Category: Nevin Manimala

Microb Pathog. 2021 Dec 6:105340. doi: 10.1016/j.micpath.2021.105340. Online ahead of print.

ABSTRACT

BACKGROUND: Growing evidence implicates the potential effect of microbiota on the pathogenesis and course of epilepsy. However, the effects of valproate (VPA), a broad spectrum anti-epileptic drugs, on gut microbiota have not been investigated in humans. This study aimed to analyze fecal microbiota in patients with epilepsy treated with valproate.

METHODS: A total of 10 participants, who were newly diagnosed of cryptogenic epilepsy with treatment naïve and received 1000 mg daily doses of VPA, were recruited in our prospective study. Microbiota compositions were evaluated at baseline and after three months of VPA treatment using 16S rDNA sequencing.

RESULTS: VPA treatment was associated with clinical improvements in all patients, but not changes in gut microbiota richness and complexity (Shannon: p = 0.82). Microbiome composition structure differences also revealed no statistical difference in dissimilarity (Adonis: p = 0.90). No statistical difference taxa were found between two groups. However, the ratio of phyla Firmicutes to Bacteriodetes (ANOVA: p = 0.037) markedly raised after three months of VPA-treatment. A correlation matrix based on the spearman correlation distance confirmed associations between specific fecal taxa and VPA-related clinical metabolic parameters, including drug concentration in the blood, total cholesterol, triglyceride, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase and weight gain. (p < 0.05) CONCLUSIONS: Among those patients treated with VPA, characterization of the gut microbiota altered, and gut microbiota associated with weight gain and clinical biochemical indexes, suggesting that microbiome composition data might involve in the mechanisms of VPA induced metabolic disorder.

PMID:34883229 | DOI:10.1016/j.micpath.2021.105340

Resuscitation. 2021 Dec 6:S0300-9572(21)00505-0. doi: 10.1016/j.resuscitation.2021.11.039. Online ahead of print.

ABSTRACT

AIM: Mathematical optimization of automated external defibrillator (AED) placement has demonstrated potential to improve survival of out-of-hospital cardiac arrest (OHCA). Existing models mostly aim to improve accessibility based on coverage radius and do not account for detailed impact of delayed defibrillation on survival. We aimed to predict OHCA survival based on time to defibrillation and developed an AED placement model to directly maximize the expected survival rate.

METHODS: We stratified OHCAs occurring in Singapore (2010 to 2017) based on time to defibrillation and developed a regression model to predict the Utstein survival rate. We then developed a novel AED placement model, the maximum expected survival rate (MESR) model. We compared the performance of MESR with a maximum coverage model developed for Canada that was shown to be generalizable to other settings (Denmark). The survival gain of MESR was assessed through 10-fold cross-validation for placement of 20 to 1000 new AEDs in Singapore. Statistical analysis was performed using χ² and McNemar’s tests.

RESULTS: During the study period, 15,345 OHCAs occurred. The power-law approximation with R² of 91.33% performed best among investigated models. It predicted a survival of 54.9% with defibrillation within the first two minutes after collapse that was reduced by more than 60% without defibrillation within the first 4 minutes. MESR outperformed the maximum coverage model with P-value <0.05 (<0.0001 in 22 of 30 experiments).

CONCLUSION: We developed a novel AED placement model based on the impact of time to defibrillation on OHCA outcomes. Mathematical optimization can improve OHCA survival.

PMID:34883217 | DOI:10.1016/j.resuscitation.2021.11.039

J Ethnopharmacol. 2021 Dec 6:114892. doi: 10.1016/j.jep.2021.114892. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: In China, Traditional Chinese medicine (TCM) is often used as the main therapy for cancer-related fatigue (CRF). However, there is limited evidence to prove its therapeutic effect and mechanism.

AIM OF THE STUDY: We aimed to provide a basis for the therapeutic effect of TCM for CRF.

MATERIALS AND METHODS: We performed a meta-analysis to investigate the efficacy of TCM treatment for CRF. Through frequency statistics and association rule mining, we screened the core Chinese medicine components, Astragalus mongholicus Bunge., root (Radix astragali, Huangqi) and Atractylodes macrocephala Koidz., rhizome (Rhizoma atractylodis macrocephalae, Baizhu). We then used animal experiments to verify the effectiveness of these two TCMs and changes in related indicators in mice. Relevant molecular mechanisms were explored through network pharmacological analysis.

RESULTS: Twenty-four randomised control trials (RCTs) involving 1865 patients were included in the meta-analysis. TCM produced more positive effects on CRF than standard therapy alone. Radix astragali and Rhizoma atractylodis macrocephalae, as the core drug pair for the treatment of CRF, enhanced the physical fitness of mice; reduced abdominal circumference, level of inflammatory factors, and tumour weight; and increased body weight and blood sugar. Network pharmacology analysis showed that the mechanism of action of Radix astragali and Rhizoma atractylodis macrocephalae on CRF mainly involved compounds, such as quercetin, kaempferol and luteolin, acting through multiple targets, such as Protein kinase B α (AKT1), Tumour necrosis factor (TNF), and Interleukin-6 (IL-6). These molecules regulate cytokines, cancer signalling, and metabolic pathways and confer an anti-CRF effect.

CONCLUSIONS: TCM may be a promising therapy to relieve CRF in cancer patients. Our research may provide a reference for the clinical application of TCM for treating CRF.

PMID:34883219 | DOI:10.1016/j.jep.2021.114892

Diabetes Res Clin Pract. 2021 Sep 14:109049. doi: 10.1016/j.diabres.2021.109049. Online ahead of print.

ABSTRACT

OBJECTIVES: To estimate the prevalence of pre-existing diabetes in pregnancy from studies published during 2010-2020.

METHODS: We searched PubMed, CINAHL, Scopus and other sources for relevant data sources. The prevalence of overall pre-existing, type 1 and type 2 diabetes, by country, region and period of study was synthesised from included studies using inverse-variance heterogeneity models and the Freeman-Tukey transformation. Heterogeneity was assessed using the I² statistic and publication bias using funnel plots.

RESULTS: We identified 2479 records, of which 42 data sources, with a total of 78 943 376 women, met the eligibility criteria. The included studies were from 17 countries in North America, Europe, the Middle East and North Africa, Australasia, Asia and Africa. The lowest prevalence was in Europe (0.5%, 95%CI 0.4 – 0.7) and the highest in the Middle East and North Africa (2.4%, 95%CI 1.5-3.1). The prevalence of pre-existing diabetes doubled from 0.5% (95%CI 0.1-1.0) to 1.0% (95%CI 0.6-1.5) during the period 1990-2020. The pooled prevalences of pre-existing type 1 and type 2 diabetes were 0.3% (95%CI 0.2-0.4) and 0.2% (95%CI 0.0-0.9) respectively.

CONCLUSION: While the prevalence of pre-existing diabetes in pregnancy is low, it has doubled from 1990 to 2020.

PMID:34883190 | DOI:10.1016/j.diabres.2021.109049

Bioresour Technol. 2021 Dec 6:126493. doi: 10.1016/j.biortech.2021.126493. Online ahead of print.

ABSTRACT

Genotoxicity-based assessments of vermitechnology for textile-sludge valorization have rarely been attempted. Therefore, waste sanitization and epigenetic stress-regulation efficiency of Eisenia fetida and Eudrilus eugeniae were evaluated in silk (DSPS) and cotton (CPWS) processing sludge-based vermibeds. Vermicomposting resulted in greater C, N, and P recovery than composting. Earthworm population reduced by 6-50% in DSPS/CPWS, while it significantly increased in cow dung (CD) mixed DSPS/CPWS. The Cr, Cd, Pb, and Zn accumulation efficiency of earthworms was higher in DSPS-based feedstocks than CPWS. However, metal-rich sludge elevated oxidative stress, causing greater inhibition of cell viability and DNA damage in Eudrilus than in Eisenia. Although histo-architecture of chloragogenous tissues was perturbed, earthworms combatted metal-induced lipid peroxidation via the activation of catalase, superoxide-dismutase, and reduced-glutathione. Correlation statistics revealed that genetic integrity in earthworms was restored through DNA-methyltransferase activity, especially in DSPS/CPWS+CD vermibeds. Overall, Eisenia was a healthier choice than Eudrilus for sustainable valorization of textile-sludge.

PMID:34883193 | DOI:10.1016/j.biortech.2021.126493

JAMA Neurol. 2021 Dec 1;78(12):1484-1493. doi: 10.1001/jamaneurol.2021.3723.

ABSTRACT

IMPORTANCE: Compared with normothermia, hypothermia has been shown to reduce death or disability in neonatal hypoxic ischemic encephalopathy but data on seizures during rewarming and associated outcomes are scarce.

OBJECTIVE: To determine whether electrographic seizures are more likely to occur during rewarming compared with the preceding period and whether they are associated with abnormal outcomes in asphyxiated neonates receiving hypothermia therapy.

DESIGN, SETTING, AND PARTICIPANTS: This prespecified nested cohort study of infants enrolled in the Optimizing Cooling (OC) multicenter Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network trial from December 2011 to December 2013 with 2 years’ follow-up randomized infants to either 72 hours of cooling (group A) or 120 hours (group B). The main trial included 364 infants. Of these, 194 were screened, 10 declined consent, and 120 met all predefined inclusion criteria. A total of 112 (90%) had complete data for death or disability. Data were analyzed from January 2018 to January 2020.

INTERVENTIONS: Serial amplitude electroencephalography recordings were compared in the 12 hours prior and 12 hours during rewarming for evidence of electrographic seizure activity by 2 central amplitude-integrated electroencephalography readers blinded to treatment arm and rewarming epoch. Odds ratios and 95% CIs were evaluated following adjustment for center, prior seizures, depth of cooling, and encephalopathy severity.

MAIN OUTCOMES AND MEASURES: The primary outcome was the occurrence of electrographic seizures during rewarming initiated at 72 or 120 hours compared with the preceding 12-hour epoch. Secondary outcomes included death or moderate or severe disability at age 18 to 22 months. The hypothesis was that seizures during rewarming were associated with higher odds of abnormal neurodevelopmental outcomes.

RESULTS: A total of 120 newborns (70 male [58%]) were enrolled (66 in group A and 54 in group B). The mean (SD) gestational age was 39 (1) weeks. There was excellent interrater agreement (κ, 0.99) in detection of seizures. More infants had electrographic seizures during the rewarming epoch compared with the preceding epoch (group A, 27% vs 14%; P = .001; group B, 21% vs 10%; P = .03). Adjusted odd ratios (95% CIs) for seizure frequency during rewarming were 2.7 (1.0-7.5) for group A and 3.2 (0.9-11.6) for group B. The composite death or moderate to severe disability outcome at 2 years was significantly higher in infants with electrographic seizures during rewarming (relative risk [95% CI], 1.7 [1.25-2.37]) after adjusting for baseline clinical encephalopathy and seizures as well as center.

CONCLUSIONS AND RELEVANCE: Findings that higher odds of electrographic seizures during rewarming are associated with death or disability at 2 years highlight the necessity of electroencephalography monitoring during rewarming in infants at risk.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01192776.

PMID:34882200 | DOI:10.1001/jamaneurol.2021.3723

Brief Bioinform. 2021 Dec 9:bbab497. doi: 10.1093/bib/bbab497. Online ahead of print.

ABSTRACT

Multiple statistical methods for aggregate association testing have been developed for whole-genome sequencing (WGS) data. Many aggregate variants in a given genomic window and ignore existing knowledge to define test regions, resulting in many identified regions not clearly linked to genes, and thus, limiting biological understanding. Functional information from new technologies (such as Hi-C and its derivatives), which can help link enhancers to their effector genes, can be leveraged to predefine variant sets for aggregate testing in WGS data. Here, we propose the eSCAN (scan the enhancers) method for genome-wide assessment of enhancer regions in sequencing studies, combining the advantages of dynamic window selection in SCANG (SCAN the Genome), a previously developed method, with the advantages of incorporating putative regulatory regions from annotation. eSCAN, by searching in putative enhancers, increases statistical power and aids mechanistic interpretation, as demonstrated by extensive simulation studies. We also apply eSCAN for blood cell traits using NHLBI Trans-Omics for Precision Medicine WGS data. Results from real data analysis show that eSCAN is able to capture more significant signals, and these signals are of shorter length (indicating higher resolution fine-mapping capability) and drive association of larger regions detected by other methods.

PMID:34882196 | DOI:10.1093/bib/bbab497

JAMA Netw Open. 2021 Dec 1;4(12):e2136809. doi: 10.1001/jamanetworkopen.2021.36809.

ABSTRACT

IMPORTANCE: Patients with large annular defects following lumbar microdiscectomy for disc herniation are at increased risk for symptomatic recurrence and reoperation.

OBJECTIVE: To determine whether a bone-anchored annular closure device in addition to lumbar microdiscectomy resulted in lower reherniation and reoperation rates vs lumbar microdiscectomy alone.

DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a multicenter randomized clinical trial reports 5-year follow-up for enrolled patients between December 2010 and October 2014 at 21 clinical sites. Patients in this study had a large annular defect (6-10 mm width) following lumbar microdiscectomy for treatment of lumbar disc herniation. Statistical analysis was performed from November to December 2020.

INTERVENTIONS: Lumbar microdiscectomy with additional bone-anchored annular closure device (device group) or lumbar microdiscectomy only (control group).

MAIN OUTCOMES AND MEASURES: The incidence of symptomatic reherniation, reoperation, and adverse events as well as changes in leg pain, Oswestry Disability Index, and health-related quality of life when comparing the device and control groups over 5 years of follow-up.

RESULTS: Among 554 randomized participants (mean [SD] age: 43 [11] years; 327 [59%] were men), 550 were included in the modified intent-to-treat efficacy population (device group: n = 272; 270 [99%] were White); control group: n = 278; 273 [98%] were White) and 550 were included in the as-treated safety population (device group: n = 267; control group: n = 283). The risk of symptomatic reherniation (18.8% [SE, 2.5%] vs 31.6% [SE, 2.9%]; P < .001) and reoperation (16.0% [SE, 2.3%] vs 22.6% [SE, 2.6%]; P = .03) was lower in the device group. There were 53 reoperations in 40 patients in the device group and 82 reoperations in 58 patients in the control group. Scores for leg pain severity, Oswestry Disability Index, and health-related quality of life significantly improved over 5 years of follow-up with no clinically relevant differences between groups. The frequency of serious adverse events was comparable between the treatment groups. Serious adverse events associated with the device or procedure were less frequent in the device group (12.0% vs 20.5%; difference, -8.5%; 95% CI, -14.6% to -2.3%; P = .008).

CONCLUSIONS AND RELEVANCE: In patients who are at high risk of recurrent herniation following lumbar microdiscectomy owing to a large defect in the annulus fibrosus, this study’s findings suggest that annular closure with a bone-anchored implant lowers the risk of symptomatic recurrence and reoperation over 5 years of follow-up.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01283438.

PMID:34882183 | DOI:10.1001/jamanetworkopen.2021.36809

Angle Orthod. 2021 Dec 9. doi: 10.2319/022521-156.1. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the effect of fixed orthodontic treatment on periodontal parameters in periodontally compromised adult orthodontic patients.

MATERIALS AND METHODS: This was a prospective, randomized, controlled clinical trial. Thirty-six periodontally compromised adult patients (mean age: 29.67 ± 4.8 years) were randomly allocated to either test (perio-ortho) or control group (perio). After periodontal stabilization in both groups, orthodontic treatment was started in the test group, whereas the control group remained on periodontal maintenance only. Evaluation and comparison of clinical parameters (plaque index [PI]; gingival index [GI]; bleeding on probing [BOP]; probing depth [PD]; clinical attachment level [CAL]) of both groups was assessed at three time intervals: T0 (base line), T1 (at start of orthodontic treatment), and T2 (1 year after start of orthodontic treatment). Radiological parameters (alveolar bone levels [ABL]) were recorded using CBCT at T1 and T2.

RESULTS: Intragroup analysis showed statistically significant improvement in all clinical and radiological periodontal parameters in both groups (P ≤ .05). Intergroup comparison revealed improvement in the periodontal parameters was not statistically significant between the groups (P ≥ .05). Subgroup analysis showed reduction in the number of moderate and severe periodontitis sites in both groups with significant more gains in ABL in the test group compared to the control group.

CONCLUSIONS: Orthodontic treatment after periodontal stabilization does not have any detrimental effect on periodontal health in adult periodontally compromised orthodontic patients and may add to the benefits achieved by periodontal treatment alone.

PMID:34882193 | DOI:10.2319/022521-156.1

JAMA Netw Open. 2021 Dec 1;4(12):e2138219. doi: 10.1001/jamanetworkopen.2021.38219.

ABSTRACT

IMPORTANCE: In March 2018, Medicare issued a national coverage determination (NCD) for next-generation sequencing (NGS) to facilitate access to NGS testing among Medicare beneficiaries. It is unknown whether the NCD affected health equity issues for Medicare beneficiaries and the overall population.

OBJECTIVE: To examine the association between the Medicare NCD and NGS use by insurance types and race and ethnicity.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort analysis was conducted using electronic health record data derived from a real-world database. Data originated from approximately 280 cancer clinics (approximately 800 sites of care) in the US. Patients with advanced non-small cell lung cancer (aNSCLC), metastatic colorectal cancer (mCRC), metastatic breast cancer (mBC), or advanced melanoma diagnosed from January 1, 2011, through March 31, 2020, were included.

EXPOSURE: Pre- vs post-NCD period.

MAIN OUTCOMES AND MEASURES: Patients were classified by insurance type and race and ethnicity to examine patterns in NGS testing less than or equal to 60 days after diagnosis. Difference-in-differences models examined changes in average NGS testing in the pre- and post-NCD periods by race and ethnicity, and interrupted time-series analysis examined whether trends over time varied by insurance type and race and ethnicity.

RESULTS: Among 92 687 patients with aNSCLC, mCRC, mBC, or advanced melanoma, mean (SD) age was 66.6 (11.2) years, 51 582 (55.7%) were women, and 63 864 (68.9%) were Medicare beneficiaries. The largest racial and ethnic categories according to the database used and further classification were Black or African American (8605 [9.3%]) and non-Hispanic White (59 806 [64.5%]). Compared with Medicare beneficiaries, changes in pre- to post-NCD NGS testing trends were similar in commercially insured patients (odds ratio [OR], 1.03; 95% CI, 0.98-1.08; P = .25). Pre- to post-NCD NGS testing trends increased at a slower rate among patients in assistance programs (OR, 0.93; 95% CI, 0.87-0.99; P = .03) compared with Medicare beneficiaries. The rate of increase for patients receiving Medicaid was not statistically significantly different compared with those receiving Medicare (OR, 0.92; 95% CI, 0.84-1.01; P = .07). The NCD was not associated with statistically significant changes in NGS use trends by racial and ethnic groups within Medicare beneficiaries alone or across all insurance types. Compared with non-Hispanic White individuals, increases in average NGS use from the pre-NCD to post-NCD period were 14% lower (OR, 0.86; 95% CI, 0.74-0.99; P = .04) among African American and 23% lower (OR, 0.77; 95% CI, 0.62-0.96; P = .02) among Hispanic/Latino individuals; increases among Asian individuals and those with other races and ethnicities were similar.

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that expansion of Medicare-covered benefits may not occur equally across insurance types, thereby further widening or maintaining disparities in NGS testing. Additional efforts beyond coverage policies are needed to ensure equitable access to the benefits of precision medicine.

PMID:34882180 | DOI:10.1001/jamanetworkopen.2021.38219