Japanese Resident Physicians' Attitudes, knowledge, and Perceived Barriers on the Practice of Evidence Based Medicine: a Survey

<p>Abstract</p> <p>Background</p> <p>Evidence based medicine plays a crucial role as a tool that helps integrate research evidence into clinical practice. However, few reports have yet to examine its application in daily practice among resident physicians in Japan. The aim of this study was to assess the attitudes towards and knowledge of EBM among resident physicians in Japanese and determine perceived barriers to its use.</p> <p>Findings</p> <p>A cross-sectional, self-administered anonymous questionnaire was distributed to 60 resident staffs at Saga University Hospital in Japan.</p> <p>Forty residents completed and returned the questionnaire. Fifty four percent of respondents understood the basic terminology of EBM, 3% could explain this to others, and 41% indicated they would like to understand the terminology more. Thirteen percent admitted having a good understanding of EBM basic skills. Fifty respondents indicated having read EBM sources, but only 3% indicated that they use these sources in clinical decision making. The most prominent barriers of EBM application revealed in this study were insufficient time to access the sources, a lack of native language references, and insufficient basic EBM skills, but not scepticism about the EBM concept.</p> <p>Conclusions</p> <p>In general, respondents positively welcomed EBM, and moderately understood and knew basic EBM skill; however, barriers in its application were shown to exist.</p

Cardiac murmurs: echocardiography in the assessment of patients requiring antibiotic prophylaxis for dental treatment

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Traditionally patients who indicate that they have a heart murmur or who indicate that they have had rheumatic fever are given antibiotic prophylaxis for dental treatment. This is commonly done without further assessment of the patient’s actual endocarditis risk. Echocardiography is a noninvasive method of assessing cardiac valve function and haemodynamics. Methods: Consecutive patients who were referred to a private practice oral and maxillofacial surgeon for dentoalveolar surgery and indicated that they had a cardiac problem and usually had antibiotic prophylaxis, were evaluated. Those with a clear indication for prophylaxis, for example had prosthetic heart valves or previous infective endocarditis, received antibiotic prophylaxis. Where there was uncertainty, they were referred for an echocardiogram, and if abnormal, a formal cardiology review. Results: Three hundred and seventy patients out of approximately 20 000 (1.85 per cent) indicated that they had a cardiac murmur and usually received antibiotic prophylaxis for dental treatment between 1 February 1997 and 1 February 2005. Two hundred and sixty-two (71 per cent) were female and 108 (29 per cent) were male; age range 0.7 to 98 years, average 37.6 years. Two hundred and seventy (72 per cent) had normal hearts with no indication for antibiotic prophylaxis. Of the 100 (28 per cent) patients with abnormal findings, they were on average older; 49.5 years, range 0.7 to 87 years. Of these, 50 (14 per cent) met current indications for antibiotic prophylaxis. Conclusion: Patients who present for dental treatment indicating that they require antibiotic prophylaxis for cardiac condition need to be fully evaluated. In this study only 50 of 370 patients (14 per cent) required antibiotic prophylaxis. The remaining 320 (86 per cent) would have no benefit but a risk of adverse reaction to the antibiotic.M. Ching, I. Straznicky and AN Gos

Total dairy consumption in relation to overweight and obesity in children and adolescents: A systematic review and meta-analysis

A systematic review and meta-analysis of cross-sectional and prospective cohort studies was conducted to assess the associations between total dairy consumption and its different subtypes with the prevalence and incidence of overweight, obesity, and overweight/obesity in children and adolescents. A literature search was conducted in Medline through PUBMED and Cochrane Library databases until October 18, 2021. Articles reporting the risk estimates as odd ratios (OR), risk ratios (RR), or hazard ratios and their corresponding 95% confidence interval (CI) for the association between dairy product consumption and the risk of overweight and/or obesity were included. In the meta-analysis from cross-sectional studies, results showed an inverse association between total dairy consumption and obesity prevalence (OR (95% CI): 0.66 (0.48–0.91). No significant associations were found between milk or yogurt and obesity prevalence risk. Regarding prospective studies, total milk consumption was positively associated with overweight prevalence (OR (95% CI): 1.13 (1.01–1.26)) and incidence (RR (95%CI): 1.17 (1.01–1.35)) risk. Evidence from pooled analysis of cross-sectional studies suggested an inverse association between total dairy consumption and obesity. However, there is limited and no conclusive evidence to confirm an inverse relationship from pooled analysis of prospective studies in children and adolescents

Niemann Pick disease: a rare lysosomal storage disease

Niemann Pick Disease (NPD) is a rare autosomal recessive lysosomal storage disease characterized by lysosomal lipid storage. The disease is caused by deficiency of enzyme, acid sphingomyelinase (ASM) which leads to accumulation of sphingomyelin & other lipids in reticuloendothelial cells of various organs like liver, spleen, bone marrow, lymph node, brain, nerves and kidney. Four types of the disease have been identified i.e. A, B, C and D. We report a case of Niemann Pick Disease type C. The patient was a 2.5 years female child who presented with developmental regression, recurrent seizures, failure to thrive and hepatospleenomegaly. Bone marrow (BM) aspiration was performed which showed hypercelluler marrow with few fat laden macrophage resembling foam cell that are characteristics of this disease. BSMMU J 2022; 15(2): 141-14

Rational Design of Protein Stability: Effect of (2S,4R)-4-Fluoroproline on the Stability and Folding Pathway of Ubiquitin

BACKGROUND: Many strategies have been employed to increase the conformational stability of proteins. The use of 4-substituted proline analogs capable to induce pre-organization in target proteins is an attractive tool to deliver an additional conformational stability without perturbing the overall protein structure. Both, peptides and proteins containing 4-fluorinated proline derivatives can be stabilized by forcing the pyrrolidine ring in its favored puckering conformation. The fluorinated pyrrolidine rings of proline can preferably stabilize either a C(γ)-exo or a C(γ)-endo ring pucker in dependence of proline chirality (4R/4S) in a complex protein structure. To examine whether this rational strategy can be generally used for protein stabilization, we have chosen human ubiquitin as a model protein which contains three proline residues displaying C(γ)-exo puckering. METHODOLOGY/PRINCIPAL FINDINGS: While (2S,4R)-4-fluoroproline ((4R)-FPro) containing ubiquitinin can be expressed in related auxotrophic Escherichia coli strain, all attempts to incorporate (2S,4S)-4-fluoroproline ((4S)-FPro) failed. Our results indicate that (4R)-FPro is favoring the C(γ)-exo conformation present in the wild type structure and stabilizes the protein structure due to a pre-organization effect. This was confirmed by thermal and guanidinium chloride-induced denaturation profile analyses, where we observed an increase in stability of -4.71 kJ·mol(-1) in the case of (4R)-FPro containing ubiquitin ((4R)-FPro-ub) compared to wild type ubiquitin (wt-ub). Expectedly, activity assays revealed that (4R)-FPro-ub retained the full biological activity compared to wt-ub. CONCLUSIONS/SIGNIFICANCE: The results fully confirm the general applicability of incorporating fluoroproline derivatives for improving protein stability. In general, a rational design strategy that enforces the natural occurring proline puckering conformation can be used to stabilize the desired target protein

Upregulation of Hemoglobin Expression by Oxidative Stress in Hepatocytes and Its Implication in Nonalcoholic Steatohepatitis

Recent studies revealed that hemoglobin is expressed in some non-erythrocytes and it suppresses oxidative stress when overexpressed. Oxidative stress plays a critical role in the pathogenesis of non-alcoholic steatohepatitis (NASH). This study was designed to investigate whether hemoglobin is expressed in hepatocytes and how it is related to oxidative stress in NASH patients. Analysis of microarray gene expression data revealed a significant increase in the expression of hemoglobin alpha (HBA1) and beta (HBB) in liver biopsies from NASH patients. Increased hemoglobin expression in NASH was validated by quantitative real time PCR. However, the expression of hematopoietic transcriptional factors and erythrocyte specific marker genes were not increased, indicating that increased hemoglobin expression in NASH was not from erythropoiesis, but could result from increased expression in hepatocytes. Immunofluorescence staining demonstrated positive HBA1 and HBB expression in the hepatocytes of NASH livers. Hemoglobin expression was also observed in human hepatocellular carcinoma HepG2 cell line. Furthermore, treatment with hydrogen peroxide, a known oxidative stress inducer, increased HBA1 and HBB expression in HepG2 and HEK293 cells. Importantly, hemoglobin overexpression suppressed oxidative stress in HepG2 cells. We concluded that hemoglobin is expressed by hepatocytes and oxidative stress upregulates its expression. Suppression of oxidative stress by hemoglobin could be a mechanism to protect hepatocytes from oxidative damage in NASH

The Bacterial Defensin Resistance Protein MprF Consists of Separable Domains for Lipid Lysinylation and Antimicrobial Peptide Repulsion

Many bacterial pathogens achieve resistance to defensin-like cationic antimicrobial peptides (CAMPs) by the multiple peptide resistance factor (MprF) protein. MprF plays a crucial role in Staphylococcus aureus virulence and it is involved in resistance to the CAMP-like antibiotic daptomycin. MprF is a large membrane protein that modifies the anionic phospholipid phosphatidylglycerol with l-lysine, thereby diminishing the bacterial affinity for CAMPs. Its widespread occurrence recommends MprF as a target for novel antimicrobials, although the mode of action of MprF has remained incompletely understood. We demonstrate that the hydrophilic C-terminal domain and six of the fourteen proposed trans-membrane segments of MprF are sufficient for full-level lysyl-phosphatidylglycerol (Lys-PG) production and that several conserved amino acid positions in MprF are indispensable for Lys-PG production. Notably, Lys-PG production did not lead to efficient CAMP resistance and most of the Lys-PG remained in the inner leaflet of the cytoplasmic membrane when the large N-terminal hydrophobic domain of MprF was absent, indicating a crucial role of this protein part. The N-terminal domain alone did not confer CAMP resistance or repulsion of the cationic test protein cytochrome c. However, when the N-terminal domain was coexpressed with the Lys-PG synthase domain either in one protein or as two separate proteins, full-level CAMP resistance was achieved. Moreover, only coexpression of the two domains led to efficient Lys-PG translocation to the outer leaflet of the membrane and to full-level cytochrome c repulsion, indicating that the N-terminal domain facilitates the flipping of Lys-PG. Thus, MprF represents a new class of lipid-biosynthetic enzymes with two separable functional domains that synthesize Lys-PG and facilitate Lys-PG translocation. Our study unravels crucial details on the molecular basis of an important bacterial immune evasion mechanism and it may help to employ MprF as a target for new anti-virulence drugs

The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder

Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either 'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of 'reactive' or 'endogenous' subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of 'reactive' and 'endogenous' depression. We then translated these findings to clinical samples using a human post-mortem mRNA study

Social dilemmas among unequals

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this record.Direct reciprocity is a powerful mechanism for evolution of cooperation, based on repeated interactions. It requires that interacting individuals are sufficiently equal, such that everyone faces similar consequences when they cooperate or defect. Yet inequality is ubiquitous among humansand is generally considered to undermine cooperation and welfar. Most previous models of reciprocity neglect inequality. They assume that individuals are the same in all relevant aspects. Here we introduce a general framework to study direct reciprocity among unequals. Our model allows for multiple sources of inequality. Subjects can differ in their endowments, their productivities, and in how much they benefit from public goods. We find that extreme inequality prevents cooperation. But if subjects differ in productivity, some endowment inequality can be necessary for cooperation to prevail. Our mathematical predictions are supported by a behavioral experiment where we vary the subjects’ endowments and their productivities. We observe that overall welfare is maximized when the two sources of heterogeneity are aligned, such that more productive individuals receive higher endowments. In contrast, when endowments and productivities are misaligned, cooperation quickly breaks down. Our findings have implications for policy-makers concerned with equity, efficiency, and public goods provisioning.European Research Council Start GrantGraph GamesAustrian Science Fund (FWF)Office of Naval ResearchJohn Templeton FoundationISTFELLOW program

Chemotherapeutic Sensitization of Leptomycin B Resistant Lung Cancer Cells by Pretreatment with Doxorubicin

The development of novel targeted therapies has become an important research focus for lung cancer treatment. Our previous study has shown leptomycin B (LMB) significantly inhibited proliferation of lung cancer cells; however, p53 wild type lung cancer cells were resistant to LMB. Therefore, the objective of this study was to develop and evaluate a novel therapeutic strategy to sensitize LMB-resistant lung cancer cells by combining LMB and doxorubicin (DOX). Among the different treatment regimens, pretreatment with DOX (pre-DOX) and subsequent treatment with LMB to A549 cells significantly decreased the 50% inhibitory concentration (IC50) as compared to that of LMB alone (4.4 nM vs. 10.6 nM, P<0.05). Analysis of cell cycle and apoptosis by flow cytometry further confirmed the cytotoxic data. To investigate molecular mechanisms for this drug combination effects, p53 pathways were analyzed by Western blot, and nuclear proteome was evaluated by two dimensional-difference gel electrophoresis (2D-DIGE) and mass spectrometry. In comparison with control groups, the levels of p53, phospho-p53 (ser15), and p21 proteins were significantly increased while phospho-p53 (Thr55) and survivin were significantly decreased after treatments of pre-DOX and LMB (P<0.05). The 2D-DIGE/MS analysis identified that sequestosome 1 (SQSTM1/p62) had a significant increase in pre-DOX and LMB-treated cells (P<0.05). In conclusion, our results suggest that drug-resistant lung cancer cells with p53 wild type could be sensitized to cell death by scheduled combination treatment of DOX and LMB through activating and restoring p53 as well as potentially other signaling pathway(s) involving sequestosome 1