Miracle-dz/UniFAR-FTUs huggingface dataset:
Circulating miR‐145 is associated with plasma high‐sensitivity C‐reactive protein in acute ischemic stroke patients

Stroke is a major cerebrovascular disease threatening human health and life with high morbidity, disability and mortality. We aimed to find effective biomarkers for the early diagnosis on stroke. Nine previously reported stroke‐associated miRNAs (miR‐21, miR‐23a, miR‐29b, miR‐124, miR‐145, miR‐210, miR‐221, miR‐223 and miR‐483‐5p) were measured by quantitative real time‐PCR, and plasma high‐sensitivity C‐reactive protein (hs‐CRP) and serum interleukin 6 (IL‐6), the pro‐inflammation markers in brain injury, were examined by enzyme‐linked immunosorbent assay in 146 acute ischemic stroke patients and 96 healthy blood donors. We found that serum miR‐145 was significantly increased within 24 h after stroke onset and serum miR‐23a and miR‐221 were decreased in patients. Moreover, serum miR‐145 was strong positively correlated with plasma hs‐CRP and moderate positively correlated with serum IL‐6. Meanwhile, serum miR‐23a and miR‐221 were moderate negatively correlated with plasma hs‐CRP but not serum IL‐6. Importantly, the combination of hs‐CRP and serum miR‐145 gained a better sensitivity/spectivity for prediction of acute ischemia stroke (area under receiver operating characteristic curve from 0.794 to 0.896). Conclusively, our preliminary findings indicate that serum miR‐145 upregulated in acute ischemic stroke might be a new biomarker for acute ischemia stroke evaluation. Copyright © 2015 John Wiley & Sons, Ltd.
Activation of Toll like receptor 3 induces spermatogonial stem cell apoptosis

Germ cell apoptosis may be associated with the male infertility. The pathogenesis is to be further understood. Viral infection is one of the causative factors of apoptosis of the body cells. This study aims to investigate the role of activation of Toll like receptor (TLR)3 in the induction of germ cell apoptosis. In this study, spermatogonial stem cells (SSC) were isolated from C57BL/6 mouse testes. The expression of TLR3 on SSC was by RT‐qPCR and Western blotting. polyinosinic–polycytidylic acid (Poly I:C) was employed to activate TLR3 on SSCs. The results showed that re‐activation by PolyI:C induced SSC apoptosis. Exposure to PolyI:C induced interferon regulatory factor 3 (IRF3) phosphorylation in SSCs. TLR3 and IRF3 formed a complex in the SSCs. The complex of TLR3/IRF3 bound to the promoter of Fas ligand and promoted Fas ligand expression in SSC, and thus induced SSC apoptosis. In conclusion, the results of the present study indicate that activation of TLR3 by PolyI:C induces the SSC apoptosis, which implies that viral infection may interfere with the male germ cell development. Copyright © 2015 John Wiley & Sons, Ltd.
Involvement of autophagy in the procedure of endoplasmic reticulum stress introduced apoptosis in bone marrow mesenchymal stem cells from nonobese diabetic mice

Recent studies showed that bone marrow mesenchymal stem cells (BM‐MSCs) from nonobese diabetic (NOD) mice exhibited the phenomenon of apoptosis. However, the mechanisms of apoptosis remained largely unknown. In this study, endoplasmic reticulum (ER) stress and autophagy were evidenced in BM‐MSCs from NOD mice for the first time. We found the ER stress‐mediated apoptosis was supported by the up‐regulation of ER stress markers including augmented phosphorylation of phosphorylated protein kinase RNA‐like ER kinase and eukaryotic translation initiator factor 2α as well as cleavage of caspase‐3. Evidence of autophagy included the formation of the acidic vesicular organelles and increase of LC3 accumulation. Intriguingly, blockage of ER stress could reduce the apoptosis of BM‐MSCs from NOD mice and alleviated accumulation of LC3, which indicated that ER stress induced apoptosis and autophagy. Furthermore, our results showed that the mechanism of ER stress‐induced autophagy was associated with the decrease of p‐S6 (a marker of mTOR activity). Here, we demonstrated that ER stress‐induced cell death was mediated by autophagy that was partly attributed to the inactivation of the mammalian target of rapamycin.
Client-reported reasons for non-engagement in drug and alcohol treatment.

INTRODUCTION AND AIMS To examine client-reported reasons for missed early appointments at a drug and alcohol treatment service and to compare characteristics of those who missed appointments with those who attended. DESIGN AND METHODS Clients who missed a first or second appointment between 1 May and 31 August 2007 at a public community-based outpatient treatment facility were invited to participate in a semistructured telephone interview. This consisted of an open-ended question asking the reason(s) for nonattendance, followed by a questionnaire of items for therapeutic alliance and service satisfaction, perceived impact of substance use and previous treatment experience, mostly rated on Likert scales. Database information on demographic and clinical variables was gathered for all clients who were accepted for treatment within the study time frame. Characteristics of those who missed a first or second appointment (n = 66) were compared with those who attended at least their first two appointments (n = 97). RESULTS Of clients who missed their appointments, 80.6% provided reasons for nonattendance, which included extraneous factors (50.0%), service shortcomings (29.7%), no further need for service (16.2%) and motivational ambivalence (4.1%). They generally had high ratings of therapeutic alliance and service satisfaction and identified their substance use as having a negative impact on their lives. Clients who missed appointments were more likely to be male, unmarried and have a history of polysubstance use. DISCUSSION AND CONCLUSIONS Extraneous issues relating to the client may be a dominant obstacle in early treatment engagement. Efforts to overcome these issues may therefore improve early engagement.
OBSERVATIONS ON VITALLY STAINABLE RETICULATION AND CHROMATIC GRANULES IN ERYTHROCYTES PRESERVED IN VITRO

These observations were made with the object of determining whether the vitally staining reticulation of young erythrocytes persists or is lost in blood preserved in vitro. In this manner it was hoped to gain some further information concerning the effect of such preservation on the erythrocyte from the point of view of the value of such cells for transfusion purposes. If it could be shown that preservation of erythrocytes in vitro for several weeks or a month did not reduce the percentage of cells in which the reticulation could be demonstrated by vital staining it might, perhaps, be assumed that the preserved erythrocytes had not aged during the period of preservation and were from this point of view as suitable for transfusion as freshly drawn cells. Rous and Turner 1 obtained the best preservation of human erythrocytes with three parts of blood in two parts of isotonic (3.8 per cent.) sodium
Lin28a enhances in vitro osteoblastic differentiation of human periosteum‐derived cells

Despite a capacity for proliferation and an ability to differentiate into multiple cell types, in long‐term culture and with ageing, stem cells show a reduction in growth, display a decrease in differentiation potential, and enter senescence without evidence of transformation. The Lin28a gene encodes an RNA‐binding protein that plays a role in regulating stem cell activity, including self‐renewal and differentiation propensity. However, the effect of the Lin28a gene on cultured human osteoprecursor cells is poorly understood. In the present study, alkaline phosphatase activity, alizarin red‐positive mineralization, and calcium content, positive indicators of osteogenic differentiation, were significantly higher in cultured human periosteum‐derived cells (hPDCs) with Lin28a overexpression compared with cells without Lin28a overexpression. Lin28a overexpression by hPDCs also increased mitochondrial activity, which is essential for cellular proliferation, as suggested by a reduced presence of reactive oxygen species and significantly enhanced lactate levels and ATP production. Our results suggest that, in hPDCs, the Lin28a gene enhances osteoblastic differentiation and increases mitochondrial activity. Although Lin28a is known as a marker of undifferentiated human embryogenic stem cell, there is limited evidence regarding the influence of Lin28a on osteoblastic differentiation of cultured osteoprecursor cells. This study was to examine the impact of Lin28a on osteogenic phenotypes of human periosteum‐derived cells. Their phenotypes can be similar to those of mesenchymal stem cells. Our results suggest that the Lin28a gene enhances the osteoblastic differentiation of human periosteum‐derived cells. In addition, the Lin28a gene increases mitochondrial activity in human periosteum‐derived cells.
Intoxigenic digital spaces? Youth, social networking sites and alcohol marketing.

INTRODUCTION AND AIMS To examine how young people in New Zealand engage with alcohol and reproduce alcohol marketing messages and alcohol-related branding in 'Bebo', a popular social networking site (SNS) on the Internet. DESIGN AND METHODS Data are drawn from information posted on approximately 150 Bebo Web pages and analysed by way of textual analysis and cyberspace ethnography. RESULTS Social networking sites, such as Bebo, provide young people with a digital space in which to share a range of alcohol marketing messages via peer-to-peer transmission. Bebo also enables youth to communicate to one another how they consume alcohol and their views of alcohol marketing messages. The information being shared by young people who use Bebo is openly provided in the form of personal information, forum comments, digital photographs and answering quizzes about their engagement with alcohol. DISCUSSION AND CONCLUSIONS Through this sharing of information in the digital Internet environment, young people are creating 'intoxigenic social identities' as well as 'intoxigenic digital spaces' that further contribute towards the normalisation of youth consumption of alcohol. A better understanding of how youth are using the Internet to share their experiences with alcohol and engagement with alcohol-related messages is crucial to public health research as alcohol marketing practices rapidly evolve.
In Vivo Imaging of a Bacterial Cell Division Protein Using a Protease‐Assisted Small‐Molecule Labeling Approach

Chemical labeling strategies developed to site specifically label proteins in their native cellular milieu have been sought as attractive approaches to obviate some of the drawbacks associated with the use of genetically encoded fusions to fluorescent proteins (FPs). Though elegant, many of these approaches necessitate the use of large protein domains/tags fused to target protein(s). Like FPs, these protein “tags” can potentially perturb the folding and/or activity of target proteins. Small peptide-recognition sequences are more desirable, but they have lower labeling efficiencies. 4] Other methods such as incorporation of unnatural amino acids and metabolic installation of reporter tags are primarily governed by the ability of the enzyme(s) to tolerate the unnatural motif to be introduced. Nevertheless, metabolic-labeling approaches have been successfully used to study glycoproteins and conjugates, which were previously inaccessible by other labeling techniques. Thus, the need still exists to develop new methods that can facilitate the routine use of small-molecule probes for the in vivo study of protein dynamics. Previously we reported an intein-mediated small-molecule approach for site-specific labeling of N-terminal cysteine-containing proteins. This method, however, had some significant drawbacks, including the relatively large size of intein tag used, as well as slow and uncontrolled self-splicing of the tag, which inevitably led to a longer labeling time. In this communication, we have sought to develop a more efficient labeling strategy and have capitalized on the highly specific tobacco etch virus (TEV) NIa protease. TEV is a 3C-type cysteine protease that recognizes a seven amino acid sequence, E-X-X-Y-XQflS/G (where X is any amino acid; and fl indicates the cleavage site). It has stringent substrate sequence requirement, with absolutely conserved residues at P6, P3, and P1 positions, and as such, has been widely used for removal of affinity tags from proteins both in vitro and in vivo. It was previously shown that mutation of the P1’ residue from S/G to cysteine does not significantly alter the efficiency of TEV cleavage. In our current strategy (Figure 1A), we used TEV for the rapid and controlled intracellular generation of N-terminal cysteine-containing proteins, which were subsequently labeled in a site-specific
Application of Metal‐Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates

The tandem 1,3‐dipolar cycloaddition‐retro‐Diels–Alder (tandem crDA) reaction is presented as a versatile method for metal‐free chemoselective conjugation of a DTPA radiolabel to N‐δ‐azido‐cyclo(‐Arg‐Gly‐Asp‐d‐Phe‐Orn‐) via oxanorbornadiene derivatives. To this end, the behavior of several trifluoromethyl‐substituted oxanorbornadiene derivatives in the 1,3‐dipolar cycloaddition was studied and optimized to give a clean and efficient method for bio‐orthogonal ligation in an aqueous environment. After radioisotope treatment, the resulting 111In‐labeled c(RGD)‐CF3‐triazole‐DTPA conjugate was subjected to preliminary biological evaluation and showed high affinity for αvβ3 (IC50=192 nM) and favorable pharmacokinetics.
The Emperor's new drugs: Exploding the antidepressant myth

Professor Kirsch begins this book with a clear-cut, yet controversial, statement: antidepressants simply do not work. In fact, he says, data from randomised controlled trials indicates that the placebo effect in depressed people may be twice as large as the drug effect. He exposes the methods employed by the pharmaceutical industry to cover up the variable results their trials have yielded, from withholding and cherry-picking data to publishing the results of positive trials several times. The basis of the book is a meta-analysis Kirsch first published in 1998 which showed that depressed patients given placebos showed far greater improvement in symptoms than expected. He goes on to explore the problems associated with the ‘gold-standard’ doubleblind randomised controlled trial, namely that many patients correctly guess which condition they have been allocated to on the basis of the side effects they experience. He asserts that less than a quarter of the antidepressant response is due to the drug effect and denounces the chemical imbalance theory as a ‘myth’ purported by the pharmaceutical companies. He delves into the placebo effect in depth, discussing placebo surgery and alternative therapies. This is, however, not a new-age tract – the bibliography is comprehensive and grounded in empirical findings. Finally, Kirsch looks to the future of depression treatment. If we accept that antidepressants are not effective in themselves, we must address the question of how depression should be best managed. He discusses the ethical dilemma of prescribing placebos by deception and cites evidence that indicates that improvements may be seen (and felt) even if patients are told they are being given placebos. He concludes, however, that there is little in the way of treatment that is as effective as psychological therapy, with our without the aid of medication. This is not entirely surprising; Kirsch is, after all, a Professor of Psychology, though, again, his assertions are grounded in research. Kirsch’s book is aimed squarely at the non-specialist reader – this is not a book full of jargon. It manages to break scientific concepts down into manageable pieces and succeeds in making large chunks of research readable. However, the constant repetition of facts, and the somewhat exasperating referencing system, can make it a frustrating read. The book begins promisingly, with an explosive exposé of the lies told by the drug companies but ends rather disappointingly. Kirsch pays no attention to the consequences of those lies; choosing to gloss over them in favour of adopting a ‘what works’ approach. It is self-evident that mental health professionals should indeed do ‘what works’ for patients; it just seems a little unlikely that any great change will come from his book. Informing patients of the questionable basis of their prescribed Journal of Mental Health, October 2011; 20(5): 494–495
The Emperor of all Maladies: A Biography of Cancer

22nd May 1948, Jimmy’s song is broadcasted on radio but it echoes in the hearts of millions. Jimmy becomes the mascot of cancer just as planned by Sidney Farber (The Doctor of the Dead). doi : 10.5214/ans.0972. 7531.1118211
Changing Morning Report: An Educational Intervention to Address Curricular Needs

Morning report is a case-based teaching session common to many residency programs with varying purposes and focuses. At our institution, physicians and residents felt our Internal Medicine morning report had lost its educational focus. The purpose of this project was to improve morning report using a well-known curriculum development framework for medical education. We conducted a focus group of residents to develop and implement changes to morning report. Themes from our focus group led us to split morning report with the first 30 minutes for postgraduate year 3 (PGY-3) residents to give handover, to receive feedback on diagnosis and management, and to either discuss an interesting case or receive teaching aimed at their final certification examination. The second 30 minutes involved PGY-3 residents leading PGY-1 residents in case-based discussions with an attending physician providing feedback on the content and process of teaching. We measured success based on a follow-up survey and comments from resident evaluations before and after the change. Overall, the changes were well received by both faculty and residents; however comments revealed that the success of morning report is preceptor dependent. In summary, we have successfully implemented a split morning report model to enhance resident education with positive feedback.
Relationship of relapse with impulsivity, novelty seeking and craving in male alcohol-dependent inpatients.

INTRODUCTION AND AIMS Aim of this study was to evaluate the relationship of relapse with impulsivity, novelty seeking (NS) and craving during 12 month follow up after inpatient treatment in male alcohol dependents. DESIGN AND METHODS Among 156 consecutively admitted male alcohol dependents, 102 were examined by face to face interview 12 months after discharge from hospital. Patients were investigated with the Barratt Impulsiveness Scale, version 11 (BIS-11), the NS dimension of the Temperament and Character Inventory, the Penn Alcohol Craving Scale (PACS) and Michigan Alcoholism Screening Test at the end of 12 months. RESULTS Among 102 alcohol-dependent inpatients 61.8% (n = 63) were considered as relapsed to alcohol use during 12 month follow up. Sociodemographic variables did not differ between relapsed and non-relapsed groups. Mean scores of BIS-11 and NS and subscales of these scales were higher in relapsed group than non-relapsed group. BIS-11 and NS and their subscales were positively correlated with each other. PACS was also positively correlated with these scales and their subscales. Only exception was 'exploratory excitability' (NS1) subscale of NS, which did not differ between groups and did not correlate with PACS or BIS-11. Extravagance (NS3) and BIS-11 non-planning impulsiveness (NPI) scores were associated with craving in Stepwise Linear Regression model. Only NS3 showed an association with relapse in the first Forward Wald logistic regression model. When severity of craving was included in the second model, as an independent variable, it was also associated with relapse additional to NS3. DISCUSSION AND CONCLUSIONS Both impulsivity and NS seem to be related with craving and relapse. Particularly, NS3 may be related with relapse both directly and indirectly via craving, whereas NPI may be related with relapse only indirectly via craving. Thus severity of craving may be a final pathway to relapse in these relationships of NS3 and NPI with relapse. These findings suggest that impulsivity, NS and craving are important variables to predict outcome and also for the treatment plan.
Blood Pressure Awareness and Self-Monitoring Practices among Primary Care Elderly Patients

Background: Seniors are perceived as relatively passive recipients of health care, and levels and predictors of blood pressure awareness and self-monitoring in these patients are poorly understood. Objectives: To determine the extent to which seniors are aware of their blood pressure status and targets and to examine correlates of blood pressure awareness and self-monitoring. Methods: We conducted a cross-sectional analysis of a 32-item baseline questionnaire that was completed by patients aged 65 years and older who were attending pharmacy-based cardiovascular health promotion sessions. The study comprised sociodemographic data, as well as data on health-related quality of life, knowledge of current blood pressure readings and targets, and treatment and monitoring of blood pressure in the previous year. Results: Of the 983 respondents, 379 (38.5%) recalled their most recent blood pressure reading. For one-third of these respondents (323/983), their physicians relayed blood pressure targets; of these, 26.9% (87/323) reported targets consistent with current guidelines. Overall, 47.1% (463/983) reported monitoring blood pressure in the past year. Multivariate logistic regression analysis revealed that older patients (aged 80 years and older) were less likely to know their blood pressure readings, compared with those who were younger. Patients with a postsecondary education, those who were diagnosed with high blood pressure, and those who were told their target blood pressure were more apt to know their readings, relative to those less educated, undiagnosed, or unaware of their target blood pressure. Participants who were aged 80 years and older were a negative predictor of self-monitoring in multivariate analysis, whereas living with someone, previous diagnosis of high blood pressure, and being advised of their target blood pressure were positive predictors. Conclusion: Seniors had a relatively poor understanding of their blood pressure readings and targets, but a subset was considerably more knowledgeable and potentially suited to be more involved in blood pressure self-management.
Prevalence and risk factors of erectile dysfunction among chronic hepatitis C male patients treated with pegylated interferon-α and ribavirin

Aim The aim of the study was to determine the prevalence and risk factors of erectile dysfunction (ED) among chronic hepatitis C male patients treated with pegylated interferon-α and ribavirin. Patients and methods The sample consisted of 85 male patients treated with pegylated interferon-α2a and ribavirin for 12 months, recruited from Tropical and Internal Medicine outpatients of Zagazig University Hospitals. ED was prospectively studied by International Index of Erectile Function questionnaire, depression was assessed by Hospital Anxiety and Depression Scale, and routine laboratory investigations in addition to serum total and free testosterone were evaluated before, during, and 6 months after treatment. Results Prevalence of ED among chronic hepatitis C male patients was 40% (34 patients). There was significant deterioration of International Index of Erectile Function scores and Hospital Anxiety and Depression Scale with respect to basal values and a significant decrease in total and free testosterone with gradual improvement toward the end of treatment period. Emotional state and physical profiles were the most significant risk factors for sexual dysfunction. Conclusion ED is common among hepatitis C virus patients treated with pegylated interferon-α and ribavirin and it is multifactorial.