Cancer-induced morphological changes in enteric glial cells in the jejunum of Walker-256 tumor-bearing rats.

Cancer-induced cachexia is associated with systemic inflammation and gastrointestinal dysfunction. How changes to cells of the enteric nervous system contribute to gut dysfunction in tumor development and cancer cachexia is unknown. Here, we tested the hypothesis that changes to enteric glia, a type of peripheral glia that surround enteric neurons and regulate gut homeostasis, are associated with tumor development and that supplementing with the antioxidant L-glutathione is protective against the changes induced. Immunohistochemistry for neurons, enteric glial cells and immune cells was performed in whole-mount preparations and frozen histological sections of the jejunum from 20 Wistar rats, distributed in 4 groups: control, tumor of Walker-256, control administered with 1 % L-glutathione, and tumor of Walker-256 administered with 1 % L-glutathione. Morphoquantitative analyses were made using Image-Pro® Plus 4.5 and ImageJ® 1.43° software. Tumor development significantly reduced neuronal and glial cell populations in the myenteric and submucosal plexuses and enlarged glial cell body area in the submucosal plexus. In contrast, tumors increased glia in the jejunal mucosa and this effect was accompanied by B-lymphocyte recruitment. GSH-supplemented diet was not sufficient to protect against changes to neurons and glia in the submucosal plexus but was partially protective in the myenteric plexus. L-glutathione had no effect on physiological parameters of cachexia but was sufficient to preserve enteric glial cell density in the myenteric plexus. These results suggest that changes to both enteric neurons and glia likely contribute to the gastrointestinal effects of tumor development and that oxidative stress contributes to these effects in the enteric nervous system.

Constructing "Burnout": A Critical Discourse Analysis of Burnout in Postgraduate Medical Education.

PURPOSE: In 1974, Dr. Herbert Freudenberger coined the term burnout. With the creation of the Maslach Burnout Inventory in 1984, burnout went from a pop psychology term to a highly studied phenomenon in medicine. Exponential growth in studies of burnout culminated in its adoption into the International Classification of Diseases-11 in 2022. Yet, despite increased awareness and efforts aimed at addressing burnout in medicine, many surveys report burnout rates have increased among trainees. The authors aimed to identify different discourses that legitimate or function to mobilize burnout in postgraduate medical education (PGME), to answer the question: Why does burnout persist in PGME despite efforts to ameliorate it? METHOD: Using a Foucauldian discourse analysis, this study examined the socializing period of PGME as an entry point into burnout's persistence. The archive from which the discourses were constructed included over 500 academic articles, numerous policy documents, autobiographies, videos, documentaries, social media, materials from conferences, and threads in forums including Reddit. RESULTS: This study identified 3 discourses of burnout from 1974-2019: burnout as illness, burnout as occupational stress, and burnout as existentialism. Each discourse was associated with statements of truth, signs and signifiers, roles that individuals play within the discourse, and different institutions that gained visibility as a result of differing discourses. CONCLUSIONS: Burnout persists despite effort to ameliorate it because it is a productive construct for organizations. In its current form, it depoliticizes issues of health in favor of wellness and gives voice to the challenge of making meaning from the experience of being a clinician.

Antiviral activity of myricetin glycosylated compounds isolated from Marcetia taxifolia against chikungunya virus.

The chikungunya virus (CHIKV) has produced epidemic outbreaks of significant public health impact. The clinical symptoms of this disease are fever, polyarthralgia, and skin rash, generally self-limiting, although patients may develop a chronic disabling condition or suffer lethal complications. Unfortunately, there is no specific treatment or vaccine available. Thus, the search for effective therapies to control CHIKV infection is an urgent need. This study evaluated the antiviral activity of flavonoids isolated from Marcetia taxifolia by in vitro and in silico analysis. Cytotoxicity of compounds was determined by MTT assay and viral load was assessed in cell substrates supernatants by plaque-forming and RT-qPCR assays. Selected molecules were analyzed by molecular docking assays. Myricetin 3-rhamnoside (MR) and myricetin 3-(6-rhamnosylgalactoside) (MRG) were tested for antiviral assays and analyzed by the TCID50 method and RT-qPCR. MR exhibited dose-dependent antiviral activity, reducing viral titer at concentrations of 150-18.8 µg/mL by at least 1-log. Similarly, MRG showed a significant decrease in viral titer at concentrations of 37.5, 9.4, and 2.3 µg/mL. RT-qPCR analysis also displayed a substantial reduction of CHIKV RNA for both flavonoids. Furthermore, molecular docking of the selected flavonoids proposed the nsP3 macrodomain as a possible target of action. Our study reveals that MR and MRG could be considered promising anti-CHIKV therapeutic agents. Molecular modeling studies showed MR and MRG ligands with a high affinity for the N-terminal region of the nsP3 macrodomain, postulating them as a potential target of action for the CHIKV control.

Understanding how and why upskilling programmes for unregulated care providers can support health equity in underserved communities: a realist review protocol.

INTRODUCTION: Foot ulcers are one of the most devastating complications of diabetes mellitus leading to leg amputations. In Canada, systematically marginalised and racialised populations are more prone to developing foot ulcers and at higher risk of limb amputations. Shortages of regulated healthcare have hindered efforts to provide foot care. Upskilling unregulated care providers (UCPs) to deliver foot screening seems a reasonable solution to reduce limb loss. UCPs can advocate for health equity and deliver appropriate care. There is a need, however, to understand how and why an educational intervention for UCPs providing foot screening for these high-risk groups may or may not work. METHODS AND ANALYSIS: This realist review will follow the Realist And Meta-narrative Evidence Syntheses: Evolving Standards standards. First, we will develop an initial programme theory (PrT) based on exploratory searches and discussions with experts and stakeholders. Then, we will search MEDLINE, Embase, PsycINFO, ERIC, CINAHL and Scopus databases along with relevant sources of grey literature. The retrieved articles will be screened for studies focusing on planned educational interventions for UCPs related to diabetic foot assessment. Data regarding contexts, mechanisms and outcomes will be extracted and analysed using a realist analysis through an iterative process that includes data reviewing and consultation with our team. Finally, we will use these results to modify the initial PrT. ETHICS AND DISSEMINATION: Ethical approval is not required for this review. The main output of this research will be an evidence-based PrT for upskilling programmes for UCPs. We will share our final PrT using text, tables and infographics to summarise our results and draw insights across papers/reports. For academic, clinical, social care and educational audiences, we will produce peer-reviewed journal articles, including those detailing the process and findings of the realist review and establishing our suggestions for effective upskilling programmes. PROSPERO REGISTRATION NUMBER: CRD42022369208.

Microstructural Alterations in Tract Development in College Football and Volleyball Players: A Longitudinal Diffusion MRI Study.

BACKGROUND AND OBJECTIVES: Repeated impacts in high-contact sports such as American football can affect the brain's microstructure, which can be studied using diffusion MRI. Most imaging studies are cross-sectional, do not include low-contact players as controls, or lack advanced tract-specific microstructural metrics. We aimed to investigate longitudinal changes in high-contact collegiate athletes compared with low-contact controls using advanced diffusion MRI and automated fiber quantification. METHODS: We examined brain microstructure in high-contact (football) and low-contact (volleyball) collegiate athletes with up to 4 years of follow-up. Inclusion criteria included university and team enrollment. Exclusion criteria included history of neurosurgery, severe brain injury, and major neurologic or substance abuse disorder. We investigated diffusion metrics along the length of tracts using nested linear mixed-effects models to ascertain the acute and chronic effects of subconcussive and concussive impacts, and associations between diffusion changes with clinical, behavioral, and sports-related measures. RESULTS: Forty-nine football and 24 volleyball players (271 total scans) were included. Football players had significantly divergent trajectories in multiple microstructural metrics and tracts. Longitudinal increases in fractional anisotropy and axonal water fraction, and decreases in radial/mean diffusivity and orientation dispersion index, were present in volleyball but absent in football players (all findings |T-statistic|> 3.5, p value <0.0001). This pattern was present in the callosum forceps minor, superior longitudinal fasciculus, thalamic radiation, and cingulum hippocampus. Longitudinal differences were more prominent and observed in more tracts in concussed football players (n = 24, |T|> 3.6, p < 0.0001). An analysis of immediate postconcussion scans (n = 12) demonstrated a transient localized increase in axial diffusivity and mean/radial kurtosis in the uncinate and cingulum hippocampus (|T| > 3.7, p < 0.0001). Finally, within football players, those with high position-based impact risk demonstrated increased intracellular volume fraction longitudinally (T = 3.6, p < 0.0001). DISCUSSION: The observed longitudinal changes seen in football, and especially concussed athletes, could reveal diminished myelination, altered axonal calibers, or depressed pruning processes leading to a static, nondecreasing axonal dispersion. This prospective longitudinal study demonstrates divergent tract-specific trajectories of brain microstructure, possibly reflecting a concussive and repeated subconcussive impact-related alteration of white matter development in football athletes.

Surgical Coaching: Patient Perspectives Regarding Surgeon Coaches in the Operating Room.

BACKGROUND: Surgical coaching programs have been introduced as platforms for ongoing professional development amongst independently practicing surgeons. While there is a plethora of evidence regarding the effectiveness of surgical coaching for practicing staff surgeons, patients' opinions regarding surgical coaching are largely unknown. OBJECTIVES: To determine patients' baseline attitudes and opinions about the hypothetical situation of their treating surgeon having a surgical coach present during their upcoming operation, and to determine patients' baseline knowledge and prior exposure to surgical coaching. DESIGN AND SETTING: This study was conducted at a tertiary hospital in Vancouver, Canada. Patients on the surgical waitlist of 2 independently practicing Otolaryngologists within the subspeciality of Neurotology were invited to participate in the study. Participants engaged in a semi-structured interview to discuss their opinions and knowledge of physician coaches and to learn about surgical coaching. The interview was conducted based on a pre-set script. RESULTS: Of the 100 patients approached, 70 consented to participate. Forty-three (61%) participants identified as female, and the mean age was 56±15 years. Initially, 84% of participants (n = 59) consented to the hypothetical presence of a surgical coach. Post-discussion, this number increased to 95.7% (n = 67, p = 0.04). Prior participant exposure to coaching related to employment, education, athletics, or music was high (90%, n = 63). Younger participants between 25 and 45 years of age were more amenable to the presence of a surgical coach compared to participants >66 years of age (p = 0.01). After the interview, 55 (79%) participants were interested in learning more about surgical coaching. CONCLUSION: Many patients were unaware of the rationale and importance of surgical coaching programs for practicing staff surgeons. Most patients, especially younger patients, were amenable to the presence of a surgical coach during their surgery, and this number increased in all age categories with patient education about surgical coaching.

Global survival trends for brain tumors, by histology: analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000-2014 (CONCORD-3).

BACKGROUND: Survival is a key metric of the effectiveness of a health system in managing cancer. We set out to provide a comprehensive examination of worldwide variation and trends in survival from brain tumors in adults, by histology. METHODS: We analyzed individual data for adults (15-99 years) diagnosed with a brain tumor (ICD-O-3 topography code C71) during 2000-2014, regardless of tumor behavior. Data underwent a 3-phase quality control as part of CONCORD-3. We estimated net survival for 11 histology groups, using the unbiased nonparametric Pohar Perme estimator. RESULTS: The study included 556,237 adults. In 2010-2014, the global range in age-standardized 5-year net survival for the most common sub-types was broad: in the range 20%-38% for diffuse and anaplastic astrocytoma, from 4% to 17% for glioblastoma, and between 32% and 69% for oligodendroglioma. For patients with glioblastoma, the largest gains in survival occurred between 2000-2004 and 2005-2009. These improvements were more noticeable among adults diagnosed aged 40-70 years than among younger adults. CONCLUSIONS: To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors by histology in adults. We have highlighted remarkable gains in 5-year survival from glioblastoma since 2005, providing large-scale empirical evidence on the uptake of chemoradiation at population level. Worldwide, survival improvements have been extensive, but some countries still lag behind. Our findings may help clinicians involved in national and international tumor pathway boards to promote initiatives aimed at more extensive implementation of clinical guidelines.

Harnessing the Electronic Health Care Record to Optimize Patient Safety in Primary Care: Framework for Evaluating e-Safety-Netting Tools.

The management of diagnostic uncertainty is part of every primary care physician's role. e-Safety-netting tools help health care professionals to manage diagnostic uncertainty. Using software in addition to verbal or paper based safety-netting methods could make diagnostic delays and errors less likely. There are an increasing number of software products that have been identified as e-safety-netting tools, particularly since the start of the COVID-19 pandemic. e-Safety-netting tools can have a variety of functions, such as sending clinician alerts, facilitating administrative tasking, providing decision support, and sending reminder text messages to patients. However, these tools have not been evaluated by using robust research designs for patient safety interventions. We present an emergent framework of criteria for effective e-safety-netting tools that can be used to support the development of software. The framework is based on validated frameworks for electronic health record development and patient safety. There are currently no tools available that meet all of the criteria in the framework. We hope that the framework will stimulate clinical and public conversations about e-safety-netting tools. In the future, a validated framework would drive audits and improvements. We outline key areas for future research both in primary care and within integrated care systems.

KIF24 depletion induces clustering of supernumerary centrosomes in PDAC cells.

Clustering of supernumerary centrosomes, which potentially leads to cell survival and chromosomal instability, is frequently observed in cancers. However, the molecular mechanisms that control centrosome clustering remain largely unknown. The centrosomal kinesin KIF24 was previously shown to restrain the assembly of primary cilia in mammalian cells. Here, we revealed that KIF24 depletion suppresses multipolar spindle formation by clustering centrosomes in pancreatic ductal adenocarcinoma (PDAC) cells harboring supernumerary centrosomes. KIF24 depletion also induced hyper-proliferation and improved mitotic progression in PDAC cells. In contrast, disruption of primary cilia failed to affect the proliferation and spindle formation in KIF24-depleted cells. These results suggest a novel role for KIF24 in suppressing centrosome clustering independent of primary ciliation in centrosome-amplified PDAC cells.

Measured weight loss as a precursor to cancer diagnosis: retrospective cohort analysis of 43 302 primary care patients.

BACKGROUND: Unexpected weight loss is a presenting feature of cancer in primary care. Data from primary care are lacking to quantify how much weight loss over what period should trigger further investigation for cancer. This research aimed to quantify cancer diagnosis rates associated with measured weight change in people attending primary care. METHODS: Retrospective cohort study of primary care electronic health records data linked to the Surveillance, Epidemiology, and End Results cancer registry (Integrated healthcare delivery system in Washington State, United States). Multivariable Cox regression incorporating time varying covariates using splines to model non-linear associations (age, percentage weight change, and weight change interval). Fifty thousand randomly selected patients aged 40 years and over followed for up to 9 years (1 January 2006 to 31 December 2014). Outcome measures are hazard ratios (95% confidence intervals) to quantify the association between percentage weight change and cancer diagnosis for all cancers combined, individual cancer sites and stages; percentage risk of cancer diagnosis within 6 months of the end of each weight change episode; and the positive predictive value for cancer diagnosis. RESULTS: There were 43 302 included in the analysis after exclusions. Over 287 858 patient-years of follow-up, including 24 272 (56.1%) females, 23 980 (55.4%) aged 40 to 59 years, 15 113 (34.9%) 60 to 79 years, and 4209 (9.7%) aged 80 years and over. Adjusted hazard ratios (95% confidence interval) for cancer diagnosis in a 60 years old ranged from 1.04 (1.02 to 1.05, P < 0.001) for 1% weight loss to 1.44 (1.23 to 1.68, P < 0.001) for 10%. An independent linear association was observed between percentage weight loss and increasing cancer risk. The absolute risk of cancer diagnosis increased with increasing age (up to 85 years) and as the weight change measurement interval decreased (<1 year). The positive predictive value for a cancer diagnosis within 1 year of ≥5% measured weight loss in a 60 to 69 years old was 3.41% (1.57% to 6.37%) in men and 3.47% (1.68% to 6.29%) in women. The risk of cancer diagnosis was significantly increased for pancreatic, myeloma, gastro-oesophageal, colorectal, breast, stage II and IV cancers. CONCLUSIONS: Weight loss is a sign of undiagnosed cancer regardless of the interval over which it occurs. Guidelines should resist giving an arbitrary cut-off for the interval of weight loss and focus on the percentage of weight loss and the patient's age. Future studies should focus on the association between diagnostic evaluation of weight change and risk of cancer mortality.

Cultivating Doctors' Gut Feeling: Experience, Temporality and Politics of Gut Feelings in Family Medicine.

For the past decade, within family medicine there has been a focus on cultivating doctors gut feelings as 'a way of knowing' in cancer diagnostics. In this paper, building on interviews with family doctors in Oxford shire, UK we explore the embodied and temporal dimensions of clinical reasoning and how the cultivation of doctors' gut feelings is related to hierarchies of medical knowledge, professional training, and doctors' fears of litigation. Also, we suggest that the introduction of gut feeling in clinical practice is an attempt to develop a theory of clinical reasoning that fits the biopolitics of our contemporary. The turn towards predictive medicine and the values introduced by accelerated diagnostic regimes, we conclude, introduce a need for situated and embodied modes of reading bodies. We contribute theoretically by framing our analysis within a sensorial anthropology approach.

Influenza and Respiratory Virus Surveillance, Vaccine Uptake, and Effectiveness at a Time of Cocirculating COVID-19: Protocol for the English Primary Care Sentinel System for 2020-2021.

BACKGROUND: The Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) and Public Health England (PHE) are commencing their 54th season of collaboration at a time when SARS-CoV-2 infections are likely to be cocirculating with the usual winter infections. OBJECTIVE: The aim of this study is to conduct surveillance of influenza and other monitored respiratory conditions and to report on vaccine uptake and effectiveness using nationally representative surveillance data extracted from primary care computerized medical records systems. We also aim to have general practices collect virology and serology specimens and to participate in trials and other interventional research. METHODS: The RCGP RSC network comprises over 1700 general practices in England and Wales. We will extract pseudonymized data twice weekly and are migrating to a system of daily extracts. First, we will collect pseudonymized, routine, coded clinical data for the surveillance of monitored and unexpected conditions; data on vaccine exposure and adverse events of interest; and data on approved research study outcomes. Second, we will provide dashboards to give general practices feedback about levels of care and data quality, as compared to other network practices. We will focus on collecting data on influenza-like illness, upper and lower respiratory tract infections, and suspected COVID-19. Third, approximately 300 practices will participate in the 2020-2021 virology and serology surveillance; this will include responsive surveillance and long-term follow-up of previous SARS-CoV-2 infections. Fourth, member practices will be able to recruit volunteer patients to trials, including early interventions to improve COVID-19 outcomes and point-of-care testing. Lastly, the legal basis for our surveillance with PHE is Regulation 3 of the Health Service (Control of Patient Information) Regulations 2002; other studies require appropriate ethical approval. RESULTS: The RCGP RSC network has tripled in size; there were previously 100 virology practices and 500 practices overall in the network and we now have 322 and 1724, respectively. The Oxford-RCGP Clinical Informatics Digital Hub (ORCHID) secure networks enable the daily analysis of the extended network; currently, 1076 practices are uploaded. We are implementing a central swab distribution system for patients self-swabbing at home in addition to in-practice sampling. We have converted all our primary care coding to Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) coding. Throughout spring and summer 2020, the network has continued to collect specimens in preparation for the winter or for any second wave of COVID-19 cases. We have collected 5404 swabs and detected 623 cases of COVID-19 through extended virological sampling, and 19,341 samples have been collected for serology. This shows our preparedness for the winter season. CONCLUSIONS: The COVID-19 pandemic has been associated with a groundswell of general practices joining our network. It has also created a permissive environment in which we have developed the capacity and capability of the national primary care surveillance systems and our unique public health institute, the RCGP and University of Oxford collaboration.

Muscle progenitor specification and myogenic differentiation are associated with changes in chromatin topology.

Using Hi-C, promoter-capture Hi-C (pCHi-C), and other genome-wide approaches in skeletal muscle progenitors that inducibly express a master transcription factor, Pax7, we systematically characterize at high-resolution the spatio-temporal re-organization of compartments and promoter-anchored interactions as a consequence of myogenic commitment and differentiation. We identify key promoter-enhancer interaction motifs, namely, cliques and networks, and interactions that are dependent on Pax7 binding. Remarkably, Pax7 binds to a majority of super-enhancers, and together with a cadre of interacting transcription factors, assembles feed-forward regulatory loops. During differentiation, epigenetic memory and persistent looping are maintained at a subset of Pax7 enhancers in the absence of Pax7. We also identify and functionally validate a previously uncharacterized Pax7-bound enhancer hub that regulates the essential myosin heavy chain cluster during skeletal muscle cell differentiation. Our studies lay the groundwork for understanding the role of Pax7 in orchestrating changes in the three-dimensional chromatin conformation in muscle progenitors.

The Karolinska Institutet Prize for Research in Medical Education: A history.

Purpose: This article presents a history of the Karolinska Institutet Prize for Medical Education (KIPRIME), highlighting the history of, and influences on, its funders Drs. Gunnar Höglund and Anna-Stina Malmborg.Methods: Historic analysis of an archive of documents developed by the authors in a prior study exploring philanthropy in medical education research. Documents in the archive were drawn from publicly available Internet sources, media reports about the KIPRIME and its winners and an interview with Drs. Höglund's and Malmborg. The latter interview was conducted with Ethics Board approval in non-anonymous fashion and with the explicit permission of the interviewees to present their personal information and to cite their words. Finally, observations were shaped iteratively by the authors on multiple trips to the Karolinska Institutet with input from the KIPRIME prize committee leaders.Findings: The results of this analysis present a history of the prize situating it in the personal histories of, and influences acting upon, Drs. Höglund and Malmborg. Special attention is given to the potential influence of the Nobel Prizes and the culture of philanthropy in Sweden.

Competencies and training of radiographers and technologists for PET/MR imaging - a study from the UK MR-PET network.

BACKGROUND: After the success of PET/CT as a clinical diagnostic tool, the introduction of PET/MRI is a natural development aimed at further improving combined diagnostic imaging and reduced ionising radiation dose for half-body imaging. As with PET and CT, the combination of PET and MRI presents a series of issues that need to be addressed regarding workforce training and education. At present, there is a lack of agreement over the competencies, training requirements and educational pathways needed for PET/MRI operation. In the UK, following the establishment of the MR-PET imaging network, a task force was created to investigate the status of the workforce training, identify gaps and make recommendations regarding staff training. To do this, we ran a national survey on the status of the workforce training and the local practices across the UK's seven PET/MRI sites, reviewed the literature, and convened a panel of experts, to assess all the evidence and make recommendations regarding PET/MRI competencies and training of nuclear medicine technologists and radiographers. RESULTS: There is limited literature available specifically on competencies and training for technologists and radiographers. The recommendations on the topic needed revisiting and adapting to the UK MR-PET network. The online survey confirmed the need for developing PET/MRI competencies and training pathways. Local organisational structures and practices were shared across the seven sites, based on models derived from experience outside the UK. The panel of experts agreed on the need for PET/MRI competencies and training strategies. Professional organisations started collaborative discussions with partners from both Nuclear Medicine and Radiography to set training priorities. Multidisciplinary collaboration and partnership were suggested as a key to a successful implementation of competencies and training. CONCLUSIONS: The report identified the need for establishing competencies for the PET/MRI workforce, particularly for technologists and radiographers. It also helped defining these competencies as well as identifying the demand for bespoke training and the development of local and national courses to be implemented to fulfil this new training need.

Paf1C regulates RNA polymerase II progression by modulating elongation rate.

Elongation factor Paf1C regulates several stages of the RNA polymerase II (Pol II) transcription cycle, although it is unclear how it modulates Pol II distribution and progression in mammalian cells. We found that conditional ablation of Paf1 resulted in the accumulation of unphosphorylated and Ser5 phosphorylated Pol II around promoter-proximal regions and within the first 20 to 30 kb of gene bodies, respectively. Paf1 ablation did not impact the recruitment of other key elongation factors, namely, Spt5, Spt6, and the FACT complex, suggesting that Paf1 function may be mechanistically distinguishable from each of these factors. Moreover, loss of Paf1 triggered an increase in TSS-proximal nucleosome occupancy, which could impose a considerable barrier to Pol II elongation past TSS-proximal regions. Remarkably, accumulation of Ser5P in the first 20 to 30 kb coincided with reductions in histone H2B ubiquitylation within this region. Furthermore, we show that nascent RNA species accumulate within this window, suggesting a mechanism whereby Paf1 loss leads to aberrant, prematurely terminated transcripts and diminution of full-length transcripts. Importantly, we found that loss of Paf1 results in Pol II elongation rate defects with significant rate compression. Our findings suggest that Paf1C is critical for modulating Pol II elongation rates by functioning beyond the pause-release step as an "accelerator" over specific early gene body regions.

A closer look at subjective caloric sensations: Is there more to vertigo than spinning?

BACKGROUND: There is a prevailing opinion that spinning sensations signify a peripheral vestibular pathology while non-spinning sensations are not of vestibular origin. OBJECTIVES: 1) Characterize the subjective sensations reported by patients during caloric testing. 2) Assess if the sensation was correlated with the peak slow phase velocity (SPV). METHODS: Retrospective chart review at a Canadian adult tertiary-quaternary care balance centre for patients undergoing diagnostic caloric testing between December 2014 and September 2015. RESULTS: Of 163 patients included, 122 had normal calorics and 41 demonstrated unilateral weakness. Spinning/rotatory movements were the most commonly reported sensations (55-70%). No sensation was reported among 10-20% of patients. Other non-rotatory sensations were reported 20-25% of the time. Both lack of sensation and other sensations were more likely to be correlated with SPVs that were significantly lower than those associated with spinning/rotating sensations. However, 18% of patients with normal calorics and robust SPVs with warm irrigation still reported non-spinning sensations. CONCLUSIONS: During caloric irrigation, subjective sensations other than spinning and rotating are reported 20-25% of the time and these tend to be associated with lower peak SPV. Non-spinning vertigo is not uncommon as a subjective description of vestibular sensation even in normal patients with strong SPVs.

Incidencia de los trastornos hipertensivos en el embarazo, y características clínico-demográficas en gestantes en tres instituciones en Bogotá, D. C., Colombia / Incidence of hypertensive disorders in pregnancy and clinical-demographic characteristics in pregnant women in three institutions in Bogotá, D. C., Colombia / Incidência de transtornos hipertensivos na gravidez e características clínico-demográficas em gestantes de três instituições em Bogotá, D. C., Colômbia

Objetivo: describir la incidencia de trastornos hipertensivos de las gestantes en 3 instituciones en Bogotá durante el periodo 2014-2016. Método: estudio observacional prospectivo, realizado entre 2014 y 2016 en 3 centros hospitalarios de la ciudad de Bogotá, D. C., Colombia. Fueron incluidas 252 gestantes, a quienes se les hizo seguimiento ecográfico trimestral, toma de variables clínicas y demográficas e indagación de resultados materno- perinatales en el momento del parto. Los datos fueron analizados a través del cálculo de medidas de tendencia central y dispersión para las variables cuantitativas, frecuencias y porcentajes para las variables cualitativas. Resultados: se encontró una incidencia de trastornos hipertensivos del 11,8 % en las gestantes incluidas en el estudio; de estos, el 62,1 % fueron preeclampsia, y el 37,9 %, hipertensión gestacional. La preeclampsia se presentó en el 7,4 % del total de la población estudiada; de dichas pacientes, el 50 % presentó preeclampsia severa. La incidencia de preeclampsia temprana fue del 17,2 %. Conclusión: la incidencia de los trastornos hipertensivos en gestantes en la población estudiada es mayor que en países desarrollados, y similar a lo descrito en la población colombiana

Objective: To describe the incidence of hypertensive disorders during pregnancy in three health institutions in Bogotá-Colombia during 2014-2016. Methods: This observational and prospective study were done in three institutions from 2014 to 2016 in Bogotá (Colombia). 252 patients were included. Fetal and maternal ultrasonography evaluations were done in each trimester of pregnancy, multiples demographic and clinical factors were evaluated, and maternal and perinatal outcomes were done at the delivery time. The data were analyzed using measures of central tendency and dispersion for the quantitative variables, and frequencies and percentages for qualitative variables. Results: The incidence of hypertensive disorders of pregnancy was 11.8 %, of these, pre-eclampsia was 62.1 % and 37.9 % of gestational hypertension. In relation to preeclampsia group, 7.4 % was presented when it was compared with the total of the study population, and form this 50 % of pregnant women were severe preeclampsia. The incidence of early pre-eclampsia was 17.2 %. Conclusion: The incidence of hypertensive disorders in pregnancy at the study population is higher than the prevalence reported in developed countries and similar than reported in Colombia

Objetivo: Descrever a incidência de hipertensivos de deficiências orgânicas do criando em três instituições em Bogotá durante o período 2014 -2016. Método: Eu estudo de observação prospectivo, levou a cabo entre 2014 e 2016 entre três hospital centra da cidade de Bogotá - a Colômbia. 252 eram criando incluídos a quem foi levado trimestralmente fora ecográfico de perseguição, enquanto levando de variáveis clínicas e demográficas e investigação perinatal materna de resultados no momento do parto. Os dados foram analisados pelo cálculo de medidas de tendência central e dispersão para as variáveis quantitativas, freqüências e porcentagens para as variáveis qualitativas. Resultados: Ele/ela era uma incidência de hipertensivos de deficiências orgânicas de 11,8% no criando incluído no estudo, destes, 62,1% preeclampsia e 37,9% gestacional de hipertensão. O preeclampsia mostraram para cima dentro um 7.4% do total da população instruída, destes pacientes, 50% apresentaram preeclampsia severo. A incidência de preeclampsia cedo era de 17,2%. Conclusão: A incidência do hipertensivos de deficiências orgânicas criando na população instruída é maior que em países desenvolvidos e semelhante a isso descrito na população colombiana