tbuckley/cabot-search huggingface dataset:
Abstract P233: PPARα-Sirt1 Complex Mediates Metabolic Adaptation in Response to Starvation in the Heart
Authors: Shinichi Oka, Peiyong Zhai, Takanobu Yamamoto, Dan Shao, Junichi Sadoshima
Journal: Circulation Research (2011)

Minimizing nutritional usage is believed to be important for prolonging survival time in organisms under starvation conditions such as fasting and hibernation. The heart is a major organ that constantly consumes nutrition coupling with mitochondrial ATP production. However, it remains unknown how mitochondrial gene expression is regulated in the heart during starvation conditions. We have previously shown that a PPARα-Sirt1 complex mediates downregulation of mitochondrial gene expression in the failing heart. Since both PPARα and Sirt1 are crucial regulators in physiological fasting responses, we hypothesized that the same mechanism is involved in the physiological fasting response in the heart. To investigate this hypothesis, heterozygous knockout PPARα (PPARα +/- ) and Sirt1 (Sirt1 +/- ) mice were subjected to 24 hours fasting. Several mitochondrial genes, such as Sdha and Atp5g1, were downregulated following fasting in wild type (WT) mice, but this downregulation was at least partly prevented in PPARα +/- and Sirt1 +/- mice, suggesting that PPARα and Sirt1 play an important role in fasting-induced downregulation of mitochondrial gene expression in the heart. After fasting, cardiac systolic function was slightly reduced in WT mice, but this response was not induced in PPARα +/- and Sirt1 +/- mice (ejection fraction (%): Fed WT 74, Fasted WT 68*, Fed PPARα +/- 76, Fasted PPARα +/- 75, Fed Sirt1 +/- 74, Fasted Sirt1 +/- 74, p&lt;0.05 vs Fed WT). Weight loss after 24 hours fasting increased in PPARα +/- mice, compared to WT mice (Body weight reduction (%): WT 9, PPARα +/- 14*, p&lt;0.05 vs WT). Under an isolated working mouse heart model with nutrient free perfusion buffer, spontaneous beating terminated earlier in hearts isolated from PPARα +/- and Sirt1 +/- mice than in hearts from WT mice (Beating time (minutes): WT 63, PPARα +/- 37*, Sirt1 +/- 36*, p&lt;0.05 vs WT). Glucose deprivation-induced cell death was cooperatively prevented by overexpression of PPARα and Sirt1 in primary cultured myocytes (Cell survival rate (%): control 54, PPARα 75*, Sirt1 60, PPARα with Sirt1 94*, PPARα with Sirt1 knockdown 52, p&lt;0.05 vs control). These results suggest that PPARα and Sirt1 are crucial regulators of adaptation to starvation in the heart.
Medical Education Theme Issue 2007
Authors: Robert M. Golub
Journal: JAMA (2006)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Assessing knowledge and attitudes towards concussion in irish footballers
Authors: Connor Gallagher, Eanna Falvey
Journal: British Journal of Sports Medicine (2017)

Objective To assess current levels of knowledge and attitude towards concussion in Irish soccer players and compare findings with other athletic groups. Design Participants completed a paper bases Rosenbaum Concussion Knowledge and Attitude Survey (RoCKAS). Results were collated and analysed using descriptive statistics to look for correlation between player subgroups. Setting UCD AFC training facility, Dublin, Ireland. Participants Seventy male semi-professional and amateur League of Ireland players. Participants had to be registered players of UCD AFC Outcome measures All 70 participants completed the questionnaire and passed the RoCKAS internal validity scale. Main results Irish players showed good concussion knowledge, broadly safe attitudes and good symptom recognition awareness. There is a positive association between safer concussion attitudes and player age (Pearson correlation coefficient 0.258, p-value 0.031), although no such relationship existed between attitude and years of playing experience (p&gt;0.05). There were no differences found in either knowledge or attitude in the subgroup of players who have a previous history of concussion. There was no association found between higher levels of player concussion knowledge and higher attitude scores (Correlation co-efficient 0.222, p-value 0.064). Current study knowledge scores were higher than those of English professional players (p ≤ 0.01) but lower than NCAA hockey players (p ≤ 0.01) but attitude scores across the three groups were similar. (Tables 5&amp;6) 1,2 Concussed Irish soccer players are less inclined to continue playing in an important game than their amateur rugby union counterparts (4.3% versus 76.0%). 3 Conclusion Safer attitudes surrounding concussion are related to increasing player age, not necessarily playing experience. Higher player knowledge does not necessarily confer safer attitudes towards concussion. Future prevention strategies that serve to only educate players may not be effective unless they tackle the reasons players are likely to engage in unsafe behaviour. Competing interests None. Abstract 160 Table 5 Pearson correletion co-efficient values comparing concussion knowledge (CKI) and attitude (CAI) among study sub groups. Abstract 160 Table 6 Comparison of current study to previous other studies using the RoCKAS concussion knowledge and attitude questionaire.
The Follicular Skin Microbiome in Patients With Hidradenitis Suppurativa and Healthy Controls
Authors: Hans Christian Ring, Jonathan Thorsen, Ditte M. Saunte, Berit Lilje, Lene Bay, Peter Theut Riis, Niels Larsen, Lee O’Brien Andersen, Henrik V. Nielsen, Iben M. Miller, Thomas Bjarnsholt, Kurt Fuursted, Gregor Borut Jemec
Journal: JAMA Dermatology (2017)

Although the pathogenesis of hidradenitis suppurativa (HS) remains enigmatic, several factors point to potential involvement of the cutaneous microbiome. Insight into the cutaneous microbiome in HS using next-generation sequencing may provide novel data on the microbiological diversity of the skin.To investigate the follicular skin microbiome in patients with HS and in healthy controls.This case-control study obtained punch biopsy specimens from patients with HS (lesional and nonlesional) and healthy controls between October 1, 2014, and August 1, 2016. Data were analyzed from March to November 2016. Patients with HS were recruited from the Department of Dermatology, Zealand University Hospital, Roskilde, Denmark. Biopsy specimens were analyzed at the Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark. None of the participants received any antibiotics (systemic or topical therapy) within 1 month before the study. In patients with HS, biopsy specimens were obtained from lesional skin (axilla or groin) and nonlesional skin. Only nodules containing at least 1 visible hair follicle were biopsied. Biopsy specimens from healthy controls were obtained from the axilla only.The different microbiomes were investigated using next-generation sequencing targeting 16S and 18S ribosomal RNA.The skin microbiome was characterized in 30 patients with HS (mean [SD] age, 46.9 [14.0] years; 19 [63% female]) and 24 healthy controls (mean [SD] age, 32.2 [12.0] years; 13 [54% female]). The next-generation sequencing data provided a previously unreported (to our knowledge) characterization of the skin microbiome in HS. The study demonstrated that the microbiome in HS differs significantly from that in healthy controls in lesional and nonlesional skin. Overall, the following 5 microbiome types were identified: Corynebacterium species (type I), Acinetobacter and Moraxella species (type II), Staphylococcus epidermidis (type III), Porphyromonas and Peptoniphilus species (type IV), and Propionibacterium acnes (type V). In lesional skin, microbiome types consisted predominantly of type I or type IV. Microbiome type IV was not detected in healthy controls. Several taxa, including Propionibacterium, showed a significantly higher relative abundance in healthy controls vs HS skin, indicating that Propionibacterium may be part of the pathogenesis in HS.The study findings suggest a link between a dysbiotic cutaneous microbiome and HS.
Poaceae pollen as the leading aeroallergen worldwide: A review
Authors: H. García‐Mozo
Journal: Allergy (2017)

Abstract The Poaceae family comprises over 12 000 wind‐pollinated species, which release large amounts of pollen into the atmosphere. Poaceae pollen is currently regarded as the leading airborne biological pollutant and the chief cause of pollen allergy worldwide. Sensitization rates vary by country, and those variations are reviewed here. Grass pollen allergens are grouped according to their protein structure and function. In Poaceae, although species belonging to different subfamilies are characterized by distinct allergen subsets, there is a considerable degree of cross‐reactivity between many species. Cross‐reactivity between grass pollen protein and fresh fruit pan‐allergens is associated with the appearance of food allergies. The additional influence of urban pollution may prompt a more severe immunological response. The timing and the intensity of the pollen season are governed by species genetics, but plant phenology is also influenced by climate; as a result, climate changes may affect airborne pollen concentrations. This article reviews the findings of worldwide research which has highlighted the major impact of climate change on plant phenology and also on the prevalence and severity of allergic disease.
Comment on Cummings and Cohen. Bariatric/Metabolic Surgery to Treat Type 2 Diabetes in Patients With a BMI <35 kg/m 2 . Diabetes Care 2016;39:924–933
Authors: Bruno Halpern, Cintia Cercato, Marcio Correa Mancini
Journal: Diabetes Care (2017)

In a recent article, Cummings and Cohen (1) compared glycemic outcomes after bariatric surgery in patients with BMI ≥35 or <35 kg/m2, concluding that there was no clear difference in outcomes between these BMI thresholds. To strengthen their argument, they discussed possible weight-independent effects of bariatric surgery on glycemic outcomes.

Their article correctly recognized the 35 kg/m2 threshold used as an indication for bariatric surgery, based on a 1991 National Institutes of Health Consensus Statement (2), as arbitrary and probably not suitable for Asian patients, and it discussed the fact that initial BMI does not predict outcome in larger cohorts. However, many points discussed in the article should be analyzed with caution, given the limited number of less obese patients with long-term follow-up after metabolic surgery and the few existing comparisons of BMI extremes. Additionally, many studies have demonstrated that diabetes remission is associated with the amount of weight loss and that, …
Thymic epithelial cells require p53 to support their long-term function in thymopoiesis in mice
Authors: Pedro M. Rodrigues, Ana R. Ribeiro, Chiara Perrod, Jonathan J. M. Landry, Leonor Araújo, Isabel Pereira-Castro, Vladimir Benes, Alexandra Moreira, Helena Xavier-Ferreira, Catarina Meireles, Nuno L. Alves
Journal: Blood (2017)
Anticystogenic activity of a small molecule PAK4 inhibitor may be a novel treatment for autosomal dominant polycystic kidney disease
Authors: Vicki J. Hwang, Xia Zhou, Xiaonan Chen, Josephine Trott, Omran Abu Aboud, Kyuhwan Shim, Lai Kuan Dionne, Kenneth J. Chmiel, William Senapedis, Erkan Baloglu, Moe R. Mahjoub, Xiaogang Li, Robert H. Weiss
Journal: Kidney International (2017)
Phase I expansion cohort trial to investigate the safety and clinical activity of avelumab (MSB0010718C) in patients with metastatic or locally advanced solid tumors.
Authors: Christopher Ryan Heery, Jeffrey R. Infante, Nicholas Iannotti, Karen Kelly, Petros Nikolinakos, Anja von Heydebreck, Kevin M. Chin, James L. Gulley
Journal: Journal of Clinical Oncology (2015)

TPS3101 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against multiple cancers. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody currently being investigated in clinical trials. Methods: This is a parallel group expansion trial of avelumab in patients (pts) with selected tumor indications following the determination of dose and regimen in a phase I, open label, dose escalation study. The dose escalation cohort has been completed (n = 53). Pts in 11 separate cohorts of advanced solid tumors will receive avelumab at 10 mg/kg as a 1h infusion, Q2W. Treatment will continue until disease progression, unacceptable toxicity, or if any criterion for withdrawal of investigational medicinal product occurs. In addition to evaluating tolerability, specific objectives for the expansion cohorts include: assessment of best overall response (BOR) and progression-free survival (PFS) according to RECIST 1.1; assessment of immune-related BOR and immune-related PFS using the modified Immune-Related Response Criteria; and assessment of overall survival. Association between tumor PD-L1 expression and efficacy will be evaluated and the PK/PD profile of avelumab characterized. This trial is in progress: recruitment for 2nd-line non-small cell lung cancer (n = 184), metastatic breast cancer (n = 168), colorectal cancer (n = 21), and ovarian cancer cohorts (n = 75) is complete. Recruitment for gastric/gastroesophageal junction cancer (n = 150), melanoma (n = 50), castration-resistant prostate cancer (n = 20), adrenocortical carcinoma (n = 50), mesothelioma (n = 50), urothelial carcinoma (n = 50), and 1st-line NSCLC (n = 150) is ongoing (target enrollment provided for each tumor type). Overall, > 700 pts have been enrolled across the dose escalation and current expansion cohorts (start Jan 2013, estimate end Oct 2016). NCT01772004. *Proposed INN. Clinical trial information: NCT01772004.
APPRAISAL OF THE FUNCTIONAL MOVEMENT SCREEN IN FOOTBALL INJURY PREDICTION
Authors: Monika Grygorowicz, Martyna Michalowska, Tomasz Piontek
Journal: British Journal of Sports Medicine (2017)

Background Functional Movement Screen (FMS) has been used in the prediction of football injuries. However, the discussion continues on how sensitive and specific the test is. Lately, systematic review [McCall et al. 2014] enrolling studies published up to September 2014 and clinical commentary [Wright et al. 2016] were published underlying caution prior to implementation of the FMS into clinical practice as an injury prediction tool. Thus, it seems necessary to up-date the debate. Objective To provide up-to-date evidence-based summary of available evidence regarding the predictive value of FMS in football players. Design Critically Appraised Topic. Setting Amateur, collegiate Division I and II. Patients (or Participants) Male and female footballers. Interventions (or Assessment of Risk Factors) Medline, SPORTDiscuss/with/Full Text, Academic Search Complete, Nursing/Academic Edition, MasterFILE Premier databases were searched (on August 31st 2016) using “football”, “soccer”, “functional movement screen” keywords. Only prospective cohort studies published as full article in reviewed journals were included. Main Outcome Measurements Between samples – injured vs. uninjured analysis, odd ratio (OR), likelihood ratio (LR), receiver operating curve (ROC). Results Our search yielded 18 studies, after abstract revision 3 articles met the criteria. The first [Warren et al . 2015] did not confirm the validity of FMS in injury prediction (OR=1.01, 95% CI 0.53–1.91). The second [ Schroeder et al . 2016 ] showed no difference between injured/uninjured players in FMS score (Z=−0.890, p=0.373), concluding FMS to be a poor predictor of injury in football players. The third [Mokha et al . 2016] found that asymmetry was a better predictor of injury than the composite FMS score. None of the studies used LR ratio or ROC curve analyses in statistical analysis. Conclusions Caution is required when applying FMS in football injury prediction. It is necessary to conduct a well-designed prospective study with sufficient statistical analysis used for predictive parameters to justify the use of FMS test in injury prediction in football players.
Review of Flexible Temperature Sensing Networks for Wearable Physiological Monitoring
Authors: Qiao Li, Li‐Na Zhang, Xiao‐Ming Tao, Xin Ding
Journal: Advanced Healthcare Materials (2017)

Physiological temperature varies temporally and spatially. Accurate and real‐time detection of localized temperature changes in biological tissues regardless of large deformation is crucial to understand thermal principle of homeostasis, to assess sophisticated health conditions, and further to offer possibilities of building a smart healthcare and medical system. Additionally, continuous temperature mapping in flexible and stretchable formats opens up many other potential areas, such as artificially electronic skins and reflection of emotional changes. This review exploits a comprehensive investigation onto recent advances in flexible temperature sensors, stretchable sensor networks, and platforms constructed in soft and compliant formats for wearable physiological monitoring. The most recent examples of flexible temperature sensors are first discussed regarding to their materials, structures, electrical and mechanical properties; temperature sensing network technologies in new materials and structural designs are then presented based on platforms comprised of multiple physical sensors and stretchable electronics. Finally, wearable applications of the sensing network are described, such as detection of human activities, monitoring of health conditions, and emotion‐related bodily sensations. Conclusions are made with emphasis on critical issues and new trends in the field of wearable temperature sensor network technologies.
TRTH-13. BMI1 IS A THERAPEUTIC TARGET IN RECURRENT MEDULLOBLASTOMA
Authors: David Bakhshinyan, Neha Garg, Branavan Manoranjan, Chitra Venugopal, Robin Hallett, Xin Wang, Michelle Kameda-smith, Ashley Adile, Vijay Ramaswamy, Thomas Davis, Marla Weetall, Young-choon Moon, Siddhartha Mitra, Yoon-Jae Cho, Michael Taylor, Sheila Singh
Journal: Neuro-Oncology (2017)

Bmi1 is a master regulatory stem cell self-renewal gene and epigenetic regulator that presents a downstream target of developmental pathways active during the genesis of the childhood brain tumor medulloblastoma (MB). Here, we describe Bmi1 as a novel therapeutic target for the treatment of recurrent human Group 3 MB, a tumor that often presents with metastasis for which there is virtually no treatment option as children are limited to palliation. Current clinical trials for recurrent MB patients based on genomic profiles of primary, treatment-naïve tumors, will provide limited clinical benefit since recurrent metastatic MBs are highly genetically divergent from their primary tumor. By applying stem cell assays to primary and matched-recurrent Group 3 MB samples, we have identified Bmi1 as a key regulator of self-renewal that has the potential to drive treatment failure. We have shown Bmi1 to be enriched in treatment-refractory fractions in vivo and in vitro. Using a small molecule inhibitor against Bmi1, PTC-028, we were able to demonstrate complete ablation of self-renewal of MB stem cells in vitro and when administered to mice xenografted with patient tumors. Oral administration of Bmi1 inhibitor in our MB patient-derived xenograft (PDX) model resulted in a marked reduction in both tumor burden, extent of spinal metastases and Bmi1 protein level in tumors post- in vivo therapy. Recurrent MB carries a mortality rate approaching 100%, and currently there exists no targeted therapy to treat recurrence. For the first time, we show that Bmi1 inhibition may present a genuine therapeutic strategy for recurrent childhood MB, inhibiting not only self-renewal but metastatic spread and spinal tumor dissemination. Selective targeting of MB stem cells using small molecules inhibitors against Bmi1 may further provide avenues for deescalating therapies that have devastating neurological and psychosocial sequela in children with MB.
Airway Closure in Acute Respiratory Distress Syndrome: An Underestimated and Misinterpreted Phenomenon
Authors: Lu Chen, Lorenzo Del Sorbo, Domenico Luca Grieco, Orest Shklar, Detajin Junhasavasdikul, Irene Telias, Eddy Fan, Laurent Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Abstract 50: Cardiomyogenesis in Hypertrophic Cardiomyopathy
Authors: Christian A Arranto, Maria R Iascone, Anna G Sanarico, Matteo Valle, Chiara M Mangiaracina, Federico Quaini, Jan Kajstura, Annarosa Leri, Paolo Ferrazzi, Piero Anversa
Journal: Circulation Research (2012)

Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiovascular disease and the leading cause of sudden death in young adults. HCM is characterized by regional ventricular hypertrophy in the absence of cavitary dilation. Myofibrillar disarray associated with mutations of sarcomeric proteins and collagen accumulation are considered major determinants of the disease phenotype. Septal hypertrophy has been viewed as the result of an increase in size of preexisting myocytes, but whether myocyte formation contributes to septal thickening has never been determined. Thus, 29 patients with HCM undergoing septal myectomy were studied, and 10 sex-, age-matched septa, collected from patients who died from causes other than cardiovascular diseases, were used as controls. Mutations of genes coding for contractile proteins were present in all cases of HCM; 79% of patients were in NYHA class III, 17% in class II, and 4% in class IV. Arrhythmic events consisting of atrial fibrillation and ventricular tachycardia were found in 11 patients. In 8 cases, HCM was diagnosed in family members as well. Septal thickness is the product of myocyte diameter and the number of myocyte across the septum. The thickness of the septum increased 2.3-fold in HCM (Controls: 11±1 mm; HCM: 25±8 mm, p&lt;0.001). Septal thickening in HCM was mediated by a 69% increase in myocyte number (Controls: 722±120; HCM: 1,217±375, p&lt;0.001) and a 31% increase in cell diameter (Controls: 16±3 λm; HCM: 21±4 λm, p&lt;0.001). Myocyte regeneration was confirmed by the expression of the cell cycle protein, Ki67. The number of Ki67-positive myocyte nuclei increased 15-fold in HCM (Controls: 400 myocytes/10 6 cells; HCM: 6,000 myocytes/10 6 cells, p&lt;0.001). In humans, myocyte formation is regulated by commitment of resident c-kit-positive cardiac stem cells (CSCs). In comparison with control hearts, the number of CSCs increased 2.7-fold in patients with HCM (Controls: 11±5 cells/mm 3 ; HCM: 30±17 cells/mm 3 , p&lt;0.01). Additionally, the expression of contractile proteins was detected in differentiating CSCs. In conclusion, myocyte regeneration and hypertrophy contribute to septal thickening in HCM and newly formed myocytes originate from growth activation and lineage specification of resident CSCs.