https://ift.tt/2EZaQ1Q
Τετάρτη 18 Απριλίου 2018
Time Out — Charting a Path for Improving Performance Measurement
https://ift.tt/2EZaQ1Q
Making Sense of Triple Inhaled Therapy for COPD
Guidelines for the treatment of chronic obstructive pulmonary disease (COPD) have consistently recommended long-acting inhaled bronchodilators — either long-acting muscarinic antagonists (LAMAs) or long-acting inhaled beta-agonists (LABAs) — as initial maintenance therapy. If disease control is not…
https://ift.tt/2JW9s3K
Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD
https://ift.tt/2HaYjdy
Infantile Spasms—Have We Made Progress?
Abstract
Purpose of the Review
The care of children with infantile spasms is full of areas of ambiguity, despite practice parameters and randomized trials. This review is to update the current care of children with infantile spasms.
Recent Findings
Several recent studies have generated new data to guide management including a randomized trial supporting combination therapy of hormone treatment and vigabatrin as an initial treatment for infantile spasms. Studies have suggested that we are not consistent in our recognition of hypsarrhythmia, while additional studies suggest that the presence or absence of this pattern may not have any predictive value. Additionally, the use of appropriate medications as well as an early diagnosis has the most impact on short-term outcomes.
Summary
Children with infantile spasms benefit most from early diagnosis and early treatment with appropriate standard medications such as hormonal therapy (ACTH or prednisolone) or vigabatrin.
https://ift.tt/2HASU2T
CD47 is a novel potent immunotherapy target in human malignancies: current studies and future promises
Future Oncology, Ahead of Print.
https://ift.tt/2qJw5Qc
Stonewall and Brickwall: Two Partially Redundant Determinants Required for the Maintenance of Female Germline in Drosophila
Proper specification of germline stem cells (GSCs) in Drosophila ovaries depends on niche derived non-autonomous signaling and cell autonomous components of transcriptional machinery. Stonewall (Stwl), a MADF-BESS family protein, is one of the cell intrinsic transcriptional regulators involved in the establishment and/or maintenance of GSC fate in Drosophila ovaries. Here we report identification and functional characterization of another member of the same protein family, CG3838/Brickwall (Brwl) with analogous functions. Loss of function alleles of brwl exhibit age dependent progressive degeneration of the developing ovarioles and loss of GSCs. Supporting the conclusion that the structural deterioration of mutant egg chambers is a result of apoptotic cell death, activated caspase levels are considerably elevated in brwl- ovaries. Moreover, as in the case of stwl mutants, on several instances, loss of brwl activity results in fusion of egg chambers and misspecification of the oocyte. Importantly, brwl phenotypes can be partially rescued by germline specific over-expression of stwl arguing for overlapping yet distinct functional capabilities of the two proteins. Taken together with our phylogenetic analysis, these data suggest that brwl and stwl likely share a common MADF-BESS ancestor and they are expressed in overlapping spatiotemporal domains to ensure robust development of the female germline.
https://ift.tt/2qJEtiy
Warming "Cold" Melanoma with TLR9 Agonists [News in Depth]
Responses seen in patients resistant to PD-1 blockade alone, when CMP-001 or SD-101 is added.
https://ift.tt/2J7F1WS
Rho Kinase Inhibition by AT13148 Blocks Pancreatic Ductal Adenocarinoma Invasion and Tumor Growth
The high mortality of pancreatic cancer demands that new therapeutic avenues be developed. The orally available small molecule inhibitor AT13148 potently inhibits ROCK1 and ROCK2 kinases that regulate the actomyosin cytoskeleton. We previously reported that ROCK kinase expression increases with human and mouse pancreatic cancer progression and that conditional ROCK activation accelerates mortality in a genetically modified LSL-KrasG12D; LSL-p53R172H; Pdx1-Cre; (KPC) mouse pancreatic cancer model. In this study, we show that treatment of KPC mouse and human TKCC5 patient-derived pancreatic tumor cells with AT13148, as well as the ROCK selective inhibitors Y27632 and H1152, act comparably in blocking ROCK substrate phosphorylation. AT13148, Y27632, and H1152 induced morphological changes and reduced cellular contractile force generation, motility on pliable discontinuous substrates, and three-dimensional collagen matrix invasion. AT13148 treatment reduced subcutaneous tumor growth and blocked invasion of healthy pancreatic tissue by KPC tumor cells in vivo without affecting proliferation, suggesting a role for local tissue invasion as a contributor to primary tumor growth. These results suggest that AT13148 has anti-tumor properties that may be beneficial in combination therapies or in the adjuvant setting to reduce pancreatic cancer cell invasion and slow primary tumor growth. AT13148 might also have the additional benefit of enabling tumor resection by maintaining separation between tumor and healthy tissue boundaries.
https://ift.tt/2H9YoC8
YAP/TAZ initiates gastric tumorigenesis via upregulation of MYC
YAP and TAZ play oncogenic roles in various organs, but the role of YAP/TAZ in gastric cancer remains unclear. Here we show that YAP/TAZ activation initiates gastric tumorigenesis in vivo and verify its significance in human gastric cancer. In mice, YAP/TAZ activation in the pyloric stem cell led to step-wise tumorigenesis. RNA sequencing identified MYC as a decisive target of YAP, which controls MYC at transcriptional and post-transcriptional levels. These mechanisms tightly regulated MYC in homeostatic conditions, but YAP activation altered this balance by impeding miRNA processing, causing a shift towards MYC upregulation. Pharmacological inhibition of MYC suppressed YAP-dependent phenotypes in vitro and in vivo, verifying its functional role as a key mediator. Human gastric cancer samples also displayed a significant correlation between YAP and MYC. We re-analyzed human transcriptome data to verify enrichment of YAP signatures in a subpopulation of gastric cancers and found that our model closely reflected the molecular pattern of patients with high YAP activity. Overall, these results provide genetic evidence of YAP/TAZ as oncogenic initiators and drivers for gastric tumors with MYC as the key downstream mediator. These findings are also evident in human gastric cancer, emphasizing the significance of YAP/TAZ signaling in gastric carcinogenesis.
https://ift.tt/2qHwnXu
Enhancer remodeling and microRNA alterations are associated with acquired resistance to ALK inhibitors
Anaplastic lymphoma kinase (ALK) inhibitors are highly effective in ALK fusion-positive lung cancer patients, but acquired resistance invariably emerges. Identification of secondary mutations has received considerable attention, but most cases cannot be explained by genetic causes alone, raising the possibility of epigenetic mechanisms in acquired drug resistance. Here we investigated the dynamic changes in the transcriptome and enhancer landscape during development of acquired resistance to ALK inhibitors. Histone H3 lysine 27 acetylation (H3K27ac) was profoundly altered during acquisition of resistance, and enhancer remodeling induced expression changes in both miRNAs and mRNAs. Decreased H3K27ac levels and reduced miR-34a expression associated with the activation of target genes such as AXL. Panobinostat, a pan-histone deacetylase inhibitor, altered the H3K27ac profile and activated tumor suppressor miRNAs such as miR-449, another member of the miR-34 family, and synergistically induced anti-proliferative effects with ALK inhibitors on resistant cells, xenografts, and EML4-ALK transgenic mice. Paired analysis of patient samples before and after treatment with ALK inhibitors revealed that repression of miR-34a or miR-449a and activation of AXL were mutually exclusive of secondary mutations in ALK. Our findings indicate that enhancer remodeling and altered expression of miRNAs play key roles in cancer drug resistance and suggest that strategies targeting epigenetic pathways represent a potentially effective method for overcoming acquired resistance to cancer therapy.
https://ift.tt/2Heahaf
Multi-kinase inhibitor CT-707 targets liver cancer by interrupting the hypoxia-activated IGF-1R-YAP axis
Given that YAP signaling acts as a critical survival input for hypoxic cancer cells in hepatocellular carcinoma (HCC), disruption of YAP function and the maintenance of hypoxia is an attractive way to treat HCC. Utilizing a cell-based YAP-TEAD luciferase reporter assay and functional analyses, we identified CT-707, a China-FDA approved multi-kinase inhibitor under clinical trial with remarkable inhibitory activity against YAP function. CT-707 exhibited prominent cytotoxicity under hypoxia on HCC cells, which was attributable to the inhibition of YAP signaling. CT-707 arrested tumor growth in HepG2-, Bel-7402-, and HCC patient-derived xenografts. Mechanistically, the inhibitory activity of CT-707 on YAP signaling was due to the interruption of hypoxia-activated IGF-1R. Overall, these findings not only identify CT-707 as a promising hypoxia-targeting agent against HCC, but they also unveil IGF-1R as a new modulator specifically regulating hypoxia-activated YAP signaling.
https://ift.tt/2qHwhPC
Silencing of long non-coding RNA MIR22HG triggers cell survival/death signaling via oncogenes YBX1, MET, and p21 in lung cancer
The long non-coding RNA (lncRNA) MIR22HG has previously been identified as a prognostic marker in hepatocellular carcinoma. Here we performed a comprehensive analysis of lncRNA expression profiles from RNA-seq data and report that MIR22HG plays a similar role in lung cancer. Analysis of 918 lung cancer and normal lung tissues and lung cancer cell lines revealed that MIR22HG was significantly downregulated in lung cancer; this decreased expression was associated with poor patient survival. MIR22HG bound and stabilized the YBX1 protein. Silencing of MIR22HG triggered both cell survival and cell death signaling through dysregulation of the oncogenes YBX1, MET, and p21. In this MIR22HG network, p21 played an oncogenic role by promoting cell proliferation and anti-apoptosis in lung cancers. MIR22HG played a tumor suppressor role as indicated by inhibition of multiple cell cycle-related genes in human primary lung tumors. These data show that MIR22HG has potential as a new diagnostic and prognostic marker and as a therapeutic target for lung cancer.
https://ift.tt/2Hea7Qb
Targeting Merkel cell carcinoma by engineered T cells specific to T-antigens of Merkel cell polyomavirus
Purpose: The causative agent of most cases of Merkel cell carcinoma (MCC) has been identified as the Merkel cell polyomavirus (MCV). MCV-encoded T-antigens (Tags) are essential not only for virus-mediated tumorigenesis but also for maintaining MCC cell lines in vitro. MCV Tags are thus an appealing target for viral oncoprotein-directed T cell therapy for MCC. With this study, we aimed to isolate and characterize Tag-specific T cell receptors (TCR) for potential use in gene therapy clinical trials. Experimental Design: T cell responses against MCV Tag epitopes were investigated by immunizing transgenic mice that express a diverse human TCR repertoire restricted to HLA-A2. Human lymphocytes genetically engineered to express Tag-specific TCRs were tested for specific reactivity against MCC cell lines. The therapeutic potential of Tag-specific TCR gene therapy was tested in a syngeneic cancer model. Results: We identified naturally processed epitopes of MCV Tags and isolated Tag-specific TCRs. T cells expressing these TCRs were activated by HLA-A2-positive cells loaded with cognate peptide or cells that stably expressed MCV Tags. We showed cytotoxic potential of T cells engineered to express these TCRs in vitro and demonstrated regression of established tumors in a mouse model upon TCR gene therapy. Conclusions: Our findings demonstrate that MCC cells can be targeted by MCV Tag-specific TCRs. Although recent findings suggest that approximately half of MCC patients benefit from PD1 pathway blockade, additional patients may benefit if their endogenous T cell response can be augmented by infusion of transgenic MCV-specific T cells such as those described here.
https://ift.tt/2qJDbE5
Cellular Biomedical Tattoo Can ID Hypercalcemia-Linked Cancer
WEDNESDAY, April 18, 2018 -- A cell-based biomedical tattoo can detect hypercalcemia associated with cancer in a murine model, according to an experimental study published in the April 18 issue of Science Translational Medicine. Aizhan Tastanova,...
https://ift.tt/2EYEkwO
Marital Status Tied to Earlier Presentation of Melanoma
WEDNESDAY, April 18, 2018 -- For patients with localized melanoma, marital status is associated with earlier presentation, according to a study published online April 18 in JAMA Dermatology. Cimarron E. Sharon, from the Hospital of the University of...
https://ift.tt/2EW3R9T
Stronger Link With Mortality for Ambulatory Versus Clinic BP
WEDNESDAY, April 18, 2018 -- Compared with clinic blood-pressure measurement, ambulatory blood-pressure measurement is more strongly associated with mortality, according to a study published in the April 18 issue of the New England Journal of...
https://ift.tt/2qHuECq
Mild TBI May Increase Risk of Parkinson's Disease
WEDNESDAY, April 18, 2018 -- Mild traumatic brain injury (TBI) is associated with increased risk of Parkinson's disease (PD) among military veterans, according to a study published online April 18 in Neurology. Raquel C. Gardner, M.D., from the...
https://ift.tt/2Hc2BkM
Nested case–control study of telomere length and lung cancer risk among heavy smokers in the β-Carotene and Retinol Efficacy Trial
Nested case–control study of telomere length and lung cancer risk among heavy smokers in the β-Carotene and Retinol Efficacy Trial
Nested case–control study of telomere length and lung cancer risk among heavy smokers in the β-Carotene and Retinol Efficacy Trial, Published online: 19 April 2018; doi:10.1038/s41416-018-0075-0
Nested case–control study of telomere length and lung cancer risk among heavy smokers in the β-Carotene and Retinol Efficacy Trial
https://ift.tt/2HMEHxe
Paracrine roles of cellular senescence in promoting tumourigenesis
Paracrine roles of cellular senescence in promoting tumourigenesis
Paracrine roles of cellular senescence in promoting tumourigenesis, Published online: 19 April 2018; doi:10.1038/s41416-018-0066-1
Paracrine roles of cellular senescence in promoting tumourigenesis
https://ift.tt/2vqnBD5
The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS)
The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS)
The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS), Published online: 19 April 2018; doi:10.1038/s41416-018-0048-3
The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS)
https://ift.tt/2HJxVZj
Mac’s Ambulance Lift featured on Ford Transit Ambulance of the Future
AEV, Ferno Middle East and Al Tayer Ford design "Ambulance of the Future" for demo at Arab Health Exhibition and Congress in Dubai.
https://ift.tt/2J6KGwo
Introductory Radiation Oncology Curriculum (IROC): Report of a National Needs Assessment and Multi-institutional Pilot Implementation
This study aimed to: 1) assess the optimal structure of an introductory curriculum for radiation oncology residents, including the perceived utility of a 2-day off-site "boot camp," and 2) evaluate the success of a pilot Introductory Radiation Oncology Curriculum (IROC) based on these initial data.
https://ift.tt/2HatQAl
Failed Randomized Clinical Trials in Radiation Oncology: What Can We Learn?
Clinical trial failure is common and can have negative repercussions including wasted time and resources. Through a review of ClinicalTrials.gov for RCTs involving radiotherapy, we found 3 key findings: 1) the rates of failure for radiotherapy trials have been increasing over time, 2) trials with a surgical comparator were likely to fail, and 3) trials with behavioral comparators were more likely to succeed.
https://ift.tt/2HbZM7x
18F-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated with Highly Conformal Radiation Therapy
18F-pentafluorinated etanidazole (18F-EF5) PET is a promising hypoxia imaging modality. We enrolled 28 patients undergoing highly conformal radiation therapy for localized lung and other tumors on a prospective clinical study to characterize the prevalence of imageable hypoxia by EF5-PET and its relationship to local tumor control after treatment. 43% of tumors demonstrated imageable hypoxia by EF5-PET, and the local tumor recurrence rate was higher in tumors with imageable hypoxia.
https://ift.tt/2qIeLuG
A founder mutation MLC1 c.736delA associated with megalencephalic leukoencephalopathy with subcortical cysts‐1 in north Indian kindred
Clinical Genetics, EarlyView.
https://ift.tt/2qIaZ4E
Children and young people's understanding of inherited conditions and their attitudes towards genetic testing: A systematic review
Clinical Genetics, EarlyView.
https://ift.tt/2H9XtSi
PACHE Spotlight: Yamilé Molina, Ph.D.
Dr. Yamilé Molina, an Assistant Professor at the University of Illinois-Chicago, discusses her work comparing intervention approaches' effects on cancer disparities. Dr. Molina also describes what CRCHD diversity training programs, including PACHE, have meant to her career.
https://ift.tt/2qI9VxG
Exploring the Use of Educational Material About Shoulder Dysfunction: A Quality Improvement Project in People With Amyotrophic Lateral Sclerosis
Shoulder pain is a common secondary complication of amyotrophic lateral sclerosis (ALS) that can contribute to functional decline and decreased participation in daily activities. The purpose of this study was to assess the effectiveness of an educational brochure aimed at improving knowledge regarding shoulder pain and dysfunction in people with ALS. Participants completed a preintervention survey with questions regarding their knowledge of how ALS may affect their shoulders. After completing the presurvey, they were mailed a brochure that described shoulder health and range of motion and stretching exercises. Four weeks after receiving the brochure, participants were then asked to determine the effectiveness of the educational materials in terms of impact on shoulder-related knowledge and self-efficacy with regard to prevention of shoulder pain and dysfunction. More than 50% of participants reported pain, decreased range of motion, or weakness in at least one shoulder since being diagnosed with ALS. All participants were interested in receiving educational materials, and all agreed that the brochure was easy to interpret and understand, with most (87%) reporting that it was helpful. Educational brochures are one strategy to improve awareness about shoulder health and to educate patients with ALS about exercises that may help reduce shoulder pain and dysfunction.https://ift.tt/2Hxp3bG
Changes in Basic Movement Ability and Activities of Daily Living After Hip Fractures: Correlation Between Basic Movement Scale and Motor-Functional Independence Measure Scores
Objective The aim of this study was to examine the correlation between basic movement ability and activities of daily living (ADL) in elderly patients after hip fracture surgery and predict ADL outcomes from changes in basic movement ability. Design Fifty-four patients receiving rehabilitation after hip fracture surgery were collected prospectively. Ambulatory ability was evaluated using a Basic Movement Scale (BMS), and ADL was evaluated using the motor subscale of the Functional Independence Measure (motor-FIM). From the results of evaluating BMS and motor-FIM weekly, the important postoperative period to regain ADL was investigated. Results There was a close correlation between BMS and motor-FIM scores at each evaluation point (r = 0.971, Phttps://ift.tt/2EZyT0n
The Link Between Cerebrovascular Hemodynamics and Rehabilitation Outcomes After Aneurysmal Subarachnoid Hemorrhage
Objective The aim of the study was to assess the relation between cerebrovascular function early after aneurysmal subarachnoid hemorrhage onset and functional and rehabilitation outcomes. Design Observational cohort study of subarachnoid hemorrhage patients (n = 133) admitted to rehabilitation (n = 49), discharged home (n = 52), or died before discharge (n = 10). We obtained hemodynamic markers of cerebral autoregulatory function from blood flow velocities in the middle cerebral artery and arterial pressure waveforms, recorded daily on days 2–4 after symptom onset, and functional independence measure (FIM) scores and FIM efficiency for those admitted to acute rehabilitation. Results Compared to those discharged home, the range of pressures within which autoregulation is effective was lower in patients admitted to rehabilitation (4.6 [0.2] vs. 3.9 [0.2] mm Hg) and those who died (2.7 [0.4], P = 0.04). For those admitted to rehabilitation, autoregulatory range and the ability of cerebrovasculature to increase flow were related to discharge FIM score (R2 = 0.33 and 0.43, Phttps://ift.tt/2qIcBfn
Disability and Health Consequences of Traumatic Brain Injury: National Prevalence
Objective The aim of the study was to measure the prevalence of traumatic brain injury (TBI)-related disability and health status in the general population. Design The French National Survey, conducted in households and institutions, assessed 33,896 adults. Data included sequelae from TBI, impairments, current health conditions, and uses of health services. Analyses, adjusted for age and sex, compared subjects who declared sequelae from TBI (n = 479) with the remaining survey population (n = 33,287). Use of weighting factors ensured that results were representative of the national population. Results Prevalence of persistent sequelae from TBI in France was 704/100,000. Median time since injury was 14 yrs. For all Core Set items of the International Classification of Functioning, subjects with TBI reported more impairments than the control population: adjusted odds ratios from 1.7 (behavioral difficulties) to 8.6 (motor difficulties). Rates of cardiovascular, respiratory, musculoskeletal, digestive, urological, neurological, and psychiatric conditions were higher in the TBI population. Use of health services was greater, and women with TBI had higher rates of unmet health needs. Conclusions Persistent sequelae from TBI significantly affect health in the general population. Planning of post-TBI care should address the chronic needs of these persons.https://ift.tt/2EZCY4S
Feasibility of Early, Motor-Assisted Cycle Ergometry in Critically Ill Neurological Patients With Upper Limb Weakness and Variable Cognitive Status: A Case Series
Upper limb paresis, common in many neurological conditions, is a major contributor of long-term disability and decreased quality of life. Evidence shows that repetitive, bilateral arm movement improves upper limb coordination after neurological injury. However, it is difficult to integrate upper limb interventions into very early rehabilitation of critically ill neurological patients because of patient arousal and medical acuity. This report describes the safety and feasibility of bilateral upper limb cycling in critically ill neurological patients with bilateral or unilateral paresis. Patients were included in this pilot observational series if they used upper limb cycle ergometry with occupational therapy while in the neurocritical care unit between May and August 2016. Patient demographics, neurological function, and hemodynamic status were recorded precycling and postcycling. Cycling parameters including duration and active and/or passive cycling were collected. No significant changes in hemodynamic or respiratory status were noted postintervention. No adverse effects or safety events were noted. In this series, upper limb cycle ergometry was a safe and feasible intervention for early rehabilitation in critically ill patients in the neurocritical care unit. Future studies will prospectively measure the impact of early upper limb cycle ergometry on neurological recovery and functional outcome in this population.https://ift.tt/2qD77mf
Immediate Effects of Simultaneous Application of Transcutaneous Electrical Nerve Stimulation and Ultrasound Phonophoresis on Active Myofascial Trigger Points: A Randomized Controlled Trial
Objective The aim of the study was to investigate the efficacy of phonophoresis with combined therapy on active myofascial trigger points. Participants One hundred participants with acute mechanical neck pain and at least one active myofascial trigger point in the upper trapezius were randomly assigned into four equal groups. Intervention Groups consisted of diclofenac phonophoresis with combined therapy, diclofenac phonophoresis, ultrasound (US) with coupling gel, and sham US and applied for 10 mins over myofascial trigger points. Measurements Measurements included pressure pain threshold and active cervical lateral flexion. Results There were statistically significant improvements in postintervention pressure pain threshold and range of motion values in treatment groups (P 0.05). Bonferroni correction test revealed that there was a significant difference between all the four groups in pressure pain threshold values (P 0.05) for range of motion. Conclusions Diclofenac phonophoresis with combined therapy, phonophoresis, and US were all effective in increasing pressure pain threshold values and range of motion. In addition, phonophoresis with combined therapy was shown to be superior over phonophoresis, and phonophoresis was superior over US in terms of reducing pain sensitivity. However, none of the treatment groups were found to be superior over the other in increasing range of motion.https://ift.tt/2HdcS0b
Diffusion Tensor Tractography for Decompressive Operation Decisions in Patients With Intracerebral Hemorrhage
No abstract availablehttps://ift.tt/2qH30W7
Priming With 1-Hz Repetitive Transcranial Magnetic Stimulation Over Contralesional Leg Motor Cortex Does Not Increase the Rate of Regaining Ambulation Within 3 Months of Stroke: A Randomized Controlled Trial
Background The potential benefits of repetitive transcranial magnetic stimulation (rTMS), applied either alone or as a combination treatment, on recovery of lower limbs after stroke have been insufficiently studied. Objective The aim of the study was to evaluate the effect of priming with 1-Hz repetitive transcranial magnetic stimulation over contralesional leg motor area with a double-cone coil before physical therapy on regaining ambulation. Methods Thirty-eight subacute stroke patients with significant leg disabilities were randomly assigned into the experimental group or control group to receive a 15-min real or sham 1-Hz repetitive transcranial magnetic stimulation, respectively, over the contralesional motor cortex representing the quadriceps muscle followed by 45-min physical therapy for 15 sessions for 3 wks. Functional measures, motor evoked potentials, and quality of life were assessed. Results There was no significant difference between experimental group and control group regarding the recovery in ambulation, balance, motor functions, and activity of daily living. No significant difference was found in other functional measures and the quality of life. Only the control group displayed significantly increased cortical excitability of the contralesional hemisphere after the intervention. Conclusions The present study found that insufficient evidence that contralesional priming with 1-Hz repetitive transcranial magnetic stimulation improves ambulatory and other motor functions among patients with a severe leg dysfunction in subacute stroke.https://ift.tt/2EXBE2v
Contralateral Involvement of Congenital Muscular Torticollis and Clavicular Fracture
Congenital muscular torticollis (CMT) is known to concur with some conditions such as developmental dysplasia of the hip or brachial plexus injury, which gives us some insights for pathogenesis of CMT. Although clavicular fracture is the most common fracture in newborns, little is known about concurrence of CMT and clavicular fracture. Our clinical experience led us to realize that concurrence of CMT and clavicular fracture tended to occur on the contralateral side for each other rather than the ipsilateral side. This study aimed to verify contralateral concurrence of CMT and clavicular fracture. This is a retrospective cohort study in a tertiary hospital, including 996 subjects with CMT. Concurrent clavicular fracture was found in 20 of 996 subjects with CMT, with the concurrence rate being 2.01%. Concurrent clavicular fracture and clavicular fracture occurred on the contralateral side for each other in 18 subjects (90%) rather than the ipsilateral side. This contralateral concurrence between side of CMT and clavicular fracture was significant (P = 0.001), with an odds ratio of 81 (P = 0.0032). Concurrent clavicular fracture and clavicular fracture seem to occur significantly more on the contralateral side for each other. Underlying mechanism for consistent contralateral concurrence needs to be verified in the near future.https://ift.tt/2qHjca1
The Natural History of Idiopathic Scoliosis During Growth: A Meta-Analysis
Objective The aim of the study was to provide a meta-analysis of current literature concerning the natural history of idiopathic scoliosis during growth. Design A comprehensive search of Medline, Embase, And Scopus databases was conducted up to November 2016. Eligible works were prospective or retrospective studies that enrolled patients with infantile idiopathic scoliosis, juvenile idiopathic scoliosis, or adolescent idiopathic scoliosis, followed up without any treatment from the time of detection. A meta-analysis for proportion was performed. The following studies were grouped per diagnosis: infantile idiopathic scoliosis, juvenile idiopathic scoliosis, and adolescent idiopathic scoliosis. Results Of the 1797 citations screened, we assessed 61 full-text articles and included 13 of these (2301 participants). Three studies included infantile idiopathic scoliosis patients (347 participants), five studies included a mixed population of juvenile idiopathic scoliosis and adolescent idiopathic scoliosis (1330 participants), and five studies included adolescent idiopathic scoliosis patients only (624 participants). The random pooled estimated progression rate was 49% (95% confidence interval = 1%–97%) for infantile idiopathic scoliosis, 49% in a mixed group of patients affected by juvenile idiopathic scoliosis or adolescent idiopathic scoliosis (95% confidence interval = 19%–79%), and 42% in adolescent idiopathic scoliosis (95% confidence interval = 11%–73%). Conclusions During growth, idiopathic scoliosis tends to progress in a high percentage of cases. The progression rate varies according to the age at diagnosis, with infantile scoliosis being the most unpredictable. There are many confounders, such as age, Risser sign and baseline Cobb angles that were not consistent among studies, making the data very heterogeneous.https://ift.tt/2EYWOgv
Two Unique Cases of Ciprofloxacin-Associated Avulsion of Ligament and Tendon
Ciprofloxacin is recognized to have a deleterious relationship with tendons, particularly Achilles tendinopathy, which makes up most case reports. Tendinopathy seems to occur because of induction of collagen-degrading enzymes causing damage and ischemia of the poorly vascularized regions preventing repair. The focus on the relationship of ciprofloxacin and the Achilles tendon leaves patients on fluoroquinolones with non-Achilles tendinopathy symptoms at risk of misdiagnosis. There have not been any documented instances of ligament damage with ciprofloxacin administration in the literature, although ligament and tendon compositions are similar and should have similar susceptibility. This report includes two cases, one presenting with right lateral thumb pain and a medical history of gastroenteritis treated with ciprofloxacin. Physical examination showed swelling of the right metacarpophalangeal joint and ultrasound confirmed disruption of the radial collateral ligament at insertion on first metacarpal; the second case is of a woman presenting with right hip pain in setting of chronic recurrent diverticulitis treated with ciprofloxacin. She received work-up for lumbar disc disease and spondylosis. After standard therapy with pharmacotherapy and physical therapy for radiculopathy failed, magnetic resonance imaging was performed showing near complete avulsion of the right hamstring tendons from the ischial tuberosity.https://ift.tt/2qGgWjg
Effect of Stretching Combined With Ultrashort Wave Diathermy on Joint Function and Its Possible Mechanism in a Rabbit Knee Contracture Model
Objective The aim of this study was to investigate the therapeutic effect of stretching combined with ultrashort wave on joint contracture and explore its possible mechanism. Design Thirty-two rabbits underwent unilateral immobilization of a knee joint at full extension to cause joint contracture. At 6 wks after immobilization, the rabbits were randomly divided into the following four groups: natural recovery group, stretching treatment group, ultrashort wave treatment group, and combined treatment group. For comparison, eight control group animals of corresponding age were also examined. The effect of stretching and ultrashort wave treatment on joint contracture was assessed by measuring the joint range of motion, evaluating the collagen deposition of joint capsule and assessing the mRNA and protein levels for transforming growth factor β1 in the joint capsule. Results The combined treatment group led to the best recovery of joint function. The combined treatment with stretching and ultrashort wave was more effective than stretching or ultrashort wave treatment alone against the synovial thickening of suprapatellar joint capsule, the collagen deposition of anterior joint capsule, and the elevated expression of transforming growth factor β1 in the joint capsule. Conclusions Stretching combined with ultrashort wave treatment was effective in improving joint range of motion, reducing the biomechanical, histological, and molecular manifestations of joint capsule fibrosis in a rabbit model of extending joint contracture.https://ift.tt/2HdqZCL
Radial Extracorporeal Shock Wave Therapy in an Individual With Primary Trigeminal Neuralgia: A Case Report and Literature Review
A patient with primary trigeminal neuralgia exhibited pain relief without medication after radial extracorporeal shock wave therapy. The 52-yr-old woman had a 3-yr history of primary trigeminal neuralgia, involving the right maxillary division (V2) and the mandibular division (V3). She became refractory to carbamazepine and exhibited hepatic dysfunction. She hence received 3000 to 6000 impulses of craniofacial radial extracorporeal shock wave therapy to the region centered on the surface projection of the trigeminal ganglion and pain areas at 10 Hz; the intensity ranged from 1.4 to 4.5 bars twice per week for 8 wks. At baseline, and 1, 2, and 5 mos after treatment, the Barrow Neurological Institute scores were IV, IIIa, II, and II, and the visual analog scale scores were 8, 3, 1, and 1, respectively. No complications or adverse effects were observed. The hepatic function returned to normal after the discontinuation of carbamazepine. This case report demonstrates the feasibility of radial extracorporeal shock wave therapy for primary trigeminal neuralgia without complications or adverse effects with careful regulation of the therapy intensity.https://ift.tt/2qHly8K
Does a Rehabilitation Program of Aerobic and Progressive Resisted Exercises Influence HIV-Induced Distal Neuropathic Pain?
Objective Distal symmetrical polyneuropathy is a common neurological sequela after HIV, which leads to neuropathic pain and functional limitations. Rehabilitation programs with exercises are used to augment pharmacological therapy to relieve pain but appropriate and effective exercises are unknown. This study explored the safety and effect of moderate-intensity aerobic exercises and progressive resisted exercises for HIV-induced distal symmetrical polyneuropathy neuropathic pain. Design A randomized pretest, posttest of 12 wks of aerobic exercise or progressive resisted exercise compared with a control. Outcome measures were assessed using the subjective periphery neuropathy, brief peripheral neuropathy screening, and numeric pain rating scale. Pain was assessed at baseline, 6 and 12 wks. Data between groups were compared using Kruskal-Wallis, Mann-Whitney U test, and within-groups Friedman and Wilcoxon signed rank tests. Results There were 136 participants (mean [SD] age = 36.79 [8.23] yrs) and the exercise groups completed the protocols without any adverse effects. Pain scores within and between aerobic exercise and progressive resisted exercise groups showed significant improvement (P 0.05). Conclusions This study supports a rehabilitation program of moderate-intensity aerobic exercise and progressive resisted exercise being safe and effective for reducing neuropathic pain and is beneficial with analgesics for HIV-induced distal symmetrical polyneuropathy.https://ift.tt/2HdAr9h
Lactotripeptides Supplementations Alleviate the Decrease in Maximal Isometric Force After High-Intensity Eccentric Exercise: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial
Objective The aim of the study was to investigate whether lactotripeptides supplementations alleviate the decrease in the maximal isometric force, an indirect marker of muscle damage, after eccentric exercise (ECC). Design Twenty-two young men performed 50 ECC of the elbow flexors using an isokinetic dynamometer. The subjects were randomly assigned to either the placebo or lactotripeptides group and were each given a 4.5 mg/d placebo or lactotripeptides thrice on the exercise day and the day after. Maximal isometric force and brachial arterial diameter were assessed before and 2 days after the ECC. Results The interaction of time and group on maximal isometric force was significant (Phttps://ift.tt/2HcO3S6
Impact of Fellowship Training Level on Colonoscopy Quality and Efficiency Metrics
Previous studies have described variable effects of fellow involvement on the adenoma detection rate (ADR), but few have stratified this effect by level of training. We aimed to evaluate the "fellow effect" on multiple procedural metrics including a newly defined adenoma management efficiency index, which may have a role in documenting colonoscopy proficiency for trainees. We also describe the impact of level of training on moderate sedation use.
https://ift.tt/2HeFGtq
Newly developed endoscopic detachable snare ligation therapy for colonic diverticular hemorrhage: a multicenter phase II trial (with videos)
We previously reported preliminary safety results for a new method, endoscopic detachable snare ligation (EDSL), for diverticular hemorrhage. This method does not need endoscope removal to attach a ligation device after detection of the bleeding site. The aim of the present study was to evaluate the efficacy and safety of EDSL in a larger patient population.
https://ift.tt/2qJYe9J
Patient-Reported Outcomes for Patients With Chronic Liver Disease
Chronic liver disease (CLD) and its complications such as decompensated cirrhosis and hepatocellular carcinoma are major causes of mortality and morbidity worldwide.1,2 In addition to its clinical impact, CLD causes impairment of health-related quality of life (HRQL) and other patient-reported outcomes (PROs).1 Furthermore, patients with CLD use a substantial amount of health care resources, making CLD responsible for tremendous economic burden to the society.1,2
https://ift.tt/2qHHqRA
Need for Randomized Controlled Trial
We thank Kawano et al1 for their interesting article about the association between intraosseous vascular access and lower survival and worse neurologic outcome in out-of-hospital cardiac arrest. However, we are concerned that the study has not accounted for important selection biases or other possible cofounding factors between the intraosseous vascular access group and the intravenous vascular access group despite the propensity score matching.
https://ift.tt/2qJyOJ5
Erratum Regarding “Low-Sodium Versus Standard-Sodium Peritoneal Dialysis Solution in Hypertensive Patients: A Randomized Controlled Trial” (Am J Kidney Dis. 2016;67[5]:753-761)
In the Original Investigation entitled "Low-Sodium Versus Standard-Sodium Peritoneal Dialysis Solution in Hypertensive Patients: A Randomized Controlled Trial" that appeared in the May 2016 issue of AJKD (Rutkowski et al, volume 67, issue 5, pages 753-761), there was an error in the final row of Table 3. The values shown pertained to dietary sodium intake, not dietary salt intake, so the row heading should have read "Dietary sodium intake, g/d."
https://ift.tt/2H9SGQQ
Rediscovering Bacteria through Single-Molecule Imaging in Living Cells
Bacteria are microorganisms central to health and disease, serving as important model systems for our understanding of molecular mechanisms and for developing new methodologies and vehicles for biotechnology. In the past few years, our understanding of bacterial cell functions has been enhanced substantially by powerful single-molecule imaging techniques. Using single fluorescent molecules as a means of breaking the optical microscopy limit, we can now reach resolutions of ∼20 nm inside single living cells, a spatial domain previously accessible only by electron microscopy.
https://ift.tt/2EZdSmv
Reply
We appreciate the comments offered by Dr Friesen in response to our study examining the impact of age and CYP2C19 genotype on the pharmacokinetics of pantoprazole in pediatric patients who are obese.1 Dr Friesen is correct in that our study cohort did not include a group of children who were not obese. Consequently, any comparisons that we offered carried the caveat of having used a historical cohort for comparison.
https://ift.tt/2HJfiol
Rituximab in The Management of Pediatric Steroid-Resistant Nephrotic Syndrome: A Systematic Review
To evaluate the efficacy and safety of rituximab in children with steroid-resistant nephrotic syndrome.
https://ift.tt/2vqGlT0
The Radish, Raphanus sativus L. Var. caudatus reduces anxiety-like behavior in mice
Abstract
Inclusion of vegetables in the diet not only provides dietary fiber, vitamins, minerals, trace elements but also significantly reduces the risk of several diseases. Raphanus sativus L. Var. caudatus belongs to the family Brassicaceae are pods of Radish, and are commonly known as Mungra or Sungra in Pakistan and India. The English name for this species is Rat-tailed radish. This variety of radish is unique, less familiar to the population, and not commonly used as a food source. Furthermore there have been very few studies that report on the potential antioxidant and anti-cancer capabilities of this radish. The present study was designed to evaluate anxiolytic potential of Raphanus caudatus in mice using different behavioral paradigms. The ethanol extract of the plant was evaluated at three different doses i.e. 250, 500 and 1000 mg/kg. The extract at doses of 250 and 500 mg/kg produced a significant (p < 0.05) reduction of anxiety-like behavior in mice and results are comparable to standard anxiolytic drug diazepam.
https://ift.tt/2qHtqr1
Indian Ginseng (Withania somnifera) supplementation ameliorates oxidative stress and mitochondrial dysfunctions in experimental model of stroke
Abstract
Stroke is an increasingly prevalent clinical condition and second leading cause of death globally. The present study evaluated the therapeutic potential of Indian Ginseng, also known as Withania somnifera (WS), supplementation on middle cerebral artery occlusion (MCAO) induced mitochondrial dysfunctions in experimental model of ischemic stroke. Stroke was induced in animals by occluding the middle cerebral artery, followed by reperfusion injury. Ischemia reperfusion injury resulted in increased oxidative stress indicated by increased reactive oxygen species and protein carbonyl levels; compromised antioxidant system; in terms of reduced superoxide dismutase and catalase activity, along with reduction in GSH levels and the redox ratio, impaired mitochondrial functions and enhanced expression of apoptosis markers. Ischemia reperfusion injury induced mitochondrial dysfunctions in terms of (i) reduced activity of the mitochondrial respiratory chain enzymes, (ii) reduced histochemical staining of complex-II and IV, (iii) reduced in-gel activity of mitochondrial complex-I to V, (iv) mitochondrial structural changes in terms of increased mitochondrial swelling, reduced mitochondrial membrane potential and ultrastructural changes. Additionally, an increase in the activity of caspase-3 and caspase-9 was also observed, along with altered expression of apoptotic proteins Bcl-2 and Bax in MCAO animals. MCAO animals also showed significant impairment in cognitive functions assessed using Y maze test. WS pre-supplementation, on the other hand ameliorated MCAO induced oxidative stress, mitochondrial dysfunctions, apoptosis and cognitive impairments. The results show protective effect of WS pre-supplementation in ischemic stroke and are suggestive of its potential application in stroke management.
https://ift.tt/2J9ECTN
Unique barriers to well‐being for pathology residents and how to address them
Cancer Cytopathology, EarlyView.
https://ift.tt/2vsMDl3
Analysis of histologic follow‐up and risk of malignancy for salivary gland neoplasm of uncertain malignant potential proposed by the milan system for reporting salivary gland cytopathology
Cancer Cytopathology, EarlyView.
https://ift.tt/2HzPywW
Tumor-associated macrophages promote progression and the Warburg effect via CCL18/NF-kB/VCAM-1 pathway in pancreatic ductal adenocarcinoma
Tumor-associated macrophages promote progression and the Warburg effect via CCL18/NF-kB/VCAM-1 pathway in pancreatic ductal adenocarcinoma
Tumor-associated macrophages promote progression and the Warburg effect via CCL18/NF-kB/VCAM-1 pathway in pancreatic ductal adenocarcinoma, Published online: 18 April 2018; doi:10.1038/s41419-018-0486-0
Tumor-associated macrophages promote progression and the Warburg effect via CCL18/NF-kB/VCAM-1 pathway in pancreatic ductal adenocarcinomahttps://ift.tt/2HtGxpc
Seipin deficiency in mice causes loss of dopaminergic neurons via aggregation and phosphorylation of α-synuclein and neuroinflammation
Seipin deficiency in mice causes loss of dopaminergic neurons via aggregation and phosphorylation of α-synuclein and neuroinflammation
Seipin deficiency in mice causes loss of dopaminergic neurons via aggregation and phosphorylation of α-synuclein and neuroinflammation, Published online: 18 April 2018; doi:10.1038/s41419-018-0471-7
Seipin deficiency in mice causes loss of dopaminergic neurons via aggregation and phosphorylation of α-synuclein and neuroinflammationhttps://ift.tt/2EXxA2b
Starvation during pregnancy impairs fetal oogenesis and folliculogenesis in offspring in the mouse
Starvation during pregnancy impairs fetal oogenesis and folliculogenesis in offspring in the mouse
Starvation during pregnancy impairs fetal oogenesis and folliculogenesis in offspring in the mouse, Published online: 18 April 2018; doi:10.1038/s41419-018-0492-2
Starvation during pregnancy impairs fetal oogenesis and folliculogenesis in offspring in the mousehttps://ift.tt/2HymBkV
REST, regulated by RA through miR-29a and the proteasome pathway, plays a crucial role in RPC proliferation and differentiation
REST, regulated by RA through miR-29a and the proteasome pathway, plays a crucial role in RPC proliferation and differentiation
REST, regulated by RA through miR-29a and the proteasome pathway, plays a crucial role in RPC proliferation and differentiation, Published online: 18 April 2018; doi:10.1038/s41419-018-0473-5
REST, regulated by RA through miR-29a and the proteasome pathway, plays a crucial role in RPC proliferation and differentiationhttps://ift.tt/2H9QIfc
Inhibition of cancer progression by a novel trans-stilbene derivative through disruption of microtubule dynamics, driving G2/M arrest, and p53-dependent apoptosis
Inhibition of cancer progression by a novel trans-stilbene derivative through disruption of microtubule dynamics, driving G2/M arrest, and p53-dependent apoptosis
Inhibition of cancer progression by a novel <i>trans</i>-stilbene derivative through disruption of microtubule dynamics, driving G2/M arrest, and p53-dependent apoptosis, Published online: 18 April 2018; doi:10.1038/s41419-018-0476-2
Inhibition of cancer progression by a novel trans-stilbene derivative through disruption of microtubule dynamics, driving G2/M arrest, and p53-dependent apoptosishttps://ift.tt/2Htw8dh
A Trib2-p38 axis controls myeloid leukaemia cell cycle and stress response signalling
A Trib2-p38 axis controls myeloid leukaemia cell cycle and stress response signalling
A Trib2-p38 axis controls myeloid leukaemia cell cycle and stress response signalling, Published online: 18 April 2018; doi:10.1038/s41419-018-0467-3
A Trib2-p38 axis controls myeloid leukaemia cell cycle and stress response signallinghttps://ift.tt/2HcN6cr
Loss of DEPTOR in renal tubules protects against cisplatin-induced acute kidney injury
Loss of DEPTOR in renal tubules protects against cisplatin-induced acute kidney injury
Loss of <i>DEPTOR</i> in renal tubules protects against cisplatin-induced acute kidney injury, Published online: 18 April 2018; doi:10.1038/s41419-018-0483-3
Loss of DEPTOR in renal tubules protects against cisplatin-induced acute kidney injuryhttps://ift.tt/2qEFE3G
Inhibition of cyclin-dependent kinase 4 as a potential therapeutic strategy for treatment of synovial sarcoma
Inhibition of cyclin-dependent kinase 4 as a potential therapeutic strategy for treatment of synovial sarcoma
Inhibition of cyclin-dependent kinase 4 as a potential therapeutic strategy for treatment of synovial sarcoma, Published online: 18 April 2018; doi:10.1038/s41419-018-0474-4
Inhibition of cyclin-dependent kinase 4 as a potential therapeutic strategy for treatment of synovial sarcomahttps://ift.tt/2H9QHb8
Noninvasive, High-throughput Determination of Sleep Duration in Rodents
We describe a high-throughput method of measuring sleep by means of activity-based home-cage monitoring. This method offers advantages over traditional EEG-based methods. It is well validated for the determination of total sleep duration and can be a powerful tool to monitor sleep in rodent models of human disease.
https://ift.tt/2JYGzDV
Study of platelet activation markers and plasma cytokines in sickle cell disease patients during vaso-occlusive pain crises
Abstract
The present study was designed to examine platelet function during the sickle cell disease (SCD) vaso-occlusive pain crisis (VOC) in comparison with steady-state SCD patients and healthy controls. Platelets were immunophenotyped using different activation CD markers in a group of 34 patients with SCD. Among those SCD patients, 19 patients were admitted to our hospital for symptoms of VOC pain crises. Fifteen patients of SCD were studied in parallel during asymptomatic steady state (SS) of their disease. Fifteen healthy control volunteers were immunophenotyped in parallel. In addition, all patients and healthy control plasma were assayed for levels of the inflammatory cytokines which are IL-8, TGF-β1, and TNF-α. Our results confirmed the strong expression of activation markers CD40, CD41a, CD42a, CD61, CD62p, CD36, CD49f, and CD59 on platelets from patients studied during VOC pain episodes (P ˂ 0.005). However, both the steady-state SCD patients and normal healthy controls did not show increased expression of any of these markers on their platelets. In addition, the mean levels of IL-8 in the plasma of VOC-SCD patients were statistically significant superior to IL-8 mean values of normal control plasma (P = 0.008). These results suggest over activation of platelets in SCD patients during VOC pain episodes compared to SCD steady state or normal controls. Alongside, we found significant increase of plasma IL-8 levels during VOC pain crises. These findings indicate over activation of platelets, together with over production of IL-8 during VOC pain crises in SCD patients.
https://ift.tt/2JVIAAR
Patient views and correlates of radiotherapy omission in a population‐based sample of older women with favorable‐prognosis breast cancer
Cancer, EarlyView.
https://ift.tt/2HfokZm
Development and validation of algorithms to differentiate ductal carcinoma in situ from invasive breast cancer within administrative claims data
Cancer, EarlyView.
https://ift.tt/2HzX2jF
Robust Visual Responses and Normal Retinotopy in Primate Lateral Geniculate Nucleus following Long-term Lesions of Striate Cortex
Lesions of striate cortex (V1) trigger massive retrograde degeneration of neurons in the LGN. In primates, these lesions also lead to scotomas, within which conscious vision is abolished. Mediation of residual visual capacity within these regions (blindsight) has been traditionally attributed to an indirect visual pathway to the extrastriate cortex, which involves the superior colliculus and pulvinar complex. However, recent studies have suggested that preservation of the LGN is critical for behavioral evidence of blindsight, raising the question of what type of visual information is channeled by remaining neurons in this structure. A possible contribution of LGN neurons to blindsight is predicated on two conditions: that the neurons that survive degeneration remain visually responsive, and that their receptive fields continue to represent the region of the visual field inside the scotoma. We tested these conditions in male and female marmoset monkeys (Callithrix jacchus) with partial V1 lesions at three developmental stages (early postnatal life, young adulthood, old age), followed by long recovery periods. In all cases, recordings from the degenerated LGN revealed neurons with well-formed receptive fields throughout the scotoma. The responses were consistent and robust, and followed the expected eye dominance and retinotopy observed in the normal LGN. The responses had short latencies and preceded those of neurons recorded in the extrastriate middle temporal area. These findings suggest that the pathway that links LGN neurons to the extrastriate cortex is physiologically viable and can support residual vision in animals with V1 lesions incurred at various ages.
SIGNIFICANCE STATEMENT Patients with a lesion of the primary visual cortex (V1) can retain certain visually mediated behaviors, particularly if the lesion occurs early in life. This phenomenon ("blindsight") not only sheds light on the nature of consciousness, but also has implications for studies of brain circuitry, development, and plasticity. However, the pathways that mediate blindsight have been the subject of debate. Recent studies suggest that projections from the LGN might be critical, but this finding is puzzling given that the lesions causes severe cell death in the LGN. Here we demonstrate in monkeys that the surviving LGN neurons retain a remarkable level of visual function and could therefore be the source of the visual information that supports blindsight.
https://ift.tt/2HdkSOC
Convergent Spinal Circuits Facilitating Human Wrist Flexors
Noninvasive assessment of spinal circuitry in humans is limited, especially for Ib pathways in the upper limb. We developed a protocol in which we evoke the H-reflex in flexor carpi radialis (FCR) by median nerve stimulation and condition it with electrical stimulation above motor threshold over the extensor carpi radialis (ECR) muscle belly. Eighteen healthy adults (8 male, 10 female) took part in the study. There was a clear reflex facilitation at a 30 ms interstimulus interval (ISI) and suppression at a 70 ms ISI, which was highly consistent across subjects. We investigated the following two hypotheses of the possible source of the facilitation: (1) ECR Ib afferents from Golgi tendon organs, activated by the twitch following ECR stimulation; and (2) FCR afferents, from spindles and/or Golgi tendon organs, activated by the wrist extension movement that follows ECR stimulation. Several human and monkey experiments indicated a role for both of these sets of afferents. Our results provide evidence for a spinal circuit in which flexor motoneurons receive convergent excitatory input from flexor afferents as well as from extensor Ib afferents; this circuit can be straightforwardly assessed noninvasively in humans.
SIGNIFICANCE STATEMENT Here we described a novel spinal circuit, which is easy to assess noninvasively in humans. Understanding this circuit in more detail could be beneficial for the design of clinical tests in neurological conditions.
https://ift.tt/2H9y6fq
Modified Origins of Cortical Projections to the Superior Colliculus in the Deaf: Dispersion of Auditory Efferents
Following the loss of a sensory modality, such as deafness or blindness, crossmodal plasticity is commonly identified in regions of the cerebrum that normally process the deprived modality. It has been hypothesized that significant changes in the patterns of cortical afferent and efferent projections may underlie these functional crossmodal changes. However, studies of thalamocortical and corticocortical connections have refuted this hypothesis, instead revealing a profound resilience of cortical afferent projections following deafness and blindness. This report is the first study of cortical outputs following sensory deprivation, characterizing cortical projections to the superior colliculus in mature cats (N = 5, 3 female) with perinatal-onset deafness. The superior colliculus was exposed to a retrograde pathway tracer, and subsequently labeled cells throughout the cerebrum were identified and quantified. Overall, the percentage of cortical projections arising from auditory cortex was substantially increased, not decreased, in early-deaf cats compared with intact animals. Furthermore, the distribution of labeled cortical neurons was no longer localized to a particular cortical subregion of auditory cortex but dispersed across auditory cortical regions. Collectively, these results demonstrate that, although patterns of cortical afferents are stable following perinatal deafness, the patterns of cortical efferents to the superior colliculus are highly mutable.
SIGNIFICANCE STATEMENT When a sense is lost, the remaining senses are functionally enhanced through compensatory crossmodal plasticity. In deafness, brain regions that normally process sound contribute to enhanced visual and somatosensory perception. We demonstrate that hearing loss alters connectivity between sensory cortex and the superior colliculus, a midbrain region that integrates sensory representations to guide orientation behavior. Contrasting expectation, the proportion of projections from auditory cortex increased in deaf animals compared with normal hearing, with a broad distribution across auditory fields. This is the first description of changes in cortical efferents following sensory loss and provides support for models predicting an inability to form a coherent, multisensory percept of the environment following periods of abnormal development.
https://ift.tt/2qFCPzc
Recombinant Adeno-Associated Virus–Based Gene Therapy for Disorders Detected by Newborn Screening: Inherent Limitations of This Approach
Human Gene Therapy, Volume 29, Issue 4, Page 401-402, April 2018.
https://ift.tt/2qHNFVz
Gene Therapy in Lipoprotein Lipase Deficiency: Case Report on the First Patient Treated with Alipogene Tiparvovec Under Daily Practice Conditions
Human Gene Therapy, Volume 29, Issue 4, Page 520-527, April 2018.
https://ift.tt/2EXOr4Q
Rapid and reliable diagnostic method to detect Zika virus by real-time fluorescence reverse transcription loop-mediated isothermal amplification
To detect Zika virus more rapidly and accurately, we developed a novel method that utilized a real-time fluorescence reverse transcription loop-mediated isothermal amplification (LAMP) technique. The NS5 gene ...
https://ift.tt/2vy6nUv
Ribosomal binding site sequences and promoters for expressing glutamate decarboxylase and producing γ-aminobutyrate in Corynebacterium glutamicum
Glutamate decarboxylase (GAD) converts l-glutamate (Glu) into γ-aminobutyric acid (GABA). Corynebacterium glutamicum that expresses exogenous GAD gene, gadB2 or gadB1, can synthesize GABA from its own produced Gl...
https://ift.tt/2qGHL6L
Modeling photocatalytic degradation of diazinon from aqueous solutions and effluent toxicity risk assessment using Escherichia coli LMG 15862
In this study, modeling and degradation of diazinon from contaminated water by advanced oxidation process together with a new test for effluent bioassay using E. coli were investigated. The experiments were desig...
https://ift.tt/2vlRpR2
Eukaryal composition and diversity in anaerobic soils influenced by the novel chiral insecticide Paichongding
Paichongding (IPP) is a neonicotinoid chiral insecticide with independent intellectual property in China. IPP application can increase crop yield, and also lead to insecticide residue and pollution in soils, w...
https://ift.tt/2qGFBUQ
Tri11, tri3, and tri4 genes are required for trichodermin biosynthesis of Trichoderma brevicompactum
Trichoderma brevicompactum and T. arundinaceum both can synthesize trichodermin with strong antifungal activity and high biotechnological value. The two Trichoderma species have a tri cluster, which includes seve...
https://ift.tt/2vsE0qF
Polypharmacy More Likely for Cancer Survivors
WEDNESDAY, April 18, 2018 -- Cancer survivors are more likely to be prescribed five or more unique medications, including drugs with abuse potential, according to a study published online April 12 in Cancer. Caitlin C. Murphy, Ph.D., M.P.H., from...
https://ift.tt/2EYGFYn
C. Difficile Risk Higher With Stoma Reversal Versus Colectomy
WEDNESDAY, April 18, 2018 -- Patients who undergo elective stoma reversal have a higher incidence of postoperative Clostridium difficile infection versus patients who undergo elective colectomy, according to a study published in the May issue of...
https://ift.tt/2qH4AHN
New Drug Combo Ups Survival in HER2/neu Uterine Serous Cancer
WEDNESDAY, April 18, 2018 -- For patients with human epidermal growth factor receptor 2 (HER2)/neu-positive uterine serous carcinoma, adding intravenous trastuzumab to treatment with carboplatin-paclitaxel is associated with increased...
https://ift.tt/2H9wUbQ
Smartphone App May Up Medication Adherence in HTN
WEDNESDAY, April 18, 2018 -- Randomization to use of a smartphone app is associated with a small improvement in medication adherence but no change in systolic blood pressure among individuals with poorly controlled hypertension, according to a study...
https://ift.tt/2HumFCj
Opiate Use Linked to Early Mortality in IBD Patients
WEDNESDAY, April 18, 2018 -- Heavy use of opiates among patients with inflammatory bowel diseases (IBD) is tied to increased risk of premature all-cause death, according to a study published in the April issue of Clinical Gastroenterology and...
https://ift.tt/2EXeJEr
Young Adults With T1DM Show Muscle Metabolic Deficiencies
WEDNESDAY, April 18, 2018 -- Physically active young adults with type 1 diabetes have alterations in mitochondrial ultrastructure and bioenergetics within skeletal muscle, according to a study published online April 18 in Diabetologia. Cynthia M.F....
https://ift.tt/2Hx3FTC
CDC: Asian U.S. Mothers More Likely to be Older, Married
WEDNESDAY, April 18, 2018 -- Non-Hispanic Asian mothers have distinct characteristics, some of which vary by Asian subgroup and place of birth, according to a National Vital Statistics Report published online April 18 by the U.S. Centers for Disease...
https://ift.tt/2Hbz9LL
Disordered Eating Among Teens Tied to Future Depression
WEDNESDAY, April 18, 2018 -- Disordered eating behavior among adolescents is associated with a significantly increased risk of future depressive symptoms and being bullied by peers, according to a study published online April 11 in JAMA...
https://ift.tt/2qH4wI3
Self-Regulation Interventions Beneficial for Children
WEDNESDAY, April 18, 2018 -- A range of interventions can successfully improve self-regulation in children and adolescents, according to research published online April 16 in JAMA Pediatrics. Anuja Pandey, M.D., from the University College London...
https://ift.tt/2H8UGop
Social Support of Autonomy Tied to Better Glycemic Control in DM
WEDNESDAY, April 18, 2018 -- Family and friends' autonomy support may lead to better glycemic control by reducing distress among patients with diabetes, according to a study published online March 29 in Diabetes Care. Aaron A. Lee, Ph.D., from the...
https://ift.tt/2qHyaN7
24-Hour Multi-Patient Use Endoscope Connectors: Letter to HealthCare Providers and Healthcare Facilities - Risk of Cross-Contamination
[Posted 04/18/2018] AUDIENCE: Gastroenterology, Health Professional, Infectious Disease, Nursing, Risk Manager, Surgery ISSUE: The FDA is alerting health care providers and facilities about the risk of cross-contamination with certain connectors...
https://ift.tt/2HwYpzm
Spatial Quantification of Drugs in Pulmonary Tuberculosis Lesions by Laser Capture Microdissection Liquid Chromatography Mass Spectrometry (LCM-LC/MS)
Here, we describe a protocol using laser capture microdissection coupled with LC/MS analysis to spatially-quantify drug distributions within pulmonary tuberculosis granulomas. The approach has broad applicability to quantifying drug concentrations within tissues at high spatial detail.
https://ift.tt/2HIe6l0
ESO continues integration of FIREHOUSE Software®
Key milestones include tighter product integration with ESO EHR; infrastructure improvements, investment in customer service and support; high volume of sales opportunities.
https://ift.tt/2qJe3gG
ESO launches surveillance form for overdose
Specialty Patient Form to help standardize definitions and data collection, highlight responder safety.
https://ift.tt/2HLM3RC
Creating a Structurally Realistic Finite Element Geometric Model of a Cardiomyocyte to Study the Role of Cellular Architecture in Cardiomyocyte Systems Biology
This protocol outlines a novel method to create a spatially detailed finite element model of the intracellular architecture of cardiomyocytes from electron microscopy and confocal microscopy images. The power of this spatially detailed model is demonstrated using case studies in calcium signaling and bioenergetics.
https://ift.tt/2J2GhdO
HIPK2-Mediated Transcriptional Control of NMDA Receptor Subunit Expression Regulates Neuronal Survival and Cell Death
NMDA receptors are critical for neuronal communication. Dysfunction in NMDA receptors has been implicated in neuropsychiatric diseases. While it is well recognized that the composition of NMDA receptors undergoes a GluN2B-to-GluN2A switch in early postnatal life, the mechanism regulating this switch remains unclear. Using transcriptomic and functional analyses in brain tissues from male and female Hipk2+/+ and Hipk2–/– mice, we showed that the HIPK2-JNK–c-Jun pathway is important in suppressing the transcription of Grin2a and Grin2c, which encodes the GluN2A and GluN2C subunits of the NMDA receptors, respectively. Loss of HIPK2 leads to a significant decrease in JNK–c-Jun signaling, which in turn derepresses the transcription of Grin2a and Grin2c mRNA and upregulates GluN2A and GluN2C protein levels. These changes result in a significant increase of GluN2A/GluN2B ratio in synapse and mitochondria, a persistent activation of the ERK-CREB pathway and the upregulation of synaptic activity-regulated genes, which collectively contribute to the resistance of Hipk2–/– neurons to cell death induced by mitochondrial toxins.
SIGNIFICANCE STATEMENT We identify HIPK2-JNK–c-Jun signaling as a key mechanism that regulates the transcription of NMDA receptor subunits GluN2A and GluN2C in vivo. Our results provide insights into a previously unrecognized molecular mechanism that control the switch of NMDA receptor subunits in early postnatal brain development. Furthermore, we provide evidence that changes in the ratio of NMDA subunits GluN2A/GluN2B can also be detected in the synapse and mitochondria, which contributes to a persistent activation of the prosurvival ERK-CREB pathway and its downstream target genes. Collectively, these changes protect HIPK2 deficient neurons from mitochondrial toxins.
https://ift.tt/2voYFf7
A Gain-of-Function Mutation in the {alpha}9 Nicotinic Acetylcholine Receptor Alters Medial Olivocochlear Efferent Short-Term Synaptic Plasticity
Gain control of the auditory system operates at multiple levels. Cholinergic medial olivocochlear (MOC) fibers originate in the brainstem and make synaptic contacts at the base of the outer hair cells (OHCs), the final targets of several feedback loops from the periphery and higher-processing centers. Efferent activation inhibits OHC active amplification within the mammalian cochlea, through the activation of a calcium-permeable α9α10 ionotropic cholinergic nicotinic receptor (nAChR), functionally coupled to calcium activated SK2 potassium channels. Correct operation of this feedback requires careful matching of acoustic input with the strength of cochlear inhibition (Galambos, 1956; Wiederhold and Kiang, 1970; Gifford and Guinan, 1987), which is driven by the rate of MOC activity and short-term facilitation at the MOC–OHC synapse (Ballestero et al., 2011; Katz and Elgoyhen, 2014). The present work shows (in mice of either sex) that a mutation in the α9α10 nAChR with increased duration of channel gating (Taranda et al., 2009) greatly elongates hair cell-evoked IPSCs and Ca2+ signals. Interestingly, MOC–OHC synapses of L9'T mice presented reduced quantum content and increased presynaptic facilitation. These phenotypic changes lead to enhanced and sustained synaptic responses and OHC hyperpolarization upon high-frequency stimulation of MOC terminals. At the cochlear physiology level these changes were matched by a longer time course of efferent MOC suppression. This indicates that the properties of the MOC–OHC synapse directly determine the efficacy of the MOC feedback to the cochlea being a main player in the "gain control" of the auditory periphery.
SIGNIFICANCE STATEMENT Plasticity can involve reciprocal signaling across chemical synapses. An opportunity to study this phenomenon occurs in the mammalian cochlea whose sensitivity is regulated by efferent olivocochlear neurons. These release acetylcholine to inhibit sensory hair cells. A point mutation in the hair cell's acetylcholine receptor that leads to increased gating of the receptor greatly elongates IPSCs. Interestingly, efferent terminals from mutant mice present a reduced resting release probability. However, upon high-frequency stimulation transmitter release facilitates strongly to produce stronger and far longer-lasting inhibition of cochlear function. Thus, central neuronal feedback on cochlear hair cells provides an opportunity to define plasticity mechanisms in cholinergic synapses other than the highly studied neuromuscular junction.
https://ift.tt/2qEoTWk
Kainate Receptors Inhibit Glutamate Release Via Mobilization of Endocannabinoids in Striatal Direct Pathway Spiny Projection Neurons
Kainate receptors are members of the glutamate receptor family that function by both generating ionotropic currents through an integral ion channel pore and coupling to downstream metabotropic signaling pathways. They are highly expressed in the striatum, yet their roles in regulating striatal synapses are not known. Using mice of both sexes, we demonstrate that GluK2-containing kainate receptors expressed in direct pathway spiny projection neurons (dSPNs) inhibit glutamate release at corticostriatal synapses in the dorsolateral striatum. This inhibition requires postsynaptic kainate-receptor-mediated mobilization of a retrograde endocannabinoid (eCB) signal and activation of presynaptic CB1 receptors. This pathway can be activated during repetitive 25 Hz trains of synaptic stimulation, causing short-term depression of corticostriatal synapses. This is the first study to demonstrate a role for kainate receptors in regulating eCB-mediated plasticity at the corticostriatal synapse and demonstrates an important role for these receptors in regulating basal ganglia circuits.
SIGNIFICANCE STATEMENT The GRIK2 gene, encoding the GluK2 subunit of the kainate receptor, has been linked to several neuropsychiatric and neurodevelopmental disorders including obsessive compulsive disorder (OCD). Perseverative behaviors associated with OCD are known to result from pathophysiological changes in the striatum and kainate receptor knock-out mice have striatal-dependent phenotypes. However, the role of kainate receptors in striatal synapses is not known. We demonstrate that GluK2-containing kainate receptors regulate corticostriatal synapses by mobilizing endocannabinoids from direct pathway spiny projection neurons. Synaptic activation of GluK2 receptors during trains of synaptic input causes short-term synaptic depression, demonstrating a novel role for these receptors in regulating striatal circuits.
https://ift.tt/2Hdl0h4
Variations in Ca2+ Influx Can Alter Chelator-Based Estimates of Ca2+ Channel-Synaptic Vesicle Coupling Distance
The timing and probability of synaptic vesicle fusion from presynaptic terminals is governed by the distance between voltage-gated Ca2+ channels (VGCCs) and Ca2+ sensors for exocytosis. This VGCC-sensor coupling distance can be determined from the fractional block of vesicular release by exogenous Ca2+ chelators, which depends on biophysical factors that have not been thoroughly explored. Using numerical simulations of Ca2+ reaction and diffusion, as well as vesicular release, we examined the contributions of conductance, density, and open duration of VGCCs, and the influence of endogenous Ca2+ buffers on the inhibition of exocytosis by EGTA. We found that estimates of coupling distance are critically influenced by the duration and amplitude of Ca2+ influx at active zones, but relatively insensitive to variations of mobile endogenous buffer. High concentrations of EGTA strongly inhibit vesicular release in close proximity (20-30 nm) to VGCCs if the flux duration is brief, but have little influence for longer flux durations that saturate the Ca2+ sensor. Therefore, the diversity in presynaptic action potential duration is sufficient to alter EGTA inhibition, resulting in errors potentially as large as 300% if Ca2+ entry durations are not considered when estimating VGCC–sensor coupling distances.
SIGNIFICANT STATEMENT The coupling distance between voltage-gated Ca2+ channels and Ca2+ sensors for exocytosis critically determines the timing and probability of neurotransmitter release. Perfusion of presynaptic terminals with the exogenous Ca2+ chelator EGTA has been widely used for both qualitative and quantitative estimates of this distance. However, other presynaptic terminal parameters such as the amplitude and duration of Ca2+ entry can also influence EGTA inhibition of exocytosis, thus confounding conclusions based on EGTA alone. Here, we performed reaction–diffusion simulations of Ca2+-driven synaptic vesicle fusion, which delineate the critical parameters influencing an accurate prediction of coupling distance. Our study provides guidelines for characterizing and understanding how variability in coupling distance across chemical synapses could be estimated accurately.
https://ift.tt/2HzyeIq
Histopathological features to define atypical meningioma: What does really matter for prognosis?
Abstract
Atypical meningiomas are diagnosed in the presence of: (1) three or more of the following minor atypical criteria: increased cellularity, small cells with a high nuclear/cytoplasmic ratio, prominent nucleoli, sheeting, and foci of spontaneous or geographic necrosis; (2) mitotic count ≥ 4 mitoses per 10 HPF (high mitotic index); (3) brain invasion. The 5-year disease-free survival (DFS) is around 50%. Due to their heterogeneous behavior, the post-surgical treatment of atypical meningiomas is controversial. This study investigated the ability of histopathological features to predict recurrence risk of atypical meningiomas. Meningiomas classified as atypical only on minor atypical criteria had low recurrence risk. Brain invasion, high mitotic index and sheeting were significantly associated with shorter disease-free survival (DFS) (P = 0.001; P = 0.01; P = 0.01). The presence of brain invasion and the co-presence of sheeting and high mitotic index had the highest ability to identify recurring meningiomas (P = 0.0001) (sensitivity: 90.9%; specificity: 86.7%). Our results suggest reconsideration of classification of meningiomas as atypical based only on minor atypical criteria. The presence of brain invasion and the co-occurrence of sheeting and high mitotic count may be useful to identify high risk cases, which may benefit from adjuvant treatments.
https://ift.tt/2JWF21o
The Role of Proteasome Inhibitor MG132 in 2,4-Dinitrofluorobenzene-Induced Atopic Dermatitis in NC/Nga Mice
Background: Although immunosuppressants for therapy of atopic dermatitis (AD) are still being sought, proteasome inhibitors are also potential candidates for the treatment of AD. Proteasome inhibitors exert various effects by blocking proteasomal degradation and help regulate processes such as apoptosis induction via caspase-9, cell cycle progression via cyclins, NF-κB inactivation via IκB, and downregulation of antigen cross-presentation. The cells targeted by proteasome inhibitors are therefore activated cells undergoing proliferation or differentiation, and antigen-presenting cells carrying out protein degradation. Objectives: This study investigated the therapeutic effects and side effects of a proteasome inhibitor, MG132, on the treatment of AD. Methods: AD-like disease in NC/Nga mice housed under specific pathogen-free conditions was induced by repeated application of 2,4-dinitrofluorobenzene (DNFB). Disease progression was evaluated by inflammation score, histopathology, and serum IgE level, and the effects of systemic MG132 administration were investigated. The percentages and absolute numbers for each population of Th1, Th2, and Th17 cells in the axillary lymph nodes were analyzed by flow cytometry. Results: DNFB application increased the expression of a unique major histocompatibility complex class I mutant molecule D/Ldm7 in dendritic cells (DCs), and increased Th1 and Th17 cells in NC/Nga mice. In vivo MG132 administration to NC/Nga mice with DNFB-induced dermatitis reduced Th17 cells but maintained the level of Th1 cells, resulting in the alleviation of dermatitis lesions by decreasing both serum IgE hyperproduction and mast cell migration. To understand the mechanisms maintaining Th1 cell levels following in vivo MG132-administration, we focused on the role of proteasomes regulating D/Ldm7 expression. Interestingly, 20S proteasome activity was higher in NC/Nga DCs than in BALB/c DCs. In vitro MG132 administration partially increased D/Ldm7 expression in a dose-dependent manner during DC maturation, and induced IFN-γ production from autoreactive CD8+ T cells but not from CD4+ T cells following coculturing with D/Ldm7-upregulated DCs. Conclusion: Although MG132 administration temporarily alleviated AD pathogenesis in NC/Nga mice, prolonged MG132 treatment may result in immunopathogenesis leading to chronic AD due to its side effect of maintaining Th1 levels via autoreactive CD8+ T cells.
Int Arch Allergy Immunol
https://ift.tt/2EXyE64
Int Arch Allergy Immunol
https://ift.tt/2EXyE64
Search for a Novel Allergen in Hen’s Egg Allergy Using an IgE Immunoblotting Assay
Background: Food allergy is a serious health issue affecting roughly 4% of children, with a substantial effect on quality of life. Chicken egg allergy is frequently observed in infants. Therefore, some of them have to exclude hen's eggs from their daily diet to avoid allergenic symptoms. Hen's egg is composed of 2 soluble parts; one is egg white, which has been characterized as the major source of allergenicity, while the other is egg yolk, which is estimated as a miner source. Only 2 allergens from egg yolk, α-livetin (Gal d 5) and YGP42 (Gal d 6), have been described to date. Methods: Sera from 53 patients allergic to hen's eggs and 2 patients allergic to sesame were obtained from the Department of Pediatrics, Chiba University Hospital. The study was performed using SDS-PAGE, IgE immunoblotting, and dot blotting. Results: Seven bands of egg yolk were detected by IgE immunoblotting. Out of these bands, a possible new allergen was further characterized by LC-MS/MS. The 33-kDa band was identified as yolk glycoprotein (YGP40) by LC-MS/MS. A total of 21 of the 53 patients (47%) had YGP40 detected by dot blotting. Conclusions: We identified YGP40 as a new hen's egg yolk allergen and detected 4 sites of YGP40 as linear epitopes.
Int Arch Allergy Immunol
https://ift.tt/2HKHgjJ
Int Arch Allergy Immunol
https://ift.tt/2HKHgjJ
Rhino 69 Extreme 50000 by AMA Wholesale: Recall - Presence of Tadalafil
[Posted 04/18/2018] AUDIENCE: Consumer ISSUE: AMA Wholesale Inc. (Distributor/Re-seller), is voluntarily recalling Rhino 69 Extreme 50000 capsules to the consumer level. FDA analysis found the product to be tainted with undeclared tadalafil....
https://ift.tt/2H9jdhb
Euphoric Capsules by Epic Products: Recall - Undeclared Sildenafil and Tadalafil
Audience: Consumer [Posted 04/18/2018] ISSUE: Overland Park, KS, Epic Products, LLC is voluntarily recalling all lots of Euphoric capsules, packaged in 1 count blister cards, 3 count bottles, and 12 count bottles to the consumer level. FDA analysis...
https://ift.tt/2qMKn2z
Rhino 69 Extreme 50000 by AMA Wholesale: Recall - Presence of Tadalafil
[Posted 04/18/2018] AUDIENCE: Consumer ISSUE: AMA Wholesale Inc. (Distributor/Re-seller), is voluntarily recalling Rhino 69 Extreme 50000 capsules to the consumer level. FDA analysis found the product to be tainted with undeclared tadalafil....
https://ift.tt/2H9jdhb
Euphoric Capsules by Epic Products: Recall - Undeclared Sildenafil and Tadalafil
Audience: Consumer [Posted 04/18/2018] ISSUE: Overland Park, KS, Epic Products, LLC is voluntarily recalling all lots of Euphoric capsules, packaged in 1 count blister cards, 3 count bottles, and 12 count bottles to the consumer level. FDA analysis...
https://ift.tt/2qMKn2z
Cervical Spine Prospective Feasibility Study
Abstract
Purpose
Diffusion tensor imaging (DTI) in flexion-extension may serve as a diagnostic tool to improve the sensitivity for detection of myelopathy. In this study, the feasibility and reproducibility of dynamic DTI in the cervical spinal cord was assessed in healthy volunteers and patients.
Methods
All subjects were examined in maximum neck flexion-extension in a 3T magnetic resonance imaging (MRI) scanner. Range of motion, space available for the spinal cord, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured and compared between the neck positions.
Results
Volunteers showed no variation in ADC and FA. In patients, extension produced higher ADC in the diseased than in the control segments (p = 0.0045). The ADC of the affected segments was higher in extension than in the neutral position (p = 0.0030) or in flexion (p = 0.0002). The FA was significantly lower in extension in patients at both the control level C2/3 (p = 0.0154) and the affected segment (p = 0.0187).
Conclusions
Dynamic DTI of the cervical spine is feasible and ADC increased in the patient group in extension. This finding may open a previously unexplored avenue to attempt an earlier identification of myelopathy.
https://ift.tt/2qEdODI
Laparoscopic paraaortic surgical staging in locally advanced cervical cancer: a single-center experience
Abstract
Background
One aim of this study was to assess the efficacy and safety of laparoscopic paraaortic lymphadenectomy for paraaortic lymph node staging in locally advanced cervical carcinoma. The second aim was to identify prognostic factors in the evolution of this disease and to evaluate how the results of the surgery modify the oncological treatment of patients.
Materials and methods
We analyzed 59 patients diagnosed with locally advanced cervical cancer International Federation of Gynecology and Obstetrics stage IB2–IVA who underwent laparoscopic paraaortic lymphadenectomy at our hospital between 2009 and 2015. Depending on the results of the paraaortic lymphadenectomy, treatment consisted of pelvic- or extended-field chemoradiotherapy.
Results
The mean age at diagnosis was 52.3 years. The median operative time was 180 min. The mean hospital stay was 1.7 days. The mean number of paraaortic lymph nodes excised was 16.4. Eight patients (13.5%) had positive paraaortic lymph nodes. Thirteen patients (22%) underwent surgery via the transperitoneal route, and 46 (78%) underwent surgery via the retroperitoneal route. The sensitivity and specificity of computerized axial tomography (CT) scanning for detecting paraaortic lymph node involvement was 75 and 86%, respectively. The statistically significant prognostic factors that affected survival were surgical paraaortic lymph node involvement, radiological pelvic lymph node involvement, and radiological tumor size as assessed with nuclear magnetic resonance. The rate of serious complications was 1.7%.
Conclusions
Pretherapeutic laparoscopic paraaortic lymphadenectomy for locally advanced cervical carcinoma allows the adaption of radiotherapy fields to avoid false-positive and false-negative imaging results.
https://ift.tt/2qHhZPT
Prognostic value of Ki-67 according to age in patients with triple-negative breast cancer
Abstract
Purpose
The prognostic value of Ki-67 in triple-negative breast cancer (TNBC) is yet unclear because the cut-off points employed differ widely and its predictive effect may vary according to age. The purpose of this study was to analyze the role of Ki-67 among patients with TNBC, and determine the optimal Ki-67 cut-off point to demonstrate its prognostic relevance associated with patient age and treatment strategy.
Methods/patients
201 consecutive patients treated for primary TNBC from 1999 to 2014 were analyzed. Clinicopathological characteristics and outcomes were compared between patients treated with neoadjuvant or adjuvant chemotherapy. We used time-dependent receiver operating characteristic (ROC) curve and time-dependent area under the ROC curve (AUC) to evaluate the discriminative ability of Ki-67 at 3 and 5 years of follow-up. A Ki-67 cut-off point that maximized sensibility and specificity was established. Interaction effect between age and Ki-67 on disease-free survival (DFS) and overall survival (OS) was evaluated by stratified analysis.
Results
According to the coordinates of the ROC curves, the best cut-off point for Ki-67 was 60% (high/low). In the whole group, there was not a statistically significant association between Ki-67 and OS and DFS, using a cut-off point of 60%. In multivariate analysis (COX proportional hazards regression), for DFS high Ki-67 (> 60%) was a poor prognostic factor in patients > 40 years old and a better prognostic factor among the patients < 40 years old.
Conclusion
Prognostic value of Ki-67 in TNBC, using a cut-off point of 60%, may vary depending on age.
https://ift.tt/2vsBQY0
Ambient benzene at the residence and risk for subtypes of childhood leukemia, lymphoma and CNS tumor
International Journal of Cancer, EarlyView.
https://ift.tt/2qI84ch
Fla. county considers waiving ambulance fees for locals
Bay County commissioners are considering a policy that would still bill insurance companies, but not require locals to pay out-of-pocket fees
https://ift.tt/2J4Rk6o
Prognostic value of systemic inflammatory markers in ovarian Cancer: a PRISMA-compliant meta-analysis and systematic review
Abstract
Background
The prognostic effect of elevated systemic inflammatory markers, including neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), remains controversial in cancer patients. This meta-analysis was conducted to evaluate the predictive values of these markers for prognoses in ovarian cancer patients.
Methods
Potentially relevant publications in PubMed, ISI Web of Science, and EBSCO were searched. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) for overall survival (OS) and progression-free survival (PFS) were determined using a fixed or random effects model.
Results
Ten studies involving 2919 patients were included in this meta-analysis. In multivariate analysis, the group with higher NLR had worse OS (HR = 1.34, 95% CI = 1.16-1.54) and shorter PFS (HR = 1.36, 95% CI = 1.17-1.57) than the control group. Furthermore, PLR values higher than the cut-off were associated with not only poorer OS (HR = 1.97, 95% CI = 1.61-2.40) but also more unfavorable PFS (HR = 1.79, 95% CI = 1.46-2.20). Univariate analysis also indicated the same results. Additionally, subgroup analysis showed that when the cut-off values for NLR and PLR were higher, their predictive effects became stronger.
Conclusion
This comprehensive meta-analysis suggested that the values of inflammatory markers such as NLR and PLR were associated with ovarian cancer survival. Therefore, inflammatory markers can potentially serve as prognostic biomarkers.
https://ift.tt/2HtZUyn
Predictive values of upper gastrointestinal cancer alarm symptoms in the general population: a nationwide cohort study
Abstract
Background
Survival rates for upper gastrointestinal (GI) cancer are poor since many are diagnosed at advanced stages. Fast track endoscopy has been introduced to prompt diagnosis for patients with alarm symptoms that could be indicative of upper GI cancer. However, these symptoms may represent benign conditions and little is known about the predictive values of alarm symptoms of upper GI cancer in the general population.
Methods
The study is a nationwide cohort study of 60,562 individuals aged 45 years or above randomly selected from the Danish general population. Participants were invited to complete a survey comprising of questions on several symptom experiences, including alarm symptoms for upper GI cancer within the past four weeks. The participants were asked about specific symptoms (repeated vomiting, difficulty swallowing, signs of upper GI bleeding or persistent and recent-onset abdominal pain) and non-specific symptoms (nausea, weight loss, loss of appetite, feeling unwell and tiredness).
We obtained information on upper GI cancer diagnosed in a 12-month period after completing the questionnaire from the Danish Cancer Registry. We calculated positive predictive values and positive likelihood ratios for the association between alarm symptom and subsequent upper GI cancer.
Results
A total of 33,040 individuals above 45 years completed the questionnaire, yielding a response rate of 54.6%. Respondents were fairly respresentative of the study sample. During the follow-up period, 18 people were diagnosed with upper GI cancer. The number of incident cancers was similar among eligible non-respondents. Two thirds of the respondents with an upper GI malignancy had experienced one or more alarm symptoms.
The positive predictive value for being diagnosed with upper GI cancer after reporting a least one alarm symptom was 0.1% (95% CI:0.0–0.1%). The positive likelihood ratio was 4.4 for specific alarm symptoms and 1.1 for non-specific alarm symptoms.
Conclusions
We found that positive predictive values of alarm symptoms of upper GI cancer experienced in the general population are low. It is important knowledge that despite denoted alarm symptoms even patients with specific alarm symptoms of upper GI cancer have a low risk of being diagnosed with upper GI cancer.
https://ift.tt/2vqS0Rx
Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) for the treatment of malignant mesothelioma
Abstract
Background
Patients with recurrent malignant epithelioid mesothelioma (MM) after surgery and standard chemotherapy with cisplatin and pemetrexed have limited treatment options.
Methods
We performed a retrospective cohort study of patients with recurrent MM undergoing Pressurized IntraPeritoneal/Thoracal Aerosol Chemotherapy (PIPAC/PITAC) with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2. Data were retrospectively collected in a prospective registry of patients undergoing PIPAC/PITAC. Study outcomes were microscopic tumor regression grade (TRG), survival and adverse events (v4.0 CTCAE).
Results
A total of 29 patients (m/f = 17/12) with MM with a mean age of 62.4 (range: 42 to 84) years were analyzed. A total of 74 PIPAC and 5 PITAC procedures were performed. The mean number of PIPAC applications was 2.5 (range: 0 to 10) per patient. Twenty patients (69%) had > 2 PIPAC procedure and were eligible for TRG analysis. TRG 1 to 4 was observed in 75% (15/20) of patients. Major regression (TRG 3) or complete regression (TRG 4) was observed in 20% and 10%, respectively. PIPAC induced significant tumor regression in 51.7% (15/29) of patients with a cumulative effect after repetitive PIPACs (PIPAC #1 vs. PIPAC #2: p = 0.001; PIPAC #1 vs. PIPAC #3: p = 0.001; PIPAC #1 vs. PIPAC #4: p = 0.001). Postoperative CTCAE grade 4 complications were observed in two patients (6.9%) who had cytoreductive surgery (CC2) and intraoperative PIPAC. One patient (3.4%) died due to postoperative kidney insufficiency. After a follow up of 14.4 (95% CI: 8.1 to 20.7) months after the last PIPAC/PITAC application, median overall survival was 26.6 (95% CI: 9.5 to 43.7) months (from the first application).
Conclusion
After prior abdominal surgery and systemic chemotherapy, repetitive PIPAC applications are feasible and safe for patients with end-stage MM. Furthermore, PIPAC induces significant histological regression of malignant mesothelioma in the majority of patients. PITAC is feasible, but its safety and efficacy to control malignant pleural effusion remain unclear.
https://ift.tt/2qIBKGT
Salivary extracellular vesicle-associated miRNAs as potential biomarkers in oral squamous cell carcinoma
Abstract
Background
Several studies in the past have investigated the expression of micro RNAs (miRNAs) in saliva as potential biomarkers. Since miRNAs associated with extracellular vesicles (EVs) are known to be protected from enzymatic degradation, we evaluated whether salivary EVs from patients with oral squamous cell carcinoma (OSCC) were enriched with specific subsets of miRNAs.
Methods
OSCC patients and controls were matched with regards to age, gender and risk factors. Total RNA was extracted from salivary EVs and the differential expression of miRNAs was evaluated by qRT-PCR array and qRT-PCR. The discrimination power of up-regulated miRNAs as biomarkers in OSCC patients versus controls was evaluated by the Receiver Operating Characteristic (ROC) curves.
Results
A preliminary qRT-PCR array was performed on samples from 5 OSCC patients and 5 healthy controls whereby a subset of miRNAs were identified that were differentially expressed. On the basis of these results, a cohort of additional 16 patients and 6 controls were analyzed to further confirm the miRNAs that were up-regulated or selectively expressed in the previous pilot study. The following miRNAs: miR-302b-3p and miR-517b-3p were expressed only in EVs from OSCC patients and miR-512-3p and miR-412-3p were up-regulated in salivary EVs from OSCC patients compared to controls with the ROC curve showing a good discrimination power for OSCC diagnosis. The Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis suggested the possible involvement of the miRNAs identified in pathways activated in OSCC.
Conclusions
In this work, we suggest that salivary EVs isolated by a simple charge-based precipitation technique can be exploited as a non-invasive source of miRNAs for OSCC diagnosis. Moreover, we have identified a subset of miRNAs selectively enriched in EVs of OSCC patients that could be potential biomarkers.
https://ift.tt/2vrTVpb
Improving quality of life through the routine use of the patient concerns inventory for head and neck cancer patients: a cluster preference randomized controlled trial
Abstract
Background
The consequences of treatment for Head and Neck cancer (HNC) patients has profound detrimental impacts such as impaired QOL, emotional distress, delayed recovery and frequent use of healthcare. The aim of this trial is to determine if the routine use of the Patients Concerns Inventory (PCI) package in review clinics during the first year following treatment can improve overall quality of life, reduce the social-emotional impact of cancer and reduce levels of distress. Furthermore, we aim to describe the economic costs and benefits of using the PCI.
Methods
This will be a cluster preference randomised control trial with consultants either 'using' or 'not using' the PCI package at clinic. It will involve two centres Leeds and Liverpool. 416 eligible patients from at least 10 consultant clusters are required to show a clinically meaningful difference in the primary outcome. The primary outcome is the percentage of participants with less than good overall quality of life at the final one-year clinic as measured by the University of Washington QOL questionnaire version 4 (UWQOLv4). Secondary outcomes at one-year are the mean social-emotional subscale (UWQOLv4) score, Distress Thermometer (DT) score ≥ 4, and key health economic measures (QALY-EQ-5D-5 L; CSRI).
Discussion
This trial will provide knowledge on the effectiveness of a consultation intervention package based around the PCI used at routine follow-up clinics following treatment of head and neck cancer with curative intent. If this intervention is (cost) effective for patients, the next step will be to promote wider use of this approach as standard care in clinical practice.
Trial registration
32,382. Clinical Trials Identifier, NCT03086629. Protocol: Version 3.0, 1st July 2017.
https://ift.tt/2HAEMGP
Small cell and non small cell lung cancer form metastasis on cellular 4D lung model
Abstract
Background
Metastasis is the main cause of death for lung cancer patients. The ex vivo 4D acellular lung model has been shown to mimic this metastatic process. However, the main concern is the model's lack of cellular components of the tumor's microenvironment. In this study, we aim to determine if the intact lung microenvironment will still allow lung cancer metastasis to form.
Methods
We harvested a heart-lung block from a rat and placed it in a bioreactor after cannulating the pulmonary artery, trachea and tying the right main bronchus for 10–15 days without any tumor cells as a control group or with NSCLC (A549, H1299 or H460), SCLC (H69, H446 or SHP77) or breast cancer cell lines (MCF7 or MDAMB231) through the trachea. We performed lobectomy, H&E staining and IHC for human mitochondria to determine the primary tumor's growth and formation of metastatic lesions. In addition, we isolated circulating tumor cells (CTC) from the model seeded with GFP tagged cells.
Results
In the control group, no gross tumor nodules were found, H&E staining showed hyperplastic cells and IHC showed no staining for human mitochondria. All of the models seeded with cancer cell lines formed gross primary tumor nodules that had microscopic characteristics of human cancer cells on H&E staining with IHC showing staining for human mitochondria. CTC were isolated for those cells labeled with GFP and they were viable in culture. Finally, all cell lines formed metastatic lesions with cells stained for human mitochondria.
Conclusion
The cellular ex vivo 4D model shows that human cancer cells can form a primary tumor, CTC and metastatic lesions in an intact cellular environment. This study suggests that the natural matrix scaffold is the only necessary component to drive metastatic progression and that cellular components play a role in modulating tumor progression.
https://ift.tt/2J4idaG
Εγγραφή σε:
Αναρτήσεις (Atom)
-
Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
-
heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
-
https://ift.tt/2MQ8Ai8
