Category: Nevin Manimala

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

J Cataract Refract Surg. 2021 Mar 9. doi: 10.1097/j.jcrs.0000000000000640. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the changes in refractive outcomes and corneal aberrations in central and paracentral keratoconus after Selective transepithelial topography-guided photorefractive keratectomy combined with Accelerated Corneal Collagen Cross-Linking (STARE-X).

SETTINGS: Centro polispecialistico Mediterraneo, Siena Crosslinking Center and University of Messina (Italy).

DESIGN: Prospective, interventional, multi-centric study.

METHODS: One hundred eyes of 100 patients underwent STARE-X protocol. Patients were subdivided into 2 groups: Group 1 with cone located within the central 3-mm zone (50 eyes); and Group 2 (50 eyes) with cone located outside the central 3-mm zone. Follow-up was two years at least for all eyes. Outcome parameters included uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA). Corneal tomography and corneal wavefront aberrations were assessed and compared before and two years after the treatment.

RESULTS: At 2 years UDVA, CDVA improved, as well as sphere, cylinder, K-max reduced after treatment in both groups (p<.001 respectively). Moreover, a statistically significant reduction was observed of total High-Order Aberrations Root Main Square (HOA RMS), Coma RMS and Spherical Aberration (SA RMS) in both groups (p<.001 respectively). However, CDVA improved more in Group 1 than in Group 2 (p<.02).

CONCLUSION: The STARE-X protocol demonstrated effective results in halting keratoconus progression and improving corneal regularity with a safe and effective profile. STARE-X improved both visual acuity and corneal aberration at 2 years. Longer follow-up studies are warranted to observe further long-term CXL flattening effect on the cone.

PMID:33770171 | DOI:10.1097/j.jcrs.0000000000000640

PLoS One. 2021 Mar 26;16(3):e0249295. doi: 10.1371/journal.pone.0249295. eCollection 2021.

ABSTRACT

STUDY DESIGN: Chart reviews were combined with neurological and functional outcome data obtained from the prospective European Multicenter Study on Spinal Cord Injury (EMSCI, www.emsci.org).

OBJECTIVES: To determine if strict physical isolation of multidrug-resistant organisms (MDRO)-positive patients negatively affects neurological recovery and functional outcome in the first year after acute spinal cord injury (SCI).

SETTING: SCI Center Heidelberg University Hospital.

METHODS: Individuals with acute (< 6 weeks) traumatic or ischemic SCI were included. During primary comprehensive care, isolated MDRO-positive patients (n = 13) were compared with a MDRO-negative control group (n = 13) matched for functional (Spinal Cord Independence Measure-SCIM) and neurological impairment (motor scores based on the International Standards for Neurological Classification of Spinal Cord Injury-ISNCSCI) at an early stage up to 40 days after SCI. SCIM scores and motor scores were obtained at 12 weeks (intermediate stage) and 24 or 48 weeks (late stage) after SCI.

RESULTS: Isolated MDRO-positive (median duration of hospitalization: 175 days, 39% of inpatient stay under isolation measures) and non-isolated MDRO-negative (median duration of hospitalization: 161 days) patients showed functional and neurological improvements, which were not statistically different between groups at the intermediate and late stage.

CONCLUSION: Prolonged isolation due to MDRO colonization for over a third of the inpatient comprehensive care period does not appear to impair neurological recovery and functional outcome within the first year after SCI.

PMID:33770131 | DOI:10.1371/journal.pone.0249295

PLoS One. 2021 Mar 26;16(3):e0249213. doi: 10.1371/journal.pone.0249213. eCollection 2021.

ABSTRACT

The aim of this study was to evaluate the influence of increase in intraocular pressure (IOP) and cooccurring changes in ocular biometry parameters on the corneal optical coherence tomography (OCT) speckle distribution in ex-vivo experiments on porcine intact eyes. Twenty-three eyeballs were used in the inflation test where IOP in the anterior chamber was precisely set from 10 mmHg to 40 mmHg in steps of 5 mmHg and where eye biometry was utilized (IOL Master 700). To assess the influence of the duration of the experiment on the OCT speckle statistics, the second experiment was performed with 10 eyeballs at the constant IOP of 15 mmHg. Based on the OCT scans of central cornea (Copernicus REVO), spatial maps of the scale parameter (a) and the shape parameter (v) of the gamma distribution speckle model were estimated. The means of both parameters for each spatial map were computed within the 2 mm of the central stroma. Both distributional parameters statistically significantly varied with IOP and time (one way repeated measures ANOVA, all p-values < 0.001). The a parameter revealed a faster statistically significant increase in IOP up to 25 mmHg, regardless of time. Central corneal thickness (CCT), the anterior chamber depth, and the mean equivalent spherical power varied significantly with IOP, whereas CCT and axial length changed statistically significantly with time. Statistically significant correlation was found between CCT and the a parameter, after removing IOP as a confounding factor (r = -0.576, p < 0.001). The parameters of the gamma distribution can be used not only for identifying IOP induced changes in the optical scattering within the corneal stroma, but also in corneal geometry. The approach of corneal speckle analysis could be potentially utilized for an indirect and noninvasive assessment of some properties of corneal stroma.

PMID:33770135 | DOI:10.1371/journal.pone.0249213

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

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

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

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

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

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