

J Cancer Res Clin Oncol. 2023 Feb 28. doi: 10.1007/s00432-023-04601-9. Online ahead of print.

ABSTRACT

PURPOSE: Hematotoxicity is a common side-effect of cytotoxic gastrointestinal (GI) cancer therapies. An unsolved problem is to predict the individual risk therefore to decide on treatment adaptions. We applied an established biomathematical prediction model and primarily evaluated its predictive value in patients undergoing chemotherapy for GI cancers in curative intent.

METHODS: In a prospective, observational multicenter study on patients with gastro-esophageal or pancreatic cancer (n = 28) receiving myelosuppressive adjuvant or neoadjuvant chemotherapy (FLO(T) or FOLFIRINOX), individual model parameters were learned based on patients’ observed laboratory values during the first chemotherapy cycle and further external data resources. Grades of hematotoxicity of subsequent cycles were predicted by model simulation and compared with observed data.

RESULTS: The most common high-grade hematological toxicity was neutropenia [19/28 patients (68%)]. For the FLO(T) regimen, individual grades of thrombocytopenia and leukopenia could be well predicted for cycles 2-4, as well as grades of neutropenia for cycle 2. Prediction accuracy for neutropenia in the third and fourth cycle differed by one toxicity grade on average. For the FOLFIRINOX-regimen, thrombocytopenia predictions showed a maximum deviation of one toxicity grade up to the end of therapy (8 cycles). Deviations of predictions were less than one degree on average up to cycle 4 for neutropenia, and up to cycle 6 for leukopenia.

CONCLUSION: The biomathematical model showed excellent short-term and decent long-term prediction performance for all relevant hematological side effects associated with FLO(T)/FOLFIRINOX. Clinical utility of this precision-medicine approach needs to be further investigated in a larger cohort.

PMID:36854800 | DOI:10.1007/s00432-023-04601-9

Sci Rep. 2023 Feb 28;13(1):3376. doi: 10.1038/s41598-023-28956-8.

ABSTRACT

Astaxanthin (ASX), as a natural carotenoid compound, exists in various types of seafood and microorganisms. It has several possible beneficial therapeutic effects for patients with polycystic ovary syndrome (PCOS). Patients with PCOS also suffer from endoplasmic reticulum (ER) stress. In the present work, it was hypothesized that ER stress could be improved by ASX in PCOS patients. Granulosa cells (GCs) were obtained from 58 PCOS patients. The patients were classified into ASX treatment (receiving 12 mg/day for 60 days) and placebo groups. The expression levels of ER stress pathway genes and proteins were explored using Western blotting and quantitative polymerase chain reaction. To assess oxidative stress markers, follicular fluid (FF) was gained from all patients. The Student’s t test was used to perform statistical analysis. After the intervention, ASX led to a considerable reduction in the expression levels of 78-kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and X-box-binding protein 1 compared to the placebo group, though the reduction in the messenger RNA (mRNA) expression level of activating transcription factor 6 was not statistically significant. However, ASX significantly increased the ATF4 expression level. GRP78 and CHOP protein levels represented a considerable decrease in the treatment group after the intervention. In addition, a statistically significant increase was found in the FF level of total antioxidant capacity in the treatment group. Based on clinical outcomes, no significant differences were found between the groups in terms of the oocyte number, fertilization rate, and fertility rate, but the ASX group had higher rates of high-quality oocytes, high-quality embryo, and oocyte maturity compared to the placebo group. Our findings demonstrated that ER stress in the GCs of PCOS patients could be modulated by ASX by changing the expression of genes and proteins included in the unfolding protein response.Trial registration This study was retrospectively registered on the Iranian Registry of Clinical Trials website ( www.irct.ir ; IRCT-ID: IRCT20201029049183N, 2020-11-27).

PMID:36854788 | DOI:10.1038/s41598-023-28956-8

Sci Rep. 2023 Feb 28;13(1):3389. doi: 10.1038/s41598-023-30415-3.

ABSTRACT

There is strong evidence showing that joint analysis of multiple phenotypes in genome-wide association studies (GWAS) can increase statistical power when detecting the association between genetic variants and human complex diseases. We previously developed the Clustering Linear Combination (CLC) method and a computationally efficient CLC (ceCLC) method to test the association between multiple phenotypes and a genetic variant, which perform very well. However, both of these methods require individual-level genotypes and phenotypes that are often not easily accessible. In this research, we develop a novel method called sCLC for association studies of multiple phenotypes and a genetic variant based on GWAS summary statistics. We use the LD score regression to estimate the correlation matrix among phenotypes. The test statistic of sCLC is constructed by GWAS summary statistics and has an approximate Cauchy distribution. We perform a variety of simulation studies and compare sCLC with other commonly used methods for multiple phenotype association studies using GWAS summary statistics. Simulation results show that sCLC can control Type I error rates well and has the highest power in most scenarios. Moreover, we apply the newly developed method to the UK Biobank GWAS summary statistics from the XIII category with 70 related musculoskeletal system and connective tissue phenotypes. The results demonstrate that sCLC detects the most number of significant SNPs, and most of these identified SNPs can be matched to genes that have been reported in the GWAS catalog to be associated with those phenotypes. Furthermore, sCLC also identifies some novel signals that were missed by standard GWAS, which provide new insight into the potential genetic factors of the musculoskeletal system and connective tissue phenotypes.

PMID:36854754 | DOI:10.1038/s41598-023-30415-3

Osteoporos Int. 2023 Feb 28. doi: 10.1007/s00198-023-06715-9. Online ahead of print.

ABSTRACT

PURPOSE: Interest in fractures in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has considerably increased in the last decade. However, few studies have compared the incidence of fractures between patients with MS and NMOSD using a nationwide database. This study aimed to evaluate the differences in the risk of fracture between patients with NMOSD and MS compared to that in healthy controls using cohort data from a Korean nationwide database.

METHODS: In this retrospective cohort study, data from the National Health Insurance Service (NHIS) database from January 2010 to December 2017 were analyzed. A total of 1,217/1,329 patients with MS/NMOSD free of fractures at the index date were included. Matched controls were selected based on age, sex, and the presence of hypertension, diabetes mellitus, and dyslipidemia. The mean follow-up durations after the index date were 4.40/4.08 years for patients with MS/NMOSD and 4.73/4.28 for their matched controls.

RESULTS: The adjusted hazard ratios (aHRs) with 95% confidence intervals of any, hip, and vertebral fractures were 1.81 (1.43-2.28), 3.36 (1.81-6.24), and 2.01 (1.42-2.99) times higher for patients with MS than for controls, respectively, and they were 1.85 (1.47-2.34), 3.82 (2.05-7.11), and 2.84 (1.92-4.21) times higher for patients with NMOSD than for controls, respectively. No significant differences were observed in the incidence of fractures between the MS and NMOSD groups. Patients with MS/NMOSD had a 1.8-fold higher risk of fracture than matched controls, and the risk of hip fracture was especially high (3- to 4-fold higher).

CONCLUSIONS: Clinicians need to regularly assess patients with MS/NMOSD for the risk of fractures and take preventative measures to reduce it.

PMID:36854747 | DOI:10.1007/s00198-023-06715-9