tbuckley/cabot-search huggingface dataset:
Food Insecurity, Food “Deserts,” and Glycemic Control in Patients With Diabetes: A Longitudinal Analysis
Authors: Seth A. Berkowitz, Andrew J. Karter, Giselle Corbie-Smith, Hilary K. Seligman, Sarah A. Ackroyd, Lily S. Barnard, Steven J. Atlas, Deborah J. Wexler
Journal: Diabetes Care (2018)

OBJECTIVE Both food insecurity (limited food access owing to cost) and living in areas with low physical access to nutritious foods are public health concerns, but their relative contribution to diabetes management is poorly understood. RESEARCH DESIGN AND METHODS This was a prospective cohort study. A random sample of patients with diabetes in a primary care network completed food insecurity assessment in 2013. Low physical food access at the census tract level was defined as no supermarket within 1 mile in urban areas and 10 miles in rural areas. HbA1c measurements were obtained from electronic health records through November 2016. The relationship among food insecurity, low physical food access, and glycemic control (as defined by HbA1c) was analyzed using hierarchical linear mixed models. RESULTS Three hundred and ninety-one participants were followed for a mean of 37 months. Twenty percent of respondents reported food insecurity, and 31% resided in an area of low physical food access. In adjusted models, food insecurity was associated with higher HbA1c (difference of 0.6% [6.6 mmol/mol], 95% CI 0.4–0.8 [4.4–8.7], P &amp;lt; 0.0001), which did not improve over time (P = 0.50). Living in an area with low physical food access was not associated with a difference in HbA1c (difference 0.2% [2.2 mmol/mol], 95% CI −0.2 to 0.5 [−2.2 to 5.6], P = 0.33) or with change over time (P = 0.07). CONCLUSIONS Food insecurity is associated with higher HbA1c, but living in an area with low physical food access is not. Food insecurity screening and interventions may help improve glycemic control for vulnerable patients.
Diabetic Cardiomyopathy
Authors: Guanghong Jia, Michael A. Hill, James R. Sowers
Journal: Circulation Research (2018)

Heart failure and related morbidity and mortality are increasing at an alarming rate, in large part, because of increases in aging, obesity, and diabetes mellitus. The clinical outcomes associated with heart failure are considerably worse for patients with diabetes mellitus than for those without diabetes mellitus. In people with diabetes mellitus, the presence of myocardial dysfunction in the absence of overt clinical coronary artery disease, valvular disease, and other conventional cardiovascular risk factors, such as hypertension and dyslipidemia, has led to the descriptive terminology, diabetic cardiomyopathy. The prevalence of diabetic cardiomyopathy is increasing in parallel with the increase in diabetes mellitus. Diabetic cardiomyopathy is initially characterized by myocardial fibrosis, dysfunctional remodeling, and associated diastolic dysfunction, later by systolic dysfunction, and eventually by clinical heart failure. Impaired cardiac insulin metabolic signaling, mitochondrial dysfunction, increases in oxidative stress, reduced nitric oxide bioavailability, elevations in advanced glycation end products and collagen-based cardiomyocyte and extracellular matrix stiffness, impaired mitochondrial and cardiomyocyte calcium handling, inflammation, renin-angiotensin-aldosterone system activation, cardiac autonomic neuropathy, endoplasmic reticulum stress, microvascular dysfunction, and a myriad of cardiac metabolic abnormalities have all been implicated in the development and progression of diabetic cardiomyopathy. Molecular mechanisms linked to the underlying pathophysiological changes include abnormalities in AMP-activated protein kinase, peroxisome proliferator-activated receptors, O-linked N-acetylglucosamine, protein kinase C, microRNA, and exosome pathways. The aim of this review is to provide a contemporary view of these instigators of diabetic cardiomyopathy, as well as mechanistically based strategies for the prevention and treatment of diabetic cardiomyopathy.
COMPARING TICAGRELOR AND ASPIRIN WITH CLOPIDOGREL AND ASPIRIN IN PATIENTS WITH PERIPHERAL ARTERIAL DISEASE: THROMBUS BURDEN ASSESSED BY OPTICAL COHERENCE TOMOGRAPHY
Authors: Mohammed Hasoon, Massoud A. Leesar, Xiao Yang, Joel Michalek, Thomas Milner, Taylor Hoyt, Marc Feldman, Mehmet Cilingiroglu
Journal: Journal of the American College of Cardiology (2018)
Integrins in wound healing, fibrosis and tumor stroma: High potential targets for therapeutics and drug delivery
Authors: Jonas Schnittert, Ruchi Bansal, Gert Storm, Jai Prakash
Journal: Advanced Drug Delivery Reviews (2018)

Wound healing is a complex process, which ultimately leads to fibrosis if not repaired well. Pathologically very similar to fibrosis is the tumor stroma, found in several solid tumors which are regarded as wounds that do not heal. Integrins are heterodimeric surface receptors which control various physiological cellular functions. Additionally, integrins also sense ECM-induced extracellular changes during pathological events, leading to cellular responses, which influence ECM remodeling. The purpose and scope of this review is to introduce integrins as key targets for therapeutics and drug delivery within the scope of wound healing, fibrosis and the tumor stroma. This review provides a general introduction to the biology of integrins including their types, ligands, means of signaling and interaction with growth factor receptors. Furthermore, we highlight integrins as key targets for therapeutics and drug delivery, based on their biological role, expression pattern within human tissues and at cellular level. Next, therapeutic approaches targeting integrins, with a focus on clinical studies, and targeted drug delivery strategies based on ligands are described.
Phase I trial of safety of combining BCG with pembrolizumab in patients with high grade superficial bladder cancer unresponsive to previous intravesical therapy.
Authors: Shaheen Riadh Alanee, Kathy Robinson, Sherjeel Sana
Journal: Journal of Clinical Oncology (2018)

TPS111 Background: Bacille Calmette-Guerin (BCG) is the most effective agent in the treatment of high grade superficial bladder cancer (HGSBC); however, not all patients respond to BCG, and recurrent disease is associated with a poor prognosis. The blockade of immune checkpoints of the pathway involving programmed death 1 (PD1) has been shown recently to be effective in cancer therapy. We started the first trial in the United States to combine an anti-PD1 drug (pembrolizumab) with BCG therapy in patients with HGSBC. Methods: The primary objective of the study was to determine the safety of administering a 200 mg fixed dose of pembrolizumab in conjunction with intravesical BCG treatment in HGSBC patients who have failed two courses of induction therapy or one course of BCG induction therapy followed by maintenance therapy. Patients included had to have pathologically documented HGSBC (Ta, T1) at time of restaging, or have pathologically documented high grade CIS of the bladder at time of initial resection for recurrent/persistent bladder cancer. Subjects were treated with six cycles (21 day cycle) of pembrolizumab treatment combined with six consecutive weeks of concurrent BCG installation beginning with cycle 3 of pembrolizumab. The first three subjects were to be treated at a dose of 100 mg pembrolizumab to ensure safety for the combination. If no safety issues were to happen, dosing was to be escalated to 200 mg every three weeks. Our secondary objective was to determine the 19 week and the three, twelve, and twenty-four month post-treatment completion complete response rate. The first patient received cycle 1 of pembrolizumab treatment in July of 2015. As of the date of writing this letter, five patients have completed treatment on this trial. The trial is soon to open a second site at Henry Ford Health System in addition to Southern Illinois University with the goal of full enrollment to be achieved in the next 6 months. Clinical trial information: NCT02324582.
Variation in assessment at UK medical schools needs investigation, researchers say
Authors: Matthew Limb
Journal: BMJ (2015)

Assessments at UK medical schools are “highly variable” and should be subject to an investigation, researchers from University College London and Keele University have said.

The researchers expressed “shock” at finding substantial differences in the “volume, format, and intensity” of summative assessment in five and six year undergraduate medical courses across the UK in their study published in BMC Medical Education .1

The differences “directly correlate” with performance in postgraduate exams, they found. This finding suggests that students at “assessment heavy” schools are “more likely to perform better” in both knowledge assessment and clinical exams for the two main qualifications (MRCP and MRCGP).

Oliver Devine, from University College London, who co-wrote the paper, told BMJ Careers, “The differences between these schools are far more profound than we ever thought. If you are a student from one particular school that doesn’t assess very much …
The importance of DNA repair for maintaining oocyte quality in response to anti-cancer treatments, environmental toxins and maternal ageing
Authors: Amy L Winship, Jessica M Stringer, Seng H Liew, Karla J Hutt
Journal: Human Reproduction Update (2018)

Within the ovary, oocytes are stored in long-lived structures called primordial follicles, each comprising a meiotically arrested oocyte, surrounded by somatic granulosa cells. It is essential that their genetic integrity is maintained throughout life to ensure that high quality oocytes are available for ovulation. Of all the possible types of DNA damage, DNA double-strand breaks (DSBs) are considered to be the most severe. Recent studies have shown that DNA DSBs can accumulate in oocytes in primordial follicles during reproductive ageing, and are readily induced by exogenous factors such as γ-irradiation, chemotherapy and environmental toxicants. DSBs can induce oocyte death or, alternatively, activate a program of DNA repair in order to restore genetic integrity and promote survival. The repair of DSBs has been intensively studied in the context of meiotic recombination, and in recent years more detail is becoming available regarding the repair capabilities of primordial follicle oocytes.This review discusses the induction and repair of DNA DSBs in primordial follicle oocytes.PubMed (Medline) and Google Scholar searches were performed using the key words: primordial follicle oocyte, DNA repair, double-strand break, DNA damage, chemotherapy, radiotherapy, ageing, environmental toxicant. The literature was restricted to papers in the English language and limited to reports in animals and humans dated from 1964 until 2017. The references within these articles were also manually searched.Recent experiments in animal models and humans have provided compelling evidence that primordial follicle oocytes can efficiently repair DNA DSBs arising from diverse origins, but this capacity may decline with increasing age.Primordial follicle oocytes are vulnerable to DNA DSBs emanating from endogenous and exogenous sources. The ability to repair this damage is essential for female fertility. In the long term, augmenting DNA repair in primordial follicle oocytes has implications for the development of novel fertility preservation agents for female cancer patients and for the management of maternal ageing. However, further work is required to fully characterize the specific proteins involved and to develop strategies to bolster their activity.
Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men
Authors: Daniel D. Sjoberg, Andrew J. Vickers, Melissa Assel, Anders Dahlin, Bing Ying Poon, David Ulmert, Hans Lilja
Journal: European Urology (2018)
PREDICTING THE NEED FOR SKILLED NURSING FACILITIES AFTER ACUTE MYOCARDIAL INFARCTION
Authors: Jason Wasfy, Kevin Kennedy, Frederick A. Masoudi, Suzanne Arnold, Vinay Kini, Tim Ferris, Pamela Peterson, Jeptha Curtis, Amit Amin, Steven Bradley, Michael Ho, John Spertus
Journal: Journal of the American College of Cardiology (2018)
Incorporation of PBRM1, BAP1, TP53 mutation status into the Memorial Sloan Kettering Cancer Center (MSKCC) risk model: A genomically annotated tool to improve stratification of patients (pts) with advanced renal cell carcinoma (RCC).
Authors: Martin Henner Voss, Yuan Cheng, Mahtab Marker, Fengshen Kuo, Toni K. Choueiri, James J Hsieh, Albert Reising, Robert J. Motzer, A. Ari Hakimi
Journal: Journal of Clinical Oncology (2018)

639 Background: The MSKCC risk model, an established prognostic tool fo r metastatic RCC, integrates clinical + laboratory data, but is ignorant to tumor genomics. Mutations in BAP1, PBRM1, TP53, cumulatively found in over 50% of pts, have prognostic value in RCC. We sought to study the use of integrating mutation status into the MSKCC model using two large clinical trial datasets. Methods: Pts had received first line sunitinib or pazopanib on the phase III COMPARZ (training set, n = 357) or the phase II RECORD3 trial (validation set, n = 130). Genes were evaluated by next generation sequencing using archival tissue. Association of mutation status and overall survival (OS) was tested by multivariate Cox regression analysis (MVA) in the training set. An annotated model was constructed combining the original clinical variables and mutation status for the 3 genes. We compared risk group assignment and concordance index (c-index) for the original vs. new model in training and validation set. Results: Mutation status for each gene: BAP1, TP53 and PBRM1 independently correlated with OS on MVA (p≤0.0035). Comparing the original (clinical only) to the annotated (clinical + genomics) model, risk categories changed in 139 pts (39%). The C-index was improved with integration of genomic information (0.595 original model - &gt; 0.628 new model). The independent validation cohort confirmed improvement of c-index for predicting OS with integration of genomic data (c-index 0.622 original model - &gt; 0.641 new model). Conclusions: Mutation status for BAP1, PBRM1, and TP53 has prognostic value in pts with advanced RCC. The annotated risk model alters risk status in over 1/3 of pts and improves accuracy of estimating outcomes in patients receiving first-line therapy. Clinical trial information: NCT00720941. [Table: see text]
NHS workforce lags behind public in attitudes to mental health, Mind says
Authors: Matthew Limb
Journal: BMJ (2015)

The NHS workforce is not keeping up with the shift in public attitudes to mental health, the mental health charity Mind has said.

Paul Farmer, chief executive of Mind, said that the positive change in public attitudes and “user voice” was perhaps the most striking development seen in mental health over the past five or six years. He said that this change was evident in campaigning by the charity and social media work but that attitudes were not shifting in the NHS …
Abstract MP18: The Risk of Venous Thromboembolism is Lower in Multiple Asian Ethnic Groups
Authors: H. Nicole Tran, Natalia Udaltsova, Stanton Siu, Jeanne Darbinian, Arthur L Klatsky
Journal: Circulation (2018)

Background: Several studies suggest a lower risk of venous thromboembolism (VTE) in Asians compared to other racial groups, and genetic mechanisms have been suspected. Despite their biological and cultural diversity, data have been sparse comparing risk of VTE among specific Asian ethnicities. Our previous report from 2000 on hospitalizations for VTEs in Asian Americans had included 337 subjects (all races) and numbers were insufficient to study specific Asian groups. We present here data from a new study with 4,674 VTE subjects. Hypothesis: Similar low VTE risk is present in multiple Asian ethnic groups. Methods: We studied composite VTE risk in 61,459 members of a comprehensive health plan, who had supplied self-classified ethnicity data on prior health examinations between 1978 and 1985 and had remained plan members in 1996, when outpatient diagnoses were added to computerized files. The subjects were 58% (n = 35,573) female and 42% (n= 25,886) male. From 1996 through 2015, at least one diagnosis of VTE was made during an outpatient visit or hospitalization for 4,675 persons. With Whites as the referent group, we performed logistic regressions controlled for age, sex, education, BMI, and smoking, yielding hazard ratios (HR) and 95% confidence intervals (CI). Results: The table shows HRs (CI) versus Whites (n=32,557) with 2,576 VTE. These lower HRs for VTE in Asians were generally similar in men and women. In the Asian stratum, a model with Chinese as referent showed an increased HR = 1.87 (1.09-3-21; p=0.02) for South Asians. Among covariates sex, education, and smoking were unrelated to VTE risk and BMI was positively associated; these results were similar in Whites, Blacks, and Asians. Conclusions: In conclusion, Chinese, Japanese, Filipinos and Other Asian Americans but not South Asians had substantially lower VTE risk compared to Whites. These data indirectly support a genetic explanation.
Acetylation within the N- and C-Terminal Domains of Src Regulates Distinct Roles of STAT3-Mediated Tumorigenesis
Authors: Chao Huang, Zhe Zhang, Lihan Chen, Hank W. Lee, Marina K. Ayrapetov, Ting C. Zhao, Yimei Hao, Jinsong Gao, Chunzhang Yang, Gautam U. Mehta, Zhengping Zhuang, Xiaoren Zhang, Guohong Hu, Y. Eugene Chin
Journal: Cancer Research (2018)

Posttranslational modifications of mammalian c-Src N-terminal and C-terminal domains regulate distinct functions. Myristoylation of G2 controls its cell membrane association and phosphorylation of Y419/Y527 controls its activation or inactivation, respectively. We provide evidence that Src-cell membrane association-dissociation and catalytic activation-inactivation are both regulated by acetylation. In EGF-treated cells, CREB binding protein (CBP) acetylates an N-terminal lysine cluster (K5, K7, and K9) of c-Src to promote dissociation from the cell membrane. CBP also acetylates the C-terminal K401, K423, and K427 of c-Src to activate intrinsic kinase activity for STAT3 recruitment and activation. N-terminal domain phosphorylation (Y14, Y45, and Y68) of STAT3 by c-Src activates transcriptionally active dimers of STAT3. Moreover, acetyl-Src translocates into nuclei, where it forms the Src-STAT3 enhanceosome for gene regulation and cancer cell proliferation. Thus, c-Src acetylation in the N-terminal and C-terminal domains play distinct roles in Src activity and regulation.Significance: CBP-mediated acetylation of lysine clusters in both the N-terminal and C-terminal regions of c-Src provides additional levels of control over STAT3 transcriptional activity. Cancer Res; 78(11); 2825-38. ©2018 AACR.
The maxillofacial factor: not just for dentists
Authors: Martin Telfer
Journal: BMJ (2004)

<b>Objective:</b> To report results of human VEEP studies in normal controls compared to patients with peripheral or central vestibular dysfunction. <b>Background</b> The VEEP has been described in animal models (cat and guinea pig) and more recently in humans. In contrast to other evoked potentials, a unique linear relationship between current strength and latency has been reported with VEEP responses in normal individuals. <b>Design/Methods:</b> Normal control subjects (n=5) and patients with vestibular dysfunction (n=3) were studied with electrical stimulation over the mastoid in one mA increments from threshold to no higher than 20 mA. Evoked potentials were recorded with standard signal averaging techniques. <b>Results:</b> In normal controls, mastoid stimulation at 2.5mA yielded Cz-A1/2 VEEP responses of median latency 10.2ms (range 6.0-13.3; SD 4.9). These responses progressively increased in latency from 8.6 to 22.6ms (mean latency increase of 1.3ms/mA) as current strength was increased in 10 steps (1mA/step) from threshold. VEEP responses differed significantly in stimulation threshold, morphology, amplitude and latency from mastoid dermatomal somatosensory evoked potentials (SEPs), great auricular sensory nerve action potentials (SNAPs), and frontalis compound muscle action potentials (CMAPs). Neither acoustic stimuli nor white noise masking affected the VEEP. In 3 patients with vestibular dysfunction (one each with acoustic neuroma, Meniere disease and multiple sclerosis as the cause) VEEP late response latencies were absent or markedly asymmetric, with recordable responses showing a median latency of 12.2ms (range 11.2-12.7; SD 0.4); none demonstrated the linear increasing current strength-latency pattern seen in normals. <b>Conclusions:</b> 1) VEEP studies produced reproducible responses in normal controls; 2) VEEP responses cannot be attributed to auditory or somatic sensory nerve responses; 3) VEEP current strength-latency curves showed a linear increase in normals in contrast to absent, flat, and/or decreasing patterns in patients with vestibular dysfunction. Supported by: Mayo Foundation. <b>Disclosure:</b> Dr. Smith has nothing to disclose. Dr. Cevette has nothing to disclose. Dr. Stepanek has nothing to disclose. Dr. Cocco has nothing to disclose. Dr. Pradhan has nothing to disclose. Dr. Brookler has nothing to disclose. Dr. Zapala has nothing to disclose. Dr. Ross has nothing to disclose.
Royal College of Psychiatrists offers free CPD in response to fee surplus
Authors: Helen Jaques
Journal: BMJ (2013)

The Royal College of Psychiatrists is making its online resources for continuing professional development (CPD) free for trainees, in response to concerns that it made £600 000 profit from membership examination fees in 2011.

Trainee doctors, college affiliates, trainees in the Republic of Ireland, and first year consultants registered with the college stand …
ACUTE EFFECTS OF COFFEE ON ENDOTHELIAL FUNCTION AND ARTERIAL REFLECTED WAVES INDEPENDENTLY OF PRIOR HABITUAL COFFEE CONSUMPTION
Authors: Evangelos Oikonomou, George-Angelo Papamikroulis, Gerasimos Siasos, Alexios Antonopoulos, Sotirios Tsalamandris, Athina Goliopoulou, Petros Fountoulakis, Georgia Vogiatzi, Panagiotis Theofilis, Georgia Skotsimara, Leonidas Koliostasis
Journal: Journal of the American College of Cardiology (2018)
Hospitals shift towards having more fully trained doctors in service delivery
Authors: Ingrid Torjesen
Journal: BMJ (2012)

The NHS is employing more consultants and senior doctors, but the number of posts available for less experienced doctors, particularly those working as locums, has fallen, show figures published by the NHS Information Centre yesterday.

Provisional figures for staff groups working in NHS hospital and community health services in England show that the NHS had 2% fewer people working in these groups in November 2011 than it did in November 2010.

Although there was a slight rise (1.5%) in the total number of whole time equivalent doctors either employed …
Proportion of consultants holding clinical excellence awards has fallen since 2010
Authors: Helen Jaques
Journal: BMJ (2013)

The proportion of NHS consultants in England who hold top or middle tier national clinical excellence or distinction awards has fallen since 2010, the Advisory Committee on Clinical Excellence Awards has reported.

The proportion holding a platinum clinical excellence award or an A+ distinction award will have fallen “significantly” since 2005, the committee said. Meanwhile the proportion of consultants holding a gold or silver clinical excellence award or an A distinction award rose from 2005 to 2009 but is expected to fall below the 2005 level in 2012, it added (figure⇓).



Percentage of consultants receiving top …