Category: Nevin Manimala

Horm Res Paediatr. 2021 Jul 8:1-7. doi: 10.1159/000517341. Online ahead of print.

ABSTRACT

OBJECTIVE: No data are available on advanced glycation end products (AGEs) and their soluble receptor (sRAGE) in pediatric patients with Hashimoto’s thyroiditis (HT). The present study was aimed to simultaneously evaluate serum levels of sRAGE, AGEs, and advanced oxidation protein products (AOPPs) and investigate the relationships between these oxidative stress markers and clinical and biochemical parameters of thyroid function in euthyroid children with HT.

DESIGN: This is a case-control study carried out in a single university hospital center.

METHODS: We enrolled 19 newly diagnosed euthyroid HT pediatric patients (3 M, 16 F; median age 12.44 years, range 6.54-15.81 years) and 16 age-, sex-, and BMI-matched healthy controls (5 M, 11 F; median age 12.83 years, range 5.68-15.07 years). None was on levothyroxine treatment. The exclusion criteria were autoimmune, inflammatory, and infection comorbidities. Patients did not differ significantly from controls with regard to lipid or for anthropometric parameters.

RESULTS: sRAGE levels were significantly lower in HT patients (median 414.30 pg/mL, range 307.30-850.30 pg/mL) than in controls (561.30, 273.20-1121.60 pg/mL; p = 0.034). No differences emerged between patients and controls with regard to serum AGEs (124.25 AU/g prot, 71.98-186.72 vs. 133.90, 94.06-200.78 AU/g prot, p = 0.707) and AOPPs (1.13 nmol/mL, 0.62-1.83 vs. 1.17, 0.76-1.42 nmol/mL, p = 0.545).

CONCLUSIONS: sRAGE levels were decreased in euthyroid children/adolescents at the onset of HT, suggesting that autoimmunity per se seems to play an important role in such a reduction of sRAGE, irrespective of any functional alteration. Children and adolescents suffering from HT may exhibit increased susceptibility to oxidative damage, even when in euthyroid status.

PMID:34237741 | DOI:10.1159/000517341

Obstet Gynecol. 2021 Jul 8. doi: 10.1097/AOG.0000000000004444. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate characteristics associated with treatment failure 1 year after midurethral sling in women with mixed urinary incontinence.

METHODS: Four-hundred three women who participated in a randomized trial that compared midurethral sling and behavioral and pelvic floor muscle therapy (combined group) compared with midurethral sling alone for mixed incontinence with 1-year follow-up data were eligible for this planned secondary analysis. Overall treatment failure was defined as meeting criteria for subjective or objective failure or both. Subjective failure was defined as not meeting the minimal clinical important difference for improvement on the UDI (Urogenital Distress Inventory) total score (26.1 points). Objective failure was defined as not achieving 70% improvement on mean incontinence episodes of any type per day or having undergone any additional treatment for persistent urinary symptoms at 12 months postoperative. Logistic regression models for treatment failure were constructed. Independent variables included site and treatment group, and clinical and demographic variables based on bivariate comparisons (P<.2). Treatment group interaction effects were evaluated.

RESULTS: One hundred twelve of 379 (29.6%) women had overall treatment failure, with 56 of 379 (14.7%) undergoing additional treatment but only two needing intervention for stress incontinence. Previous overactive bladder (OAB) medication (unadjusted odds ratio [OR] 2.19, adjusted odds ratio [aOR] 1.96, 95% CI 1.17-3.31); detrusor overactivity on cystometrogram (OR 2.25, aOR 2.82, 95% CI 1.60-4.97); and higher volume at first urge (OR 1.03, aOR 1.04, 95% CI 1.01-1.07) were associated with overall failure. Worse UDI-urgency scores were associated with failure, with an added interaction effect in the midurethral sling-alone group.

CONCLUSIONS: Certain clinical and urodynamic variables are associated with treatment failure after midurethral sling in women with mixed urinary incontinence. Women with more severe urgency symptoms at baseline may benefit from perioperative behavioral and pelvic floor muscle therapy combined with midurethral sling. Overall, the need for additional urinary treatment was low and primarily for OAB.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01959347.

PMID:34237755 | DOI:10.1097/AOG.0000000000004444

Aging (Albany NY). 2021 Jul 8;13(undefined). doi: 10.18632/aging.203249. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the two most common pathology subtypes of primary liver cancer (PLC). Identifying DNA methylation biomarkers for diagnosis of PLC and further distinguishing HCC from ICC plays a vital role in subsequent treatment options selection. To obtain potential diagnostic DNA methylation sites for PLC, differentially methylated CpG (DMC) sites were first screened by comparing the methylation data between normal liver samples and PLC samples (ICC samples and HCC samples). A random forest algorithm was then used to select specific DMC sites with top Gini value. To avoid overfitting, another cohort was taken as an external validation for evaluating the area under curves (AUCs) of different DMC sites combination. A similar model construction strategy was applied to distinguish HCC from ICC. In addition, we identified DNA Methylation-Driven Genes in HCC and ICC via MethylMix method and performed pathway analysis by utilizing MetaCore. Finally, we not only performed methylator phenotype based on independent prognostic sites but also analyzed the correlations between methylator phenotype and clinical factors in HCC and ICC, respectively. To diagnose PLC, we developed a model based on three PLC-specific methylation sites (cg24035245, cg21072795, and cg00261162), whose sensitivity and specificity achieved 98.8%,94.8% in training set and 97.3%,81% in validation set. Then, to further divide the PLC samples into HCC and ICC, we established another mode through three methylation sites (cg17769836, cg17591574, and cg07823562), HCC accuracy and ICC accuracy achieved 95.8%, 89.8% in the training set and 96.8%,85.4% in the validation set. In HCC, the enrichment pathways were mainly related to protein folding, oxidative stress, and glutathione metabolism. While in ICC, immune response, embryonic hepatocyte maturation were the top pathways. Both in HCC and ICC, methylator phenotype correlated well with overall survival time and clinical factors involved in tumor progression. In summary, our study provides the biomarkers based on methylation sites not only for the diagnosis of PLC but also for distinguishing HCC from ICC.

PMID:34237708 | DOI:10.18632/aging.203249

J Neural Eng. 2021 Jul 8. doi: 10.1088/1741-2552/ac127f. Online ahead of print.

ABSTRACT

OBJECTIVE: Asynchronous brain-computer interfaces (BCIs) show significant advantages in many practical application scenarios. Compared with the rapid development of synchronous BCIs technology, the progress of asynchronous BCI research, in terms of containing multiple targets and training-free detection, is still relatively slow. In order to improve the practicability of the brain-computer interface, a spatio-temporal equalization multi-window algorithm (STE-MW) was proposed for asynchronous detection of steady-state visual evoked potential (SSVEP) without the need for acquiring calibration data.

APPROACH: The algorithm used spatio-temporal equalization strategy to intercept EEG signals of different lengths through multiple stacked time windows and statistical decisions-making based on Bayesian risk decision-making. Different from the traditional asynchronous algorithms based on the “non-control state detection” methods, this algorithm was based on the “statistical inspection-rejection decision” mode and did not require a separate classification of non-control states, so it can be effectively applied to detections for large-scale candidates.

MAIN RESULTS: Online experimental results involving fourteen healthy subjects showed that, in the continuously input experiments of 40 targets, the algorithm achieved the average recognition accuracy of 97.2%±2.6% and the average information transfer rate of 106.3±32.0 bits/min. At the same time, the average false alarm rate in the 240-seconds resting state test was 0.607±0.602 min^(-1). In the free spelling experiments involving patients with severe amyotrophic lateral sclerosis, the subjects achieved an accuracy of 92.7% and an average information transfer rate of 43.65 bits/min in two free spelling experiments.

SIGNIFICANCE: This algorithm can achieve high-performance, high-precision, and asynchronous detection of SSVEP signals with low algorithm complexity and false alarm rate under multi-targets and training-free conditions, which is helpful for the development of asynchronous BCI systems.

PMID:34237711 | DOI:10.1088/1741-2552/ac127f

Phys Med Biol. 2021 Jul 8. doi: 10.1088/1361-6560/ac127d. Online ahead of print.

ABSTRACT

We try to develop an atlas-guided automatic planning (AGAP) approach and evaluate its feasibility and performance in rectal cancer intensity-modulated radiotherapy. The developed AGAP approach consisted of four independent modules: patient atlas, similar patient retrieval, beam morphing, and plan fine-tuning modules. The atlas was setup using anatomy and plan data from Pinnacle auto-planning (P-auto) plans. Given a new patient, the retrieval function searched the top similar patient by a generic Fourier descriptor algorithm and retrieved its plan information. The beam morphing function generated an initial plan for the new patient by morphing the beam aperture from the top similar patient plan. The beam aperture and calculated dose of the initial plan were used to guide the new plan optimization in the plan fine-tuning function. The AGAP approach was tested on 96 patients by the leave-one-out validation and plan quality was compared with the P-auto plans. The AGAP and P-auto plans had no statistical difference for target coverage and dose homogeneity in terms of V100%(p=0.76) and homogeneity index (HI)(p=0.073), respectively. The CI index showed they had a statistically significant difference. but the ΔCI was both 0.02 compared to the perfect CI index of 1. The AGAP approach reduced the bladder mean dose by 152.1cGy (p<0.05) and V50 by 0.9% (p<0.05), and slightly increased the left and right femoral head mean dose by 70.1cGy (p<0.05) and 69.7cGy (p<0.05), respectively. This work developed an efficient and automatic approach that could fully automate the IMRT planning process in rectal cancer radiotherapy. It reduced the plan quality dependence on the planner experience and maintained the comparable plan quality with P-auto plans.

PMID:34237715 | DOI:10.1088/1361-6560/ac127d

Eur Neuropsychopharmacol. 2021 Jul 5;52:18-30. doi: 10.1016/j.euroneuro.2021.06.003. Online ahead of print.

ABSTRACT

Sodium oxybate (SMO) has been approved in Italy and Austria for the maintenance of abstinence in alcohol dependent (AD) patients. Although SMO is well tolerated in AD patients, cases of abuse and misuse have been reported outside the therapeutic setting. Here we report on a phase IIb double-blind, randomized, placebo-controlled trial for the maintenance of abstinence in AD patients with a new abuse and misuse deterrent formulation of SMO. A total of 509 AD patients were randomized to 12 weeks of placebo or one of four SMO doses (0.75, 1.25, 1.75 or 2.25 g t.i.d.) followed by a one-week medication-free period. The primary endpoint was the percentage of days abstinent (PDA) at end of treatment. An unexpectedly high placebo response (mean 73%, median 92%) was observed. This probably compromised the demonstration of efficacy in the PDA, but several secondary endpoints showed statistically significant improvements. A post-hoc subgroup analysis based on baseline severity showed no improvements in the mild group, but statistically significant improvements in the severe group: PDA: mean difference +15%, Cohen’s d = 0.42; abstinence: risk difference +18%, risk ratio = 2.22. No safety concerns were reported. Although the primary endpoint was not significant in the overall population, several secondary endpoints were significant in the intent-to-treat population and post-hoc results showed that treatment with SMO was associated with a significant improvement in severe AD patients which is consistent with previous findings. New trials are warranted that take baseline severity into consideration.

PMID:34237655 | DOI:10.1016/j.euroneuro.2021.06.003

Clin Nutr. 2021 Jun 5;40(7):4644-4652. doi: 10.1016/j.clnu.2021.05.026. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the linear and nonlinear dose-response associations of animal-based dietary protein intake and risk of developing rheumatoid arthritis (RA).

METHODS: A systematic search of MEDLINE, Scopus and Embase was conducted up to October 2020. Observational studies that report risk estimates of RA for animal-based protein consumption were included. We calculated pooled relative risks (RRs) by using a random-effects model. Linear and non-linear dose-response analyses were performed to examine the dose-response relations between animal-based protein consumption and RA.

RESULTS: Seven cohort studies (n = 457,554) with 3545 incident cases and six case-control studies with 3994 cases and 5252 controls were identified. Highest compared with the lowest category of fish consumption was inversely associated with risk of RA (RR: 0.89; 95% CI, 0.80 to 0.99; I² = 0%, n = 10). Also, a 100 g/day increment in fish intake was associated with a 15% decreased risk of RA. Dose-response analysis showed a modest U-shaped association between fish consumption and incidence of RA, with the lowest risk at a fish intake of 20-30 g/day (P_{non-linearity} = 0.04). We found no significant association between consumption of red meat, poultry or dairy and the risk of RA.

CONCLUSION: The present study revealed a significant reverse association between fish consumption and risk of RA. While we observed no association between red meat, dairy or poultry consumption and risk of RA. Further well-designed prospective studies are needed to support our findings.

PMID:34237693 | DOI:10.1016/j.clnu.2021.05.026

Drug Alcohol Depend. 2021 Jun 30;226:108868. doi: 10.1016/j.drugalcdep.2021.108868. Online ahead of print.

ABSTRACT

BACKGROUND: The American Society of Addiction Medicine (ASAM) criteria were developed to provide a systematic, evidence-based, and transparent approach to addiction treatment assessment and level-of-care recommendations. In 2017, California began a Medicaid demonstration that required that providers in participating counties to adopt ASAM-based intake assessments and level-of-care criteria. We hypothesized that ASAM implementation would increase the proportion of patients retained in addiction treatment and successfully completing their treatment plan.

METHODS: We implemented a comparative interrupted time series analysis with 407,792 treatment episodes by Medicaid beneficiaries in specialty addiction treatment settings from 2015 to mid-2019. We compared the change in retention rates and successful completion rates in counties that adopted ASAM-based assessments relative to counties that did not adopt ASAM-based assessments and used only clinical judgment for level-of-care decisions. Treatment retention was defined as staying in addiction treatment for at least 30 days. Successful completion of the treatment plan was determined by the patient’s clinician.

RESULTS: After one year, ASAM implementation was associated with a 9% increase in 30-day retention among treatment episodes that started in a residential setting, but no change in retention among episodes starting in outpatient settings. We found no statistically significant association between ASAM adoption and successful treatment completion.

CONCLUSIONS: Implementation of ASAM-based assessment may lead to improved retention for individuals who begin treatment in residential treatment, which may be encouraging to the many state Medicaid programs that are adopting ASAM-based criteria. More research is needed to clarify the mechanism by which ASAM leads to improved outcomes and to clarify how to maximize the potential benefits of ASAM, such as through patient-centered implementation.

PMID:34237614 | DOI:10.1016/j.drugalcdep.2021.108868

J Surg Res. 2021 Jul 5;267:443-451. doi: 10.1016/j.jss.2021.06.001. Online ahead of print.

ABSTRACT

BACKGROUND: Previous studies have suggested that large preoperative AAA size may impact late survival after elective EVAR. It is unclear, however, whether this association applies to patients with smaller AAA between 5.0-5.5 cm, who constitute a substantial portion of patients undergoing elective EVAR. The purpose of this study was to delineate the effect of AAA size between 5.0 and 5.5 cm on mid-term mortality after EVAR by analyzing a large national cohort, the Vascular Quality Initiative (VQI) database.

METHODS: Using the Vascular Quality Initiative (VQI) national database, patients who underwent EVAR for intact AAA between 2003 and 2018 were identified and stratified based on maximal AAA diameter into 3 groups: Group 1 (4.0 cm ≤ AAA <5.0 cm); Group 2 (5.0 cm ≤ AAA < 5.5 cm); and Group 3 (AAA ≥ 5.5 cm). Cox proportional hazard model and propensity score matching method were used to estimate AAA size effect on all-cause mortality at 1, 3, and 5 years after EVAR while adjusting for potential confounders.

RESULTS: The study included 32,398 patients, of whom 81% were men with a mean age of 74. The most common group who underwent EVAR was Group 2 (5.0 cm ≤ AAA < 5.5 cm). Larger AAA size was associated with male sex (75% versus 79% versus 84%, for Groups 1, 2, and 3 respectively; P < 0.0001) and with coronary artery disease (27% versus 29% versus 31%, for Groups 1, 2, and 3 respectively, P< 0.0001); but was negatively associated with active smoking (33% versus 31% versus 30%, for Groups 1, 2, and 3, respectively, P< 0.001). While 10% of the largest and smallest AAA groups (Groups 3 and 1, respectively) were symptomatic, only 5% of patients in Group 2 were symptomatic (P < 0.01). Adjusted Cox proportional hazard modeling revealed that patients in Group 2 were at significantly lower risk of 5-year mortality when compared to patients in Group 3 (HR 0.66, 95% CI 0.61-0.72, P< 0.01), while similar in risk when compared to patients in Group 1 (HR 1.11, 95% CI 0.93-1.32, P= 0.26).

CONCLUSION: Our analysis found that over 40% of EVAR in the national VQI cohort were performed for AAA < 5.5 cm, with the greatest number of patients undergoing EVAR at AAA size 5.0-5.5cm. Patients with AAA size 5.0-5.5 cm had better 5-year survival outcomes than patients with AAA ≥ 5.5 cm, and similar survival to patients with small AAA between 4.0-5.0 cm.

PMID:34237629 | DOI:10.1016/j.jss.2021.06.001

Environ Pollut. 2021 Jul 3;288:117683. doi: 10.1016/j.envpol.2021.117683. Online ahead of print.

ABSTRACT

Reservoirs are an important type of drinking water source for megacities, while lots of reservoirs are threatened by odor problems during certain seasons. The influencing factors of odor compounds in reservoirs are still unclear. During August 2019, a nationwide survey investigating the distribution of odor compounds in reservoirs used as drinking water sources was conducted on seven reservoirs. 2-methylisoborneol (2-MIB) and geosmin were detected in almost every reservoir, and some odor compound concentrations even exceeded the odor threshold concentration. The average concentration of 2-MIB was 2.68 ng/L, and geosmin was 3.63 ng/L. The average chlorophyll a concentration was 8.25 μg/L. The dominant genera of phytoplankton in these reservoirs belonged to cyanobacteria and diatom. Statistical analysis showed that odor compound concentration was significantly related to the chlorophyll a concentration and indicated that the odor compounds mainly came from phytoplankton. The concentration of odor compounds in the euphotic zone was significantly related to phytoplankton species and biomass. Therefore, the odor compound concentrations in the subsurface chlorophyll maxima layer was generally higher than in the surface layer. However, the odor compounds in the hypolimnion layer were related to the density current. This research suggests that both phytoplankton proliferation events and heavy storm events are important risk factors increasing odor compounds in reservoirs. Control of algal bloom, in-situ profile monitoring system and depth-adjustable pumping system will greatly reduce the risk of odor problems in reservoirs using as water supplies for large cities.

PMID:34237652 | DOI:10.1016/j.envpol.2021.117683