Disease burden attributable to influenza is substantial in subtropical regions. Our study aims to estimate excess pneumonia and influenza (P&I) mortality associated with influenza by subtypes/lineages in Shang...
http://ift.tt/2B8hoxu
Τετάρτη 6 Δεκεμβρίου 2017
Excess pneumonia and influenza mortality attributable to seasonal influenza in subtropical Shanghai, China
Successfully implementing and embedding guidelines to improve the nutrition and growth of preterm infants in neonatal intensive care: a prospective interventional study
Objectives
We aimed to improve the nutritional care of preterm infants by developing a complex (multifaceted) intervention intended to translate current evidence into practice. We used the sociological framework of Normalization Process Theory (NPT), to guide implementation in order to embed the new practices into routine care.
DesignA prospective interventional study with a before and after methodology.
ParticipantsInfants <30 weeks gestation or <1500 g at birth.
SettingTertiary neonatal intensive care unit.
InterventionsThe intervention was introduced in phases: phase A (control period, January–August 2011); phase B (partial implementation; improved parenteral and enteral nutrition solutions, nutrition team, education, August–December 2011); phase C (full implementation; guidelines, screening tool, 'nurse champions', January–December 2012); phase D (postimplementation; January–June 2013). Bimonthly audits and staff NPT questionnaires were used to measure guideline compliance and 'normalisation', respectively. NPT Scores were used to guide implementation in real time. Data on nutrient intakes and growth were collected continuously.
ResultsThere were 52, 36, 75 and 35 infants in phases A, B, C and D, respectively. Mean guideline compliance exceeded 75% throughout the intervention period, peaking at 85%. Guideline compliance and NPT scores both increased over time, (r=0.92 and 0.15, p<0.03 for both), with a significant linear association between the two (r=0.21, p<0.01). There were significant improvements in daily protein intake and weight gain between birth and discharge in phases B and Ccompared with phase A (p<0.01 for all), which were sustained into phase D.
ConclusionsNPT and audit results suggest that the intervention was rapidly incorporated into practice, with high guideline compliance and accompanying improvements in protein intake and weight gain. NPT appears to offer an effective way of implementing new practices such that they lead to sustained changes in care. Complex interventions based on current evidence can improve both practice and clinical outcomes.
http://ift.tt/2zXDv5O
Can traditional risk factors explain the higher risk of cardiovascular disease in South Asians compared to Europeans in Norway and New Zealand? Two cohort studies
Objectives
The objective was to prospectively examine potential differences in the risk of first cardiovascular disease (CVD) events between South Asians and Europeans living in Norway and New Zealand, and to investigate whether traditional risk factors could explain any differences.
MethodsWe included participants (30–74 years) without prior CVD in a Norwegian (n=16 606) and a New Zealand (n=129 449) cohort. Ethnicity and cardiovascular risk factor information was linked with hospital registry data and cause of death registries to identify subsequent CVD events. We used Cox proportional hazards regression to investigate the relationship between risk factors and subsequent CVD for South Asians and Europeans, and to calculate age-adjusted HRs for CVD in South Asians versus Europeans in the two cohorts separately. We sequentially added the major CVD risk factors (blood pressure, lipids, diabetes and smoking) to study their explanatory role in observed ethnic CVD risk differences.
ResultsSouth Asians had higher total cholesterol (TC)/high-density lipoprotein (HDL) ratio and more diabetes at baseline than Europeans, but lower blood pressure and smoking levels. South Asians had increased age-adjusted risk of CVD compared with Europeans (87%–92% higher in the Norwegian cohort and 42%–75% higher in the New Zealand cohort) and remained with significantly increased risk after adjusting for all major CVD risk factors. Adjusted HRs for South Asians versus Europeans in the Norwegian cohort were 1.57 (95% CI 1.19 to 2.07) in men and 1.76 (95% CI 1.09 to 2.82) in women. Corresponding figures for the New Zealand cohort were 1.64 (95% CI 1.43 to 1.88) in men and 1.39 (95% CI 1.11 to 1.73) in women.
ConclusionDifferences in TC/HDL ratio and diabetes appear to explain some of the excess risk of CVD in South Asians compared with Europeans. Preventing dyslipidaemia and diabetes in South Asians may therefore help reduce their excess risk of CVD.
http://ift.tt/2nD1sxi
The association between the use of biomedical services and the holistic use of traditional East Asian medicine: a national survey of outpatients in South Korea
Objectives
The holistic use of a system of complementary and alternative medicine (CAM) is potentially linked to its treatment outcomes. This paper examines how the use of biomedicine is associated with the holistic use of CAM, focusing on traditional East Asian medicine (EM) that is uniquely integrated in the medical system in South Korea.
Design/SettingsA representative national sample of EM outpatients in South Korea.
Participants3861 survey respondents.
MethodsBy using the 2011 Korean National Survey of EM patients, ordered logistic regression models specify the relationship between EM outpatients' use of biomedicine and their holistic use of EM modalities.
ResultsAmong EM outpatients who used at least one EM modality in the past 3 months, people who used two (33.3%) or three (29.4%) modalities together are the two highest proportions, followed by users of four (18.1%), five (7.2%), six (2.1%) and seven (0.6%) modalities. The odds for EM users to use EM holistically are 17% greater among EM users who used biomedicine as well, compared with EM users who did not use biomedicine.
ConclusionsThe healthcare community should recognise that CAM use likely becomes holistic as people use biomedicine concomitantly, when the practice rights over a CAM system are comprehensively and exclusively entitled to a group of CAM professionals who are independent from practitioners of biomedicine.
http://ift.tt/2zXD9w0
Likelihood of death among hospital inpatients in New Zealand: prevalent cohort study
Objectives
(1) To establish the likelihood of dying within 12 months for a cohort of hospital inpatients in New Zealand (NZ) on a fixed census date; (2) to identify associations between likelihood of death and key sociodemographic, diagnostic and service-related factors and (3) to compare results with, and extend findings of, a Scottish study undertaken for the same time period and census date. National databases of hospitalisations and death registrations were used, linked by unique health identifier.
Participants6074 patients stayed overnight in NZ hospitals on the census date (10 April 2013), 40.8% of whom were aged ≥65 years; 54.4% were women; 69.1% of patients were NZ European; 15.3% were Maori; 7.6% were Pacific; 6.1% were Asian and 1.9% were 'other'.
SettingAll NZ hospitals.
Results14.5% patients (n=878) had died within 12 months: 1.6% by 7 days; 4.5% by 30 days; 8.0% by 3 months and 10.9% by 6 months. In logistic regression models, the strongest predictors of death within 12 months were: age ≥80 years (OR=5.52(95% CI 4.31 to 7.07)); a history of cancer (OR=4.20(3.53 to 4.98)); being Māori (OR=1.62(1.25 to 2.10)) and being admitted to a medical specialty, compared with a surgical specialty (OR=3.16(2.66 to 3.76)).
ConclusionWhile hospitals are an important site of end of life care in NZ, their role is less significant than in Scotland, where 30% of an inpatient cohort recruited using similar methods and undertaken on the same census date had died within 12 months. One reason for this finding may be the extended role of residential long-term care facilities in end of life care provision in NZ.
http://ift.tt/2zXwYb0
'At-risk individuals responses to direct to consumer advertising of prescription drugs: a nationally representative cross-sectional study
Objectives
The factors determining individuals' self-reported behavioural responses to direct to consumer advertising of prescription drugs were explored with an emphasis on 'at-risk' individuals' responses.
DesignNationally representative cross-sectional survey.
SettingCommunity living adults in New Zealand.
Participants2057 adults (51% women).
Primary outcome measuresSelf-reported behavioural responses to drug advertising (asking a physician for a prescription, asking a physician for more information about an illness, searching the internet for more information regarding an illness and asking a pharmacist for more information about a drug).
MethodsMultivariate logistic regressions determined whether participants' self-reported behavioural responses to drug advertising were predicted by attitudes towards advertising and drug advertising, judgements about safety and effectiveness of advertised drugs, self-reported health status, materialism, online search behaviour as well as demographic variables.
ResultsIdentifying as Indian and to a less extent Chinese, Māori and 'other' ethnicities were the strongest predictors of one or more self-reported responses (ORs 1.76–5.00, Ps<0.05). Poorer self-reported health status (ORs 0.90–0.94, all Ps<0.05), favourable attitude towards drug advertising (ORs 1.34–1.61, all Ps<0.001) and searching for medical information online (ORs 1.32–2.35, all Ps<0.01) predicted all self-reported behavioural outcomes. Older age (ORs 1.01–1.02, Ps<0.01), less education (OR 0.89, P<0.01), lower income (ORs 0.89–0.91, Ps<0.05) and higher materialism (ORs 1.02–1.03, Ps<0.01) also predicted one or more self-reported responses.
ConclusionsTaken together, the findings suggest individuals, especially those who are 'at-risk' (ie, with poorer self-reported health status, older, less educated, lower income and ethnic minorities), may be more vulnerable to drug advertising and may make uninformed decisions accordingly. The outcomes raise significant concerns relating to the ethicality of drug advertising and suggest a need for stricter guidelines to ensure that drug advertisements provided by pharmaceutical companies are ethical.
http://ift.tt/2nAYzxf
Insights from Australians with respiratory disease living in the community with experience of self-managing through an emergency department 'near miss for breathlessness: a strengths-based qualitative study
Objectives
Breathlessness 'crises' in people with chronic respiratory conditions are a common precipitant for emergency department (ED) presentations, many of which might be avoided through improved self-management and support. This study sought insights from people with experience of ED 'near misses' where they considered going to the ED but successfully self-managed instead.
Design and methodsA qualitative approach was used with a phenomenological orientation. Participants were eligible if they reported breathlessness on most days from a diagnosed respiratory condition and experience of ≥1 ED near miss. Recruitment was through respiratory support groups and pulmonary rehabilitation clinics. Semistructured interviews were conducted with each participant via telephone or face-to-face. Questions focused on ED-related decision-making, information finding, breathlessness management and support. This analysis used an integrative approach and independent coding by two researchers. Lazarus and Cohen's Transactional Model of Stress and Coping informed interpretive themes.
ResultsInterviews were conducted with 20 participants, 15 of whom had chronic obstructive pulmonary disease. Nineteen interviews were conducted via telephone. Analysis identified important factors in avoiding ED presentation to include perceived control over breathlessness, self-efficacy in coping with a crisis and desire not to be hospitalised. Effective coping strategies included: taking a project management approach that involved goal setting, monitoring and risk management; managing the affective dimension of breathlessness separately from the sensory perceptual and building three-way partnerships with primary care and respiratory services.
ConclusionsIn addition to teaching non-pharmacological and pharmacological management of breathlessness, interventions should aim to develop patients' generic self-management skills. Interventions to improve self-efficacy should ensure this is substantiated by transfer of skills and support, including knowledge about when ED presentation is necessary. Complementary initiatives are needed to improve coordinated, person-centred care. Future research should seek ways to break the cyclical relationship between affective and sensory-perceptual dimensions of breathlessness.
http://ift.tt/2nAEZAZ
Atrial fibrillation in patients with severe mental disorders and the risk of stroke, fatal thromboembolic events and bleeding: a nationwide cohort study
Objectives
Outcomes of atrial fibrillation (AF) in patients with severe mental disorders are largely unknown. We compared rates of stroke, fatal thromboembolic events and bleeding in patients with AF with and without mental disorders.
DesignNationwide registry-based cohort study.
SettingDenmark (population 5.6 million), 2000–2015.
ParticipantsPatients with AF with schizophrenia (n=534), severe depression (n=400) or bipolar disease (n=569) matched 1:5 on age, sex and calendar time to patients with AF without mental disorders.
ExposureInpatient or hospital-based outpatient diagnosis of schizophrenia, severe depression or bipolar disease.
Primary and secondary outcome measuresHRs for stroke, fatal thromboembolic events and major bleeding comparing patients with and without mental disorders estimated by Cox regression with sequential adjustment for risk factors for stroke and bleeding, comorbidity and initiation of oral anticoagulant therapy (OAT).
ResultsCompared with matched comparisons, crude 5-year HRs of ischaemic stroke were 1.37 (95% CI 0.88 to 2.14) for schizophrenia, 1.36 (95% CI 0.89 to 2.08) for depression and 1.04 (95% CI 0.69 to 1.56) for bipolar disease. After adjusting for risk factors, comorbidity and OAT, these HRs declined towards the null. Crude HRs of fatal thromboembolic events were 3.16 (95% CI 1.78 to 5.61) for schizophrenia, 1.31 (95% CI 0.67 to 2.56) for depression and 1.53 (95% CI 0.93 to 2.53) for bipolar disease. Rates of major bleeding were increased in patients with schizophrenia (crude HR 1.37, 95% CI 0.99 to 1.90) and severe depression (HR 1.25, 95% CI 0.87 to 1.78) but not bipolar disease (HR 0.82, 95% CI 0.58 to 1.15).
ConclusionPatients with AF with schizophrenia or severe depression experienced increased rates of stroke and major bleeding compared with matched comparisons. This increase was largely explained by differences in the prevalence of risk factors for stroke and bleeding, comorbidity and initiation of OAT during follow-up. Patients with AF with schizophrenia further experienced higher mortality following thromboembolic events than matched comparisons without mental disorders.
http://ift.tt/2nzxoCG
Advancing the science of health research capacity strengthening in low-income and middle-income countries: a scoping review of the published literature, 2000-2016
Objectives
Substantial development assistance and research funding are invested in health research capacity strengthening (HRCS) interventions in low-income and middle-income countries, yet the effectiveness, impact and value for money of these investments are not well understood. A major constraint to evidence-informed HRCS intervention has been the disparate nature of the research effort to date. This review aims to map and critically analyse the existing HRCS effort to better understand the level, type, cohesion and conceptual sophistication of the current evidence base. The overall goal of this article is to advance the development of a unified, implementation-focused HRCS science.
MethodsWe used a scoping review methodology to identify peer-reviewed HRCS literature within the following databases: PubMed, Global Health and Scopus. HRCS publications available in English between the period 2000 and 2016 were included. 1195 articles were retrieved of which 172 met the final inclusion criteria. A priori thematic analysis of all included articles was completed. Content analysis of identified HRCS definitions was conducted.
ResultsThe number of HRCS publications increased exponentially between 2000 and 2016. Most publications during this period were perspective, opinion or commentary pieces; however, original research publications were the primary publication type since 2013. Twenty-five different definitions of research capacity strengthening were identified, of which three aligned with current HRCS guidelines.
ConclusionsThe review findings indicate that an HRCS research field with a focus on implementation science is emerging, although the conceptual and empirical bases are not yet sufficiently advanced to effectively inform HRCS programme planning. Consolidating an HRCS implementation science therefore presents as a viable option that may accelerate the development of a useful evidence base to inform HRCS programme planning. Identifying an agreed operational definition of HRCS, standardising HRCS-related terminology, developing a needs-based HRCS-specific research agenda and synthesising currently available evidence may be useful first steps.
http://ift.tt/2nFodRw
Acupuncture for patients with vascular dementia: a systematic review protocol
Introduction
This systematic review protocol aims to provide the methods used to evaluate the effectiveness and safety of acupuncture therapy for treating vascular dementia.
Methods and analysisThe following eight databases will be searched from inception to July 2017: Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database and Wanfang Database. All randomised controlled trials in English or Chinese related to acupuncture for vascular dementia will be included. Outcomes will include change in cognitive function and activities of daily living. The incidence of adverse events will be assessed for safety evaluation. Study inclusion, data extraction and quality assessment will be performed independently by two reviewers. Assessment of risk of bias and data synthesis will be performed using Review Manager software.
Ethics and disseminationEthics approval is not required because individual patient data are not included. The findings of this systematic review will be disseminated through peer-reviewed publication or conference presentations.
PROSPERO registration numberhttp://ift.tt/2zXrn4L
Social networks, leisure activities and maximum tongue pressure: cross-sectional associations in the Nagasaki Islands Study
Objectives
Social environment is often associated with health outcomes, but epidemiological evidence for its effect on oral frailty, a potential risk factor for aspiration, is sparse. This study aimed to assess the association between social environment and tongue pressure, as an important measure of oral function. The study focused on family structure, social networks both with and beyond neighbours, and participation in leisure activities.
DesignA population-based cross-sectional study.
SettingAnnual health check-ups in a rural community in Japan.
ParticipantsA total of 1982 participants, all over 40 years old. Anyone with missing data for the main outcome (n=14) was excluded.
Outcome measuresTongue pressure was measured three times, and the maximum tongue pressure was used for analysis. A multivariable adjusted regression model was used to calculate parameter estimates (B) for tongue pressure.
ResultsHaving a social network involving neighbours (B=2.43, P=0.0001) and taking part in leisure activities (B=1.58, P=0.005) were independently associated with higher tongue pressure, but there was no link with social networks beyond neighbours (B=0.23, P=0.77). Sex-specific analyses showed that for men, having a partner was associated with higher tongue pressure, independent of the number of people in the household (B=2.26, P=0.01), but there was no association among women (B=–0.24, P=0.72; P-interaction=0.059).
ConclusionsHaving a social network involving neighbours and taking part in leisure activities were independently associated with higher tongue pressure. Marital status may be an important factor in higher tongue pressure in men.
http://ift.tt/2zYh28n
Nanoparticle-based lateral flow biosensor combined with multiple cross displacement amplification for rapid, visual and sensitive detection of Vibrio cholerae
Abstract
Vibrio cholerae is an important human pathogen that is responsible for cholera, a severe acute watery diarrhea. In the current study, a multiple cross displacement amplification (MCDA) coupled with amplicon detection by chromatographic lateral flow biosensor (LFB) method (MCDA-LFB) was successfully established and evaluated for the identification of V. cholerae. A set of 10 primers was designed specifically to recognize 10 different regions of the V. cholerae-specific gene ompW. The optimized time and temperature conditions for the MCDA were 30 min and 63°C, respectively. The MCDA-LFB assay correctly identified 31 strains of V. cholerae but did not detect 13 non-cholerae Vibrio strains and 30 non-Vibrio strains. The sensitivity of MCDA-LFB for target pathogen detection in pure culture was 10 fg per reaction. In the case of spiked shrimp samples without enrichment, the limit of detection was 4.1 CFUs per reaction or equivalent to 4.1 × 102 CFU g−1. The whole process, including shrimp homogenates processing (30 min), MCDA reaction (30 min) and results reporting (2 min), could be finished within 65 min. These results show that this assay is suitable for the rapid, sensitive and specific detection of V. cholerae in food, environmental and clinical samples.http://ift.tt/2AM0Rex
Study of mesophilic Aeromonas salmonicida A527 strain sheds light on the species’ lifestyles and taxonomic dilemma
Abstract
The Gram-negative bacterium Aeromonas salmonicida contains five subspecies: salmonicida, smithia, achromogenes, masoucida and pectinolytica. Pectinolytica is a mesophilic subspecies with the ability to thrive at a wide range of temperatures, including 37°C, while the four other subspecies are psychrophilic, restricted to lower temperatures. The psychrophilic subspecies are known to infect a wide range of fishes. However, there is no evidence of pathogenicity for the mesophilic subspecies pectinolytica. Study of the differences between the mesophilic and psychrophilic subspecies is hampered by the lack of completely sequenced and closed genomes from the mesophilic subspecies. A previous study reported that insertion sequences, which can induce genomic rearrangements at temperatures around 25°C, could be one of the determinants explaining the differences in lifestyle (mesophilic or psychrophilic) between the subspecies. In this study, the genome of mesophilic strain A527 of A. salmonicida was sequenced, closed and analyzed to investigate the mesophilic–psychrophilic discrepancy. This reference genome supports the hypothesis that insertion sequences are major determinants of the lifestyle differences between the A. salmonicida subspecies. Moreover, the phylogenetic analysis performed to position strain A527 within the taxonomy raises an issue regarding the intraspecies structure of A. salmonicida.http://ift.tt/2m4KeIl
Overproduction of Sinorhizobium meliloti ArgC ( N -acetyl-gamma-glutamyl phosphate reductase) promotes growth delay and inefficient nodules
Abstract
argC encodes N-acetyl-gamma-glutamyl phosphate reductase, the enzyme that catalyzes the high-energy-consuming third step in the arginine synthesis pathway. A comparative analysis revealed two translation start sites in argC from Sinorhizobium meliloti. To determine whether both protein versions are synthesized in the organism and their functional role, we obtained genetic constructs with one (1S) or two (2S) start sites, with promoters of low (pspeB) or high (plac) transcriptional rate. The constructs were transferred to the S. meliloti 1021 derivative argC mutant strain. Both protein versions were found in the free-living proteomes, but only ArgC 1S showed post-translational modification. Expression levels from argC 1S were five times higher than those of 2S, when transcribed by plac, and in concordance, its protein activity was 3-fold greater. The overexpression of both versions under plac delayed cellular growth. Inoculation of Medicago sativa plants with the S. meliloti strain harboring the argC 1S under plac induced nodulation but not nitrogen fixation. However, the strain with the argC 2S under the same promoter had a positive phenotype. Overproduction of ArgC protein for the synthesis of arginine induced physiological and symbiotic effects.http://ift.tt/2ybASfD
Packaging of Mycobacterium smegmatis bacteria into fecal pellets by the ciliate Tetrahymena pyriformis
Abstract
Mycobacteria are widespread microorganisms that live in various environments, including man-made water systems where they cohabit with protozoa. Environmental mycobacterial species give rise to many opportunistic human infections and can infect phagocytic protozoa. Protozoa such as amoebae and ciliates feeding on bacteria can sometimes get rid of non-digestible or pathogenic material by packaging it into secreted fecal pellets. Usually, packaged bacteria are still viable and are protected against chemical and physical stresses. We report here that mycobacteria can be packaged into pellets by ciliates. The model bacterium Mycobacterium smegmatis survived digestion in food vacuoles of the ciliate Tetrahymena pyriformis and was included in expelled fecal pellets. LIVE/DEAD® staining confirmed that packaged M. smegmatis cells preserved their viability through the process. Scanning and transmission electron microscopy revealed that bacteria are packaged in undefined filamentous and/or laminar substances and that just a thin layer of material seemed to keep the pellet contents in a spherical shape. These results imply that packaging of bacteria is more common than expected, and merits further study to understand its role in persistence and dissemination of pathogens in the environment.http://ift.tt/2zhaEfs
Methicillin - resistant Staphylococcus aureus in minas frescal cheese: evaluation of classic enterotoxin genes, antimicrobial resistance and clonal diversity
Abstract
This study aimed to investigate classical enterotoxin (sea to see) and mecA genes, by polymerase chain reaction and anitimicrobial susceptibility, by disk diffusion test of Staphylococcus aureus isolated from minas frescal cheese (MFC). All methicillin-resistant S. aureus (MRSA) isolates were investigated for the presence of Panton-Valentine leukocidin (PVL) genes and clonal diversity. Thirty-one S. aureus were isolated from four MFC samples. Seven (22.6%) S. aureus carried mecA gene and two of them carried enterotoxin genes seb/sec and sea/seb. Five (16.1%) S. aureus isolates showed induced resistance to clindamycin and nine (29%) were resistant to multiple –antibiotics (MDR), among these, six were MRSA. No MRSA isolates presented the PVL genes. Four MRSA were grouped into three clones and three isolates were not typable by pulsed field gel electrophoresis. MRSA isolates showed, by multilocus sequence typing, sequence types ST1, ST5, ST72 and ST4304 (new ST) and S. aureus protein A (spa type) t127, t568 and t2703. These data suggest that MFC may constitute a risk to the consumer because of its potential for staphylococcal food poisoning; however it might, also, become one of MRSA and MDR strains disseminator, including clones usually found in the hospital environment.http://ift.tt/2z33KYB
Antibiotic stewardship: a European perspective
Abstract
Antibiotic stewardship programmes, which are a set of interventions aiming at prescribing antibiotics appropriately and responsibly, are one of the key strategies to tackle the current worldwide bacterial resistance crisis. We will present here some examples of international and national initiatives, with a focus on Europe, discuss the role of clinical microbiologists, and present some perspectives and future developments.http://ift.tt/2gWaT8H
Potential for plant biocontrol activity of isolated Pseudomonas aeruginosa and Bacillus stratosphericus strains against bacterial pathogens acting through both induced plant resistance and direct antagonism
Abstract
Phytopathogenic bacteria have caused significant damage to agricultural crops in both controlled and open cultivation practices, imposing heavy losses to farmers. Thereby, the goal of this study was to evaluate Pseudomonas aeruginosa and Bacillus stratosphericus isolated from soil has antagonistic activity against bacterial phytopathogens with the potential to control plant diseases. Isolated novel strains of P. aeruginosa and B. stratosphericus showed broad spectrum of antagonistic activity against five bacterial phytopathogens. Antagonistic activity was examined under optimized pH (8 and 7), carbon sources (lactose and starch), nitrogen sources (ammonium chloride, peptone and ammonium nitrate) for P. aeruginosa and B. stratosphericus, respectively, and biocatalyst production (chitinase, protease and amylase) was studied. Additionally, up-regulation of defense-related genes (PR-1a and PAL) was studied in tomato plants treated with P. aeruginosa and B. stratosphericus. The induction of defense-related genes in tomato plant was triggered after 12 h treatment with a cell concentration of 0.20 O.D. for P. aeruginosa and 0.21 O.D. for B. stratosphericus during treatment period. Broad spectrum antagonistic activity was observed due to antibiotic and siderophore production by P. aeruginosa and B. stratosphericus.http://ift.tt/2ktAtTQ
Potential impact of global climate change on benthic deep-sea microbes
Abstract
Benthic deep-sea environments are the largest ecosystem on Earth, covering ∼65% of the Earth surface. Microbes inhabiting this huge biome at all water depths represent the most abundant biological components and a relevant portion of the biomass of the biosphere, and play a crucial role in global biogeochemical cycles. Increasing evidence suggests that global climate changes are affecting also deep-sea ecosystems, both directly (causing shifts in bottom-water temperature, oxygen concentration and pH) and indirectly (through changes in surface oceans' productivity and in the consequent export of organic matter to the seafloor). However, the responses of the benthic deep-sea biota to such shifts remain largely unknown. This applies particularly to deep-sea microbes, which include bacteria, archaea, microeukaryotes and their viruses. Understanding the potential impacts of global change on the benthic deep-sea microbial assemblages and the consequences on the functioning of the ocean interior is a priority to better forecast the potential consequences at global scale. Here we explore the potential changes in the benthic deep-sea microbiology expected in the coming decades using case studies on specific systems used as test models.http://ift.tt/2iXY5iW
Impact of inappropriate antifungal therapy according to current susceptibility breakpoints on Candida bloodstream infection mortality, a retrospective analysis
The mortality of Candida Bloodstream Infection (CBSI) remains high. Antifungal susceptibility breakpoints were recently updated for Candida species, the impact remains unknown. In this study we evaluated the impa...
http://ift.tt/2k2RRuJ
Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria
Recognizing increasing interest in community disease surveillance globally, the goal of this study was to investigate whether respiratory viruses circulating in the community may be represented through clinica...
http://ift.tt/2jlvr8u
Bacteriological study of calf colisepticemia in Alage Dairy Farm, Southern Ethiopia
This study was designed to estimate the prevalence of E. coli which is the main cause of colisepticemia and the potential risk factors associated with the disease. A total of 74 calves less than 6 months age were...
http://ift.tt/2AxoJWp
Clinical interval and diagnostic characteristics in a cohort of bladder cancer patients in Spain: a multicenter observational study
We performed a cohort study in seven hospitals in Spain to determine the clinical characteristics of incident patients with bladder cancer, the diagnostic process, and the conditions that might affect health c...
http://ift.tt/2jncfax
A systematic review and meta-analysis of psychological predictors of successful assisted reproductive technologies
The aim of this systematic review and meta-analysis was to perform an updated investigation of the effects of depression and anxiety on pregnancy outcomes following assisted reproductive technologies. A biblio...
http://ift.tt/2AzODcf
Benefits of a mentoring support program for individuals with an eating disorder: a proof of concept pilot program
The aim of this proof-of-concept pilot study was to assess the usefulness of a mentoring support program with a goal to improve hope for recovery in people with an eating disorder.
http://ift.tt/2jlzyBC
The mechanism study of miR-125b in occurrence and progression of multiple myeloma
Abstract
Although many efforts have contributed to improve our knowledge of molecular pathogenesis about multiple myeloma (MM), the role and significance of microRNAs and long noncoding RNAs in MM cells, along with the core mechanism remains virtually absent. The mRNA levels of miR-125b and MALAT1 in MM cell lines were detected by qRT-PCR. The influence of Lenti-Sh-miR-125b on cell viability and the Notch-1 pathway-related proteins were assessed by MTT method and western blot, respectively. We also investigated the regulation effect between MALAT1 and Notch1 pathway. Moreover, the connection between Notch1 signaling and MM cell growth was discussed in-depth. The reverse effect of pcDNA-Notch1 on the cell viability and Notch-1 pathway proteins induced by Si-MALAT1 was also studied. Furthermore, miR-125b overexpressing MM cell lines were injected subcutaneously into nude mice. MiR-125b and MALAT1 were inversely expressed in MM cell lines. Lenti-Sh-miR-125b inhibited the expression of MALAT1 and Notch-1 protein. Binding sites were confirmed between miR-125b and MALAT1, and silencing MALAT1 did not alter the expression of Notch-1. The apoptosis rate was increased and the survival rate was decreased obviously in GSI XII (targeted cleavage of Notch-1 receptor) group, along with the inhibited Notch1 and HES1 proteins. Moreover, the decreased cell viability and Notch-1 pathway proteins induced by Si-MALAT1 could be reversed by pcDNA-Notch1. Lenti-Sh-miR-125b promoted survival and decreased Notch1 and HES1 proteins levels, while this effect was reversed by si -MALAT1. MiR-125b regulated MALAT1 expression via Notch1 signaling pathway to regulate cell growth, thus participating in the occurrence and progression of MM, which functioned as a therapeutic target for tracking MM.
To investigate the mechanism of long noncoding RNA MALAT1 and miR-125b in the progression of multiple myeloma (MM), through our current study, we found that loss of miR-125b contributes to lncRNA MALAT1 expression through Notch-1 pathway, further regulating cell growth. Therefore, the current findings not only provide new insight in clarifying the complex molecular mechanisms of specific miR-125b and MALAT1 but also facilitate the development.
http://ift.tt/2k2dMlK
Widespread enlarged perivascular spaces associated with dementia and focal brain dysfunction: case report
Enlarged perivascular spaces (PVS) are common magnetic resonance imaging (MRI) findings, whereas widespread enlarged PVS are extremely rare. Although most patients with widespread enlarged PVS remain asymptoma...
http://ift.tt/2AD9gSP
Restrictive surgical approach to palliate angina in a patient with coronary three vessel disease and biventricular metastatic hepatocellular carcinoma
Abstract
Background
Metastatic cardiac tumors may cause different symptoms including angina, symptoms of heart failure and/or arrhythmia. In patients with concomitant coronary artery disease, it may be difficult to distinguish between angina caused by metastases to the heart, for example, by stealing perfusion from the coronary arteries, and angina caused by coronary stenosis. Identifying the origin of the symptoms is, however, essential for designing appropriate surgical strategies.
Case presentation
A 69-year-old male with multifocal recurrence of a hepatocellular carcinoma (HCC) presented with increasing ventricular arrhythmia and angina several weeks after posterior myocardial infarction and PCI of the RCA culprit lesion during which two further lesions present in the distal RCX and a posterolateral branch, and a chronically occluded LAD had not been addressed. MRI showed a large metastatic tumor infiltrating the walls of both ventricles as well as the interventricular septum. His debilitating symptoms were attributed to steal phenomena and/or perivascular compression caused by the metastatic tumor rather than the remaining coronary lesions, and he was offered a restrictive surgical approach consisting of debulking of the metastasis with an option for subsequent coronary intervention. The palliative surgical procedure resulted in a reduction of the tumor mass by half and sufficiently reduced the patient's symptoms so that further coronary intervention was not required.
Conclusions
Palliative surgery for metastases to the heart may benefit patients, provided that the origin of symptoms is identified correctly. It goes without saying that in a palliative setting, surgery should be limited to treating symptoms rather than performing extensive procedures addressing, for example, coronary artery or valve disease. Interventional cardiac procedures addressing not only CAD but also valve disease may supplement palliative tumor surgery.
http://ift.tt/2AiKcDm
Flat foveal contour simulating macular hole
Description
A 40-year-old healthy female was referred for macular hole in his both eyes detected during routine examination. Visual acuity was 20/20 OU unaided. Ocular examination of OD was unremarkable except for the presence of round red lesion at fovea (figure 1A, arrow) that was more prominent on green reflectance imaging (figure 1B, arrow). Spectral-domain optical coherence tomography showed a flattened foveal contour (figure 1C, arrows), which explained the appearance of macular hole. Similar findings were seen in OS. There were no ocular or systemic features suggestive of albinism.
Figure 1
Multicolour scanning laser image of right eye showing small red lesion (arrow) simulating macular hole (A) that is better seen on red free image (B). Apparent macular hole corresponds to flat foveal contour on optical coherence tomography (C).
The foveal contour and anatomy may vary...
http://ift.tt/2AfLlM7
Complication of deep brain stimulation for Parkinsons disease
Description
A 58-year-old man with advanced Parkinson disease diagnosed 13 years before, was admitted for surgical placing of continuous bilateral high-frequency stimulation of the subthalamic nucleus.
The procedure was uneventful (lead used Medtronic DBS 3387; antibiotic prophylaxis: cefazolin 2 g at time of anaesthetic induction and 1 g every 8 hours in the first 24 hours) with a postoperative control CT scan showing good placement of the electrodes and no abnormalities (figure 1). The stimulation was switched on 72 hours after the procedure and within 24 hours the patient presented two epileptic seizures controlled with diazepam and stimulation was switched off. The head CT showed intra-axial hypodensity more prominent in the frontal area with a gaseous collection and oedema surrounding the right electrode pathway (figure 2). At the time there was no fever, no increase in inflammatory markers and a normal cell count in the lumbar puncture. However, antibiotic therapy (ceftriaxone...
http://ift.tt/2B8bPiP
Mycobacterium tuberculosis of the elbow joint
Mycobacterium tuberculosis(TB) affecting the elbow joint is rarely reported in the developed world. We present the case of an 85-year-old Caucasian female who complained of a chronically discharging and painful wound across her left elbow during her admission for an ischaemic stroke. This was initially deemed to be either a bursitis or local manifestation of amyloid by her general practitioner and dermatologist respectively prior to admission. She was commenced on flucloxacillin by the medical team for presumed cellulitis with minimal response. A synovial fluid sample and repeated wound swabs yielded no growth from routine bacterial culture. Radiological assessment together with knowledge of her husband having previous TB raised the possibility of TB arthritis. Synovial fluid aspirate was subsequently sent for acid–alcohol fast bacilli microscopy and mycobacterial culture that confirmed M. tuberculosis. She was consequently started on multidrug TB therapy, over a year after the onset of her symptoms.
http://ift.tt/2Afmloa
Coptis Chinensis affects the function of glioma cells through the down-regulation of phosphorylation of STAT3 by reducing HDAC3
Glioma remains the most common cause of brain cancer-related mortality. Glioma accounts for 50–60% of brain cancer. Due to their low toxicity and infrequent side effects, traditional herbs have been increasing...
http://ift.tt/2B94lvP
Cannabinoids for epilepsy: What do we know and where do we go?
Summary
Over the past decade there has been an increasing interest in using cannabinoids to treat a range of epilepsy syndromes following reports of some remarkable responses in individual patients. The situation is complicated by the fact that these agents do not appear to work via their attachment to endogenous cannabinoid receptors. Their pharmacokinetics are complex, and bioavailability is variable, resulting in difficulty in developing a suitable formulation for oral delivery. Drug interactions also represent another complication in their everyday use. Nevertheless, recent randomized, placebo-controlled trials with cannabidiol support its efficacy in Dravet and Lennox-Gastaut syndromes. Further placebo-controlled studies are underway in adults with focal epilepsy using cannabidivarin. The many unanswered questions in the use of cannabinoids to treat epileptic seizures are briefly summarized in the conclusion.
http://ift.tt/2AfpLaz
Electroencephalography and behavior patterns during experimental status epilepticus
Summary
Objective
To characterize the evolution of behavioral and electrographic seizures in an experimental electrical stimulation-based model of status epilepticus (SE) in C57Bl/6 mice, and to relate SE to various outcomes, including death and epileptogenesis.
Methods
SE was induced by continuous hippocampal stimulation and was evaluated by review of electroencephalographic recordings, spectral display, and behavior.
Results
Seizures were initially locked to the electrical trains but later became independent of them. Following the end of stimulation, autonomous seizures continued for >5 minutes in 85% of the animals. There was ongoing 2-3-Hz rhythmic, high-amplitude, slow spike-wave discharges (HASDs) associated with purposeless, repetitive, continuously circling and exploratory behavior. There were high-amplitude fast discharges (HAFDs) associated with worsening of behavioral seizures that were interspersed with the ongoing HASDs. Death during SE occurred in 23% of the animals, and it was preceded by a stage 5 behavioral seizure. In the waning stage of SE, severe seizures and HAFDs dissipated, HASDs slowed down, and normal behavior was restored in most animals. Epilepsy developed in 33% of the animals monitored after SE.
Significance
The electrical stimulation model of SE can be used to study mechanisms of SE and its adverse consequences, including death and epileptogenesis.
http://ift.tt/2B9RERy
Surface characterization of titanium implant healing abutments before and after placement
Abstract
Background
Implant healing abutments (IHA) have a vital role in soft tissue healing after implant placement. Although there is thorough investigation on the implant surface, little is known about the effects potentially damaging oral conditions impose on healing abutments.
Purpose
To characterize the surface of titanium healing abutments before and after clinical placement to understand the effects of the oral environment and time on the device surface.
Materials and Methods
Ten regular Straumann IHA were subjected to characterization pre and postplacement to elucidate the effects of the oral environment on device surfaces. Changes in surface crystallinity, morphology, and elemental composition were monitored with Raman spectroscopy, scanning electron microscopy, optical microscopy, and x-ray photoelectron spectroscopy, respectively. In addition, corrosion rate and polarization resistance were obtained to assess electrochemical device stability after placement.
Results
Control analysis indicated the titanium oxide of IHAs was thicker than natural commercially pure titanium and had the structure of crystalline anatase. After removal, the abutments possessed large amounts of biological debris, visible scratches, and discoloration sparsely on the surface. Spectroscopic analysis revealed the titanium oxide on the surface of IHAs was structurally unchanged, with crystalline titanium dioxide still present on the surface. Electrochemical results revealed that implanted healing abutments possessed a significantly higher corrosion rate than controls (change in corrosion rate = 2.34 ± 0.58 nm/year).
Conclusions
Healing abutments were stable in the oral environment due to the chemical stability of the oxide, and were likely subjected to abrasions from unintentional loading and oral hygiene techniques.
http://ift.tt/2iZUwJ6
Analysis of Drug Development Paradigms for Immune Checkpoint inhibitors
Immune checkpoint inhibitors have unique toxicities and response kinetics compared to cytotoxics and gene-targeted anti-cancer agents. We investigated the impact of innovative/accelerated immunotherapy drug development/approval models on the accuracy of safety and efficacy assessments by searching the US Food and Drug Administration (FDA) website. Initial phase I trials for each agent were reviewed and safety and efficacy data compared to that found in later trials leading to regulatory approvals of the same agents. As of June 2017, the FDA approved six checkpoint inhibitors for a variety of cancer types. All checkpoint inhibitors received a priority review status and access to at least two additional FDA special access programs, more often breakthrough designation and accelerated approval. Median clinical development time (investigational new drug application to approval) was 60.77 months (avelumab had the shortest timeline (52.33 months)). Response rates during early phase I trials (median =16%) are higher than for phase I trials of other agents (with the exception of gene-targeted agents tested with a biomarker). Doses approved were usually not identical to doses recommended on phase I trials. Approximately 50% of types of immune-related and 43% of types of clinically relevant toxicities from later trials were identified in early phase trials. Even so, treatment-related mortality remains exceedingly low in later studies (0.33% of patients). In conclusion, efficacy and safety of immune checkpoint inhibitors appear to be reasonably predicted from the dose-finding portion of phase I trials, indicating that the fast-track development of these agents is safe and justified.
http://ift.tt/2kqWWRr
Pharmacotherapies for apnoea of prematurity: Time to pause and consider targeted sex-specific strategies?
Abstract
Developmental plasticity in the neural network orchestrating respiratory control is such that pre-term birth is associated with the elaboration of dysrhythmic breathing patterns characterized by periodic suppression of the central drive to breathe, evoking recurrent respiratory pauses termed central apnoeas.
This article is protected by copyright. All rights reserved
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Heme oxygenase-1 is a potent inhibitor of placental ischemia-mediated endothelin-1 production in cultured human glomerular endothelial cells
Preeclampsia is a pregnancy-specific disorder of maternal hypertension and reduced renal hemodynamics linked to reduced endothelial function. Placental ischemia is thought to be the culprit of this disease, as it causes the release of factors like tumor necrosis factor (TNF)-α that induce vascular endothelin-1 (ET-1) production. Interestingly, placental ischemia-induced hypertension in rats (reduced uterine perfusion pressure, RUPP model) is abolished by ETA receptor blockade, suggesting a critical role for ET-1. While it has been found that systemic induction of heme oxygenase (HO)-1 is associated with reduced ET-1 production and attenuated hypertension, it is unclear whether HO-1 directly modulates the increased ET-1 response to placental factors. We tested the hypothesis that HO-1 or its metabolites inhibit ET-1 production in human glomerular endothelial cells induced by serum of RUPP rats or TNF-α. Serum (5%) from RUPP hypertensive (mean arterial blood pressure 119±9 mmHg) versus normotensive pregnant (NP, 101±6 mmHg, P<0.001) rats increased ET-1 production (RUPP, 168.8±18.1 pg/mL, NP, 80.3±22.7 pg/mL, P<0.001, n=12/group). HO-1 induction (25µM cobalt photoporphyrin; CoPP) abolished RUPP serum-induced ET-1 production (1.6±0.8 pg/mL, P<0.001), while bilirubin (10µM) significantly attenuated ET-1 release (125.3±5.2 pg/mL P=0.005). Furthermore, TNF-α-induced ET-1 production (TNF-α, 31.0±8.4 vs. untreated, 7.5±0.4 pg/mL, P<0.001) was reduced by CoPP (1.5±0.8 pg/mL, P<0.001) and bilirubin (10.5±4.3 pg/mL, P<0.001). These results suggest that circulating factors released during placental ischemia target the maternal glomerular endothelium to increase ET-1, and that pharmacological induction of HO-1 or bilirubin could be a treatment strategy to block this pro-hypertensive pathway in preeclampsia.
http://ift.tt/2AZMZ4a
Altered Expression of Hepatic {beta}-Adrenergic Receptors in Aging Rats: Implications for Age-Related Metabolic Dysfunction in Liver
Increased β-adrenergic receptor (β-AR)-mediated activation of adenylyl cyclase (AC) in rat liver during aging has been linked to age-related increases in hepatic glucose output and hepatosteatosis. In this study we investigated the expression of β-ARs, individual receptor subtypes, and G protein-coupled receptor (GPCR) regulatory proteins in livers from aging rats. Radioligand binding studies demonstrated that β-AR density increased by >3-fold in hepatocyte membranes from senescent (24 mo old) compared to young adult (7 mo old) rats, and that this phenomenon was blocked by food restriction which is known to retard aging processes in rodents. Competition binding studies revealed a mixed population of β1- and β2-AR subtypes in liver membranes over the adult life span, with a trend for greater β2-AR density with age. Expression of both β-AR subtype mRNAs in rat liver increased with age, while β2- but not β1-AR protein levels declined in livers of old animals. Immunoreactive β2- but not β1-ARs were preferentially distributed in pericentral hepatic regions. Levels of GRK2/3 and β-arrestin 2 proteins, which are involved in downregulation of agonist-activated GPCRs including β-ARs, increased during aging. Insofar as sympathetic tone increases with age, our findings suggest that, despite enhanced agonist-mediated downregulation of hepatic β-ARs preferentially affecting the β2-AR subtype, increased generation of both receptor subtypes during aging augments the pool of plasma membrane bound β-ARs coupled to AC in hepatocytes. This study thus identifies one or both β-AR subtypes as possible therapeutic targets involved in aberrant hepatic processes of glucose and lipid metabolism during aging.
http://ift.tt/2AECQaB
The independent and interactive effects of incremental heat strain, orthostatic stress and mild hypohydration on cerebral perfusion
The purpose of this study was to identify the dose-dependent effects of heat strain and orthostasis (via lower-body negative pressure; LBNP), with and without mild hypohydration, on systemic function and cerebral perfusion. Eleven males (Mean ±SD: 27 ±7 y; body mass 77 ±6 kg), resting supine in a water-perfused suit, underwent progressive passive heating [0.5°C increments in core temperature (Tc, oesophageal to +2.0°C)] whilst euhydrated (EUH) or hypohydrated (HYPO, 1.5-2% body mass deficit). At each thermal state, mean cerebral artery blood velocity (MCAvmean, Transcranial Doppler), partial pressure of end-tidal carbon dioxide (PETCO2), heart rate (HR) and mean arterial blood pressure (MAP, photoplethysmography) were measured continuously during LBNP (0, -15, -30, -45 mm Hg). Four subjects became intolerant before +2.0°C Tc, unrelated to hydration status. Without LBNP, decreases in PETCO2 accounted fully for reductions in MCAvmean across all Tc. With LBNP at heat tolerance (+1.5°C or +2.0°C), PETCO2 accounted for 69 ±25% of the change in MCAvmean. The HYPO condition did not affect MCAvmean or any cardiovascular variables during combined LBNP and passive heat stress (all p>0.13). These findings indicate that hypocapnia accounted fully for the reduction in MCAvmean when passively heat stressed in the absence of LBNP, and for two thirds of the reduction when at heat tolerance combined with LBNP. Further, when elevations in Tc are matched, mild hypohydration does not influence cerebrovascular or cardiovascular responses to LBNP, even when stressed by a combination of hyperthermia and LBNP.
http://ift.tt/2AUZpu5
Animal models of preeclampsia: translational failings and why
Preeclampsia affects up to 8% of pregnancies worldwide and is a leading cause of both maternal and fetal morbidity and mortality. Our current understanding of the cause(s) of preeclampsia is far from complete, and the lack of a single reliable animal model that recapitulates all aspects of the disease further confounds our understanding. This is partially due to the heterogeneous nature of the disease, coupled with our evolving understanding of its etiology. Nevertheless, animal models are still highly relevant and useful tools that help us better understand the pathophysiology of specific aspects of preeclampsia. This review summarizes the various types and characteristics of animal models used to study preeclampsia, highlighting particular features of these models relevant to clinical translation. This review points out the strengths and limitations of these models to illustrate the importance of using the appropriate model depending on the research question.
http://ift.tt/2ACRJd8
Gestational age at time of in utero lipopolysaccharide exposure influences the severity of inflammation-induced diaphragm weakness in lambs
The preterm diaphragm is functionally immature compared to its term counterpart. In utero inflammation further exacerbates preterm diaphragm dysfunction. We hypothesized that preterm lambs are more vulnerable to in utero inflammation induced diaphragm dysfunction compared with term lambs. Pregnant ewes received intra-amniotic (IA) injections of saline or 10mg lipopolysaccharide (LPS) 2d or 7d prior to delivery at 121d (preterm) or 145d (term) gestation. Diaphragm contractile function was assessed in vitro. Plasma cytokines and diaphragm myosin heavy chain (MHC) isoforms and oxidative stress were evaluated. Maximum diaphragm force in preterm control lambs was significantly lower (22%) than in term control lambs (p<0.001). Despite similar inflammatory cytokine responses to in utero LPS exposure, diaphragm function in preterm and term lambs was affected differentially. In term lambs, maximum force after a 2d LPS exposure was significantly lower than controls (by ~20%; p<0.05). In preterm lambs, maximum forces after 2d and 7d LPS exposures were significantly lower than controls (by ~30%; p<0.05). Peak twitch force after LPS exposure was significantly lower than controls in preterm, but not in term lambs. In term lambs, LPS exposure increased the proportion of MHC-I fibers, increased twitch contraction times and increased fatigue resistance relative to controls. In preterm diaphragm, the cross-sectional area of embryonic MHC fibers was significantly lower after 7d versus 2d LPS exposures. We conclude that preterm lambs are more vulnerable to IA LPS-induced diaphragm dysfunction than term lambs. In utero inflammation exacerbates diaphragm dysfunction and may increase susceptibility to postnatal respiratory failure.
http://ift.tt/2AB4vc9
T cell densities in brain metastases are associated with patient survival times and diffusion tensor MRI changes
Brain metastases are common and are usually detected by magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) is a derivative MRI technique which can detect disruption of white matter tracts in the brain. We have matched preoperative DTI with image-guided sampling of the brain-tumor interface in 26 patients during resection of a brain metastasis and assessed mean diffusivity (MD) and fractional anisotropy (FA). The tissue samples were analysed for vascularity, inflammatory cell infiltration, growth pattern, and tumor expression of proteins associated with growth or local invasion such as Ki67, S100A4, and MMP2, 9, and 13. A lower FA in the peritumoral region indicated more white matter tract disruption and independently predicted longer overall survival times (HR for death = 0.21, 95% CI 0.06 - 0.82, p=0.024). Of all the biological markers studied, only increased density of CD3+ lymphocytes in the same region correlated with decreased FA (Mann Whitney U, p=0.037) as well as confounding completely the effect of FA in multivariate survival analyses. We conclude that the T cell response to brain metastases is not a surrogate of local tumor invasion, primary cancer type, or aggressive phenotype and is associated with patient survival time regardless of these biological factors. Furthermore, it can be assayed by DTI, potentially offering a quick, non-invasive, clinically available method to detect an active immune microenvironment and, in principle, to measure susceptibility to immunotherapy.
http://ift.tt/2B8PP79
Mutational mechanisms that activate Wnt signaling and predict outcomes in colorectal cancer patients
APC biallelic loss-of-function mutations are the most prevalent genetic changes in colorectal tumors, but it is unknown whether these mutations phenocopy gain-of-function mutations in the CTNNB1 gene encoding ß-catenin that also activate canonical WNT signaling. Here we demonstrate that these two mutational mechanisms are not equivalent. Further, we show how differences in gene expression produced by these different mechanisms can stratify outcomes in more advanced human colorectal cancers. Gene expression profiling in Apc-mutant and Ctnnb1-mutant mouse colon adenomas identified candidate genes for subsequent evaluation of human TCGA data for colorectal cancer outcomes. Transcriptional patterns exhibited evidence of activated canonical Wnt signaling in both types of adenomas, with Apc-mutant adenomas also exhibiting unique changes in pathways related to proliferation, cytoskeletal organization and apoptosis. Apc-mutant adenomas were characterized by increased expression of the glial nexin Serpine2, the human ortholog of which was increased in advanced human colorectal tumors. Our results support the hypothesis that APC-mutant colorectal tumors are transcriptionally distinct from APC-wild-type colorectal tumors with canonical WNT signaling activated by other mechanisms, with possible implications for stratification and prognosis.
http://ift.tt/2Afgsat
Tamoxifen resistance in breast cancer is regulated by the EZH2-ER{alpha}-GREB1 transcriptional axis
Resistance to cancer treatment can be driven by epigenetic reprogramming of specific transcriptomes in favor of the refractory phenotypes. Here we discover that tamoxifen resistance in breast cancer is driven by a regulatory axis consisting of a master transcription factor, its cofactor and an epigenetic regulator. The oncogenic histone methyltransferase EZH2 conferred tamoxifen resistance by silencing the expression of the estrogen receptor α (ERα) cofactor GREB1. In clinical specimens, induction of DNA methylation of a particular CpG enriched region at the GREB1 promoter negatively correlated with GREB1 levels and cell sensitivity to endocrine agents. GREB1 also ensured proper cellular reactions to different ligands by recruiting distinct sets of ERα cofactors to cis-regulatory elements, which explains the contradictory biological effects of GREB1 on breast cancer cell growth in response to estrogen or anti-estrogen. In refractory cells, EZH2-dependent repression of GREB1 triggered chromatin reallocation of ERα coregulators, converting the anti-estrogen into an agonist. In clinical specimens from patients receiving adjuvant tamoxifen treatment, expression levels of EZH2 and GREB1 were correlated negatively, and taken together better predicted patient responses to endocrine therapy. Overall, our work suggests a new strategy to overcome endocrine resistance in metastatic breast cancer by targeting a particular epigenetic program.
http://ift.tt/2B8PH7F
Emergence of High-Avidity Melan-A-Specific Clonotypes as a Reflection of Anti-PD-1 Clinical Efficacy
Therapeutic strategies using anti–PD-1–blocking antibodies reported unparalleled effectiveness for melanoma immunotherapy, but deciphering immune responses modulated by anti–PD-1 treatment remains a crucial issue. Here, we analyzed the composition and functions of the large Melan-A–specific T-cell repertoire in the peripheral blood of 9 melanoma patients before and after 2 months of treatment with anti–PD-1. We observed amplification of Melan-A–specific Vß subfamilies undetectable before therapy (thereafter called emerging Vß subfamilies) in responding patients, with a predominant expansion in patients with a complete response. These emerging Vß subfamilies displayed a higher functional avidity for their cognate antigen than Vß subfamilies not amplified upon anti–PD-1 therapy and could be identified by a sustained coexpression of PD-1 and TIGIT receptors. Thus, in addition to the emergence of neoantigen-specific T cells previously documented upon anti–PD-1 therapy, our work describes the emergence of high-avidity Melan-A–specific clonotypes as a surrogate marker of treatment efficacy. Cancer Res; 77(24); 1–11. ©2017 AACR.
http://ift.tt/2k3Qwnv
Erol Başar, 1938–2017
It is our deep regret to announce Erol Başar's passing on the 28th of October 2017 in Istanbul.
http://ift.tt/2BScylg
Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation
Cytomegalovirus (CMV) remains the most common clinically significant infection after allogeneic hematopoietic-cell transplantation. Although ganciclovir and valganciclovir are routinely used in solid-organ transplantation, ganciclovir and valganciclovir prophylaxis for CMV is limited by clinically…
http://ift.tt/2AztnTV
Mangiferin prevents the growth of gastric carcinoma by blocking the PI3K-Akt signalling pathway
http://ift.tt/2iuM4xw
Efficacy and safety of apatinib as second-line therapy for advanced gastric cancer: a single-center observational study
http://ift.tt/2k1BLkU
Prognostic factors of nasopharyngeal carcinoma patients in a tertiary referral hospital: a retrospective cohort study
Nasopharyngeal carcinoma (NPC) exhibits a distinctive racial and geographic distribution. Many studies have reported varied significant prognostic factors affect the survival of NPC patients. Hence, this curre...
http://ift.tt/2B8p8zO
Hepatitis A Outbreak in California — Addressing the Root Cause
On October 13, 2017, Governor Jerry Brown of California declared a state of emergency in response to a hepatitis A outbreak that began in the homeless population in San Diego. In the past year, more than 649 people throughout California have been infected, 417 have been hospitalized, and 21 have…
http://ift.tt/2jn6OrZ
Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation
Cytomegalovirus (CMV) remains the most common clinically significant infection after allogeneic hematopoietic-cell transplantation. Although ganciclovir and valganciclovir are routinely used in solid-organ transplantation, ganciclovir and valganciclovir prophylaxis for CMV is limited by clinically…
http://ift.tt/2AztnTV
Hepatitis A Outbreak in California — Addressing the Root Cause
On October 13, 2017, Governor Jerry Brown of California declared a state of emergency in response to a hepatitis A outbreak that began in the homeless population in San Diego. In the past year, more than 649 people throughout California have been infected, 417 have been hospitalized, and 21 have…
http://ift.tt/2jn6OrZ
Trials of transvaginal mesh devices for pelvic organ prolapse: a systematic database review of the US FDA approval process
Introduction
Transvaginal mesh devices are approved in the USA by the Food and Drug Administration (FDA), through the 510(k) system. However, there is uncertainty about the benefit to harm balance of mesh approved for pelvic organ prolapse. We, therefore, assessed the evidence at the time of approval for transvaginal mesh products and the impact of safety studies the FDA mandated in 2012 because of emerging harms.
MethodsWe used FDA databases to determine the evidence for approval of transvaginal mesh. To create a 'family tree' of device equivalence, we used the 510(k) regulatory approval of the 1985 Mersilene Mesh (Ethicon) and the 1996 ProteGen Sling (Boston Scientific), searched for all subsequently related device approvals, and for the first published randomised trial evidence. We assessed compliance with all FDA 522 orders issued in 2012 requiring postmarketing surveillance studies.
ResultsWe found 61 devices whose approval ultimately relied on claimed equivalence to the Mersilene Mesh and the ProteGen Sling. We found no clinical trials evidence for these 61 devices at the time of approval. Publication of randomised clinical trials occurred at a median of 5 years after device approval (range 1–14 years). Analysis of 119 FDA 522 orders revealed that in 79 (66%) the manufacturer ceased market distribution of the device, and in 26 (22%) the manufacturer had changed the indication. Only seven studies (six cohorts and new randomised controlled trial) covering 11 orders were recruiting participants (none had reported outcomes).
ConclusionsTransvaginal mesh products for pelvic organ prolapse have been approved on the basis of weak evidence over the last 20 years. Devices have inherited approval status from a few products. A publicly accessible registry of licensed invasive devices, with details of marketing status and linked evidence, should be created and maintained at the time of approval.
http://ift.tt/2kuaETt
Occipitocervical Hemolymphangioma in an Adult with Neck Pain and Stiffness: Case Report and Literature Review
Introduction. Hemolymphangioma is an extremely rare malformation of the lymphatic and blood vessels. A limited number of hemolymphangioma cases occurring in the pancreas, extremities, spleen, and other organs have been reported until September 2017. To the best of our knowledge, no cases of hemolymphangioma in the occipitocervical region have been reported in the literature. Case Presentation. We reported the case of a 23-year-old male patient with an occipitocervical lesion presenting atypically as neck pain and stiffness over a period of five months. Although hemolymphangioma has historically demonstrated a female predilection (2.25 : 1 female to male) and presentation in the third to fourth decades of life, this case is an atypical manifestation occurring in a young male patient. The clinical characteristics and management choices of this uncommon case of hemolymphangioma in the occipitocervical region are discussed, and a review based on the available literature is also presented. Conclusion. Hemolymphangioma of the occipitocervical region is an uncommon presentation of a rare lesion. Although rare, hemolymphangioma should be considered a differential diagnosis for masses occurring in the occipitocervical region. Complete surgical resection is the treatment of choice and affords a good prognosis.
http://ift.tt/2ktk7KS
Characteristics and Outcomes of Pediatric Heart Failure-Related Emergency Department Visits in the United States: A Population-Based Study
To describe the frequency, characteristics, and outcomes of heart failure-related emergency department (ED) visits in pediatric patients. We aimed to test the hypothesis that these visits are associated with higher admission rates, mortality, and resource utilization.
http://ift.tt/2nAtwl4
Reply
We appreciate the opportunity to respond to the comments by Shalish and Sant'Anna regarding our publication in which the factors associated with failed elective extubation among extremely premature infants were described. The study was a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network's "Surfactant, Positive Pressure, and Oxygenation Randomized Trial" that included extremely preterm infants born at 240/7 to 276/7 weeks of gestation.
http://ift.tt/2nzv0vN
Fertility Preservation in Pediatric Subspecialties: A Pilot Needs Assessment Beyond Oncology
Physicians from 6 non-oncology pediatric subspecialties were surveyed about fertility preservation (FP) to assess education/service needs. Almost all (96%; 25 of 26) reported having patients at risk of infertility; however, only 58% (15 of 26) had discussed FP with patients' families. Most subspecialists (92%; 23 of 25) would like access to an FP program. Our data support exploring the expansion of FP programs beyond oncology.
http://ift.tt/2zUje0K
Development of Late Circadian Preference: Sleep Timing From Childhood to Late Adolescence
To assess differences relating to circadian preference in objectively measured sleep patterns from childhood to adolescence over a 9-year period. We hypothesized there is developmental continuity in sleep timing and duration according to circadian preference.
http://ift.tt/2zUQODH
Sleep-Disordered Breathing among Newborns with Myelomeningocele
In a matched cohort study, we report that the apnea-hypopnea index is significantly higher in neonates with myelomeningocele (34 ± 22) compared with age-matched controls (19 ± 11; P = .021). Assessment of newborns with myelomeningocele for sleep-disordered breathing may facilitate early treatment; the impact on long-term neurodevelopment is unknown.
http://ift.tt/2nzZsGl
PHACE Syndrome—before and after Propranolol Therapy
A 5-week-old girl presented to our neuropediatric department to rule out Sturge-Weber syndrome. Eventually, our investigations led to a suspicion of posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities (PHACE) syndrome, a different phacomatosis. We then successfully initiated treatment with propranolol for an extensive facial hemangioma. Postnatally, the mother noted a reddish shimmer on the girl's face, growing rapidly (Figure, A). Initially, the facial lesion was considered to be an atypical port wine-stain, unresponsive to beta-blockers.
http://ift.tt/2zUj5KK
Antenatal Consultations at Extreme Prematurity: A Systematic Review of Parent Communication Needs
To synthesize and describe parental expectations on how healthcare professionals should interact with them during a peripartum, antenatal consultation for extremely preterm infants.
http://ift.tt/2nzyuP5
Impact of Obesity on Modality Longevity, Residual Kidney Function, Peritonitis, and Survival Among Incident Peritoneal Dialysis Patients
The prevalence of severe obesity, often considered a contraindication to peritoneal dialysis (PD), has increased over time. However, mortality has decreased more rapidly in the PD population than the hemodialysis (HD) population in the United States. The association between obesity and clinical outcomes among patients with end-stage kidney disease remains unclear in the current era.
http://ift.tt/2Az8HeA
Palliative Care Need and Availability in Four Referral Hospitals in Senegal: Results from a Multi-Component Assessment
With prevalence of non-communicable diseases and life expectancy rising in Senegal, the need for palliative care is likely growing. No national palliative care needs assessments have been carried out.
http://ift.tt/2zTx5nX
Hepatitis A Outbreak in California — Addressing the Root Cause
On October 13, 2017, Governor Jerry Brown of California declared a state of emergency in response to a hepatitis A outbreak that began in the homeless population in San Diego. In the past year, more than 649 people throughout California have been infected, 417 have been hospitalized, and 21 have…
http://ift.tt/2jn6OrZ
Evaluating bevacizumab in combination with FOLFIRI after the failure of platinum-etoposide regimen in patients with advanced poorly differentiated neuroendocrine carcinoma: the PRODIGE 41 − BEVANEC randomized phase II study
Patients with gastroenteropancreatic (GEP), metastatic or locally advanced, non-resectable, grade 3 poorly-differentiated neuroendocrine carcinoma (NEC) are treated with cisplatin (or carboplatin)-etoposide in first-line palliative chemotherapy (CT1). However, nearly all patients will develop resistance and there is no standard second-line treatment.
http://ift.tt/2jnfvm4
Efficacy of Fluoride Varnishes with Added Calcium Phosphate in the Protection of the Structural and Mechanical Properties of Enamel
The aim of this study was to investigate the efficacy of various fluoride varnishes in the protection of the structural and nanomechanical properties of dental enamel. Demineralized enamel specimens were imaged using a high-resolution micro-CT system and lesion parameters including mineral density and lesion depth were extracted from mineral density profiles. Nanoindentation elastic modulus and hardness were calculated as a function of penetration depth from the load-displacement curves. The average depth of the lesion in specimens with no prior fluoride varnish treatment was μm whereas the varnish treated specimens had an average depth of μm (). The mineral density of enamel lesions with no fluoride varnish treatment had an average of 1.85 gr/cm3 which was 25% lower than the corresponding value in varnish treated enamel and 37% lower than sound enamel. While, in the varnish treated group, elastic modulus and hardness values had decreased by 18% and 23%, respectively, the corresponding values in the non-varnish treated specimens had a reduction of 43% and 54% compared to the sound enamel. The findings from this study highlight the preventive role of fluoride varnishes. Addition of calcium and phosphate does not seem to enhance or inhibit the prevention or remineralization performance of fluoride varnishes.
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Numeracy and Interpretation of Prognostic Estimates in Intracerebral Hemorrhage Among Surrogate Decision Makers in the Neurologic ICU
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Ventilator-Free Day Outcomes Can Be Misleading
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Has the Licensing Act 2003 affected violence rates in England and Wales? A systematic review of hospital and police studies
Violence has been declining in the UK for two decades, with most assaults being alcohol related. The Licensing Act 2003 (England and Wales) aimed to reduce alcohol-related crime, giving local authorities control over premises licensing. We performed a systematic review of original research with the primary outcome of change in violence rates since the Act's implementation, including hospital-defined and police-defined measures of violence. Our secondary outcome was temporal distribution of violence. Fifteen studies were included, which were of overall poor quality. Seven found reduced violence rates after the Act's implementation, three found increased rates and five found no significant change. A subset of nine studies analysed temporal distribution, eight finding displacement of incidents later. This is the most complete analysis to date of the effect of this Act on violence, finding a lack of reliable evidence to answer the research question, but little to suggest that the Act has markedly impacted already-declining violence rates. Correspondence to Caitríona M. Callan, MBBChir, North Middlesex University Hospital, NHS Trust N18 1QX, London, UK Tel/fax: +44 208 887 2481; e-mail: caitriona.callan@nhs.net Received April 20, 2017 Accepted October 28, 2017 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
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http://ift.tt/2k1gesQ
Applying the Ottawa subarachnoid haemorrhage rule on a cohort of emergency department patients with headache
Objective The Ottawa subarachnoid haemorrhage (SAH) rule suggests that alert patients older than 15 years with a severe nontraumatic headache reaching maximum intensity within 1 h and absence of high-risk variables effectively have a SAH ruled out. We aimed to determine the proportion of emergency department (ED) patients with any headache fulfilling the entry criteria for the Ottawa SAH rule. Patients and methods The Ottawa SAH rule was applied retrospectively in a substudy of a prospective snapshot of 34 EDs in Queensland, Australia, carried out over 4 weeks in September 2014. Patients older than 18 years or more with a nontraumatic headache of any potential cause were included. Clinical data and results of investigations were collected. Results Data were available for 644 (76%) patients. A total of 149 (23.1%, 95% confidence interval: 20.0–26.5%) fulfilled and 495 (76.9%, 95% confidence interval: 73.5–80.0%) did not fulfil the entry criteria. In patients who fulfilled the entry criteria, 30 (
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http://ift.tt/2BOHwdX
Response to Pioglitazone in Patients With Nonalcoholic Steatohepatitis With vs Without Type 2 Diabetes
Pioglitazone is effective for long-term treatment of patients with nonalcoholic steatohepatitis (NASH) with prediabetes or type-2 diabetes. However, it is not clear how the presence of type-2 diabetes affects the drug's efficacy. We compared metabolic and histologic responses to pioglitazone in patients with NASH and prediabetes vs type-2 diabetes.
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Association of Vedolizumab Level, Anti-drug Antibodies, and α4β7 Occupancy With Response in Patients With Inflammatory Bowel Diseases
There are few data available on the real-life pharmacokinetic and pharmacodynamics features of vedolizumab, a monoclonal antibody against integrin α4β7. We performed a prospective study of patients with inflammatory bowel diseases (IBD) treated with vedolizumab to determine serum drug concentrations, formation of anti-vedolizumab antibodies (AVAs), and integrin α4β7 saturation.
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Blocking IL4- and IL13-mediated phosphorylation of STAT6 (Tyr641) decreases M2 polarization of macrophages and protects against macrophage-mediated radioresistance of inflammatory breast cancer
Here we show that M2-polarized macrophages upon co-culture with IBC cells, promote radioresistance of IBC cells, and this effect was inhibited by PM37, a phosho-STAT6 inhibitor. M2-macrophages mediated radioresistance of KPL4 IBC cells is associated with increased protein expression of PRKCZ kinase in KPL4 cells, after M2-macrophage co-culture, and this was prevented by PM37-mediated inhibition of M2 polarization of THP1 macrophages prior to coculture with KPL4 cells.
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The Effect of Dietary Nitrate on Nocturnal Sleep-Disordered Breathing and Arterial Oxygen Desaturation at High Altitude
High Altitude Medicine & Biology , Vol. 0, No. 0.
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Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure
ABSTRACT
Tissue engineering with scaffolds to form transplantable organs is of wide interest. Decellularized tissues have been tested for this purpose, although supplies of healthy donor tissues, vascular recellularization for perfusion and tissue homeostasis in engineered organs pose challenges. We hypothesized decellularized human placenta will be suitable for tissue engineering. The universal availability and unique structures of placenta for accommodating tissue, including presence of embedded vessels, were major attractions. We found decellularized placental vessels were re-endothelialized by adjacent native cells and bridged vessel defects in rats. Also, implantation of liver fragments containing all cell types successfully hepatized placenta with maintenance of albumin and urea synthesis, as well as hepatobiliary transport of 99mTc-mebrofenin, over up to three days in vitro. After hepatized placenta containing autologous liver was transplanted into sheep, tissue units were well-perfused and self-assembled. Histological examination indicated transplanted tissue retained hepatic cord structures with characteristic hepatic organelles, such as gap junctions, and hepatic sinusoids lined by endothelial, Kupffer, and other cell types. Hepatocytes in this neo-organ expressed albumin and contained glycogen. Moreover, transplantation of hepatized placenta containing autologous tissue rescued sheep in extended partial hepatectomy-induced acute liver failure. This rescue concerned amelioration of injury and induction of regeneration in native liver. The grafted hepatized placenta was intact with healthy tissue that neither proliferated nor was otherwise altered. Conclusions: The unique anatomic structure and matrix of human placenta were effective for hepatic tissue engineering. This will advance applications ranging from biological studies, drug development and toxicology to therapies in people. This article is protected by copyright. All rights reserved.
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Patterns of Care and Outcomes of Hypofractionated Chemoradiation Versus Conventionally Fractionated Chemoradiation for Glioblastoma in the Elderly Population
Purpose: This study evaluated practice patterns, outcomes, and predictors of survival for elderly patients with glioblastoma (GBM) receiving definitive chemoradiotherapy (CRT) with either hypofractionated radiotherapy or conventionally fractionated radiotherapy. Materials and Methods: The National Cancer Data Base was queried for patients age 65 years and above diagnosed with GBM between 2006 and 2012 that received definitive CRT with either hypofractionated radiotherapy (hCRT) or conventionally fractionated radiotherapy (cCRT). Patient, tumor, and treatment parameters were extracted. Statistics included Kaplan-Meier analysis to evaluate overall survival (OS) as well as Cox proportional hazards modeling to determine variables associated with OS. Propensity score matching was performed in order to assess groups in a balanced manner while reducing indication biases. Results: Altogether, 5126 patients met inclusion criteria; 126 (2.5%) underwent hCRT, while 5000 (97.5%) received cCRT. Temporal trends revealed that the use of hCRT is rising, especially in more recent years. Patients undergoing hCRT were older, with worse performance status, treated with biopsy only, and more likely to receive treatment at an academic facility. cCRT was associated with improved median OS (10.7 vs. 6.2 mo, P
http://ift.tt/2B8fygf
http://ift.tt/2B8fygf
Improving Patient-reported Pain During Radiotherapy Through Nurse Involvement and Patient Education
Objectives: Pain management during radiotherapy helps assess quality of care. By establishing an intervention to address pain during on-treatment visits (OTVs), we aim to lower patient-reported pain scores. Methods: A total of 171 patients were included in the analysis: 58 were retrospectively reviewed to provide a control and 113 were prospectively enrolled and evaluated after the intervention. The intervention included (1) a pain management in-service performed with the resident physician and nurses, (2) distribution of pain management educational materials, and (3) nurse consultation for patients with a pain score ≥5 within 2 days of the in-service. Study aims were to reduce the number of pain scores ≥5 by 30% and increase the number of pain scores documented during every OTV to >90%. Results: Median patient age was 65 years. Before the intervention, the average DVPRS score at initial consultation was 2 (range, 0 to 9) and 98% of patients had scores documented during OTVs. Overall, 26% (44/171) of OTV scores measured ≥5. Following the intervention, average DVPRS score at initial consultation was 2 (range, 0 to 10) and 99% of scores were documented during OTVs. About 14% (49/341) of patient-reported scores were ≥5, representing an ~50% relative reduction (P=0.023). The number of patients with 2+ pain scores ≥5 was reduced from 21% (12/58) before the intervention to 11% (12/109) after the intervention (P=0.1068). Conclusion: Involving nursing staff in the education and follow-up of patients with uncontrolled pain during radiotherapy led to an ~50% relative reduction in patient-reported DVPRS scores of 5+ during weekly OTVs. Presented at ASTRO's 58th Annual Meeting in Boston, MA, USA. The authors declare no conflicts of interest. Reprints: Anamaria R. Yeung, MD, 2000 SW Archer Road, P.O. Box 100385, Gainesville, FL 32610-0385. E-mail: areyna@ufl.edu. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
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http://ift.tt/2AeYNQg
Complete B Cell Deficiency Reduces Allograft Inflammation and Intragraft Macrophages a Rat Kidney Transplant Model
ABSTRACT Background Increasingly it is being appreciated that B cells have broad roles beyond the humoral response, and are able to contribute to and regulate inflammation. The specific role of B cells in the pathogenesis of early allograft inflammation remains unclear. Methods To address this question, we generated B cell deficient Lewis rats via CRISPR technology. In a full mismatch transplant model, kidneys from Brown Norway donors were transplanted into B cell deficient Lewis recipients (B-/-) or wild type Lewis recipients. T cell mediated rejection was attenuated with cyclosporine. Results Renal inflammation was reduced at 1 week after transplant (Banff scores for interstitial inflammation, microvascular inflammation, glomerulitis, and C4d) in allografts from B-/- recipients. The reduction in interstitial inflammation was predominantly due to a decline in graft infiltrating macrophages. Intragraft T cell numbers remained unchanged. In addition, B cell deficiency was associated with increased T regulatory cells and reduced splenic T follicular helper cells at baseline; and significantly increased intragraft and splenic IL-10 mRNA levels after transplant. In vitro, B-/- and wild type splenic T cells produced similar levels of IFN-γ in response to T cell specific activation. Conclusions B cell deficiency in this model produced an anti-inflammatory phenotype with a shift towards regulatory T cell populations, production of anti-inflammatory cytokines (IL-10), and a reduction in allograft inflammation. These findings define a role for B cells to influence the cell populations and mediators involved in the pathogenesis of early allograft inflammation. Corresponding author: Sarah E. Panzer, MD, Division of Nephrology, Department of Medicine, 1685 Highland Avenue, Madison, WI 53705, sepanzer@medicine.wisc.edu Authorship statement: Sarah E. Panzer: concept, study design, performance of research, data analysis, writing of paper Nancy A. Wilson: performance of research, data analysis, writing of paper Bret M. Verhoven: performance of research, data analysis, writing of paper Ding Xiang: performance of research, review of manuscript C. Dustin Rubinstein: performance of research, data analysis, writing of paper Robert R. Redfield: data analysis, review of manuscript Weixiong Zhong: performance of research, review of manuscript Shannon R. Reese: study design, performance of research, data analysis, writing of paper Disclosure: The authors declare no conflict of interest. Funding: This project was supported by the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant UL1TR000427, and the KL2 training Award (KL2TR000428). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
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http://ift.tt/2AyDkRh
Comparison of Preemptive Therapy and Antiviral Prophylaxis for Prevention of Cytomegalovirus in Seropositive Liver Transplant Recipients
Background Few studies have directly compared preemptive therapy (PET) and antiviral prophylaxis (AP) for prevention of cytomegalovirus disease in CMV seropositive (R+) orthotopic liver transplant (OLT) recipients. Methods We prospectively assessed CMV disease and clinical outcomes among 160 consecutive R+ OLT recipients who received PET (weekly plasma CMV PCR for 3 months, oral valganciclovir 900 mg twice daily for CMV viremia >250 IU/mL, until 2 consecutive negative weekly PCR results) and compared them to a historical cohort of 156 R+ recipients who received AP (valganciclovir 900 mg daily for 3 months). Results Patient characteristics were similar between PET and AP cohorts (p>0.05 all comparisons). In the PET group, 24% (39/160) developed CMV viremia >250 IU/mL at a median of 42 (range 7-93) days post-OLT. CMV monitoring adherence in the PET cohort was 85% (1488/1760 required tests) and 86% (30/36) initiated PET within 3 days of the CMV result. By 12 months post-OLT, the incidence of CMV disease, acute allograft rejection, major infection, or death in the PET and AP cohorts was not significantly different: 2% vs 2%, 19% vs 16%, 10.5% vs 10.8%, and 5% vs 8%, respectively (p > 0.05 all comparisons). The estimated proportion of drug-exposed patients and average antiviral drug exposure were significantly lower with PET vs AP: 24% vs 100%, p
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http://ift.tt/2B5QiqN
Influence of Blood Pressure and Calcineurin Inhibitors on Kidney Function After Heart or Liver Transplantation
ABSTRACT Background Chronic kidney disease is common after heart or liver transplantation, with calcineurin inhibitors (CNI) considered the key contributor. A possible influence of posttransplant blood pressure has not been extensively examined. Methods Data from adult recipients of a first heart or liver transplant were analyzed regarding the relationship between blood pressure at year 1, renal function at year 5, and CNI therapy. Results Whereas we confirmed the well-known detrimental effect of increased 1-year systolic blood pressure on 5-year kidney graft survival, heart or liver graft survival were not affected. However, among 2,534 heart transplant recipients with good renal function at year 1, increasing systolic blood pressure at year 1 was associated with higher rates of poor renal function at year 5 posttransplant. This association was confirmed on multivariate analysis overall (odds ratio [OR] 1.25 per 20 mmHg increment, P
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http://ift.tt/2AyjsxM
Liver Transplantation in Cryptogenic Cirrhosis: Outcome comparisons between NASH, Alcoholic and AIH cirrhosis
ABSTRACT Background The outcomes of liver transplantation (LT) in patients with cryptogenic cirrhosis (CC) have not been adequately examined except for small case series. We believe that patients currently listed as CC have truly cryptogenic liver disease and may have different post-LT outcomes compared to nonalcoholic steatohepatitis (NASH). Methods: We compared the post-LT outcomes of adults with CC (n=3241) and compared them with cirrhosis from NASH (n=4089), alcohol (AC, n=7837) and autoimmune hepatitis (AIH, n=1435) using the UNOS database from 2002-16. We excluded those who had multi-organ transplantation and hepatocellular carcinoma. In addition to the well-known predictors of liver transplant outcomes, we analyzed the impact of Karnofsky Performance Status (KPS) score at LT on immediate and late outcomes. Results There were significant differences in clinical characteristics between the groups. Despite these differences in clinical characteristics and risk factors, CC had similar graft and patient survival to NASH, AC and AIH when assessed by Kaplan-Meier survival. Multivariate Cox regression analysis showed that graft and patient survival was similar in all 4 groups after adjusting for other confounders. Hispanics had a 24% lower risk of death (Hazard Ratio {HR} 0.76) compared to Whites in these combined cohorts after adjusting for all risk factors. In addition to other known risk factors, KPS score of 30% or less was associated with a 33% increase in risk of death (HR 1.33) on multivariate analysis. Conclusion Patients with CC had similar graft and patient survival when compared to NASH, AC and AIH cirrhosis. Address for correspondence: Paul J. Thuluvath, MD, FAASLD, FRCP, Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore, MD 21202, Tel: 410 332 9308; Fax: 410 659 1178; Email: thuluvath@gmail.com Conflicts of interest: None; Financial support: None Contributions: PJT and SH contributed to the idea, YS did the statistical analysis, PJT wrote the manuscript, SH and YS reviewed the final manuscript Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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