tbuckley/cabot-search huggingface dataset:
Randomized, controlled trial evaluating the effect of multi-strain probiotic on the mucosal microbiota in canine idiopathic inflammatory bowel disease
Authors: Robin White, Todd Atherly, Blake Guard, Giacomo Rossi, Chong Wang, Curtis Mosher, Craig Webb, Steve Hill, Mark Ackermann, Peter Sciabarra, Karin Allenspach, Jan Suchodolski, Albert E. Jergens
Journal: Gut Microbes (2017)

The intestinal microbiota is increasingly linked to the pathogenesis of idiopathic inflammatory bowel disease (IBD) in dogs. While studies have reported alterations in fecal (luminal) microbial populations, only limited information is available about the mucosal microbiota of IBD dogs at diagnosis and following medical therapy. Our aim was to characterize the mucosal microbiota and determine the clinical, microbiological, and mucosal homeostatic effects of probiotic treatment in dogs with IBD. Thirty four IBD dogs were randomized to receive standard therapy (ST = diet + prednisone) with or without probiotic. Tissue sections from endoscopic biopsies were evaluated by fluorescence in situ hybridization (FISH) on a quantifiable basis. Disease activity and changes in mucosal microbiota and tight junction protein (TJP) expression were assessed before and after 8 weeks of IBD therapy. ST and ST/probiotic therapy modulated the number of mucosal bacteria of IBD dogs in a similar fashion. Both treatments increased the numbers of total bacteria and individual species residing within adherent mucus, with ST therapy increasing Bifidobacterium spp. and ST/probiotic therapy increasing Lactobacillus spp (P < 0.05 for both), respectively. Both treatments were associated with rapid clinical remission but not improvement in histopathologic inflammation. Probiotic therapy was associated with upregulated (P < 0.05) expression of TJPs E-cadherin, occludin, and zonulin versus ST. The probiotic effect on mucosal bacteria is similar to that of IBD dogs receiving ST. IBD dogs fed probiotic had increased TJP expression suggesting that probiotic may have beneficial effects on mucosal homeostasis.
Transient Notch Activation Induces Long-Term Gene Expression Changes Leading to Sick Sinus Syndrome in Mice
Authors: Yun Qiao, Catherine Lipovsky, Stephanie Hicks, Somya Bhatnagar, Gang Li, Aditi Khandekar, Robert Guzy, Kel Vin Woo, Colin G. Nichols, Igor R. Efimov, Stacey Rentschler
Journal: Circulation Research (2017)

Notch signaling programs cardiac conduction during development, and in the adult ventricle, injury-induced Notch reactivation initiates global transcriptional and epigenetic changes.To determine whether Notch reactivation may stably alter atrial ion channel gene expression and arrhythmia inducibility.To model an injury response and determine the effects of Notch signaling on atrial electrophysiology, we transiently activate Notch signaling within adult myocardium using a doxycycline-inducible genetic system (inducible Notch intracellular domain [iNICD]). Significant heart rate slowing and frequent sinus pauses are observed in iNICD mice when compared with controls. iNICD mice have structurally normal atria and preserved sinus node architecture, but expression of key transcriptional regulators of sinus node and atrial conduction, including Nkx2-5 (NK2 homeobox 5), Tbx3, and Tbx5 are dysregulated. To determine whether the induced electrical changes are stable, we transiently activated Notch followed by a prolonged washout period and observed that, in addition to decreased heart rate, atrial conduction velocity is persistently slower than control. Consistent with conduction slowing, genes encoding molecular determinants of atrial conduction velocity, including Scn5a (Nav1.5) and Gja5 (connexin 40), are persistently downregulated long after a transient Notch pulse. Consistent with the reduction in Scn5a transcript, Notch induces global changes in the atrial action potential, including a reduced dVm/dtmax. In addition, programmed electrical stimulation near the murine pulmonary vein demonstrates increased susceptibility to atrial arrhythmias in mice where Notch has been transiently activated. Taken together, these results suggest that transient Notch activation persistently alters ion channel gene expression and atrial electrophysiology and predisposes to an arrhythmogenic substrate.Our data provide evidence that Notch signaling regulates transcription factor and ion channel gene expression within adult atrial myocardium. Notch reactivation induces electrical changes, resulting in sinus bradycardia, sinus pauses, and a susceptibility to atrial arrhythmias, which contribute to a phenotype resembling sick sinus syndrome.
Radiation exposure during lung cancer diagnostic work-up: how important in the wider picture?
Authors: Nick Watson
Journal: Thorax (2017)

The paper by Rintoul et al 1 has highlighted the radiation burden for patients undergoing imaging investigations for lung cancer and calculated the lifetime attributable risk of developing a further malignancy as a result of that radiation exposure. Patients who underwent curative-intent surgery or radical (chemo)radiotherapy received an average radiation dose of approximately 28 mSv in their work-up. As might be expected, those patients with more advanced disease, in whom radical treatment was not possible and underwent best supportive care, received approximately half the radiation dose (approximately 15 mSv).

Using standard conversion factors, the authors have derived the lifetime risk of developing a second cancer as a consequence of the radiation exposure as approximately 1:1700 for all cancers and 1:5000 specifically for lung cancer in patients undergoing curative-intent surgery or radical (chemo)radiotherapy. It is important for the physician, radiologist and, of course, the patient to determine whether this risk is acceptable by evaluating the benefits gained from the diagnostic imaging undertaken and putting that risk into context of other causes of morbidity and mortality that the patient might suffer.

Accurate staging is essential to identify those patients with resectable, potentially curable disease but equally to avoid undertaking …
Abstract A42: The role of M1 and M2 macrophage in the cycling phase of breast cancer
Authors: Nykia D. Walker, Michael Elias, Steve Greco, Pranela Rameshwar
Journal: Cancer Research (2016)

Abstract Breast cancer malignancy is the second leading cause of death among women. The majority of deaths associated with cancer, from solid tumors are the result of metastasis and not from the primary tumor site Clinical evidence indicates that breast cancer (BC) cells (BCC) can exist in dormancy within the bone marrow (BM), for &amp;gt;10 years. Methods by which BCCs adapt dormancy as well as reversed dormancy into metastatic cells are highly significant for the development of new and safe therapies. This research focuses on the BM because it is the preferred organ for dormant BCCs. Furthermore, in several cases, the BM has been identified as a source of BCCs during clinical resurgence. A subset of BCCs with tumor initiating property (cancer stem cells, CSCs) has been identified as those responsible for dormancy and chemoresistance. We will take advantage of our working hierarchy of BCCs to determine how M2 macrophage (MΦ) facilitates dormancy or clinical resurgence into metastatic cells. The mechanisms by which dormancy occurs followed by later resurgence into metastatic role for the BM microenvironment to facilitate CSC dormancy. CSCs can form gap junctional intercellular communication (GJIC) with stroma, by release of miRNA, which induces cycling quiescence. MΦ are classified into two subsets, either M1 or M2 type. M1 are mostly pro-inflammatory (classically activated to kill microorganisms and tumor cells), while M2 are non-inflammatory (alternatively activated to promote tissue repair). M2 MΦ is one cell type that comprises the stromal compartment inside the BM hematopoietic microenvironment. We studied how activated MSCs can influence M1 or M2 polarization. Our supporting studies indicate that M2 MΦ can arrest BCCs in G1/G0, while M1 MΦ can induce cell cycle progression. Activated MSCs transitioned M2 into M1 phenotype whereas inactivated MSCs maintains M2 MΦ phenotype. Here we present how the transitional changes in M2 to M1 MΦ affect the behavior of the CSCs within the BM stromal compartment. Citation Format: Nykia D. Walker, Michael Elias, Steve Greco, Pranela Rameshwar. The role of M1 and M2 macrophage in the cycling phase of breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A42.
Endosonographically guided gallbladder drainage to treat neoplastic jaundice after Roux-en-Y gastric resection
Authors: Paolo Cecinato, Maurizio Cavina, Giuliana Sereni, Francesco Decembrino, Veronica Iori, Cristiana Tioli, Romano Sassatelli
Journal: Endoscopy (2017)

A 81-year-old man, who had undergone subtotal gastric resection with Roux-en-Y anastomosis for gastric adenocarcinoma 2 years earlier, was admitted to our hospital for obstructive jaundice. Abdominal computed tomography showed a solid mass (30 × 30 mm) at the pancreatic head, involving the common bile duct and the duodenum and suspicious for portal vein and mesenteric axis invasion ([Fig. 1]). An endoscopic ultrasonography (EUS)-guided fine needle aspiration was performed and a diagnosis of metastasis of gastric adenocarcinoma was made.
Abstract 349: Gene Regulatory Modules Regulate Cardiac Lineage Specification Revealed by Single-cell Rna Sequencing
Authors: Wuming Gong, Satyabrata Das, Tara L Rasmussen, Naoko Koyano-Nakagawa, Wei Pan, Daniel J Garry
Journal: Circulation Research (2015)

Background: The molecular definition of the differentiation process is of intense interest for cardiovascular developmental biologists. With the advent of single cell technologies, a number of a transcriptomic approaches have been developed to obtain a complete description of gene expression. While single cell RNA sequencing is a significant advance for describing gene expression at the cellular resolution, novel obstacles have emerged such as computational management of dropout events, discovery of the gene regulatory modules responsible for lineage specification and identification of novel lineage markers. Methods: Using Etv2- and Nkx2-5 EYFP transgenic embryos, from which progenitors of hematopoietic, endothelial and cardiac lineages can be isolated with high purity, we performed single cell transcriptome analysis. We developed a Bayesian statistical framework to (1) model the dropout events, (2) reconstruct the lineage specification pathways from mesodermal progenitors to hematopoietic, endothelial and cardiac lineages, (3) discover the core gene regulatory modules that govern lineage specification and (4) predict novel cell surface markers for cardiac components. We developed a structural stochastic variational inference method to efficiently estimate the model parameters for sequencing data with thousands of cells. Results: The analysis of 421 Etv2- and Nkx2-5 EYFP positive cells predicted the core regulatory networks involving transcription factors, signaling molecules and cell surface proteins, where the signaling cascades are significantly correlated the specification of the endothelial, hematopoietic and various cardiac lineages from the mesodermal progenitors. The method also predicted novel cell surface markers for the first and second heart fields. Conclusions: We report the analysis of complete gene expression profiles of mesodermal lineage specification at single cell resolution. We provide the first unified statistical framework to systematically analyze single cell RNA-seq data and quantitatively couple the network analysis and lineage specification. This strategy provides a platform for the identification of regulatory nodes and cascades that govern mesodermal and cardiovascular development.
High Placebo Response Rates Hamper the Discovery of Antidepressants for Depression in Children and Adolescents
Authors: Lujin Li, Yanfei Li, Qingshan Zheng
Journal: American Journal of Psychiatry (2017)

DiscussionThis is the first attempt to characterize practice patterns among physicians providing ketamine as a treatment for psychiatric disorders.Although there are limitations to this approach, including the inability to ensure that this is a representative sample of all ketamine providers across the country, we identified a rapidly growing number of physicians in a variety of specialties and geographic locations offering ketamine treatment for psychiatric disorders.Various dosing protocols were reported, although the majority of research studies have used only one protocol (2).These results underscore the urgent need for more research on the use of ketamine in psychiatric disorders in clinical settings in order to establish evidence-based treatment regimens and the safety of long-term use.The growing use of ketamine in this population, coupled with the concern for potential adverse clinical consequences of repeated dosing (e.g., abuse liability [3], cognitive impairment [4]), argues for the importance of a registry (5) to longitudinally follow psychiatric patients who receive ketamine.
Abstract 14842: Half of the Implantable Cardioverter Defibrillator-Eligible Patients That Undergo Coronary Artery Bypass Graft Surgery Improve Their Ejection Fraction to Above 35% Post-operatively
Authors: Ryan J Koene, Jessica Voight, Viorel G Florea, Kairav Vakil, Selcuk Adabag
Journal: Circulation (2015)

Background: In patients with preoperative ejection fraction (EF) ≤35%, a 90-day waiting period after coronary artery bypass grafting (CABG) is recommended to assess the impact of revascularization on left ventricular (LV) EF, prior to considering implantable cardioverter-defibrillator (ICD) therapy for primary prevention of sudden cardiac death. However, there is very little data to show whether EF improves to &gt;35% after CABG, rendering these patients ICD-ineligible postoperatively. We sought to determine the incidence and predictors of EF improvement to &gt;35% in ICD-eligible patients undergoing CABG. Methods: Of the 2,838 patients who underwent isolated CABG between 2001 and 2014 at the Minneapolis Veterans Affairs Medical Center, 375 had echocardiographic assessment of LV EF before (within 6 months) and after (3-24 months) CABG. Of these 375 patients, 74 (20%) had an LV EF ≤35% prior to CABG and were examined in this analysis. Logistic regression was used to examine the variables associated with perioperative improvement in LV EF. Results: Mean age of the 74 patients was 65±9 years. Mean preoperative EF was 28±6%, and improved to 36±12% postoperatively (p&lt; 0.001). In 38 (51%) patients, EF improved to &gt;35% after CABG (mean EF in this subgroup increased from 29±5% to 46±8% postoperatively, p&lt; 0.001). Improvement in EF to &gt;35% was 5 times more likely in patients with a preoperative EF of 26-35% than those with preoperative EF ≤25% (odds ratio 4.95, 95% confidence interval 1.73 to 14.1; p=0.003). Other baseline clinical characteristics were similar between patients with vs. without an improvement in EF to &gt;35%. Conclusion: More than 50% of the ICD-eligible patients who underwent CABG with a preoperative EF ≤35% improved their EF to &gt;35% after CABG and became disqualified for primary prevention ICD therapy. Preoperative EF was a strong determinant of EF improvement postoperatively. These results provide evidence for the current practice guideline recommendation of reassessing EF 90 days after CABG in ICD-eligible patients. They also suggest that it is less likely for patients with a preoperative EF ≤25% to become ineligible for primary-prevention ICD after CABG.
Gender dysphoria: assessment and management for non-specialists
Authors: James Barrett
Journal: BMJ (2017)

#### What you need to know

About 0.6% of the population identifies as transgender1 2 according to healthcare records, although the actual number might be higher. In the 50 years since UK NHS services started, more than 130 000 people have changed social gender role. A variety of doctors, including non-specialists, might at some time in their career be approached for help by someone with gender dysphoria.

Various specialist clinicians are involved in the care of patients being assessed and treated at a gender identity clinic. Specialist clinics obviate the need for any psychiatric assessment in advance of referral. Gender dysphoria is not a mental health disorder. After treatment is complete, doctors from all specialties will encounter patients who earlier changed gender role. People with gender dysphoria have described their experience of interacting with healthcare services as variable to poor, according to the Women and Equalities Parliamentary Select Committee.3 In the UK, the General Medical Council has recently emphasised medical duties in this regard,4,advising that treatment for transgender patients should be as respectful as for any other group. Feelings of “inexperience” with the field can prompt learning by collaboration with a gender identity clinic, rather than act as a justification for non-involvement.

This article …
GLUT-1 Staining Pattern in Contiguous and Non Contiguous Colorectal Adenomas and their Corresponding Tumours
Authors: S Bakhiet, J O'Sullivan, M Izzuan, G Keating, J Gorman, H Mulcahy, J Hyland, D O'Donoghue, K Sheahan
Journal: Endoscopy (2006)

Background: Glucose Transporter 1 (GLUT-1) is a high affinity glucose transporter. Increased glucose uptake at cell membranes is a metabolic characteristic of tumour cells. GLUT-1 at the membrane represents the active form of the protein in cancers. Elevated levels of GLUT-1 have been reported in many human malignancies however the correlation between levels in contiguous and non-contiguous adenomas in colorectal cancer has not yet been elucidated.
GC1118, an anti-EGFR monoclonal antibody, blocks irinotecan-induced EGFR activation and exhibits synergistic tumor regression in gastric cancer model
Authors: Jae-Chul Lee, Hyung Jun Cho, Minkyu Hur, Yangmi Lim, Shi-Nai Lee, Eun Hee Lee, Jonghwa Won, Minkyu Hur
Journal: Annals of Oncology (2017)
METHODS TO ASSESS WEARABLE HEAD IMPACT RESPONSE DEVICES
Authors: Andrew McIntosh, Catherine Willmott, Biswadev Mitra, James Brennan, Bleydy Dimech-Betancourt, Teresa Howard, Jeffrey Rosenfeld, Declan Patton
Journal: British Journal of Sports Medicine (2017)

Background There is a growing range of wearable non-helmet mounted devices on the market and/or in use that purport to measure head impact responses. There is potential for these devices to be useful tools in research and injury management programs. Objective Describe methods for assessing the validity of wearable head impact response devices. Design Laboratory and qualitative observational methods. Tests on an exemplar wearable head impact response measurement “device” were undertaken in a laboratory using an instrumented Hybrid III head and neck and linear impactor. Football players in competitive matches wore the device and games were videoed. A qualitative protocol was applied to correlated device head impact events were those observed on video to examine sensitivity and specificity. Setting Contact sport. Participants Community level Australian football players. Interventions None. Main Outcome Measurements Head impact responses in vitro (linear and angular accelerations) and vivo (observed head impact characteristics). Results Laboratory head impacts were performed at a number of impact sites and velocities. Laboratory tests identified significant correlations (p&lt;0.05) between in-headform measured peak resultant linear and resultant angular accelerations and HIC with the device measured parameters. However, the device estimates of HIC were incorrect by a factor of 2 and angular acceleration by a factor of 0.7. Linear acceleration measurement was more accurate, but lacked precision. Qualitative video analysis showed approximately 60% correlation of device measured &gt;30 g in game head impact events with observed head impacts, but in 18% events were not correlated with any head impact, and there were other errors. Conclusions A combination of laboratory and field tests are critical in establishing the validity of wearable head impact response devices and should be performed as the first stage of research with these devices.
The incidence, risk factors predicting injury and severity of injuries sustained during professional mixed martial arts (mma) competition in africa
Authors: Santa-Marie Venter, CC Grant, Lizelle Fletcher
Journal: British Journal of Sports Medicine (2017)

Objective To determine the incidence of injuries and associated risk factors, as well as the severity of injuries sustained by professional male MMA athletes competing at the Extreme Fighting Championships Africa (EFC Africa) from 2010 to June. Design Results from this descriptive study were compared to a similar study done in the United States of America (USA). Setting Medical records of all professional events (2010–2014) were obtained from EFC Africa (custodian). Participants Data was obtained from 173 male competitors aged 18 to 44 years, participating in 300 professional MMA fights. Outcome measures Statistical analyses include descriptive statistics and a stepwise logistic regression. The odds of an injury were predicted with six independent variables: fight outcome, age, weight division, number of fights, injuries in preceding fight and years of fighter experience. Main results Injuries to the head, face and neck were most common (45.9%), followed by traumatic brain injuries (knock-outs) (16.6%) and hypoxic brain injuries (chokes) (10.2%). Losing a fight was a significant predictor of injury when a stepwise logistic regression model was employed (p=0.040). The odds ratio indicated that preceding fight injury almost doubled the risk of sustaining an injury in following fight (1.91; p=0.163). TBI in the SA group (16.6%) was substantially higher than the USA group (1.8%). Conclusion The high rate of TBI’s in SA competition is concerning. This could reflect superior refereeing in the USA group, as fights may be ended sooner by referee stoppage, versus allowing fights to continue until one fighter is knocked-out. Competing interests None.