tbuckley/cabot-search huggingface dataset:
Trichinellosis Outbreak Linked to Consumption of Privately Raised Raw Boar Meat — California, 2017
Authors: Dustin Heaton, Sandra Huang, Rita Shiau, Shannon Casillas, Anne Straily, Li Kuo Kong, Valerie Ng, Viviana Petru
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

On January 15, 2017, a hospital physician notified the Alameda County Public Health Department (ACPHD) in California of a patient with a suspected diagnosis of trichinellosis, a roundworm disease transmitted by the consumption of raw or undercooked meat containing Trichinella spp. larvae (1). A family member of the initial patient reported that at least three other friends and family members had been evaluated at area hospitals for fever, myalgia, abdominal pain, diarrhea, and vomiting. The patients had attended a celebration on December 28, 2016, at which several pork dishes were served, including larb, a traditional Laotian raw pork dish, leading the hospital physician to suspect a diagnosis of trichinellosis. Although the event hosts did not know the exact number of attendees, ACPHD identified 29 persons who attended the event and seven persons who did not attend the event, but consumed pork taken home from the event by attendees. The event hosts reported that the meat had come from a domesticated wild boar raised and slaughtered on their private family farm in northern California. ACPHD conducted a case investigation that included identification of additional cases, testing of leftover raw meat, and a retrospective cohort study to identify risk factors for infection.
Impact of intravenous acetaminophen on outcomes following radical nephrectomy.
Authors: Dimitar V. Zlatev, David F. Friedlander, Ilker Tinay, Ye Wang, Daniel Pucheril, Benjamin I. Chung, Steven Lee Chang
Journal: Journal of Clinical Oncology (2018)

663 Background: Intravenous acetaminophen (IVA) was approved for use in the United States (US) for moderate to severe pain in 2010. The role of postoperative IVA following radical nephrectomy (RN) is of particular interest given the potential nephrotoxic and bleeding risks associated with other non-opioid alternatives such as parenteral non-steroidal anti-inflammatory drugs. However, given the relatively high cost of IVA versus other pain medications, the benefit of IVA in the postoperative period is unclear. We sought to determine if the use of postoperative IVA is associated with improved outcomes following RN. Methods: Using the Premier Hospital Database (Premier, Inc., Charlotte, NC), we retrospectively identified patients who underwent RN for a diagnosis of kidney cancer or renal mass in the US between 2011 and 2015. To limit confounding, only elective procedures and those with no complications (Clavien Classification of Surgical Complications score of 0) were included for analysis. Analysis was furthermore limited to patients of surgeons who either uniformly used or never used postoperative IVA. Chargemaster data for each patient was reviewed to determine use of IVA and narcotic pain medications postoperatively. Multivariable logistic regression was used to assess the relationship between postoperative IVA and the odds of a prolonged length of stay (LOS, top quartile). Multivariable quantile regression was used to determine the association of postoperative IVA with the use of narcotic pain medications (measured by morphine equivalents) and direct index hospitalization costs. Results: Among our cohort of 9,809 patients undergoing RN, 1,147 (11.7%) received postoperative IVA. The use of postoperative IVA was associated with a 64% decreased odds of prolonged LOS (OR 0.36, 95% CI: 0.19 to 0.69, p &lt; 0.05). There was no significant impact of postoperative IVA on the use of narcotic pain medications or direct costs during the index hospitalization ($12,567 vs. $12,533, p &gt; 0.05). Conclusions: The use of IVA following RN is associated with a reduced length of stay, no change in use of narcotic pain medications, and no increase in hospitalization costs.
What is the role of the PMETB for SAS doctors?
Authors: Romeh Gupta
Journal: BMJ (2005)

<h3>Background</h3> In sarcoidosis, blood monocytes, circulating precursors of granuloma macrophages, display enhanced inflammatory cytokine production, reduced expression of the regulatory (inhibitory) receptor CD200R, and altered subsets defined by CD14 and CD16. Regulatory receptors serve to dampen monocyte and macrophage inflammatory responses. We investigated the relationship between monocyte subsets and regulatory receptor expression in sarcoidosis. <h3>Methods</h3> Multi-parameter flow cytometry was used to perform detailed analyses of cell surface regulatory molecules on freshly isolated blood immune cells from patients with chronic pulmonary sarcoidosis and age-matched healthy controls. <h3>Results</h3> Twenty-five patients with chronic pulmonary sarcoidosis (median duration of disease 22 months) who were not taking oral corticosteroids or other immunomodulators were recruited. Non-classical monocytes were expanded in sarcoidosis and exhibited significantly lower expression of regulatory receptors CD200R, SIRP-α, and CD47 than classical or intermediate monocytes. In sarcoidosis, all three monocyte subsets had significantly reduced CD200R and CD47 expression compared with healthy controls. A dichotomous distribution of CD200R was seen on classical and intermediate monocytes in the sarcoidosis population, with 14/25 (56%) sarcoidosis patients having a CD200R-low phenotype, and 11/25 (44%) CD200R-high. These distinct sarcoidosis monocyte phenotypes remained consistent over time. <h3>Conclusion</h3> Non-classical monocytes, which are expanded in sarcoidosis, express very low levels of regulatory receptors. Two distinct and persistent phenotypes of CD200R expression in classical and intermediate monocytes could be evaluated as sarcoidosis biomarkers.
Women are “often better leaders,” says Jeremy Hunt
Authors: Abi Rimmer
Journal: BMJ (2014)

Women often make better leaders than men, England’s health secretary has said. Speaking at a conference on advancing women in medicine, Jeremy Hunt said that the health service needed to learn more about what women brought to leadership roles in healthcare. 

“There is a lot of evidence that women are often better leaders, and we need to think hard about why that is,” he said. “I personally am an advocate of saying that the best leaders are ego-free, and I think women tend to be better at that than men. But of course there are women with huge egos and plenty of men who are brilliant leaders who don’t have those.”

Hunt backed a culture change in the NHS that would allow all staff to feel supported and able to speak out about poor care. “We’re going to move away from a culture where there has been too much bullying and too much of a feeling of a macho, top-down approach to management which has made it hard for people to speak out with concerns,” he said.

Bruce Keogh, medical director of NHS England, told the conference that he supported diversity in senior leadership. “Difference stimulates innovation. Difference stimulates productive discussion,” he said. “There is little doubt that oestrogen dilutes testosterone and results in more innovative and productive endeavour.”

Keogh said that the medical profession’s “tribal” attitudes could exclude women from senior positions. “When I look at medicine I see something that is really tribal,” he said. “If you look at our workforce, people are a nurse, a physiotherapist, a speech and language therapist, a doctor. 

“If you’re a doctor . . . you have an allegiance to your specialty and, within that, your subspecialty. The end result is that people have a far stronger allegiance with their peer group …
Abstract 16744: Cardiac Expression Profiles of Cofilin-2 and H2S-Producing Enzyme 3-Mercaptopyruvate Sulfurtransferase in Patients With End-Stage Ischemic Cardiomyopathy
Authors: Vinh Q Chau, Teja Devarakonda, Francisco Romeo, Bharat Balan, Chad Cain, Stefano Toldo, Daniel Tang, Keyur Shah, Vigneshwar Kasirajan, Fadi N Salloum
Journal: Circulation (2017)

Background: Abnormal regulation of cofilin-2, an actin depolymerizing protein, is pathogenic in patients with idiopathic dilated cardiomyopathy. We showed that cofilin-2 expression and phosphorylat...
Enhanced response to peginterferon-alpha-2a based triple therapy in previously non-responsive chronic hepatitis C: Final results of PRETTY study.
Authors: A. Mangia, L. Cimino, M. Persico, L. Demelia, M. Rumi, G. Spinzi, F. Fatuzzo, M. Levrero, P. L. Frugiuele, G. Fornaciari, G. De Stefano, L. Venturoni, Enrico Roda, Stefano Brillanti
Journal: Journal of Hepatology (2005)
SCN5A MUTATION INCREASES THE RISK OF MAJOR ARRHYTHMIC EVENTS IN BRUGADA SYNDROME: SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Pattara Rattanawong, Jirat Chenbhanich, Poemlarp Mekraksakit, Wasawat Vutthikraivit, Tanawan Riangwiwat, Pakawat Chongsathidkiet, Eugene H. Chung
Journal: Journal of the American College of Cardiology (2018)
Chemically Modified Cpf1-CRISPR RNAs Mediate Efficient Genome Editing in Mammalian Cells
Authors: Moira A. McMahon, Thazha P. Prakash, Don W. Cleveland, C. Frank Bennett, Meghdad Rahdar
Journal: Molecular Therapy (2018)

CRISPR-based gene editing is a powerful technology for engineering mammalian genomes. It holds the potential as a therapeutic, although much-needed in vivo delivery systems have yet to be established. Here, using the Cpf1-crRNA (CRISPR RNA) crystal structure as a guide, we synthesized a series of systematically truncated and chemically modified crRNAs, and identify positions that are amenable to modification while retaining gene-editing activity. Modified crRNAs were designed with the same modifications that provide protection against nucleases and enable wide distribution in vivo. We show crRNAs with chemically modified terminal nucleotides are exonuclease resistant while retaining gene-editing activity. Chemically modified or DNA-substituted nucleotides at select positions and up to 70% of the crRNA DNA specificity region are also well tolerated. In addition, gene-editing activity is maintained with phosphorothioate backbone substitutions in the crRNA DNA specificity region. Finally, we demonstrate that 42-mer synthetic crRNAs from the similar CRISPR-Cas9 system are taken up by cells, an attractive property for in vivo delivery. Our study is the first to show that chemically modified crRNAs of the CRISPR-Cpf1 system can functionally replace and mediate comparable gene editing to the natural crRNA, which holds the potential for enhancing both viral- and non-viral-mediated in vivo gene editing. CRISPR-based gene editing is a powerful technology for engineering mammalian genomes. It holds the potential as a therapeutic, although much-needed in vivo delivery systems have yet to be established. Here, using the Cpf1-crRNA (CRISPR RNA) crystal structure as a guide, we synthesized a series of systematically truncated and chemically modified crRNAs, and identify positions that are amenable to modification while retaining gene-editing activity. Modified crRNAs were designed with the same modifications that provide protection against nucleases and enable wide distribution in vivo. We show crRNAs with chemically modified terminal nucleotides are exonuclease resistant while retaining gene-editing activity. Chemically modified or DNA-substituted nucleotides at select positions and up to 70% of the crRNA DNA specificity region are also well tolerated. In addition, gene-editing activity is maintained with phosphorothioate backbone substitutions in the crRNA DNA specificity region. Finally, we demonstrate that 42-mer synthetic crRNAs from the similar CRISPR-Cas9 system are taken up by cells, an attractive property for in vivo delivery. Our study is the first to show that chemically modified crRNAs of the CRISPR-Cpf1 system can functionally replace and mediate comparable gene editing to the natural crRNA, which holds the potential for enhancing both viral- and non-viral-mediated in vivo gene editing.
Academy seeks views on Foundation Programme Curriculum
Authors: Abi Rimmer
Journal: BMJ (2014)

The Academy of Medical Royal Colleges is seeking views on the Foundation Programme Curriculum (FPC).

The academy is currently working on the next version of the curriculum, which will be ready for foundation year 1 and 2 doctors starting in 2016.1 The academy said that the revision of the curriculum would “address any issues related to the …
I want to know how I can work as a medical journalist. I have worked in this field in addition to general practice for more than eight years.
Authors: Rachel Hooke
Journal: BMJ (2006)

Have a career or related problem that needs answering? Can't find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. [www.bmjcareers.com/advicezone][1] [1]: http://www.bmjcareers.com/advicezone
Receiving an MD at 90: an interview with Gillian Hunt
Authors: Rosalind McLean
Journal: BMJ (2013)

Born in 1922, when few women had careers, Gillian Hunt received an MD for her research in November 2012 at the same ceremony as her youngest daughter, Alison Poulton, received her MD. Her granddaughter <b>Rosalind McLean</b> spoke to her about her experiences.
One in six hospitals in England paying locums more than £1000 a shift
Authors: Helen Jaques
Journal: BMJ (2013)

NHS hospitals in England are paying up to £2000 a shift for a locum doctor, with 16% spending more than £1000 a shift for locum cover, an investigation by the Telegraph has found.1

Based on freedom of information requests completed by 99 of the 164 hospital trusts in England, spending by NHS hospital trusts in England on agency locums is estimated to have reached £2.06bn during 2010-13. NHS Employers has estimated that around 50% of expenditure on agency staff in the NHS …
Focused ultrasound with microbubbles induces sterile inflammatory response proportional to the blood brain barrier opening: Attention to experimental conditions
Authors: Zsofia I. Kovacs, Scott R. Burks, Joseph A. Frank
Journal: Theranostics (2018)

This editorial highlights the findings of McMahon [1] and demonstrates the need for careful attention to experimental conditions that influence microbubble concentration and pharmacokinetics contributed to focused ultrasound-induced blood brain barrier opening and sterile inflammation.
Is my membership of the Royal College of Physicians (MRCP) qualification any use to me if I go into general practice?
Authors: Dave Triffit
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site:</i>
Stem Cell Transplantation Improves Scleroderma Outcomes
Authors: Anita Slomski
Journal: JAMA (2018)

Myeloablative autologous hematopoietic stem cell transplantation resulted in significantly better long-term clinical outcomes—although greater toxicity–in patients with scleroderma than did cyclophosphamide, found a trial published in the New England Journal of Medicine.
Doctors are now more willing to raise patient safety concerns
Authors: Caroline White
Journal: BMJ (2013)

Doctors now seem to be more willing to raise concerns about issues of patients’ safety than they were five years ago, a small survey carried out by the Medical Defence Union indicates.1

Of 470 respondents among 7000 doctors polled in June, over half (259 or 55%) thought that doctors were more willing to raise concerns than …
Identification of T‐cell epitopes from benzylpenicillin conjugated to human serum albumin and implication in penicillin allergy
Authors: M. E. Azoury, L. Filì, R. Bechara, N. Scornet, L. de Chaisemartin, R. J. Weaver, N. Claude, B. Maillere, P. Parronchi, D. Joseph, M. Pallardy
Journal: Allergy (2018)

There is in vitro evidence that T cells from allergic patients react to benzylpenicillin-human serum albumin (BP-HSA) bioconjugates. Our group has recently shown the existence of naïve CD4+ T cells recognizing BP-HSA in healthy donors. However, BP-haptenated peptides from HSA participating in the immunization of allergic patients have never been identified. The purpose of the present study is to identify immunodominant BP-haptenated peptides from HSA involved in immunization of patients to BP and to refine the frequency calculation of naïve CD4+ T cells recognizing BP.Co-cultures were established with CD4+ T cells from non-allergic donors and mature autologous dendritic cells (DCs) loaded with BP-HSA or BP-haptenated peptides from HSA. The CD4+ T-cell response specific for BP-HSA or for individual BP-haptenated peptides was measured using an interferon-γ (IFN-γ) ELISpot assay. The frequency of BP-specific CD4+ T cells was then calculated using the Poisson distribution. BP-HSA and BP-haptenated peptides recognition by allergic patients was evaluated on peripheral blood mononuclear cells (PBMCs) using a lymphocyte transformation test (LTT).Results showed that BP-HSA and BP-haptenated peptides were recognized by naïve T cells from 15/16 and 13/14 tested healthy donors, respectively. Most donors responded to 3 peptides with BP covalently bound on lysines 159, 212, and 525. Two of these benzylpenicilloylated peptides (lysines 159 and 525) were also found to induce PBMCs proliferation in patients with allergic reaction to penicillins.This study identifies and characterizes for the first time the BP-haptenated peptides from HSA involved in the immunization of patients to penicillins.
Abstract BS3-1: Manifestations and implications of subclonal alterations in metastatic breast cancer
Authors: S Chandarlapaty
Journal: Cancer Research (2018)

Abstract Clinical and pathological evidence for intratumoral heterogeneity (ITH) in breast cancer has long existed, however recent advances in genomic sequencing have revealed a remarkable depth and complexity to ITH. This is further magnified in the study of metastatic breast cancer where there has been significant expansion in the number of tumors as well as the selective pressures faced by individual tumor cells. The near universality of such heterogeneity has led many to question whether ITH is of any biologic or clinical significance or it is simply an intrinsic property of a large population of cancer cells with unstable genomes. We would posit that the significance of ITH can be observed by understanding the pressures that may have generated them. In particular, drug therapy such as anti-estrogen or HER2 targeted therapy can influence the manifestation of ITH. This can reveal underlying vulnerabilities and resiliencies in different cases. In this talk, we will review the evidence that ITH exists for important drivers of breast cancer growth, elucidate the biologic and clinical significance of such findings with a focus on resistance to hormone therapy, and discuss potential strategies to overcome it. Citation Format: Chandarlapaty S. Manifestations and implications of subclonal alterations in metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr BS3-1.
DEP domain–containing mTOR–interacting protein suppresses lipogenesis and ameliorates hepatic steatosis and acute‐on‐chronic liver injury in alcoholic liver disease
Authors: Hanqing Chen, Feng Shen, Alex Sherban, Allison Nocon, Yu Li, Hua Wang, Ming‐Jiang Xu, Xianliang Rui, Jinyan Han, Bingbing Jiang, Donghwan Lee, Na Li, Farnaz Keyhani‐Nejad, Jian‐gao Fan, Feng Liu, Amrita Kamat, Nicolas Musi, Leonard Guarente, Pal Pacher, Bin Gao, Mengwei Zang
Journal: Hepatology (2018)

Alcoholic liver disease (ALD) is characterized by lipid accumulation and liver injury. However, how chronic alcohol consumption causes hepatic lipid accumulation remains elusive. The present study demonstrates that activation of the mechanistic target of rapamycin complex 1 (mTORC1) plays a causal role in alcoholic steatosis, inflammation, and liver injury. Chronic‐plus‐binge ethanol feeding led to hyperactivation of mTORC1, as evidenced by increased phosphorylation of mTOR and its downstream kinase S6 kinase 1 (S6K1) in hepatocytes. Aberrant activation of mTORC1 was likely attributed to the defects of the DEP domain‐containing mTOR‐interacting protein (DEPTOR) and the nicotinamide adenine dinucleotide–dependent deacetylase sirtuin 1 (SIRT1) in the liver of chronic‐plus‐binge ethanol‐fed mice and in the liver of patients with ALD. Conversely, adenoviral overexpression of hepatic DEPTOR suppressed mTORC1 signaling and ameliorated alcoholic hepatosteatosis, inflammation, and acute‐on‐chronic liver injury. Mechanistically, the lipid‐lowering effect of hepatic DEPTOR was attributable to decreased proteolytic processing, nuclear translocation, and transcriptional activity of the lipogenic transcription factor sterol regulatory element‐binding protein‐1 (SREBP‐1). DEPTOR‐dependent inhibition of mTORC1 also attenuated alcohol‐induced cytoplasmic accumulation of the lipogenic regulator lipin 1 and prevented alcohol‐mediated inhibition of fatty acid oxidation. Pharmacological intervention with rapamycin alleviated the ability of alcohol to up‐regulate lipogenesis, to down‐regulate fatty acid oxidation, and to induce steatogenic phenotypes. Chronic‐plus‐binge ethanol feeding led to activation of SREBP‐1 and lipin 1 through S6K1‐dependent and independent mechanisms. Furthermore, hepatocyte‐specific deletion of SIRT1 disrupted DEPTOR function, enhanced mTORC1 activity, and exacerbated alcoholic fatty liver, inflammation, and liver injury in mice. Conclusion : The dysregulation of SIRT1–DEPTOR–mTORC1 signaling is a critical determinant of ALD pathology; targeting SIRT1 and DEPTOR and selectively inhibiting mTORC1–S6K1 signaling may have therapeutic potential for treating ALD in humans. (H epatology 2018).
Working time directive has had little negative effect on anaesthetists’ training
Authors: Caroline White
Journal: BMJ (2012)

Legal limits on the number of hours doctors can work instigated by the European Working Time Directive seem to have had little negative effect on anaesthetists’ specialist training, research published in Anaesthesia indicates.1

The study, conducted in one anaesthetic department of a London teaching hospital, found that years 1 and 2 specialty trainees spent more time in theatre and being supervised by consultants than before the directive was introduced, whereas those in years 3-7 had fewer theatre sessions overall but more supervised sessions.

The findings run counter to the widely held view that the directive has curbed the amount of time available for and the quality of specialist medical training.2

The researchers analysed working patterns during two identical six month …