bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Vascular Smooth Muscle Cell Dysfunction Under Diabetic Conditions by miR-504
Authors: Reddy Marpadga A. , Das Sadhan , Zhuo Chen , Jin Wen , Wang Mei , Lanting Linda , Natarajan Rama 
Published: March 2016

Objective—
Diabetes mellitus accelerates proatherogenic and proinflammatory phenotype of vascular smooth muscle cell (VSMC) associated with vascular complications. Evidence shows that microRNAs (miRNAs) play key roles in VSMC functions, but their role under diabetic conditions is unclear. We profiled miRNAs in VSMC from diabetic mice and examined their role in VSMC dysfunction.

Approach and Results—

High throughput small RNA-sequencing identified 135 differentially expressed miRNAs in VSMC from type 2 diabetic db/db mice (db/dbVSMC) versus nondiabetic db/+ mice. Several of these miRNAs were known to regulate VSMC functions. We further focused on miR-504, because it was highly upregulated in db/dbVSMC, and its function in VSMC is unknown. miR-504 and its host gene
Fgf13
were significantly increased in db/dbVSMC and in aortas from db/db mice. Bioinformatics analysis predicted that miR-504 targets including signaling adaptor Grb10 and transcription factor Egr2 could regulate growth factor signaling. We experimentally validated
Grb10
and
Egr2
as novel targets of miR-504. Overexpression of miR-504 in VSMC inhibited contractile genes and enhanced extracellular signal-regulated kinase 1/2 activation, proliferation, and migration. These effects were blocked by miR-504 inhibitors. Grb10 knockdown mimicked miR-504 functions and increased inflammatory genes. Egr2 knockdown-inhibited anti-inflammatory
Socs1
and increased proinflammatory genes. Furthermore, high glucose and palmitic acid upregulated miR-504 and inflammatory genes, but downregulated
Grb10
.

Conclusions—
Diabetes mellitus misregulates several miRNAs including miR-504 that can promote VSMC dysfunction. Because changes in many of these miRNAs are sustained in diabetic VSMC even after in vitro culture, they may be involved in metabolic memory of vascular complications. Targeting such mechanisms could offer novel therapeutic strategies for diabetic complications.
Characterizing Cathepsin Activity and Macrophage Subtypes in Excised Human Carotid Plaques
Authors: Abd-Elrahman Ihab , Meir Karen , Kosuge Hisanori , Ben-Nun Yael , Weiss Sadan Tommy , Rubinstein Chen , Samet Yaacov , McConnell Michael V. , Blum Galia 
Published: March 2016

Background and Purpose—
Atherosclerosis is a leading cause of mortality worldwide, contributing to both strokes and heart attacks. Macrophages are key players in atherogenesis, promoting vascular inflammation and arterial remodeling through cysteine cathepsin proteases. We used a cathepsin-targeted activity-based probe in human carotid plaque to assess its diagnostic potential and evaluate macrophage subtypes ex vivo.

Methods—
Carotid plaque specimens surgically removed during endarterectomy from 62 patients (age range, 38% female, 28% symptomatic) were graded pathologically as either stable (Grade 1) or unstable (Grade 2 or 3). A cathepsin activity-based probe was used to quantify individual cathepsins in plaque tissue and macrophage subtypes.

Results—

Cathepsin B and S activities were increased in unstable carotid plaques. They were quantified using the probe to biochemically investigate individual cathepsins (Cathepsin B and S: 0.97 and 0.90 for grade 3 versus 0.51 and 0.59 for grade 1;
P
=0.006 and
P
=0.03 arbitrary units (AU), respectively). Higher cathepsin activity was observed in carotid plaques from symptomatic patients (Cathepsin B and S: 0.65 and 0.77 for asymptomatic, 0.99 and 1.17 for symptomatic;
P
=0.008 and
P
=0.005 AU, respectively). Additionally, it was demonstrated that M2 macrophages from unstable plaques express cathepsin activity 5-fold higher than M2 macrophages from stable plaques (25.52 versus 5.22;
P
=0.008 AU).

Conclusions—
Targeting cathepsin activity in human carotid plaques may present a novel diagnostic tool for characterizing high-risk plaques. Novel cathepsin activity patterns within plaques and macrophage subpopulations suggest their involvement in the transition to active disease.
Balancing the benefits and detriments among women targeted by the Norwegian Breast Cancer Screening Program
Authors: Hofvind Solveig , Román Marta , Sebuødegård Sofie , Falk Ragnhild S 
Published: March 2016

Objective To compute a ratio between the estimated numbers of lives saved from breast cancer death and the number of women diagnosed with a breast cancer that never would have been diagnosed during the woman’s lifetime had she not attended screening (epidemiologic over-diagnosis) in the Norwegian Breast Cancer Screening Program. Methods The Norwegian Breast Cancer Screening Program invites women aged 50–69 to biennial mammographic screening. Results from published studies using individual level data from the programme for estimating breast cancer mortality and epidemiologic over-diagnosis comprised the basis for the ratio. The mortality reduction varied from 36.8% to 43% among screened women, while estimates on epidemiologic over-diagnosis ranged from 7% to 19.6%. We computed the average estimates for both values. The benefit–detriment ratio, number of lives saved, and number of women over-diagnosed were computed for different scenarios of reduction in breast cancer mortality and epidemiologic over-diagnosis. Results For every 10,000 biennially screened women, followed until age 79, we estimated that 53–61 (average 57) women were saved from breast cancer death, and 45–126 (average 82) were over-diagnosed. The benefit–detriment ratio using average estimates was 1:1.4, indicating that the programme saved about one life per 1–2 women with epidemiologic over-diagnosis. Conclusion The benefit–detriment ratio estimates of the Norwegian Breast Cancer Screening Program, expressed as lives saved from breast cancer death and epidemiologic over-diagnosis, should be interpreted with care due to substantial uncertainties in the estimates, and the differences in the scale of values of the events compared.
Perspectives of Health-Care Providers Toward Advance Care Planning in Patients With Advanced Cancer and Congestive Heart Failure
Authors: Chandar Manisha , Brockstein Bruce , Zunamon Alan , Silverman Irwin , Dlouhy Sarah , Ashlevitz Kathryn , Tabachow Cory , Lapin Brittany , Ewigman Bernard , Mazzone Theodore , Obel Jennifer 
Published: March 2016

Background: Advance care planning (ACP) discussions afford patients and physicians a chance to better understand patients’ values and wishes regarding end-of-life care; however, these conversations typically take place late in the course of a disease. The goal of this study was to clarify attitudes of oncologists, cardiologists, and primary care physicians (PCPs) toward ACP and to identify persistent barriers to timely ACP discussion following a quality improvement initiative at our health system geared at improvement in ACP implementation. Methods: A 20-question, cross-sectional online survey was created and distributed to cardiologists, oncologists, PCPs, and cardiology and oncology support staff at the NorthShore University HealthSystem (NorthShore) from February to March 2015. A total of 117 individuals (46% of distributed) completed the surveys. The results were compiled using an online survey analysis tool (SurveyMonkey, Inc., Palo Alto, California, USA). Results: Only 15% of cardiologists felt it was their responsibility to conduct ACP discussions with their patients having congestive heart failure (CHF). In contrast, 68% of oncologists accepted this discussion as their responsibility in patients with terminal cancer ( P < .01). These views were mirrored by PCPs, as 68% of PCPs felt personally responsible for ACP discussion with patients having CHF, while only 34% felt the same about patients with cancer. Reported documentation of these discussions in the electronic health record was inconsistent between specialties. Among all surveyed specialties, lack of time was the major barrier limiting ACP discussion. Perceived patient discomfort and discomfort of the patient’s family toward these discussions were also significant reported barriers. Conclusion: Attitudes toward ACP implementation vary considerably by medical specialty and medical condition, with oncologists in this study tending to feel more personal responsibility for these discussions with patients having cancer than cardiologists with their patients having heart failure. Robust implementation of ACP across the spectrum of medical diagnoses is likely to require a true collaboration between office-based PCPs and specialists in both the inpatient and the ambulatory settings.
Peroneal Tendon Abnormalities on Routine Magnetic Resonance Imaging of the Foot and Ankle
Authors: O’Neil Joseph T. , Pedowitz David I. , Kerbel Yehuda E. , Codding Jason L. , Zoga Adam C. , Raikin Steven M. 
Published: March 2016

Background: Abnormalities of the peroneal tendons can frequently be identified on routine MRI of the foot and ankle. Previous studies in the orthopedic literature have discussed the prevalence of abnormal MRI findings in asymptomatic patients, most notably with regards to the spine and shoulder. The purpose of this study was to determine the prevalence of abnormal findings of the peroneal tendons on MRI in asymptomatic individuals. Methods: We retrospectively reviewed all foot and ankle MRIs from 2 independent time periods that were either performed or reviewed at our institution. Studies were excluded if performed on patients with documented inversion injuries, ankle sprains, or lateral ankle trauma. A total of 294 (of 617) MRIs were eligible for inclusion in this study. A single attending musculoskeletal radiologist reviewed each MRI. Pathologies of the peroneal tendons included tendinosis, tenosynovitis, acute tears, chronic tears, and tendon splits. Additionally, the primary pathology encountered on each MRI was noted. The mean age of the MRIs included in this study was 46.8 years (range 9-82) with 155 females and 139 males. Results: The most commonly occurring primary pathology was Achilles tendinosis/tears (86), followed by posterior tibial tendon dysfunction (43). With regards to the peroneal tendons, 103 of the 294 (35%) MRIs demonstrated some pathology. Conclusion: The results of this study demonstrated that a sizeable percentage of asymptomatic individuals could have peroneal tendon pathology on MRI of the foot and ankle. This study can have important clinical implications for when patients present with concerning MRI findings that do not correlate clinically. Physicians providing musculoskeletal care can counsel and reassure patients who present with peroneal pathology on MRI but an absence of clinical findings. Level of Evidence: Level IV, case series.
Nicorandil, a Nitric Oxide Donor and ATP-Sensitive Potassium Channel Opener, Protects Against Dystrophin-Deficient Cardiomyopathy
Authors: Afzal Muhammad Z. , Reiter Melanie , Gastonguay Courtney , McGivern Jered V. , Guan Xuan , Ge Zhi-Dong , Mack David L. , Childers Martin K. , Ebert Allison D. , Strande Jennifer L. 
Published: March 2016

Background: Dystrophin-deficient cardiomyopathy is a growing clinical problem without targeted treatments. We investigated whether nicorandil promotes cardioprotection in human dystrophin-deficient induced pluripotent stem cell (iPSC)-derived cardiomyocytes and the muscular dystrophy mdx mouse heart. Methods and Results: Dystrophin-deficient iPSC-derived cardiomyocytes had decreased levels of endothelial nitric oxide synthase and neuronal nitric oxide synthase. The dystrophin-deficient cardiomyocytes had increased cell injury and death after 2 hours of stress and recovery. This was associated with increased levels of reactive oxygen species and dissipation of the mitochondrial membrane potential. Nicorandil pretreatment was able to abolish these stress-induced changes through a mechanism that involved the nitric oxide–cyclic guanosine monophosphate pathway and mitochondrial adenosine triphosphate-sensitive potassium channels. The increased reactive oxygen species levels in the dystrophin-deficient cardiomyocytes were associated with diminished expression of select antioxidant genes and increased activity of xanthine oxidase. Furthermore, nicorandil was found to improve the restoration of cardiac function after ischemia and reperfusion in the isolated mdx mouse heart. Conclusion: Nicorandil protects against stress-induced cell death in dystrophin-deficient cardiomyocytes and preserves cardiac function in the mdx mouse heart subjected to ischemia and reperfusion injury. This suggests a potential therapeutic role for nicorandil in dystrophin-deficient cardiomyopathy.
Can teledermatology be a useful diagnostic tool in dermatology practice in remote areas? An Egyptian experience with 600 patients
Authors: Saleh Nadia , Abdel Hay Rania , Hegazy Rehab , Hussein Marwa , Gomaa Dalia 
Published: March 2016

Introduction The paucity of studies evaluating teledermatology (TD) in developing countries was the impetus behind conducting this work. We aimed to evaluate the feasibility and reliability of TD in remote areas where medical facilities and consultant dermatologists are not available, through measurement of diagnostic concordance rates between face-to-face diagnosis and store-and-forward (SAF) TD diagnosis. Methods A total of 600 patients with dermatological ailments who attended Abshway Hospital were recruited into the study, examined by an on-site dermatology resident, and offered a diagnosis. The clinical images and patients’ history were collected and transferred (through the Dropbox application) to two remote consultant dermatologists. The reliability of the three physicians’ agreement rates was assessed. Results Diagnostic agreement rates between the face-to-face dermatologist and the two teledermatologists were 86.7% and 87% respectively. Of the cases, 97% had complete or partial agreement and 81.3% of cases showed complete agreement between the three physicians. The reliability of the three physicians’ agreement rates was assessed statistically using Cohen’s kappa coefficient (κ) and this showed a range of 0.46–0.52. Conclusion This study might aid in enhancing the utilization of this tool in our country, especially in remote areas with a lack of a proper dermatological service. The simplicity and low cost of the adopted technique might facilitate its use over large sectors. It opens the door for gaining the benefit of this technology in other aspects such as teaching and monitoring health care providers.
Examining the Relationship between Turnover Intention of Nurses with Job Satisfaction, Affective, Occupational, and Group Commitments: Study in Private Hospitals
Authors: Dasgupta Prasanjit 
Published: March 2016

High turnover of nurses is detrimental to patients’ well-being and costly to the organizations. Study was conducted in private hospitals considering their high rate of nurse attrition. Research has indicated that Job satisfaction and commitments to the organization, occupation, and group influenced the turnover of the employees in several countries. Some studies have also shown interrelationships between job satisfaction and commitments. India is culturally different from those countries and cultural variation plays a significant role in job satisfaction and these commitments. The study showed that job satisfaction, affective commitment, and occupational commitment of nurses negatively relate to their turnover intentions, although no significant relationship between group commitments and turnover intentions was established. Job satisfaction and group commitment significantly relate to affective commitments and group commitment relate to job satisfaction of the nurses. Affective commitments mediate in the relationship between job satisfaction and turnover intention of nurses. Relationship between occupational commitment with that of job satisfaction, affective and group commitments was not found significant. This research may help health-care managers to devise suitable plan for retention of nurses.
Complement factor H and susceptibility to major depressive disorder in Han Chinese
Authors: Zhang Chen , Zhang Deng-Feng , Wu Zhi-Guo , Peng Dai-Hui , Chen Jun , Ni Jianliang , Tang Wenxin , Xu Lin , Yao Yong-Gang , Fang Yi-Ru 
Published: March 2016

BackgroundAccumulating evidence suggests that altered immunity contributes to the development of major depressive disorder (MDD).AimsTo examine whether complement factor H (CFH), a regulator of activation of the alternative pathway of the complement cascade, confers susceptibility to MDD.MethodExpression analyses were tested in 53 unmedicated people with MDD and 55 healthy controls. A two-stage genetic association analysis was performed in 3323 Han Chinese with or without MDD. Potential associations betweenCFHsingle nucleotide polymorphisms and age at MDD onset were evaluated.ResultsCFHlevels were significantly lower in the MDD group at both protein and mRNA levels (P= 0.009 andP= 0.014 respectively). A regulatory variant in theCFHgene, rs1061170, showed statistically significant genotypic and allelic differences between the MDD and control groups (genotypicP= 0.0005, allelicP= 0.0001). Kaplan–Meier survival analysis showed that age at onset of MDD was significantly associated with theCallele of rs1061170 (log rank statistic χ2= 6.82,P= 0.009). TheC-allele carriers had a younger age at onset of MDD (22.2 years, s.d. = 4.0) than those without theCallele (23.6 years, s.d. = 4.3).ConclusionsCFHis likely to play an important role in the development of MDD. rs1061170 has an important effect on age at onset of MDD in Han Chinese and may therefore be related to early pathogenesis of MDD, although further study is needed.
Patient characteristics as a moderator of posttraumatic stress disorder treatment outcome: combining symptom burden and strengths
Authors: Cloitre Marylene , Petkova Eva , Su Zhe , Weiss Brandon J. 
Published: March 2016

BackgroundPost-traumatic stress disorder (PTSD) psychotherapy research has failed to identify patient characteristics that consistently predict differential outcome.AimsTo identify patient characteristics associated with differential outcome via a statistically generated composite moderator among women with childhood abuse-related PTSD in a randomised controlled trial comparing exposure therapy, skills training and their combination.MethodSix baseline patient characteristics were combined in a composite moderator of treatment effects for PTSD symptoms across the three treatment conditions through a 6-month follow-up.ResultsThe optimal moderator was the combined burden of all symptoms and emotion regulation strength. Those with high moderator scores, reflecting high symptom load relative to emotion regulation, did least well in exposure, moderately well in skills and best in the combination.ConclusionsA clinically meaningful moderator, which combines patient symptom burden and strengths, was identified. Assessment at follow-up may provide a more accurate indicator of variability in outcome than that obtained immediately post-treatment.
Protocol investigating the clinical outcomes and
cost-effectiveness of cognitive–behavioural therapy delivered remotely for
unscheduled care users with health anxiety: randomised controlled
trial
Authors: Patel Shireen , Malins Sam , Guo Boliang , James Marilyn , Kai Joe , Kaylor-Hughes Catherine , Rowley Emma , Simpson Jayne , Smart David , Stubley Michelle , Tyrer Helen , Morriss Richard 
Published: March 2016

BackgroundHealth anxiety and medically unexplained symptoms cost the National
Health Service (NHS) an estimated £3 billion per year in unnecessary
costs with little evidence of patient benefit. Effective treatment is
rarely taken up due to issues such as stigma or previous negative
experiences with mental health services. An approach to overcome this
might be to offer remotely delivered psychological therapy, which can be
just as effective as face-to-face therapy and may be more accessible and
suitable.AimsTo investigate the clinical outcomes and cost-effectiveness of remotely
delivered cognitive–behavioural therapy (CBT) to people with high health
anxiety repeatedly accessing unscheduled care (trial registration:
NCT02298036).MethodA multicentre randomised controlled trial (RCT) will be undertaken in
primary and secondary care providers of unscheduled care across the East
Midlands. One hundred and forty-four eligible participants will be
equally randomised to receive either remote CBT (6–12 sessions) or
treatment as usual (TAU). Two doctoral research studies will investigate
the barriers and facilitators to delivering the intervention and the
factors contributing to the optimisation of therapeutic outcome.ResultsThis trial will be the first to test the clinical outcomes and
cost-effectiveness of remotely delivered CBT for the treatment of high
health anxiety.ConclusionsThe findings will enable an understanding as to how this intervention
might fit into a wider care pathway to enhance patient experience of
care.
Peripubertal Stress With Social Support Promotes Resilience in the Face of Aging
Authors: Morrison Kathleen E. , Narasimhan Sneha , Fein Ethan , Bale Tracy L. 
Published: March 2016

AbstractThe peripubertal period of development is a sensitive window, during which adverse experiences can increase the risk for presentation of cognitive and affective dysfunction throughout the lifespan, especially in women. However, such experiences in the context of a supportive social environment can actually ameliorate this risk, suggesting that resilience can be programmed in early life. Affective disorders and cognitive deficits commonly emerge during aging, with many women reporting increased difficulty with prefrontal cortex (PFC)-dependent executive functions. We have developed a mouse model to examine the interaction between peripubertal experience and age-related changes in cognition and stress regulation. Female mice were exposed to peripubertal chronic stress, during which they were either individually housed or housed with social interaction. One year after this stress experience, mice were examined in tasks to access their cognitive ability and flexibility in stress reactive measures. In a test of spatial memory acquisition and reversal learning where aged females normally display a decreased performance, the females that had experienced stress with social interaction a year earlier showed improved performance in reversal learning, a measure of cognitive flexibility. Because peripuberty is a time of major PFC maturation, we performed transcriptomic and biochemical analysis of the aged PFC, in which long-term changes in microRNA expression and in myelin proteins were found. These data suggest that stress in the context of social support experienced over the pubertal window can promote epigenetic reprogramming in the brain to increase the resilience to age-related cognitive decline in females.