tbuckley/cabot-search huggingface dataset:
Design and characterization of clindamycin-loaded nanofiber patches composed of polyvinyl alcohol and tamarind seed gum and fabricated by electrohydrodynamic atomization
Authors: Tanikan Sangnim, Sontaya Limmatvapirat, Jurairat Nunthanid, Pornsak Sriamornsak, Wancheng Sittikijyothin, Sumalee Wannachaiyasit, Kampanart Huanbutta
Journal: Asian Journal of Pharmaceutical Sciences (2018)

In this study, we developed a polymeric nanofiber patch (PNP) for topical disease treatment using electrohydrodynamic atomization (EHDA). The nanofibers were prepared using various concentrations of polyvinyl alcohol (PVA) and tamarind seed gum and loaded with clindamycin HCl as a model drug. The precursor polymer solutions were sprayed using the EHDA technique; the EHDA processing parameters were optimized to obtain blank and drug-loaded PNPs. The skin adherence, translucence, and ventilation properties of the prepared PNPs indicated that they are appropriate for topical application. The conductivity of the polymer solution increased with increasing PVA and clindamycin concentrations, and increasing the PVA concentration enhanced the solution viscosity. Based on scanning electron microscopy analysis, the PVA concentration had a pronounced effect on the morphology of the sprayed product. Nanofibers were fabricated successfully when the solution PVA concentration was 10%, 13%, or 15% (w/v). The applied voltage significantly affected the diameters of the prepared nanofibers, and the minimum nanofiber diameter was 163.86 nm. Differential scanning calorimetry and X-ray diffraction analyses indicated that the model drug was dispersed in PVA in an amorphous form. The PNP prepared with a PVA:gum ratio of 9:1 absorbed water better than the PVA-only PNP and the PNP with a PVA:gum ratio of 9.5:0.5. Moreover, the PNPs loaded with clindamycin at concentrations of 1%-3% prohibited the growth of Staphylococcus aureus more effectively than clindamycin gel, a commercially available product.
Ticagrelor for Secondary Prevention of Atherothrombotic Events in Patients With Multivessel Coronary Disease
Authors: Sameer Bansilal, Marc P. Bonaca, Jan H. Cornel, Robert F. Storey, Deepak L. Bhatt, Ph. Gabriel Steg, Kyungah Im, Sabina A. Murphy, Dominick J. Angiolillo, Robert G. Kiss, Alexander N. Parkhomenko, Jose Lopez-Sendon, Daniel Isaza, Assen Goudev, Frederic Kontny, Peter Held, Eva C. Jensen, Eugene Braunwald, Marc S. Sabatine, A.J. Oude Ophuis
Journal: Journal of the American College of Cardiology (2018)
Men’s dominance of surgery could be creating a self perpetuating cycle
Authors: Tom Moberly
Journal: BMJ (2014)

Despite an increase in the proportion of women starting careers in medicine, the number of female surgeons remains low. <b>Tom Moberly</b> reports on research showing that the high proportion of men in surgery is undermining women’s sense of their identity as surgeons and may be causing women to leave the specialty, perpetuating male dominance
Rates of Mutation and Recombination in Siphoviridae Phage Genome Evolution over Three Decades
Authors: Anne Kupczok, Horst Neve, Kun D Huang, Marc P Hoeppner, Knut J Heller, Charles M A P Franz, Tal Dagan
Journal: Molecular Biology and Evolution (2018)

The evolution of asexual organisms is driven not only by the inheritance of genetic modification but also by the acquisition of foreign DNA. The contribution of vertical and horizontal processes to genome evolution depends on their rates per year and is quantified by the ratio of recombination to mutation. These rates have been estimated for bacteria; however, no estimates have been reported for phages. Here, we delineate the contribution of mutation and recombination to dsDNA phage genome evolution. We analyzed 34 isolates of the 936 group of Siphoviridae phages using a Lactococcus lactis strain from a single dairy over 29 years. We estimate a constant substitution rate of 1.9 × 10-4 substitutions per site per year due to mutation that is within the range of estimates for eukaryotic RNA and DNA viruses. The reconstruction of recombination events reveals a constant rate of five recombination events per year and 4.5 × 10-3 nucleotide alterations due to recombination per site per year. Thus, the recombination rate exceeds the substitution rate, resulting in a relative effect of recombination to mutation (r/m) of ∼24 that is homogenous over time. Especially in the early transcriptional region, we detect frequent gene loss and regain due to recombination with phages of the 936 group, demonstrating the role of the 936 group pangenome as a reservoir of genetic variation. The observed substitution rate homogeneity conforms to the neutral theory of evolution; hence, the neutral theory can be applied to phage genome evolution and also to genetic variation brought about by recombination.
Hemoptysis or Hematemesis?—The Importance of Professional Medical Interpretation
Authors: Jason H. Maley
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
I am ambitious and family life is important to me. Are there any female oncologists who would recommend clinical oncology as an option where one can have both a career and a family?
Authors: Rebecca Fitzgerald
Journal: BMJ (2005)

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 (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.
COMPARISON OF HIGH EFFICACY CZT SPECT MYOCARDIAL PERFUSION IMAGING (MPI) AND NA-I SPECT MPI WITH GOLD STANDARD CORONARY ANGIOGRAPHY
Authors: Harsh Rawal, Roma Mehta, Niyati Gupta, Srinivasan Sattiraju, Sanjay Mehta
Journal: Journal of the American College of Cardiology (2018)
Revisiting Interleukin-12 as a Cancer Immunotherapy Agent
Authors: Pedro Berraondo, Iñaki Etxeberria, Mariano Ponz-Sarvise, Ignacio Melero
Journal: Clinical Cancer Research (2018)

IL12 antitumor activities are mediated by the activation of T and natural killer (NK) lymphocytes to produce IFNγ. Systemically, recombinant IL12 has a narrow therapeutic window that favors local delivery, for instance, by gene therapy approaches. IL12 is a powerful partner in immunotherapy combinations with checkpoint inhibitors and adoptive T-cell transfer. Clin Cancer Res; 24(12); 2716-8. ©2018 AACRSee related article by Hu et al., p. 2920.
Perioperative and long-term impact of neoadjuvant chemoradiotherapy using full-dose gemcitabine and concurrent radiation for resectable pancreatic cancer.
Authors: Minako Nagai, Takahiro Akahori, Satoshi Nishiwada, Kenji Nakagawa, Kota Nakamura, Toshihiro Tanaka, Hideyuki Nishiofuku, Kimihiko Kichikawa, Tetsuro Tamamoto, Masatoshi Hasegawa, Naoya Ikeda, Masayuki Sho
Journal: Journal of Clinical Oncology (2018)

367 Background: Although much attention has been paid to neoadjuvat treatment for pancreatic cancer (PC), its efficacy remains to be established. In this study, we have retrospectively evaluated the impact of neoadjuvant chemoradiotherapy (NACRT) on perioperative and long-term clinical outcome in PC. Methods: One hundred sixty patients who preoperatively received full-dose gemcitabine (1000 mg/m 2 ) with concurrent radiation of 54 Gy between 2006 and 2016 were analyzed. One hundred thirty patients who underwent upfront surgery were served as control. Results: Among the 160 patients treated with NACRT, 153 patients (96%) completed the protocol treatment. The reasons of failure to complete NACRT were drug-induced pneumonia, acute mucosal injury, severe cholangitis and poor performance status (PS). Furthermore 21 (13%) couldn’t undergo pancreatic resection after NACRT because of distant metastasis in 9 patients, tumor progression in 7 and poor PS in 5. The rate of pancreatic fistula was lower and hospital stay was shorter in the NACRT group compared to the control group (P = 0.033, P = 0.002). Furthermore, the rate of lymph node metastasis, R0 resection and pathological stage were favorable in the NACRT group (P &lt; 0.0001, P = 0.006, P &lt; 0.0001). The completion rate of adjuvant chemotherapy was also higher in the NACRT group (P = 0.015). Importantly, patients treated with NACRT had a better prognosis than those without (median survival time: 60.2 vs. 28.5M, P = 0.008). In addition, according to tumor resectability status, patients were classified as R (resectable), BR-P (borderline resectable with venous involvement) and BR-A (borderline resectable with arterial involvement) groups. As a result, patients treated with NACRT had a better prognosis than those without in the R and BR-P groups (58.6 vs. 34.2M, P = 0.013, 62.4 vs. 18.8M, P = 0.015), while NACRT had no significant impact on prognosis in the BR-A group. Conclusions: Neoadjuvant chemoradiotherapy may have a variety of favorable impact in pancreatic cancer treatment. Furthermore, NACRT may improve the prognosis especially in resectable and borderline resectable pancreatic cancer with venous involvement.
End “Black Wednesday” by starting specialty posts a month after foundation programme, royal colleges say
Authors: Abi Rimmer
Journal: BMJ (2014)

Specialty training should begin in September, a month after the start of the foundation programme, the Academy of Medical Royal Colleges has said.

The move is designed to bring an end to the handover challenges seen when medical trainees across the UK move to a new hospital post on the first Wednesday in August. This has traditionally been accompanied by a spike in death rates and has become known as “Black Wednesday.” The change would also improve patient safety and the quality of care and reduce stress on doctors in training, the academy said.

Proposals for the change were made by the academy’s …
Unilateral F-18 FDG Uptake in the Neck, in Patients With Sympathetic Denervation
Authors: Lizza Lebron, Alexander J. Chou, Jorge A. Carrasquillo
Journal: Clinical Nuclear Medicine (2010)

There is great interest in the study of brown fat and its importance in human metabolism. Since the routine use of fluorodeoxyglucose (FDG) F-18 positron emission tomography-computed tomography (PET/CT) imaging, it has been recognized that brown adipose tissue (BAT) is often visualized in adults. BAT typically appears as symmetrical uptake of FDG, most frequently seen in the cervical/supraclavicular region. In this report, we describe 2 cases with Horner syndrome and 1 case with surgical sympathectomy, which had unilateral FDG uptake in BAT contralateral to the affected side. This imaging study emphasizes the importance of sympathetic innervation in activation of BAT. Adipose tissue is classified by its coloration in 2 types, white adipose tissue and BAT. White adipose tissue is composed of a single lipid droplet and acts as the primary site of energy storage and as a modulator of whole-body metabolism and insulin resistance. BAT is characterized by small cells, multilocularity, large number of mitochondria, increased vascularity, and abundant sympathetic noradrenergic innervations. The brown adipocyte itself has an uncoupling protein 1 that mediates thermogenesis. Thermogenesis in BAT is controlled by norepinephrine released from the sympathetic nervous system; which interacts mainly with β-adrenergic receptors in BAT. BAT uptake of FDG, a surrogate for imaging glucose metabolism, and of I-123 metaiodobenzylguanidine (MIBG) and F-18 fluorodopamine, surrogates for imaging sympathetic innervation, has been described. A recent study with FDG showed that functional BAT is prevalent in adult humans, with a significant female predominance. The most conspicuous BAT depot detected in the human adult with PET-CT technique localizes to the supraclavicular/cervical area; but it may also be found in paravertebral, mediastinal, and perinephric fat. Physiologic uptake in the supraclavicular and cervical region is generally symmetric. The use of PET imaging may provide insight into physiology and regulation of BAT. We present 3 cases that illustrate, with imaging, the importance of sympathetic innervation in activation of BAT.
A phase 2 trial of lenvatinib 18 mg versus 14 mg once daily (QD) in combination with everolimus (5 mg QD) in renal cell carcinoma (RCC) after 1 prior VEGF-targeted treatment.
Authors: Hilary Glen, Javier Puente, Daniel Yick Chin Heng, Sun Young Rha, Di Li, Daniel E. Stepan, Corina E. Dutcus, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2018)

TPS707 Background: Based on findings from a randomized phase 2 study (Study 205), lenvatinib (LEN) + everolimus (EVE) was approved in the United States and European Union for patients (pts) with advanced RCC following 1 prior anti-angiogenic therapy. In that study, LEN 18 mg QD + EVE 5 mg QD significantly prolonged progression-free survival (PFS) compared with either monotherapy. In the LEN+EVE cohort, grades 3 and 4 treatment-emergent adverse events (TEAEs) occurred in 71% of pts. We report the design of an ongoing, multicenter, randomized, double-blind, phase 2 study (Study 218) to evaluate if a lower LEN starting dosage regimen provides similar efficacy with a better safety profile than LEN 18 mg + EVE 5 mg (NCT03173560). Methods: Eligible pts are aged ≥ 18 years with advanced clear cell RCC, 1 prior anti-VEGF therapy, ≥ 1 measurable target lesion per RECIST 1.1, a KPS score of ≥ 70, and prior nivolumab is allowed. Pts will receive LEN 18 mg or 14 mg QD + EVE 5 mg QD in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The LEN 14-mg dose will be escalated to 18 mg if no intolerable grade 2, or any grade ≥ 3 TEAEs requiring dose reduction occur in cycle 1. The primary endpoints are objective response rate (ORR) at week 24 (ORR 24W ) and the proportion of pts with intolerable grade 2 and any grade ≥ 3 TEAEs within 24 wks after randomization. Secondary endpoints include PFS and ORR. An estimated 306 pts will be randomized. Sample size is based on detecting noninferiority (NI) of ORR 24W and superiority of the primary safety endpoint. Two interim analyses (IA) will be performed when 150 and 200 pts have completed 24 wks of follow-up or discontinue earlier. Each analysis will test NI and futility of the LEN 14-mg arm ORR 24W vs the 18-mg arm ORR 24W . An O’Brien-Fleming boundary will be used for NI. If the 1-sided P-value is ≤ 0.005 at the first IA, ≤ 0.014 at the second IA, or ≤ 0.045 at the final analysis, then NI in ORR 24W will be claimed. If the futility boundary is crossed (ie, 1-sided P-value is ≥ 0.776 at the first IA or ≥ 0.207 at the second IA), then futility will be claimed. Clinical trial information: NCT03173560.
Tumorigenic and Antiproliferative Properties of the TALE-Transcription Factors MEIS2D and MEIS2A in Neuroblastoma
Authors: Anja Groß, Catrine Schulz, Jasmine Kolb, Jan Koster, Sibylle Wehner, Sebastian Czaplinski, Abdulghani Khilan, Hermann Rohrer, Patrick N. Harter, Thomas Klingebiel, Julian D. Langer, Dirk Geerts, Dorothea Schulte
Journal: Cancer Research (2018)

Neuroblastoma is one of only a few human cancers that can spontaneously regress even after extensive dissemination, a poorly understood phenomenon that occurs in as many as 10% of patients. In this study, we identify the TALE-homeodomain transcription factor MEIS2 as a key contributor to this phenomenon. We identified MEIS2 as a MYCN-independent factor in neuroblastoma and showed that in this setting the alternatively spliced isoforms MEIS2A and MEIS2D exert antagonistic functions. Specifically, expression of MEIS2A was low in aggressive stage 4 neuroblastoma but high in spontaneously regressing stage 4S neuroblastoma. Moderate elevation of MEIS2A expression reduced proliferation of MYCN-amplified human neuroblastoma cells, induced neuronal differentiation and impaired the ability of these cells to form tumors in mice. In contrast, MEIS2A silencing or MEIS2D upregulation enhanced the aggressiveness of the tumor phenotype. Mechanistically, MEIS2A uncoupled a negative feedback loop that restricts accumulation of cellular retinoic acid, an effective agent in neuroblastoma treatment. Overall, our results illuminate the basis for spontaneous regression in neuroblastoma and identify an MEIS2A-specific signaling network as a potential therapeutic target in this common pediatric malignancy.Significance: This study illuminates the basis for spontaneous regressions that can occur in a common pediatric tumor, with implications for the development of new treatment strategies. Cancer Res; 78(8); 1935-47. ©2018 AACR.
Biomarker Discovery from We to Me: Is Learning from Each Patient a New Approach?
Authors: Stephanie Lheureux
Journal: Clinical Cancer Research (2018)

Abstract The immune response is a dynamic multistep process with a complex system regulation. Identification of predictive biomarkers is therefore challenging. Deep investigation of an exceptional responder to pembrolizumab in ovarian cancer identifies a new mechanism of response and highlights the interest of individualized medicine strategy. Clin Cancer Res; 24(14); 3233–5. ©2018 AACR. See related article by Bellone et al., p. 3282
Natural environments and suicide mortality in the Netherlands: a cross-sectional, ecological study
Authors: Marco Helbich, Derek de Beurs, Mei-Po Kwan, Rory C O'Connor, Peter P Groenewegen
Journal: The Lancet Planetary Health (2018)

BackgroundNatural outdoor environments, such as green spaces (ie, grass, forests, or parks), blue spaces (ie, visible bodies of fresh or salt water), and coastal proximity, have been increasingly shown to promote mental health. However, little is known about how and the extent to which these natural environments are associated with suicide mortality. Our aim was to investigate whether the availability of green space and blue space within people's living environments and living next to the coast are protective against suicide mortality.MethodsIn this cross-sectional, ecological study, we analysed officially confirmed deaths by suicide between 2005 and 2014 per municipality in the Netherlands. We calculated indexes to measure the proportion of green space and blue space per municipality and the coastal proximity of each municipality using a geographical information system. We fitted Bayesian hierarchical Poisson regressions to assess associations between suicide risk, green space, blue space, and coastal proximity, adjusted for risk and protective factors.FindingsMunicipalities with a large proportion of green space (relative risk 0·879, 95% credibility interval 0·779–0·991) or a moderate proportion of green space (0·919, 0·846–0·998) showed a reduced suicide risk compared with municipalities with less green space. Green space did not differ according to urbanicity in relation to suicide. Neither blue space nor coastal proximity was associated with suicide risk. The geographical variation in the residual relative suicide risk was substantial and the south of the Netherlands was at high risk.InterpretationOur findings support the notion that exposure to natural environments, particularly to greenery, might have a role in reducing suicide mortality. If confirmed by future studies on an individual level, the consideration of environmental exposures might enrich suicide prevention programmes.FundingEuropean Research Council (grant agreement number 714993).
Gabapentin for Chronic Neuropathic Pain
Authors: Andrew Moore, Sheena Derry, Philip Wiffen
Journal: JAMA (2018)

<h3>Clinical Question</h3> Is gabapentin associated with pain relief in people with chronic neuropathic pain? <h3>Bottom Line</h3> Oral gabapentin (1200-3600 mg/d for 4-12 weeks) for patients with moderate or severe neuropathic pain from postherpetic neuralgia (PHN) or painful diabetic neuropathy (PDN) is associated with pain reduction of at least 50% in 14% to 17% more patients than placebo.
Risk of basal cell carcinoma in a randomized clinical trial of aspirin and folic acid for the prevention of colorectal adenomas
Authors: M.N. Passarelli, E.L. Barry, D. Zhang, P. Gangar, J.R. Rees, R.S. Bresalier, G. McKeown-Eyssen, M.R. Karagas, J.A. Baron
Journal: British Journal of Dermatology (2018)

Aspirin may reduce the risk of several types of cancer.To evaluate if folic acid is associated with risk of basal cell carcinoma (BCC).BCC incidence was evaluated in a randomized, double-blind, placebo-controlled clinical trial of aspirin (81 mg daily or 325 mg daily for ~3 years) and/or folic acid (1 mg daily for ~6 years) for the prevention of colorectal adenomas among 1121 participants with a previous adenoma. BCC was confirmed by blinded review of pathology reports.One hundred and four of 958 non-Hispanic white participants were diagnosed with BCC over a median follow-up of 13·5 years. Cumulative incidence of BCC was 12% [95% confidence interval (CI) 7-17] for placebo, 16% (95% CI 11-21) for 81 mg aspirin daily and 15% (95% CI 10-20) for 325 mg aspirin daily [hazard ratio (HR) for any aspirin 1·45 (95% CI 0·93-2·26); HR for 81 mg daily 1·57 (95% CI 0·96-2·56); HR for 325 mg daily 1·33 (95% CI 0·80-2·20)]. BCC risk was higher with aspirin use in those without previous skin cancer but lower with aspirin use in those with previous skin cancer (Pinteraction = 0·02 for 81 mg aspirin daily; Pinteraction = 0·03 for 325 mg aspirin daily). Folic acid supplementation was unrelated to BCC incidence (HR 0·85; 95% CI 0·57-1·27).Neither aspirin nor folic acid treatment had a statistically significant effect on risk of BCC. Subgroup analysis suggested that chemopreventive effects of nonsteroidal anti-inflammatory drugs may be specific to those at high risk for BCC.
The resident medical officer
Authors: Khurshid R Ghani, Paul Hadway, Ken Anson
Journal: BMJ (2004)

<i>Ever wondered what it9s like to be a resident medical officer in a private hospital?</i> Khurshid Ghani, Paul Hadway, <i>and</i> Ken Anson <i>think it9s a useful experience with time to study on the job</i>