Category: Nevin Manimala

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

Hypertens Res. 2023 Feb 28. doi: 10.1038/s41440-023-01231-z. Online ahead of print.

ABSTRACT

Resveratrol (RES) has been demonstrated to be protective in the cardiovascular system in animal studies, but the evidence is limited in humans. The purpose of the study was to evaluate the effect of RES supplementation on cardiac remodeling in patients with hypertension. Eighty Subjects were randomly divided into RES group (plus RES 400 mg/d in addition to conventional therapy, n = 43) and control group (conventional therapy, n = 37). The main outcomes of the study were changes within cardiac-remodeling parameters. Secondary outcomes were changes in anthropometric parameters, arterial stiffness parameters and mechanism indices. There was no statistically significant difference between the RES group and control group in terms of baseline characteristics. After 6 months, the RES group had smaller left atrial, lower E/e’, higher left ventricular global longitudinal strain and lower biomarkers indicating cardiac fibrosis (expressed by decreases in procollagen type I C-peptide and galectin-3) compared to the control group. However, there was no significant difference in left ventricular structure between the two groups. Although the RES group showed a significant decrease in brachial-ankle pulse wave velocity compared to the pre-intervention value, the difference between the RES and the control groups was not obvious. What’s more, compared with the control group, the serum levels of sirtuin3, superoxide dismutase and klotho were significantly increased in the RES group. In conclusion, RES supplementation can alleviate left atrial remodeling, improve left ventricular diastolic function and may alleviate cardiac fibrosis in hypertensive patients, and could be used as an adjunct to conventional therapies of hypertensive heart disease.

PMID:36854725 | DOI:10.1038/s41440-023-01231-z

Zhongguo Dang Dai Er Ke Za Zhi. 2023 Feb 15;25(2):140-146. doi: 10.7499/j.issn.1008-8830.2209142.

ABSTRACT

OBJECTIVES: To study new biomarkers for the early diagnosis of retinopathy of prematurity (ROP) by analyzing the differences in blood metabolites based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and metabolomics.

METHODS: Dried blood spots were collected from 21 infants with ROP (ROP group) and 21 infants without ROP (non-ROP group) who were hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2013 to December 2016. LC-MS/MS was used to measure the metabolites, and orthogonal partial least squares-discriminant analysis was used to search for differentially expressed metabolites and biomarkers.

RESULTS: There was a significant difference in blood metabolic profiles between the ROP and non-ROP groups. The pattern recognition analysis, Score-plot, and weight analysis obtained 10 amino acids with a relatively large difference. Further statistical analysis showed that the ROP group had significant increases in blood levels of glutamic acid, leucine, aspartic acid, ornithine, and glycine compared with the non-ROP group (P<0.05). The receiver operating characteristic curve analysis showed that glutamic acid and ornithine had the highest value in diagnosing ROP.

CONCLUSIONS: Blood metabolites in preterm infants with ROP are different from those without ROP. Glutamic acid and ornithine are the metabolic markers for diagnosing ROP. LC-MS/MS combined with metabolomics analysis has a potential application value in the early identification and diagnosis of ROP.

PMID:36854689 | DOI:10.7499/j.issn.1008-8830.2209142

Sci Rep. 2023 Feb 28;13(1):3401. doi: 10.1038/s41598-023-29975-1.

ABSTRACT

This study describes the clinical anatomical topography and relationship of the terminal branches of the maxillary artery to the bony wall of the maxillary sinus in the pterygopalatine fossa (PPF) to estimate the bleeding risk during surgical interventions. Using contrasted computer tomography records, (i) the route of the maxillary artery in the infratemporal fossa, (ii) the number of the arteries in the critical PPF surgery plane, (iii) the diameter of the largest artery in the area and (iv) its relation to the posterior wall of the maxillary sinus were examined. Furthermore, measurements were extended with (v) the minerality of the bony posterior wall of the maxillary sinus on bone-window images. For statistical analyses Student’s t- and Fisher-test were applied. 50 patients (n = 50, 100 cases including both sides) were examined in this study. The maxillary artery reached the pterygomaxillary fissure on the lateral side of the lateral pterygoid muscle in 56% of the cases (n = 32), in 37% (n = 23) on its medial side and in 7% (n = 4) on both sides. The number of arteries at the level of the Vidian canal in the PPF varied between 1 and 4 with a median of 2. The diameter of the biggest branch was 1.2-4.7 mm, the median diameter was 1.90 mm. In 41% (n = 30) of the cases the biggest artery directly contacted the posterior wall of the maxillary sinus, and the mineral density of the posterior wall was decreased in 14.3% (n = 12) of all investigated cases. The present description and statistical analysis of the vasculature of the PPF optimizes operative planning-like clip size or the type and direction of the surgical approach-in this hidden and deep head/neck region.

PMID:36854685 | DOI:10.1038/s41598-023-29975-1

Nat Commun. 2023 Feb 28;14(1):1131. doi: 10.1038/s41467-023-36490-4.

ABSTRACT

Mendelian randomization using GWAS summary statistics has become a popular method to infer causal relationships across complex diseases. However, the widespread pleiotropy observed in GWAS has made the selection of valid instrumental variables problematic, leading to possible violations of Mendelian randomization assumptions and thus potentially invalid inferences concerning causation. Furthermore, current MR methods can examine causation in only one direction, so that two separate analyses are required for bi-directional analysis. In this study, we propose a ststistical framework, MRCI (Mixture model Reciprocal Causation Inference), to estimate reciprocal causation between two phenotypes simultaneously using the genome-scale summary statistics of the two phenotypes and reference linkage disequilibrium information. Simulation studies, including strong correlated pleiotropy, showed that MRCI obtained nearly unbiased estimates of causation in both directions, and correct Type I error rates under the null hypothesis. In applications to real GWAS data, MRCI detected significant bi-directional and uni-directional causal influences between common diseases and putative risk factors.

PMID:36854672 | DOI:10.1038/s41467-023-36490-4

Int J Environ Health Res. 2023 Feb 28:1-13. doi: 10.1080/09603123.2023.2185209. Online ahead of print.

ABSTRACT

In this study, it is aimed to examine the relationship between green behaviors of health professionals and green practices in the workplace. The study sample consisted of 174 health professionals from 34 Family Healthcare Centers (FHCs) in Turkey. Number, percent, mean, standard deviation, student’s test, Mann – Whitney U test, One Way Anova test, Kruskal-Wallis H test, linear regression analysis were used for statistical analysis. Energy-saving (β: 0.197; 95%CI: 0.040;0.266) and waste reduction practices (β: 0.174; 95%CI: 0.019;0.256) in the workplace were positive associated with environmental sensitivity. Waste reduction practices (β: 0.228; 95%CI: 0.093;0.478) in the workplace were positive associated with environmental participation. Recycling bins (β: 0.181; 95%CI :0.084;0.799) and using solar energy (β: 0.198; 95%CI: 0.030; 0.785) in the workplace were positive associated with technological sensitivity. Health professionals who work in workplaces with energy-saving, waste reduction practices, recycling bins and using solar energy more likely to display green behaviors.

PMID:36854645 | DOI:10.1080/09603123.2023.2185209