tbuckley/cabot-search huggingface dataset:
Deimmunization for gene therapy: host matching of synthetic zinc finger constructs enables long-term mutant Huntingtin repression in mice
Authors: Carmen Agustín-Pavón, Michal Mielcarek, Mireia Garriga-Canut, Mark Isalan
Journal: Molecular Neurodegeneration (2016)

Synthetic zinc finger (ZF) proteins can be targeted to desired DNA sequences and are useful tools for gene therapy. We recently developed a ZF transcription repressor (ZF-KOX1) able to bind to expanded DNA CAG-repeats in the huntingtin (HTT) gene, which are found in Huntington's disease (HD). This ZF acutely repressed mutant HTT expression in a mouse model of HD and delayed neurological symptoms (clasping) for up to 3 weeks. In the present work, we sought to develop a long-term single-injection gene therapy approach in the brain. Since non-self proteins can elicit immune and inflammatory responses, we designed a host-matched analogue of ZF-KOX1 (called mZF-KRAB), to treat mice more safely in combination with rAAV vector delivery. We also tested a neuron-specific enolase promoter (pNSE), which has been reported as enabling long-term transgene expression, to see whether HTT repression could be observed for up to 6 months after AAV injection in the brain. After rAAV vector delivery, we found that non-self proteins induce significant inflammatory responses in the brain, in agreement with previous studies. Specifically, microglial cells were activated at 4 and 6 weeks after treatment with non-host-matched ZF-KOX1 or GFP, respectively, and this was accompanied by a moderate neuronal loss. In contrast, the host-matched mZF-KRAB did not provoke these effects. Nonetheless, we found that using a pCAG promoter (CMV early enhancer element and the chicken β-actin promoter) led to a strong reduction in ZF expression by 6 weeks after injection. We therefore tested a new non-viral promoter to see whether the host-adapted ZF expression could be sustained for a longer time. Vectorising mZF-KRAB with a promoter-enhancer from neuron-specific enolase (Eno2, rat) resulted in up to 77 % repression of mutant HTT in whole brain, 3 weeks after bilateral intraventricular injection of 1010 virions. Importantly, repressions of 48 % and 23 % were still detected after 12 and 24 weeks, respectively, indicating that longer term effects are possible. Host-adapted ZF-AAV constructs displayed a reduced toxicity and a non-viral pNSE promoter improved long-term ZF protein expression and target gene repression. The optimized constructs presented here have potential for treating HD.
Renal replacement therapy during Stevens-Johnson syndrome and toxic epidermal necrolysis: a retrospective observational study of 238 patients
Authors: M. Papo, L. Valeyrie-Allanore, K. Razazi, G. Carteaux, P. Wolkenstein, O. Chosidow, C. Brun-Buisson, A. Mekontso Dessap, N. de Prost
Journal: British Journal of Dermatology (2016)

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are rare but serious life-threatening adverse cutaneous drug reactions1. The mortality of SJS/TEN patients ranges from 3-4% in those with SJS to 30-50% in the most severe TEN patients, requiring intensive care unit (ICU) admission2,3. Several prognostic factors associated with an elevated risk of mortality have been reported in SJS/TEN, including a SCORTEN (i.e., a specific severity score based on seven items) ≥24, or mechanical ventilation requirement5. To our knowledge, no study has assessed the impact of acute renal failure (ARF) requiring renal replacement therapy (RRT) on outcomes among a large cohort of patients.

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Increase in reptile-associated human salmonellosis and shift toward adulthood in the age groups at risk, the Netherlands, 1985 to 2014
Authors: Lapo Mughini-Gras, Max Heck, Wilfrid van Pelt
Journal: Eurosurveillance (2016)

While the contribution of the main food-related sources to human salmonellosis is well documented, knowledge on the contribution of reptiles is limited. We quantified and examined trends in reptile-associated salmonellosis in the Netherlands during a 30-year period, from 1985 to 2014. Using source attribution analysis, we estimated that 2% (95% confidence interval: 1.3-2.8) of all sporadic/domestic human salmonellosis cases reported in the Netherlands during the study period (n = 63,718) originated from reptiles. The estimated annual fraction of reptile-associated salmonellosis cases ranged from a minimum of 0.3% (corresponding to 11 cases) in 1988 to a maximum of 9.3% (93 cases) in 2013. There was a significant increasing trend in reptile-associated salmonellosis cases (+ 19% annually) and a shift towards adulthood in the age groups at highest risk, while the proportion of reptile-associated salmonellosis cases among those up to four years-old decreased by 4% annually and the proportion of cases aged 45 to 74 years increased by 20% annually. We hypothesise that these findings may be the effect of the increased number and variety of reptiles that are kept as pets, calling for further attention to the issue of safe reptile-human interaction and for reinforced hygiene recommendations for reptile owners.
Trends in Emergency Department Visits Among Medicaid Patients—Reply
Authors: Ning Tang, John Stein, Renee Hsia
Journal: JAMA (2011)

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 2022 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
Health Research and the HIPAA Privacy Rule—Reply
Authors: Roberta B. Ness
Journal: JAMA (2008)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
CCG ditches plan to suspend non-urgent referrals
Authors: Anne Gulland
Journal: BMJ (2016)

A clinical commissioning group has withdrawn a plan to suspend non-urgent referrals in light of feedback showing that the proposal was “not supported.”

In its two year financial recovery plan, launched at the beginning of August, St Helens CCG proposed that non-urgent referrals to hospital be “paused” for four months over the winter in a bid to save at least £2.5m (€3m; $3.3m) …
Nucleophosmin (NPM) Has Increased Expression and Shuttling Activity in Chronic Lymphocytic Leukaemia without Somatic Hypermutation of the Immunoglubulin Gene (UM-CLL) and Is Linked to Ribosomal Proteins: A Possible Role for Increased Protein biosynthesis in the Adverse Outcome of UM-CLL.
Authors: Karen S Rees-Unwin, Robin Faragher, Claire V Hutchinson, Richard D Unwin, Julie Adams, Andrew Pettitt, Alison H Banham, Karen Pulford, John Burthem
Journal: Blood (2008)
Fentanyl Law Enforcement Submissions and Increases in Synthetic Opioid–Involved Overdose Deaths — 27 States, 2013–2014
Authors: R. Matthew Gladden, Pedro Martinez, Puja Seth
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

In March and October 2015, the Drug Enforcement Administration (DEA) and CDC, respectively, issued nationwide alerts identifying illicitly manufactured fentanyl (IMF) as a threat to public health and safety (1,2). IMF is unlawfully produced fentanyl, obtained through illicit drug markets, includes fentanyl analogs, and is commonly mixed with or sold as heroin (1,3,4). Starting in 2013, the production and distribution of IMF increased to unprecedented levels, fueled by increases in the global supply, processing, and distribution of fentanyl and fentanyl-precursor chemicals by criminal organizations (3). Fentanyl is a synthetic opioid 50-100 times more potent than morphine (2).* Multiple states have reported increases in fentanyl-involved overdose (poisoning) deaths (fentanyl deaths) (2). This report examined the number of drug products obtained by law enforcement that tested positive for fentanyl (fentanyl submissions) and synthetic opioid-involved deaths other than methadone (synthetic opioid deaths), which include fentanyl deaths and deaths involving other synthetic opioids (e.g., tramadol). Fentanyl deaths are not reported separately in national data. Analyses also were conducted on data from 27 states(†) with consistent death certificate reporting of the drugs involved in overdoses. Nationally, the number of fentanyl submissions and synthetic opioid deaths increased by 426% and 79%, respectively, during 2013-2014; among the 27 analyzed states, fentanyl submission increases were strongly correlated with increases in synthetic opioid deaths. Changes in fentanyl submissions and synthetic opioid deaths were not correlated with changes in fentanyl prescribing rates, and increases in fentanyl submissions and synthetic opioid deaths were primarily concentrated in eight states (high-burden states). Reports from six of the eight high-burden states indicated that fentanyl-involved overdose deaths were primarily driving increases in synthetic opioid deaths. Increases in synthetic opioid deaths among high-burden states disproportionately involved persons aged 15-44 years and males, a pattern consistent with previously documented IMF-involved deaths (5). These findings, combined with the approximate doubling in fentanyl submissions during 2014-2015 (from 5,343 to 13,882) (6), underscore the urgent need for a collaborative public health and law enforcement response.
An unusual endoscopic ultrasound diagnosis in kidney-transplant patient
Authors: Luca Barresi, Ilaria Tarantino, Dario Ligresti, Gabriele Curcio, Antonino Granata, Gaia Chiarello, Mario Traina
Journal: Gut (2016)

A 29-year-old man who had undergone kidney transplantation in 1999 for chronic glomerular disease, on treatment with ciclosporin, azathioprine and steroids, was admitted for severe, diffuse abdominal pain. No fever or other symptoms were present. Multidetector CT (MDCT) scan showed several chest and abdominal lymphadenopathies and pericardial, pleural and abdominal effusions. A post-transplant lymphoproliferative disorder (PTLD) was suspected and, therefore, azathioprine and ciclosporin were suspended with resolution of serosal effusions. However, cytology and cytofluorimetry from ascites and pleural effusion and surgical histology from supraclavicular lymph node showed no lymphoproliferative disease. Epstein-Barr virus (EBV)-DNA was repeatedly negative, as was serology for HIV. …
Drug-induced photosensitivity: new insights into pathomechanisms and clinical variation through basic and applied science
Authors: S. Khandpur, R.M. Porter, S.J. Boulton, A. Anstey
Journal: British Journal of Dermatology (2016)

Drug‐induced photosensitivity occurs when a drug is capable of absorbing radiation from the sun (usually ultraviolet A) leading to chemical reactions that cause cellular damage (phototoxicity) or, more rarely, form photoallergens (photoallergy). The manifestation varies considerably in presentation and severity from mild pain to severe blistering. Despite screening strategies and guidelines in place to predict photoreactive drugs during development there are still new drugs coming onto the market that cause photosensitivity. Thus, there is a continuing need for dermatologists to be aware of the different forms of presentation and the culprit drugs. Management usually involves photoprotection and cessation of drug treatment. However, there are always cases where the culprit drug is indispensable. The reason why some patients are susceptible while others remain asymptomatic is not known. A potential mechanism for the phototoxic reactions is the generation of reactive oxygen species (ROS), and there are a number of reasons why some patients might be less able to cope with enhanced levels of ROS.
Occupational Exposure to Endocrine-Disrupting Chemicals and Birth Weight and Length of Gestation: A European Meta-Analysis
Authors: Laura Birks, Maribel Casas, Ana M. Garcia, Jan Alexander, Henrique Barros, Anna Bergström, Jens Peter Bonde, Alex Burdorf, Nathalie Costet, Asta Danileviciute, Merete Eggesbø, Mariana F. Fernández, M. Carmen González-Galarzo, Wojciech Hanke, Vincent Jaddoe, Manolis Kogevinas, Inger Kull, Aitana Lertxundi, Vasiliki Melaki, Anne-Marie Nybo Andersen, Nicolás Olea, Kinga Polanska, Franca Rusconi, Loreto Santa-Marina, Ana Cristina Santos, Tanja Vrijkotte, Daniela Zugna, Mark Nieuwenhuijsen, Sylvaine Cordier, Martine Vrijheid
Journal: Environmental Health Perspectives (2016)

Women of reproductive age can be exposed to endocrine-disrupting chemicals (EDCs) at work, and exposure to EDCs in pregnancy may affect fetal growth.We assessed whether maternal occupational exposure to EDCs during pregnancy as classified by application of a job exposure matrix was associated with birth weight, term low birth weight (LBW), length of gestation, and preterm delivery.Using individual participant data from 133,957 mother-child pairs in 13 European cohorts spanning births from 1994 through 2011, we linked maternal job titles with exposure to 10 EDC groups as assessed through a job exposure matrix. For each group, we combined the two levels of exposure categories (possible and probable) and compared birth outcomes with the unexposed group (exposure unlikely). We performed meta-analyses of cohort-specific estimates.Eleven percent of pregnant women were classified as exposed to EDCs at work during pregnancy, based on job title. Classification of exposure to one or more EDC group was associated with an increased risk of term LBW [odds ratio (OR) = 1.25; 95% CI: 1.04, 1.49], as were most specific EDC groups; this association was consistent across cohorts. Further, the risk increased with increasing number of EDC groups (OR = 2.11; 95% CI: 1.10, 4.06 for exposure to four or more EDC groups). There were few associations (p < 0.05) with the other outcomes; women holding job titles classified as exposed to bisphenol A or brominated flame retardants were at higher risk for longer length of gestation.Results from our large population-based birth cohort design indicate that employment during pregnancy in occupations classified as possibly or probably exposed to EDCs was associated with an increased risk of term LBW. Citation: Birks L, Casas M, Garcia AM, Alexander J, Barros H, Bergström A, Bonde JP, Burdorf A, Costet N, Danileviciute A, Eggesbø M, Fernández MF, González-Galarzo MC, Gražulevičienė R, Hanke W, Jaddoe V, Kogevinas M, Kull I, Lertxundi A, Melaki V, Andersen AM, Olea N, Polanska K, Rusconi F, Santa-Marina L, Santos AC, Vrijkotte T, Zugna D, Nieuwenhuijsen M, Cordier S, Vrijheid M. 2016. Occupational exposure to endocrine-disrupting chemicals and birth weight and length of gestation: a European meta-analysis. Environ Health Perspect 124:1785-1793; http://dx.doi.org/10.1289/EHP208.
EML4-ALK fusion gene in lung adenocarcinoma: A retrospective analysis of the outcome of cisplatin plus pemetrexed treated patients.
Authors: G. Altavilla, M. Santarpia, C. Arrigo, M. Rizzo, G. Galletti, G. Marabello, A. Gnani, V. Pitini
Journal: Journal of Clinical Oncology (2010)

7610 Background: A subset of lung adenocarcinomas harbors a small inversion within chromosome 2p, giving rise to a transforming fusion gene EML4-ALK (ALK) which encodes an activated tyrosine kinase. To help identification of this gene within the NSCLC population of South Italy, we retrospectively examined its incidence in a cohort of lung adenocarcinomas, the clinical characteristics and treatment outcomes of pts who had a rearranged ALK. Methods: Ninety-six lung adenocarcinoma pts. (58 male, 38 female, median age 64 years), who received cisplatin (75 mg/m2) plus pemetrexed (500 mg/m2) or cisplatin plus gemcitabine (1,250 mg/m2) every 21 days, were retrospectively analyzed. Cytology or histology samples were reviewed to reconfirm the diagnosis; ALK and EGFR amplification were identified by FISH. The ALK FISH positive samples were tested for EGFR and K-Ras mutations by DNA sequencing; ALK rearrangements were confirmed by immunohistochemistry for ALK expression. Results: Of 96 screened tumors 8 (8.3%) were EML4-ALK mutants; none of them showed EGFR and/or k-Ras mutations and all were detected in non smoking and younger men (median age 52 years, range 32-56). Within the EML4-ALK cohort all pts were treated with cisplatin plus pemetrexed. Two of evaluable pts. had a PR, four had SD and two had PD. At the time of this review the median TTP was 9 months and the median OS 17 months in ALK positive pts. The 32 ALK negative Cisplatin Pemetrexed treated pts achieved a median TTP of 6.2 months and a median OS of 11 months. Conclusions: According to our results ALK positive tumors may constitute a distinct entity among lung adenocarcinomas and be characterized by younger onset, absence of mutations in EGFR and RAS and prevalence in non or light smokers. Overall the presence of EML4-ALK fusion gene in our pts is suggestive of a better therapeutic outcome. No significant financial relationships to disclose.
The Survival Benefit of “Fistula First, Catheter Last” in Hemodialysis Is Primarily Due to Patient Factors
Authors: Robert S. Brown, Bhanu K. Patibandla, Alexander S. Goldfarb-Rumyantzev
Journal: Journal of the American Society of Nephrology (2016)

Patients needing hemodialysis are advised to have arteriovenous fistulas rather than catheters because of significantly lower mortality rates. However, disparities in fistula placement raise the possibility that patient factors have a role in this apparent mortality benefit. We derived a cohort of 115,425 patients on incident hemodialysis ≥67 years old from the US Renal Data System with linked Medicare claims to identify the first predialysis vascular access placed. We compared mortality outcomes in patients initiating hemodialysis with a fistula placed first, a catheter after a fistula placed first failed, or a catheter placed first ( n =90,517; reference group). Of 21,436 patients with a fistula placed first, 9794 initiated hemodialysis with that fistula, and 8230 initiated dialysis with a catheter after failed fistula placement. The fistula group had the lowest mortality over 58 months (hazard ratio, 0.50; 95% confidence interval, 0.48 to 0.52; P &lt;0.001), with mortality rates at 6, 12, and 24 months after initiation of 9%, 17%, and 31%, respectively, compared with 32%, 46%, and 62%, respectively, in the catheter group. However, the group initiating hemodialysis with a catheter after failed fistula placement also had significantly lower mortality rates than the catheter group had over 58 months (hazard ratio, 0.66; 95% confidence interval, 0.64 to 0.68; P &lt;0.001), with mortality rates of 15%, 25%, and 42% at 6, 12, and 24 months, respectively. Thus, patient factors affecting fistula placement, even when patients are hemodialyzed with a catheter instead, may explain at least two thirds of the mortality benefit observed in patients with a fistula.
NICE consults on child vaccination rates
Authors: Gareth Iacobucci
Journal: BMJ (2016)

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Improvements in health related quality of life (HRQL) correlate positively with clinical reponses in ankylosing spondylitis (AS) patients - Results from ATLAS
Authors: D Van der Heijde, M P Luo, J Davis, H Zeidler, P J Mease, M Breban, F Cantini, R Westhovens, P Wordsworth, R Wong, H Kupper, D Revicki
Journal: Annals of the Rheumatic Diseases (2006)