Objective. The outcomes of biatrial ablation (BA) and isolated left atrial ablation (LA) in atrial fibrillation remain inconclusive. In this meta-analysis, we assess the currently available evidence to compare outcomes between BA and LA. Methods. Electronic searches were performed from database inception to December 2016, and relevant studies were accessed. Odds ratios and weight mean differences with 95% confidence intervals are reported. Twenty-one studies comprising 3609 patients were included in the present meta-analysis. Results. The prevalence of sinus rhythm in the BA cohort was similar to that in the LA cohort at discharge, at 12 months, and after more than 1 year of follow-up. However, at 6 months, the prevalence of sinus rhythm was higher in the BA cohort than in the LA cohort. The rate of permanent pacemaker implantation was higher in the BA cohort than in the LA cohort. However, 30-day and late mortality and neurological events were similar between the BA and LA groups. Conclusion. There was no significant difference in the rate of restored sinus rhythm, the risk of death, and cerebrovascular events between BA and LA, but BA had a higher rate of permanent pacemaker implantation.
https://ift.tt/2JE5GuV
Σάββατο 28 Απριλίου 2018
Biatrial versus Isolated Left Atrial Ablation in Atrial Fibrillation: A Systematic Review and Meta-Analysis
Learning on the Fly: The Interplay between Caspases and Cancer
The ease of genetic manipulation, as well as the evolutionary conservation of gene function, has placed Drosophila melanogaster as one of the leading model organisms used to understand the implication of many proteins with disease development, including caspases and their relation to cancer. The family of proteases referred to as caspases have been studied over the years as the major regulators of apoptosis: the most common cellular mechanism involved in eliminating unwanted or defective cells, such as cancerous cells. Indeed, the evasion of the apoptotic programme resulting from caspase downregulation is considered one of the hallmarks of cancer. Recent investigations have also shown an instrumental role for caspases in non-lethal biological processes, such as cell proliferation, cell differentiation, intercellular communication, and cell migration. Importantly, malfunction of these essential biological tasks can deeply impact the initiation and progression of cancer. Here, we provide an extensive review of the literature surrounding caspase biology and its interplay with many aspects of cancer, emphasising some of the key findings obtained from Drosophila studies. We also briefly describe the therapeutic potential of caspase modulation in relation to cancer, highlighting shortcomings and hopeful promises.
https://ift.tt/2JC1mvU
Automatic Spine Tissue Segmentation from MRI Data Based on Cascade of Boosted Classifiers and Active Appearance Model
The study introduces a novel method for automatic segmentation of vertebral column tissue from MRI images. The paper describes a method that combines multiple stages of Machine Learning techniques to recognize and separate different tissues of the human spine. For the needs of this paper, 50 MRI examinations presenting lumbosacral spine of patients with low back pain were selected. After the initial filtration, automatic vertebrae recognition using Cascade Classifier takes place. Afterwards the main segmentation process using the patch based Active Appearance Model is performed. Obtained results are interpolated using centripetal Catmull–Rom splines. The method was tested on previously unseen vertebrae images segmented manually by 5 physicians. A test validating algorithm convergence per iteration was performed and the Intraclass Correlation Coefficient was calculated. Additionally, the 10-fold cross-validation analysis has been done. Presented method proved to be comparable to the physicians (). Moreover results confirmed a proper algorithm convergence. Automatically segmented area correlated well with manual segmentation for single measurements () and for average measurements () with . The 10-fold cross-validation analysis () confirmed a good model generalization resulting in practical performance.
https://ift.tt/2r80cSd
Fat Embolism Syndrome: A Case Report and Review Literature
Fat embolism syndrome (FES) is a life-threatening complication in patients with orthopedic trauma, especially long bone fractures. The diagnosis of fat embolism is made by clinical features alone with no specific laboratory findings. FES has no specific treatment and requires supportive care, although it can be prevented by early fixation of bone fractures. Here, we report a case of FES in a patient with right femoral neck fracture, which was diagnosed initially by Gurd's criteria and subsequently confirmed by typical appearances on magnetic resonance imaging (MRI) of the brain. The patient received supportive management and a short course of intravenous methylprednisolone.
https://ift.tt/2JAuBiN
The impact of complete embedding of remaining tissue in gynecological lymph node dissection specimen in surgical pathology on lymph node yield: is it clinically relevant?
Abstract
The assessment of nodal metastases in gynecological surgical specimen is an important staging parameter, directing further therapeutic procedures. Since the number of lymph nodes (LNs) removed is seen as an indicator of surgical and pathological quality, the demand for higher lymph node (LN) counts is raising. The goal of this prospective study was the comparison between lymph node counts of macroscopically detectable LNs and the LN yield by complete embedding and proceeding of all submitted LN-containing tissue in the pathology laboratory. One hundred six cases of cervical, uterine, or ovarian cancer, treated in three different hospitals within 3 years, were analyzed. All tissue submitted to the pathology from the surgically performed LN dissections was completely dissected and embedded in the institute of pathology. Subsequently, the amount of LN of all macroscopically detectable nodes was compared to the final histologically reached numbers of LN. Furthermore the histologically visible area of the LNs and their metastases was analyzed to assess the relation of LN numbers to the whole examined LN area. Complete embedding raises the average number of LN counted by 3 to 7 but did only minimally increase the LN area for microscopical examination by about 5% due to the small area of the additional LNs in the remaining fat tissue. The staging was in no case altered by complete embedding, even when additional nodal metastases were detected in the remaining fat tissue, since this was only seen in cases which had already metastatic nodes. Complete embedding of LN-containing tissue did not provide relevant additional staging information and seems therefore unnecessarily laborious, careful pathological work-up assumed.
https://ift.tt/2vXd0j6
Histopathological variables in liver metastases of patients with stage IV colorectal cancer: potential prognostic relevance of poorly differentiated clusters
The prognosis of patients with colorectal liver metastases (LM) is mostly established on clinical variables or on the anatomic extent of colorectal cancer (CRC). Histopathological factors of LM which may actually reflect the biological aggressiveness of the tumor are not routinely considered to define the risk of worse clinical outcome in those patients. The number of poorly differentiated clusters (PDC) of neoplastic cells in primary CRC is associated with metastatic risk and bad prognosis, but PDC presence in LM has been barely analyzed thus far.
https://ift.tt/2w0DPmO
Morphological changes induced by Intraprostatic PSA-based vaccine in prostate Cancer biopsies (phase I clinical trial)
Immunotherapy is a novel treatment for many tumors including prostate cancer. Little is known about the histological changes in prostate biopsies caused by the prostatic-specific antigen (PSA)-based vaccine. This study evaluated the histopathological effects in prostate biopsies of recombinant fowlpox (rF) virus-based vaccine engineered to present the PSA and three costimulatory molecules (collectively labeled as PSA-TRICOM). This vaccine has shown that it can break tolerance of the PSA, and its administration directly into a tumor enables the affected tumor cells to act as antigen-presenting cells activating new T-cells, and broadening the immune response to recognize and kill tumor.
https://ift.tt/2HYGSR6
Ecological Expansion and Extinction in the Late Ediacaran: Weighing the Evidence for Environmental and Biotic Drivers
https://ift.tt/2JxCrtF
Neural Crest Transplantation Reveals Key Roles in the Evolution of Cavefish Development
https://ift.tt/2jgnuRH
Understanding molecular evolution and development of the organ of Corti can provide clues for hearing restoration
https://ift.tt/2JBS3MG
Pancreatic β cells overexpressing hIAPP impaired mitophagy and unbalanced mitochondrial dynamics
Pancreatic β cells overexpressing hIAPP impaired mitophagy and unbalanced mitochondrial dynamics
Pancreatic β cells overexpressing hIAPP impaired mitophagy and unbalanced mitochondrial dynamics, Published online: 29 April 2018; doi:10.1038/s41419-018-0533-x
Pancreatic β cells overexpressing hIAPP impaired mitophagy and unbalanced mitochondrial dynamicshttps://ift.tt/2jfoXYb
Understanding the gut-kidney axis in nephrolithiasis: an analysis of the gut microbiota composition and functionality of stone formers
Objectives
The involvement of the gut microbiota in the pathogenesis of calcium nephrolithiasis has been hypothesised since the discovery of the oxalate-degrading activity of Oxalobacter formigenes, but never comprehensively studied with metagenomics. The aim of this case–control study was to compare the faecal microbiota composition and functionality between recurrent idiopathic calcium stone formers (SFs) and controls.
DesignFaecal samples were collected from 52 SFs and 48 controls (mean age 48±11). The microbiota composition was analysed through 16S rRNA microbial profiling approach. Ten samples (five SFs, five controls) were also analysed with deep shotgun metagenomics sequencing, with focus on oxalate-degrading microbial metabolic pathways. Dietary habits, assessed through a food-frequency questionnaire, and 24-hour urinary excretion of prolithogenic and antilithogenic factors, including calcium and oxalate, were compared between SFs and controls, and considered as covariates in the comparison of microbiota profiles.
ResultsSFs exhibited lower faecal microbial diversity than controls (Chao1 index 1460±363vs 1658±297, fully adjusted p=0.02 with stepwise backward regression analysis). At multivariate analyses, three taxa (Faecalibacterium, Enterobacter, Dorea) were significantly less represented in faecal samples of SFs. The Oxalobacter abundance was not different between groups. Faecal samples from SFs exhibited a significantly lower bacterial representation of genes involved in oxalate degradation, with inverse correlation with 24-hour oxalate excretion (r=–0.87, p=0.002). The oxalate-degrading genes were represented in several bacterial species, whose cumulative abundance was inversely correlated with oxaluria (r=–0.85, p=0.02).
ConclusionsIdiopathic calcium SFs exhibited altered gut microbiota composition and functionality that could contribute to nephrolithiasis physiopathology.
https://ift.tt/2KkJLKg
Lemierres syndrome: a rare cause of sepsis presenting with an absence of throat symptoms
A 16-year-old boy presented to hospital with a 6-day history of diarrhoea, vomiting and abdominal pain. During his admission he was found to be hypotensive, tachycardic and persistently feverish. Blood cultures taken on admission isolated Fusobacterium necrophorum. CT scanning of his neck showed a non-occlusive thrombus of the right internal jugular vein and a small right parapharyngeal abscess. CT scans of the chest and abdomen revealed multiple pulmonary abscesses, bilateral pleural effusions and splenomegaly. Treatment consisted of an unfractionated heparin infusion and intravenous antibiotics. A right-sided intercostal drain was inserted for a complex right-sided empyema. He subsequently developed a left-sided pleural effusion which was treated with a video-assisted thoracoscopic surgery (VATS) pleurodesis procedure. His fever resolved after his VATS pleurodesis procedure 3 weeks after initial presentation. Clinically he made a slow recovery but now is improved after 6 weeks of intravenous antibiotics and was discharged home.
https://ift.tt/2JB1XxY
Novel management of vaginal chronic graft-versus-host disease causing haematometra and haematocolpos
Genital chronic graft-versus-host disease (GVHD) in women posthaematopoietic cell transplantation may cause vaginal mucosal sclerosis. Human papillomavirus (HPV) reactivation, also common post-transplantation, limits local immunosuppressive, but not oestrogen treatment. A 36-year-old nulliparous woman developed coincidental genital chronic GVHD and HPV 22 months after transplant for aplastic anaemia. Topical immunosuppression for GVHD led to an eruption of warts successfully treated with laser surgery and cone biopsy. She maintained normal ovarian function and used extended cycle combined hormonal contraception. A vaginal oestrogen ring used continuously limited most scarring for 8 years. Progressive apical vaginal scarring obstructed menstrual flow leading to haematocolpos and haematometra. Normal anatomy was restored with a cruciate incision in the cervicovaginal scar performed during menses. When HPV disease limits use of topical immunosuppression in women with vaginal GVHD, the local scar-reducing effect of a vaginal oestrogen ring is limited, and surgery may be needed and can be successful in treating haematocolpos.This study was registered in ClinicalTrials.gov with trial registration number of NCT00003838.
https://ift.tt/2jf7aAk
Treatment of end-stage renal disease with continuous ambulatory peritoneal dialysis in rural Guatemala
A 42-year-old indigenous Maya man presented to a non-profit clinic in rural Guatemala with signs, symptoms and laboratory values consistent with uncontrolled diabetes. Despite appropriate treatment, approximately 18 months after presentation, he was found to have irreversible end-stage renal disease (ESRD) of uncertain aetiology. He was referred to the national public nephrology clinic and subsequently initiated home-based continuous ambulatory peritoneal dialysis. With primary care provided by the non-profit clinic, his clinical status improved on dialysis, but socioeconomic and psychological challenges persisted for the patient and his family. This case shows how care for people with ESRD in low- and middle-income countries requires scaling up renal replacement therapy and ensuring access to primary care, mental healthcare and social work services.
https://ift.tt/2Jwtu3y
Correction: Unilateral retinitis pigmentosa occurring in an individual with a mutation in the CLRN1 gene
Sim PY, Jeganathan VSE, Wright AF et al. Unilateral retinitis pigmentosa occurring in an individual with a mutation in the CLRN1 gene. BMJ Case Rep 2018; doi: 10.1136/bcr-2017-222045.
The following text should have been included in the 'Presented at' section:
Dr V. Swetha E. Jeganathan was finalist for the Novartis Retina Case Awards, held on 27th February 2013 at the City Hospital, Birmingham. Her case presentation was subsequently published in the Eye News supplement in March 2013.
https://ift.tt/2jd3n6E
Treatment and reconstruction of a complicated infected scalp squamous cell carcinoma with CNS invasion
A 60-year-old male patient with a large infected cranial apex lesion was admitted with lethargy and mental status changes. The patient underwent evaluation with imaging studies, a skin biopsy, cultures with microscopy and a diagnostic burr hole. MRI and positron emission tomography/CT scan revealed a squamous cell carcinoma with ingrowth in the midline of the brain and subdural empyema infected with Streptococcus anginosus and Staphylococcus aureus.
High dose intravenous antibiotic treatment was initiated and the patient subsequently underwent a surgical resection of the carcinoma with a 1 cm margin of surrounding skin and skull. The defect was reconstructed using a titanium plate and a free microvascular lattisimus dorsi muscle flap then covered with a split skin graft.
The patient received 37 radiation therapy sessions (66 GY) as adjuvant therapy.
Intensive neurorehabilitation slowly improved an initial paraparesis. The 7-month follow-up revealed a satisfactory cosmetic result and residual gait impairment secondary to central nervous system invasion.
https://ift.tt/2JB1FqS
The behavioural variant frontotemporal dementia phenocopy syndrome is a distinct entity - evidence from a longitudinal study
This study aimed to i) examine the frequency of C9orf72 expansions in a cohort of patients with the behavioural variant frontotemporal dementia (bvFTD) phenocopy syndrome, ii) observe outcomes in a group of pheno...
https://ift.tt/2FqfeXF
Platelet activation and aggregation after aneurysmal subarachnoid hemorrhage
Endovascular techniques have proven beneficial in the treatment of aneurysmal subarachnoid hemorrhage (aSAH), but with high risk of arterial clotting, emboli and dissection. Platelet activation and alterations...
https://ift.tt/2KjsXTU
Critical contribution of RIPK1 mediated mitochondrial dysfunction and oxidative stress to compression-induced rat nucleus pulposus cells necroptosis and apoptosis
Abstract
The aim of this study was to investigate whether RIPK1 mediated mitochondrial dysfunction and oxidative stress contributed to compression-induced nucleus pulposus (NP) cells necroptosis and apoptosis, together with the interplay relationship between necroptosis and apoptosis in vitro. Rat NP cells underwent various periods of 1.0 MPa compression. To determine whether compression affected mitochondrial function, we evaluated the mitochondrial membrane potential, mitochondrial permeability transition pore (mPTP), mitochondrial ultrastructure and ATP content. Oxidative stress-related indicators reactive oxygen species, superoxide dismutase and malondialdehyde were also assessed. To verify the relevance between oxidative stress and necroptosis together with apoptosis, RIPK1 inhibitor necrostatin-1(Nec-1), mPTP inhibitor cyclosporine A (CsA), antioxidants and small interfering RNA technology were utilized. The results established that compression elicited a time-dependent mitochondrial dysfunction and elevated oxidative stress. Nec-1 and CsA restored mitochondrial function and reduced oxidative stress, which corresponded to decreased necroptosis and apoptosis. CsA down-regulated mitochondrial cyclophilin D expression, but had little effects on RIPK1 expression and pRIPK1 activation. Additionally, we found that Nec-1 largely blocked apoptosis; whereas, the apoptosis inhibitor Z-VAD-FMK increased RIPK1 expression and pRIPK1 activation, and coordinated regulation of necroptosis and apoptosis enabled NP cells survival more efficiently. In contrast to Nec-1, SiRIPK1 exacerbated mitochondrial dysfunction and oxidative stress. In summary, RIPK1-mediated mitochondrial dysfunction and oxidative stress play a crucial role in NP cells necroptosis and apoptosis during compression injury. The synergistic regulation of necroptosis and apoptosis may exert more beneficial effects on NP cells survival, and ultimately delaying or even retarding intervertebral disc degeneration.
https://ift.tt/2vTZywv
Shared research priorities for pessary use in women with prolapse: results from a James Lind Alliance Priority Setting Partnership
Objectives
To identify the shared priorities for future research of women affected by and clinicians involved with pessary use for the management of prolapse.
DesignA priority setting project using a consensus method.
SettingA James Lind Alliance Pessary use for prolapse Priority Setting Partnership (JLA Pessary PSP) conducted from May 2016 to September 2017 in the UK.
ParticipantsThe PSP was run by a Steering Group of three women with experience of pessary use, three experienced clinicians involved with management of prolapse, two researchers with relevant experience, a JLA adviser and a PSP leader. Two surveys were conducted in 2016 and 2017. The first gathered questions about pessaries, and the second asked respondents to prioritise a list of questions. A final workshop was held on 8 September 2017 involving 10 women and 13 clinician representatives with prolapse and pessary experience.
ResultsA top 10 list of priorities for future research in pessary use for prolapse was agreed by consensus.
ConclusionsWomen with experience of pessary use and clinicians involved with prolapse management have worked together to determine shared priorities for future research. Aligning the top 10 results with existing research findings will highlight the gaps in current evidence and signpost future research to areas of priority. Effective dissemination of the results will enable research funding bodies to focus on gathering the evidence to answer the questions that matter most to those who will be affected.
https://ift.tt/2JxFmCC
High-intensity interval training or continuous training, combined or not with fasting, in obese or overweight women with cardiometabolic risk factors: study protocol for a randomised clinical trial
Introduction
Physical inactivity and increased caloric intake play important roles in the pathophysiology of obesity. Increasing physical activity and modifying eating behaviours are first-line interventions, frequently hampered by lack of time to exercise and difficulties in coping with different diets. High-intensity interval training (HIIT) may be a time-efficient method compared with moderate-intensity continuous training (CT). Conversely, diets with a fasting component may be more effective than other complex and restrictive diets, as it essentially limits caloric intake to a specified period without major diet composition changes. Therefore, the combination of HIIT and fasting may provide incremental benefits in terms of effectiveness and time efficiency in obese and sedentary populations. The aim of this study is to determine the effect of HIIT versus CT, combined or not with fasting, on microcirculatory function, cardiometabolic parameters, anthropometric indices, cardiorespiratory fitness and quality of life in a population of sedentary overweight or obese women with cardiometabolic risk factors.
Methods and analysisSedentary women aged 30–50 years, with a body mass index ≥25 kg/m2 and cardiometabolic risk factors, will be randomised to HIIT performed in the fasting state, HIIT performed in the fed state, CT in the fasting state or CT in the fed state. Cardiometabolic parameters, anthropometric indices, cardiorespiratory fitness, quality of life and microvascular function (cutaneous capillary density and microvascular reactivity evaluated by laser speckle contrast imaging) will be evaluated before initiation of the interventions and 16 weeks thereafter.
Ethics and disseminationThe trial complies with the Declaration of Helsinki and has been approved by the local ethics committee (Instituto Nacional de Cardiologia, Rio de Janeiro, Brazil). All patients provide written informed consent before enrolment and randomisation. The study's results will be disseminated to the healthcare community by publications and presentations at scientific meetings.
Trial registration numberhttps://ift.tt/2jdHT9L
Development of prediction models of stress and long-term disability among claimants to injury compensation systems: a cohort study
Objectives
We sought to develop prognostic risk scores for compensation-related stress and long-term disability using markers collected within 3 months of a serious injury.
DesignCohort study. Predictors were collected at baseline and at 3 months postinjury. Outcome data were collected at 72 months postinjury.
SettingHospitalised patients with serious injuries recruited from four major trauma hospitals in Australia.
Participants332 participants who made claims for compensation for their injuries to a transport accident scheme or a workers' compensation scheme.
Primary outcome measures12-item WHO Disability Assessment Schedule and 6 items from the Claims Experience Survey.
ResultsOur model for long-term disability had four predictors (unemployed at the time of injury, history of a psychiatric disorder at time of injury, post-traumatic stress disorder symptom severity at 3 months and disability at 3 months). This model had good discrimination (R2=0.37) and calibration. The disability risk score had a score range of 0–180, and at a threshold of 80 had sensitivity of 56% and specificity of 86%. Our model for compensation-related stress had five predictors (intensive care unit admission, discharged to home, number of traumatic events prior to injury, depression at 3 months and not working at 3 months). This model also had good discrimination (area under the curve=0.83) and calibration. The compensation-related stress risk score had score range of 0–220 and at a threshold of 100 had sensitivity of 74% and specificity of 75%. By combining these two scoring systems, we were able to identify the subgroup of claimants at highest risk of experiencing both outcomes.
ConclusionsThe ability to identify at an early stage claimants at high risk of compensation-related stress and poor recovery is potentially valuable for claimants and the compensation agencies that serve them. The scoring systems we developed could be incorporated into the claims-handling processes to guide prevention-oriented interventions.
https://ift.tt/2JyI0YD
Novel augmented reality solution for improving health literacy around antihypertensives in people living with type 2 diabetes mellitus: protocol of a technology evaluation study
Introduction
Low health literacy is common in people with type 2 diabetes mellitus (T2DM) (up to 40%), associated with decreased self-efficacy in managing T2DM and its important complications, mainly hypertension. This study introduces, for the first time, an easy-to-use solution based on augmented reality (AR) on smartphones, to enhance health literacy around antihypertensive medicines. It assesses the feasibility of the solution for improving health literacy, oriented specifically to angiotensin II receptor blockers; embedding the health literacy improvement into the use cycle of angiotensin II receptor blockers and providing continuous access to information as a form of patient engagement.
Methods and analysisThis is a technology evaluation study with one technology group (AR plus usual care) and one non-technology group (usual care). Both groups receive face-to-face communications with community pharmacists regarding angiotensin II receptor blockers; the technology group receive additional AR-enhanced digital consumer medicine information throughout the use of their medications. The primary outcome is the change in health literacy and the hypothesis is that the proportions of people who show high health literacy will be larger in the technology group. Mixed effects models will be used to analyse solution effectiveness on outcomes. Multiple regression models will be used to find additional variables that might affect the relationship between health literacy and the AR solution.
Ethics and disseminationQueensland University of Technology (QUT) Human Research Ethics Committee has approved the study as a low-risk technology evaluation study (approval number: 1700000275). Findings will be disseminated via attending scientific conferences and publishing in peer-reviewed journals. Facilitated by QUT, two press releases have been published in public media and two presentations have been made in university classrooms.
https://ift.tt/2jeUxFq
Should surgery be delayed in patients taking direct oral anticoagulants who suffer a hip fracture? A retrospective, case-controlled observational study at a UK major trauma centre
Objective
To determine whether not waiting for the elimination of direct oral anticoagulants (DOACs) has an effect on the amount of perioperative bleeding in patients who undergo operative treatment of a hip fracture.
DesignObservation, retrospective case–control study.
SettingA single UK major trauma centre.
ParticipantsPatients who sustained a hip fracture were identified using the National Hip Fracture Database (NHFD). All those found to be taking a DOAC at the time of fracture were identified (n=63). A matched group not taking a DOAC was also identified from the NHFD (n=62).
Main outcomePerioperative drop in haemoglobin concentration.
ResultsThere was no relationship between admission to operation interval and perioperative change in haemoglobin concentration in patients taking DOACs (regression coefficient=–0.06 g/L/hour; 95% CI –0.32–0.20; p=0.64). No relationship was found between the time from admission to operation interval and the probability of transfusion (OR=0.94; 95% CI 0.85 to 1.90; p=0.16) or reoperation (OR=1.04; 95% CI 0.93 to 1.16; p=0.49). One mortality was recorded in the DOAC group within 30 days of admission, and this compared with five in the matched group of patients (p=0.2).
ConclusionsDelaying surgery in patients who sustain a hip fracture who are taking a DOAC drug has not been shown to reduce perioperative bleeding or affect their mortality in this study.
https://ift.tt/2Jw7ZzS
Chemical peels for acne vulgaris: a systematic review of randomised controlled trials
Objective
We evaluated current evidence from randomised controlled trials (RCTs) regarding the effectiveness of chemical peeling for treating acne vulgaris.
MethodsStandard Cochrane methodological procedures were used. We searched MEDLINE, Cochrane Central Register of Controlled Trials and EMBASE via OvidSP through April 2017. Reviewers independently assessed eligibility, risk of bias and extracted data.
ResultsTwelve RCTs (387 participants) were included. Effectiveness was not significantly different: trichloroacetic acid versus salicylic acid (SA) (percentage of total improvement: risk ratio (RR) 0.89; 95% CI 0.73 to 1.10), glycolic acid (GA) versus amino fruit acid (the reduction of inflammatory lesions: mean difference (MD), 0.20; 95% CI –3.03 to 3.43), SA versus pyruvic acid (excellent or good improvement: RR 1.11; 95% CI 0.73 to 1.69), GA versus SA (good or fair improvement: RR 1.00; 95% CI 0.85 to 1.18), GA versus Jessner's solution (JS) (self-reported improvements: RR 1.00; 95% CI 0.44 to 2.26), and lipohydroxy acid versus SA (reduction of non-inflammatory lesions: 55.6%vs48.5%, p=0.878). Combined SA and mandelic acid peeling was superior to GA peeling (percentage of improvement in total acne score: 85.3%vs68.5%, p<0.001). GA peeling was superior to placebo (excellent or good improvement: RR 2.30; 95% CI 1.40 to 3.77). SA peeling may be superior to JS peeling for comedones (reduction of comedones: 53.4%vs26.3%, p=0.001) but less effective than phototherapy for pustules (number of pustules: MD –7.00; 95% CI –10.84 to –3.16).
LimitationsThe methodological quality of the included RCTs was very low to moderate. Meta-analysis was not possible due to the significant clinical heterogeneity across studies.
ConclusionCommonly used chemical peels appear to be similarly effective for mild-to-moderate acne vulgaris and well tolerated. However, based on current limited evidence, a robust conclusion cannot be drawn regarding any definitive superiority or equality among the currently used chemical peels. Well-designed RCTs are needed to identify optimal regimens.
https://ift.tt/2r71Aoe
PRactice of VENTilation in Middle-Income Countries (PRoVENT-iMIC): rationale and protocol for a prospective international multicentre observational study in intensive care units in Asia
Introduction
Current evidence on epidemiology and outcomes of invasively mechanically ventilated intensive care unit (ICU) patients is predominantly gathered in resource-rich settings. Patient casemix and patterns of critical illnesses, and probably also ventilation practices are likely to be different in resource-limited settings. We aim to investigate the epidemiological characteristics, ventilation practices and clinical outcomes of patients receiving mechanical ventilation in ICUs in Asia.
Methods and analysisPRoVENT-iMIC (study of PRactice of VENTilation in Middle-Income Countries) is an international multicentre observational study to be undertaken in approximately 60 ICUs in 11 Asian countries. Consecutive patients aged 18 years or older who are receiving invasive ventilation in participating ICUs during a predefined 28-day period are to be enrolled, with a daily follow-up of 7 days. The primary outcome is ventilatory management (including tidal volume expressed as mL/kg predicted body weight and positive end-expiratory pressure expressed as cm H2O) during the first 3 days of mechanical ventilation—compared between patients at no risk for acute respiratory distress syndrome (ARDS), patients at risk for ARDS and in patients with ARDS (in case the diagnosis of ARDS can be made on admission). Secondary outcomes include occurrence of pulmonary complications and all-cause ICU mortality.
Ethics and disseminationPRoVENT-iMIC will be the first international study that prospectively assesses ventilation practices, outcomes and epidemiology of invasively ventilated patients in ICUs in Asia. The results of this large study, to be disseminated through conference presentations and publications in international peer-reviewed journals, are of ultimate importance when designing trials of invasive ventilation in resource-limited ICUs. Access to source data will be made available through national or international anonymised datasets on request and after agreement of the PRoVENT-iMIC steering committee.
Trial registration numberNCT03188770; Pre-results.
https://ift.tt/2JAstHR
Cohort profile: China respiratory illness surveillance among pregnant women (CRISP), 2015-2018
Purpose
We established the China Respiratory Illness Surveillance among Pregnant women (CRISP) to conduct active surveillance for influenza-associated respiratory illness during pregnancy in China from 2015 to 2018. Among annual cohorts of pregnant women, we assess the incidence of acute respiratory illness (ARI), influenza-like illness (ILI), laboratory-confirmed influenza virus infection and the seroconversion proportion during the winter influenza season. We also plan to examine the effect of influenza virus infection on adverse pregnancy, delivery and infant health outcomes with cumulative data from the three annual cohorts.
ParticipantsCohort nurses enrol pregnant women in different trimesters of pregnancy from prenatal care facilities in Suzhou, Jiangsu Province, eastern China. Pregnant women who plan to deliver in the study facilities are eligible. Pregnant women who are seeking care for anything other than routine prenatal care, such as confirmation of low progesterone and threatened miscarriage, are excluded. At enrolment, study nurses collect baseline information on demographics, education-level attained, underlying medical conditions, seasonal influenza vaccination receipt, risk factors for influenza infection, gravidity and parity and contact information. For each participant, cohort nurses conduct twice weekly follow-up contacts, one phone call and one WeChat message (free instant messaging), from the time of enrolment until delivery or termination of pregnancy. During follow-up, study nurses ask about symptoms, timing and characteristics of ARI, healthcare-seeking behaviour and medications taken for participants reporting respiratory illness since the last contact. In addition, we collect combined nasal and throat swabs for identified ARI to test for influenza viruses. We collect paired sera before and after the influenza season. Active respiratory illness surveillance and seroinfection data during pregnancy of participants are linked to their medical record and the Suzhou Maternal Child Information System for detailed information on clinical treatment for respiratory illness, pregnancy, delivery and infant health outcomes.
Findings to dateIn 2015–2016, of 4915 pregnant women approached, 192 (4%) refused to participate, 91 (2%) were ineligible because they did not plan to deliver in one of the study hospitals or because their visit was for anything other than routine prenatal care and 4632 (94%) were enrolled, 46% during their first trimester of pregnancy (range 5–12 weeks), 48% during the second trimester (range 13–27 weeks) and 6% during the third trimester (range 28–37 weeks). The median age of the enrollees was 27 years (range 16–45) and two (0.04%, 95% CI 0.01% to 0.17%) reported influenza vaccination in the previous 12 months before pregnancy, while zero reported influenza vaccination in the previous 12 months during pregnancy. During the observation time of 648 518 person-days, 1355 ARI episodes were identified. Among 1127 swabs collected (for 83% of all ARIs), 68 (6%) tested positive for influenza virus, for a laboratory-confirmed influenza incidence of 0.31 (95% CI 0.25 to 0.40) per 100 person-months during pregnancy in the study cohort.
Future plansResults will be used to describe influenza disease burden in this population to model potential numbers of influenza illnesses averted if influenza vaccination coverage were increased and to support enhanced influenza prevention and control strategies among pregnant women in China. We also plan to enrol and follow three cohorts of pregnant women over three influenza seasons during 2015–2018 which will allow an analysis of the effect of influenza virus infection during pregnancy on adverse pregnancy, delivery and infant outcomes.
https://ift.tt/2jeUwBm
Quality of evidence considered by Health Canada in granting full market authorisation to new drugs with a conditional approval: a retrospective cohort study
Objectives
This study examines the characteristics of studies that Health Canada uses to grant full marketing authorisation for products given a conditional approval between 1 January 1998 and 30 June 2017.
DesignCohort study.
Data sourcesJournal articles listing drugs that fulfilled their conditions and received full marketing authorisation, Notice of Compliance database, Notice of Compliance with conditions website, Qualifying Notices listing required confirmatory studies, clinicaltrials.gov, PubMed, Embase, companies making products being analysed, journal articles resulting from confirmatory studies.
InterventionsNone.
Primary and secondary outcome measuresCharacteristics of studies—study design (randomised controlled trials, observational), primary outcome used (clinical, surrogate), blinding, number of patients in studies, patient median age, number of men and women.
ResultsEleven companies confirmed 36 publications for 19 products (21 indications). Twenty-nine out of the 36 studies were randomised controlled trials (RCTs) but only 10 stated if they were blinded. Twenty used surrogate outcomes. The median age of patients was 56 (IQR 44–61). The median number of men per study/trial was 184 (IQR 58–514) versus women 141 (IQR 46–263).
ConclusionsPostmarket studies required by Health Canada had more rigorous methodology than those required by either the Food and Drug Administration or the European Medicines Agency. There were still deficiencies in these studies. The absence of blinding in the majority of RCTs may introduce bias in their results. The use of surrogate outcomes especially in oncology trials means that improvements in survival are not available. The relatively young age of patients, even for products for cancer, means that predicting how the elderly will respond is often unknown. The almost universal finding that men outnumbered women may make it hard to differentiate responses by sex. These results raise potential concerns about the quality of evidence that Health Canada accepts.
https://ift.tt/2JCpj6H
Identification and initial response to childrens exposure to intimate partner violence: a qualitative synthesis of the perspectives of children, mothers and professionals
Objectives
To synthesise evidence on the acceptable identification and initial response to children's exposure to intimate partner violence (IPV) from the perspectives of providers and recipients of healthcare and social services.
DesignWe conducted a thematic synthesis of qualitative research, appraised the included studies with the modified Critical Appraisal Skills Programme checklist and undertook a sensitivity analysis of the studies scored above 15.
Data sourcesWe searched eight electronic databases, checked references and citations and contacted authors of the included studies.
Eligibility criteriaWe included qualitative studies with children, parents and providers of healthcare or social services about their experiences of identification or initial responses to children's exposure to IPV. Papers that have not been peer-reviewed were excluded as well as non-English papers.
ResultsSearches identified 2039 records; 11 studies met inclusion criteria. Integrated perspectives of 42 children, 212 mothers and 251 professionals showed that sufficient training and support for professionals, good patient-professional relationship and supportive environment for patient/clients need to be in place before enquiry/disclosure of children's exposure to IPV should occur. Providers and recipients of care favour a phased enquiry about IPV initiated by healthcare professionals, which focuses on 'safety at home' and is integrated into the context of the consultation or visit. Participants agreed that an acceptable initial response prioritises child safety and includes emotional support, education about IPV and signposting to IPV services. Participants had conflicting perspectives on what constitutes acceptable engagement with children and management of safety. Sensitivity analysis produced similar results.
ConclusionsHealthcare and social service professionals should receive sufficient training and ongoing individual and system-level support to provide acceptable identification of and initial response to children's exposure to IPV. Ideal identification and responses should use a phased approach to enquiry and the WHO Listen, Inquire about needs and concerns, Validate, Enhance safety and Support principles integrated into a trauma-informed and violence-informed model of care.
https://ift.tt/2r6y95P
Does practice analysis agree with the ambulatory care sensitive conditions list of avoidable unplanned admissions?: a cross-sectional study in the East of England
Objectives
To use significant event audits (SEAs) in primary care to determine which of a sample of emergency (unplanned) admissions were potentially avoidable; and compare with the National Health Service (NHS) list of ambulatory care sensitive conditions (ACSCs).
DesignAnalysis of unplanned medical admissions randomly identified in secondary care.
SettingPrimary care in the East of England.
Participants20 general practice teams trained to use SEA on unplanned admissions to identify potentially preventable factors.
InterventionsSEA of admissions.
Main outcome measuresLevel of agreement between those admissions identified as potentially preventable by SEA and the NHS ACSC list.
Results132 (26%) of randomly selected patients with unplanned admissions gave consent and an SEA was performed by their primary practice team. 130 SEA reports had sufficient data for our analysis. Practices concluded that 17 (13%) admissions were potentially preventable. The NHS ACSC list identified 36 admissions (28%) as potentially preventable. There was a low level of agreement between the practices and the NHS list as to which admissions were preventable (kappa=0.253). The ACSC list consisted mainly of respiratory admissions whereas the practice list identified a wider range of cases and identified context-specific factors as important.
ConclusionsThere was disagreement between the NHS list and practice conclusions of potentially avoidable admissions. The SEAs suggest that the pathway into unplanned admission may be less dependent on the condition than on context-specific factors, and the assumption that unplanned admissions for ACSCs are reasonable indicators of performance for primary care may not be valid.
https://ift.tt/2JyVTWJ
Vietnamese medical students and binge drinking: a qualitative study of perceptions, attitudes, beliefs and experience
Objectives
To explore the perceptions, attitudes, beliefs, and experiences related to Vietnamese medical students' binge drinking.
DesignA qualitative study comprising semi-structured focus groups/interviews with medical students and semi-structured interviews with key informants. Thematic analysis of data.
SettingParticipants were a convenience sample of usual volunteers from a medical university in Viet Nam.
Participants19 medical students from year 1 to 6 and 4 key informants agreed to participate in the study.
ResultsThe study found participants believe medical students drink less than other students and are not binge drinkers yet they experience and/or witness many binge drinking occasions among medical students. Participants consider alcohol use as culturally acceptable in Vietnamese society and a way for medical students to create and improve relationships with their friends, teachers, or work colleagues. Group affiliation and peer pressure to drink excessive alcohol are identified among medical students, especially male students.
ConclusionThe culture of drinking behaviour was explored among medical students in Viet Nam. This study reveals a dichotomy between the belief of not being binge drinkers and the experience of many binge drinking occasions among medical students. This tension suggests future research about binge drinking behaviour of Vietnamese medical students is required.
https://ift.tt/2r71s8e
Sonic and ultrasonic oscillating devices for the management of pain and dental fear in children or adolescents that require caries removal: a systematic review
Objectives
To evaluate the effectiveness and degree of acceptance by children and adolescents of the use of oscillating tips compared with rotating drills.
DesignSystematic review.
Data sourcesPubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library and Web of Science (October 2017).
Eligibility criteriaControlled randomised or non-randomised trials that evaluated sonic and ultrasonic oscillating devices versus rotating drill.
Data extractionEligible studies were selected and data extracted independently by two reviewers. Risk of bias was assessed using the Cochrane Method.
ResultsTwo controlled clinical trials comprising 123 children aged 2–12 years old were identified. Both trials were at high risk of selection bias and unclear risk of detection bias. In one trial, pain due to the use of oscillating drill resulted lower than employing rotating drill (Verbal Hochman Scale: RR 0.64 (95% CI 0.41 to 1.00); Visual Facial Expression Scale: RR 0.64 (95% CI 0.44 to 0.94)). In another study, compared with traditional drill ultrasonic tip was associated with a lower level of patient's discomfort (RR 0.40 (95% CI 0.20 to 0.79)) but not with dental anxiety (RR 1.29 (95% CI 0.97 to 1.71)). The effectiveness of the removal of caries as well as fillings durability were only considered in one study, but no statistically significant differences were found between the two interventions.
ConclusionsThe evidence based on two low-quality studies was insufficient to conclude that the use of oscillating tips for the management of pain and dental fear in children or adolescents compared with rotating drills was more effective.
https://ift.tt/2JyVKTb
Education, job position, income or multidimensional indices? Associations between different socioeconomic status indicators and chronic low back pain in a German sample: a longitudinal field study
Objective
To investigate associations between socioeconomic status (SES) indicators (education, job position, income, multidimensional index) and the genesis of chronic low back pain (CLBP).
DesignLongitudinal field study (baseline and 6-month follow-up).
SettingFour medical clinics across Germany.
Participants352 people were included according to the following criteria: (1) between 18 and 65 years of age, (2) intermittent pain and (3) an understanding of the study and the ability to answer a questionnaire without help. Exclusion criteria were: (1) pregnancy, (2) inability to stand upright, (3) inability to give sick leave information, (4) signs of serious spinal pathology, (5) acute pain in the past 7 days or (6) an incomplete SES indicators questionnaire.
Outcome measuresSubjective intensity and disability of CLBP.
ResultsAnalysis showed that job position was the best single predictor of CLBP intensity, followed by a multidimensional index. Education and income had no significant association with intensity. Subjective disability was best predicted by job position, succeeded by the multidimensional index and education, while income again had no significant association.
ConclusionThe results showed that SES indicators have different strong associations with the genesis of CLBP and should therefore not be used interchangeably. Job position was found to be the single most important indicator. These results could be helpful in the planning of back pain care programmes, but in general, more research on the relationship between SES and health outcomes is needed.
https://ift.tt/2jdHQe5
Educational differences in psychological distress? Results from a population-based sample of men and women in Sweden in 2012
Background
Mental health problems are more frequent in socially disadvantaged groups, but the results vary between different studies, different populations and different measures of mental health. This paper investigated the association between educational level, economic difficulties and psychological distress in men and women in Sweden.
MethodsThe study population included 24 510 respondents aged 25–74 years who responded to a survey questionnaire in Mid-Sweden in 2012 (response rate 53%). Psychological distress was measured with the 12-item version of the General Health Questionnaire, and multivariate logistic regression models were used in statistical analyses, adjusting for age, employment status and social support.
ResultsThe prevalence of psychological distress was higher in women (16.4%) than in men (11.3%; p<0.001). Persons with low and medium educational level had a lower risk of psychological distress than persons with high educational level after adjustment for confounders. Economic difficulties had a strong association with psychological distress (OR 2.80 (95% CI 2.39 to 3.27) and OR 2.40 (95% CI 2.12 to 3.71) in men and women, respectively) after adjustment for confounders.
ConclusionWe found a strong association between economic difficulties and psychological distress in this study, but no inverse association between educational level and psychological distress. On the contrary, persons with high education had more psychological distress than persons with low and medium education when age, employment status and social support were taken into account. The findings were similar in men and women.
https://ift.tt/2JAUWNM
Soil-transmitted helminth infections and nutritional status in Ecuador: findings from a national survey and implications for control strategies
Objective
The estimation of prevalence and intensity of soil-transmitted helminth (STH) infections at a country-level is an essential prerequisite for the implementation of a rational control programme. The aim of this present study was to estimate the prevalence and distribution of STH infections and malnutrition in school-age children in rural areas of Ecuador.
DesignCross-sectional study from October 2011 to May 2012.
SettingEighteen rural schools were randomly selected from the three ecological regions of Ecuador (coastal, highlands and Amazon basin).
Participants920 children aged 6–16 years.
Main outcome measuresPrevalence and intensity of STH infections associated with malnutrition (thinness/wasting or stunting).
ResultsThe results showed that 257 (27.9%) children were infected with at least one STH parasite. The prevalence of Trichuris trichiura, Ascaris lumbricoides and hookworm was 19.3%, 18.5% and 5.0%, respectively. Malnutrition was present in 14.2% of children and most common was stunting (12.3%). Compared with other regions, schoolchildren in the Amazon region had the highest STH prevalence (58.9%) of which a greater proportion of infections were moderate/heavy intensity (45.6%) and had the highest prevalence of malnutrition (20.4%). A positive association was observed between moderate to heavy infections with A. lumbricoides and malnutrition (adjusted OR 1.85, 95% CI 1.04 to 3.31, p=0.037).
ConclusionsOur estimate of the prevalence of STH infections of 27.9% at a national level in Ecuador is lower than suggested by previous studies. Our data indicate that schoolchildren living in the Amazon region have a greater risk of STH infection and stunting compared with children from other regions. The implementation of school-based preventive chemotherapy and nutritional supplement programmes within the Amazon region should be prioritised. Long-term control strategies require improvements in water, sanitation and hygiene.
https://ift.tt/2jeHELW
Spatial and temporal variation in the community prevalence of antibiotic resistance in Bangladesh: an integrated surveillance study protocol
Introduction
Increasing antibiotic resistance (ABR) in low-income and middle-income countries such as Bangladesh presents a major health threat. However, assessing the scale of the health risk is problematic in the absence of reliable data on the community prevalence of antibiotic-resistant bacteria. We describe the protocol for a small-scale integrated surveillance programme that aims to quantify the prevalence of colonisation with antibiotic-resistant bacteria and concentrations of antibiotic-resistant genes from a 'One Health' perspective. The holistic assessment of ABR in humans, animals and within the environment in urban and rural Bangladesh will generate comprehensive data to inform human health risk.
Methods and analysisThe study design focuses on three exposure-relevant sites where there is enhanced potential for transmission of ABR between humans, animals and the environment: (1) rural poultry-owning households, (2) commercial poultry farms and (3) urban live-bird markets. The comparison of ABR prevalence in human groups with high and low exposure to farming and poultry will enable us to test the hypothesis that ABR bacteria and genes from the environment and food-producing animals are potential sources of transmission to humans. Escherichia coli is used as an ABR indicator organism due to its widespread environmental presence and colonisation in both the human and animal gastrointestinal tract.
Ethics and disseminationThe study has been approved by the Institutional Review Board of the International Centre for Diarrhoeal Disease Research, Bangladesh, and Loughborough University Ethics Committee. Data for the project will be stored on the open access repository of the Centre for Ecology and Hydrology, Natural Environment Research Council. The results of this study will be published in peer-reviewed journals and presented at national and international conferences.
https://ift.tt/2JxFli2
Ongoing training of community health workers in low-income andmiddle-income countries: a systematic scoping review of the literature
Objectives
Understanding the current landscape of ongoing training for community health workers (CHWs) in low-income and middle-income countries (LMICs) is important both for organisations responsible for their training, as well as researchers and policy makers. This scoping review explores this under-researched area by mapping the current delivery implementation and evaluation of ongoing training provision for CHWs in LMICs.
DesignSystematic scoping review.
Data sourcesMEDLINE, Embase, AMED, Global Health, Web of Science, Scopus, ASSIA, LILACS, BEI and ERIC.
Study selectionOriginal studies focusing on the provision of ongoing training for CHWs working in a country defined as low income and middle income according to World Bank Group 2012 classification of economies.
ResultsThe scoping review found 35 original studies that met the inclusion criteria. Ongoing training activities for CHWs were described as supervision (n=19), inservice or refresher training (n=13) or a mixture of both (n=3). Although the majority of studies emphasised the importance of providing ongoing training, several studies reported no impact of ongoing training on performance indicators. The majority of ongoing training was delivered inperson; however, four studies reported the use of mobile technologies to support training delivery. The outcomes from ongoing training activities were measured and reported in different ways, including changes in behaviour, attitudes and practice measured in a quantitative manner (n=16), knowledge and skills (n=6), qualitative assessments (n=5) or a mixed methods approach combining one of the aforementioned modalities (n=8).
ConclusionsThis scoping review highlights the diverse range of ongoing training for CHWs in LMICs. Given the expansion of CHW programmes globally, more attention should be given to the design, delivery, monitoring and sustainability of ongoing training from a health systems strengthening perspective.
https://ift.tt/2jeIJmD
Systematic review of prediction models for delirium in the older adult inpatient
Objective
To identify existing prognostic delirium prediction models and evaluate their validity and statistical methodology in the older adult (≥60 years) acute hospital population.
DesignSystematic review.
Data sources and methodsPubMed, CINAHL, PsychINFO, SocINFO, Cochrane, Web of Science and Embase were searched from 1 January 1990 to 31 December 2016. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses and CHARMS Statement guided protocol development. Inclusion criteria: age >60 years, inpatient, developed/validated a prognostic delirium prediction model. Exclusion criteria: alcohol-related delirium, sample size ≤50. The primary performance measures were calibration and discrimination statistics. Two authors independently conducted search and extracted data. The synthesis of data was done by the first author. Disagreement was resolved by the mentoring author.
ResultsThe initial search resulted in 7,502 studies. Following full-text review of 192 studies, 33 were excluded based on age criteria (<60 years) and 27 met the defined criteria. Twenty-three delirium prediction models were identified, 14 were externally validated and 3 were internally validated. The following populations were represented: 11 medical, 3 medical/surgical and 13 surgical. The assessment of delirium was often non-systematic, resulting in varied incidence. Fourteen models were externally validated with an area under the receiver operating curve range from 0.52 to 0.94. Limitations in design, data collection methods and model metric reporting statistics were identified.
ConclusionsDelirium prediction models for older adults show variable and typically inadequate predictive capabilities. Our review highlights the need for development of robust models to predict delirium in older inpatients. We provide recommendations for the development of such models.
https://ift.tt/2Jw7WnG
Post-treatment surveillance testing of patients with colorectal cancer and the association with survival: protocol for a retrospective cohort study of the Surveillance, Epidemiology, and End Results (SEER)-Medicare database
Introduction
Although the colorectal cancer (CRC) mortality rate has significantly improved over the past several decades, many patients will have a recurrence following curative treatment. Despite this high risk of recurrence, adherence to CRC surveillance testing guidelines is poor which increases cancer-related morbidity and potentially, mortality. Several randomised controlled trials (RCTs) with varying surveillance strategies have yielded conflicting evidence regarding the survival benefit associated with surveillance testing. However, due to differences in study protocols and limitations of sample size and length of follow-up, the RCT may not be the best study design to evaluate this relationship. An observational comparative effectiveness research study can overcome the sample size/follow-up limitations of RCT designs while assessing real-world variability in receipt of surveillance testing to provide much needed evidence on this important clinical issue. The gap in knowledge that this study will address concerns whether adherence to National Comprehensive Cancer Network CRC surveillance guidelines improves survival.
Methods and analysisPatients with colon and rectal cancer aged 66–84 years, who have been diagnosed between 2002 and 2008 and have been included in the Surveillance, Epidemiology, and End Results-Medicare database, are eligible for this retrospective cohort study. To minimise bias, patients had to survive at least 12 months following the completion of treatment. Adherence to surveillance testing up to 5 years post-treatment will be assessed in each year of follow-up and overall. Binomial regression will be used to assess the association between patients' characteristics and adherence. Survival analysis will be conducted to assess the association between adherence and 5-year survival.
Ethics and disseminationThis study was approved by the National Cancer Institute and the Institutional Review Board of the University of Central Florida. The results of this study will be disseminated by publishing in the peer-reviewed scientific literature, presentation at national/international scientific conferences and posting through social media.
https://ift.tt/2jdHO5X
How long does it take to recover from a wisdom tooth extraction?
Removal of the wisdom teeth is a common dental surgery, and there is a variety of reasons for doing it. The most common reason is that there is not enough room in the mouth for the teeth to grow, which causes pain. This article looks at how long it takes to recover after having wisdom teeth out and how to speed it up.
https://ift.tt/2HZTgAj
Somatic mutations in neurons during aging and neurodegeneration
Abstract
The nervous system is composed of a large variety of neurons with a diverse array of morphological and functional properties. This heterogeneity is essential for the construction and maintenance of a distinct set of neural networks with unique characteristics. Accumulating evidence now indicates that neurons do not only differ at a functional level, but also at the genomic level. These genomic discrepancies seem to be the result of somatic mutations that emerge in nervous tissue during development and aging. Ultimately, these mutations bring about a genetically heterogeneous population of neurons, a phenomenon that is commonly referred to as "somatic brain mosaicism". Improved understanding of the development and consequences of somatic brain mosaicism is crucial to understand the impact of somatic mutations on neuronal function in human aging and disease. Here, we highlight a number of topics related to somatic brain mosaicism, including some early experimental evidence for somatic mutations in post-mitotic neurons of the hypothalamo-neurohypophyseal system. We propose that age-related somatic mutations are particularly interesting, because aging is a major risk factor for a variety of neuronal diseases, including Alzheimer's disease. We highlight potential links between somatic mutations and the development of these diseases and argue that recent advances in single-cell genomics and in vivo physiology have now finally made it possible to dissect the origins and consequences of neuronal mutations in unprecedented detail.
https://ift.tt/2jfylLC
The Effect of Psychosocial Interventions on Outcomes for Caregivers of Hematopoietic Cell Transplant Patients
Abstract
Purpose of Review
Hematopoietic cell transplant (HCT) patients are required to have a caregiver present for up to 100 days post-transplant. Caregivers provide essential support during HCT but experience immense stress and burden. Increasing research has developed interventions for HCT caregivers. This review systematically evaluates psychosocial interventions for caregivers of HCT patients.
Recent Findings
The search yielded 12 studies (7 efficacy and 5 feasibility studies) enrolling 931 caregivers. Interventions were feasible and acceptable as evidenced by high rates of completion (70–100%) with attrition due to patient morbidity or mortality. Feasibility was augmented by flexible delivery (in-person, teleconference, smartphones, or Web-based platforms). Acceptability was demonstrated by objective measures of satisfaction. Effectiveness was found for fatigue and mental health service use, but not for burden, sleep-quality, and inconsistently for caregiver depression, anxiety, coping, and quality of life.
Summary
Psychosocial interventions are feasible, acceptable, and show mixed effects on HCT caregiver outcomes.
https://ift.tt/2JCcf0V
Performance validation of an amplicon-based targeted next-generation sequencing assay and mutation profiling of 648 Chinese colorectal cancer patients
Abstract
Next-generation sequencing (NGS) has become a promising approach for tumor somatic mutation detection. However, stringent validation is required for its application on clinical specimens, especially for low-quality formalin-fixed paraffin-embedded (FFPE) tissues. Here, we validated the performance of an amplicon-based targeted NGS assay, OncoAim™ DNA panel, on both commercial reference FFPE samples and clinical FFPE samples of Chinese colorectal cancer (CRC) patients. Then we profiled the mutation spectrum of 648 Chinese CRC patients in a multicenter study to explore its clinical utility. This NGS assay achieved 100% test specificity and 95–100% test sensitivity for variants with mutant allele frequency (MAF) ≥ 5% when median read depth ≥ 500×. The orthogonal methods including amplification refractory mutation system (ARMS)-PCR and Sanger sequencing validated that NGS generated three false negatives (FNs) but no false positives (FPs) among 516 clinical samples for KRAS aberration detection. Genomic profiling of Chinese CRC patients with this assay revealed that 63.3% of the tumors harbored clinically actionable alterations. Besides the commonly mutated genes including TP53 (52.82%), KRAS (46.68%), APC (24.09%), PIK3CA (18.94%), SMAD4 (9.47%), BRAF (6.15%), FBXW7 (5.32%), and NRAS (4.15%), other less frequently mutated genes were also identified. Statistically significant association of specific mutated genes with certain clinicopathological features was detected, e.g., both BRAF and PIK3CA were more prevalent in right-side CRC (p < 0.001 and p = 0.002, respectively). We concluded this targeted NGS assay is qualified for clinical practice, and our findings could help the diagnosis and prognosis of Chinese CRC patients.
https://ift.tt/2r7L7iP
Analysis of the correlation between non-alcoholic fatty liver disease and bone metabolism indicators in healthy middle-aged men
L'articolo Analysis of the correlation between non-alcoholic fatty liver disease and bone metabolism indicators in healthy middle-aged men sembra essere il primo su European Review.
https://ift.tt/2HzcYn5
Linc-ROR promotes endometrial cell proliferation by activating the PI3K-Akt pathway
OBJECTIVE: To observe the expressions of Linc-ROR and proteins in the PI3K-Akt pathway in an ectopic lesion of adenomyosis.
PATIENTS AND METHODS: The expression of Linc-ROR in the ectopic endometrium, eutopic endometrium, and normal endometrium of adenomyosis was detected by qRT-PCR. Western blot was used to detect the protein expressions of PI3K-Akt in endometriosis and lesion endometriosis. Cell counting kit-8 (CCK-8) assay was utilized to detect cell proliferative activity. After interfering or overexpressing Linc-ROR, protein expressions of the PI3K-Akt pathway were detected by Western blot.
RESULTS: Linc-ROR expression in the ectopic endometrium of adenomyosis was higher than that in the eutopic endometrium and normal endometrium, and the expression level of PTEN in adenomyosis tissues was decreased, whilst expression levels of Akt, p-Akt, p-PTEN were increased. Clinical data of enrolled patients indicated that there was a relationship between Linc-ROR expression and the type and severity of dysmenorrhea of adenomyosis. However, no relationship was observed between Linc-ROR expression and age, cesarean section, uterine surgery, and menstrual cycle. Cell counting kit-8 (CCK-8) assay showed that the proliferative activity of cells was significantly decreased after knockdown of Linc-ROR in the adenomyosis cells. Western blot revealed that the expression level of PTEN increased but the expression levels of p-Akt, p-PTEN and p-PDK1 decreased. Overexpression of Linc-ROR obtained the opposite results.
CONCLUSIONS: Linc-ROR is highly expressed in the ectopic endometrium of adenomyosis, and it can promote the proliferative activity of endometrial cells by activating the PI3K-Akt pathway.
L'articolo Linc-ROR promotes endometrial cell proliferation by activating the PI3K-Akt pathway sembra essere il primo su European Review.
https://ift.tt/2HwTsHM
The influencing mechanism of mTOR signal pathway mediated by mitofusin-2 in development of follicle
OBJECTIVE: To investigate the influencing mechanism of mammalian target of rapamycin (mTOR) signal pathway mediated by mitofusin-2 (Mfn2) in the development of follicle.
MATERIALS AND METHODS: We selected 20 healthy Sprague Dawley (SD) female rats aging between 6 and 8 weeks were divided into the control group and the polycystic ovarian syndrome (PCOS) model group. Rats in PCOS group received the lavage using 0.4 mL 1% carboxymethyl cellulose solution containing letrozole (1 mg/kg/d) consecutively for 20 to 25d. We compared the body weight and ovary weight of rats, and detected levels of sera E2, T, P, FSH and LH through RIA measurement. We also observed the histological morphology of ovary through hematoxylin eosin (HE) staining, as well as the positive expression and location of rMfn2 through immunohistochemistry staining. Finally, we detected the expressions of mTOR, p-Akt, β-catenin, caspase-3, Bcl-2 and Bax in Mfn2 and mTOR signal pathways in the tissues through RT-PCR and Western blot assay.
RESULTS: In the PCOS group, the body weight of rats was lower than that of the control group, but the ovary weight of rats was higher than that in the control group. The levels of T and LH in serum were elevated, the levels of E2, P and FSH were decreased (p < 0.05). In the model group, typical polycystic changes were observed in the rats under the microscope, but no corpus luteum was observed, and a significant decrease was identified in the layers of the granular cell of the follicle. Mfn2 was widely expressed in the granular cells of the ovary, follicular fluid, inner theca cells, corpus luteum, and ovarian stroma. However, the expression in the outer theca cells was relatively low. In the observation group, the positive expression rate of Mfn2 was significantly lower (p < 0.05) than that in the control group. In the PCOS group, the mRNA and protein relative expression levels of mTOR, p-Akt, β-catenin, and Bcl-2 were significantly lower (p < 0.05) than those in the control group. Conversely, the levels of caspase-3 and Bax were significantly higher (p < 0.05) than those in the control group.
CONCLUSIONS: Downregulated expression of Mfn2 may affect the regular development of follicle through the mediation of mTOR signal pathway.
L'articolo The influencing mechanism of mTOR signal pathway mediated by mitofusin-2 in development of follicle sembra essere il primo su European Review.
https://ift.tt/2r1FpPo
MiR-134 inhibits infiltration of trophoblast cells in placenta of patients with preeclampsia by decreasing ITGB1 expression
OBJECTIVE: Preeclampsia (PE) is an idiopathic disorder of pregnancy. The specific regulatory mechanisms of microRNAs (miRs) in the placenta of PE patients have not yet been completely revealed. This study mainly explored the mechanism of miR-134 in preeclampsia.
PATIENTS AND METHODS: Real-time PCR and Western blot were used to detect the expression of miR-134 and ITGB1 in the placenta of patients with preeclampsia and normal pregnant women. Dual luciferase reporter assay was performed to detect luciferase activity in miR-134 and NC groups, respectively. Cell proliferation ability after transfection was evaluated by MTS colorimetric assay, and the effect of miR-134 on the infiltration of trophoblast cells was explored by cell invasion experiment. In addition, co-transfection of miR-134 and ITGB1 expression plasmids was carried out, and then changes in the cell invasiveness were also detected by cell invasion experiment.
RESULTS: Compared with placenta of normal pregnant women, miR-134 was significantly up-regulated in the placenta of patients with preeclampsia and negatively correlated with the expression of ITGB1. MiR-134 suppressed the infiltration of trophoblast cells by targeting ITGB1. When ITGB1 was overexpressed, the suppression of invasiveness of trophoblast cells by miR-134 was almost abolished. Meanwhile, we found that miR-134 inhibitor could promote the invasiveness of trophoblast cells. In addition, tumor necrosis factor-α (TNF-α) was found to enhance miR-134 expression as well as inhibit ITGB1 expression.
CONCLUSIONS: MiR-134 inhibited the infiltration of trophoblast cells in preeclampsia by down-regulating ITGB1 expression.
L'articolo MiR-134 inhibits infiltration of trophoblast cells in placenta of patients with preeclampsia by decreasing ITGB1 expression sembra essere il primo su European Review.
https://ift.tt/2HAjsCl
Relation between mycoplasma infection and recurrent spontaneous abortion
OBJECTIVE: This study explores the possible relation between cervical infections with Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) and the occurrence of recurrent spontaneous abortion (RSA).
PATIENTS AND METHODS: 132 patients with RSA (observation group) and 96 normal pregnancy volunteers undergoing planned abortions (control group) were selected successively and enrolled in the investigation. Cervical secretion samples were obtained for each subject. Bacterial cultures were started to detect UU, MH and other bacterial infections, and fluorescence quantitative PCR was used to detect gene copy number in chorion and decidual tissues. Additionally, ELISA (enzyme-linked immunosorbent assay) was used to detect anticardiolipin antibody (ACA) to rate positivity of Immunoglobulin M (IgM) and IgG in secretions, and Western blot was applied to quantify the expression levels of Interleukin (IL)-6, tumor necrosis factor-α (TNF-α), prostacyclin (PGI2) and bax/bcl-2.
RESULTS: Our results showed the UU, MH, and overall bacterial infection rate of chorionic and decidual tissues, and the gene copy number of UU, MH were higher in the observation group than those in the control group (p<0.05). Moreover, the ACA-IgM and IgG positive rates in secretions of the observation group were significantly higher than those in the control group (p<0.05). Finally, the expression levels of IL-6, TNF-α, PGI2, and bax/bcl-2 were higher than those in the control group as well (p<0.05).
CONCLUSIONS: Our results support the notion that RSA might be associated with UU and MH infection, could influence the occurrence of other bacterial infections and could stimulate ACA expression, inflammatory response, thrombogenesis, and factors associated with cell apoptosis, increasing the risk for an abortion during pregnancy.
L'articolo Relation between mycoplasma infection and recurrent spontaneous abortion sembra essere il primo su European Review.
https://ift.tt/2r6O5nF
Cardiac magnetic resonance in systemic sclerosis patients with cardiac symptoms: do we really need it?
L'articolo Cardiac magnetic resonance in systemic sclerosis patients with cardiac symptoms: do we really need it? sembra essere il primo su European Review.
https://ift.tt/2HAR7LO
Titanium alloy vs. stainless steel miniscrews: an in vivo split-mouth study
OBJECTIVE: To compare in vivo Titanium Alloy (TiA) with Stainless Steel (SS) miniscrews Temporary Anchorage Devices (TADs) using removal torque and Scanning Electron Microscopic (SEM) analysis.
PATIENTS AND METHODS: 15 subjects (6 males and 9 females) who required maximum anchorage were recruited. For each patient, a TiA TAD and a SS TAD with same length and width were implanted following a randomized split-mouth study design. Retraction was carried out with nickel-titanium spring ligated directly from the anterior hooks of the archwire to the TADs to produce 90 to 100 g of force. When no further anchorage supplementation was needed, the TADs were removed. The removal torque values were registered with a digital screwdriver. After removal, the TADs were collected in a fixed solution and examined using SEM and X-ray microanalysis.
RESULTS: All TADs remained intact, with a 100% success rate. There was no difference in removal torque between TiA and SS miniscrews (4.4 ± 1.3 N-cm and 5.1 ± 0.7 N-cm, respectively). All specimens' loss of gloss with signs of biological contaminations resulted in a dull implant surface. SEM photomicrographs of TiA miniscrews showed predominantly blood cells while SS miniscrews showed the precipitation of an amorphous layer with low cellular component. There was no difference in spectroscopic analysis between TiA and SS miniscrews.
CONCLUSIONS: TiA and SS miniscrews had comparable removal torque values. SEM photomicrographs showed no evidence of osseointegration with both TADs having similar biological responses.
L'articolo Titanium alloy vs. stainless steel miniscrews: an in vivo split-mouth study sembra essere il primo su European Review.
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Upregulation of long non-coding RNA HNF1A-AS1 is associated with poor prognosis in urothelial carcinoma of the bladder
OBJECTIVE: Long noncoding RNAs (lncRNAs) play important roles in the pathogenesis of bladder cancer. A recent study reported that lncRNA HNF1A-AS1 (HNF1A-AS1) was upregulated in urothelial carcinoma of the bladder (UCB) and served as a tumor promoter. However, the clinical significance of HNF1A-AS1 in the prognosis of patients with UCB was poorly understood. This work was designed to investigate the relationship between HNF1A-AS1 expression level and the prognosis of UCB.
PATIENTS AND METHODS: Relative expression levels of HNF1A-AS1 in UCB tissues were determined by qRT-PCR. Then, the associations between HNF1A-AS1 expression and clinical pathological parameters were further evaluated. Survival and Cox proportional-hazards regression analyses were performed to determine the correlation between HNF1A-AS1 expression levels and prognosis in the patients.
RESULTS: Data showed that the majority of UCB tissues showed higher HNF1A-AS1 levels than the corresponding normal tissues controls (p < 0.01). Statistical assay revealed that high HNF1A-AS1 expression was significantly correlated with histological grade (p = 0.008), tumor stage T (p = 0.003) and lymph nodes metastasis (p = 0.007). In addition, the overall survival time of patients with high HNF1A-AS1 expression was significantly shorter compared to those with low HNF1A-AS1 expression. Furthermore, multivariate analysis confirmed that relative HNF1A-AS1 expression was an independent predictor of overall survival in patients with UCB.
CONCLUSIONS: HNF1A-AS1 expression was upregulated in UCB, and it may be a useful prognostic biomarker for patients with UCB.
L'articolo Upregulation of long non-coding RNA HNF1A-AS1 is associated with poor prognosis in urothelial carcinoma of the bladder sembra essere il primo su European Review.
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MicroRNA-9 enhances invasion and migration of cervical carcinomas by directly targeting FOXO1
OBJECTIVE: Cervical carcinoma is the third frequently diagnosed cancer among women worldwide. Increasing evidence suggests that dysfunctions of miRNAs are involved in human cancers and could act as either tumor suppressors or oncogenes. The purpose of this study is to elucidate pathobiological functions of miR-9 expression by targeting FOXO1 in cervical carcinoma.
PATIENTS AND METHODS: Real-time-PCR was utilized to detect miR-9 and FOXO1 level in cervical carcinoma tissues and cells. Transwell assays were employed to check out the roles of miR-9 on cells invasive and migratory potency. Luciferase reporter and Western blot were applied to verify FOXO1 as a target gene of miR-9.
RESULTS: The results showed that miR-9 was significantly high expressed in cervical carcinoma cell lines and clinical tissues. miR-9 enhanced the ability of migration and invasion of C33A and HeLa cells. FOXO1 was confirmed as the direct target of miR-9, and miR-9 over-expression down-regulated the expression level of FOXO1.
CONCLUSIONS: Our data demonstrate that miR-9 enhances invasion and migration of cervical carcinomas by directly targeting FOXO1. This may lead to a modern therapeutic strategy for the treatment of cervical carcinomas.
L'articolo MicroRNA-9 enhances invasion and migration of cervical carcinomas by directly targeting FOXO1 sembra essere il primo su European Review.
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The prognostic role of platelet to lymphocyte ratio and mean platelet volume in critically ill patients
OBJECTIVE: The aim of this study was to identify the relationship between complete blood count parameters, mean platelet volume (MPV), and platelet to lymphocyte ratio (PLR) with mortality and hospitalization duration in critically ill patients.
PATIENTS AND METHODS: A retrospective analysis was made of patients admitted to our tertiary adult i̇ntensive Care Unit (ICU) between January 2015 and January 2016. Hemoglobin (Hb), white blood cell (WBC), lymphocyte and platelet counts were obtained from the complete blood count performed at the time of admission. MPV and PLR levels were calculated from these data. Other data were retrieved from the patient follow-up records.
RESULTS: The investigation included a total of 306 patients. The total mortality rate was 40.2%. The initial median PLR level was 206.7 (8.1-1675.0) for non-survivor patients and 194.5 (12.8-1236.6) for survivor patients. The PLR level was higher in the non-survivor group, but there was no statistically significant difference between the groups (p>0.05). The median MPV level was 7.66 (5.17-15.25) for the survivors and 8.09 (4.36-16.19) for the non-survivors, and there was no statistically significant difference between the groups (p=0.237). The median length of stay (LOS) of all patients was 7 (2-61) days. Only the Acute Physiology and Chronic Health Evaluation (APACHE) II score was found to have a positive correlation with LOS (p<0.05).
CONCLUSIONS: PLR has no effect on mortality rates regardless of whether the patient has thrombocytopenia or not at the time of admission. MPV levels have no significant relationship with mortality. Neither MPV nor PLR have an effect on LOS. The use of these as a prognostic factor for mortality in critically ill patients is still unclear.
L'articolo The prognostic role of platelet to lymphocyte ratio and mean platelet volume in critically ill patients sembra essere il primo su European Review.
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Cancers, Vol. 10, Pages 128: Targeting Epigenetic Aberrations in Pancreatic Cancer, a New Path to Improve Patient Outcomes?
Cancers, Vol. 10, Pages 128: Targeting Epigenetic Aberrations in Pancreatic Cancer, a New Path to Improve Patient Outcomes?
Cancers doi: 10.3390/cancers10050128
Authors: Brooke D. Paradise Whitney Barham Martín E. Fernandez-Zapico
Pancreatic cancer has one of the highest mortality rates among all types of cancers. The disease is highly aggressive and typically diagnosed in late stage making it difficult to treat. Currently, the vast majority of therapeutic regimens have only modest curative effects, and most of them are in the surgical/neo-adjuvant setting. There is a great need for new and more effective treatment strategies in common clinical practice. Previously, pathogenesis of pancreatic cancer was attributed solely to genetic mutations; however, recent advancements in the field have demonstrated that aberrant activation of epigenetic pathways contributes significantly to the pathogenesis of the disease. The identification of these aberrant activated epigenetic pathways has revealed enticing targets for the use of epigenetic inhibitors to mitigate the phenotypic changes driven by these cascades. These pathways have been found to be responsible for overactivation of growth signaling pathways and silencing of tumor suppressors and other cell cycle checkpoints. Furthermore, new miRNA signatures have been uncovered in pancreatic ductal adenocarcinoma (PDAC) patients, further widening the window for therapeutic opportunity. There has been success in preclinical settings using both epigenetic inhibitors as well as miRNAs to slow disease progression and eliminate diseased tissues. In addition to their utility as anti-proliferative agents, the pharmacological inhibitors that target epigenetic regulators (referred to here as readers, writers, and erasers for their ability to recognize, deposit, and remove post-translational modifications) have the potential to reconfigure the epigenetic landscape of diseased cells and disrupt the cancerous phenotype. The potential to “reprogram” cancer cells to revert them to a healthy state presents great promise and merits further investigation.
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Analysis of the correlation between non-alcoholic fatty liver disease and bone metabolism indicators in healthy middle-aged men
L'articolo Analysis of the correlation between non-alcoholic fatty liver disease and bone metabolism indicators in healthy middle-aged men sembra essere il primo su European Review.
https://ift.tt/2HzcYn5
Free fatty acids mediates human umbilical vein endothelial cells inflammation through toll-like receptor-4
OBJECTIVE: To investigate the role of Toll-like receptor-4 (TLR4) in the free fatty acids (FFAs) induced human umbilical vein endothelial cells (HUVECs) inflammation and to explore the underlying mechanisms.
MATERIALS AND METHODS: HUVECs and HEK293 cell lines were obtained from Shanghai Type Culture Collection. Cell counting kit-8 (CCK8) and flow cytometry (FCM) were performed to examine the cell viability and apoptosis rate of HUVECs induced by FFAs treatments with or without infection of toll-like receptor-4 interference (TLR4i) adenovirus. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the inflammatory cytokines release. Quantitative polymerase chain reaction (qPCR) and Western Blot (WB) were used to test the molecular mechanisms of inflammation.
RESULTS: FFAs induced inflammatory responses in HUVECs via modulating the TLR4 receptor complex. TLR4i adenovirus interference increased cell viability and decreased cell apoptosis rate. FFAs treatments significantly increased the expressions of inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), C-C motif chemokine ligand 5 (CCL5) and CXC chemokine ligand 10 (CXCL10), while TLR4i adenovirus interference significantly reduced these cytokines levels. TLR4-mediated myeloid differential protein-88 (MyD88) expression activating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and inhabiting kappa B kinase-beta (IKK-β). TLR4i adenovirus interference decreased the expressions of these genes at both mRNA level and protein level.
CONCLUSIONS: TLR4 mediates FFAs induced inflammatory responses in HUVECs. TLR4 interference in HUVECs significantly reduces the inflammatory cytokines expression, decreases the cell apoptosis rate and increases cell viability.
L'articolo Free fatty acids mediates human umbilical vein endothelial cells inflammation through toll-like receptor-4 sembra essere il primo su European Review.
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The effect of miR-146a gene silencing on drug-resistance and expression of protein of P-gp and MRP1 in epilepsy
OBJECTIVE: To investigate the effect of miR-146a gene silencing on brain tissue and related drug-resistance proteins in rats and explore its resistance mechanism.
MATERIALS AND METHODS: A rat model of chronic refractory epilepsy was established. The rats were divided into four groups: Normal group, Model group, Negative control group and AntagomiR-146a group. Hematoxylin and eosin (HE) stain was used to detect brain histopathological changes. We examined the expression of mRNA of miR-146a, multidrug resistance (MDR1) and multidrug-resistant associated protein (MRP1) by RT-PCR. The expressions of protein of High motility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear transcription factor-κB (NF-κB) pathway and P-glycoprotein (P-gp), MRP1 were detected by Western-blotting.
RESULTS: We demonstrated that the pathological lesion was lighter in antagomiR-146a group compared with the model group. The mRNA expression of miR-146a in AntagomiR-146a group was significantly decreased compared to the model group. Furthermore, the mRNA expression of MDR1 and MRP1 in AntagomiR-146a group was lower than that in the model group. In addition, the protein expression of HMGB1, TLR4, NF-κB and P-gp, MRP1 in AntagomiR-146a group was lower than that in model group.
CONCLUSIONS: These results demonstrated that miR-146a gene silencing can attenuate pathological changes and improve drug resistance in refractory epilepsy. Also, it is closely related to the HMGB1/TLR4/NF-κB signaling pathway regulation.
L'articolo The effect of miR-146a gene silencing on drug-resistance and expression of protein of P-gp and MRP1 in epilepsy sembra essere il primo su European Review.
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Interobserver Variability of Sonographic Features Used in the American College of Radiology Thyroid Imaging Reporting and Data System
American Journal of Roentgenology, Ahead of Print.
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A Women in Radiology Group Fosters Career Development for Faculty and Trainees
American Journal of Roentgenology, Ahead of Print.
https://ift.tt/2HyHQ7h
A Third-Generation Adaptive Statistical Iterative Reconstruction Technique: Phantom Study of Image Noise, Spatial Resolution, Lesion Detectability, and Dose Reduction Potential
American Journal of Roentgenology, Ahead of Print.
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Percutaneous Ablation for Hepatocellular Carcinoma
American Journal of Roentgenology, Ahead of Print.
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VIDEO: Preoperative CT Angiography for Fibular Free Flap Reconstructions
American Journal of Roentgenology, Ahead of Print.
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Skeletal Metastases and Benign Mimics on NaF PET/CT: A Pictorial Review
American Journal of Roentgenology, Ahead of Print.
https://ift.tt/2r7cU2D
Comparing the Diagnostic Accuracy of Ultrasound and CT in Evaluating Acute Cholecystitis
American Journal of Roentgenology, Ahead of Print.
https://ift.tt/2r6Jm5z
Is Prostate Imaging Reporting and Data System Version 2 Sufficiently Discovering Clinically Significant Prostate Cancer? Per-Lesion Radiology-Pathology Correlation Study
American Journal of Roentgenology, Ahead of Print.
https://ift.tt/2Hwv1KF
Static and Functional MR Urography to Assess Congenital Anomalies of the Kidney and Urinary Tract in Infants and Children: Comparison With MAG3 Renal Scintigraphy and Sonography
American Journal of Roentgenology, Ahead of Print.
https://ift.tt/2r6PwCG
Circulating UCA1 is highly expressed in patients with systemic lupus erythematosus and promotes the progression through the AKT pathway
OBJECTIVE: To investigate the role of Urothelial Carcinoma Associated 1 (UCA1) during the progression of systemic lupus erythematosus (SLE) and the underlying mechanism.
PATIENTS AND METHODS: UCA1 expression in peripheral blood of SLE patients, as well as the expression of protein kinase B (AKT) in the peripheral blood mononuclear cell (PBMC), was detected by qRT-PCR. Expression differences in UCA1 and AKT between different groups were compared by t-test or univariate analysis. Through correlation analysis, the correlation between UCA1, AKT and clinical indicators of patients was analyzed. After overexpression and knockout of UCA1, the effect on phenotypes of BaF3 cell was examined. Finally, we analyzed the correlation between AKT and UCA1, and the effect on AKT pathway after overexpression and knockout of UCA1.
RESULTS: We found that plasma level of UCA1 and AKT was significantly enhanced in SLE patients. By analyzing the clinical data, a higher UCA1 level was observed in female patients than in males. In addition, UCA1 level in SLE patients with active stage and pathological lesions was higher than those in a stable stage without organ involvement. Correlation analysis showed that there was a positive correlation between UCA1 and C3, anti-ds-DNA, ESR and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Similarly, there was a positive correlation between AKT and C3, anti-ds-DNA, erythrocyte sedimentation rate (ESR) and SLEDAI, respectively. After overexpression and knockdown of UCA1, it was found that overexpression of UCA1 significantly enhanced cell proliferation, while the interference with UCA1 significantly inhibited cell proliferation. Western blot revealed increased expressions of PI3K and AKT after overexpressing UCA1, whereas knockdown of UCA1 led significantly decreased expressions of PI3K and AKT.
CONCLUSIONS: UCA1 expression was significantly increased in SLE, which promoted the progression of SLE by activating AKT pathway.
L'articolo Circulating UCA1 is highly expressed in patients with systemic lupus erythematosus and promotes the progression through the AKT pathway sembra essere il primo su European Review.
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High-depth whole genome sequencing of an Ashkenazi Jewish reference panel: enhancing sensitivity, accuracy, and imputation
Abstract
While increasingly large reference panels for genome-wide imputation have been recently made available, the degree to which imputation accuracy can be enhanced by population-specific reference panels remains an open question. Here, we sequenced at full-depth (≥ 30×), across two platforms (Illumina X Ten and Complete Genomics, Inc.), a moderately large (n = 738) cohort of samples drawn from the Ashkenazi Jewish population. We developed a series of quality control steps to optimize sensitivity, specificity, and comprehensiveness of variant calls in the reference panel, and then tested the accuracy of imputation against target cohorts drawn from the same population. Quality control (QC) thresholds for the Illumina X Ten platform were identified that permitted highly accurate calling of single nucleotide variants across 94% of the genome. QC procedures also identified numerous regions that are poorly mapped using current reference or alternate assemblies. After stringent QC, the population-specific reference panel produced more accurate and comprehensive imputation results relative to publicly available, large cosmopolitan reference panels, especially in the range of rare variants that may be most critical to further progress in mapping of complex phenotypes. The population-specific reference panel also permitted enhanced filtering of clinically irrelevant variants from personal genomes.
https://ift.tt/2HyIDF0
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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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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
