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Nevin Manimala Statistics

Proton pump inhibitors affect capecitabine efficacy in patients with stage II-III colorectal cancer: a multicenter retrospective study

Sci Rep. 2022 Apr 21;12(1):6561. doi: 10.1038/s41598-022-10008-2.

ABSTRACT

The association between capecitabine efficacy and proton pump inhibitors (PPIs) is controversial. Here, we determined whether co-administration of PPIs affects the real-world effectiveness of capecitabine. This retrospective observational study included consecutive patients with stage II-III colorectal cancer (CRC) who received adjuvant capecitabine monotherapy or CapeOX (capecitabine and oxaliplatin) between January 2009 and December 2014 at nine participating institutions. The primary endpoint was the difference in relapse-free survival (RFS) between patients who received PPIs and those who did not and was estimated using the Kaplan-Meier method. Overall survival (OS) was the secondary endpoint. Multivariable analysis of RFS and OS was performed using a Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting (IPTW) analyses. Data from 606 patients were evaluated, 54 of whom had received a PPI. PPI-treated patients tended to have poorer RFS and OS than patients treated without PPIs. The hazard ratio for RFS with capecitabine monotherapy was 2.48 (95% confidence interval: 1.22-5.07). These results were consistent with sensitivity analyses performed using propensity score adjustment and IPTW methods. Co-administration of PPIs may reduce the effectiveness of capecitabine and negatively impact patients with stage II-III CRC.

PMID:35449143 | DOI:10.1038/s41598-022-10008-2

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Chained multimediator model of sexual orientation disclosure, sexual minority stigma, sexual minority identity, social support, and resilience among ymsms

BMC Public Health. 2022 Apr 21;22(1):797. doi: 10.1186/s12889-022-13231-8.

ABSTRACT

INTRODUCTION: This study aimed to investigate sexual orientation disclosure and mental health among young men who have sex with men (YMSMs). To this end, we constructed a chained multimediator model of sexual minority stigma, sexual minority identity, social support, and resilience, with the moderator of sexual orientation disclosure.

METHODS: We conducted a cross-sectional survey of 345 YMSMs in Nanning, China. Bivariate analysis was used to evaluate factors associated with sexual orientation disclosure. Sexual minority stigma was used to predict identity, with social support as the step 1 mediator and resilience as the step 2 mediator. Sexual minority identity was analyzed using a chained moderated mediation model; sexual orientation disclosure was included as a moderator in all models to control its confounding effect.

RESULTS: The average age of YMSMs was 20.0 ± 1.3 years. Bivariate analysis indicated that YMSMs who disclosed sexual orientation may have experienced less stigma (15.49 ± 3.02 vs 16.21 ± 2.74), obtained more social support (65.98 ± 11.18 vs 63.19 ± 11.13), had strong psychological resilience (37.40 ± 8.57 vs 35.39 ± 7.73), and had a more positive self-identity (104.12 ± 21.10 vs 95.35 ± 16.67); differences between subgroups were statistically significant (p < 0.05). Sexual minority stigma, perceived stigma, and enacted stigma were significantly associated with social support and resilience. The association between sexual minority stigma and sexual minority identity was significantly mediated by social support (indirect effect [95% CI] = – 3.307 [- 4.782, – 1.907]). Resilience significantly mediated the same association for identity (- 2.544 [- 4.052, – 1.114]). The chained relationship from sexual minority stigma to social support, resilience, and identity was also significant, with an indirect effect of – 0.404 [- 0.621, – 0.249].

CONCLUSION: Among YMSMs in China, sexual minority stigma affects sexual minority identity through social support and resilience. Given the psychological effects of stigma, social support and resilience must be considered to better promote positive self-identity and mental health among YMSMs.

PMID:35449098 | DOI:10.1186/s12889-022-13231-8

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ACE2 immunohistochemistry in salivary and tracheal glands related to age

BMC Res Notes. 2022 Apr 21;15(1):144. doi: 10.1186/s13104-022-06031-1.

ABSTRACT

OBJECTIVE: SARS-CoV-2 is the cause of COVID-19, the rapidly spreading pandemic. When SARS-CoV-2 enters the target cells in the respiratory system, the spike glycoprotein binds to a cellular receptor angiotensin converting enzyme 2 (ACE2). The susceptibility to infection in individuals under 20 years of age is approximately half that of adults aged over 20 years. In this study, we investigated the immunohistochemical protein expressions of ACE2 in mandibular salivary glands and tracheal glands from forensic autopsy specimens covering adults and children.

RESULTS: The ACE2 immunohistochemistry of autopsy specimens was performed, and the percentages of the immuno-positive areas in the cell layers of the glands were calculated. Our results demonstrate that the ACE2 positivity in mandibular salivary gland and tracheal glands showed the statistically significant decrease with the increase of age, which indicates that the susceptibility of aged individuals to SARS-CoV-2 may be due to various factors including but not limited to ACE2 protein expressions.

PMID:35449115 | DOI:10.1186/s13104-022-06031-1

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Comparison of post-operative bleeding incidence in laser hemorrhoidoplasty with and without hemorrhoidal artery ligation: a double-blinded randomized controlled trial

BMC Surg. 2022 Apr 21;22(1):146. doi: 10.1186/s12893-022-01594-z.

ABSTRACT

INTRODUCTION: The effectiveness of hemorrhoidal artery ligation supplementation in reducing the incidence of post laser hemorrhoidoplasty bleeding has not been investigated.

METHODS: This was a double-blind, randomized controlled trial comparing post-operative bleeding incidence in patients undergoing laser hemorrhoidoplasty (LHP) only versus LHP with hemorrhoidal artery ligation (HAL). Outcome measures included post-operative bleeding and its severity (i.e. verbal rating scale and Clavien-Dindo classification), presence of perianal swelling and pain score (visual analog score) at 1-day, 1-week and 6-weeks post-operatively. Statistical tests were performed and a value of P < 0.05 was considered significant.

RESULTS: Seventy-six patients were randomized. There was no difference in median operating time. The bleeding incidence was highest at 1-week post-operatively (17.1%), and decreased to 1.3% at 6-weeks. There was no significant difference in bleeding incidence between both groups at any of the measured timepoints (P > 0.05). Severity of bleeding and incidence of post-operative perianal swelling were similar in both groups (P > 0.05). There was no difference in median pain scores.

CONCLUSION: Supplementation of HAL to LHP does not reduce the post-operative bleeding incidence. LHP is sufficient as a stand-alone procedure for treating haemorrhoids.

TRIAL REGISTRATION: National Registration Number is NMRR-15-1112-24065 (IIR). The trial start date was 1st January 2015 with the ClinicalTrials.gov identifier and registration number as NCT04667169.

PMID:35449097 | DOI:10.1186/s12893-022-01594-z

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Opinion: regulatory genotoxicity: past, present and future

Genes Environ. 2022 Apr 22;44(1):13. doi: 10.1186/s41021-022-00242-5.

ABSTRACT

I will reflect on the role of genotoxicity in the regulation of chemical safety, summarizing the past and current situation, and giving personal views for the future. This includes how genotoxicity information has been, and is being, used in the evaluation of the safety of chemical substances including pharmaceuticals, pesticides, food additives and industrial chemicals before they are introduced into the market for sale.In Japan, the Industrial Safety and Health Act, enacted in 1972, assures workers’ safety by including safety assessment of chemicals to which workers may be exposed in the workplace. The law firstly included the bacterial gene mutation assay with rat liver microsome fraction (Ames test) for the evaluation of chemical mutagenicity to predict carcinogenic potential, which was the forerunner of requiring a genotoxicity test by law. Since then, genotoxicity, especially the Ames test and the in vitro chromosomal aberration test using cultured mammalian cells (especially Chinese hamster cells) have been incorporated into several laws to assess the safety of various chemicals. Many test systems for different endpoints have been developed, improved, and used in practice. The battery strategy, combining several test systems to detect as many genotoxic chemicals as possible, was implemented because no one test system can detect all genotoxic agents with different mechanisms of genetic damage. In general, the standard battery consists of the Ames test, in vitro chromosomal aberration test and the in vivo rodent erythrocyte micronucleus test as a representative in vivo assay. Many other test systems have been used for supplementary testing as well as for research studies. Important keywords for regulatory science include 1) guidelines, 2) Good Laboratory Practice, 3) evaluation and interpretation of test results. Here, I discuss on these key points, and give personal opinions for the future.

PMID:35449081 | DOI:10.1186/s41021-022-00242-5

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The retinal ganglion cell layer reflects neurodegenerative changes in cognitively unimpaired individuals

Alzheimers Res Ther. 2022 Apr 21;14(1):57. doi: 10.1186/s13195-022-00998-6.

ABSTRACT

BACKGROUND: To evaluate a wide range of optical coherence tomography (OCT) parameters for possible application as a screening tool for cognitively healthy individuals at risk of Alzheimer’s disease (AD), assessing the potential relationship with established cerebrospinal fluid (CSF) core AD biomarkers and magnetic resonance imaging (MRI).

METHODS: We studied 99 participants from the Valdecilla Study for Memory and Brain Aging. This is a prospective cohort for multimodal biomarker discovery and validation that includes participants older than 55 years without dementia. Participants received a comprehensive neuropsychological battery and underwent structural 3-T brain MRI, lumbar puncture for CSF biomarkers (phosphorylated-181-Tau (pTau), total Tau (tTau), beta-amyloid 1-42 (Aβ 1-42), and beta-amyloid 1-40 (Aβ 1-40)). All individuals underwent OCT to measure the retinal ganglion cell layer (GCL), the retinal nerve fiber layer (RFNL), the Bruch’s membrane opening-minimum rim width (BMO-MRW), and choroidal thickness (CT). In the first stage, we performed a univariate analysis, using Student’s t-test. In the second stage, we performed a multivariate analysis including only those OCT parameters that discriminated at a nominal level, between positive/negative biomarkers in stage 1.

RESULTS: We found significant differences between the OCT measurements of pTau- and tTau-positive individuals compared with those who were negative for these markers, most notably that the GCL and the RNFL were thinner in the former. In stage 2, our dependent variables were the quantitative values of CSF markers and the hippocampal volume. The Aβ 1-42/40 ratio did not show a significant correlation with OCT measurements while the associations between pTau and tTau with GCL were statistically significant, especially in the temporal region of the macula. Besides, the multivariate analysis showed a significant correlation between hippocampal volume with GCL and RNFL. However, after false discovery rate correction, only the associations with hippocampal volume remained significant.

CONCLUSIONS: We found a significant correlation between Tau (pTau) and neurodegeneration biomarkers (tTau and hippocampus volume) with GCL degeneration and, to a lesser degree, with damage in RFNL. OCT analysis constitutes a non-invasive and unexpensive biomarker that allows the detection of neurodegeneration in cognitively asymptomatic individuals.

PMID:35449033 | DOI:10.1186/s13195-022-00998-6

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Assessment of the toxicity and carcinogenicity of double-walled carbon nanotubes in the rat lung after intratracheal instillation: a two-year study

Part Fibre Toxicol. 2022 Apr 22;19(1):30. doi: 10.1186/s12989-022-00469-8.

ABSTRACT

BACKGROUND: Considering the expanding industrial applications of carbon nanotubes (CNTs), safety assessment of these materials is far less than needed. Very few long-term in vivo studies have been carried out. This is the first 2-year in vivo study to assess the effects of double walled carbon nanotubes (DWCNTs) in the lung and pleura of rats after pulmonary exposure.

METHODS: Rats were divided into six groups: untreated, Vehicle, 3 DWCNT groups (0.12 mg/rat, 0.25 mg/rat and 0.5 mg/rat), and MWCNT-7 (0.5 mg/rat). The test materials were administrated by intratracheal-intrapulmonary spraying (TIPS) every other day for 15 days. Rats were observed without further treatment until sacrifice.

RESULTS: DWCNT were biopersistent in the rat lung and induced marked pulmonary inflammation with a significant increase in macrophage count and levels of the chemotactic cytokines CCL2 and CCL3. In addition, the 0.5 mg DWCNT treated rats had significantly higher pulmonary collagen deposition compared to the vehicle controls. The development of carcinomas in the lungs of rats treated with 0.5 mg DWCNT (4/24) was not quite statistically higher (p = 0.0502) than the vehicle control group (0/25), however, the overall incidence of lung tumor development, bronchiolo-alveolar adenoma and bronchiolo-alveolar carcinoma combined, in the lungs of rats treated with 0.5 mg DWCNT (7/24) was statistically higher (p < 0.05) than the vehicle control group (1/25). Notably, two of the rats treated with DWCNT, one in the 0.25 mg group and one in the 0.5 mg group, developed pleural mesotheliomas. However, both of these lesions developed in the visceral pleura, and unlike the rats administered MWCNT-7, rats administered DWCNT did not have elevated levels of HMGB1 in their pleural lavage fluids. This indicates that the mechanism by which the mesotheliomas that developed in the DWCNT treated rats is not relevant to humans.

CONCLUSIONS: Our results demonstrate that the DWCNT fibers we tested are biopersistent in the rat lung and induce chronic inflammation. Rats treated with 0.5 mg DWCNT developed pleural fibrosis and lung tumors. These findings demonstrate that the possibility that at least some types of DWCNTs are fibrogenic and tumorigenic cannot be ignored.

PMID:35449069 | DOI:10.1186/s12989-022-00469-8

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Lifestyle in adulthood can modify the causal relationship between BMI and islet function: using Mendelian randomization analysis

Diabetol Metab Syndr. 2022 Apr 21;14(1):55. doi: 10.1186/s13098-022-00828-7.

ABSTRACT

BACKGROUND: Body mass index was intimately associated with islet function, which was affected by various confounding factors. Among all methods of statistical analysis, Mendelian randomization best ruled out bias to find the causal relationship. In the present study, we explored the relationship between 13 East Asian body mass index-related genes reported previously and islet function using the Mendelian randomization method.

METHODS: A total of 2892 participants residing in northern China were enrolled. Anthropological information, such as sex, age, drinking status, smoking status, weight, height and blood pressure, was recorded for all participants. Fasting glucose and insulin were detected, and the insulin sensitivity index was calculated. 13 single nucleotide polymorphismss in East Asian body mass index -related genes were analysed with the ABI7900HT system.

RESULTS: Five genetic locus mutations, CDKAL1, MAP2K5, BDNF, FTO and SEC16B, were found to be associated with body mass index and were used to estimate the genetic risk score. We found that the genetic risk score was negatively associated with the insulin sensitivity index. Even after adjusted of confounding factors, the relationship showed statistical significance. A subsequent interaction effect analysis suggested that the negative relationship between the genetic risk score and insulin sensitivity index no longer existed in the nondrinking population, and smokers had a stronger negative relationship than nonsmokers.

CONCLUSION: We found a negative causal relationship between body mass index-related genetic locus mutations and insulin resistance, which might be increased by acquired lifestyle factors, such as drinking and smoking status.

PMID:35449023 | DOI:10.1186/s13098-022-00828-7

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The KIDSCREEN-27 scale: translation and validation study of the Slovenian version

Health Qual Life Outcomes. 2022 Apr 21;20(1):67. doi: 10.1186/s12955-022-01973-3.

ABSTRACT

BACKGROUND: There are many methods available for measuring social support and quality of life (QoL) of adolescents, of these, the KIDSCREEN tools are most widely used. Thus, we aimed to translate and validate the KIDSCREEN-27 scale for the usage among adolescents aged between 10 and 19 years old in Slovenia.

METHODS: A cross-sectional study was conducted among 2852 adolescents in primary and secondary school from November 2019 to January 2020 in Slovenia. 6-steps method of validation was used to test psychometric properties of the KIDSCREEN-27 scale. We checked descriptive statistics, performed a Mokken scale analysis, parametric item response theory, factor analysis, classical test theory and total (sub)scale scores.

RESULTS: All five subscales of the KIDSCREEN-27 formed a unidimensional scale with good homogeneity and reliability. The confirmatory factor analysis showed poor fit in user model versus baseline model metrics (CFI = 0.847; TLI = 0.862) and good fit in root mean square error (RMSEA = 0.072; p(χ2) < 0.001). A scale reliability was calculated using Cronbach’s α (0.93), beta (0.86), G6 (0.95) and omega (0.93).

CONCLUSIONS: The questionnaire showed average psychometric properties and can be used among adolescents in Slovenia to find out about their quality of life. Further research is needed to explore why fit in user model metrics is poor.

PMID:35448993 | DOI:10.1186/s12955-022-01973-3

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The variables associated with dental anxiety and their management in primary care dental clinics in Bahrain: a cross-sectional study

BMC Oral Health. 2022 Apr 21;22(1):137. doi: 10.1186/s12903-022-02173-7.

ABSTRACT

BACKGROUND: 20-80% of adults presenting to a dental clinic experience anxiety. Negative past dental experiences and environmental factors such as the waiting area of a dental clinic or sound of a drill are commonly considered triggering factors for anxiety. Anxiety management strategies are considered a part of routine dental procedure, due to increased prevalence and compromised patient care. Hence the aim of the present study is to identify the prevalence and variables associated with dental anxiety and their management in patients visiting the primary care dental clinics in Bahrain.

METHOD: Four hundred and eighty participants were included. A 3-part questionnaire deciphered the demographic characteristics of the participants, the dental procedure undertaken, the level of anxiety, and the management strategy used by the dentist. The pre and post-treatment MDAS scores were recorded. Paired t test, ANOVA and Wilcoxon signed rank test was used to test the level of significance between the variables and the mean MDAS scores. The p ≤ 0.05 was considered statistically significant.

RESULTS: The prevalence of dental anxiety was 23.7% with moderate anxiety, and 11.4% with high anxiety. Females presented with a higher mean MDAS both pre and post-treatment compared with males. A statistically significant difference between the pre and post-treatment MDAS scores were observed in educated patients less than 50 years of age. Those with unpleasant previous dental experience showed statistically significant difference. Analyses of anxiety management techniques showed that single techniques worked better than combination techniques. Rest and breaks combined with any other technique of choice showed significant reduction in the MDAS scores post treatment.

CONCLUSION: To conclude, all patients attending the dental clinic present with some level of anxiety that necessitates the dentist to use anxiety management strategies. Non-pharmacological methods that are non-invasive must be the first choice. Rests and breaks, with any technique of choice provides the best possible anxiety management. It is possible to achieve the desired anxiety reduction in single visit to complete the planned dental intervention, other than in patients who are dental phobic.

PMID:35448999 | DOI:10.1186/s12903-022-02173-7