Use of mutant mcm strain in purification of Neurospora crassa transformants resistant to hygromycin

DNA-mediated transformation in Neurospora crassa results in the formation of heterokaryons comprising a mixture of both transformed and untransformed nuclei. This makes it imperative to resolve the transformed nuclei from the untransformed ones. The present methods for purifying the transformed nuclei from primary transformants include repeated plating of macroconidial transformant to enrich the transformed nuclei or producing uninucleate microconidia. Both these methods are labour intensive and time consuming. We report here a simple and efficient method of purifying the transformed nuclei by the induction of microconidiation in an otherwise non-microconidiating strain using a mcm mutant strain

ESTABLISHMENT OF A MECHANISM OF POLYHERBAL FORMULATION FOR ANTI-RHEUMATISM

Objective: A marketed product Dr. Ortho has been used by many patients and is gaining a positive feedback from the patients. A study is designed to establish its mechanism of action on various anti-rheumatic models in experimental animals. No studies have been investigated on this product for its anti-rheumatic activity.Methods: Dr. Ortho (55 mg/kg, p. o.) was administered during adjuvant-induced arthritis, phlogistic agents (Histamine, bradykinin, and serotonin) induced paw edema, Acetic acid induced writhing test in mice, and Eddy's hot plate. Histopathology (T. S. of knee joint) and various hematological parameters (WBC's, RBC's, and ESR count) were observed during the study.Results: Dr. Ortho decreases arthritis induced inflammation by antagonizing or inhibiting the inflammatory mediators, i.e., histamine, 5-hydroxy tryptamine and bradykinin. (20% (P<0.05) of carrageenan, 10.01%, (P<0.05) of histamine, 8% (P<0.05) of 5-hydroxy tryptamine induced paw volume). Dr. Ortho acts as both peripheral and central analgesic. Histopathology findings revealed that there is a reduction in the neutrophil infiltration, pannus formation, and bone. Hematological parameters show that Dr. Ortho decreases the elevated level of the WBC's count.Conclusion: The present study revealed some facts regarding the mechanism of Dr. Ortho in reducing arthritis induced inflammation. However study may be done further to illustrate its complete mechanism.Â

Effect of Intraoperative Goal-directed Balanced Crystalloid versus Colloid Administration on Major Postoperative Morbidity

BACKGROUND: Crystalloid solutions leave the circulation quickly, whereas colloids remain for hours, thus promoting hemodynamic stability. However, colloids are expensive and promote renal toxicity in critical care patients. This study tested the hypothesis that goal-directed colloid administration during elective abdominal surgery decreases 30-day major complications more than goal-directed crystalloid administration. METHODS: In this parallel-arm double-blinded multicenter randomized trial, adults having moderate- to high-risk open and laparoscopically assisted abdominal surgery with general anesthesia were randomly assigned to Doppler-guided intraoperative volume replacement with 6% hydroxyethyl starch 130/0.4 (n = 523) or lactated Ringer's solution (n = 534). The primary outcome was a composite of serious postoperative cardiac, pulmonary, infectious, gastrointestinal, renal, and coagulation complications that were assessed with a generalized estimating equation multivariate model. The primary safety outcome was a change in serum creatinine concentration up to 6 months postoperatively, compared to baseline concentrations. RESULTS: A total of 1,057 patients were included in the analysis. Patients assigned to crystalloid received a median [quartile 1, quartile 3] amount of 3.2 l [2.3, 4.4] of crystalloid, and patients assigned to colloid received 1.0 l [0.5, 1.5] of colloid and 1.8 l [1.2, 2.4] of crystalloid. The estimated intention-to-treat common effect relative risk for the primary composite was 0.90 for colloids versus crystalloids (95% CI: 0.65 to 1.23, P = 0.51), and 18% (91 of 523) of colloid patients and 20% (103 of 534) of crystalloid patients incurred at least one component of the primary outcome composite. There was no evidence of renal toxicity at any time. CONCLUSIONS: Doppler-guided intraoperative hydroxyethyl starch administration did not significantly reduce a composite of serious complications. However, there was also no indication of renal or other toxicity

Predicting hypotension in perioperative and intensive care medicine

Blood pressure is the main determinant of organ perfusion. Hypotension is common in patients having surgery and in critically ill patients. The severity and duration of hypotension are associated with hypoperfusion and organ dysfunction. Hypotension is mostly treated reactively after low blood pressure values have already occurred. However, prediction of hypotension before it becomes clinically apparent would allow the clinician to treat hypotension pre-emptively, thereby reducing the severity and duration of hypotension. Hypotension cannowbepredictedminutes before it actually occurs from the blood pressure waveform using machine-learning algorithms that can be trained to detect subtle changes in cardiovascular dynamics preceding clinically apparent hypotension. However, analyzing the complex cardiovascular system is a challenge because cardiovascular physiology is highly interdependent, works within complicated networks, and is influenced by compensatory mechanisms. Improved hemodynamic data collection and integration will be a key to improve current models and develop new hypotension prediction models. (C) 2019 Elsevier Ltd. All rights reserved

Multimodal Machine Learning for Automated ICD Coding

This study presents a multimodal machine learning model to predict ICD-10 diagnostic codes. We developed separate machine learning models that can handle data from different modalities, including unstructured text, semi-structured text and structured tabular data. We further employed an ensemble method to integrate all modality-specific models to generate ICD-10 codes. Key evidence was also extracted to make our prediction more convincing and explainable. We used the Medical Information Mart for Intensive Care III (MIMIC -III) dataset to validate our approach. For ICD code prediction, our best-performing model (micro-F1 = 0.7633, micro-AUC = 0.9541) significantly outperforms other baseline models including TF-IDF (micro-F1 = 0.6721, micro-AUC = 0.7879) and Text-CNN model (micro-F1 = 0.6569, micro-AUC = 0.9235). For interpretability, our approach achieves a Jaccard Similarity Coefficient (JSC) of 0.1806 on text data and 0.3105 on tabular data, where well-trained physicians achieve 0.2780 and 0.5002 respectively.Comment: Machine Learning for Healthcare 201

Subcostal Anterior Quadratus Lumborum Block Versus Epidural Block for Analgesia in Open Nephrectomy: A Randomized Clinical Trial

BACKGROUND: Epidural block are often used for analgesia after open nephrectomy surgery. Subcostal anterior quadratus lumborum block may be an alternative. We therefore tested the hypothesis that the continuous subcostal anterior quadratus lumborum block is noninferior to epidural block for analgesia in patients having open partial nephrectomies. METHODS: Adults having open partial nephrectomies were randomly allocated to epidural or unilateral subcostal anterior quadratus lumborum block. The joint primary outcomes were opioid consumption measured in morphine equivalents and pain measured on a numeric rating scale (0-10) from postanesthesia care unit (PACU) until 72 hours after surgery. The noninferiority deltas were 30% for opioid consumption and 1 point on a 0-10 scale for pain. Secondary outcomes included patient global assessment of pain management on the third postoperative day, the number of antiemetic medication doses through the third postoperative day, duration of PACU stay, and postoperative duration of hospitalization. RESULTS: Twenty-six patients were randomized to anterior quadratus lumborum block and 29 to epidural analgesia. Neither pain scores nor opioid consumption in the quadratus lumborum patients were noninferior to epidural analgesia. At 72 hours, mean ± standard deviation pain scores in subcoastal anterior quadratus lumborum block and epidural group were 4.7 ± 1.8 and 4.1 ± 1.7, with an estimated difference in pain scores of 0.62 (95% confidence interval [CI], 0.74-1.99; noninferiority P = .21). The median [Q1, Q3] opioid consumption was more than doubled in quadratus lumborum patients at 70 mg [43, 125] versus 30 mg [18, 75] in the epidural group with an estimated ratio of geometric means of 1.69 (95% CI, 0.66-4.33; noninferiority P = .80). Patient global assessment and duration of PACU and hospital stays did not differ significantly in the 2 groups. CONCLUSIONS: We were unable to show that subcostal anterior quadratus lumborum block are noninferior to epidural analgesia in terms of pain scores and opioid consumption for open partial nephrectomies. Effectiveness of novel blocks should be rigorously tested in specific surgical setting before widespread adoption

Treatment of Hepatitis C as Prevention: A Modeling Case Study in Vietnam

Background: Treatment of hepatitis C (HCV) is very effective, achieving a cure in 50–90 % of patients. Besides its own good for individuals, this most likely translates in reduced transmission, but this phenomenon has yet to be fully explored. Methods and Findings: In this mathematical modeling study done in the context of Vietnam, we estimated the public health benefit that HCV therapy for injecting drug users (IDUs) may achieve. Treatment coverage of 25, 50 and 75 % of chronically HCV-infected IDUs (4 years into infection) is predicted to reduce the chronic HCV viremia prevalence respectively by 21, 37 and 50%, 11 years after full scale up to the intended coverage. At a constant 50 % coverage level, earlier treatment, 3, 2, and 1 year into infection is predicted to reduce the chronic HCV viremia prevalence by 46, 60 and 85%. In these later 3 scenarios, for every 100 treatment courses provided, a total of respectively 50, 61 and 94 new infections could be averted. These benefits were projected in the context of current low coverage of methadone maintenance therapy and needles/ syringes exchange programs, and these services expansion showed complementary preventive benefits to HCV therapy. The program treatment commitment associated with the various scenarios is deemed reasonable. Our model projections are robust under adjustment for uncertainty in the model parameter values. Conclusions: In this case study in Vietnam, we project that treatment of HCV for injecting drug users will have a preventative herd effect in addition to curing patients in need for therapy, achieving a substantial reduction in HCV transmission an

Chronic Hepatitis C

The goal of antiviral therapy for patients with chronic hepatitis C virus (HCV) infection is to attain a sustained virologic response (SVR), which is defined as undetectable serum HCV-RNA levels at 6 months after the cessation of treatment. Major improvements in antiviral therapy for chronic hepatitis C have occurred in the past decade. The addition of ribavirin to interferon-alfa therapy and the introduction of pegylated interferon (PEG-IFN) have substantially improved SVR rates in patients with chronic hepatitis C. The optimization of HCV therapy with PEG-IFN and ribavirin continues to evolve. Studies are ongoing that use viral kinetics to tailor therapy to an individual's antiviral response and determine the ideal length of treatment to maximize the chance of SVR. Improved SVR can be achieved with new specific inhibitors that target the HCV NS3/4A protease and the NS5B polymerase. Several long-term follow-up studies have shown that SVR, when achieved, is associated with a very low risk of virologic relapse. Furthermore, antiviral therapy can reduce the morbidity and mortality rates associated with chronic hepatitis C by reducing fibrosis progression, the incidence of cirrhosis, and hepatocellular carcinoma