tbuckley/cabot-search huggingface dataset:
Can diaspora-led organisations play a prominent part in global surgery?
Authors: Faheem Ahmed, Na'eem Ahmed, Bruce Keogh, David Nicholson, Haile T Debas, Paul E Farmer
Journal: The Lancet Global Health (2015)

The high number of trained staff in countries with a disproportionately small burden of disease has exacerbated inequalities in global health and surgery. It is estimated that in low-income countries there is a shortage of about 2·5 million members of staff , including surgeons and midwives, to provide essential health interventions. Better fi nancial and education opportunities have been cited as common incentives for workers to emigrate, with risk of conflict and disease threatening their safety and security in their own countries. By training providers who later migrate overseas, lowincome countries are losing more than $500 million each year as they effectively subsidise their wealthier counterparts. D i a s p o r a l e d o r g a n i s a t i o n s (DLOs) can have an important role in addressing unmet surgical need in low-income and middle-income countries. These organisations have the unique advantage of being able to relate to the cultural sensitivities of local populations, which is particularly pert inent with mult ifaceted conditions such as obstetric fi stula. In many ways, obstetric fi stula represents a microcosm of the international community’s failure to emphasise the need for cost-effective surgical interventions, and the inability to encourage community-level initiatives that empower women. Although maternal mortality has almost halved over the past two decades, there exists a need to address underlying social causes such as early marriage, which substantially contribute to maternal morbidity. By facilitating clinical and reproductive sexual health programmes for women in rural Bangladesh, DLOs such as Selfl ess are well placed to achieve this. DLOs are better able to expand community links and develop longterm partnerships, contributing to a more meaningful collaboration between high-income and low-income countries. In an era of globalisation, policy makers must capitalise on this underused resource by supporting diaspora communities to improve care in their countries of origin. In so doing, this support will not only alleviate the burden of the so-called brain drain but also address widening inequalities in surgical care. If low-income countries do not address such issues by seeking solutions from within its own communities both at home and overseas, they will struggle to achieve sustainability in the post-2015 agenda.
Molecular Evolution of α-Latrotoxin, the Exceptionally Potent Vertebrate Neurotoxin in Black Widow Spider Venom
Authors: Jessica E. Garb, Cheryl Y. Hayashi
Journal: Molecular Biology and Evolution (2013)

Black widow spiders (members of the genus Latrodectus) are widely feared because of their potent neurotoxic venom. α-Latrotoxin is the vertebrate-specific toxin responsible for the dramatic effects of black widow envenomation. The evolution of this toxin is enigmatic because only two α-latrotoxin sequences are known. In this study, ∼4 kb α-latrotoxin sequences and their homologs were characterized from a diversity of Latrodectus species, and representatives of Steatoda and Parasteatoda, establishing the wide distribution of latrotoxins across the mega-diverse spider family Theridiidae. Across black widow species, α-latrotoxin shows ≥94% nucleotide identity and variability consistent with purifying selection. Multiple codon and branch-specific estimates of the nonsynonymous/synonymous substitution rate ratio also suggest a long history of purifying selection has acted on α-latrotoxin across Latrodectus and Steatoda. However, α-latrotoxin is highly divergent in amino acid sequence between these genera, with 68.7% of protein differences involving non-conservative substitutions, evidence for positive selection on its physiochemical properties and particular codons, and an elevated rate of nonsynonymous substitutions along α-latrotoxin's Latrodectus branch. Such variation likely explains the efficacy of red-back spider, L. hasselti, antivenom in treating bites from other Latrodectus species, and the weaker neurotoxic symptoms associated with Steatoda and Parasteatoda bites. Long-term purifying selection on α-latrotoxin indicates its functional importance in black widow venom, even though vertebrates are a small fraction of their diet. The greater differences between Latrodectus and Steatoda α-latrotoxin, and their relationships to invertebrate-specific latrotoxins, suggest a shift in α-latrotoxin toward increased vertebrate toxicity coincident with the evolution of widow spiders.
Regulated Cell Death in AKI
Authors: Andreas Linkermann, Guochun Chen, Guie Dong, Ulrich Kunzendorf, Stefan Krautwald, Zheng Dong
Journal: Journal of the American Society of Nephrology (2014)

AKI is pathologically characterized by sublethal and lethal damage of renal tubules. Under these conditions, renal tubular cell death may occur by regulated necrosis (RN) or apoptosis. In the last two decades, tubular apoptosis has been shown in preclinical models and some clinical samples from patients with AKI. Mechanistically, apoptotic cell death in AKI may result from well described extrinsic and intrinsic pathways as well as ER stress. Central converging nodes of these pathways are mitochondria, which become fragmented and sensitized to membrane permeabilization in response to cellular stress, resulting in the release of cell death-inducing factors. Whereas apoptosis is known to be regulated, tubular necrosis was thought to occur by accident until recent work unveiled several RN subroutines, most prominently receptor-interacting protein kinase-dependent necroptosis and RN induced by mitochondrial permeability transition. Additionally, other cell death pathways, like pyroptosis and ferroptosis, may also be of pathophysiologic relevance in AKI. Combination therapy targeting multiple cell-death pathways may, therefore, provide maximal therapeutic benefits.
IL-21R signaling is critical for induction of spontaneous experimental autoimmune encephalomyelitis
Authors: Youjin Lee, Meike Mitsdoerffer, Sheng Xiao, Guangxiang Gu, Raymond A. Sobel, Vijay K. Kuchroo
Journal: Journal of Clinical Investigation (2015)

IL-17-producing CD4+ T cells (Th17 cells) have well-described pathogenic roles in tissue inflammation and autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE); however, the involvement of IL-21 in these processes has remained controversial. While IL-21 is an essential autocrine amplification factor for differentiation of Th17 cells, the loss of IL-21 or IL-21 receptor (IL-21R) does not protect mice from actively induced EAE. Here, we utilized a transgenic EAE mouse model, in which T and B cells overexpress receptors for myelin oligodendrocyte glycoprotein (MOG) (referred to as 2D2xTH mice), and demonstrated that IL-21 is critical for the development of a variant form of spontaneous EAE in these animals. Il21r deletion in 2D2xTH mice reduced the incidence and severity of spontaneous EAE, which was associated with a defect in Th17 cell generation. Moreover, IL-21R deficiency limited IL-23R expression on Th17 cells and inhibited expression of key molecules involved in the generation of pathogenic Th17 cells. Conversely, loss of IL-23R in 2D2xTH mice resulted in complete resistance to the development of spontaneous EAE. Our data identify a previously unappreciated role for IL-21 in EAE and reveal that IL-21-mediated signaling supports generation and stabilization of pathogenic Th17 cells and development of spontaneous autoimmunity.
Periventricular Heterotopia: An X-Linked Dominant Epilepsy Locus Causing Aberrant Cerebral Cortical Development
Authors: Y.Z. Eksioğlu, I.E. Scheffer, P. Cardenas, J. Knoll, F. DiMario, G. Ramsby, M. Berg, K. Kamuro, S.F. Berkovic, G.M. Duyk, J. Parisi, P.R. Huttenlocher, C.A. Walsh
Journal: Neuron (1996)

Periventricular heterotopia (PH) involves dramatic malformations of the human cerebral cortex. Here we show that PH is closely linked to markers in distal Xq28 (maximal two-point lod score = 4.77 for F8C at θ = 0; maximal multipoint lod score = 5.37), so that affected females are obligatory mosaics for the mutation; that PH is lethal to at least some affected males; that PH malformations consist of well-differentiated cortical neurons filling the adult subependymal zone; and that individuals with PH are at high risk for epilepsy, though they have no other neurological or external stigmata. The PH gene may represent an important epilepsy susceptibility locus in addition to playing a key role in normal cortical development.
Echocardiogram in Ebstein's Anomaly with Wolff-Parkinson-White Preexcitation Syndrome, Type B
Authors: ABDUL J. TAJIK, GERALD T. GAU, EMILIO R. GIULIANI, DONALD G. RITTER, THOMAS T. SCHATTENBERG
Journal: Circulation (1973)

The echocardiographic features of Ebstein's anomaly include a large anterior chamber, paradoxic ventricular septal motion (type B), increased velocity and amplitude of anterior tricuspid leaflet (ATL) motion, and delayed closure of the ATL. This delayed closure has been thought to be secondary to right bundle-branch block (RBBB). We have studied two patients by simultaneous echocardiography and phonocardiography. The findings in both patients were similar. One patient had RBBB and therefore resembles the previously reported patients. However, the other patient had W-P-W preexcitation syndrome, type B, and is reported here in more detail. The ATL closure of this patient was markedly delayed in spite of right ventricular preexcitation. This finding gives further insight into the altered pathophysiology in Ebstein's anomaly and implies that the delayed ATL closure is probably not due to RBBB and may be a specific feature of this anomaly.
Posttraumatic Stress Symptoms During Treatment in Parents of Children With Cancer
Authors: Anne E. Kazak, C. Alexandra Boeving, Melissa A. Alderfer, Wei-Ting Hwang, Anne Reilly
Journal: Journal of Clinical Oncology (2005)

Purpose The conceptualization of childhood cancer and its treatment as traumatic has gained increasing support in the growing literature on medically related posttraumatic stress. Posttraumatic stress symptoms (PTSS) such as intrusive thoughts, physiologic arousal, and avoidance have been documented in mothers and fathers of childhood cancer survivors. In this study we investigated the presence of PTSS in parents of children currently in treatment and their association with treatment intensity and length of time since diagnosis. Methods Mothers (N = 119) and fathers (N = 52) of children currently in treatment for a childhood malignancy completed questionnaire measures of PTSS. Outcomes on these measures were compared with a sample of parents of childhood cancer survivors from our hospital. Oncologist ratings of treatment intensity were obtained based on diagnosis, treatment modalities, and protocol number. Results All but one parent reported PTSS. Mean scores indicated moderate PTSS for both mothers and fathers. In families with two participating parents, nearly 80% had at least one parent with moderate-to-severe PTSS. There were minimal associations between PTSS and length of time since diagnosis. Conclusion PTSS are common among parents of children currently undergoing cancer treatment. Trauma-informed psychosocial interventions can be used to help patients and families, including normalizing the experience as potentially traumatic and using evidence-based interventions that are emerging to facilitate long-term well-being.
Drop out rate in medical schools seems reasonable
Authors: I C Mcmanus
Journal: BMJ (1996)

Table 1-Number of laboratories (n = 103) making tests for H pyloni available to gastroenterologists, other hospital doctors, and general practitioners (GPs) Other hospital Test Gastroenterologists doctors GPs Urea breath test only (13C or 14C, or both) 7 4 4 Urea breath test and serum assay 14 4 1 Serum assay only 53 57 59* Near patient test only 1 1 1 Total offering service 75 66 65 No service offered 28 37 38 *Two further laboratories offered serum tests to fundholding GPs only.all.Fourteen planned to introduce a noninvasive test within the next 12 months, though six would be restricting this service to hospital doctors.Many of the guidelines on managing dyspepsia that emanate from secondary care advise that the success of eradication treatment should be confirmed by a laboratory test.However, the urea breath test, which is most suitable for this, was provided to gastroenterologists by only 20% ofthe laboratories and to general practitioners by only 8%.Some gastroenterology units have their own facilities for urea breath tests and make these available to general practitioners on an ad hoc basis.Near patient testing kits can also be bought by general practitioners.These alternative sources are unlikely to have an appreciable impact on the overall availability to general prac- titioners of tests for Hpylori.The restricted availability of non-invasive tests for H pylori limits both the effective use of gastroscopy services and the implementation of management guidelines for peptic ulcer disease.These tests, particularly urea breath tests, should be more widely available, and they should be as accessible to general practitioners, who manage 90% of peptic ulcer disease, as they are to gastroenterologists.
Achalasia complicated by oesophageal squamous cell carcinoma: a prospective study in 195 patients.
Authors: M A Meijssen, H W Tilanus, M van Blankenstein, W C Hop, G L Ong
Journal: Gut (1992)

To determine the incidence of oesophageal carcinoma in patients with achalasia and to establish the efficacy of endoscopic surveillance, 195 consecutive patients with achalasia (90 men and 105 women, mean age 52 years), who were treated by pneumatic dilatation in our institution between 1973 and 1988 were prospectively studied. None of the patients had undergone cardiomyotomy. Follow up totalled 874 person years after pneumatic dilatation. In this period three patients developed an oesophageal squamous cell carcinoma. The mean age at diagnosis of the oesophageal carcinoma was 68 years (37, 77, and 89 years). The mean period between the onset of dysphagia and the diagnosis of the tumour was 17 years (19, 28, and 5 years); the mean interval between the diagnosis of achalasia and carcinoma was 5.7 years (5, 8, and 4 years). The incidence of oesophageal squamous cell carcinoma in this series (3.4/1000 patients per year) is significantly higher than the statistically expected incidence (0.104/1000 patients per year) using age and sex specific incidence data from the population of the Netherlands (Poisson statistics: p less than 0.001). The risk of developing oesophageal squamous cell carcinoma in patients with achalasia is therefore increased 33 fold. Periodic endoscopy showed the potential for detecting early stage oesophageal carcinoma in two cases but a larger study with a longer follow up is required to determine the efficacy of endoscopic screening in improving the prognosis for patients with achalasia who develop oesophageal squamous cell carcinoma.
Effectiveness of Primary Care–Relevant Treatments for Obesity in Adults: A Systematic Evidence Review for the U.S. Preventive Services Task Force
Authors: Erin S. LeBlanc, Elizabeth O'Connor, Evelyn P. Whitlock, Carrie D. Patnode, Tanya Kapka
Journal: Annals of Internal Medicine (2011)

Background: Overweight and obesity in adults are common and adversely affect health. Purpose: To summarize effectiveness and harms of primary care–relevant weight-loss interventions for overweight and obese adults. Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO from January 2005 to September 2010; systematic reviews for identifying trials before 2005. Study Selection: Two investigators appraised 6498 abstracts and 648 articles. Clinical trials were included if control groups received minimal interventions. Articles were rated as good, fair, or poor by using design-specific criteria. Data Extraction: One investigator abstracted study characteristics and findings for good- and fair-quality studies; a second checked them. Data Synthesis: Behaviorally based treatment resulted in 3-kg (6.6-lb) greater weight loss in intervention than control participants after 12 to 18 months, with more treatment sessions associated with greater loss. Limited data suggest weight-loss maintenance for 1 year or more. Orlistat plus behavioral intervention resulted in 3-kg (6.6-lb) more weight loss than did placebo after 12 months. Metformin resulted in less weight loss. Data on effects of weight-loss treatment on long-term health outcomes (for example, death and cardiovascular disease) were insufficient. Weight-loss treatment reduced diabetes incidence in participants with prediabetes. Effects on intermediate outcomes (for example, lipids and blood pressure) were mixed and small. Data on serious medication harms were insufficient. Medications commonly caused withdrawals due to gastrointestinal symptoms. Limitations: Few studies reported health outcomes. Behaviorally based treatments were heterogeneous and specific elements were not well-described. Many studies could not be pooled because of insufficient reporting of variance data. Medication trials had high attrition, lacked postdiscontinuation data, and were inadequately powered for rare adverse effects. Conclusion: Behaviorally based treatments are safe and effective for weight loss and maintenance. Primary Funding Source: Agency for Healthcare Research and Quality.
Gene Expression Signature–Based Prognostic Risk Score in Gastric Cancer
Authors: Jae Yong Cho, Jae Yun Lim, Jae Ho Cheong, Yun-Yong Park, Se-Lyun Yoon, Soo Mi Kim, Sang-Bae Kim, Hoguen Kim, Soon Won Hong, Young Nyun Park, Sung Hoon Noh, Eun Sung Park, In-Sun Chu, Waun Ki Hong, Jaffer A. Ajani, Ju-Seog Lee
Journal: Clinical Cancer Research (2011)

Despite continual efforts to develop a prognostic model of gastric cancer by using clinical and pathologic parameters, a clinical test that can discriminate patients with good outcomes from those with poor outcomes after gastric cancer surgery has not been established. We aim to develop practical biomarker-based risk score that can predict relapse of gastric cancer after surgical treatment.Microarray technologies were used to generate and analyze gene expression profiling data from 65 gastric cancer patients to identify biomarker genes associated with relapse. The association of expression patterns of identified genes with relapse and overall survival was validated in independent gastric cancer patients.We uncovered two subgroups of gastric cancer that were strongly associated with the prognosis. For the easy translation of our findings into practice, we developed a scoring system based on the expression of six genes that predicted the likelihood of relapse after curative resection. In multivariate analysis, the risk score was an independent predictor of relapse in a cohort of 96 patients. We were able to validate the robustness of the six-gene signature in an additional independent cohort.The risk score derived from the six-gene set successfully prognosticated the relapse of gastric cancer patients after gastrectomy.
Three distinct classes of regulatory cytokines control endothelial cell MHC antigen expression. Interactions with immune gamma interferon differentiate the effects of tumor necrosis factor and lymphotoxin from those of leukocyte alpha and fibroblast beta interferons.
Authors: L A Lapierre, W Fiers, J S Pober
Journal: The Journal of Experimental Medicine (1988)

Recombinant preparations of TNF and lymphotoxin (LT) increase the expression of class I MHC antigens on cultured human endothelial cells (EC) without inducing expression of class II antigens. These actions are similar to those of rIFN-alpha or rIFN-beta. However, TNF and LT differ from IFN-alpha/beta in that the former synergize with IFN-gamma for class I regulation whereas the latter do not. Furthermore, LT or TNF do not affect IFN-gamma-mediated class II induction at optimal class I inducing concentrations (100 U/ml), whereas IFN-alpha and IFN-beta (at their optimal concentrations of 1,000 U/ml) are strikingly inhibitory. LT and TNF also can further increase expression of class I antigens on cells already maximally stimulated by IFN-alpha or IFN-beta. A recombinant preparation of IL-6 (formerly called 26-kD protein, IFN-beta 2, or B cell stimulating factor 2) was without effect on class I expression in EC. These data make it seem unlikely that the actions of LT or TNF on EC expression of MHC antigens are mediated through autocrine or paracrine production of IFN-alpha, IFN-beta or IL-6. More importantly, they suggest that LT or TNF are more likely to be immunostimulatory, whereas IFN-alpha or IFN-beta are more likely to be immunoinhibitory in vivo, a consideration of potential relevance for cytokine administration to various patient populations.
Bariatric Surgery, Exercise, and Inpatient Glycemia Treatment
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2010)

Bariatric surgery in diabetesLee Kaplan (Boston, MA) discussed new information based on studies of bariatric surgery in diabetes.Surgery is performed in 0.25% of Americans with obesity, so it is unlikely that it in itself can address the U.S. diabetes or obesity issues, but lessons from its use may shed light on the approach to obesity and diabetes for the overall population.The biology of obesity suggests that it is caused by inactivity and overnutriton and likely stress as well.There is a huge burden of obesityassociated illness, including malignancy, and obesity has a devastating effect on quality of life and also on what is termed societal "efficacy" and socioeconomic status.The physiology of obesity involves central regulation of food intake, nutrient handling, and energy expenditure, with adipose tissue energy stores regulating levels of signals such as leptin, and information from liver, muscle, and bone on metabolic needs coupled with information from the gastrointestinal tract and sensory organs regarding the quantity and quality of nutrient intake.A unifying theme is the body's defense of fat (rather than of total body weight).Surgery includes the Roux-en-Y combination gastric restriction and bypass (RYGB) of distal stomach, duodenum, and proximal jejunum, which is the most effective, and may be the most appropri-
Monoclonal immunoglobulin A antibody directed against serotype-specific epitope of Shigella flexneri lipopolysaccharide protects against murine experimental shigellosis.
Authors: A Phalipon, M Kaufmann, P Michetti, J M Cavaillon, M Huerre, P Sansonetti, J P Kraehenbuhl
Journal: The Journal of Experimental Medicine (1995)

To determine the role of humoral mucosal immune response in protection against shigellosis, we have obtained a monoclonal dimeric immunoglobulin A (IgA) antibody specific for Shigella flexneri serotype 5a lipopolysaccharide (mIgA) and used a murine pulmonary infection model that mimics the lesions occurring in natural intestinal infection. Adult BALB/c mice challenged with 10(7) S. flexneri organisms developed a rapid inflammatory response characterized by polymorphonuclear cell infiltration around and within the bronchi and strong systemic interleukin 6 response. Implantation of hybridoma cells in the back of mice, resulting in the development of a myeloma tumor producing mIgA in the serum and subsequently secretory mIgA in local secretions, or direct intranasal administration of these antibodies, protected the animals against subsequent intranasal challenge with S. flexneri serotype 5a. Absence of histopathological lesion and significant decrease in bacterial load of the lungs and of systemic interleukin 6 response were the three major criteria of protection. This protection was shown to be serotype-specific and dependent on local concentration of mIgA. These data demonstrate that mucosal antibodies directed against a single polysaccharidic surface epitope of Shigella can protect against the disease.