Category: Nevin Manimala

JMIR Med Educ. 2021 Jun 10;7(2):e22745. doi: 10.2196/22745.

ABSTRACT

BACKGROUND: Shared decision-making (SDM) is a process in which clinicians and patients work together to select tests, treatments, management, or support packages based on clinical evidence and the patient’s informed preferences. Similar to any skill, SDM requires practice to improve. Virtual patients (VPs) are simulations that allow one to practice a variety of clinical skills, including communication. VPs can be used to help professionals and students practice communication skills required to engage in SDM; however, this specific focus has not received much attention within the literature. A multiple-choice VP was developed to allow students the opportunity to practice SDM. To interact with the VP, users chose what they wanted to say to the VP by choosing from multiple predefined options, rather than typing in what they wanted to say.

OBJECTIVE: This study aims to evaluate a VP workshop for medical students aimed at developing the communication skills required for SDM.

METHODS: Preintervention and postintervention questionnaires were administered, followed by semistructured interviews. The questionnaires provided cohort-level data on the participants’ views of the VP and helped to inform the interview guide; the interviews were used to explore some of the data from the questionnaire in more depth, including the participants’ experience of using the VP.

RESULTS: The interviews and questionnaires suggested that the VP was enjoyable and easy to use. When the participants were asked to rank their priorities in both pre- and post-VP consultations, there was a change in the rank position of respecting patient choices, with the median rank changing from second to first. Owing to the small sample size, this was not analyzed for statistical significance. The VP allowed the participants to explore a consultation in a way that they could not with simulated or real patients, which may be part of the reason that the VP was suggested as a useful intervention for bridging from the early, theory-focused years of the curriculum to the more patient-focused ones later.

CONCLUSIONS: The VP was well accepted by the participants. The multiple-choice system of interaction was reported to be both useful and restrictive. Future work should look at further developing the mode of interaction and explore whether the VP results in any changes in observed behavior or practice.

PMID:34110299 | DOI:10.2196/22745

Phys Rev Lett. 2021 May 21;126(20):201102. doi: 10.1103/PhysRevLett.126.201102.

ABSTRACT

The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.

PMID:34110215 | DOI:10.1103/PhysRevLett.126.201102

J Phys Chem B. 2021 Jun 10. doi: 10.1021/acs.jpcb.1c00898. Online ahead of print.

ABSTRACT

We use Langevin dynamics simulations to model, at an atomistic resolution, how various natively knotted proteins are unfolded in repeated allosteric translocating cycles of the ClpY ATPase. We consider proteins representative of different topologies, from the simplest knot (trefoil 3₁), to the three-twist 5₂ knot, to the most complex stevedore, 6₁, knot. We harness the atomistic detail of the simulations to address aspects that have so far remained largely unexplored, such as sequence-dependent effects on the ruggedness of the landscape traversed during knot sliding. Our simulations reveal the combined effect on translocation of the knotted protein structure, i.e., backbone topology and geometry, and primary sequence, i.e., side chain size and interactions, and show that the latter can dominate translocation hindrance. In addition, we observe that due to the interplay between the knotted topology and intramolecular contacts the transmission of tension along the polypeptide chain occurs very differently from that of homopolymers. Finally, by considering native and non-native interactions, we examine how the disruption or formation of such contacts can affect the translocation processivity and concomitantly create multiple unfolding pathways with very different activation barriers.

PMID:34110163 | DOI:10.1021/acs.jpcb.1c00898

J Sports Med Phys Fitness. 2021 Jun;61(6):844-850. doi: 10.23736/S0022-4707.20.11382-3.

ABSTRACT

BACKGROUND: Cardiovascular diseases (CVD) are still a leading cause of death worldwide. The modification of risk factors and lifestyle is more important than pharmacotherapy and it is the most effective way to combat cardiovascular diseases. Recommendations to undertake physical activity are vital to the prevention of cardiovascular diseases. The aim of the study was to analyze the impact of physical activity on the modifiable risk factors of cardiovascular diseases.

METHODS: Seventy-six participants, including 38 men, with a mean age of 37±9 were enrolled into the study in 2012-2013. Six months of advanced personal training program “You can be a marathon runner too” (twice a week for 3-4 hours) was carried out. Advice on healthy eating and changes in lifestyle were given. The following parameters: body composition analysis, Body Mass Index, lipids profile, glucose and morphology were measured twice at the beginning and after 6 months of the study. The data were statistically analyzed.

RESULTS: A positive trend in some parameters was observed in all the respondents. The BMI decreased from 25 kg/m² to 23 kg/m² and the percentage of body fat – from 25% to 21%. Furthermore, some blood parameters decreased: cholesterol from 217mg/dL to 196mg/dL, triglycerides from 128 mg/dL to 97 mg/dL, and glucose from 82 mg/dL to 79 mg/dL. However, HDL increased from 66 mg/dL to 75 mg/dL.

CONCLUSIONS: Regular physical activity has a positive influence on lowering the risk factors of cardiovascular diseases. Encouraging the implementation of behavioral changes and greater everyday physical activity may contribute to maintaining health for a long time.

PMID:34110121 | DOI:10.23736/S0022-4707.20.11382-3

Cancer Med. 2021 Jun 10. doi: 10.1002/cam4.4021. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study was to determine the impact of prehabilitation exercise intervention with respect to (1) acceptability, feasibility, and safety; and (2) physical function, measured by 6-minute-walk test (6MWT).

DATA SOURCES: PRISMA guidelines were used to systematically search PubMed, Embase, and CINAHL databases evaluating prehabilitation exercise interventions.

STUDY SELECTION: The inclusion criteria were studies investigating patients who underwent surgery for their cancer and underwent prehabilitation exercise.

DATA EXTRACTION AND SYNTHESIS: Guidelines were applied by independent extraction by multiple observers. Data were pooled using a random-effects model.

MAIN OUTCOME(S) AND MEASURE(S): Acceptability, feasibility, and safety rates were calculated. 6MWT (maximum distance a person can walk at their own pace on a hard, flat surface, measured in meters, with longer distance indicative of better performance status) was compared using two arms using the DerSimonian and Laird method.

RESULTS: Objective 1. Across 21 studies included in this review, 1564 patients were enrolled, 1371 (87.7%) accepted the trial; of 1371, 1230 (89.7% feasibility) completed the intervention. There was no grade 3+ toxicities. Objective 2. Meta-analysis of five studies demonstrated a statistically significant decrease in 6MWT distance postoperatively in the control group (mean difference = +27.9 m; 95% confidence interval (CI): 9.3; 46.6) and a significant improvement postoperatively in the prehabilitation group (mean difference = -24.1 m; 95% CI: -45.7; -2.6). Meta-analysis demonstrated improvements in 6MWT distance 4-8 weeks postoperatively in the prehabilitation group compared to the control group (mean difference = -58.0 m, 95% CI: -92.8; -23.3).

CONCLUSIONS AND RELEVANCE: Prehabilitation exercise for cancer patients undergoing surgery was found to be safe, acceptable, and feasible with a statistically significant improvement in the 6MWT, indicating that prehabilitation can improve postoperative functional capacity.

PMID:34110101 | DOI:10.1002/cam4.4021

Cancer Commun (Lond). 2021 Jun 10. doi: 10.1002/cac2.12164. Online ahead of print.

ABSTRACT

BACKGROUND: Y-box binding protein 1 (YB1 or YBX1) plays a critical role in tumorigenesis and cancer progression. However, whether YB1 affects malignant transformation by modulating non-coding RNAs remains largely unknown. This study aimed to investigate the relationship between YB1 and microRNAs and reveal the underlying mechanism by which YB1 impacts on tumor malignancy via miRNAs-mediated regulatory network.

METHODS: The biological functions of YB1 in hepatocellular carcinoma (HCC) cells were investigated by cell proliferation, wound healing, and transwell invasion assays. The miRNAs dysregulated by YB1 were screened by microarray analysis in HCC cell lines. The regulation of YB1 on miR-205 and miR-200b was determined by quantitative real-time PCR, dual-luciferase reporter assay, RNA immunoprecipitation, and pull-down assay. The relationships of YB1, DGCR8, Dicer, TUT4, and TUT1 were identified by pull-down and coimmunoprecipitation experiments. The cellular co-localization of YB1, DGCR8, and Dicer were detected by immunofluorescent staining. The in vivo effect of YB1 on tumor metastasis was determined by injecting MHCC97H cells transduced with YB1 shRNA or shControl via the tail vein in nude BALB/c mice. The expression levels of epithelial to mesenchymal transition markers were detected by immunoblotting and immunohistochemistry assays.

RESULTS: YB1 promoted HCC cell migration and tumor metastasis by regulating miR-205/200b-ZEB1 axis partially in a Snail-independent manner. YB1 suppressed miR-205 and miR-200b maturation by interacting with the microprocessors DGCR8 and Dicer as well as TUT4 and TUT1 via the conserved cold shock domain. Subsequently, the downregulation of miR-205 and miR-200b enhanced ZEB1 expression, thus leading to increased cell migration and invasion. Furthermore, statistical analyses on gene expression data from HCC and normal liver tissues showed that YB1 expression was positively associated with ZEB1 expression and remarkably correlated with clinical prognosis.

CONCLUSION: This study reveals a previously undescribed mechanism by which YB1 promotes cancer progression by regulating the miR-205/200b-ZEB1 axis in HCC cells. Furthermore, these results highlight that YB1 may play biological functions via miRNAs-mediated gene regulation, and it can serve as a potential therapeutic target in human cancers.

PMID:34110104 | DOI:10.1002/cac2.12164

Cancer Sci. 2021 Jun 10. doi: 10.1111/cas.15020. Online ahead of print.

ABSTRACT

Despite immune checkpoint inhibitors(ICIs) have achieved unprecedented success in dMMR tumours, pMMR tumors accounting for 85% of colorectal cancer(CRC) cases remains unresponsive. Lactate dehydrogenase A(LDH-A) is the rate-limiting enzyme that catalyses the transformation of pyruvate to lactate in the process of glycolysis. We investigate the relationship between LDH-A and dMMR with the purpose of exploring the treatment strategy for pMMR CRC patients . We herein show that LDH-A can promote the proliferation of dMMR and pMMR CRC cells by positively regulating MMR proteins both in vitro and in vivo. LDH-A inhibition can improve the efficacy of PD-1 blockade in pMMR CRC xenograft model.. A statistical analysis of 186 CRC specimens showed a significant correlation between LDH-A and dMMR status. Moreover, patients with both low LDH-A expression and dMMR exhibited better disease free survival than patients with other combinations. The close correlation of LDH-A and dMMR may offer the promising therapeutic strategy that combination of LDH-A inhibitor and ICIs may improve the clinical benefit for pMMR CRC patients.

PMID:34110068 | DOI:10.1111/cas.15020

Wound Repair Regen. 2021 Jun 10. doi: 10.1111/wrr.12948. Online ahead of print.

ABSTRACT

Complex surgery of abdominal wall hernia continues to bear the major concern of wound healing disorders. Technical modifications have not been able to sufficiently prevent wound healing impairments or infections, even in clean elective cases, especially when dealing with large-scale hernia defects. Incisional negative pressure wound therapy (iNPWT) in its intentional use as a preventive tool has recently found its way from theoretical and experimental advantages to the clinical routine. Different indications have been defined but evidence is lacking. We performed a retrospective analysis (1/2014-5/2019) of all ventral hernia repairs (n = 386) done in our institution as open sublay mesh reinforcement, partially requiring component separation (CS), receiving iNPWT in selected cases based on single surgeon experience. Pre- and perioperative data included patient and hernia characteristics as well as the employed mesh sizes. Postoperative follow-up (median 38.5 months [interquartile range: 23.4, 53.3]) extended beyond patient dismissal and included the rate of re-admission due to wound healing disorders. The primary outcome was the incidence of surgical site occurrences (SSO). Secondary endpoints included wound-related readmissions, reoperations and recurrences. Patients were matched based on propensity scores in a 1:1 ratio. Propensity scores were calculated based on five preoperative variables, including sex, body-mass-index, American Society of Anesthesiology classification, recurrent hernia repair and operation technique, to identify significant parameters. The rate of SSO was 12% (n = 46) for all operated cases, and the rate of surgical site infection (SSI) was 8.8% (n = 34). In the subgroup of CS (n = 40), the rate increased to 15% (n = 6). The usage of iNPWT (n = 54) led to an in-hospital SSO rate of 14.8% (n = 8) but increased to 33.3% (n = 18) when including the re-admission rate. The SSI rate for the iNPWT cohort was 14.8% (n = 8) with a consecutive need for reoperation (Clavien-Dindo IIIb) in 87.5% (n = 7). In the matched-pair analysis, the hernia-size and mesh-size were the main risk factors for SSO. The use of iNPWT significantly reduced this statistical effect (p = 0.405). In a large and representative patient cohort, we were able to demonstrate that the advantage of iNPWT used after complex abdominal wall repair does not come first hand. Especially in the follow-up, we found a relevant increase in wound healing problems after dismissal. To proof the benefit of iNPWT in these heterogeneous patients, we could identify hernia size and mesh size as individual risk factors that were nihilated by the use of iNPWT. We found it to be favourable to use iNPWT when mesh-size exceeded 450 cm² .

PMID:34110077 | DOI:10.1111/wrr.12948

Indoor Air. 2021 Jun 10. doi: 10.1111/ina.12867. Online ahead of print.

ABSTRACT

Although solid fuel use has been increasingly linked to cardiovascular events (CVEs), conclusions have been inconsistent. We systematically searched 3 databases (PubMed, Embase, and Web of Science) up to July 3, 2020, to identify English language reports that assessed the association of solid fuel use with CVEs. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated with a random-effects model. Subgroup analyses and sensitivity analyses were conducted to explore the potential sources of heterogeneity and to test the stability of the results. We finally included 13 observational studies (8 cohort, 3 cross-sectional, and 2 case-control studies comprising 791,220 participants) in the meta-analysis. The risk of CVEs was increased 21% with the highest versus the lowest solid fuel use (highest/lowest, RR_pooled = 1.21, 95% CI: 1.10-1.34). As for the subgroup analyses on study design, the pooled RR for cohort studies, case-control studies, and cross-sectional studies were 1.11 (95%CI: 1.03-1.19), 4.80 (95%CI: 2.22-10.39), and 1.46 (95%CI: 0.82-2.62), respectively. The results of this study suggested that high solid fuel use was associated with increased CVE risk, and that reducing the use of solid fuel will be important for improving the health of the populations in developing countries.

PMID:34110043 | DOI:10.1111/ina.12867

J Anim Physiol Anim Nutr (Berl). 2021 Jun 10. doi: 10.1111/jpn.13588. Online ahead of print.

ABSTRACT

The objectives of this study were to investigate the relationship between the in vitro ruminal ammonia nitrogen (NH₃ -N) concentration and the Cornell Net Carbohydrate and Protein System (CNCPS) N-fractions of feeds for cattle and further compare the performance of developing multiple linear regression (MLR) and artificial neural network (ANN) models in estimating the NH₃ -N concentration in rumen fermentation. Two data sets were established, of which the training data set containing forty-five rations for cattle with concentrate/roughage ratios of 50:50, 40:60, 30:70, 20:80 and 10:90 used for developing models and the test data set containing ten other rations with the same concentrate/roughage ratios with the training data set were used for validating of models. The NH₃ -N concentrations of feed samples were measured using an in vitro incubation technique. The CNCPS N-fractions (g), for example PB₁ (rapidly degraded true protein), PB₂ (neutral detergent soluble nitrogen), PB₃ (acid detergent soluble nitrogen) of rations, were calculated based on chemical analysis. Statistical analysis indicated that the NH₃ -N concentration (mg) was significantly correlated with the CNCPS N-fractions (g) PB₁ , PB₂ and PB₃ in a multiple linear pattern: NH₃ -N = (130.70±33.80) PB₁ + (155.83±17.89) PB₂ – (85.44±37.69) PB₃ + (42.43±1.05), R² = 0.77, p < 0.0001, n = 45. The results indicated that both MLR and ANN models were suitable for predicting in vitro NH₃ -N concentration of rations using CNCPS N-fractions PB₁ , PB₂ , and PB₃ as independent variables while the neural network model showed better performance in terms of greater r² , CCC and lower RMSPE between the observed and predicted values.

PMID:34110053 | DOI:10.1111/jpn.13588