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Repeated Ivermectin Treatment Induces Ivermectin Resistance in Strongyloides ratti by Upregulating the Expression of ATP-Binding Cassette Transporter Genes

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

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UHPLC-MS-based metabolomics and chemoinformatics study reveals the neuroprotective effect and chemical characteristic in Parkinson’s disease mice after oral administration of Wen-Shen-Yang-Gan decoction

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

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A review of machine learning for cardiology

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

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Medical malpractice in aortic valve and mitral valve replacement surgery in North America

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

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Assessment of cardiovascular risk in patients with metabolic syndrome working in the agricultural sector

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

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Duration-dependent effects of high dose of phthalate exposure on semen quality in adult male rats

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

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Epidemiological and microbiological aspects of healthcare-associated infections in Ukraine during the 2009-2019 period

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

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Short-term outcomes after laparoscopic right hemicolectomy for colon cancer: intracorporeal versus extracorporeal anastomosis

Minerva Surg. 2021 Aug 2. doi: 10.23736/S2724-5691.21.08934-6. Online ahead of print.

ABSTRACT

BACKGROUND: The purpose of this study was to compare the short-term outcomes of laparoscopic right hemicolectomy between intracorporeal (IA) and extracorporeal (EA) anastomosis techniques.

METHODS: A retrospective chart review of 77 consecutive patients who underwent laparoscopic right hemicolectomy from January 2016 to June 2018 was performed. The intracorporeal group included 36 patients and the extracorporeal group 41 patients.

RESULTS: Patient demographics and disease-related characteristics were similar. Mean operative time was 152±38.3 minutes in IA vs. 148±34.8 minutes in EA (p = 0.664). IA was not associated with less overall postoperative complications and decreased rate of surgical site infections. There was no statistically significant difference in the incidence of postoperative leak, length of stay, mortality in both groups. There was no perioperative difference in median number of lymph node harvested. There was statistically significant difference in the length of larger incision [50 (50-70) mm in IA vs 80 (70-100) mm in EA; p<0.001], length of the specimen (323 ±52.7 mm in IA vs 295±64.7 mm in EA; p<0.05), free tumor margin (113.6±47.4 in IA vs 75.6±37.4 mm in EA; p<0.001). There was a statistically significant difference in IA in the less postoperative use of analgesics (p<0.032), and return of bowel function (p<0.021).

CONCLUSIONS: IA seems feasible and safe; it does not significantly affect the length of surgery, and it guarantees maintenance of radical oncological standards. Furthermore, IA significantly improves cosmesis and patient comfort postoperatively, reducing the rates of emesis, which leads to higher rates of early regular diet tolerance. Therefore, laparoscopic right hemicolectomy with intracorporeal anastomosis is associated with improved short-term outcomes.

PMID:34338461 | DOI:10.23736/S2724-5691.21.08934-6

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Relevance of pneumoperitoneum in the conservative approach to complicated acute diverticulitis. A retrospective study identifying risk factors associated with treatment failure

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

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Learning curve for completely thoracoscopic anatomic sublobar resection

Minerva Surg. 2021 Aug 2. doi: 10.23736/S2724-5691.21.08895-X. Online ahead of print.

ABSTRACT

BACKGROUND: Minimally invasive anatomic sublobar resection is increasingly being considered as an alternative to lobectomy in selected cases. However, this remains a technically challenging procedure and only 5 studies evaluating learning curves have been published to date. The aim of this study was to evaluate a single surgeon’s learning curve for completely thoracoscopic anatomic sublobar resection.

METHODS: A retrospective review was conducted of all thoracoscopic anatomic sublobar resections by one surgeon proficient in VATS lobectomy between January 2015 and January 2020. The primary outcome was operative time. Secondary outcomes were perioperative complications, duration of chest tube drainage and length of stay.

RESULTS: There were 67 thoracoscopic anatomic sublobar resections performed in 66 patients. A Time-series plot and Cumulative Sum analysis of operative times showed a drop off after case 32, suggesting achievement of competency. After case 32, mean operative times were decreased (128,59+/- 32,42min. vs 153,63+/-40,16 min, p=0,013) and there was a trend toward decreased blood loss (124,26+/- 76,0 vs 175,0ml+/-141,99, p=0,073). 13,6% of patients had postoperative complications other than air leak and 88,9% of these were Clavien-Dindo class 1-2; postoperative complications were evenly distributed before and after case 32. Cumlulative Sum curves for the duration of chest tube drainage and length of stay did not show any significant change during the study period.

CONCLUSIONS: This study suggests that for a surgeon proficient in VATS lobectomy, competency in completely thoracoscopic anatomic sublobar resection can be achieved after 32 cases and can be accomplished in a way that does not compromise perioperative outcomes.

PMID:34338457 | DOI:10.23736/S2724-5691.21.08895-X