tbuckley/cabot-search huggingface dataset:
Distinct effects of acute exercise and breaks in sitting on working memory and executive function in older adults: a three-arm, randomised cross-over trial to evaluate the effects of exercise with and without breaks in sitting on cognition
Authors: Michael J Wheeler, Daniel J Green, Kathryn A Ellis, Ester Cerin, Ilkka Heinonen, Louise H Naylor, Robyn Larsen, Patrik Wennberg, Carl-Johan Boraxbekk, Jaye Lewis, Nina Eikelis, Nicola T Lautenschlager, Bronwyn A Kingwell, Gavin Lambert, Neville Owen, David W Dunstan
Journal: British Journal of Sports Medicine (2019)

Sedentary behaviour is associated with impaired cognition, whereas exercise can acutely improve cognition.We compared the effects of a morning bout of moderate-intensity exercise, with and without subsequent light-intensity walking breaks from sitting, on cognition in older adults.Sedentary overweight/obese older adults with normal cognitive function (n=67, 67±7 years, 31.2±4.1 kg/m2) completed three conditions (6-day washout): SIT (sitting): uninterrupted sitting (8 hours, control); EX+SIT (exercise + sitting): sitting (1 hour), moderate-intensity walking (30 min), uninterrupted sitting (6.5 hours); and EX+BR (exercise + breaks): sitting (1 hour), moderate-intensity walking (30 min), sitting interrupted every 30 min with 3 min of light-intensity walking (6.5 hours). Cognitive testing (Cogstate) was completed at four time points assessing psychomotor function, attention, executive function, visual learning and working memory. Serum brain-derived neurotrophic growth factor (BDNF) was assessed at six time points. The 8-hour net area under the curve (AUC) was calculated for each outcome.Working memory net AUC z-score·hour (95% CI) was improved in EX+BR with a z-score of +28 (-26 to +81), relative to SIT, -25 (-79 to +29, p=0.04 vs EX+BR). Executive function net AUC was improved in EX+SIT, -8 (- 71 to +55), relative to SIT, -80 (-142 to -17, p=0.03 vs EX+SIT). Serum BDNF net AUC ng/mL·hour (95% CI) was increased in both EX+SIT, +171 (-449 to +791, p=0.03 vs SIT), and EX+BR, +139 (-481 to +759, p=0.045 vs SIT), relative to SIT, -227 (-851 to +396).A morning bout of moderate-intensity exercise improves serum BDNF and working memory or executive function in older adults, depending on whether or not subsequent sitting is also interrupted with intermittent light-intensity walking.ACTRN12614000737639.
Viewpoint: Hunger in the midst of plenty
Authors: Rebecca Slack
Journal: BMJ (2007)

I am as familiar as most with the hubbub of the busy ward—telephones, bleeps, voices, and footsteps mixing among the sea of gatherings of uniformed people. But having been a recent inpatient myself, I now recognise what an illusion the bustling ward environment is. Being in hospital was the loneliest experience I have had and I felt I had no control. I entered hospital thinking that I would be cared for by fellow medics who would give me guidance and treatment for the short and longer term …
Refining the dermatological spectrum in primary immunodeficiency: mucosa‐associated lymphoid tissue lymphoma translocation protein 1 deficiency mimicking Netherton/Omenn syndromes
Authors: H. Wiegmann, J. Reunert, D. Metze, T. Marquardt, T. Engel, V. Kunde, S. Ehl, D. Foell, I. Heuvel, V. Oji, H. Wittkowski
Journal: British Journal of Dermatology (2019)

The proteinase mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), which forms part of the caspase recruitment domain-containing protein 11-B-cell lymphoma 10-MALT1 signalosome complex, plays a direct role in nuclear factor kappa B activation. Here, we describe the case of a female infant with severe immune dysregulation leading to recurrent systemic infections, failure to thrive and severe crises of ichthyosiform erythroderma with high levels of serum IgE. Hence, initial symptoms indicated Netherton syndrome or Omenn syndrome. Surprisingly, sequence analyses of SPINK5 and RAG1/RAG2, respectively, excluded these diseases. During the hospital stay the patient's health deteriorated, despite intensive care therapy, and she died. In order to delineate the diagnosis, whole-exome sequencing was performed. Two compound heterozygous mutations in MALT1 were found and verified by Sanger sequencing (exon 2 c.245T>C, exon 2 c.310dup), which led to a MALT1 deficiency at the protein level. Based on these results, an immunological analysis was performed, as was immunofluorescence staining of key skin proteins, to confirm a diagnosis of MALT1 deficiency. This case report provides a closer description of the clinical and histological skin phenotype of MALT1 deficiency, and we conclude that MALT1 deficiency must be considered a possible differential diagnosis of Netherton and Omenn syndromes. What's already known about this topic? Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) deficiency is a combined immunodeficiency. MALT1 is part of the caspase recruitment domain-containing protein 11-B-cell lymphoma 10-MALT1 signalosome complex, which is essential for nuclear factor kappa B activation. Current publications describe a phenotype of recurrent systemic infections; only in a few cases has an inflammatory involvement of the integument been described. What does this study add? A closer description of the cutaneous phenotype of MALT1 deficiency in a patient with two novel MALT1 mutations. Immune mapping of follicular epidermis shows lympho-epithelial Kazal-type-related inhibitor is reduced in MALT1 deficiency and absent on interfollicular staining. Clinically, MALT1 deficiency mimics Netherton syndrome and Omenn syndrome, and should be considered a differential diagnosis.
Coping as an oncology secretary
Authors: Katherine Anderson
Journal: BMJ (2000)

Coping as an oncology secretary I am a mature medical student and while waiting to take up my place at medical school I worked as a temporary medical secretary. For six months I worked in an oncology and palliative care department, and it was here that I learnt a great deal about the hassle that secretaries endure at the hands of consultants and patients.

While the consultants were sympathetic and approachable, the severity of the problems were such that any mistakes by the secretary were potentially hazardous, making my work in this department more stressful than in others.

This was apparent as soon as the phone started to ring on my first day - the phone quickly becoming an instrument to be feared and avoided. Relatives at the end of the line were desperate for comfort, reassurance, and threads of hope.

Because of the demand on the doctors the secretaries had to shield and screen calls, …
The Small GTPase ARF6 Activates PI3K in Melanoma to Induce a Prometastatic State
Authors: Jae Hyuk Yoo, Samuel W. Brady, Lehi Acosta-Alvarez, Aaron Rogers, Jingfu Peng, Lise K. Sorensen, Roger K. Wolff, Tara Mleynek, Donghan Shin, Coulson P. Rich, David A. Kircher, Andrea Bild, Shannon J. Odelberg, Dean Y. Li, Sheri L. Holmen, Allie H. Grossmann
Journal: Cancer Research (2019)

Abstract Melanoma has an unusual capacity to spread in early-stage disease, prompting aggressive clinical intervention in very thin primary tumors. Despite these proactive efforts, patients with low-risk, low-stage disease can still develop metastasis, indicating the presence of permissive cues for distant spread. Here, we show that constitutive activation of the small GTPase ARF6 (ARF6Q67L) is sufficient to accelerate metastasis in mice with BRAFV600E/Cdkn2aNULL melanoma at a similar incidence and severity to Pten loss, a major driver of PI3K activation and melanoma metastasis. ARF6Q67L promoted spontaneous metastasis from significantly smaller primary tumors than PTENNULL, implying an enhanced ability of ARF6-GTP to drive distant spread. ARF6 activation increased lung colonization from circulating melanoma cells, suggesting that the prometastatic function of ARF6 extends to late steps in metastasis. Unexpectedly, ARF6Q67L tumors showed upregulation of Pik3r1 expression, which encodes the p85 regulatory subunit of PI3K. Tumor cells expressing ARF6Q67L displayed increased PI3K protein levels and activity, enhanced PI3K distribution to cellular protrusions, and increased AKT activation in invadopodia. ARF6 is necessary and sufficient for activation of both PI3K and AKT, and PI3K and AKT are necessary for ARF6-mediated invasion. We provide evidence for aberrant ARF6 activation in human melanoma samples, which is associated with reduced survival. Our work reveals a previously unknown ARF6-PI3K-AKT proinvasive pathway, it demonstrates a critical role for ARF6 in multiple steps of the metastatic cascade, and it illuminates how melanoma cells can acquire an early metastatic phenotype in patients. Significance: These findings reveal a prometastatic role for ARF6 independent of tumor growth, which may help explain how melanoma spreads distantly from thin, early-stage primary tumors.
Tips for Choosing a Deep Brain Stimulation Device
Authors: Michael S. Okun
Journal: JAMA Neurology (2019)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
Light therapies to improve sleep in intrinsic circadian rhythm sleep disorders and neuro-psychiatric illness: A systematic review and meta-analysis
Authors: Sophie M. Faulkner, Penny E. Bee, Nicholas Meyer, Derk-Jan Dijk, Richard J. Drake
Journal: Sleep Medicine Reviews (2019)

Circadian dysregulation causes sleep disturbance and impacts quality of life and functioning. Some interventions target circadian entrainment through modifying light exposure, but existing reviews of light interventions for sleep improvement include few studies in psychiatric populations. We examined effect of light interventions on sleep quality, duration and timing, and effect moderators. We included controlled studies in intrinsic circadian rhythm disorders (such as advanced or delayed sleep) and in neuropsychiatric disorders with assumed high prevalence of circadian dysregulation (such as affective and psychotic disorders). Articles were identified through database searching: 40 studies reporting 49 relevant intervention comparisons met inclusion criteria. Meta-analysis showed improvements in sleep continuity (ES = -0.23, p = 0.000), self-reported sleep disturbance (ES = -0.32, p = 0.014), and advancement of delayed sleep timing (ES = -0.34, p = 0.010). Although the small number of studies limited meta-regression, evening light avoidance was associated with greater increase in total sleep time. Effects of light on sleep and circadian outcomes have received limited attention in studies in psychiatric disorders, but results were promising in these groups. These findings invite further refinement and testing of light interventions to improve sleep in psychiatric disorders, with improved assessment and specification of problems, and the development and implementation of light schedule interventions for delayed sleep.
Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer
Authors: Payal Tiwari, Ariane Blank, Chang Cui, Kelly Q. Schoenfelt, Guolin Zhou, Yanfei Xu, Galina Khramtsova, Funmi Olopade, Ajay M. Shah, Seema A. Khan, Marsha Rich Rosner, Lev Becker
Journal: The Journal of Experimental Medicine (2019)

Obesity is associated with increased incidence and severity of triple-negative breast cancer (TNBC); however, mechanisms underlying this relationship are incompletely understood. Here, we show that obesity reprograms mammary adipose tissue macrophages to a pro-inflammatory metabolically activated phenotype (MMe) that alters the niche to support tumor formation. Unlike pro-inflammatory M1 macrophages that antagonize tumorigenesis, MMe macrophages are pro-tumorigenic and represent the dominant macrophage phenotype in mammary adipose tissue of obese humans and mice. MMe macrophages release IL-6 in an NADPH oxidase 2 (NOX2)-dependent manner, which signals through glycoprotein 130 (GP130) on TNBC cells to promote stem-like properties including tumor formation. Deleting Nox2 in myeloid cells or depleting GP130 in TNBC cells attenuates obesity-augmented TNBC stemness. Moreover, weight loss reverses the effects of obesity on MMe macrophage inflammation and TNBC tumor formation. Our studies implicate MMe macrophage accumulation in mammary adipose tissue as a mechanism for promoting TNBC stemness and tumorigenesis during obesity.
Mens' brains have built in sexual censor
Authors: Siân Knight
Journal: BMJ (2001)

She got legs, she knows how to use 'em



Scientists at the University of Montreal have located the part of the brain that controls primitive sexual urges in men. The study, in the Journal of Neuroscience (2001;21:1-6), reports that when a group of 12 men were asked to do whatever necessary to avoid sexual arousal while watching erotic films, the prefrontal cortex of the brain of the subjects was …
Social responsibility: a missing ingredient
Authors: Larry R Faulkner
Journal: BMJ (2001)

A crucial component of medical education As academic medicine enters the 21st century, some educators are concerned that the profession is in danger of losing sight of its fundamental purposes and values.1 There has also been a call for more attention to be paid to the moral development and character of medical students.23 It seems that the fiscal, legal, and political realities of the new healthcare era may easily distract from the true purpose of medical education. The American Association of Medical Colleges (AAMC) has recognised the vital importance of understanding and nurturing the social contract that exists between medical schools and the public. The best way to fulfill this contract is to educate medical students “in a manner that instills appropriate professional attitudes, values, and skills.”4 If the AAMC is correct, and I believe it is, then it also follows that part of the social contract for medical schools is a duty to educate their students to be socially responsible doctors.

The first question to logically follow from this discussion is, “What …
NHS England finalises procurement to eliminate hepatitis C
Authors: Nigel Hawkes
Journal: BMJ (2019)

After lengthy negotiations and a court battle,1 NHS England has reached agreement with three drug companies to supply drugs to eliminate hepatitis C.

The procurement, said to be the largest ever negotiated by the NHS, was complex because it set out to acquire treatments on the best possible terms for the NHS while avoiding the “winner takes all” approach based simply on price. The aim was to provide certainty so that the companies could plan several years ahead.

NHS England also wanted the companies to help find patients, many of whom might not even realise they carry hepatitis C. More than two thirds of the estimated 160 000 people infected with the virus don’t currently have a diagnosis.

A further complication was that of the three companies—Gilead Sciences, Merck Sharp and …
BMA supports junior doctors who boycott training reforms
Authors: Richard Hurley
Journal: BMJ (2004)

Junior doctors unanimously backed a vote of no confidence in the UK government's reforms to their training at the BMA's annual junior doctors' conference in London on 8 May. The BMA pledged support for junior doctors who boycott new training programmes, expressed concern over the possible lowering of professional standards, and intends to lobby for a delay in implementation of new reforms.

The government describes its reforms--Modernising Medical Careers--as a means of improving “the quality of training for …
Consent for intimate examinations may not be adequate
Authors: Mareeni Raymond
Journal: BMJ (2003)

Doctors teaching students to do intimate examinations on anaesthetised patients do not obtain adequate consent in almost a quarter of cases, a study has shown. The study, led by a medical student, surveyed 386 students in the second, third, and fourth years of one medical school and asked students about intimate examinations they had done.

Around 702 examinations were done on sedated or anaesthetised patients. In only 24%, written consent was obtained, and a further 24% were apparently conducted without written or oral …
Abstract 18387: Applicability of Randomized Controlled Trials for Coronary Revascularization for Angina to Real World Academic Practice
Authors: John B Wong, Hui-Jie Lee, Linda K Shaw, Issa J Dahabreh, Elizabeth R DeLong
Journal: Circulation (2017)

Introduction: Although randomized controlled trials (RCT) limit bias and confounding, their restrictive selection criteria have led to concerns about their representativeness of real world practice...
Recent advances in understanding tumor stroma-mediated chemoresistance in breast cancer
Authors: Jana Plava, Marina Cihova, Monika Burikova, Miroslava Matuskova, Lucia Kucerova, Svetlana Miklikova
Journal: Molecular Cancer (2019)

Although solid tumors comprise malignant cells, they also contain many different non-malignant cell types in their micro-environment. The cellular components of the tumor stroma consist of immune and endothelial cells combined with a heterogeneous population of stromal cells which include cancer-associated fibroblasts. The bi-directional interactions between tumor and stromal cells therefore substantially affect tumor cell biology. Herein, we discuss current available information on these interactions in breast cancer chemo-resistance. It is acknowledged that stromal cells extrinsically alter tumor cell drug responses with profound consequences for therapy efficiency, and it is therefore essential to understand the molecular mechanisms which contribute to these substantial alterations because they provide potential targets for improved cancer therapy. Although breast cancer patient survival has improved over the last decades, chemo-resistance still remains a significant obstacle to successful treatment. Appreciating the important experimental evidence of mesenchymal stromal cells and cancer-associated fibroblast involvement in breast cancer clinical practice can therefore have important therapeutic implications.
Spinal Claudication Secondary to Anterior Disco-Osteo-Arterial Conflict and Mimicking Stiff Person Syndrome
Authors: Olwen C. Murphy, Philippe Gailloud, Scott D. Newsome
Journal: JAMA Neurology (2019)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
Network approach identifies Pacer as an autophagy protein involved in ALS pathogenesis
Authors: S. Beltran, M. Nassif, E. Vicencio, J. Arcos, L. Labrador, B. I. Cortes, C. Cortez, C. A. Bergmann, S. Espinoza, M. F. Hernandez, J. M. Matamala, L. Bargsted, S. Matus, D. Rojas-Rivera, M. J. M. Bertrand, D. B. Medinas, C. Hetz, P. A. Manque, U. Woehlbier
Journal: Molecular Neurodegeneration (2019)

Amyotrophic lateral sclerosis (ALS) is a multifactorial fatal motoneuron disease without a cure. Ten percent of ALS cases can be pointed to a clear genetic cause, while the remaining 90% is classified as sporadic. Our study was aimed to uncover new connections within the ALS network through a bioinformatic approach, by which we identified C13orf18, recently named Pacer, as a new component of the autophagic machinery and potentially involved in ALS pathogenesis.Initially, we identified Pacer using a network-based bioinformatic analysis. Expression of Pacer was then investigated in vivo using spinal cord tissue from two ALS mouse models (SOD1G93A and TDP43A315T) and sporadic ALS patients. Mechanistic studies were performed in cell culture using the mouse motoneuron cell line NSC34. Loss of function of Pacer was achieved by knockdown using short-hairpin constructs. The effect of Pacer repression was investigated in the context of autophagy, SOD1 aggregation, and neuronal death.Using an unbiased network-based approach, we integrated all available ALS data to identify new functional interactions involved in ALS pathogenesis. We found that Pacer associates to an ALS-specific subnetwork composed of components of the autophagy pathway, one of the main cellular processes affected in the disease. Interestingly, we found that Pacer levels are significantly reduced in spinal cord tissue from sporadic ALS patients and in tissues from two ALS mouse models. In vitro, Pacer deficiency lead to impaired autophagy and accumulation of ALS-associated protein aggregates, which correlated with the induction of cell death.This study, therefore, identifies Pacer as a new regulator of proteostasis associated with ALS pathology.
Dose–response curves for co-exposure inhalation challenges with ozone and pollen allergen
Authors: Pia Viuf Ørby, Jakob Hjort Bønløkke, Bo Martin Bibby, Peter Ravn, Ole Hertel, Torben Sigsgaard, Vivi Schlünssen
Journal: European Respiratory Journal (2019)

<b>Exposure to low, naturally occurring, levels of ozone do not alter the bronchial response profile to pollen allergen, or lower the PD<sub>20</sub> in atopic individuals, estimated by applying a novel non-linear model approach</b>http://bit.ly/2XQjzwI
They F**** You Up: How to Survive Family Life
Authors: Sabina Dosani
Journal: BMJ (2003)

Apparently, your parents are more likely to attribute your successes to their prudent nurture but blame genes for their less successful offspring. Where do you stand in the nature versus nurture debate? Clinical child psychologist Oliver James believes our earliest experiences make us who we are. Understand your past, he says, and you control your future. What if you do not believe that it is entirely nature or nurture that defines us, but a bit of both? James is dismissive of fence …