tbuckley/cabot-search huggingface dataset:
Making the World Health Assembly fit for the 21st century
Authors: I. Kickbusch, M. Bonk
Journal: BMJ (2014)

Needs better quality of debate and use of technology

The 67th World Health Assembly, the annual meeting of the 194 member states of the World Health Organization and its supreme decision making body, ended on 24 May this year. This latest assembly was record breaking: it had 3500 registered participants—2200 delegates of member states led by more than 130 ministers of health and about 1300 observers from international and non-governmental organisations officially related to WHO. This does not include all the others who come to Geneva to lobby and to network. The assembly discussed 66 agenda items; it passed 20 resolutions and 10 decisions based on 80 background papers amounting to about 1000 pages. Some debates continued until 3.30 am, and many agenda items reached their final conclusion only late on Saturday evening, when most participants had left.

It was clear that the assembly is changing its nature. For some, this assembly was the most exhausting meeting they had ever attended, and the director general conceded that the pace of work had been “unhealthy.” Yet for others it reflected the extraordinary vigour of the global health community. Although the deliberations of member states remain at its core—in plenary, in committees A and B—many …
Paroxetine Controlled Release in the Treatment of Menopausal Hot Flashes
Authors: Vered Stearns, Katherine L. Beebe, Malini Iyengar, Eric Dube
Journal: JAMA (2003)

Context Standard therapy for hot flashes has been hormone replacement with estradiol or progestational agents, but recent data suggest that antidepressants inhibiting serotonin reuptake may also be effective. Objective To evaluate a selective serotonin reuptake inhibitor (paroxetine controlled release [CR]) in treating the vasomotor symptoms displayed by a general cross-section of menopausal women. Design and Setting Randomized, double-blind, placebo-controlled, parallel group study conducted across 17 US sites, including urban, suburban, and rural clinics. Patients A total of 165 menopausal women aged 18 years or older experiencing at least 2 to 3 daily hot flashes and must have discontinued any hormone replacement therapy for at least 6 weeks. Women were excluded if they had any signs of active cancer or were undergoing chemotherapy or radiation therapy. Intervention After a 1-week placebo run-in phase, study participants were randomized to receive placebo or receive 12.5 mg/d or 25.0 mg/d of paroxetine CR (in a 1:1:1 ratio) for 6 weeks. Main Outcome Measures Mean change from baseline to week 6 in the daily hot flash composite score (frequency × severity). Results Fifty-six participants were randomly assigned to receive placebo and 51 to receive 12.5 mg/d and 58 to receive 25.0 mg/d of paroxetine CR. The mean reductions in the hot flash frequency composite score from baseline to week 6 were statistically significantly greater for those receiving paroxetine CR than for those receiving placebo. By week 6, the mean daily hot flash frequency went from 7.1 to 3.8 (mean reduction, 3.3) for those in the 12.5-mg/d and from 6.4 to 3.2 (mean reduction, 3.2) for those in the 25-mg/d paroxetine CR groups and from 6.6 to 4.8 (mean reduction, 1.8) for those in the placebo group. Mean placebo-adjusted reduction in hot flash composite scores were −4.7 (95% confidence interval, − 8.1 to −1.3; P = .007) comparing 12.5-mg/d paroxetine CR with placebo; and −3.6 (95% confidence interval, −6.8 to −0.4; P = .03) comparing 25.0-mg/d paroxetine CR with placebo. This corresponded to median reductions of 62.2% for those in the 12.5-mg/d and 64.6% for those in the 25.0-mg/d paroxetine CR groups compared with 37.8% for those in the placebo group. Conclusion Paroxetine CR may be an effective and acceptable alternative to hormone replacement and other therapies in treating menopausal hot flash symptoms.
Some effects of fats with dietary carbohydrates on the lipids on the surface of the skin
Authors: IAN MACDONALD
Journal: British Journal of Dermatology (1973)

Young men and women were given diets containing various carbohydrate mixtures given with either sunflower seed oil or cream and the triglyceride and cholesterol concentration on the surface of the skin above the right scapula was determined. In men, the triglyceride level on the surface of the skin was reduced by sunflower seed oil. In young women the nature of the dietary constituents seemed to have no marked effect on the lipids on the surface of the skin.
Role of CAAT/Enhancer Binding Protein Homologous Protein in Panobinostat-Mediated Potentiation of Bortezomib-Induced Lethal Endoplasmic Reticulum Stress in Mantle Cell Lymphoma Cells
Authors: Rekha Rao, Srilatha Nalluri, Warren Fiskus, Andrew Savoie, Kathleen M. Buckley, Kyungsoo Ha, Ramesh Balusu, Atul Joshi, Veena Coothankandaswamy, Jianguo Tao, Eduardo Sotomayor, Peter Atadja, Kapil N. Bhalla
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Bortezomib induces unfolded protein response (UPR) and endoplasmic reticulum stress, as well as exhibits clinical activity in patients with relapsed and refractory mantle cell lymphoma (MCL). Here, we determined the molecular basis of the improved in vitro and in vivo activity of the combination of the pan-histone deacetylase inhibitor panobinostat and bortezomib against human, cultured, and primary MCL cells. Experimental Design: Immunoblot analyses, reverse transcription-PCR, and immunofluorescent and electron microscopy were used to determine the effects of panobinostat on bortezomib-induced aggresome formation and endoplasmic reticulum stress in MCL cells. Results: Treatment with panobinostat induced heat shock protein 90 acetylation; depleted the levels of heat shock protein 90 client proteins, cyclin-dependent kinase 4, c-RAF, and AKT; and abrogated bortezomib-induced aggresome formation in MCL cells. Panobinostat also induced lethal UPR, associated with induction of CAAT/enhancer binding protein homologous protein (CHOP). Conversely, knockdown of CHOP attenuated panobinostat-induced cell death of MCL cells. Compared with each agent alone, cotreatment with panobinostat increased bortezomib-induced expression of CHOP and NOXA, as well as increased bortezomib-induced UPR and apoptosis of cultured and primary MCL cells. Cotreatment with panobinostat also increased bortezomib-mediated in vivo tumor growth inhibition and improved survival of mice bearing human Z138C MCL cell xenograft. Conclusion: These findings suggest that increased UPR and induction of CHOP are involved in enhanced anti-MCL activity of the combination of panobinostat and bortezomib. Clin Cancer Res; 16(19); 4742–54. ©2010 AACR.
Serum vitamin D-binding protein is a third member of the albumin and alpha fetoprotein gene family.
Authors: N E Cooke, E V David
Journal: Journal of Clinical Investigation (1985)

A near full-length cDNA encoding the human vitamin D-binding protein (hDBP) was isolated from a human liver mRNA expression library. Complete sequence analysis of this clone predicts the full-length amino acid sequence of the pre-hDBP. Comparison of the sequence of the hDBP mRNA and protein to existing protein and nucleic acid data banks demonstrates a strong and highly characteristic homology of the hDBP with human albumin (hALB) and human alpha-fetoprotein (hAFP). Based upon this structural comparison, we establish that DBP is a member of the ALB and AFP gene family.
Burden of disease in adults admitted to hospital in a rural region of coastal Kenya: an analysis of data from linked clinical and demographic surveillance systems
Authors: Anthony O Etyang, Kenneth Munge, Erick W Bunyasi, Lena Matata, Carolyne Ndila, Sailoki Kapesa, Maureen Owiti, Iqbal Khandwalla, Andrew J Brent, Benjamin Tsofa, Pamela Kabibu, Susan Morpeth, Evasius Bauni, Mark Otiende, John Ojal, Philip Ayieko, Maria D Knoll, Liam Smeeth, Thomas N Williams, Ulla K Griffiths, J Anthony G Scott
Journal: The Lancet Global Health (2014)

Estimates of the burden of disease in adults in sub-Saharan Africa largely rely on models of sparse data. We aimed to measure the burden of disease in adults living in a rural area of coastal Kenya with use of linked clinical and demographic surveillance data.We used data from 18,712 adults admitted to Kilifi District Hospital (Kilifi, Kenya) between Jan 1, 2007, and Dec 31, 2012, linked to 790,635 person-years of observation within the Kilifi Health and Demographic Surveillance System, to establish the rates and major causes of admission to hospital. These data were also used to model disease-specific disability-adjusted life-years lost in the population. We used geographical mapping software to calculate admission rates stratified by distance from the hospital.The main causes of admission to hospital in women living within 5 km of the hospital were infectious and parasitic diseases (303 per 100,000 person-years of observation), pregnancy-related disorders (239 per 100,000 person-years of observation), and circulatory illnesses (105 per 100,000 person-years of observation). Leading causes of hospital admission in men living within 5 km of the hospital were infectious and parasitic diseases (169 per 100,000 person-years of observation), injuries (135 per 100,000 person-years of observation), and digestive system disorders (112 per 100,000 person-years of observation). HIV-related diseases were the leading cause of disability-adjusted life-years lost (2050 per 100,000 person-years of observation), followed by non-communicable diseases (741 per 100,000 person-years of observation). For every 5 km increase in distance from the hospital, all-cause admission rates decreased by 11% (95% CI 7–14) in men and 20% (17–23) in women. The magnitude of this decline was highest for endocrine disorders in women (35%; 95% CI 22–46) and neoplasms in men (30%; 9–45).Adults in rural Kenya face a combined burden of infectious diseases, pregnancy-related disorders, cardiovascular illnesses, and injuries. Disease burden estimates based on hospital data are affected by distance from the hospital, and the amount of underestimation of disease burden differs by both disease and sex.The Wellcome Trust, GAVI Alliance.
Advanced Life Support for Out-of-Hospital Respiratory Distress
Authors: Ian G. Stiell, Daniel W. Spaite, Brian Field, Lisa P. Nesbitt, Doug Munkley, Justin Maloney, Jon Dreyer, Lorraine Luinstra Toohey, Tony Campeau, Eugene Dagnone, Marion Lyver, George A. Wells
Journal: New England Journal of Medicine (2007)

Respiratory distress is a common symptom of patients transported to hospitals by emergency medical services (EMS) personnel. The benefit of advanced life support for such patients has not been established.The Ontario Prehospital Advanced Life Support (OPALS) Study was a controlled clinical trial that was conducted in 15 cities before and after the implementation of a program to provide advanced life support for patients with out-of-hospital respiratory distress. Paramedics were trained in standard advanced life support, including endotracheal intubation and the administration of intravenous drugs.The clinical characteristics of the 8138 patients in the two phases of the study were similar. During the first phase, no patients were treated by paramedics trained in advanced life support; during the second phase, 56.6% of patients received this treatment. Endotracheal intubation was performed in 1.4% of the patients, and intravenous drugs were administered to 15.0% during the second phase. This phase of the study was also marked by a substantial increase in the use of nebulized salbutamol and sublingual nitroglycerin for the relief of symptoms. The rate of death among all patients decreased significantly, from 14.3% to 12.4% (absolute difference, 1.9%; 95% confidence interval [CI], 0.4 to 3.4; P=0.01) from the basic-life-support phase to the advanced-life-support phase (adjusted odds ratio, 1.3; 95% CI, 1.1 to 1.5).The addition of a specific regimen of out-of-hospital advanced-life-support interventions to an existing EMS system that provides basic life support was associated with a decrease in the rate of death of 1.9 percentage points among patients with respiratory distress.
Crohn's disease of the mouth: an indicator of intestinal involvement.
Authors: C Scully, K M Cochran, R I Russell, M M Ferguson, M A Ghouri, F D Lee, D G MacDonald, P B McIntyre
Journal: Gut (1982)

Nineteen patients with clinical evidence of oral Crohn's disease but no intestinal symptoms were studied. Oral lesions in all patients were shown histologically to have lymphoedema with or without chronic granulomas consistent with Crohn's disease. Seven patients (37%) had demonstrable intestinal disease on rectal biopsy and four of these had abnormal bowel radiology. All seven had evidence of nutritional deficiency. Patients with clinical features suggesting oral Crohn's disease may have evidence of Crohn's disease in the intestine, although this may not be clinically apparent.
Blood Pressure and Cardiovascular Disease Risk in the Veterans Affairs Diabetes Trial
Authors: Robert J. Anderson, Gideon D. Bahn, Thomas E. Moritz, Derrick Kaufman, Carlos Abraira, William Duckworth
Journal: Diabetes Care (2010)

OBJECTIVE Blood pressure ranges associated with cardiovascular disease (CVD) events in advanced type 2 diabetes are not clear. Our objective was to determine whether baseline and follow-up (On-Study) systolic blood pressure (SBP), diastolic blood pressure (DBP), and SBP combined with DBP predict CVD events in the Veterans Affairs Diabetes Trial (VADT). RESEARCH DESIGN AND METHODS Participants in the VADT (n = 1,791) with hypertension received stepped treatment to maintain blood pressure below the target of 130/80 mmHg in standard and intensive glycemic treatment groups. Blood pressure levels of all subjects at baseline and On-Study were analyzed to detect associations with CVD risk. The primary outcome was the time from randomization to the first occurrence of myocardial infarction, stroke, congestive heart failure, surgery for vascular disease, inoperable coronary disease, amputation for ischemic gangrene, or CVD death. RESULTS Separated SBP ≥140 mmHg had significant risk at baseline (hazards ratio [HR] 1.508, P &amp;lt; 0.001) and On-Study (HR 1.469, P = 0.002). DBP &amp;lt;70 mmHg increased CVD events at baseline (HR 1.482, P &amp;lt; 0.001) and On-Study (HR 1.491, P &amp;lt; 0.001). Combined blood pressure categories indicated high risk for CVD events for SBP ≥140 with DBP &amp;lt;70 mmHg at baseline (HR 1.785, P = 0.03) and On-Study (HR 2.042, P = 0.003) and nearly all SBP with DBP &amp;lt;70 mmHg. CONCLUSIONS Increased risk of CVD events with SBP ≥140 mmHg emphasizes the urgency for treatment of systolic hypertension. Increased risk with DBP &amp;lt;70 mmHg, even when combined with SBP in guideline-recommended target ranges, supports a new finding in patients with type 2 diabetes. The results emphasize that DBP &amp;lt;70 mmHg in these patients was associated with elevated CVD risk and may best be avoided.
Preclinical evidences toward the use of triterpenoid CDDO-Me for solid cancer prevention and treatment
Authors: Yan-Yang Wang, Hong Zhe, Ren Zhao
Journal: Molecular Cancer (2014)

Solid cancer remains a major cause of death in the world. As limited treatment options are currently available to patients with solid cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. The plant-derived triterpenoids, commonly used for medicinal purposes in many Asian countries, poses various pharmacological properties. A large number of triterpenoids exhibit cytotoxicity against a variety of cancer cells, and cancer preventive, as well as anticancer efficacy in preclinical animal models. To improve antitumor activity, some synthetic triterpenoid derivatives have been synthesized, including cyano-3,12-dioxooleana-1,9(11)- dien-28-oic (CDDO), its methyl ester (CDDO-Me), and imidazolide (CDDO-Im) derivatives. In this review, we will critically examine the current preclinical evidences of cancer preventive and therapeutic activity about one of the synthetic triterpenoids, CDDO-Me. Both in vitro and in vivo effects of this agent and related molecular mechanisms are presented.
PWE-167 Anvil suture pull-through technique for laparoscopic circular stapled oesophagojejunostomy: technical report and outcomes: Abstract PWE-167 Figure 1
Authors: G Bouras, S-W Lee, E Nomura, T Tokuhara, N Tanigawa
Journal: Gut (2012)

<h3>Introduction</h3> The development of laparoscopic gastrectomy has lead to the need for intracorporeal stapled oesophagojejunostomy. Described techniques include overlap with a linear stapler<sup>1</sup> and oral insertion of the anvil of a circular stapler.<sup>2</sup> At our unit, we use a novel technique for laparoscopic oesophagojejunostomy by laparoscopic insertion of anvil into the gastrointestinal tract. Here we present our outcomes from laparoscopic oesophagojejunostomy performed by the anvil suture pull-through technique. <h3>Methods</h3> After attaching a suture to the end of the spike of the anvil of a circular stapler, the anvil is inserted into the gastrointestinal tract through a proximal gastrotomy and pushed into the distal oesophagus. The oesophagus is divided below the anvil with a linear stapler. The suture poking out of the staple line is pulled and a small incision is made to allow the spike of the anvil to be delivered. The body of the circular stapler is inserted into the jejunum and combined with the anvil before firing the stapler and completing the double-stapled anastomosis. Intracorporeal oesophagojejunostomy using this technique was performed during laparoscopic proximal and total gastrectomy between 1998 and 2011. <h3>Results</h3> A total of 82 anastomoses were performed using the anvil suture pull-through technique as part of 35 total and 47 proximal gastric resections for gastric cancer. 69 patients (84%) had early gastric cancer. Anastomotic leakage occurred in three patients (3.7%) and stenosis occurred in seven patients (8.5%). Post-operative stasis occurred in one patient (1.2%). No anastomotic bleeding was encountered. Recurrence at the site of the anastomosis was not detected during routine follow-up endoscopy in any of the patients. <h3>Conclusion</h3> Intracorporeal oesophagojejunostomy using our anvil suture pull-through technique is feasible, safe and associated with good outcomes in the context of early gastric cancer. It is a reliable first-line technique and a useful alternative strategy when overlap is not possible or oral anvil insertion is contraindicated. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Okabe H</b>, Obama K, Tanaka E, <i>et al.</i> Intracorporeal esophagojejunal anastomosis after laparoscopic total gastrectomy for patients with gastric cancer. <i>Surg Endosc</i> 2009;<b>23</b>:2167–71. 2. <b>Jeong O</b>, Park YK. Intracorporeal circular stapling esophagojejunostomy using the transorally inserted anvil (OrVil) after laparoscopic total gastrectomy. <i>Surg Endosc</i> 2009;<b>23</b>:2624–30.
Too Much Medicine Happens Too Often
Authors: Tanner J. Caverly, Brandon P. Combs, Christopher Moriates, Neel Shah, Deborah Grady
Journal: JAMA Internal Medicine (2013)

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 Internal Medicine 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 Internal Medicine journal
Wnt Signaling in Neural Circuit Assembly
Authors: Patricia C. Salinas, Yimin Zou
Journal: Annual Review of Neuroscience (2008)

The Wnt family of secreted proteins plays a crucial role in nervous system wiring. Wnts regulate neuronal positioning, polarization, axon and dendrite development, and synaptogenesis. These diverse roles of Wnt proteins are due not only to the large numbers of Wnt ligands and receptors but also to their ability to signal through distinct signaling pathways in different cell types and developmental contexts. Studies on Wnts have shed new light on novel molecular mechanisms that control the development of complex neuronal connections. This review discusses recent advances on how Wnt signaling influences different aspects of neuronal circuit assembly through changes in gene expression and/or cytoskeletal modulation.
Short Communication: The Cardiac Myosin Binding Protein C Arg502Trp Mutation
Authors: Adam J. Saltzman, Debora Mancini-DiNardo, Chumei Li, Wendy K. Chung, Carolyn Y. Ho, Stephanie Hurst, Julia Wynn, Melanie Care, Robert M. Hamilton, Gregor W. Seidman, Joshua Gorham, Barbara McDonough, Elizabeth Sparks, J.G. Seidman, Christine E. Seidman, Heidi L. Rehm
Journal: Circulation Research (2010)

Rationale : The myosin-binding protein C isoform 3 ( MYBPC3 ) variant Arg502Trp has been identified in multiple hypertrophic cardiomyopathy (HCM) cases, but compelling evidence to support or refute the pathogenicity of this variant is lacking. Objective : To determine the prevalence, origin and clinical significance of the MYBPC3 Arg502Trp variant. Methods and Results : The prevalence of MYBPC3 Arg502Trp was ascertained in 1414 sequential HCM patients of primarily European descent. MYBPC3 Arg502Trp was identified in 34 of these 1414 unrelated HCM patients. Segregation of MYBPC3 Arg502Trp with clinical status was assessed in family members. Disease haplotypes were examined in 17 families using two loci flanking MYBPC3 . Family studies identified an additional 43 variant carriers, many with manifest disease, yielding a calculated odds ratio of 11 000:1 for segregation of MYBPC3 Arg502Trp with HCM. Analyses in 17 families showed at least 4 independent haplotypes flanked MYBPC3 Arg502Trp. Eight individuals (4 probands and 4 family members) also had another sarcomere protein gene mutation. Major adverse clinical events occurred in approximately 30% of MYBPC3 Arg502Trp carriers by age 50; these were significantly more likely ( P &lt;0.0001) when another sarcomere mutation was present. Conclusions : MYBPC3 Arg502Trp is the most common and recurrent pathogenic mutation in a diverse primarily European descent HCM cohort, occurring in 2.4% of patients. MYBPC3 Arg502Trp conveys a 340-fold increased risk for HCM by 45 years of age, when more than 50% of carriers have overt disease. HCM prognosis worsens when MYBPC3 Arg502Trp occurs in the setting of another sarcomere protein gene mutation.