Tag: nevin manimala

Brain Stimul. 2022 Jan 26:S1935-861X(22)00019-5. doi: 10.1016/j.brs.2022.01.014. Online ahead of print.

ABSTRACT

Noninvasive brain stimulation using transcranial focused ultrasound (FUS) has many potential applications as a research and clinical tool, including incorporation into neural prosthetics for cognitive rehabilitation. To develop this technology, it is necessary to evaluate the safety and efficacy of FUS neuromodulation for specific brain targets and cognitive functions. It is also important to test whether repeated long-term application of FUS to deep brain targets improves or degrades behavioral and cognitive function. To this end, we investigated the effects of FUS in the dorsal striatum of nonhuman primates (NHP) performing a visual-motor decision-making task for small or large rewards. Over the course of 2 years, we performed 129 and 147 FUS applications, respectively, in two NHP. FUS (0.5 MHz @ 0.2-0.8 MPa) was applied to the putamen and caudate in both hemispheres to evaluate the effects on movement accuracy, motivation, decision accuracy, and response time. Sonicating the caudate or the putamen unilaterally resulted in modest but statistically significant improvements in motivation and decision accuracy, but at the cost of slower reaction times. The effects were dose (i.e., FUS pressure) and reward dependent. There was no effect on reaching accuracy, nor was there long-term behavioral impairment or neurological trauma evident on T1-weighted, T2-weighted, or susceptibility-weighted MRI scans. Sonication also resulted in significant changes in resting state functional connectivity between the caudate and multiple cortical regions. The results indicate that applying FUS to the dorsal striatum can positively impact the motivational and cognitive aspects of decision making. The capability of FUS to improve motivation and cognition in NHPs points to its therapeutic potential in treating a wide variety of human neural diseases, and warrants further development as a novel technique for non-invasive deep brain stimulation.

PMID:35092823 | DOI:10.1016/j.brs.2022.01.014

J Glob Antimicrob Resist. 2022 Jan 26:S2213-7165(22)00022-4. doi: 10.1016/j.jgar.2022.01.018. Online ahead of print.

ABSTRACT

OBJECTIVES: Aim of this study was to evaluate the impact of resistance mutations on efficacy of dolutegravir-based 2-drug regimens (2DR).

METHODS: Virologically suppressed HIV-1 infected patients switching to dolutegravir+lamivudine or +rilpivirine, or to a dolutegravir-based 3-drug regimen (3DR), with pre-baseline genotype were selected. Virological failure (VF) was defined as one HIV-RNA (viral load, VL) >200 cps/mL or two consecutive VL >50 cps/mL; treatment failure (TF) was defined as VF or treatment discontinuation (TD). Resistance was defined as at least low-level resistance (LLR) to at least one drug of the current regimen. Propensity score matching was used to conduct adjusted analyses within a competing risks framework.

RESULTS: A total of 971 dolutegravir-based regimens were selected: 339 (34.9%) 2DR and 632 (65.1%) 3DR. The adjusted cumulative 48-weeks incidence of VF was 4.2% (90% CI 3.1-5.3%) with 2DR and 4.7% (90% CI 3.5-5.8%) with 3DR. The cumulative 48-weeks incidence of TF was 15.8% (90% CI 13.9-17.9%) with 2DR and 24.5% (90% CI 22.2-27.0%) with 3DR. For VF, the estimated hazard ratio (HR) for 2DR vs 3DR was 1.02 (90% CI: 0.78, 1.34), with evidence of effect modification by LLR (HR 3.96, 90% CI: 2.10, 7.46). The estimated HR of TF for 2DR vs 3DR was 0.54 (90% CI: 0.48, 0.60). The 48-weeks cumulative incidence of TD was 11.7% (8.7%, 14.6%) in 2DR and 19.6% (16.9%, 22.4%) in 3DR.

CONCLUSIONS: Dolutegravir-based 2DR showed high virological efficacy and durability, however past resistance increased the risk of VF, but not of TD or TF.

PMID:35092828 | DOI:10.1016/j.jgar.2022.01.018

Genomics. 2022 Jan 26:110273. doi: 10.1016/j.ygeno.2022.110273. Online ahead of print.

ABSTRACT

Cucumber fruits are perishable in nature and become unfit for market within 2-3 days of harvesting. A natural variant, DC-48 with exceptionally high shelf life was developed and used to dissect the genetic architecture and molecular mechanism for extended shelf life through RNA-seq for first time. A total of 1364 DEGs were identified and cell wall degradation, chlorophyll and ethylene metabolism related genes played key role. Polygalacturunase (PG), Expansin (EXP) and xyloglucan were down regulated determining fruit firmness and retention of fresh green colour was mainly attributed to the low expression level of the chlorophyll catalytic enzymes (CCEs). Gene regulatory networks revealed the hub genes and cross-talk associated with wide variety of the biological processes. Large number of SSRs (21524), SNPs (545173) and InDels (126252) identified will be instrumental in cucumber improvement. A web genomic resource, CsExSLDb developed will provide a platform for future investigation on cucumber post-harvest biology.

PMID:35092817 | DOI:10.1016/j.ygeno.2022.110273

J Clin Lab Anal. 2022 Jan 29:e24257. doi: 10.1002/jcla.24257. Online ahead of print.

ABSTRACT

BACKGROUND: It is known that inflammatory responses play an important role in the pathophysiology of COVID-19.

AIMS: In this study, we aimed to examine the role of kynurenine (KYN) metabolism on the severity of COVID-19 disease AQ5.

MATERIALS & METHODS: Seventy COVID-19 patients of varying severity and 30 controls were included in the study. In addition to the classical laboratory parameters, KYN, tryptophan (TRP), kynurenic acid (KYNA), 3 hydroxykynurenine (3OHKYN), quinolinic acid (QA), and picolinic acid (PA) were measured with mass spectrometry.

RESULTS: TRP, KYN, KYN:TRP ratio, KYNA, 3OHKYN, PA, and QA results were found to be significantly different in COVID-19 patients (p < 0.001 for all). The KYN:TRP ratio and PA of severe COVID-19 patients was statistically higher than that of mild-moderate COVID-19 patients (p < 0.001 for all). When results were examined, statistically significant correlations with KYN:TRP ratio, IL-6, ferritin, and procalcitonin were only found in COVID-19 patients. ROC analysis indicated that highest AUC values were obtained by KYN:TRP ratio and PA (0.751 vs 0.742). In determining the severity of COVID-19 disease, the odd ratios (and confidence intervals) of KYN:TRP ratio and PA levels that were adjusted according to age, gender, and comorbidity were determined to be 1.44 (1.1-1.87, p = 0.008) and 1.06 (1.02-1.11, p = 0.006), respectively.

DISCUSSION & CONCLUSION: According to the results of this study, KYN metabolites play a role in the pathophysiology of COVID-19, especially KYN:TRP ratio and PA could be markers for identification of severe COVID-19 cases.

PMID:35092710 | DOI:10.1002/jcla.24257

Chest. 2022 Jan 26:S0012-3692(22)00192-1. doi: 10.1016/j.chest.2022.01.031. Online ahead of print.

ABSTRACT

BACKGROUND: Severe pulmonary hypertension (PH) is prognostically highly relevant in patients with COPD. The criteria for severe PH have been defined based on hemodynamic thresholds in right heart catheterization.

RESEARCH QUESTION: Can non-invasive clinical tools predict severe PH in COPD patients? How does the mortality risk change with increasing severity of airflow-limitation and pulmonary vascular disease?

STUDY DESIGN AND METHODS: We retrospectively analyzed all consecutive COPD patients with suspected PH undergoing in-depth clinical evaluation including right heart catheterization in our PH clinic between 2005 and 2018. Clinical variables potentially indicative of severe PH or death were analyzed using uni- and stepwise multivariable logistic regression and Cox regression analysis adjusted for age and sex.

RESULTS: We included 142 patients (FEV₁: median: 55.0 IQR: 42.4-69.4%, mean pulmonary arterial pressure (mPAP): 35 mmHg (IQR: 27-43). A multivariable model combining echocardiographic systolic PAP ≥ 56 mmHg, N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels ≥ 650 pg/ml and main pulmonary artery / ascending aorta diameter ratio (PA/Ao-ratio) in chest CT ≥ 0.93 predicted severe PH with high positive and negative predictive values (both 94%). After correction for age and gender, both airflow-limitation (p=0.002; GOLD 1-2 vs. 3: HR 1.56 [95%CI: 0.90 – 2.71]; GOLD 1-2 vs. 4: HR 3.45 [95%CI: 1.75 – 6.79]) and PH severity (p=0.012; HR: 1.85 [95%CI: 1.15 – 2.99]) remained independently associated with survival. The combination of GOLD 3-4 airflow-limitation and severe PH had the poorest survival (HR for death 3.26 [95% CI: 1.62-6.57], p=0.001 vs. GOLD 1-2 combined with non-severe PH).

INTERPRETATION: In COPD patients, the combination of echocardiography, NT-proBNP and PA/Ao-ratio predicts severe PH with high sensitivity and specificity. The contribution of severe PH and severe airflow-limitation to impaired survival is comparable.

PMID:35092746 | DOI:10.1016/j.chest.2022.01.031

Adv Clin Exp Med. 2022 Jan 29. doi: 10.17219/acem/144170. Online ahead of print.

ABSTRACT

BACKGROUND: Aberrant DNA methylation is an important mechanism by which the normal patterns of microRNA expression are disrupted in human cancers including B-cell precursor acute lymphoblastic leukemia (BCP ALL), the most common pediatric malignancy.

OBJECTIVES: To characterize the methylation profile landscape of microRNA genes in BCP ALL patients.

MATERIAL AND METHODS: We employed Infinium® MethylationEPIC BeadChip Arrays to measure the methylation of microRNA genes from bone marrow samples of children with BCP ALL (n = 38) and controls without neoplasms (n = 4).

RESULTS: This analysis revealed differential methylation of the microRNA genes in the pediatric BCP ALL when compared to the control. A subcluster amongst BCP ALL patients with TCF3-PBX1 genetic subtype was also observed. No other differences were observed in association with age, gender or risk group. Several interesting leukemia-related phenotypes are enriched by the genes with hyperand hypomethylated sites located in promoters as well as gene bodies. The top 3 miRNA genes, promoters of which were the most statistically significantly hypermethylated in BCP ALL were MIR1273G, MIR1304 and MIR663, and the top 3 hypomethylated were MIR4442, MIR155 and MIR3909.

CONCLUSIONS: In this study, a different microRNA genes methylation landscape was shown in pediatric BCP ALL compared to children without neoplasms. A visible subcluster among BCP ALL samples consisted of individuals with TCF3-PBX1 genetic subtype. No other differences were observed in association with age, gender or risk group. Several interesting leukemia-connected phenotypes were found, associated with genes with hyperand hypomethylated sites located on promoters as well as gene bodies.

PMID:35092653 | DOI:10.17219/acem/144170

Am J Vet Res. 2022 Jan 28:1-7. doi: 10.2460/ajvr.21.08.0114. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare single and triplicate applanation tonometry values across previous intraocular pressure (IOP) studies in dogs.

ANIMALS: 116 ophthalmologically normal dogs.

PROCEDURES: Triplicate IOP readings (n = 1432) from studies evaluating effect of anesthetic protocols were analyzed to estimate a range of probable differences between averaged triplicate and first, averaged and lowest, and first and lowest IOPs. The decrease in variability with triplicate measurements and the magnitude of effects on statistical power were quantified.

RESULTS: The 2.5th to 97.5th interpercentile range for differences of averaged triplicate values minus first IOP readings was -3 to 2.7 mm Hg; for averaged minus lowest: 0 to 3.7 mm Hg; for first minus lowest: 0 to 5 mm Hg. The 95% prediction interval for differences in study group means (n = 160 groups, n = 5 to 11 eyes per group) based on averaged minus first measurements was -1.0 to 0.9 mm Hg with associated SDs reduced by 4% on average. Analysis of previous studies using averaged instead of first IOP values resulted in minimal decreases in SEs of 3-9% (0.03 to 0.09 mm Hg). Of 11 comparisons found significant with averaged data, 2 (18%) were found nonsignificant with first measurements. Of 96 comparisons found nonsignificant with averaged data, 3 (3%) were found significant with first measurements.

CLINICAL RELEVANCE: With applanation tonometry in ophthalmologically normal dogs, no clinically meaningful difference was found between the first, lowest, or averaged triplicate IOP measurements, but the first reading has a larger variance and hence will result in lower statistical power.

PMID:35092667 | DOI:10.2460/ajvr.21.08.0114

Adv Clin Exp Med. 2022 Jan 29. doi: 10.17219/acem/145510. Online ahead of print.

ABSTRACT

BACKGROUND: Male infertility is mostly due to low sperm quality, which accounts for about 50% of the causes of infertility. The reasons for low sperm quality are still unclear. Nowadays, many drinks contain high levels of fat, and its effect on fertility is not yet known.

OBJECTIVES: To investigate the effect of cholesterol-containing water on male fertility.

MATERIAL AND METHODS: Forty BALB/c male mice were divided into 2 groups: the control group and the water-induced obesity (WIO) group. Body and testicular weights were recorded and analyzed statistically. Testicular tissues were examined. Serum contents of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), free testosterone (FT), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were determined. Motility count and morphology of sperm were analyzed. Real-time polymerase chain reaction (RT-PCR) was performed for SYCP3, VEGFA and WT1 genes.

RESULTS: The results showed that the WIO group presented the highly significant values for mice body and testis weight, and TC, TG and LDL level in serum (p < 0.05), when compared to the control group. The level of FT, LH and FSH in serum was significantly decreased (p < 0.05) in the WIO group compared with the control group. Seminiferous tubules of testes became thin, and Sertoli cells showed mild atrophy in this group. Also, the count and motility of sperm significantly reduced while the ratio of sperm abnormalities significantly increased in the WIO group compared with the control group (p < 0.05). The results of RT-PCR showed that SYCP3, VEGFA and WT1 genes were significantly downregulated (p < 0.05) in the WIO group compared with the control group.

CONCLUSIONS: This study indicated that drinks containing high levels of fat may have negative effects on male fertility due to the reduction of the sexual hormones level in serum, the expression of SYCP3, VEGFA and WT1 genes, count and motility of sperm, as well as an increase in sperm abnormalities and pathological changes in the testicular tissues.

PMID:35092652 | DOI:10.17219/acem/145510

Rev Cardiovasc Med. 2022 Jan 19;23(1):34. doi: 10.31083/j.rcm2301034.

ABSTRACT

BACKGROUND: Perioperative anticoagulation management with uninterrupted or minimally interrupted anticoagulation during atrial fibrillation (AF) ablation is thought to be critical to minimize thromboembolic complications. Protamine is often administered to neutralize the effects of heparin and expedite vascular hemostasis post-procedure.

OBJECTIVE: We performed a systematic review and meta-analysis to determine the effectiveness of protamine to expedite vascular hemostasis and ambulation in patients undergoing AF ablation.

METHODS: Electronic searches on PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from the inception through August 7, 2021, were performed. The primary outcomes included-time to hemostasis (minutes) and time to ambulation (minutes). The secondary outcomes included – any vascular complications (excluding minor hematoma), minor hematoma, or cerebrovascular accidents (CVA).

RESULTS: A total of 5 eligible studies (3 retrospective cohort studies and two randomized trials) consisting of 1012 patients (515 patients received protamine group and 497 patients did not receive protamine group) were included in the meta-analysis. There was a significant reduction in time to ambulation [weighted mean difference (WMD) -176.6 minutes, 95% Confidence interval (CI) -266.9 to -86.3; p < 0.01] and time to hemostasis (WMD -13.72 minutes, 95% CI -22 to -5.4, p < 0.01) in the protamine group compared to the contrary. At a follow-up up to 3 months, there was no statistical difference between the two groups with regards to vascular complications (2.9% vs. 7.4%; Risk ratio (RR) 0.46 95% CI 0.17 to 1.24; p = 0.12), minor hematoma (2.1% vs. 5.8%; RR 0.43, 95% CI 0.16 to 1.2; p = 0.11) or CVA (0 vs. 0.3%; RR 0.62, 95% CI 0.08 to 4.98; p = 0.65).

CONCLUSION: Protamine administration was associated with reduced time to ambulation (176 minutes reduction) and time to hemostasis (13 minutes reduction) without an increase in any adverse events.

PMID:35092226 | DOI:10.31083/j.rcm2301034

Rev Cardiovasc Med. 2022 Jan 18;23(1):31. doi: 10.31083/j.rcm2301031.

ABSTRACT

BACKGROUND: Citations are used to assess the importance of authors, articles and journals in the scientific community, but do not examine how they affect general public journal readership. The Altmetric Attention Score (AAS) is a new metric for measuring media attention of the published paper.

METHODS: We examined cardiovascular (CV) randomized clinical trials (RCTs), published in the 3 highest Web of Science Impact Factor journals (Journal Citation Reports 2019: category “Medicine, General & Internal”) and in the 3 highest Web of Science Impact Factor CV journals (Journal Citation Reports 2019: category “Cardiac & Cardiovascular Systems”), through the calendar year of 2017, 2018 and 2019. The primary outcomes were the assessment of the difference between number of citations and AAS among positive and negative CV RCTs.

RESULTS: Among the included 262 RCTs, more positive CV RCTs were published (p = 0.002). There was no significant statistical difference between the positive and negative trials, considering the number of citations (p = 0.61). Interestingly, positive trials had a tendency towards a higher AAS (p = 0.058). The correlation between the AAS and the number of citations was moderate positively correlated (ρ = 0.47, p < 0.001).

CONCLUSION: We did not find any differences between CV RCTs with positive vs CV RCTs with negative results considering the number of their citations. A tendency towards a higher AAS among positive CV RCTs could indicate higher activity on social media regarding CV trials with positive results. A higher number of published positive CV RCTs among all published CV RCTs could indicate the presence of publication bias but further investigation of unpublished RCTs in trial registries (e.g., clinicaltrials.gov) is needed.

PMID:35092223 | DOI:10.31083/j.rcm2301031