Tag: nevin manimala

Am Heart J. 2021 Feb 21:S0002-8703(21)00057-0. doi: 10.1016/j.ahj.2021.01.020. Online ahead of print.

ABSTRACT

BACKGROUND: Recent studies show a mechanistic link between gut microbiota-dependent formation of the atherosclerosis- and thrombosis-promoting metabolite trimethylamine N-oxide (TMAO) and cardiovascular disease (CVD). The clinical utility of TMAO in apparently healthy subjects for predicting incident CVD risks is unclear.

METHODS AND RESULTS: In the EPIC-Norfolk community-based study, we examined baseline fasting levels of TMAO and two of its nutrient precursors, choline and betaine, in a case:control design study comparing apparently European healthy middle-aged participants who subsequently develop CVD (Cases, n=908) versus those who did not (Controls, n=1,273) over an ensuing average follow-up period of 8 years. In participants who developed CVD vs controls, higher plasma TMAO (3.70 [IQR 2.50-6.41]μM vs 3.25 [IQR 2.19-52,1.15]μM; p<0.001) and choline levels (9.09 [IQR 7.87-10.53]μM vs 8.89 [IQR 7.66-10.13]μM; p=0.001) were observed. Following adjustments for traditional risk factors, elevated TMAO (adjusted odds ratio (OR) 1.58 [95% confidence interval (CI) 1.21-2.06], p<0.001) and choline levels (adjusted OR 1.31 [95%CI 1.00-1.72], p<0.05) remained predictive of incident CVD development. The clinical prognostic utility of TMAO remained significant and essentially unchanged regardless of the level of cutoff chosen between 1.5 uM (10%ile) to 10.5 uM (90%ile).

CONCLUSION: In apparently healthy participants of the community-based middle-aged EPIC-Norfolk population, elevated plasma levels of the gut microbe-dependent metabolite TMAO, and its nutrient precursor choline, predict incident risk for CVD development independent of traditional risk factors.

PMID:33626384 | DOI:10.1016/j.ahj.2021.01.020

Life Sci. 2021 Feb 21:119265. doi: 10.1016/j.lfs.2021.119265. Online ahead of print.

ABSTRACT

The objective of the current study was examining early and late (3, 24 h) responses to acute, chronic swimming exercise as muscle damage and regeneration in gastrocnemius-soleus muscle complexes. We also aimed to reveal the signaling pathways involved. 8-12 weeks old mice were grouped as control, exercise. Exercising groups were firstly divided into two as acute and chronic, later every group was again divided in terms of time (3, 24 h) passed from the last exercise session until exsanguination. Acute exercise groups swam 30 min, while chronic swimming groups exercised 30 min/day, 5 days/week, 6 weeks. Histological investigations were performed to determine muscle damage and regeneration. Whole-genome expression analysis was applied to total RNA samples. Microarray data was confirmed by quantitative real-time PCR. Exercising mice muscle revealed enhanced damage, leukocyte infiltration. Increments in acute and chronic 3 h groups were statistically significant. Car3, Neb, Obscn, Ttn, Igfbp5, Igfbp7, Gsk3β, and Usp2 were down-regulated in muscles of swimming mice. The exercise-induced signaling pathways involved in muscle damage and regeneration were drawn. Our findings demonstrate that swimming induces muscle damage. Samples were obtained at 3 and 24 h following exercise, this time duration seems not sufficient for the development of myofibrillogenesis.

PMID:33626393 | DOI:10.1016/j.lfs.2021.119265

Eur J Oncol Nurs. 2021 Feb 15;51:101908. doi: 10.1016/j.ejon.2021.101908. Online ahead of print.

ABSTRACT

PURPOSE: To test the effectiveness of henna in the management of palmar-plantar erythrodysesthesia (PPE) in patients receiving treatment with capecitabine or pegylated liposomal doxorubicin (PLD).

METHOD: This was a randomized controlled feasibility study in three specialized tertiary cancer centers with 56 patients with a PPE grade 1 or above and various cancer diagnoses. The intervention included the local application of henna to the affected areas. The control group followed the same process with a henna inert. Primary outcome was PPE grade and secondary outcomes were the EORTC QLQ-C30, PPE-related QoL (HFS-14), activities of daily living (ECOG) and pain. Patients in both groups were assessed at baseline and then weekly at four follow-ups.

RESULTS: PPE grade in the intervention group (1-3.8%) was lower compared to the control group (4-13.38%) and also lower levels of pain were reported by the patients in the intervention group (2.46 ± 1.17) compared to the control (5.57 ± 2.01). ECOG status in the intervention group was improved compared to the control (p = 0.039). The intervention group, experienced higher Global Health Status (p ≤ 0.008), Physical function (p ≤ 0.001), Emotional Function (p = 0.029), Social function (p ≤ 0.001) and lower Fatigue (p ≤ 0.001) and Pain (p ≤ 0.001) compared to the Control group. A statistically significant interaction was found between Group and Time over the weekly measurements of HFS-14 scores (F = 5,009, p ≤ 0.002) indicating the significant effect of the intervention throughout the weekly assessments.

CONCLUSION: The trial provided preliminary evidence on henna’s effectiveness for treating PPE during treatment with capecitabine or PLD, with lower PPE grades, better performance status and better HRQoL observed in the henna group. CLINICALTRIALS.

GOV IDENTIFIER: NCT01751893.

PMID:33626423 | DOI:10.1016/j.ejon.2021.101908

Pregnancy Hypertens. 2021 Feb 14;24:13-21. doi: 10.1016/j.preghy.2021.02.001. Online ahead of print.

ABSTRACT

Hypertensive disorders in pregnancy (HDP) are associated with various maternal and fetal adverse outcomes and become an increasingly significant threat to Chinese pregnant women. Yet, the prevalence of HDP in China is not clear. We conducted this meta-analysis to estimate the prevalence of HDP and specific subtypes in China. We searched PubMed, Embase, Web of Science, CNKI, Wangfang, and CMB for studies on prevalence of HDP and specific subtypes, published from 1990 to Jan 21, 2020, without language restrictions. We included all studies reported the prevalence of HDP and specific subtypes in Chinese pregnant women. We excluded qualitative studies, case reports, reviews, conference presentations, and studies only provided abstracts. We using a standard self-developed form to extract information from eligible studies. We did meta-analyses by random-effect models and estimated the pooled prevalence of HDP and specific subtypes. In order to explore potential sources of heterogeneity and subgroup effects, we did and meta-regression and subgroup analyses by pre-specified covariates. This study is registered with PROSPERO, number CRD42020166001. We initially identified 4179 records, of which 92 studies with 1,377,448 participants were eligible in the final systematic review and meta-analyses. The pooled prevalence (95% CI) of HDP, gestational hypertension, preeclampsia, mild preeclampsia, severe preeclampsia, eclampsia, chronic hypertension, and chronic hypertension with superimposed preeclampsia were 7.30% (6.60%-8.00%), 3.30% (2.90%-3.70%), 4.50% (4.00%-5.00%), 2.00% (1.70%-2.30%), 2.60% (2.10%-3.00%), 0.11% (0.08%-0.15%), 0.60% (0.30%-0.90%), and 0.60% (0.40%-0.80%), respectively. No publication bias was identified, although heterogeneity was high (I² statistics: 92.0%-99.3%). High prevalence of HDP and the subtypes frequently reported in Western and Northern China. Pregnant women who were aged 35 years and above had high prevalence of HDP and subtypes; women who were overweight or obese had high prevalence of HDP, gestational hypertension and preeclampsia. The prevalence of HDP and the subtypes vary in different areas in China. Given to increasingly prevalent of the risk factors, such as overweight, obesity, and advance maternal age, strategies to prevent and manage HDP need to be improved, especially for women living in Western and Northern China.

PMID:33626437 | DOI:10.1016/j.preghy.2021.02.001

Neurotoxicol Teratol. 2021 Feb 21:106963. doi: 10.1016/j.ntt.2021.106963. Online ahead of print.

ABSTRACT

Methylmercury (MeHg) is a persistent environmental neurotoxicant that may cause adverse neurodevelopmental effects. Previous studies showed that developmental MeHg exposure caused damage to brain functions that were unmasked after a silent period of years or decades. However, the underlying mechanisms of the latent neurotoxicity associated with MeHg exposure from earlier developmental stages have yet to be fully understood. Herein, we established a Caenorhabditis elegans (C. elegans) model of developmental MeHg latent toxicity. Synchronized L1 stage worms were exposed to MeHg (0, 0.05, 0.5 and 5 μM) for 48 h. Swimming moving speeds at adulthood were analyzed in worms exposed to MeHg exposure at early larvae stages. Worms developmentally exposed to MeHg had a significant decline in swimming moving speed on day 10 adult stage, but not on day 1 or 5 adult stage, even though the mercury level in the worms exposed to 0.05 or 0.5 μM MeHg were below the quantification limit on day 10 adult. Day 10 adult worms treated with MeHg showed a significant decrease in bending angle and bending frequency during swimming. Furthermore, their reduced moving speeds tended to increase during the 300-s swimming experiment. Dopamine signaling is known to be involved in the regulation of worms’ moving speed. Accordingly, the moving speed of worms with cat-2 (mammalian tyrosine hydroxylase homolog) mutation or dat-1 deletion were assayed on day 10 adult. The cat-2 mutant worms did not show a decline in moving speeds, body bends or bending angles during swimming on day 10 adult stage. Analyses of moving speeds of worms with dat-1 deletion showed that the moving speeds were further reduced after MeHg exposure. However, the effects of MeHg and dat-1 deletion were not synergistic, as the interaction between these parameters did not attain statistical significance. Altogether, our results suggest that developmental MeHg exposure reduced moving speed, and this latent toxicity was less pronounced in the context of deficient production of dopamine synthesis. Tyrosine hydroxylase plays an important role in regulating dopamine-mediated modulation of neurobehavioral functions. These findings uncovered a pivotal role of dopamine and its metabolism in the latent neurotoxic effects of MeHg.

PMID:33626374 | DOI:10.1016/j.ntt.2021.106963

Ann Oncol. 2021 Jan 21:S0923-7534(21)00014-4. doi: 10.1016/j.annonc.2021.01.006. Online ahead of print.

ABSTRACT

BACKGROUND: We predicted cancer mortality statistics for 2021 for the European Union (EU) and its five most populous countries plus the UK. We also focused on pancreatic cancer and female lung cancer.

MATERIALS AND METHODS: We obtained cancer death certifications and population data from the World Health Organization and Eurostat databases for 1970-2015. We predicted numbers of deaths and age-standardized (world population) rates for 2021 for total cancers and 10 major cancer sites, using a joinpoint regression model. We calculated the number of avoided deaths over the period 1989-2021.

RESULTS: We predicted 1,267,000 cancer deaths for 2021 in the EU, corresponding to age-standardized rates of 130.4/100,000 men (-6.6% since 2015) and 81.0 for women (-4.5%). We estimated further falls in male lung cancer rates, but still trending upward in women by +6.5%, reaching 14.5/100,000 in 2021. Breast cancer predicted rate in the EU was 13.3 (-7.8%). Rates for stomach and leukaemias in both sexes and for bladder in males are predicted to fall by over 10%; trends for other cancer sites were also favourable, except for pancreas, which showed stable patterns in both sexes, with predicted rates of 8.1/100,000 men and 5.6 for women. Rates for pancreas in EU men aged 25-49 and 50-64 declined, respectively, by 10% and 1.8%, while for those aged 65+ increased by 1.3%. Rates fell for young women only (-3.4%). Over 1989-2021, about 5 million cancer deaths were avoided in the EU27 compared with peak rates in 1988.

CONCLUSION: Overall cancer mortality continues to fall in both sexes. However, specific focus is needed on pancreatic cancer, which shows some hint of decline for young men only. Tobacco control remains a priority for the prevention of pancreatic and other tobacco-related cancers, which account for a third of the total EU cancer deaths, especially in women, who showed less favourable trends.

PMID:33626377 | DOI:10.1016/j.annonc.2021.01.006

JAMIA Open. 2020 Dec 14;3(4):557-566. doi: 10.1093/jamiaopen/ooaa060. eCollection 2020 Dec.

ABSTRACT

BACKGROUND: Synthetic data may provide a solution to researchers who wish to generate and share data in support of precision healthcare. Recent advances in data synthesis enable the creation and analysis of synthetic derivatives as if they were the original data; this process has significant advantages over data deidentification.

OBJECTIVES: To assess a big-data platform with data-synthesizing capabilities (MDClone Ltd., Beer Sheva, Israel) for its ability to produce data that can be used for research purposes while obviating privacy and confidentiality concerns.

METHODS: We explored three use cases and tested the robustness of synthetic data by comparing the results of analyses using synthetic derivatives to analyses using the original data using traditional statistics, machine learning approaches, and spatial representations of the data. We designed these use cases with the purpose of conducting analyses at the observation level (Use Case 1), patient cohorts (Use Case 2), and population-level data (Use Case 3).

RESULTS: For each use case, the results of the analyses were sufficiently statistically similar (P > 0.05) between the synthetic derivative and the real data to draw the same conclusions.

DISCUSSION AND CONCLUSION: This article presents the results of each use case and outlines key considerations for the use of synthetic data, examining their role in clinical research for faster insights and improved data sharing in support of precision healthcare.

PMID:33623891 | PMC:PMC7886551 | DOI:10.1093/jamiaopen/ooaa060

JAMIA Open. 2020 Dec 31;3(4):602-610. doi: 10.1093/jamiaopen/ooaa058. eCollection 2020 Dec.

ABSTRACT

OBJECTIVE: Patient information can be retrieved more efficiently in electronic medical record (EMR) systems by using machine learning models that predict which information a physician will seek in a clinical context. However, information-seeking behavior varies across EMR users. To explicitly account for this variability, we derived hierarchical models and compared their performance to nonhierarchical models in identifying relevant patient information in intensive care unit (ICU) cases.

MATERIALS AND METHODS: Critical care physicians reviewed ICU patient cases and selected data items relevant for presenting at morning rounds. Using patient EMR data as predictors, we derived hierarchical logistic regression (HLR) and standard logistic regression (LR) models to predict their relevance.

RESULTS: In 73 pairs of HLR and LR models, the HLR models achieved an area under the receiver operating characteristic curve of 0.81, 95% confidence interval (CI) [0.80-0.82], which was statistically significantly higher than that of LR models (0.75, 95% CI [0.74-0.76]). Further, the HLR models achieved statistically significantly lower expected calibration error (0.07, 95% CI [0.06-0.08]) than LR models (0.16, 95% CI [0.14-0.17]).

DISCUSSION: The physician reviewers demonstrated variability in selecting relevant data. Our results show that HLR models perform significantly better than LR models with respect to both discrimination and calibration. This is likely due to explicitly modeling physician-related variability.

CONCLUSION: Hierarchical models can yield better performance when there is physician-related variability as in the case of identifying relevant information in the EMR.

PMID:33623894 | PMC:PMC7886572 | DOI:10.1093/jamiaopen/ooaa058

Transp Res Interdiscip Perspect. 2021 Feb 18:100327. doi: 10.1016/j.trip.2021.100327. Online ahead of print.

ABSTRACT

During the COVID-19 period and particularly during lockdown, deviations from nominal operations have shown to become more frequent. To confirm this observation this paper proposes to evaluate the impact of COVID-19, and more generally of crises that lead to a sharp drop in traffic, on the pilot/controller system, especially during the critical approach and landing phases. To study the influence of this type of crisis on flight operations at Charles De Gaulle airport, an existing energy atypicality metric is applied on a reference period before COVID-19 and compared to the COVID-19 period. Whereas the traffic at Charles De Gaulle airport has decreased by around 90% on April 2020, the obtained statistics underlined an increase in the atypical flight ratio of around 50%. This trend can be explained in part by the appearance of glide interceptions from above as a result of trajectory shortenings, and an increase in the proportion of high speed approaches.

PMID:33623897 | PMC:PMC7891053 | DOI:10.1016/j.trip.2021.100327

North Clin Istanb. 2020 Nov 23;8(1):1-7. doi: 10.14744/nci.2020.10586. eCollection 2021.

ABSTRACT

OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is a health problem that has increasing importance in society. In the literature, many studies about an audition in patients with OSAS are present. In this study, the effects of hypoxia on an audition that develop during the apnea attacks in OSAS were investigated experimentally.

METHODS: This study was conducted in Inonu University Audiology Laboratory after the approval of Inonu University Faculty of Medicine Experimental Animal Research Ethics Committee (Protocol Number: 2011/A-102). In this study, 15 Wistar albino rats with a weight of 250-300 g were used. Anesthesia was performed by 40 mg/kg Ketamine and 5 mg/kg Xylazine through intramuscular administration. The processes were applied in the silence. This study involved 15 rats with normal auditory functions. Only tracheotomy was performed in the control group. Auditory assays were administered with otoacoustic emission (DP gram) before and after the process. In hypoxia group, hypoxia was created by making apnea attacks that lasted at least 10 seconds after the tracheotomy process. Auditory assays using DP gram were performed before tracheotomy and during hypoxia in the hypoxia group.

RESULTS: In the control group, statistically significant values were not found. In the hypoxia group, statistically significant differences were detected in high frequencies.

CONCLUSION: In conclusion, cochlear reply decreased in high frequencies during hypoxia that was created by apnea attacks.

PMID:33623866 | PMC:PMC7881432 | DOI:10.14744/nci.2020.10586