The probability of treatment success,failure and duration—what can be learned from empirical data to support decision making in clinical practice?

Empirical methods have been found to be superior to clinical judgment for the purpose of correctly identifying patients at risk for treatment failure and, hence, to enhance psychotherapy outcomes. The development and evaluation of an empirical approach aimed at supporting clinical decisions during the course of psychotherapy is described. The tool provides predictions based on a patient‐specific sampling strategy called the nearest neighbors method and on growth curve approaches to model an expected treatment course for each patient. Using session‐by‐session data from an outpatient center in the US (N = 4365), this new empirically derived decision model was evaluated and compared with a clinically based approach loosely based on an adaptation of clinically significant change concepts. The empirically derived decision system was found to be superior to the rational clinically based one in almost all measures of prediction accuracy, indicating its potential to identify patients at risk for treatment failure. Copyright © 2006 John Wiley & Sons, Ltd.     

Reversal to normal anatomy after one-anastomosis/mini gastric bypass,indications and results: a systematic review and meta-analysis

This review evaluates the indications and outcomes of one-anastomosis/mini gastric bypass (OAGB/MGB) reversal to normal anatomy. A systematic literature search and meta-analysis was performed in PubMed, Web of Science, and Scopus for articles published by October 1, 2020, including the keywords “one anastomosis gastric bypass,” “OAGB,” “mini gastric bypass,” “MGB,” “reversal,” “reverse,” “malnutrition,” and “reversal bariatric surgery”. After examining 182 papers involving 11,578 patients, 14 studies were included. A reversal was performed in 119 patients on average 23.6 months after the primary OAGB/MGB surgery. The mean body mass index (BMI) was 22.92 ± 3.47 kg/m² and the mean albumin level was 25.17 ± 4.21 g/L at reversal. The mean length of the common channel (CC) was 383.57 ± 159.35 cm, with a mean biliopancreatic limb (BPL) length of 214.21 ± 48.45 cm. Pooled estimation of the meta-analysis of prevalence studies reported a prevalence of 1% for reversal. The major signs and symptoms of protein-energy malnutrition were the leading causes of the reversal of OAGB/MGB. Bleeding, leakage, and death due to severe liver failure were the most reported complications after reversal, with an overall incidence of 10.9%. In conclusion, OAGB/MGB reversal has a prevalence of 1% and has a complication rate of 10.9%. Protein-energy malnutrition with hypoalbuminemia was the most common etiology. The mean lengths of BPL and CC were reported as 215 cm and 380 cm, respectively, in the cases. Therefore, special attention should be paid to malnutrition in all OAGB/MGB patients during follow-up to prevent severe malnutrition and subsequent increase in reversal procedures.     

Molecular dynamics simulation on the low sensitivity of mutants of NEDD-8 activating enzyme for MLN4924 inhibitor as a cancer drug

MLN4924 is an experimental cancer drug known as inhibitor of NEDD8-activating enzyme (NAE). This anti-tumor candidate is a selective small-molecule inhibitor of NAE which is conjugated to cullin protein on Cullin-RING ligases (CRLs). This covalent modification actives cullin complex to recruit an ubiquitin-charged E2 and leads to downstream target protein polyubiquitination and proteasomal degradation. MLN4924, which can form a covalent adduct with NEDD8, and block NAE at the first step in this pathway, has shown anti-tumor activity in many kinds of cancer cell lines and also xenograft models, including lung cancer, colon cancer, melanoma and lymphoma. The anti-tumor activity of MLN4924 results from inactivation of CLRs, which causes DNA re-replication and inhibition of nuclear factor (NF)-κB signaling, thus leading to cancer cell death. A mutation can reduce the enzyme’s sensitivity to MLN4924. Verma et al. in 2013 studied on molecular dynamics simulation of a mutant A171T and consequently found out that this mutation reduce MLN4924 interaction with DNA Binding site of enzyme as a result of reduction of enzyme affinity to ATP. One year later, in 2014, Wei Xu et al. carried out a research on inhibitor resistant cell lines and revealed that a couple of mutations so called Y352H and I310N leads to enzyme resistance to MLN4924 inhibitor, interestingly, the cause reported was the increase of enzyme affinity to ATP. As in Wei Xu et al. experiment the molecular dynamics simulation was not considered, present study is conducted to identify enzyme mutation mechanism by molecular dynamics approach using advantages of Gromacs software version 4.5.6.     

Highly accelerated,real‐time phase‐contrast MRI using radial k‐space sampling and GROG‐GRASP reconstruction: a feasibility study in pediatric patients with congenital heart disease

Retrospective electrocardiogram‐gated, 2D phase‐contrast (PC) flow MRI is routinely used in clinical evaluation of valvular/vascular disease in pediatric patients with congenital heart disease (CHD). In patients not requiring general anesthesia, clinical standard PC is conducted with free breathing for several minutes per slice with averaging. In younger patients under general anesthesia, clinical standard PC is conducted with breath‐holding. One approach to overcome this limitation is using either navigator gating or self‐navigation of respiratory motion, at the expense of lengthening scan times. An alternative approach is using highly accelerated, free‐breathing, real‐time PC (rt‐PC) MRI, which to date has not been evaluated in CHD patients. The purpose of this study was to develop a 38.4‐fold accelerated 2D rt‐PC pulse sequence using radial k‐space sampling and compressed sensing with 1.5 × 1.5 × 6.0 mm³ nominal spatial resolution and 40 ms nominal temporal resolution, and evaluate whether it is capable of accurately measuring flow in 17 pediatric patients (aortic valve, pulmonary valve, right and left pulmonary arteries) compared with clinical standard 2D PC (either breath‐hold or free breathing). For clinical translation, we implemented an integrated reconstruction pipeline capable of producing DICOMs of the order of 2 min per time series (46 frames). In terms of association, forward volume, backward volume, regurgitant fraction, and peak velocity at peak systole measured with standard PC and rt‐PC were strongly correlated (R² > 0.76; P < 0.001). Compared with clinical standard PC, in terms of agreement, forward volume (mean difference = 1.4% (3.0% of mean)) and regurgitant fraction (mean difference = ?2.5%) were in good agreement, whereas backward volume (mean difference = ?1.1 mL (28.2% of mean)) and peak‐velocity at peak systole (mean difference = ?21.3 cm/s (17.2% of mean)) were underestimated by rt‐PC. This study demonstrates that the proposed rt‐PC with the said spatial resolution and temporal resolution produces relatively accurate forward volumes and regurgitant fractions but underestimates backward volumes and peak velocities at peak systole in pediatric patients with CHD.     

Effects of Fenugreek Seed Extract and Swimming Endurance Training on Plasma Glucose and Cardiac Antioxidant Enzymes Activity in Streptozotocin-induced Diabetic Rats

Objective

Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia condition resulting from defective insulin secretion or resistance insulin action, or both. The purpose of this study was to evaluate the effect of 6 weeks swimming training and Trigonella foenum-graecum seed (fenugreek) extract, alone and in combination, on plasma glucose and cardiac antioxidant enzyme activity of streptozotocin-induced diabetic rats.

Methods

Fifty male Wistar rats were divided into five groups: diabetic control (DC, n = 8); healthy control (HC, n = 11); swimming training (S, n = 11); swimming training + fenugreek seed extract (1.74 g/kg body weight; SF1, n = 11); and swimming training + fenugreek seed extract (0.87 g/kg body weight; SF2, n = 9). Streptozotocin was used for the induction of diabetes. Results were analyzed using one-way analysis of variance followed by Tukey test.

Results

In comparison with the DC group, all groups exhibited a significant decrease in body weight (p < 0.05), except for the HC group. SF1 and HC groups showed significant decreases in plasma glucose levels compared with the DC group (p < 0.05). S, SF1, SF2, and HC groups showed significant elevations in cardiac antioxidant enzymes activity in comparison with the DC group.

Conclusion

The results indicated that the combination of endurance swimming training and fenugreek seed extract can significantly reduce the plasma glucose levels and increase cardiac antioxidant enzymes activity in diabetic rats. Our findings suggest that this combination could be useful for the treatment of hyperglycemia and cardiac oxidative stress induced by diabetes mellitus.     

Disruption of PPT1 or PPT2 causes neuronal ceroid lipofuscinosis in knockout mice

PPT1 and PPT2 encode two lysosomal thioesterases that catalyze the hydrolysis of long chain fatty acyl CoAs. In addition to this function, PPT1 (palmitoyl-protein thioesterase 1) hydrolyzes fatty acids from modified cysteine residues in proteins that are undergoing degradation in the lysosome. PPT1 deficiency in humans causes a neurodegenerative disorder, infantile neuronal ceroid lipofuscinosis (also known as infantile Batten disease). In the current work, we engineered disruptions in the PPT1 and PPT2 genes to create "knockout" mice that were deficient in either enzyme. Both lines of mice were viable and fertile. However, both lines developed spasticity (a "clasping" phenotype) at a median age of 21 wk and 29 wk, respectively. Motor abnormalities progressed in the PPT1 knockout mice, leading to death by 10 mo of age. In contrast, the majority of PPT2 mice were alive at 12 mo. Myoclonic jerking and seizures were prominent in the PPT1 mice. Autofluorescent storage material was striking throughout the brains of both strains of mice. Neuronal loss and apoptosis were particularly prominent in PPT1-deficient brains. These studies provide a mouse model for infantile neuronal ceroid lipofuscinosis and further suggest that PPT2 serves a role in the brain that is not carried out by PPT1.     

Are the results of electrophysiological study different in patients with a pre-excitation syndrome, with and without syncope?

AIMS: Syncope in Wolff-Parkinson-White (WPW) syndrome may reveal an arrhythmic event or is not WPW syndrome related. The aim of the study is to evaluate the results of electrophysiological study in WPW syndrome according to the presence or not of syncope and the possible causes of syncope. METHODS AND RESULTS: Among 518 consecutive patients with diagnosis of WPW syndrome, 71 patients, mean age 34.5 +/- 17, presented syncope. Transoesophageal electrophysiological study in control state and after isoproterenol infusion was performed in the out-patient clinic. Atrioventricular re-entrant tachycardia (AVRT) was more frequently induced than in asymptomatic patients (n = 38, 53.5%, P < 0.01), less frequently than in those with tachycardia; atrial fibrillation (AF) and/or antidromic tachycardia (ATD) was induced in 28 patients (39%) more frequently (P < 0.05) than in asymptomatic patients or those with tachycardia. The incidence of high-risk form [rapid conduction over accessory pathway (AP) and AF or ATD induction] was higher in syncope group (n = 18, 25%, P < 0.001) than in asymptomatic subjects (8%) or those with tachycardias (7.5%). Maximal rate conducted over AP was similar in patients with and without syncope, and higher in patients with spontaneous AF, but without syncope. Results were not age-related. CONCLUSION: Tachycardia inducibility was higher in patients with syncope than in the asymptomatic group. The incidence of malignant WPW syndrome was higher in patients with syncope than in asymptomatic or symptomatic population, but the maximal rate conducted over AP was not higher and another mechanism could be also implicated in the mechanism of syncope.     

Detection of vertical root fractures using digitally enhanced images: reverse‐contrast and colorization

Abstract – Root fracture diagnosis is a clinical difficulty that in most cases can only be detected through radiography. The objective of this study was to compare the diagnostic accuracy of two types of digitally enhanced images (reverse‐contrast and colorization) with original digital radiographies in detecting experimental root fractures. Two hundred extracted single‐rooted human teeth were endodontically instrumented and then divided in two groups, one control group and one test group, including fractured teeth. Vertical root fractures were experimentally made in the fractured group. The digital image of each tooth was taken, using the paralleling technique. There were three groups of images: (i) original, (ii) reverse contrast, and (iii) colorized. Three experienced dental specialists examined the images with no prior knowledge of the distribution of the root fractures. Two‐way analysis of variance was used to assess the differences in accuracy, sensitivity, and specificity of each technique in detecting root fractures. Cohen’s kappa coefficients were calculated to investigate the degree of interobserver agreement. The accuracy, sensitivity, and specificity of original images were 67.4%, 66.7%, and 68%, respectively; these amounts were 61.5%, 61%, and 65.5% in reverse contrast images and 66.4%, 70.7%, and 62% in colorized digital radiography. The original images had the best inter observer kappa coefficients (between 0.45 and 0.55). The results showed that the accuracy of original images is better than reverse contrast and colorized images. Use of reverse‐contrast and colorization digital images in root fracture detection should be regarded as an adjunct to other diagnostic methods not as a highly critical diagnostic aid.