tbuckley/cabot-search huggingface dataset:
King’s Fund management course for specialist trainee registrars in diabetes and endocrinology
Authors: Arif Ullah
Journal: BMJ (2012)

The King’s Fund management course for specialist trainee registrars in diabetes and endocrinology is considered the gold standard for diabetologists because it is designed to cover management and leadership issues specific to the specialty. It was introduced three years ago with the blessing and positive feedback of diabetes and endocrinology consultants.

The course is intended for diabetes and endocrinology specialist trainee registrars in their final year of training to equip them with leadership and management skills before they become consultants.

I attended the course to develop the leadership and management skills that will be expected of me as a consultant in the health service. I was also interested to know more about personality types, team working, and microfinance …
IS IT SAFE TO SWITCH OAC IN PATIENTS WITH ATRIAL FIBRILLATION UNDERGOING PERCUTANEOUS CORONARY INTERVENTION? RESULTS FROM A RE-DUAL PCI SUBANALYSIS
Authors: Jurrien Ten Berg, Anne de Veer, Jonas Oldgren, Philippe Steg, Dmitry Aleksandrovich Zateyshchikov, Petr Janský, Ki-Bae Seung, Stefan Hohnloser, Gregory Lip, Matias Nordaby, Eva Kleine, Deepak Bhatt, Christopher Cannon
Journal: Journal of the American College of Cardiology (2018)
DIFFERENCES IN THE RISK OF STROKE, BLEEDING, AND MORTALITY BETWEEN FEMALE AND MALE PATIENTS WITH ATRIAL FIBRILLATION DURING WARFARIN THERAPY
Authors: Tero Penttilä, Mika Lehto, Jussi Niiranen, Juha Mehtälä, Houssem Khanfir, Riitta Lassila, Pekka Raatikainen
Journal: Journal of the American College of Cardiology (2018)
Abortion is over-regulated in US, study says
Authors: Janice Hopkins Tanne
Journal: BMJ (2018)

Abortion is safe but too regulated in the US, sometimes to the detriment of patient care, says a report from the National Academies of Sciences.1

“Overall, the committee concludes that the quality of abortion care depends to a great extent on where women live,” because of restrictions in some states, the report said. The expert committee reviewed trends in abortion between 1973, when the Supreme Court legalised it, and 2016.

“Legal abortions are safe and effective. Safety and quality are optimized when the abortion is performed as early in pregnancy as possible,” the report said. But state requirements may delay the …
Development of glioma prodrugs with site-specific activation by bioorthogonal palladium implants
Authors: Catherine Adam, Belén Rubio-ruiz, Jason T Weiss, Paul Brennan, Asier Unciti-broceta
Journal: Neuro-Oncology (2018)

As the effectiveness of surgery is limited by the risk of injury to normal brain tissue, improving the prognosis for patients diagnosed with malignant glioma will require novel therapeutic approaches. Over many years this has focused attention on drug discovery strategies to identify efficacious new agents, but without success. Our innovative approach is to focus on improving drug tolerability, maximising dose delivery and reducing side effects. The invention of drug-releasing devices implanted in a tumour cavity after surgery provides an opportunity to overcome the limitation on clinical doses of cytotoxic drugs due to unwanted side‑effects. In the brain such a strategy delivers chemotherapy to the diseased area and circumvents the blood-brain barrier. However, to date such implants have suffered from problems such as limited carrying capacity and toxicity to the healing of surgical wound by the immediate release of chemotherapeutics after implantation at surgery. Our unique approach couples a prodrug with the use of a non-toxic and catalytic implant to trigger local release of cytotoxic agents. The prodrugs are rendered non-toxic by masking the functional-groups key to its mode of action, then unmasked by the palladium in the implant. This approach has potential to decrease side-effects, increasing the maximum therapeutic dose, and could improve the pharmacokinetic properties of the drug, potentially increasing penetration across the blood-brain barrier. Furthermore, as our palladium device catalytically unmasks the prodrug, the treatment course would not be limited by the lifetime of the implant and could be readily repeated in cases of recurrence. Our results in live cancer cells demonstrate that the cytotoxic activity of drugs can be switched off with our masking strategy and restored with the palladium implant, with no toxicity of the prodrug or implant alone. Ongoing in vivo experiments have also established that the palladium implant is biocompatible.
I am temporarily working in Australia until Autumn 2006, at which point I intend to return home and apply for a London basic surgical training. I was wondering if you knew when the last rotations will be out before the Modernising Medical Careers scheme begins, ie do you think I will be able to apply for a rotation starting in February 2007?
Authors: Simon Eccles
Journal: BMJ (2006)

Have 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 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. <b>www.bmjcareers.com/advicezone</b>
PROGNOSTIC IMPORTANCE OF LEFT VENTRICULAR MECHANICAL DYSSYNCHRONY IN PREDICTING CARDIOVASCULAR DEATH IN THE GENERAL POPULATION: THE COPENHAGEN CITY HEART STUDY
Authors: Daniel Modin, Sofie Reumert Biering-Sørensen, Rasmus Møgelvang, Jan Jensen, Tor Biering-Sorensen
Journal: Journal of the American College of Cardiology (2018)
Aspirin or its analogues, a treatment for glioblastoma?
Authors: Joud Sabouni, Chris Perry, Iain Nicholl, Tim Snape, Gail Welsby, Philip Welsby
Journal: Neuro-Oncology (2018)

Glioblastoma is the most common malignant primary brain tumour in adults with approximately two thousand cases reported annually in England. Standard treatment approach is maximal surgical resection, followed by radiotherapy and chemotherapy with the alkylating agent temozolomide, but median survival time remains less than one year. Aspirin or its structural analogues have been suggested for the treatment or prevention of glioma with reduced cell viability and apoptosis induction reported in vitro. Hypoxia is central to glioblastoma pathophysiology and progression, with oxygen levels negatively correlating with tumour grade. Despite grade IV glioblastoma oxygen levels typically ranging from 0.1 to 2.5% pO2, in vitro studies seldom consider oxygen levels. U87-MG and SVG-p12 cell lines were maintained in normoxic (20% O2) or hypoxic (1% O2) atmosphere. Following treatment with the aspirin analogue fumaryl diaspirin, aspirin, temozolomide, cisplatin or combinations cell proliferation was examined using the proliferation marker CFDA-SE and cell cycle distribution determined using propidium iodide staining. Experiments were performed in triplicate and statistical significance determined by ANOVA with significance set at p<0.05. Under normoxia, drug treatments reduced U87-MG cell proliferation with the most significant inhibition occurring following treatment with the combination of aspirin and cisplatin for 48 hours, where CFDA-SE fluorescence was 76 ± 14.4% of day zero control, compared to 30 ± 8.6% in untreated cells (p<0.05). Similar results were observed under hypoxia. In U87-MG cells under normoxic conditions, cell cycle analysis determined that each of cisplatin, temozolomide, and drug combinations, when compared to control after 24 hours treatment, showed lower percentages of cells in the G0/Gl phase (p<0.001) and higher percentages in the G2/M phase (p≤0.05). Again, similar results were observed under hypoxia. The results demonstrate that under normoxia and hypoxia, the combination of aspirin or fumaryl diaspirin with temozolomide or cisplatin may have therapeutic potential in glioblastoma.
British Society of Otology’s balance course
Authors: Julian Danino
Journal: BMJ (2011)

The course is mainly for consultants, specialist registrars, and other junior doctors in ear, nose, and throat medicine, although it would be useful for general practitioners with a special interest in the specialty, audiological physicians, audiological scientists, balance physiotherapists, and physicians and neurologists with an interest in falls medicine. The aim is to provide an overview of the topic, to improve knowledge and skills, and in particular to provide information about the latest developments from leaders in the field.

The course is run by a well known and respected international faculty under the auspices of the British Society of Otology and ENT UK (British Association of Otorhinolaryngology—Head and Neck Surgery).

The one day course, which is run annually, was well structured. In the morning were didactic lectures that were all …
Subcutaneous co-administration of a potent bisphosphonate with recombinant human hyaluronidase (rHuPH20) inhibits injection site reactions with systemic bioavailability comparable to intravenous bisphosphonate administration in preclinical animal models
Authors: Ping Jiang, Curtis Thompson, Ryan Osgood, Alistair Quimbo, Adrian Radi, Gerald Fu, Walter Bee, Gregory Frost
Journal: Cancer Research (2008)

4033  Bisphosphonates (BPs) inhibit osteoclastic bone resorption and are used clinically to reduce elevated blood calcium levels and maintain skeletal bone mass. Typically administered by intravenous administration, bisphosphonates are indicated for the treatment of metastatic bone disease, multiple myeloma and hypercalcemia of malignancy. Subcutaneous (SC) injection of BP’s are associated with considerable cutaneous toxicity. The tolerability of SC BP with recombinant human hyaluronidase (rHuPH20), an enzyme that increases the absorption of locally injected drugs by degrading hyaluronan (HA) in the skin interstitium was therefore explored. Specifically, we investigated BP and rHuPH20 by local co-administration in both a rat interdermal (ID) model, as a high-throughput surrogate for human SC injection site reactions (ISRs); and in a porcine pharmacokinetic (PK) model, as a surrogate for human BP pharmacokinetics.  To evaluate whether rHuPH20 co-administration could alleviate ISRs associated with SC BP administration, rats were dosed ID with BP at 0.05 - 0.6 mg/ml, in admixture with rHuPH20. ID injections with BP resulted in reproducible ISRs that were quantified by adverse effect parameters including induration, erythema, and ulceration. All ISR parameters increased by BP dose in a concentration dependent manner. Co-administration of BP with 100 micrograms/mL rHuPH20 eliminated indurations and ulcerations in animals receiving doses
Tc-99m Sestamibi SPECT/CT as a New Tool for Monitoring Perfusion and Viability of Buried Perforator Based Free Flaps in Breast Reconstruction After Breast Cancer
Authors: Adrian Dragu, Rainer Linke, Torsten Kuwert, Frank Unglaub, Ulrich Kneser, Michael Stürzl, Raymund E. Horch, Alexander D. Bach
Journal: Clinical Nuclear Medicine (2009)

We report a case of a 53-year-old woman with ductal carcinoma in situ of the right breast. Skin-sparing mastectomy and single-stage reconstruction of the right breast with a "buried" free deep inferior epigastric perforator flap was performed. Classic clinical monitoring was not possible due to the buried situation of the free flap. To assess the perfusion and viability of the perforator based free flap we performed a Tc-99m-sestamibi-SPECT/CT. The results confirmed the intraoperative clinical findings. Tc-99m-sestamibi-SPECT/CT may be a new tool for the postoperative evaluation of regional perfusion and viability of buried perforator based free flaps.
RETRACTED ARTICLE: Linc00210 drives Wnt/β-catenin signaling activation and liver tumor progression through CTNNBIP1-dependent manner
Authors: Xiaomin Fu, Xiaoyan Zhu, Fujun Qin, Yong Zhang, Jizhen Lin, Yuechao Ding, Zihe Yang, Yiman Shang, Li Wang, Qinxian Zhang, Quanli Gao
Journal: Molecular Cancer (2018)

Abstract Background Liver tumor initiating cells (TICs) have self-renewal and differentiation properties, accounting for tumor initiation, metastasis and drug resistance. Long noncoding RNAs are involved in many physiological and pathological processes, including tumorigenesis. DNA copy number alterations (CNA) participate in tumor formation and progression, while the CNA of lncRNAs and their roles are largely unknown. Methods LncRNA CNA was determined by microarray analyses, realtime PCR and DNA FISH. Liver TICs were enriched by surface marker CD133 and oncosphere formation. TIC self-renewal was analyzed by oncosphere formation, tumor initiation and propagation. CRISPRi and ASO were used for lncRNA loss of function. RNA pulldown, western blot and double FISH were used to identify the interaction between lncRNA and CTNNBIP1. Results Using transcriptome microarray analysis, we identified a frequently amplified long noncoding RNA in liver cancer termed linc00210 , which was highly expressed in liver cancer and liver TICs. Linc00210 copy number gain is associated with its high expression in liver cancer and liver TICs. Linc00210 promoted self-renewal and tumor initiating capacity of liver TICs through Wnt/β-catenin signaling. Linc00210 interacted with CTNNBIP1 and blocked its inhibitory role in Wnt/β-catenin activation. Linc00210 silencing cells showed enhanced interaction of β-catenin and CTNNBIP1, and impaired interaction of β-catenin and TCF/LEF components. We also confirmed linc00210 copy number gain using primary hepatocellular carcinoma (HCC) samples, and found the correlation between linc00210 CNA and Wnt/β-catenin activation. Of interest, linc00210, CTNNBIP1 and Wnt/β-catenin signaling targeting can efficiently inhibit tumor growth and progression, and liver TIC propagation. Conclusion With copy-number gain in liver TICs, linc00210 is highly expressed along with liver tumorigenesis. Linc00210 drives the self-renewal and propagation of liver TICs through activating Wnt/β-catenin signaling. Linc00210 interacts with CTNNBIP1 and blocks the combination between CTNNBIP1 and β-catenin, driving the activation of Wnt/β-catenin signaling. Linc00210 -CTNNBIP1-Wnt/β-catenin axis can be targeted for liver TIC elimination.
Impending Atypical Femoral Fracture in a Patient of Breast Cancer With Bone Metastases Receiving Long-term Denosumab
Authors: Tsutomu Sugihara, Mitsuru Koizumi, Keiko Hayakawa, Yoshinori Ito, Naohiro Sata
Journal: Clinical Nuclear Medicine (2018)

Abstract Atypical femoral fractures (AFFs) occur in both osteoporosis patients and cancer patients who receive long-term bisphosphonate treatment. Denosumab offers an alternative approach for the treatment of bone metastases. We describe a 59-year-old woman with a history of breast carcinoma and bone metastasis who was prescribed denosumab for 4 years. The patient had no history of any prior bisphosphonate use. Bone scintigraphy showed an abnormal uptake in the right femur, which was confirmed as an impending AFF or atypical femoral stress reaction. In oncological patients receiving long-term denosumab, AFF should be included as a differential diagnosis for focal femoral findings.
The ABC of change: P, Q, R
Authors: Susan E Kersley
Journal: BMJ (2004)

<i>Positive thinking gives you power. Easy? Well, no. You need persistence with it, so that your quest for quality is not thrown by too many questions.</i> Susan Kersley <i>covers P, Q, and R in her series and explains how resistance will cause you to avoid reality, and so not get results</i>
Signing the talk
Authors: Peter Cross
Journal: BMJ (2005)

One of the missions we set ourselves is to alert readers to specialist career opportunities they might otherwise overlook. We are therefore delighted to start this week's issue with Nasreen Khan's piece on allergists, doctors dedicating their time to working with patients who have allergies. It's a specialty straddling various disciplines and requires a mindset different from organ based professions or immunology.

Apart …
ATRIAL FIBRILLATION RECURRENCE AFTER CATHETER ABLATION: THE VALUE OF EPICARDIAL FAT LOCATED POSTERIOR TO THE LEFT ATRIUM
Authors: Alexander van Rosendael, Jeff Smit, Philippe Van Rosendael, Melissa Leung, Mohammed El Mahdiui, Arthur Scholte, Victoria Delgado, James K. Min, Jeroen J. Bax
Journal: Journal of the American College of Cardiology (2018)
Royal colleges are urged to provide more support to reduce need for remediation
Authors: Matthew Billingsley
Journal: BMJ (2012)

The UK medical royal colleges have been urged to provide better induction, support, and training for their members to reduce the likelihood of doctors needing remediation.

In a report of its remediation working group, the Academy of Medical Royal Colleges said that royal colleges should provide more structured support for doctors appointed to their first career grade post and for doctors who have not worked in the UK before.

The report also recommends that when …
Abstract 15633: No Significant Difference in Yield of Obstructive Coronary Artery Disease Between an Initial Testing Strategy With Stress or Anatomical Imaging and Exercise Stress Testing in Ontario, Canada
Authors: Idan Roifman, Harindra C Wijeysundera, Peter C Austin, Graham A Wright, Jack V Tu
Journal: Circulation (2016)

Introduction: The optimal initial non-invasive diagnostic testing strategy for stable coronary artery disease (CAD) is unknown. While the American guidelines recommend an exercise stress test (GXT)...
The Circadian Clock in White and Brown Adipose Tissue: Mechanistic, Endocrine, and Clinical Aspects
Authors: Oren Froy, Marta Garaulet
Journal: Endocrine Reviews (2018)

Obesity is a major risk factor for the development of illnesses, such as insulin resistance and hypertension, and has become a serious public health problem. Mammals have developed a circadian clock located in the hypothalamic suprachiasmatic nuclei (SCN) that responds to the environmental light-dark cycle. Clocks similar to the one located in the SCN are found in peripheral tissues, such as the kidney, liver, and adipose tissue. The circadian clock regulates metabolism and energy homeostasis in peripheral tissues by mediating activity and/or expression of key metabolic enzymes and transport systems. Knockouts or mutations in clock genes that lead to disruption of cellular rhythmicity have provided evidence to the tight link between the circadian clock and metabolism. In addition, key proteins play a dual role in regulating the core clock mechanism, as well as adipose tissue metabolism, and link circadian rhythms with lipogenesis and lipolysis. Adipose tissues are distinguished as white, brown, and beige (or brite), each with unique metabolic characteristics. Recently, the role of the circadian clock in regulating the differentiation into the different adipose tissues has been investigated. In this review, the role of clock proteins and the downstream signaling pathways in white, brown, and brite adipose tissue function and differentiation will be reviewed. In addition, chronodisruption and metabolic disorders and clinical aspects of circadian adiposity will be addressed.
MDSC clinical assay for cancer detection and monitoring in urothelial carcinoma.
Authors: Arnab Basu, Ali Rafatnia, Hugh Manoli, Genevieve Danenberg, Alan L. Epstein, Jacek K. Pinski
Journal: Journal of Clinical Oncology (2018)

TPS110 Background: Human Myeloid Derived Suppressor Cells (MDSCs) have gained recognition as a significant population of cells that arise in cancer patients to mediate immune tolerance. Some studies have shown MDSC concentrations to be associated with overall survival and response to therapy in urothelial carcinoma. MDSCs comprise a heterogenous population that are yet to be fully characterized. We have identified a set of biomarkers uniquely expressed by the suppressive human MDSC phenotype and have developed an assay targeted to these markers. MDSCs are potentially a relatively cheap and easily performed screening and monitoring tool in cancers. This study will examine how a proprietary clinical assay works in detecting and monitoring MDSCs in blood and urine samples from patients with or without localized or metastatic bladder cancer. Methods: The pilot research trial will enroll 63 subjects in a 1:1:1 ratio in three groups, normal controls over age 40 without evidence of any malignancy, patients with metastatic disease and localized muscle invasive disease prior to cystectomy. This sample size provides 80% power to detect a 1SD difference in MDSC concentrations in these groups on an F test. Blood and urine samples will be drawn at baseline and at 4 months for comparison. The percent CD33+ HLA-DRlow HIF1a+, CD33+ HLADRlow C/EBPb+, CD11b+ HLA-DRlow HIF1a+, and CD11b+ HLA-DRlow C/EBPb+cells as a fraction of PBMC will be determined. Primary Outcome Measures will be 1. Change in MDSC levels in patients with known localized, muscle-invasive bladder cancer who undergo neoadjuvant and surgical treatment. 2. Change in MDSC level in patients with known metastatic bladder cancer who undergo systemic treatment and 3. The direction and magnitude of the changes compared with radiographically assessed tumor burden. Secondary outcome measures are to assess MDSC level measurements in urine cytology analysis at baseline and after treatment to determine whether the two tests correlate in any of the 3 groups of patients defined in this study. Conclusion: This pilot study will examine if a MDSC clinical assay works in detecting and monitoring MDSCs. Recruitment is open to patients at the USC Cancer center and LAC+USC medical center. Clinical trial information: NCT02735512.
ASSOCIATION OF HYPERLEPTINEMIA WITH SUBCLINICAL CARDIAC DYSFUNCTION IN OBESE ADOLESCENTS
Authors: Duangduan Siriwittayawan, Thamonwan Imerbtham, Teonchit Nuamchit, Piyanuch Thitiwuthikiat, Teerapat Yingchoncharoen
Journal: Journal of the American College of Cardiology (2018)
Risk factors for, and prevention of, shoulder injuries in overhead sports: a systematic review with best-evidence synthesis
Authors: Martin Asker, Hannah L Brooke, Markus Waldén, Ulrika Tranaeus, Fredrik Johansson, Eva Skillgate, Lena W Holm
Journal: British Journal of Sports Medicine (2018)

Objective To assess the evidence for risk factors and prevention measures for shoulder injuries in overhead sports. Design Systematic review with best-evidence synthesis. Data sources Medline (Ovid), PubMed (complementary search), Embase (Elsevier), Cochrane (Wiley), SPORTDiscus (Ebsco) and Web of Science Core Collection (Thomson Reuters), from 1 January 1990 to 15 May 2017. Eligibility criteria for selecting studies Randomised controlled trials, cohort studies and case-control studies on risk factors or prevention measures for shoulder injuries in overhead sports. The eligible studies were quality assessed using the Scottish Intercollegiate Guidelines Network criteria. Results Of 4778 studies identified, 38 were eligible for quality review and 17 met the quality criteria to be included in the evidence synthesis. One additional quality study presented a shoulder injury prevention programme. Most studies focused on baseball, lacrosse or volleyball (n=13). The risk factors examined included participation level (competition vs training) (n=10), sex (n=4), biomechanics (n=2) and external workload (n=2). The evidence for all risk factors was limited or conflicting. The effect of the prevention programme within the subgroup of uninjured players at baseline was modest and possibly lacked statistical power. Conclusions All investigated potential risk factors for shoulder injury in overhead sports had limited evidence, and most were non-modifiable (eg, sex). There is also limited evidence for the effect of shoulder injury prevention measures in overhead sports. PROSPERO trial registration number CRD42015026850 .