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Nevin Manimala Statistics

Genetic Predisposition to Type 2 Diabetes and Insulin Levels is Positively Associated with Serum Urate Levels

J Clin Endocrinol Metab. 2021 Mar 26:dgab200. doi: 10.1210/clinem/dgab200. Online ahead of print.

ABSTRACT

PURPOSE: Previous epidemiological evidence showed that type 2 diabetes (T2D) is related with gout. However, the causality and the direction of this association are still not definitely elucidated. We aimed to investigate bidirectional associations of T2D and glycemic traits with serum urate concentrations and gout using a Mendelian randomization (MR) approach.

METHODS: Summary statistics from the large-scale genome-wide association studies conducted for T2D (Ncase=62,892, Ncontrol=596,424), fasting glucose (N=133,010), fasting insulin (N=133,010), hemoglobinA1c (N=123,665), homeostasis model assessment of insulin resistance (N=46,186), urate (N=110,347) and gout (Ncase=2,115, Ncontrol=67,259) among participants of European ancestry were analyzed. For each trait of interest, independent genome-wide significant (p<5×10 -8) single nucleotide polymorphisms were selected as instrumental variables. The inverse-variance weighted method was used for the primary analyses.

RESULTS: Genetic predisposition to higher risk of T2D (beta=0.042; 95% CI=0.016-0.068; p=0.002) and higher levels of fasting insulin (beta=0.756; 95% CI=0.408-1.102; p=1.96e-05) were significantly associated with increased serum urate concentrations. Moreover, we found suggestively significant evidence supporting a causal role of fasting insulin on risk of developing gout (OR=3.06; 95% CI=0.88-10.61; p=0.078). In the reverse direction analysis, both genetic predisposition to urate and gout were not associated with T2D and any of four glycemic traits being investigated.

CONCLUSIONS: This study provides supportive evidence on causal associations of T2D and fasting insulin with serum urate concentrations, and suggestive association of fasting insulin with risk of gout. Future research is required to examine the underlying biological mechanisms on such relationships.

PMID:33770169 | DOI:10.1210/clinem/dgab200

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Nevin Manimala Statistics

Maternal health care services utilization amidstCOVID-19 pandemic in West Shoa zone, central Ethiopia

PLoS One. 2021 Mar 26;16(3):e0249214. doi: 10.1371/journal.pone.0249214. eCollection 2021.

ABSTRACT

The novel coronavirus (COVID-19) is an infectious disease caused by a newly discovered coronavirus. Despite strong efforts that have been taking place to control the pandemic globally, the virus is on the rise in many countries. Hence, this study assessed the maternal health care services utilization amidst the COVID-19 pandemic in West Shoa zone, Central Ethiopia. A community-based cross-sectional study was conducted among 844 pregnant women or those who gave birth in the last 6 months before the study. A multi-stage sampling technique was used to select the study participants. The data were collected through face-to-face interviews using a semi-structured questionnaire. Logistic regressions were performed to identify the presence of significant associations, and an adjusted odds ratio with 95%CI was employed for the strength and directions of association between the independent and outcome variables. A P-value of <0.05 was used to declare statistical significance. The prevalence of maternal health service utilization during the COVID-19 pandemic was 64.8%. The odds of maternal health service utilization was higher among mothers who had primary (AOR = 2.16, 95%CI: 1.29-3.60), secondary (AOR = 1.97, 95%CI: 1.13-3.44), and college and above education (AOR = 2.89, 95%CI: 1.34-6.22) than those who could not read and write. Besides, mothers who did travel 30-60 minutes (AOR = 0.37, 95%CI: 0.23-0.59) and 60-90minutes (AOR = 0.10, 95%CI: 0.05-0.19) to reach the health facility had a lower odds of maternal health service utilization than those who did travel <30 minutes. Moreover, mothers who earn 1000-2000 (AOR = 3.10, 95%CI: 1.73-5.55) and > 2000 birrs (AOR = 2.66 95%CI: 1.52-4.64) had higher odds of maternal health service utilization than those who earn <500 birrs. Similarly, the odds of utilizing maternal health service were higher among mothers who did not fear COVID-19 infection (AOR = 2.79, 95%CI: 1.85-4.20), who had not had to request permission from husband to visit the health facility (AOR = 7.24, 95%CI: 2.65-19.75), who had practicedCOVID-19 prevention measure (AOR = 5.82, 95%CI: 3.87-8.75), and used face mask (AOR = 2.06, 95% CI: 1.28-3.31) than their counterpart. Empowering mothers and creating awareness on COVID-19 preventionis recommended to improve maternal health service utilization during the COVID-19 pandemic.

PMID:33770120 | DOI:10.1371/journal.pone.0249214

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Nevin Manimala Statistics

The Exponentiated Exponential Burr XII distribution: Theory and application to lifetime and simulated data

PLoS One. 2021 Mar 26;16(3):e0248873. doi: 10.1371/journal.pone.0248873. eCollection 2021.

ABSTRACT

The paper addresses a new four-parameter probability distribution called the Exponentiated Exponential Burr XII or abbreviated as EE-BXII. We derive various statistical properties in addition to the parameter estimation, moments, and asymptotic confidence bounds. We estimate the precision of the maximum likelihood estimators via a simulation study. Furthermore, the utility of the proposed distribution is evaluated by using two lifetime data sets and the results are compared with other existing probability distributions. The results clarify that the proposed distribution provides a better fit to these data sets as compared to the existing probability distributions.

PMID:33770126 | DOI:10.1371/journal.pone.0248873

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Nevin Manimala Statistics

A genetic analysis identifies haplotype at adiponectin locus: association with the metabolic health and obesity phenotypes

Gene. 2021 Mar 22:145593. doi: 10.1016/j.gene.2021.145593. Online ahead of print.

ABSTRACT

BACKGROUND: Obesity and metabolic syndrome frequently co-exist and define obese individuals into different obesity phenotypes, such as metabolically health obese (MHO), metabolically unhealth obese (MUO) and metabolically unhealth normal weight (MUNW). Growing evidence suggests that genetic predisposition and environmental factor can explain the heterogeneity among these phenotypes.

METHODS: We conducted a case-control study including 130 MHO, 251 MUNW, 208 MUO and 336 health controls by genotyping 2 SNPs (rs2241766, rs1501299) in ADIPOQ to investigate possible associations between SNPs in the ADIPOQ gene with susceptibility to three obese phenotypes respectively in Chinese Han population. Unconditional logistic regressions were used to detect the association between ADIPOQ SNPs and MHO/MUNW/MUO risks.

RESULTS: Variant G allele of rs2241766 was associated with a reduced odds of MUO (additive model: Adjusted OR=0.55; 95% CI=0.40-0.75; P<0.001) and no evidence of any significant association between rs2241766 and MHO phenotype (additive model: Adjusted OR=0.84; 95% CI=0.61-1.16; P=0.306) or MUNW phenotype (additive model: Adjusted OR=0.95; 95% CI=0.73-1.24; P=0.720) was found. Minor allele T of rs1501299 were significantly associated with decreased risk of MHO (Adjusted OR=0.53; 95% CI=0.37-0.76; P<0.001), MUNW (Adjusted OR=0.63; 95% CI=0.48-0.83; P=0.001) in additive genetic model after correction for multiple testing.

CONCLUSIONS: The variant G allele of rs2241766 was negatively associated with risk of MUO and variant T allele of rs1501299 exhibited reduced odds for MHO and MUNW. Beyond that, future studies are warranted to validate and extend our findings.

PMID:33766710 | DOI:10.1016/j.gene.2021.145593

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Nevin Manimala Statistics

Combination of biomarkers for neoadjuvant systemic chemotherapy before cystectomy in patients with urinary bladder cancer

Transl Res. 2021 Mar 22:S1931-5244(21)00076-1. doi: 10.1016/j.trsl.2021.03.013. Online ahead of print.

ABSTRACT

Clinical utility of cisplatin based neoadjuvant chemotherapy (NAC) prior to radical cystectomy is limited because of lack of tools that can guide for a better patient selection. We aim to explore if a combination of biomarkers is superior to a single marker. Pretreatment tumor specimens and clinical data from two randomized trials including 250 patients with T2-T4 urothelial bladder cancer, were used. The information on the expressions on tumor tissue of four biomarkers; CCTα, emmprin, survivin, and BCL-2, detected by immunohistochemistry in our previous studies, was used. Cox proportional hazard models, including treatment-by-biomarker interaction terms, were used to assess the predictive value of the biomarkers for efficacy of NAC on overall survival. CCTα provided predictive information about the efficacy of NAC (interaction P=0.009). None of the other biomarkers provided statistically significant information additional to CCTα. The adjusted hazard ratio for NAC treated versus no-NAC was 0.42 (95% CI: 0.27-0.64) for patients with negative CCTα expression, when adding information about emmprin it decreased to 0.33 (95% CI: 0.19-0.56) for patients with both negative CCTα and emmprin. This corresponds to a decrease in number needed to treat from 4 to 3 patients. The combination of CCTα with survivin or BCL-2 yielded similar results. In a group of patients with muscle invasive bladder cancer a combination of two biomarkers might improve the possibility to identify patients most likely to benefit from the use of NAC. Further studies designed to have sufficient power to detect an interaction effect are needed.

PMID:33766713 | DOI:10.1016/j.trsl.2021.03.013

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Nevin Manimala Statistics

An early-morning gene network controlled by phytochromes and cryptochromes regulates photomorphogenesis pathways in Arabidopsis

Mol Plant. 2021 Mar 22:S1674-2052(21)00094-0. doi: 10.1016/j.molp.2021.03.019. Online ahead of print.

ABSTRACT

Light perception at dawn plays a key role in coordinating multiple molecular processes and in entraining the plant circadian clock. An Arabidopsis mutant lacking the main photoreceptors however still shows clock entrainment, indicating that the integration of light into the morning transcriptome is not well understood. We performed a high-resolution RNA-seq time series experiment, sampling every two-minutes from dawn. In parallel experiments, we perturbed temperature, the circadian clock, photoreceptor signalling and chloroplast-derived light signalling. We used this data to infer a gene network that describes the gene expression dynamics after light stimulus in the morning, and then we validated key edges. By sampling time points at high density, we are able to identify three light- and temperature-sensitive bursts of transcription factor activity, one of which lasts for only about eight minutes. Phytochrome and cryptochrome mutants cause a delay in the transcriptional bursts at dawn, and completely remove a burst of expression in key photomorphogenesis genes (HY5 and BBX family). Our complete network is available online (http://www-users.york.ac.uk/∼de656/dawnBurst/dawnBurst.html). Taken together, our results show that phytochrome and cryptochrome signaling is required for fine-tuning the dawn transcriptional response to light, but separate pathways can robustly activate much of the programme in their absence.

PMID:33766657 | DOI:10.1016/j.molp.2021.03.019

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Nevin Manimala Statistics

Elevated Risk of Venous Thromboembolism in Patients Undergoing Therapeutic Hypothermia After Cardiac Arrest

Resuscitation. 2021 Mar 22:S0300-9572(21)00117-9. doi: 10.1016/j.resuscitation.2021.03.013. Online ahead of print.

ABSTRACT

INTRODUCTION: Targeted Temperature Management (TTM) reduces mortality and improves neurological outcomes after cardiac arrest. Cardiac arrest is considered a pro-thrombotic state. Endovascular cooling catheters may increase the risk of thrombosis. Targeted Temperature Management, however, increases fibrinolysis. The net outcome of these opposing effects remains largely unexplored. Moreover, the exact rate of venous thromboembolism (VTE) is uncertain in these patients. We sought to determine the incidence and potential predictors of VTE in patients undergoing TTM.

METHODS: Single center retrospective analysis. Participants were age ≥18 years old, admitted with out-of-hospital or in-hospital cardiac arrest, underwent TTM between January 1, 2007 and April 30, 2019 with endovascular cooling catheter. A total of 562 patients who underwent TTM (Study group) were compared to 562 patients treated for ARDS (control group). This control group was based on presumed similarities in factors affecting VTE: intensive care setting, immobility, length of stay and likely presence of central venous catheters.

RESULTS: Patients who underwent TTM had a significantly higher rate of VTE (6.6% vs 2.3%, p = 0.006) and deep vein thrombosis (DVT) (4.6% vs 1.3%, p = 0.011) when compared to control group. In multivariate analysis age, gender, race and hospital length of stay were not associated with development of VTE in the study group.

CONCLUSION: Patients undergoing TTM after cardiac arrest have statistically higher incidence of VTE and DVT compared to patients with ARDS. This risk is independent of age, gender, race or length of stay.

PMID:33766667 | DOI:10.1016/j.resuscitation.2021.03.013

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Nevin Manimala Statistics

Single dose high-dose-rate brachytherapy with focal dose escalation: mature results of a phase 2 clinical trial

Radiother Oncol. 2021 Mar 22:S0167-8140(21)06144-2. doi: 10.1016/j.radonc.2021.03.018. Online ahead of print.

ABSTRACT

AIM: The dominant intraprostatic lesion (DIL) is the commonest site of relapse after single dose high-dose-rate brachytherapy (HDR-BT) for localised prostate cancer. This study investigated toxicity and clinical outcomes of focal dose escalation to the DIL with dose de-escalation to the remaining prostate.

MATERIALS: /Methods Between November 2012 and July 2016, 50 patients with localised prostate adenocarcinoma received single fraction HDR-BT. 21Gy was prescribed to the DIL, with two de-escalation prescription schedules for the remaining prostate. Primary outcomes included biochemical no evidence of disease (bNED), local recurrence free survival (LRFS), and metastasis free survival (MFS). Secondary outcomes included late genitourinary, gastrointestinal and sexual toxicity. Kaplan-Meier analyses with log rank tests were used to estimate bNED, LRFS and MFS.

RESULTS: With a median follow up of 70.6 months, 15 patients developed biochemical failure, including 8 in the group that received minor dose de-escalation to the non-DIL prostate (group 1) and 7 in the group that received moderate de-escalation (group 2). Five-year bNED was 88% in group 1 and 76% in group 2 (p=0.05). Overall 4-year and 5-year FFLF in group 1 was 100% and 96% and in group 2 92% and 84%. These differences were statistically significant (p=0.03). No acute ≥G3 genitourinary or ≥G2 gastrointestinal toxicity was reported. The median IIEF decreased in the first 6 months improving to a peak median score of 20 at 54 months.

CONCLUSION: Focal boost to the DIL did not improve biochemical or local control after single-fraction HDR monotherapy compared to what would be expected from 19Gy single fraction treatment to the whole gland.

PMID:33766703 | DOI:10.1016/j.radonc.2021.03.018

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Nevin Manimala Statistics

The novel galactosyl transferase-like (SbGalT) gene from Salicornia brachiata maintains photosynthesis and enhances abiotic stress tolerance in transgenic tobacco

Gene. 2021 Mar 22:145597. doi: 10.1016/j.gene.2021.145597. Online ahead of print.

ABSTRACT

We hereby report in planta function characterization of a novel galactosyl transferase-like (SbGalT) gene from Salicornia brachiata for enhanced abiotic stress tolerance. The SbGalT gene had an open reading frame of 1563 bp. The ectopic expression of SbGalT gene in tobacco improved the seed germination, seedling growth, biomass accumulation and potassium/sodium ratio under salt and osmotic stress. The SbGalT over-expression delayed stress-induced senescence, pigment breakdown and ionic cytotoxicity in tobacco. Higher contents of organic solutes and potassium under stress maintained the osmotic homeostasis and relative water content in tobacco. Higher activity of antioxidant enzymes under stress in transgenic tobacco curtailed accumulation of reactive oxygen species (ROS) and maintained the membrane integrity. The chlorophyll a fluorescence transient indicated no influences of imposed strengths of stress on basal state of photosystem (PS) I in transgenic tobacco over-expressing the SbGalT gene. Due to better membrane integrity the transgenic tobacco exhibited improved photosynthesis, stomatal conductance, intercellular CO2, transpiration, maximum quantum yield and operating efficiency of PSII, electron transport, photochemical and non-photochemical quenching. In agreement with photosynthesis, physiological health, tolerance index and growth data, transgenic tobacco accumulated higher contents of sugar, starch, amino acid, polyphenol and proline under stress conditions. The multivariate data analysis exhibited significant statistical distinctions among osmotic adjustment, physiological health and growth, and photosynthetic responses in control and SbGalT transgenic tobacco under stress conditions. The results strongly indicated novel SbGalT gene as a potential candidate for developing smart agriculture.

PMID:33766708 | DOI:10.1016/j.gene.2021.145597

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Nevin Manimala Statistics

How can food choice best be trained? Approach-avoidance versus go/no-go training

Appetite. 2021 Mar 22:105226. doi: 10.1016/j.appet.2021.105226. Online ahead of print.

ABSTRACT

Behavior toward appetitive stimuli can be changed by motor response training procedures in which participants approach or respond to some stimuli and avoid or inhibit behavior to other stimuli. There is discussion in the literature whether effects are different when participants approach versus avoid stimuli during approach-avoidance training compared to when they respond versus not respond to stimuli during go/no-go training. Here, we directly compared effects of approach-avoidance training and go/no-go training on food choice within the same rigorous experimental protocol. Results showed that both training procedures influence food choice such that participants preferred Approach over Avoidance food items, and Go over NoGo food items, and these training effects were not statistically different. The present work suggests any inconsistencies in the literature on possible differences in effectiveness of these training procedures may be explained by differences in methods employed. The present work also raises new theoretical and applied questions about motor response training as a means to change behavior.

PMID:33766617 | DOI:10.1016/j.appet.2021.105226