tbuckley/cabot-search huggingface dataset:
Localized delivery of curcumin into brain with polysorbate 80-modified cerasomes by ultrasound-targeted microbubble destruction for improved Parkinson's disease therapy
Authors: Nisi Zhang, Fei Yan, Xiaolong Liang, Manxiang Wu, Yuanyuan Shen, Min Chen, Yunxue Xu, Guangyang Zou, Peng Jiang, Caiyun Tang, Hairong Zheng, Zhifei Dai
Journal: Theranostics (2018)

Rationale:Treatment for Parkinson's disease (PD) is challenged by the presence of the blood-brain barrier (BBB) that significantly limits the effective drug concentration in a patient's brain for therapeutic response throughout various stages of PD.Curcumin holds the potential for α-synuclein clearance to treat PD; however, its applications are still limited due to its low bioavailability and poor permeability through the BBB in a free form.Methods: Herein, this paper fabricated curcumin-loaded polysorbate 80-modified cerasome (CPC) nanoparticles (NPs) with a mean diameter of ~110 nm for enhancing the localized curcumin delivery into the targeted brain nuclei via effective BBB opening in combination with ultrasound-targeted microbubble destruction (UTMD).Results: The liposomal nanohybrid cerasome exhibited superior stability towards PS 80 surfactant solubilization and longer circulation lifetime (t1/2 = 6.22 h), much longer than free curcumin (t1/2 = 0.76 h).The permeation was found to be 1.7-fold higher than that of CPC treatment only at 6 h after the systemic administration of CPC NPs.Notably, motor behaviors, dopamine (DA) level and tyrosine hydroxylase (TH) expression all returned to normal, thanks to α-synuclein (AS) removal mediated by efficient curcumin delivery to the striatum.Most importantly, the animal experiment demonstrated that the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice had notably improved behavior disorder and dopamine depletion during two-week post-observation after treatment with CPC NPs (15 mg curcumin/kg) coupled with UTMD. Conclusion:This novel CPC-UTMD formulation approach could be an effective, safe and amenable choice with higher therapeutic relevance and fewer unwanted complications than conventional chemotherapeutics delivery systems for PD treatment in the near future.
Reply letter to: Letter to the editor on the article "The seroprevalence rate and population genetic structure of human cystic echinococcosis in the Middle East: A systematic review and meta-analysis"
Authors: Tahereh Mikaeili Galeh, Adel Spotin, Mahmoud Mahami-Oskouei, David Carmena, Mohammad Taghi Rahimi, Aleksandra Barac, Roghayeh Ghoyounchi, Reza Berahmat, Ehsan Ahmadpour
Journal: International Journal of Surgery (2018)
The founder of the Canadian Association of Physicians with Disabilities
Authors: Olubimpe Ayeni
Journal: BMJ (2004)

A shok Muzumdar, a semiretired specialist in rehabilitation medicine, has been gradually losing his vision over the past 20 years. Now he can see only outlines and can't appreciate detail. He founded the Canadian Association of Physicians with Disabilities (CAPD) in August 2000, and, at that time, it was the first association of its kind in the world to represent disabled doctors. The CAPD now has 72 members across Canada, with different physical and mental disabilities, and it is an affiliated society of the Canadian Medical Association (CMA).

After graduating from the University of Indore, India, in 1964, Ashok moved to England to train before finally settling in Canada. In 1985 he became the director and head of the department of physical medicine and rehabilitation at the Queen Elizabeth Hospital in Charlottetown, Prince Edward Island.

I had called a [telephone] number a couple of times but was told that it was out of service. When I asked my secretary to call, I was surprised that she was able to get through. I then realised that I had read …
Systematic Assessment of Strategies for Lung-targeted Delivery of MicroRNA Mimics
Authors: Kenny Schlosser, Mohamad Taha, Duncan J. Stewart
Journal: Theranostics (2018)

There is considerable interest in the use of synthetic miRNA mimics (or inhibitors) as potential therapeutic agents in pulmonary vascular disease; however, the optimal delivery method to achieve high efficiency, selective lung targeting has not been determined. Here, we sought to investigate the relative merits of different lung-targeted strategies for delivering miRNA mimics in rats. Methods: Tissue levels of a synthetic miRNA mimic, cel-miR-39-3p (0.5 nmol in 50 µL invivofectamine/PBS vehicle) were compared in male rats (n=3 rats/method) after delivery by commonly used lung-targeting strategies including intratracheal liquid instillation (IT-L), intratracheal aerosolization with (IT-AV) or without ventilator assistance (IT-A), intranasal liquid instillation (IN-L) and intranasal aerosolization (IN-A). Intravenous (IV; via jugular vein), intraperitoneal (IP) and subcutaneous (SC) delivery served as controls. Relative levels of cel-miR-39 were quantified by RT-qPCR. Results: At 2 h post delivery, IT-L showed the highest lung mimic level, which was significantly higher than levels achieved by all other methods (from ~10- to 10,000-fold, p<0.05). Mimic levels remained detectable in the lung 24 h after delivery, but were 10- to 100-fold lower. The intrapulmonary distribution of cel-miR-39 was comparable when delivered as either a liquid or aerosol, with evidence of mimic distribution to both the left and right lung lobes and penetration to distal regions. All lung-targeted strategies showed lung-selective mimic uptake, with mimic levels 10- to 100-fold lower in heart and 100- to 10,000-fold lower in liver, kidney and spleen. In contrast, IV, SC and IP routes showed comparable or higher mimic levels in non-pulmonary tissues. Conclusions: miRNA uptake in the lungs differed markedly by up to 4 orders of magnitude, demonstrating that the choice of delivery strategy could have a significant impact on potential therapeutic outcomes in preclinical investigations of miRNA-based drug candidates.
NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial
Authors: Stephen A Harrison, Mary E Rinella, Manal F Abdelmalek, James F Trotter, Angelo H Paredes, Hays L Arnold, Marcelo Kugelmas, Mustafa R Bashir, Mark J Jaros, Lei Ling, Stephen J Rossi, Alex M DePaoli, Rohit Loomba
Journal: The Lancet (2018)
Government takes steps to reduce annual burden of medication errors in England
Authors: Jacqui Wise
Journal: BMJ (2018)

Medication errors lead to an estimated 712 deaths in England every year and could be a contributory factor in 1700 to 22 303 deaths a year, concludes a report from the Universities of York, Manchester, and Sheffield.1

In response to the report the health and social care secretary, Jeremy Hunt, announced steps to improve patients’ safety. Speaking at the Global Patient Safety Summit in London on 23 February, he said, “Part of the change needs also to be cultural: moving from a blame culture to a learning culture, so doctors and nurses are supported to be open about mistakes rather than cover them up for fear of losing their job.”

The report, funded by …
Abstract 15845: The Relationship Between Chronic Health Conditions and Outcome Following Out-of hospital Ventricular Fibrillation Cardiac Arrest
Authors: Florence Dumas, Jennifer Blackwood, Lindsay White, Carol Fahrenburg, Xavier Jouven, Alain Cariou, Thomas D Rea
Journal: Circulation (2016)

Introduction: The cumulative burden of chronic health conditions could contribute to out-of-hospital cardiac arrest (OHCA) physiology and response to therapy during attempted resuscitation. Yet lit...
Newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with DAAs: A prospective population study
Authors: Antonietta Romano, Paolo Angeli, Sara Piovesan, Franco Noventa, Georgios Anastassopoulos, Liliana Chemello, Luisa Cavalletto, Martina Gambato, Francesco Paolo Russo, Patrizia Burra, Valter Vincenzi, Pier Giorgio Scotton, Sandro Panese, Diego Tempesta, Tosca Bertin, Maurizio Carrara, Antonio Carlotto, Franco Capra, Giada Carolo, Giovanna Scroccaro, Alfredo Alberti
Journal: Journal of Hepatology (2018)
PERSISTENCE OF PERIODIC BREATHING/CHEYNE-STOKES RESPIRATION AFTER TILT TABLE TEST DURING SHORT TERM RESPIRATORY MONITORING IN PATIENTS WITH SYSTOLIC HEART FAILURE
Authors: Chiara Borrelli, Francesco Gentile, Federico Rossari, Paolo Sciarrone, Claudio Passino, Gianluca Mirizzi, Francesca Bramanti, Giovanni Iudice, Michele Emdin, Alberto Giannoni
Journal: Journal of the American College of Cardiology (2018)
AIDS malignancy consortium (AMC) 095: A phase I study of ipilimumab (IPI) and nivolumab (NIVO) in advanced HIV-associated solid tumors (ST) with expansion cohorts in HIV-associated solid tumors and classical Hodgkin lymphoma (cHL).
Authors: Lakshmi Rajdev, Elizabeth Chiao, Shelly Lensing, Howard Streicher, Richard F. Little, Dirk Dittmer, Mark Einstein, Missak Haigentz, Joseph A. Sparano, Ronald T. Mitsuyasu
Journal: Journal of Clinical Oncology (2018)

TPS44 Background: Immune checkpoint blockade (ICB) using agents that target the priming phase (i.e. CTLA-4) and effector phase (e.g. PD-1) of host immunity, used individually or in combination, has emerged as a therapeutic strategy for cancers. However, little is known about the safety, tolerability and efficacy of ICB in patients (pts) with HIV infection and cancer. Methods: AMC 095 (NCT02408861) is a multicenter, international phase I study of the PD-1 inhibitor, nivo alone or in combination with a CTLA-4 inhibitor, ipi, in 2 cohorts stratified by CD4 counts (Stratum 1: CD4 counts≥200/uL and Stratum 2: CD4 count 100-200/uL) with additional expansion cohorts at the recommended phase II dose in pts with ST and cHL. The primary study objective is to determine the safety and feasibility of nivo alone and the nivo+ipi combination. Secondary objectives are to evaluate the effects of single agent nivo, and ipi+ nivo, on HIV replication and immune function (HIV viral load in plasma using conventional assay, CD4+, and CD8+ cells), and to obtain preliminary information regarding response. The trial was initiated in 8/15, as of 9/30/17, the study is ongoing, and 14 pts have been enrolled. Updated information on the safety and responses will be presented. Clinical trial information: NCT02408861. Funded by the NCI Grant #UM1CA121947.[Table: see text]
P073 Regulation of joint destruction by activin a in rheumatoid arthritis
Authors: V Kracke, J Intemann, M Fennen, T Pap, B Dankbar
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Activins and inhibins belong to the transforming growth factor β family. Activins are disulphide-linked homo- or heterodimers consisting of two inhibin β chains (βA, βB) that are expressed in many cell types. However, activin A (βA βA) is the only activin that is expressed in bone and cartilage. Moreover, activin A has been demonstrated not only to stimulate receptor activator of NF-κB ligand (RANKL)-induced osteoclast (OC) differentiation but also to inhibit osteoblast differentiation. <h3>Objectives</h3> Here we investigate the impact of activin a on joint destruction in rheumatoid arthritis. <h3>Methods</h3> Synovial tissue samples from rheumatoid arthritis (RA) and osteoarthritis (OA) patients were analysed by immunohistochemical staining. For <i>in vitro</i> experiments, bone marrow-derived macrophages (BMM) were isolated from femurs and tibias of WT mice and differentiated into osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF) and RANKL with or without activin A. OC differentiation was characterised by TRAP staining. Resorption activity was determined by quantification of osteoclast-mediated pit formation on a calcium phosphate-coated plate. Proliferation of BMMs was evaluated using the CyQUANT Cell Proliferation Assay Kit. Furthermore, osteoclast-specific gene expression as well as the activation of SMAD2, MAPK and NF-kB signalling were analysed by immunoblotting. The interaction of phospho-SMAD2 with NFATc1 was evaluated by co-immunoprecipitation using Dynabeads. <h3>Results</h3> We demonstrate that activin A is highly abundant in the synovium of RA but not of OA patients. <i>In vitro</i>, activin A strongly enhanced the RANKL-mediated differentiation of BMMs into mature OCs, reflected by a significantly increased OC number, OC size and number of nuclei per OC compared to the conventional treatment with RANKL alone. Moreover, concomitant administration of activin A led to a significant increase of the total resorption area as well as resorption area per pit, indicating an increased activity of individual OCs. Effects of activin A on BMMs were not caused by increased proliferation since no effect on M-CSF-driven proliferation was observed. Furthermore, activin A alone was not able to induce the expression of OC differentiation markers, but the RANKL-induced expression was enhanced by activin A. After stimulation with activin A, BMMs showed an activation of SMAD2, but not of MAPK p38, ERK, JNK or NF-kB. Finally, co-stimulation of RANKL and activin A resulted in an increased interaction of activated SMAD2 with NFATc1. <h3>Conclusions</h3> The data strongly suggest that increased expression of activin A in the arthritic joint is most likely associated with enhanced osteoclast formation, promoting joint destruction in rheumatoid arthritis. <h3>Disclosure of interest</h3> None declared
Daily home spirometry to detect early steroid treatment effects in newly treated pulmonary sarcoidosis
Authors: Caroline E. Broos, Monique Wapenaar, Caspar W.N. Looman, Johannes C.C.M. in ’t Veen, Leon M. van den Toorn, Maria J. Overbeek, Marco J.J.H. Grootenboers, Roxane Heller, Rémy L. Mostard, Linda H.C. Poell, Henk C. Hoogsteden, Mirjam Kool, Marlies S. Wijsenbeek, Bernt van den Blink
Journal: European Respiratory Journal (2018)

Prednisone is the mainstay of sarcoidosis treatment. However, prednisone treatment optimisation is warranted, since prolonged high-dose prednisone therapy is associated with burdensome and harmful side-effects [1, 2]. Early prednisone dose tapering has the potential to reduce side-effects. Gaining insight in the early treatment response can help to determine when tapering could be initiated. To date, there are no prospective studies that look at early treatment response to prednisone in sarcoidosis by monitoring clinical symptoms and daily patient-administered lung function. Therefore, we initiated a multicentre, prospective and observational study with daily home spirometry to detect early steroid treatment effects in newly treated pulmonary sarcoidosis (Dutch National Trial Register NTR4328; [www.trialregister.nl/trialreg][1]). The major treatment effect of prednisone on FVC is reached within 2 to 3 weeks in newly treated sarcoidosis patients <http://ow.ly/3A3E30h5ZuT> The authors gratefully acknowledge patients, research nurses, respiratory function technologists and physicians participating in this study from Erasmus MC, Franciscus Gasthuis & Vlietland, Ikazia hospital, Amphia hospital, Haaglanden Medical Centre and Zuyderland Medical Center Heerlen (all the Netherlands). The authors thank Mirjam van Manen, Linda de Kleer, Frans Mertens and Hadassa de Raaf (Dept of Pulmonary Medicine, Erasmus MC, Rotterdam, the Netherlands) for technical assistance. The authors contributed as follows. C.E. Broos, M. Wapenaar, J.C.C.M. in 't Veen, L.M. van den Toorn, M.J.J.H. Grootenboers, R. Heller, L.H.C. Poell, H.C. Hoogsteden, M.S. Wijsenbeek and B. van den Blink contributed to the study concept and design. C.E. Broos, M. Wapenaar, J.C.C.M. in 't Veen, L.M. van den Toorn, M.J.J.H. Grootenboers, R. Heller M.J. Overbeek, R.L. Mostard, L.H.C. Poell, H.C. Hoogsteden, M. Kool, M.S. Wijsenbeek and B. van den Blink, patient recruitment and data collection. C.E. Broos, M. Wapenaar, C.W.N. Looman, M.S. Wijsenbeek and B. van den Blink, data analysis and interpretation. C.E. Broos, M. Wapenaar, C.W.N. Looman, M.S. Wijsenbeek and B. van den Blink, manuscript preparation and manuscript drafting. All authors gave final approval on the manuscript.. [1]: http://www.trialregister.nl/trialreg
Health Care Spending in the United States Compared With 10 Other High-Income Countries
Authors: Howard Bauchner, Phil B. Fontanarosa
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Safety and efficacy of biological therapies in patients with psoriasis with alcoholic cirrhosis: a French retrospective study of 23 cases
Authors: E. Begon, N. Beneton, C. Poiraud, C. Droitcourt, C. Jacobzone, A. Vermersch-Langlin, V. Descamps, J.L. Perrot, A. Khemis, V. Pallure, A.C. Fougerousse, M. Sigal-Grinberg, J.-L. Schmutz, C. Goujon, Z. Reguiai
Journal: British Journal of Dermatology (2018)
How do I choose an MBA (master of business administration) degree course and how much will it cost?
Authors: Wai-Ching Leung
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>
Association of preoperative neutrophil-to-lymphocyte ratio with immune populations in the tumor microenvironment of patients with clear cell renal cell carcinoma.
Authors: Alejandro Sanchez, Ming Liu, Briana Nixon, Mazyar Ghanaat, Renzo DiNatale, Kyle A Blum, Paul Russo, Victor E. Reuter, Ming Li, A. Ari Hakimi
Journal: Journal of Clinical Oncology (2018)

688 Background: Currently, there are no blood biomarkers that reflect the composition of immune cells in the tumor microenvironment (TME) of patients with clear cell renal cell carcinoma (ccRCC). High pre-operative neutrophil-to-lymphocyte ratio (NLR) is associated with adverse oncologic outcomes in ccRCC. However, how NLR relates to the immune cell composition in the TME is not well understood. Methods: We performed flow cytometry on tumor and adjacent normal renal tissue from a prospective cohort of patients who underwent surgery from 6/2015-7/2017. Immune cell populations, as a percent of total CD45+, were compared to baseline age, sex, body mass index (BMI), SSIGN score, sarcomatoid differentiation, and AJCC stage (I-IV). NLR was calculated using pre-operative absolute neutrophil-to-lymphocyte counts and further categorized as inflamed if NLR was ≥ 3. Correlations between continuous variables were performed using Spearman’s rank correlation. Comparisons of means were made using the Wilcoxon signed-rank test. Results: Among 48 patients, 32 (71%) were male, median age was 59 (IQR 52-66), BMI of 38.5 (IQR 26-32.6), SSIGN score of 8 (IQR 5-12), 9 (20%) had sarcomatoid differentiation, and 20 (44%) had metastases at presentation. No correlations were found between age, BMI, and different immune cell populations or NLR. A higher ratio of tissue resident (CD8a+CD49a+CD103+) to circulating (CD8a+CD49a-CD103-) CD8+ T-cells in the TME was associated with increasing stage at presentation (p = 0.02). Inflamed patients had similar total CD45+, CD8+ T cell, CD4+ T cell, and macrophage immune infiltration. However, inflamed patients had a higher proportion of CD8+ Tres infiltration (p = 0.04) and a trend towards higher neutrophil infiltration (p = 0.15). Conclusions: A higher proportion of resident CD8+T-cells correlated with advanced disease at presentation. NLR may reflect a change in the type of CD8+T cell population found in the TME. This population of CD8+ T-cells, and NLR as a possible biomarker should be validated and further investigated in a larger cohort of patients. Funding: Ruth L. Kirschstein Research Service Award T32CA082088 (A.S., M.G.)
Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series
Authors: S. Kommoss, M.K. McConechy, F. Kommoss, S. Leung, A. Bunz, J. Magrill, H. Britton, F. Kommoss, F. Grevenkamp, A. Karnezis, W. Yang, A. Lum, B. Krämer, F. Taran, A. Staebler, S. Lax, S.Y. Brucker, D.G. Huntsman, C.B. Gilks, J.N. McAlpine, A. Talhouk.
Journal: Annals of Oncology (2018)
Ultrasound of the breast
Authors: Michelle Mullan, Kylie Snook, Caroline Taylor
Journal: BMJ (2009)

This course is aimed mainly at medical professionals who regularly work in the field of breast disease, such as general surgical trainees with an interest in the breast; breast clinicians; radiographers; and general practitioners who do breast clinics.

We did this course during our final year of surgical training. It is expected that the course will take six months to complete.

There has been considerable debate about whether breast training should be separate from general surgical training. A recent statement from the ex-president of the Association of Breast Surgeons, Hugh Bishop, states that “unless trainee breast surgeons learn a lot more about breast imaging, particularly breast ultrasound, then they will rapidly be reduced to the status of a greeter in a new breast patient clinic.”1

We felt as surgeons that we would like to offer our patients a more holistic experience when they come to the breast clinic, rather than …
CONTROLLED CORONARY FLOW INFUSION MEASURES MYOCARDIAL MICROVASCULAR RESISTANCE IN REAL TIME DURING EXPERIMENTAL ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Robert S. Schwartz, Jon Hoem, Oliver Bludau, Nikola Cesarovic, Mareika Gastl, Blathnaid Feldman, Martin Rothman
Journal: Journal of the American College of Cardiology (2018)
TCTAP A-089 Are There Gender Differences in 5-Year Clinical Outcomes Following Successful Endovascular Revascularization for Peripheral Arterial Disease?
Authors: Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Ahmed Mashaly, Yoonjee Park, Won Young Jang, Woo Hyeun Kim, Eun Jin Park, Jah Yeon Choi, Jin Oh Na, Cheolung Choi, Hong Euy Lim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2018)