Nevin Manimala

PLoS One. 2021 Aug 2;16(8):e0255128. doi: 10.1371/journal.pone.0255128. eCollection 2021.

ABSTRACT

OBJECTIVE: To assess the effectiveness of mindfulness-based interventions on people with dementia and mild cognitive impairment.

METHODS: We searched several electronic databases, namely Cochrane Library, EMBASE, and MEDLINE with no limitations for language or document type (last search: 1 February 2020). Randomized controlled trials of mindfulness-based interventions for people with dementia and mild cognitive impairment compared to active-control interventions, waiting lists, or treatment as usual were included. Predefined outcomes were anxiety symptoms, depressive symptoms, cognitive function, quality of life, mindfulness, ADL and attrition. We used the random effects model (DerSimonian-Laird method) for meta-analysis, reporting effect sizes as Standardized Mean Difference. Heterogeneity was assessed with the I2 statistics.

RESULTS: Eight randomized controlled trials, involving 276 patients, met the eligibility criteria and were included in the meta-analysis. We found no significant effects for mindfulness-based interventions in either the short-term or the medium- to long-term on any outcomes, when compared with control conditions. The number of included studies and sample sizes were too small. Additionally, the quality of evidence was low for each randomized controlled trial included in the analysis. This is primarily due to lack of intent-to-treat analysis, high risk of bias, and imprecise study results. The limited statistical power and weak body of evidence prevented us from reaching firm conclusions.

CONCLUSIONS: We found no significant effects of mindfulness-based interventions on any of the outcomes when compared with control conditions. The evidence concerning the efficacy of mindfulness-based interventions in this population is scarce in terms of both quality and quantity. More well-designed, rigorous, and large-scale randomized controlled trials are needed.

PMID:34339428 | DOI:10.1371/journal.pone.0255128

PLoS Comput Biol. 2021 Aug 2;17(8):e1009266. doi: 10.1371/journal.pcbi.1009266. Online ahead of print.

ABSTRACT

It is of great interest and potential to discover causal relationships between pairs of exposures and outcomes using genetic variants as instrumental variables (IVs) to deal with hidden confounding in observational studies. Two most popular approaches are Mendelian randomization (MR), which usually use independent genetic variants/SNPs across the genome, and transcriptome-wide association studies (TWAS) (or their generalizations) using cis-SNPs local to a gene (or some genome-wide and likely dependent SNPs), as IVs. In spite of their many promising applications, both approaches face a major challenge: the validity of their causal conclusions depends on three critical assumptions on valid IVs, and more generally on other modeling assumptions, which however may not hold in practice. The most likely as well as challenging situation is due to the wide-spread horizontal pleiotropy, leading to two of the three IV assumptions being violated and thus to biased statistical inference. More generally, we’d like to conduct a goodness-of-fit (GOF) test to check the model being used. Although some methods have been proposed as being robust to various degrees to the violation of some modeling assumptions, they often give different and even conflicting results due to their own modeling assumptions and possibly lower statistical efficiency, imposing difficulties to the practitioner in choosing and interpreting varying results across different methods. Hence, it would help to directly test whether any assumption is violated or not. In particular, there is a lack of such tests for TWAS. We propose a new and general GOF test, called TEDE (TEsting Direct Effects), applicable to both correlated and independent SNPs/IVs (as commonly used in TWAS and MR respectively). Through simulation studies and real data examples, we demonstrate high statistical power and advantages of our new method, while confirming the frequent violation of modeling (including valid IV) assumptions in practice and thus the importance of model checking by applying such a test in MR/TWAS analysis.

PMID:34339418 | DOI:10.1371/journal.pcbi.1009266

Aging (Albany NY). 2021 Aug 2;13(undefined). doi: 10.18632/aging.203361. Online ahead of print.

ABSTRACT

Parkinson’s disease (PD), the typical neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN). However, no therapeutic agent used currently could slow down neuronal cell loss so as to decelerate or halt the progression of PD. Traditional Chinese medicine (TCM) has been utilized to treat the dysfunction of the autonomic nervous system. Wen-Shen-Yang-Gan decoction (WSYGD) has a good effect on the clinical treatment of PD with constipation. However, it is not clear which ingredients and what mechanism are responsible for the therapeutic effect. In this study, the pharmacodynamic study of WSYGD in PD mice was applied. Concurrently, a novel method for the identification of metabolic profiles of WSYGD has been developed. Finally, we found that WSYGD could protect the PD mice induced by rotenone. The underlying mechanism of the protective effect may be related to the reduction of the DA neurons apoptosis via reducing inflammatory reaction. By virtue of UPLC-MS and chemoinformatics method, 35 prototype compounds and 27 metabolites were filtered out and tentatively characterized. In conclusion, this study provides an insight into the metabolism of WSYGD in vivo to enable understanding of the metabolic process and therapeutic mechanism of PD.

PMID:34339394 | DOI:10.18632/aging.203361

Am J Trop Med Hyg. 2021 Aug 2:tpmd210377. doi: 10.4269/ajtmh.21-0377. Online ahead of print.

ABSTRACT

Ivermectin (IVM) is a widely used anthelmintic. However, with widespread use comes the risk of the emergence of IVM resistance, particularly in strongyloidiasis. Adenosine triphosphate (ATP)-binding cassette (ABC) transporter genes play an important role in the IVM-resistance mechanism. Here, we aimed to establish an animal experimental model of IVM resistance by frequent treatment of Strongyloides ratti with subtherapeutic doses of IVM, resistance being evaluated by the expression levels of ABC transporter genes. Rats infected with S. ratti were placed in experimental groups as follows: 1) untreated control (control); 2) treated with the mutagen ethyl methanesulfonate (EMS); 3) injected with 100 µg/kg body weight of IVM (IVM); 4) treated with a combination of EMS and IVM (IVM+EMS). Parasites were evaluated after four generations. Extent of IVM resistance was assessed using IVM sensitivity, larval development, and expression of ABC genes. By the F4 generation, S. ratti in the IVM group exhibited significantly higher levels of IVM resistance than did other groups according to in vitro drug-sensitivity tests and inhibition of larval development (IC50 = 36.60 ng/mL; 95% CI: 31.6, 42.01). Expression levels of ABC isoform genes (ABCA, ABCF, and ABCG) were statistically significantly higher in the IVM-resistant line compared with the susceptible line. In conclusion, IVM subtherapeutic doses induced IVM resistance in S. ratti by the F4 generation with corresponding upregulation of some ABC isoform genes. The study provides a model for inducing and assessing drug resistance in Strongyloides.

PMID:34339389 | DOI:10.4269/ajtmh.21-0377

J Cardiovasc Surg (Torino). 2021 Aug 2. doi: 10.23736/S0021-9509.21.11945-7. Online ahead of print.

ABSTRACT

BACKGROUND: Aortic and mitral valve replacement are commonly performed by cardiovascular surgeons, but little data quantitatively analyzes the etiology and prevalence of medical malpractice litigations involving these operations. This study aims to analyze incidence, cause, and resolution of medical malpractice lawsuits involving aortic and mitral valve replacements, alone and in combination with coronary artery bypass and/or aortic procedures.

METHODS: The Westlaw legal database was utilized to compile relevant litigations across the United States from 1994-2019. Clinical data, verdict data, demographic data, and litigation attributes were compiled. Fisher-exact tests and Mann-Whitney tests were performed for statistical analyses.

RESULTS: One hundred four malpractice litigations involving aortic valve replacement and 55 litigations involving mitral valve replacement were included in this analysis. The mean age of patients was 55.2 years and proportion of female patients was 32.7% in aortic valve replacements litigations, compared to a mean age of 54.1 years and female patients in 61.8% of mitral valve replacements litigations. Significant relationships exist between an alleged failure to monitor the patient and defendant verdicts (p=0.01), delayed treatment and defendant verdicts (p=0.04), and incidence of infective endocarditis and plaintiff verdicts (p=0.04) in aortic valve replacement litigations. Similarly, significant relationships exist between an alleged failure to diagnose and settlement verdicts (p=0.047), and stroke incidence and defendant verdicts (p=0.03) in mitral valve replacement litigations.

CONCLUSIONS: In addition to excellent surgeon patient/family communication, administering surgical treatment in a timely manner, diagnosing and acting on concomitant medical conditions, and close patient monitoring may diminish medical malpractice litigation involving aortic and mitral valve replacement operations.

PMID:34338496 | DOI:10.23736/S0021-9509.21.11945-7

Minerva Cardiol Angiol. 2021 Aug 2. doi: 10.23736/S2724-5683.21.05709-4. Online ahead of print.

ABSTRACT

This paper reviews recent cardiology literature and reports how Artificial Intelligence Tools (specifically, Machine Learning techniques) are being used by physicians in the field. Each technique is introduced with enough details to allow the understanding of how it works and its intent, but without delving into details that do not add immediate benefits and require expertise in the field. We specifically focus on the principal Machine Learning based risk scores used in cardiovascular research. After introducing them and summarizing their assumptions and biases, we discuss their merits and shortcomings. We report on how frequently they are adopted in the field and suggest why this is the case based on our expertise in Machine Learning. We complete the analysis by reviewing how corresponding statistical approaches compare with them. Finally, we discuss the main open issues in applying Machine Learning tools to cardiology tasks, also drafting possible future directions. Despite the growing interest in these tools, we argue that there are many still underutilized techniques: while Neural Networks are slowly being incorporated in cardiovascular research, other important techniques such as Semi-Supervised Learning and Federated Learning are still underutilized. The former would allow practitioners to harness the information contained in large datasets that are only partially labeled, while the latter would foster collaboration between institutions allowing building larger and better models.

PMID:34338485 | DOI:10.23736/S2724-5683.21.05709-4

JBRA Assist Reprod. 2021 Aug 2;0(0):0. doi: 10.5935/1518-0557.20210033. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the length of exposure to high doses of phthalate that might affect sperm quality in adult male Wistar rats.

METHODS: Forty-two (42) adult male Wistar rats (weighing 150-200 g) were randomly assigned into six groups (n=7): Group A received 0.5 mL of distilled water – placebo – and served as controls; groups B, C, D, E and F received Phthalate (750 mg/kgbw) for 1, 3, 5, 7 and 9 weeks, respectively. The data obtained from the study was expressed as Mean ± SEM with a p-value <0.05 considered significant. The data was analyzed with one-way analysis of variance (ANOVA) followed by Tukey’s post-hoc test using GraphPad Prism, version 8.

RESULTS: The results showed a statistically significant (p<0.05) decrease in testicular weight in the rats exposed to 750 mg/kg of phthalate for 3, 5, 7 and 9 weeks when compared with the controls. Sperm count, motility and viability were also significantly (p<0.05) reduced, while sperm cells with abnormal morphology had increased counts in the groups exposed for 3, 5, 7 and 9 weeks when compared with controls. Serum zinc and magnesium were also significantly reduced (p<0.05) in the subjects treated for 1, 3, 5, 7 and 9 weeks when compared with controls.

CONCLUSIONS: The dosage of phthalate adopted in this study was deleterious to testicular function when rats were exposed to it for as short a period as three weeks.

PMID:34338483 | DOI:10.5935/1518-0557.20210033

Przegl Epidemiol. 2021;75(1):108-118. doi: 10.32394/pe.75.11.

ABSTRACT

INTRODUCTION: Cardiovascular diseases are the main death cause in Poland. Several clinical studies showed association between metabolic syndrome and higher prevalence of diabetes mellitus, cardiac events and mortality. The aim of the study was to estimate cardiovascular complications and death risk in subjects with metabolic syndrome (MS) working in agriculture.

MATERIAL AND METHODS: The study included 332 people working in agriculture in Lodz voivodeship, 231 with MS and 101 healthy ones. Increased risk of cardiovascular complications was determined for pulse pressure (pp) >63 mmHg. Based on the SCORE index, 10-year death risk due to cardiovascular complications was estimated taking into account sex, age, smoking, systolic blood pressure and total cholesterol concentration. A value ≥5% was accepted as high risk of death within 10 years.

RESULTS: Increased risk of cardiovascular complications (pulse pressure >63 mmHg) was found in 31.60% subjects with MS and 6.93% healthy ones.

CONCLUSIONS: High risk of cardiovascular complications and death occurs statistically more frequently in subjects with MS than in the rest of the population.

PMID:34338476 | DOI:10.32394/pe.75.11

Przegl Epidemiol. 2021;75(1):86-95. doi: 10.32394/pe.75.09.

ABSTRACT

INTRODUCTION: Healthcare-associated infections (HCAIs) are a global health problem, and the problem of HCAIs in Ukraine remains poorly understood because of problems with the registration system.

OBJECTIVE: To analyze the official data of the number of registered HCAIs in Ukraine for the period 2009-2019, compare them with the available data in scientific publications.

MATERIAL AND METHODS: Statistical analysis of information from the “Laboratory Centers of the Ministry of Health of Ukraine” kindly provided by the State Institution “Public Health Center of the Ministry of Health of Ukraine”.

RESULTS: In 2019, 2,611 cases of HCAIs were registered, the lowest annual number of registered HCAIs in the last twelve years. The maximum number of HCAIs in 2011 was 7,448. An average of 5,089±756 cases of HCAIs has been registered annually. By age structure, the average for 2009-2019 was 78.0±5.8 % for adults and 22.0 % for children (0-17 y.o.). In 2019 13.8% of registered potential HCAIs agents were identified as MDR, and 80.0-87.0% belongs to the group of 12-17, the most common pathogens.

CONCLUSIONS: The estimated minimum number of HCAIs in Ukraine was expected to be about 1 million per year. Official statistics on registered cases of HCAIs in Ukraine do not reflect reality, so the registration system and investigation of HCAIs in Ukraine needs to be reformed.

PMID:34338474 | DOI:10.32394/pe.75.09

Minerva Surg. 2021 Aug 2. doi: 10.23736/S2724-5691.21.08997-8. Online ahead of print.

ABSTRACT

BACKGROUND: The aim was to evaluate the relevance of pneumoperitoneum on the success rate of non-operative management (NOM) of patients with complicated acute diverticulitis (AD), and the risk factors associated with failure.

METHODS: Observational retrospective cohort study of patients attended at the emergency department for AD from January 2015-August 2019. Patient demographics, blood tests, radiological data and initial treatment strategies were registered. NOM, based on intravenous antibiotics (ATB) and bowel rest, was defined as unsuccessful when emergency surgery (ES) and/or infection-related death took place. Patients initially treated with ES were excluded. Analysis was done with the IBM SPSS statistics 23.0.0.2 software.

RESULTS: According to modified Hinchey and WSES criteria, 99 (12%) of 826 AD episodes were complicated, with pneumoperitoneum on the CT scan in 89 (90.5%). NOM was undertaken in 93 (94%) cases, with a 91.5% success rate. Multivariate analysis revealed ASA class III-IV, and the presence of fluid collections >3cm in diameter, but not distant free air, to be associated with NOM failure. However, the success rate of NOM was significantly higher in patients with pericolic pneumoperitoneum (98.5%) than in those with distant free air (80%) (p=0.02). Risk factors of NOM failure were an advanced age, high CRP and WBC values, and the presence of free fluid in >2 abdominal quadrants.

CONCLUSIONS: NOM in hemodynamically stable patients with complicated AD is a safe and feasible approach, even in the context of distant free air. Nevertheless, patients with isolated pericolic air did better in our series.

PMID:34338467 | DOI:10.23736/S2724-5691.21.08997-8