Nevin Manimala

Vet Rec. 2021 Aug 10:e775. doi: 10.1002/vetr.775. Online ahead of print.

ABSTRACT

BACKGROUND: Farm management practices have a major impact on nematode population dynamics. The presented study aimed to understand current nematode management practices on UK sheep farms; with a particular focus on Nematodirus battus because of the changing epidemiology, and emerging anthelmintic resistance observed in this species.

METHODS: A 42 question online survey covering grazing management, farm demographics and parasite control strategies was developed and distributed to the farming community in 2016. Analysis of the 187 completed questionnaires explored regional variations in practices.

RESULTS: Uptake of recommendations was variable, particularly quarantine practices and monitoring tools. Results also highlighted variation in the epidemiology of N. battus; respondents in the north (Scotland, north-west and north-east England) typically reported N. battus in spring with a perception of more severe clinical symptoms than those from the south (Midlands, Wales, south-east and south-west England; p = 0.03). Farms in the south observed greater changes in the timing of disease (p = 0.006) with N. battus being reported throughout the year on some holdings and more frequent use of faecal egg count monitoring (p = 0.006).

CONCLUSIONS: Control of N. battus infection is challenging and ‘one-size-fits-all’ advice is not applicable; however, the information gathered will enable the development of effective, adaptable control strategies.

PMID:34375447 | DOI:10.1002/vetr.775

Eur J Clin Invest. 2021 Aug 10:e13663. doi: 10.1111/eci.13663. Online ahead of print.

ABSTRACT

BACKGROUND: There is still a lack of consensus on the efficacy of convalescent plasma (CP) treatment in COVID-19 patients. We performed a systematic review and meta-analysis to investigate the efficacy of CP vs standard treatment/non-CP on clinical outcomes in COVID-19 patients.

METHODS: Cochrane Library, PubMed, Embase, and ClinicalTrial.gov were searched from December 2019 to 16^th July 2021, for data from clinical trials and observational studies. The primary outcome was all-cause mortality. Risk estimates were pooled using a random-effect model. Risk of bias was assessed by Cochrane Risk of Bias tool for clinical trials and Newcastle-Ottawa Scale for observational studies.

RESULTS: In total, 18 peer-review clinical trials, 3 preprints, and 26 observational studies met the inclusion criteria. In the meta-analysis of 18 peer-reviewed trials, CP use had a 31% reduced risk of all-cause mortality compared to standard treatment use (pooled risk ratio [RR]=0.69, 95% confidence interval [CI]: 0.56-0.86, p=0.001, I² =50.1%). Based on severity and region, CP treatment significantly reduced risk of all-cause mortality in patients with severe and critical disease and studies conducted in Asia, pooled RR=0.61, 95% CI: 0.47-0.81, p=0.001, I² =0.0%, pooled RR=0.67, 95% CI: 0.49-0.92, p=0.013, I² =0.0%, and pooled RR=0.62, 95% CI: 0.48- 0.80, p<0.001, I² =20.3%, respectively. The meta-analysis of observational studies showed the similar results to the clinical trials.

CONCLUSIONS: CP use was associated with reduced risk of all-cause mortality in severe or critical COVID-19 patients. However, the findings were limited with a moderate degree of heterogeneity. Further studies with well-designed and larger sample size are needed.

PMID:34375445 | DOI:10.1111/eci.13663

J Am Geriatr Soc. 2021 Aug 10. doi: 10.1111/jgs.17416. Online ahead of print.

ABSTRACT

The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at greatest risk for morbidity and mortality from SARS-CoV-2 infection. SARS-CoV-2 complications include cytokine storm and multi-organ failure mediated by the same factors as often produced by SnCs through their senescence-associated secretory phenotype (SASP). The SASP can be amplified by infection-related pathogen-associated molecular profile factors (PAMPs). Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty, obesity/diabetes, osteoporosis, and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS-CoV-2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS-CoV-2 progression and morbidity in hospitalized older adults. We describe here an NIH-funded, multi-center, placebo-controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS-CoV-2 rtPCR-positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long-term care settings in the SARS-CoV-2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials. This article is protected by copyright. All rights reserved.

PMID:34375437 | DOI:10.1111/jgs.17416

J Clin Endocrinol Metab. 2021 Aug 10:dgab591. doi: 10.1210/clinem/dgab591. Online ahead of print.

ABSTRACT

PURPOSE: Although homocysteine accumulation is a reported risk factor for several age-related disorders, little is known on its relationship with osteoarthritis (OA). We therefore investigated for associations of homocysteine and C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR), which is involved in homocysteine clearance, with the development and progression of spinal OA, through a combined cross-sectional and longitudinal cohort study.

METHODS: A total of 1306 Japanese postmenopausal outpatients participating in the Nagano Cohort Study were followed for a 9.7-year mean period. Cross-sectional multiple logistic regression for spinal OA prevalence at registration by serum homocysteine level was performed with adjustment for confounders. In addition to Kaplan-Meier analysis, multivariate Cox regression was employed to examine the independent risk of MTHFR C677T variant for spinal OA progression.

RESULTS: Multivariate regression analysis revealed a significant association between homocysteine and spinal OA prevalence (odds ratio 1.38; 95% confidence interval [CI] 1.14-1.68). Kaplan-Meier curves showed a gene dosage effect of the T allele in MTHFR C677T polymorphism on the accelerated progression of spinal OA severity (P = 0.003). A statistically significant independent risk of the T allele for spinal OA advancement was validated by Cox regression analysis. Respective adjusted hazard ratios for the CT/TT and TT genotypes were 1.68 (95% CI 1.16-2.42) and 1.67 (95% CI 1.23-2.28).

CONCLUSIONS: Circulating homocysteine and C677T variant in MTHFR are associated with the prevalence rate and ensuing progression, respectively, of spinal OA. These factors may represent potential interventional targets to prevent OA development and improve clinical outcomes.

PMID:34375425 | DOI:10.1210/clinem/dgab591

Am J Clin Nutr. 2021 Aug 10:nqab253. doi: 10.1093/ajcn/nqab253. Online ahead of print.

ABSTRACT

BACKGROUND: Both obesity and hypogonadism are common in older men which could additively exacerbate age-related declines in cognitive function. However, little is known about the effects of lifestyle intervention plus testosterone replacement therapy in this population.

OBJECTIVES: In this secondary analysis of the LITROS (Lifestyle Intervention and Testosterone Replacement in Obese Seniors) trial, we examined whether testosterone replacement therapy would improve cognitive function when added to intensive lifestyle intervention in older men with obesity and hypogonadism.

METHODS: Eighty-three older, obese hypogonadal men with frailty were randomly assigned to lifestyle therapy (weight management and exercise training) plus testosterone (LT + Test) or lifestyle therapy plus placebo (LT + Pbo) for 6 mo. For this report, the primary outcome was change in the global cognition composite z score. Secondary outcomes included changes in z score subcomponents: attention/information processing, memory, executive function, and language. Changes between groups were analyzed using mixed-model repeated-measures ANCOVAs following the intention-to-treat principle.

RESULTS: Global cognition z score increased more in the LT + Test than in the LT + Pbo group (mean change: 0.49 compared with 0.21; between-group difference: -0.28; 95% CI: -0.45, -0.11; Cohen’s d = 0.74). Moreover, attention/information z score and memory z score increased more in the LT + Test than in the LT + Pbo group (mean change: 0.55 compared with 0.23; between-group difference: -0.32; 95% CI: -0.55, -0.09; Cohen’s d = 0.49 and mean change: 0.90 compared with 0.37; between-group difference: -0.53; 95% CI: -0.93, -0.13; Cohen’s d = 1.43, respectively). Multiple regression analyses showed that changes in peak oxygen consumption, strength, total testosterone, and luteinizing hormone were independent predictors of the improvement in global cognition (R2 = 0.38; P < 0.001).

CONCLUSIONS: These findings suggest that in the high-risk population of older men with obesity and hypogonadism, testosterone replacement may improve cognitive function with lifestyle behaviors controlled via lifestyle intervention therapy.This trial was registered at clinicaltrials.gov as NCT02367105.

PMID:34375393 | DOI:10.1093/ajcn/nqab253

Am J Clin Nutr. 2021 Aug 10:nqab261. doi: 10.1093/ajcn/nqab261. Online ahead of print.

ABSTRACT

BACKGROUND: Both diet and familial factors have a major role in the development of cardiovascular disease (CVD). However, it remains unclear whether familial predisposition to CVD modifies the association between dietary factors and CVD.

OBJECTIVES: The aim was to assess whether the association between diet and CVD varies with familial predisposition to CVD.

METHODS: In this prospective cohort of the UK Biobank, 462,155 CVD-free participants were included in 2006-2010 and followed for CVD incidence until 2020. Food intake was measured using a short food-frequency questionnaire. Familial predisposition was measured by self-reported family history of CVD and by polygenic risk score (PRS) for CVD based on summary statistics of independent genome-wide association studies.

RESULTS: During a median follow-up of 11.2 y, 46,164 incident CVD cases were identified. A moderately higher risk of CVD was associated with more frequent processed-meat consumption, with an adjusted HR of 1.07 (95% CI: 1.03, 1.11; highest vs. lowest level). Conversely, intakes of fish, cheese, vegetables, and fruit were each associated with reduced CVD risk [HR (95% CI): 0.92 (0.89, 0.96), 0.90 (0.86, 0.94), 0.98 (0.95, 1.00), and 0.93 (0.89, 0.96), respectively]. Stratification analyses by family history of CVD and by PRS for CVD revealed an inverse association between CVD and intakes of fish and cheese, for both subgroups with and without a familial predisposition to CVD. Notably, while the association between processed-meat intake and CVD was restricted to individuals with a familial predisposition to CVD [e.g., HR: 1.11 (1.05, 1.16) and 1.03 (0.97, 1.10) for with and without a family history, respectively, P-interaction < 0.001], the risk reduction of CVD associated with vegetable and fruit intake was only noted among participants without a CVD familial predisposition [e.g., HR for fruit consumption: 1.00 (0.97, 1.03) and 0.91 (0.87, 0.95), respectively, P < 0.001].

CONCLUSIONS: Familial factors modify the association between diet and CVD, underscoring the need for personalized dietary guidelines for CVD prevention.

PMID:34375391 | DOI:10.1093/ajcn/nqab261

Am J Prev Cardiol. 2021 Mar 29;5:100154. doi: 10.1016/j.ajpc.2021.100154. eCollection 2021 Mar.

ABSTRACT

[This corrects the article DOI: 10.1016/j.ajpc.2020.100035.].

PMID:34375372 | PMC:PMC8315598 | DOI:10.1016/j.ajpc.2021.100154

PLoS One. 2021 Aug 10;16(8):e0255852. doi: 10.1371/journal.pone.0255852. eCollection 2021.

ABSTRACT

INTRODUCTION: The number of elderly patients undergoing major surgery is rapidly increasing. They are particularly at risk of developing postoperative neurocognitive disorders (NCD). Earlier studies suggested that processed electroencephalographic (EEG) monitors may reduce the incidence of postoperative NCD. However, none of these studies controlled for intraoperative nociception levels or personalized blood pressure targets. Their results remain unclear if the reduction in the incidence of postoperative NCD relates to avoidance of any electroencephalographic pattern suggesting excessive anesthesia depth.

OBJECTIVE: The objective of this trial is to investigate-in patients ≥ 70 years old undergoing major non-cardiac surgery-the effect of EEG-guided anesthesia on postoperative NCD while controlling for intraoperative nociception, personalized blood pressure targets, and using detailed information provided by the EEG monitor (including burst suppression ratio, density spectral array, and raw EEG waveform).

MATERIAL AND METHODS: This prospective, randomized, controlled trial will be conducted in a single Canadian university hospital. Patients ≥ 70 years old undergoing elective major non-cardiac surgery will be included in the trial. The administration of sevoflurane will be adjusted to maintain a BIS index value between 40 and 60, to keep a Suppression Ratio (SR) at 0%, to keep a direct EEG display without any suppression time and a spectrogram with most of the EEG wave frequency within the alpha, theta, and delta frequencies in the EEG-guided group. In the control group, sevoflurane will be administered to achieve an age-adjusted minimum alveolar concentration of [0.8-1.2]. In both groups, a nociception monitor will guide intraoperative opioid administration, individual blood pressure targets will be used, and cerebral oximetry used to tailor intraoperative hemodynamic management. The primary endpoint will be the incidence of NCD at postoperative day 1, as evaluated by the Montreal Cognitive Assessment (MoCA). Secondary endpoints will include the incidence of postoperative NCD at different time points and the evaluation of cognitive trajectories up to 90 days after surgery among EEG-guided and control groups.

STUDY REGISTRATION: NCT04825847 on ClinicalTrials.gov.

PMID:34375362 | DOI:10.1371/journal.pone.0255852

PLoS One. 2021 Aug 10;16(8):e0255446. doi: 10.1371/journal.pone.0255446. eCollection 2021.

ABSTRACT

BACKGROUND: Obesity is the cause of cardiovascular diseases and other diseases, leading to increased medical costs, and causing a great burden to individuals, families and society. The prevalence of obesity is increasing and has become a global health problem. There is growing evidence that gut microbiota plays an important role in obesity. In this article, we revealed the differences in the gut microbiota between 21 people with obesity and 21 control subjects, and predicted the functional potential changes by 16S rRNA sequencing of the fecal bacteria of the subjects.

METHODS: The raw sequencing data of 21 healthy Beijing volunteers was downloaded from Microbial Genome Database System. Microbial 16S rRNA genes of 21 adults with obesity were sequenced on an Illumina MiSeq instrument and analyzed by using bioinformatics and statistical methods.

RESULTS: The diversity of gut microbiota in people with obesity decreased significantly. There were significant differences in gut microbiota between the Obesity and Control group at different levels. At the phylum level, Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria are significantly different between the Obesity and Control group. In people with obesity, the ratio of Firmicutes/Bacteroidetes decreased significantly. At the genus level, there were significant differences among the 16 major genera, of which four genera Prevotella, Megamonas, Fusobacterium and Blautia increased significantly in people with obesity, while the remaining 12 genera, Faecalibacterium, Lachnospiracea_incertae_sedis, Gemmiger and Clostridium XlVa, etc. decreased significantly. At the species level, nine species including Bacteroides uniformis and Prevotella copri had significant differences. Compared with the control group, subjects with obesity were abnormalities in 57 pathways, mainly in Carbohydrate metabolism and Lipid metabolism.

CONCLUSIONS: Overall, our study revealed differences in the gut microbiota between people with obesity and control subjects, providing novel target for the treatment of individuals with obesity.

PMID:34375351 | DOI:10.1371/journal.pone.0255446

PLoS One. 2021 Aug 10;16(8):e0254959. doi: 10.1371/journal.pone.0254959. eCollection 2021.

ABSTRACT

The Depressive and Anxious Avoidance in Prolonged Grief Questionnaire (DAAPGQ) was developed to measure depressive and anxious avoidance behaviors, which, according to cognitive-behavioral models, are supposed to play an important role in the development and maintenance of prolonged grief. The present study aimed to develop a German version of the DAAPGQ and evaluate its psychometric properties and validity within a representative sample of the German general population (N = 2531). The German-language DAAPGQ was developed using a forward-backward translation procedure. Then, a subsample of individuals who reported having lost a significant other (N = 1371) of a representative sample was assessed with the German DAAPGQ, along with information on sociodemographic characteristics, prolonged grief symptom severity (PG-13), general anxiety (GAD-2) and depression (PHQ-2). The factor structure of the DAAPGQ was evaluated using confirmatory factor analyses, reliability by calculating internal consistency on subscale level and convergent validity by correlations between DAAPQG subscale sores with PG-13, GAD-2 and PHQ-2 sum scores. As expected, a two-factor model with correlated latent variables showed good fit to the data, replicating findings from the original version. Internal consistency was high for both subscales (Cronbach’s α .86 and .95, respectively). Convergent validity was established by theoretically expected and statistically significant positive correlations of DAAPGQ subscales with symptom severity of prolonged grief, depression, and anxiety and negative correlations with time since loss. Furthermore, the addition of depressive and anxious avoidance significantly improved the prediction of prolonged grief symptom severity over sociodemographic and loss-related information. In sum, our results suggest that the German-language DAAPGQ is a reliable and valid measure of depressive and anxious avoidance and a useful tool to improve our knowledge on the role of avoidance in prolonged grief. We also provide descriptive data to improve the applicability of the DAAPGQ for individual diagnostics.

PMID:34375341 | DOI:10.1371/journal.pone.0254959