Nevin Manimala

Water Res. 2022 Jan 22;212:118115. doi: 10.1016/j.watres.2022.118115. Online ahead of print.

ABSTRACT

Poor lipid degradation limits low-temperature anaerobic treatment of domestic wastewater even when psychrophiles are used. We combined metagenomics and metaproteomics to find lipolytic bacteria and their potential, and actual, cold-adapted extracellular lipases in anaerobic membrane bioreactors treating domestic wastewater at 4 and 15 °C. Of the 40 recovered putative lipolytic metagenome-assembled genomes (MAGs), only three (Chlorobium, Desulfobacter, and Mycolicibacterium) were common and abundant (relative abundance ≥ 1%) in all reactors. Notably, some MAGs that represented aerobic autotrophs contained lipases. Therefore, we hypothesised that the lipases we found are not always associated with exogenous lipid degradation and can have other roles such as polyhydroxyalkanoates (PHA) accumulation/degradation and interference with the outer membranes of other bacteria. Metaproteomics did not provide sufficient proteome coverage for relatively lower abundant proteins such as lipases though the expression of fadL genes, long-chain fatty acid transporters, was confirmed for four genera (Dechloromonas, Azoarcus, Aeromonas and Sulfurimonas), none of which were recovered as putative lipolytic MAGs. Metaproteomics also confirmed the presence of 15 relatively abundant (≥ 1%) genera in all reactors, of which at least 6 can potentially accumulate lipid/polyhydroxyalkanoates. For most putative lipolytic MAGs, there was no statistically significant correlation between the read abundance and reactor conditions such as temperature, phase (biofilm and bulk liquid), and feed type (treated by ultraviolet light or not). Results obtained by metagenomics and metaproteomics did not confirm each other and extracellular lipases and lipolytic bacteria were not easily identifiable in the anaerobic membrane reactors used in this study. Further work is required to identify the true lipid degraders in these systems.

PMID:35092910 | DOI:10.1016/j.watres.2022.118115

Heart Lung. 2022 Jan 26;52:165-169. doi: 10.1016/j.hrtlng.2022.01.009. Online ahead of print.

ABSTRACT

PURPOSE: Acute pulmonary edema is characterized by increased levels of fluid in the interstitial and alveolar space of the lung and requires emergency treatment. In acute pulmonary edema, the amount of fluid in the intra-alveolar, interstitial space, and pleural space vary considerably and this fluid will evaporate in different amounts compared to the physiological fluid. The aim of this study was to compare the humidity rates of expiratory air measured before and after pulmonary edema induced by α-naphthylthiourea (ANTU) in rats.

METHODS: The study included twenty healthy adult rats divided equally into a healthy control group and a pulmonary edema group. Pulmonary edema was induced by administering ANTU intraperitoneally in the rats in the study group. Humidity, temperature, lung weight, pleural effusion, and histopathological changes in the respiratory system due to pulmonary edema were examined in the ANTU group. Control measurments were taken before administration of ANTU and again 4 h after administration of ANTU when lung damage was considred to be at maximum levels.

RESULTS: Mean expiratory air humidity was 71.22±3.59% before ANTU and 56.28±3.94% after administration of ANTU. The mean humidity difference of -14.94±5.96% was considered statistically different (p = 0.01).

CONCLUSION: Humidity rate in expiratory air was significantly lower in rats with acute pulmonary edema compared to healthy rats. This result supports the hypothesis that humidity in expiratory air can be considered an important parameter in patients during clinical are follow-up for pulmonary edema.

PMID:35092906 | DOI:10.1016/j.hrtlng.2022.01.009

Semin Thorac Cardiovasc Surg. 2022 Jan 26:S1043-0679(22)00005-3. doi: 10.1053/j.semtcvs.2022.01.001. Online ahead of print.

ABSTRACT

Survival analyses are a group of statistical principles applied to accurately analyze the length of time until a previously defined event occurs. Increasing survival is the underlying goal for most medical interventions, and is particularly critical in oncology-related surgical fields. In order to justify the application of a novel surgical intervention or other cancer therapy, one must first definitively show improvements in patient survival compared to the existing method of treatment. In order to definitively recommend one treatment option over another, it is paramount to design a study that addresses and minimizes sources of bias where possible. This can be challenging due to numerous factors including selecting an appropriate study design, dealing with censored data, obtaining an appropriate sample size, and performing robust statistical analysis. It is critical for surgeons in every stage of training to be able to both understand and apply these methods in order to improve patient care. In this review, we discuss approaches to design survival studies, relevant errors/biases and how to account for them, and cover several field-standard methods to analyze survival data including Kaplan-Meier plots, the log-rank test, and Cox Proportional Hazards Models. Importantly, this is accompanied by easily repurposable examples of how to implement these analyses in both R and GraphPad Prism using a publicly available survival dataset. This review will assist surgeons of all training levels in the design and analysis of survival studies and serve as a starting point for advancing patient care.

PMID:35092846 | DOI:10.1053/j.semtcvs.2022.01.001

J Thorac Oncol. 2022 Jan 26:S1556-0864(22)00051-X. doi: 10.1016/j.jtho.2022.01.006. Online ahead of print.

ABSTRACT

INTRODUCTION: We analysed a comprehensive national radiotherapy dataset to compare outcome of the most frequently used moderate hypofractionation regimen (55Gy in 20 fractions) and conventional fractionation (60-66Gy in 30-33 fractions).

PATIENTS & METHODS: 169,863 cases of non-small cell lung cancer (NSCLC) registered in England from January 2012 to December 2016 obtained from Public Health England were divided into Cohort 1 (training set) diagnosed 2012-13 and Cohort 2 (validation set) diagnosed 2014-16. Radiotherapy data was obtained from the National Radiotherapy Dataset and linked by NHS number to survival data from Office of National Statistics and Hospital Episode Statistics from which surgical data and Charlson comorbidity Index were obtained. Of 73186 patients with stage I-III NSCLC 12898 received radical fractionated radiotherapy (cohort 1 – 4894; cohort 2 – 8004). Multivariate proportional hazards model was used to investigate overall survival from time of diagnosis. Survival was adjusted for the prognostic factors of age, gender, stage of disease, comorbidity, other radical treatments and adjuvant chemotherapy and the difference between the treatment schedules was summarised by the hazard ratio (HR) and 95% confidence interval (95% CI). The significance of any difference was assessed by the log likelihood test.

RESULTS: 17-18% of patients with stage I-III NSCLC received fractionated radical radiotherapy. After adjustment for independent prognostic factors of age, stage, comorbidity and other radical and adjuvant treatments, patients in Cohort 1 treated with the 2.75 Gy per fraction regimen had a median survival of 25 months compared to 29 months for patients treated with the 2 Gy per fraction regimen (HR = 1.16; p=0.001). Similarly in Cohort 2 the respective median survival values were 25 and 28 months (HR=1.10; p=0.02).

CONCLUSION: Big data analysis of a comprehensive national cohort of NSCLC patients treated in England suggests that compared to a 4-week regimen of 55Gy in 20 fractions, a 6-week regimen of conventional daily fractionation to a dose of 60-66 Gy at 2 Gy per fraction is associated with a survival benefit. Within the limitations of retrospective big data analysis with potential selection bias and in the absence of randomised trials, the results suggest that conventional fractionation regimens should remain the standard of care.

PMID:35092841 | DOI:10.1016/j.jtho.2022.01.006

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

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

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

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

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

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