Compositional asymmetry between the leaflets of bilayer membranes modifies their phase behaviour, and is thought to influence other important features such as mechanical properties and protein activity. We address here how phase behaviour is affected by passive phospholipid flip-flop, such that the compositional asymmetry is not fixed. We predict transitions from "pre flip-flop" behaviour to a restricted set of phase equilibria that can persist in the presence of passive flip-flop. Surprisingly, such states are not necessarily symmetric.
https://ift.tt/2QEtEJM
Τρίτη 9 Οκτωβρίου 2018
Effects of passive phospholipid flip-flop and asymmetric external fields on bilayer phase equilibria
Forces on nascent polypeptides during membrane insertion and translocation via the Sec translocon
During ribosomal translation, nascent polypeptide chains (NCs) undergo a variety of physical processes that determine their fate in the cell. This study utilizes a combination of arrest peptide (AP) experiments and coarse-grained molecular dynamics (CGMD) to measure and elucidate the molecular origins of forces that are exerted on NCs during co-translational membrane insertion and translocation via the Sec translocon. The approach enables deconvolution of force contributions from NC-translocon and NC-ribosome interactions, membrane partitioning, and electrostatic coupling to the membrane potential.
https://ift.tt/2A1ysDR
Incident cognitive impairment: longitudinal changes in molecular, structural and cognitive biomarkers
Abstract
Longer periods are needed to examine how biomarker changes occur relative to incident sporadic cognitive impairment. We evaluated molecular (CSF and imaging), structural, and cognitive biomarkers to predict incident cognitive impairment and examined longitudinal biomarker changes before and after symptomatic onset. Data from participants who were cognitively normal, underwent amyloid imaging using Pittsburgh compound B and/or CSF studies, and at least two clinical assessments were used. Stepwise Cox proportional hazards models tested associations of molecular (Pittsburgh compound B; CSF amyloid-β42, tau, ptau181, tau/amyloid-β42, ptau181/amyloid-β42), structural (normalized hippocampal volume, normalized whole brain volume), and cognitive (Animal Naming, Trail Making A, Trail Making B, Selective Reminding Test - Free Recall) biomarkers with time to Clinical Dementia Rating (CDR) > 0. Cognitively normal participants (n = 664), aged 42 to 90 years (mean ± standard deviation = 71.4 ± 9.2) were followed for up to 16.9 years (mean ± standard deviation = 6.2 ± 3.5 years). Of these, 145 (21.8%) participants developed a CDR > 0. At time of incident cognitive impairment, molecular, structural, and cognitive markers were abnormal for CDR > 0 compared to CDR = 0. Linear mixed models indicated rates of change in molecular biomarkers were similar for CDR = 0 and CDR > 0, suggesting that the separation in values between CDR = 0 and CDR > 0 must have occurred prior to the observation period. Rate of decline for structural and cognitive biomarkers was faster for CDR > 0 compared to CDR = 0 (P < 0.0001). Structural and cognitive biomarkers for CDR > 0 diverged from CDR 0 at 9 and 12 years before incident cognitive impairment, respectively. Within those who developed CDR > 0, a natural separation occurred for Pittsburgh compound B values. In particular, CDR > 0 who had at least one APOE ɛ4 allele had higher, and more rapid increase in Pittsburgh compound B, while APOE ɛ2 was observed to have slower increases in Pittsburgh compound B. Of molecular biomarker-positive participants followed for at least 10 years (n = 16–23), ∼70% remained CDR = 0 over the follow-up period. In conclusion, conversion from cognitively normal to CDR > 0 is characterized by not only the magnitude of molecular biomarkers but also rate of change in cognitive and structural biomarkers. Findings support theoretical models of biomarker changes seen during transition to cognitive impairment using longitudinal data and provide a potential time for changes seen during this transition. These findings support the use of molecular biomarkers for trial inclusion and cognitive/structural biomarkers for evaluating trial outcomes. Finally, results support a potential role for APOE ɛ in modulating amyloid accumulation in CDR > 0 with APOE ɛ4 being deleterious and APOE ɛ2 protective.https://ift.tt/2INtjlo
Phase I/II clinical trial of a Wilms’ tumor 1-targeted dendritic cell vaccination-based immunotherapy in patients with advanced cancer
Abstract
Dendritic cell (DC)-based immunotherapies have been created for a broad expanse of cancers, and DC vaccines prepared with Wilms' tumor protein 1 (WT1) peptides have shown great therapeutic efficacy in these diseases. In this paper, we report the results of a phase I/II study of a DC-based vaccination for advanced breast, ovarian, and gastric cancers, and we offer evidence that patients can be effectively vaccinated with autologous DCs pulsed with WT1 peptide. There were ten patients who took part in this clinical study; they were treated biweekly with a WT1 peptide-pulsed DC vaccination, with toxicity and clinical and immunological responses as the principal endpoints. All of the adverse events to DC vaccinations were tolerable under an adjuvant setting. The clinical response was stable disease in seven patients. Karnofsky Performance Scale scores were enhanced, and computed tomography scans revealed tumor shrinkage in three of seven patients. Human leukocyte antigen (HLA)/WT1-tetramer and cytoplasmic IFN-γ assays were used to examine the induction of a WT-1-specific immune response. The immunological responses to DC vaccination were significantly correlated with fewer myeloid-derived suppressor cells (P = 0.045) in the pretreated peripheral blood. These outcomes offered initial clinical evidence that the WT1 peptide-pulsed DC vaccination is a potential treatment for advanced cancer.
https://ift.tt/2yaypnU
Cancers, Vol. 10, Pages 375: Energy Stress-Mediated Cytotoxicity in Tuberous Sclerosis Complex 2-Deficient Cells with Nelfinavir and Mefloquine Treatment
Cancers, Vol. 10, Pages 375: Energy Stress-Mediated Cytotoxicity in Tuberous Sclerosis Complex 2-Deficient Cells with Nelfinavir and Mefloquine Treatment
Cancers doi: 10.3390/cancers10100375
Authors: Henry D. McCann Charlotte E. Johnson Rachel J. Errington D. Mark Davies Elaine A. Dunlop Andrew R. Tee
To find new anti-cancer drug therapies, we wanted to exploit homeostatic vulnerabilities within Tuberous Sclerosis Complex 2 (TSC2)-deficient cells with mechanistic target of rapamycin complex 1 (mTORC1) hyperactivity. We show that nelfinavir and mefloquine synergize to selectively evoke a cytotoxic response in TSC2-deficient cell lines with mTORC1 hyperactivity. We optimize the concentrations of nelfinavir and mefloquine to a clinically viable range that kill cells that lack TSC2, while wild-type cells tolerate treatment. This new clinically viable drug combination causes a significant level of cell death in TSC2-deficient tumor spheroids. Furthermore, no cell recovery was apparent after drug withdrawal, revealing potent cytotoxicity. Transcriptional profiling by RNA sequencing of drug treated TSC2-deficient cells compared to wild-type cells suggested the cytotoxic mechanism of action, involving initial ER stress and an imbalance in energy homeostatic pathways. Further characterization revealed that supplementation with methyl pyruvate alleviated energy stress and reduced the cytotoxic effect, implicating energy deprivation as the trigger of cell death. This work underpins a critical vulnerability with cancer cells with aberrant signaling through the TSC2-mTORC1 pathway that lack flexibility in homeostatic pathways, which could be exploited with combined nelfinavir and mefloquine treatment.
https://ift.tt/2RFyGqJ
Several household chemical exposures are associated with pediatric‐onset multiple sclerosis
Annals of Clinical and Translational Neurology, EarlyView.
https://ift.tt/2CAqEeM
Distribution of tumor-infiltrating immune cells in glioblastoma
CNS Oncology, Ahead of Print.
https://ift.tt/2EaCPAw
Effect of Exogenous Zinc on MsrB1 Expression and Protein Oxidation in Human Lens Epithelial Cells
Abstract
Aging has been related to zinc deficiency, resulting in protein oxidation and age-related decline of methionine sulfoxide reductase (Msr) activity. This study was designed to investigate the levels of methionine sulfoxide reductase B1 (MsrB1) mRNA and oxidized proteins in human lens epithelial (hLE) cells after treatment with exogenous zinc. The role of exogenous zinc in regulation of MsrB1 gene expression and protein oxidation in hLE cells was studied by MTT assay, oxidized protein measurement kit, and real-time PCR. The results showed that hLE cell viability was significantly decreased by MsrB1 gene knockdown or peroxynitrite (ONOO−) treatment, while it was significantly increased after treatment with exogenous zinc (P < 0.05). Protein carbonyl content in hLE cell by MsrB1 gene knockdown or ONOO− treatment was significantly decreased after treatment with ZnSO4 (P < 0.01). And exogenous zinc could increase the level of MsrB1 in hLE cell under normal (P < 0.001) and oxidative stress (P < 0.01) conditions. In conclusion, exogenous zinc could protect hLE cells against MsrB1 gene knockdown or ONOO−-induced cell death by upregulation of MsrB1 involved in the elimination of reactive oxygen species (ROS) and oxidized proteins.
https://ift.tt/2NyUkd7
Melatonin Ameliorates Neuropharmacological and Neurobiochemical Alterations Induced by Subchronic Exposure to Arsenic in Wistar Rats
Abstract
An experimental study was conducted in Wistar rats to characterize the arsenic ("As")-induced alterations in neurobiochemistry in brain and its impact on neuropharmacological activities with or without the melatonin (MLT) as an antioxidant given exogenously. Male Wistar rats were randomly divided in to four groups of six each. Group I served as untreated control, while group II received As [sodium (meta) arsenite; NaAsO2] at 10 mg/kg bw (p.o.) for a period of 56 days. Experimental rats in group III received treatment similar to group II but in addition received MLT at 10 mg/kg bw (p.o.) from day 32 onwards. Rats in group IV received MLT alone from day 32 onwards similar to group III. Sub-chronic exposure to As (group II) significantly reduced both voluntary locomotor and forced motor activities and melatonin supplementation (group III) showed a significant improvement in motor activities, when subjected to test on day 42 or 56. Rats exposed to As showed a significant increase in anxiety level and a marginal nonsignificant reduction in pain latency. Sub-chronic administration of As induced (group II) significant increase in the levels of thiobarbituric acid reactive substance (TBARS) called malondialdehyde (MDA) in the brain tissue (5.55 ± 0.57 nmol g−1), and their levels were significantly reduced by MLT supplementation (group III 3.96 ± 0.15 nmol g−1). The increase in 3-nitrotyrosine (3-NT) levels in As-exposed rats indicated nitrosative stress due to the formation of peroxynitrite (ONOO−). However, exogenously given MLT significantly reduced the 3-NT formation as well as prostaglandin (PGE2) levels in the brain. Similarly, MLT administration have suppressed the release of pro-inflammatory cytokines (viz., IL-1β, IL-6, and TNF-α) and amyloid-β1–40 (Aβ) deposition in the brain tissues of experimental rats. To conclude, exogenous administration of melatonin can overcome the sub-chronic As-induced oxidative and nitrosative stress in the CNS, suppressed pro-inflammatory cytokines, and restored certain disturbed neuropharmacological activities in Wistar rats.
https://ift.tt/2ONrcn7
Neuromuscular electrical stimulation increases serum brain-derived neurotrophic factor in humans
Abstract
Brain-derived neurotrophic factor (BDNF) plays several important roles in nervous system function including neuronal growth and plasticity. The purpose of the present study was to clarify whether neuromuscular electrical stimulation (NMES) and voluntary exercise to the same integrated force as by the NMES-induced exercise would enhance serum BDNF. Eleven healthy male subjects completed three interventions (NMES, voluntary exercise, and resting interventions) for 20 min on different days. In the NMES intervention, NMES was applied to the quadriceps femoris muscles. The stimulus intensity of NMES was progressively increased to the highest tolerated intensity during the experiment. In the voluntary exercise intervention, subjects performed an isometric knee-extension task; in this intervention, the target torque was calculated in accordance with the integrated force of knee extension obtained during the NMES intervention. In the resting intervention, subjects relaxed in a sitting posture. We measured serum BDNF, blood lactate, heart rate, oxygen uptake, respiratory ratio, and blood pressure. Serum BDNF was increased in the NMES (p = 0.003) and voluntary exercise interventions (p = 0.004) after each intervention. At the post-timepoint, serum BDNF in the NMES intervention was highest among all interventions (p = 0.038) and significantly higher than in the voluntary exercise (p = 0.036) and resting (p = 0.037) interventions. Our results showed that NMES was more effective for enhancing serum BDNF than voluntary exercise at least when employing the same method and integrated force.
https://ift.tt/2EcrMXr
Phase I/II clinical trial of a Wilms’ tumor 1-targeted dendritic cell vaccination-based immunotherapy in patients with advanced cancer
Abstract
Dendritic cell (DC)-based immunotherapies have been created for a broad expanse of cancers, and DC vaccines prepared with Wilms' tumor protein 1 (WT1) peptides have shown great therapeutic efficacy in these diseases. In this paper, we report the results of a phase I/II study of a DC-based vaccination for advanced breast, ovarian, and gastric cancers, and we offer evidence that patients can be effectively vaccinated with autologous DCs pulsed with WT1 peptide. There were ten patients who took part in this clinical study; they were treated biweekly with a WT1 peptide-pulsed DC vaccination, with toxicity and clinical and immunological responses as the principal endpoints. All of the adverse events to DC vaccinations were tolerable under an adjuvant setting. The clinical response was stable disease in seven patients. Karnofsky Performance Scale scores were enhanced, and computed tomography scans revealed tumor shrinkage in three of seven patients. Human leukocyte antigen (HLA)/WT1-tetramer and cytoplasmic IFN-γ assays were used to examine the induction of a WT-1-specific immune response. The immunological responses to DC vaccination were significantly correlated with fewer myeloid-derived suppressor cells (P = 0.045) in the pretreated peripheral blood. These outcomes offered initial clinical evidence that the WT1 peptide-pulsed DC vaccination is a potential treatment for advanced cancer.
https://ift.tt/2yaypnU
Syringomyelia-like syndrome in neuromyelitis optica spectrum disorder complicated with Sjogren’s syndrome: a case report
Besides CSF-flow obstruction, syringomyelia is associated with inflammatory spinal cord lesions. However, syringomyelia-like syndrome concomitant with neuromyelitis optica spectrum disorder (NMOSD) and primary...
https://ift.tt/2OQP7Ce
Castleman disease of the hyaline vascular variant transforming to POEMS syndrome as endpoint: a case report
POEMS syndrome is a rare neoplastic syndrome reflected by plasma cell disorder. It is composed by polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. It is also reported to asso...
https://ift.tt/2NyQL6J
Gaze and the Eye Pupil Adjust to Imagined Size and Distance
Cognitive Science, EarlyView.
https://ift.tt/2C6nxtM
The role of tissue and serum carcinoembryonic antigen in stages I to III of colorectal cancer—A retrospective cohort study
Cancer Medicine, EarlyView.
https://ift.tt/2OQTs8n
A p53-responsive microRNA network promotes cancer cell quiescence
Cancer cells in quiescence (G0 phase) are resistant to death, and re-entry of quiescent cancer cells into the cell cycle plays an important role in cancer recurrence. Here we show that two p53-responsive microRNAs (miRNAs) utilize distinct but complementary mechanisms to promote cancer cell quiescence by facilitating stabilization of p27. Purified quiescent B16 mouse melanoma cells expressed higher levels of miRNA-27b-3p and miRNA-455-3p relative to their proliferating counterparts. Induction of quiescence resulted in increased levels of these miRNAs in diverse types of human cancer cell lines. Inhibition of miRNA-27b-3p or miRNA-455-3p reduced, whereas its overexpression increased, the proportion of quiescent cells in the population, indicating that these miRNAs promote cancer cell quiescence. Accordingly, cancer xenografts bearing miRNA-27b-3p or miRNA-455-3p mimics were retarded in growth. miRNA-27b-3p targeted cyclin-dependent kinase regulatory subunit 1 (CKS1B), leading to reduction in p27 polyubiquitination mediated by S-phase kinase-associated protein 2 (Skp2). miRNA-455-3p targeted CDK2-associated cullin domain 1 (CACUL1), which enhanced CDK2-mediated phosphorylation of p27 necessary for its polyubiquitination. Of note, the gene encoding miRNA-27b-3p was embedded in the intron of the chromosome 9 open reading frame 3 gene that was transcriptionally activated by p53. Similarly, the host gene of miRNA-455-3p, collagen alpha-1 chain, was also a p53 transcriptional target. Collectively, our results identify miRNA-27b-3p and miRNA-455-3p as important regulators of cancer cell quiescence in response to p53 and suggest that manipulating miRNA-27b-3p and miRNA-455-3p may constitute novel therapeutic avenues for improving outcomes of cancer treatment.
https://ift.tt/2Pmd7tT
LPA4-mediated vascular network formation increases the efficacy of anti-PD-1 therapy against brain tumors
The structure and function of tumor blood vessels profoundly impacts the tumor microenvironment. Signals mediated through the lysophosphatidic acid receptor 4 (LPA4) promote vascular network formation to restore normal vascular barrier function in subcutaneous tumors and thus improve drug delivery. However, the characteristics of the vasculature vary by organ and tumor types, and how drug delivery and leukocyte trafficking are affected by modification of vascular function by LPA in different cancers is unclear. Here we show that LPA4 activation promotes the formation of fine vascular structures in brain tumors. RhoA/ROCK signaling contributed to LPA-induced endothelial cell-cell adhesion, and RhoA/ROCK activity following LPA4 stimulation regulated expression of VCAM-1. This resulted in increased lymphocyte infiltration into the tumor. LPA improved delivery of exogenous IgG into brain tumors and enhanced the anticancer effect of anti-programmed cell death (PD)-1 antibody therapy. These results indicate the effects of LPA on vascular structure and function apply not only to chemotherapy, but also immunotherapy.
https://ift.tt/2yadn8R
A multimodal molecular imaging study evaluates pharmacological alteration of the tumor microenvironment to improve radiation response.
Hypoxic zones in solid tumors contribute to radioresistance, and pharmacological agents that increase tumor oxygenation prior to radiation, including anti-angiogenic drugs, can enhance treatment response to radiotherapy. Although such strategies have been applied, imaging assessments of tumor oxygenation to identify an optimum time window for radiotherapy have not been fully explored. In this study, we investigated the effects of alpha-sulfoquinovosylacyl-1,3-propanediol (SQAP; a synthetic derivative of an anti-angiogenic agent) on the tumor microenvironment in terms of oxygen partial pressure (pO2), oxyhemoglobin saturation (sO2), blood perfusion, and microvessel density using electron paramagnetic resonance imaging, photoacoustic imaging, dynamic contrast-enhanced MRI with Gd-DTPA injection, and T2*-weighted imaging with ultrasmall superparamagnetic iron oxide (USPIO) contrast. SCCVII and A549 tumors were grown by injecting tumor cells into the hind legs of mice. Five days of daily radiation (2 Gy) combined with intravenous injection of SQAP (2 mg/kg) 30 min prior to irradiation significantly delayed growth of tumor xenografts. Three days of daily treatment improved tumor oxygenation and decreased tumor microvascular density on T2*-weighted images with USPIO, suggesting vascular normalization. Acute effects of SQAP on tumor oxygenation were examined by pO2, sO2, and Gd-DTPA contrast-enhanced imaging. SQAP treatment improved perfusion and tumor pO2 (ΔpO2: 3.1±1.0 mmHg) and was accompanied by decreased sO2 (20-30% decrease) in SCCVII implants 20-30 min after SQAP administration. These results provide evidence that SQAP transiently enhances tumor oxygenation by facilitating oxygen dissociation from oxyhemoglobin and improving tumor perfusion. Therefore, SQAP-mediated sensitization to radiation in vivo can be attributed to increased tumor oxygenation.
https://ift.tt/2Pmd5SN
Lorcaserin Beneficial for Diabetes in Overweight, Obese
TUESDAY, Oct. 9, 2018 -- Lorcaserin reduces the risk for diabetes in obese or overweight patients with prediabetes or without diabetes and reduces hemoglobin A1c (HbA1c) among those with diabetes, according to a study published online Oct. 4 in The...
https://ift.tt/2OhKwJA
FDA Approves HPV Vaccine for People Through Age 45
TUESDAY, Oct. 9, 2018 -- U.S. Food and Drug Administration approval of the Gardasil 9 human papillomavirus (HPV) vaccine has been expanded to include people ages 27 through 45, the agency said in a news release. Gardasil 9, approved in 2014 for...
https://ift.tt/2yr2GOh
Polio-Like Condition in Children on Rise Again in the United States
TUESDAY, Oct. 9, 2018 -- A rare, polio-like condition in children is on the rise again in the United States, with 38 confirmed cases in 16 states so far this year, the U.S. Centers for Disease Control and Prevention says. The condition, acute...
https://ift.tt/2OgqvU0
Timing of Pushing Does Not Impact Spontaneous Vaginal Delivery
TUESDAY, Oct. 9, 2018 -- For nulliparous women receiving neuraxial analgesia, the timing of second-stage pushing does not impact the rate of spontaneous vaginal delivery, according to a study published in the Oct. 9 issue of the Journal of the...
https://ift.tt/2yvigIH
Flea-Borne Typhus Outbreak in Los Angeles County
TUESDAY, Oct. 9, 2018 -- An outbreak of flea-borne typhus in Los Angeles County has so far resulted in 57 cases, including 20 in Pasadena and nine in downtown Los Angeles, public health officials say. Symptoms of the bacterial disease include high...
https://ift.tt/2OcfjHM
Genotype-by-Environment-by-Environment Interactions in the Saccharomyces cerevisiae Transcriptomic Response to Alcohols and Anaerobiosis
Next generation biofuels including longer-chain alcohols such as butanol are attractive as renewable, high-energy fuels. A barrier to microbial production of butanols is the increased toxicity compared to ethanol; however, the cellular targets and microbial defense mechanisms remain poorly understood, especially under anaerobic conditions used frequently in industry. Here we took a comparative approach to understand the response of Saccharomyces cerevisiae to 1-butanol, isobutanol, or ethanol, across three genetic backgrounds of varying tolerance in aerobic and anaerobic conditions. We find that strains have different growth properties and alcohol tolerances with and without oxygen availability, as well as unique and common responses to each of the three alcohols. Our results provide evidence for strain-by-alcohol-by-oxygen interactions that moderate how cells respond to alcohol stress.
https://ift.tt/2pMh9R0
Nitazoxanide, an antiprotozoal drug, inhibits late-stage autophagy and promotes ING1-induced cell cycle arrest in glioblastoma
Nitazoxanide, an antiprotozoal drug, inhibits late-stage autophagy and promotes ING1-induced cell cycle arrest in glioblastoma
Nitazoxanide, an antiprotozoal drug, inhibits late-stage autophagy and promotes ING1-induced cell cycle arrest in glioblastoma, Published online: 09 October 2018; doi:10.1038/s41419-018-1058-z
Nitazoxanide, an antiprotozoal drug, inhibits late-stage autophagy and promotes ING1-induced cell cycle arrest in glioblastomahttps://ift.tt/2yr7kMd
Alpha-fetoprotein inhibits autophagy to promote malignant behaviour in hepatocellular carcinoma cells by activating PI3K/AKT/mTOR signalling
Alpha-fetoprotein inhibits autophagy to promote malignant behaviour in hepatocellular carcinoma cells by activating PI3K/AKT/mTOR signalling
Alpha-fetoprotein inhibits autophagy to promote malignant behaviour in hepatocellular carcinoma cells by activating PI3K/AKT/mTOR signalling, Published online: 09 October 2018; doi:10.1038/s41419-018-1036-5
Alpha-fetoprotein inhibits autophagy to promote malignant behaviour in hepatocellular carcinoma cells by activating PI3K/AKT/mTOR signallinghttps://ift.tt/2OfxlZD
Apelin inhibited epithelial−mesenchymal transition of podocytes in diabetic mice through downregulating immunoproteasome subunits β5i
Apelin inhibited epithelial−mesenchymal transition of podocytes in diabetic mice through downregulating immunoproteasome subunits β5i
Apelin inhibited epithelial−mesenchymal transition of podocytes in diabetic mice through downregulating immunoproteasome subunits β5i, Published online: 09 October 2018; doi:10.1038/s41419-018-1098-4
Apelin inhibited epithelial−mesenchymal transition of podocytes in diabetic mice through downregulating immunoproteasome subunits β5ihttps://ift.tt/2OhMKsq
Correction to: TRIM50 suppressed hepatocarcinoma progression through directly targeting SNAIL for ubiquitous degradation
Correction to: TRIM50 suppressed hepatocarcinoma progression through directly targeting SNAIL for ubiquitous degradation
Correction to: TRIM50 suppressed hepatocarcinoma progression through directly targeting SNAIL for ubiquitous degradation, Published online: 09 October 2018; doi:10.1038/s41419-018-0835-z
Correction to: TRIM50 suppressed hepatocarcinoma progression through directly targeting SNAIL for ubiquitous degradationhttps://ift.tt/2ynmG4k
Apatinib-induced protective autophagy and apoptosis through the AKT–mTOR pathway in anaplastic thyroid cancer
Apatinib-induced protective autophagy and apoptosis through the AKT–mTOR pathway in anaplastic thyroid cancer
Apatinib-induced protective autophagy and apoptosis through the AKT–mTOR pathway in anaplastic thyroid cancer, Published online: 09 October 2018; doi:10.1038/s41419-018-1054-3
Apatinib-induced protective autophagy and apoptosis through the AKT–mTOR pathway in anaplastic thyroid cancerhttps://ift.tt/2OcOYcJ
Mitochondrial fusion and Bid-mediated mitochondrial apoptosis are perturbed by alcohol with distinct dependence on its metabolism
Mitochondrial fusion and Bid-mediated mitochondrial apoptosis are perturbed by alcohol with distinct dependence on its metabolism
Mitochondrial fusion and Bid-mediated mitochondrial apoptosis are perturbed by alcohol with distinct dependence on its metabolism, Published online: 09 October 2018; doi:10.1038/s41419-018-1070-3
Mitochondrial fusion and Bid-mediated mitochondrial apoptosis are perturbed by alcohol with distinct dependence on its metabolismhttps://ift.tt/2yqgMPZ
Role of PI3K-Akt and MAPK Signaling in Uranyl Nitrate-Induced Nephrotoxicity
Abstract
Uranium is a heavy metal of considerable environmental and occupational concern. It is well-known that the kidney is the major target organ of uranium exposure. Elucidating the mechanistic basis of uranium interactions is essential for monitoring the health risk. In the present study, we investigated the cellular mechanisms involved in uranyl nitrate-induced nephrotoxicity. Male Swiss albino mice were administrated with a single intraperitoneal dose of 2 and 4 mg/kg of uranyl nitrate at different time points 1, 3, 5, 7, 14, and 28 days. Uranyl nitrate intoxication-induced apoptosis in the kidney tissue was observed by TUNEL assay. To assess the proliferation, immunohistochemistry was performed using Ki67 proliferative marker followed by western blotting to confirm the involvement of key signaling molecules. The number of TUNEL positive nuclei peaked at third day after uranyl nitrate insult. The increased expression of proliferation marker Ki67 suggests the enhanced DNA repair process prominently at seventh day. Uranyl nitrate administration also resulted in activation of extracellular signal-regulated kinases (ERK), Akt, and c-Jun N-terminal kinases (JNK) expression. All these changes were found to be time-dependent. The result of the current study suggests that uranyl nitrate induces acute renal injury by activation of apoptosis through JNK pathway, while the early activation of signaling molecules Akt and ERK promotes the tubular cell proliferation and cell survival.
https://ift.tt/2Ea7VZ5
Visual Estimation of Force Applied During Simulated Deliveries Complicated by Shoulder Dystocia
AJP Rep 2018; 08: e206-e211
DOI: 10.1055/s-0038-1673377
Background Shoulder dystocia occurs when the fetal head delivers, but the shoulder is lodged behind the pubic symphysis. Training for these emergency deliveries is not optimized, and litigation can occur around a shoulder dystocia delivery. Objective Evaluate the ability of an outside observer to visually estimate the amount of traction applied to the fetal head during simulated deliveries complicated by shoulder dystocia. Study Design Simulated deliveries with an objective measurement of traction were randomly organized for estimation of traction applied. Videos show providers applying a "normal" (75 N) and "excessive" (150 N) amount of force in both a "calm" and "stressed" delivery. Results Fifty participants rated the amount of force applied. Observers estimated traction, on a scale from 1 to 5, higher in the 150-N deliveries as compared with 75-N deliveries ("calm" environment: 3.1 vs. 2.8, p < 0.001; and "stressed" environment: 3.2 vs. 2.8, p < 0.001). Only 15% of observers rated force "above average" or "excessive" in a "calm" environment, as opposed to 30% of observers in the "stressed" environment. Conclusion Observers are not able to determine when "excessive force" is used and are twice as likely to overestimate the force applied to a fetal head when an average amount of force is used and the delivery environment is stressful. Precis Observers are unable to determine when excessive traction is applied to the fetal head during simulated deliveries complicated by shoulder dystocia.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | open access Full text
https://ift.tt/2OVtctL
Fetal Congenital Peripheral Bronchial Atresia Diagnosed by Magnetic Resonance Imaging: Two Case Reports
AJP Rep 2018; 08: e201-e205
DOI: 10.1055/s-0038-1673620
Two types of congenital bronchial atresia (proximal and peripheral) have been classified. We report two cases of peripheral bronchial atresia diagnosed by prenatal ultrasonography (US) and magnetic resonance imaging (MRI). Evaluating an enlarged lung mass that is homogeneously hyperechoic on US and hyperintense on T2-weighted MRI can help in determining whether bronchial atresia is present. Proximal type is suggested when a dilated main bronchus is observed as a tubule structure of an involved lung hilum. In our cases, T2-weighted MRI revealed homogeneously hyperintense lung lesion with decreased signal intensity of adjacent lobe, flattening diaphragm, and mediastinal shift. Dilatation of the main bronchus was not observed and the opposite lung was normal in appearance. These findings were explained by secondary compression due to enlargement of the involved lung. The preservation of vascular structure and the retained normal shape, though enlarged, in the affected lobe were observed, which demonstrated undisrupted pulmonary architecture of the lobe. Thus, congenital cystic adenomatoid malformation was excluded because pulmonary architecture was relatively preserved. Finally, presumed diagnoses of the peripheral bronchial atresia were made and confirmed by postnatal chest computed tomography.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | open access Full text
https://ift.tt/2NxWcmd
Adipocyte proteome and secretome influence inflammatory and hormone pathways in glioma
Abstract
Gliomas represent the most common primary malignant brain tumors in adults, with an extremely poor prognosis. Among several risk factors, lifestyle was also recently identified as a major risk factor for the development of primary glioma. In the present study, we explore the relationship between obesity and glioma in a cellular model. Thus, we have study the influence of adipocytes secretome on glioma cell line GL261. Using the 3T3-L1 adipocyte cell line, and its conditioned medium (adipokines-enriched medium), we showed that adipocyte-released factors relate with glioma angiogenic, growth, hormones and metabolic behavior by MALDI-TOF-MS and proteomic array analysis. In a first view, STI1, hnRNPs and PGK1 are under expressed on CGl. Similarly, both carbonic anhydrase and aldose reductase are even suppressed in glioma cells that grown under adipokines-enriched environment. Contrariwise, RFC1, KIF5C, ANXA2, N-RAP and RACK1 are overexpressed in GL261 cell the in the presence of the adipokines-enriched medium. We further identified the factors that are released by adipocyte cells, and revealed that several pro-inflammatory and angiogenic factors, such as IL-6, IL-11, LIF, PAI-1, TNF-α, endocan, HGF, VEGF IGF-I, were secreted to the medium into a high extent, whereas TIMP-1 and SerpinE1 were under expressed on CGl. This study discloses an interesting in vitro model for the study of glioma biology under a "obesity" environment, that can be explored for the understanding of cancer cells biology, for the search of biomarkers, prognostic markers and therapeutic approaches.
https://ift.tt/2C696pK
Smoking cessation among men following cancer diagnosis: a matched cohort study
Abstract
Purpose
Cigarette smoking among cancer survivors increases the risk of recurrence and secondary cancers. We sought to investigate smoking cessation following diagnosis of cancer compared to those not diagnosed with cancer. We also investigated cessation following diagnosis of a smoking-related and non-smoking-related cancer separately.
Methods
We conducted a matched cohort study within the Health Professionals Follow-Up Study (HPFS). We identified 566 men diagnosed with cancer who were current cigarette smokers at the time of diagnosis between 1986 and 2010 (exposed). Men diagnosed with cancer were age-matched 1:4 to men without a diagnosis of cancer who were also current cigarette smokers (unexposed). Multivariable conditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) to evaluate the association between a cancer diagnosis and smoking cessation within 2 and 4 years post diagnosis adjusted for potential confounders, overall and for smoking-related and non-smoking-related cancers.
Results
Of the men with cancer, 38% quit within 2 years and 42% within 4 years of diagnosis. Men diagnosed with cancer were more likely to quit smoking within 2 (OR = 2.5, 95% CI: 2.0–3.0) and 4 years (OR = 1.6, 95% CI: 1.3–2.0) post diagnosis, compared to matched men without cancer. The association was similar for smoking-related (OR = 3.4, 95%: 1.6–7.2) and non-smoking-related cancers (OR = 3.8, 95%: 2.8–5.2).
Conclusions
Men diagnosed with cancer were more likely to quit smoking compared to men not diagnosed with cancer. A cancer diagnosis may be a "teachable moment" in which strategies to promote smoking cessation for individuals diagnosed with smoking-related and non-smoking-related cancers should be investigated.
Implications for Cancer Survivors
There is a continued need for the widespread implementation of cessation interventions for cancer survivors.
https://ift.tt/2CARrYr
Polyp Sizing Poster Improve Polyp Measurement but not Adenoma Detection Rates by Endoscopists in a Large Community Practice
Accurate sizing of polyps and improving adenoma detection rates (ADR) are important goals for high-quality colonoscopy. Surveillance intervals are based on accurate sizing of polyps. There are no clinical tools or interventions that have demonstrated improvement in both these metrics. We investigated the efficacy of a simple, low-cost intervention, based on use of polyp sizing posters to improve measurements of polyps and increase ADRs during colonoscopy at a large gastroenterology community practice.
https://ift.tt/2C60UWw
Management Algorithm for Interrupting Mother to Child Transmission of Hepatitis B Virus
In areas where hepatitis B virus (HBV) is endemic, mother to child transmission (MTCT) is the major route of infection of children. Blocking MTCT of HBV would therefore reduce its prevalence. The China Foundation of Hepatitis Prevention and Control organized a team of specialists in infectious diseases, hepatology, immunology, obstetrics, and public health to develop an algorithm for interrupting MTCT of HBV, based on the most recent hepatitis B guidelines and latest evidence. This algorithm comprises 10 steps and has been adopted in clinical practice in China.
https://ift.tt/2CxKWoZ
Risk Factors for Rate of Relapse and Effects of Steroid Maintenance Therapy in Patients with Autoimmune Pancreatitis: Systematic Review and Meta-analysis
Risk for relapse after induction of remission with steroid therapy has been extensively studied in patients with autoimmune pancreatitis (AIP), but findings are equivocal. We performed a systematic review and meta-analysis were to estimate the rate of rate of AIP following initial remission after steroid treatment and to identify factors associated with relapse.
https://ift.tt/2C619ko
A Prospective Phase II Trial of Trans-perineal Ultrasound-Guided Brachytherapy for Locally Recurrent Prostate Cancer after External Beam Radiotherapy (NRG Oncology/RTOG -0526)
We report the primary endpoint of the phase 2 NRG/RTOG 0526 trial of salvage low dose rate prostate brachytherapy for locally recurrent prostate cancer following prior external beam radiotherapy (EBRT). Eligible patients initially presented with favorable or intermediate risk prostate cancer. At a median follow up of 54 months, 12 of 92 analyzable patients (14%) had late grade 3 gastrointestinal or genitourinary adverse events, which did not exceed the previously set threshold for unacceptable toxicity.
https://ift.tt/2pILIHd
Function indices of liver and kidney and haematological parameters of male Wistar rats after oral administration of aqueous extract of Terminalia avicennioides root barks
Abstract
Terminalia avicennioides is a member of the Combretaceae family with a lot of medicinal properties. This study aims to investigate the effects of aqueous extract of T. avicennioides root barks on biochemical and haematological parameters of Wistar rats. Male rats were distributed randomly into four groups (A–D) and orally administered aqueous root bark extract of T. avicennioides (250, 500 and 1000 mg/kg body weight) for 7 days. Liver, kidney and serum enzymes, function indices and malondialdehyde, as well as haematological parameters were monitored. The extract significantly (p < 0.05) reduced the activities of alanine aminotransferase, aspartate aminotransferase and gamma glutamyltransferase in the liver, serum alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, serum conjugated bilirubin and malondialdehyde in the liver and kidney. The extract also significantly (p < 0.05) elevated the levels of alkaline phosphatase in the liver and kidney, serum gamma glutamyltransferase, total protein, urea, Na+, K+, Cl− and HCO3−. The extract did not significantly (p > 0.05) alter kidney alkaline phosphatase at 250 and 500 mg/kg body weight, liver alanine aminotransferase at 250 and 1000 mg/kg body weight and serum chloride ions at 250 mg/kg body weight, serum total bilirubin, albumin, creatinine and haematological parameters at all the experimental doses. Overall, the findings in this study revealed that the extract at 250, 500 and 1000 mg/kg body weight when administered repeatedly for 7 days has adverse effects on hepatic and renal functions without evidence of systemic toxicity.
https://ift.tt/2NwfWXy
When Do Clinicians Decide to Screen Children for Mental Health-Behavioral-Developmental Delays/Disorders: Is it Time to Reconsider Policy Recommendations?
To determine at which ages providers choose to screen for mental, behavioral, and developmental disorder/delay (MBDD), and what they find; and which, if any, public and professional guidelines are most effective at identification.
https://ift.tt/2NyNc0a
Multiple Endocrine Neoplasia Type 2B Presents Early in Childhood but Often Is Undiagnosed for Years
We describe the presenting symptoms and signs of multiple endocrine neoplasia type 2B in a cohort of children. Improved awareness of the early nonendocrine signs of multiple endocrine neoplasia type 2B could lead to earlier diagnosis before the development of medullary thyroid cancer and possibly its metastasis.
https://ift.tt/2NyN8gW
Relationship of Weight Outcomes, Co-Occurring Conditions, and Severity of Autism Spectrum Disorder in the Study to Explore Early Development
To assess contributing factors to increased obesity risk, by comparing children with autism spectrum disorder (ASD), developmental delays/disorders, and general population controls in weight status, and to examine associations between weight status and presence of co-occurring medical, behavioral, developmental, or psychiatric conditions across groups and ASD severity among children with ASD.
https://ift.tt/2OT6FxG
Pulse Oximeter Saturation Targeting and Oximeter Changes in the Benefits of Oxygen Saturation Targeting (BOOST)-II Australia and BOOST-II UK Oxygen Trials
Infants in the Australian and UK Benefits of Oxygen Saturation Targeting-II trials treated using revised oximeters spent more time within their planned pulse oximeter saturation target ranges than infants treated using the original oximeters (P < .001). This may explain the larger mortality difference seen with revised oximeters. If so, average treatment effects from the Neonatal Oxygen Prospective Meta-analysis trials may be underestimates.
https://ift.tt/2OT4PMW
Efficacy and Safety of Anti-D Immunoglobulins versus Intravenous Immunoglobulins for Immune Thrombocytopenia in Children: Systematic Review and Meta-analysis of Randomized Controlled Trials
To compare the efficacy and safety of intravenous immunoglobulins (IVIG) and anti-D immunoglobulin (anti-D) in pediatric immune thrombocytopenia (ITP).
https://ift.tt/2OMO2eB
Cancer Prevention Education for Providers, Staff, Parents, and Teens Improves Adolescent Human Papillomavirus Immunization Rates
To develop a program to educate providers, office staff, patients, and parents on life-long cancer prevention strategies, including the use of human papillomavirus (HPV) vaccine to improve adolescent HPV vaccination rates.
https://ift.tt/2NyNdBg
Urinary TIMP-2 predicts the presence and duration of delayed graft function in donation after circulatory death kidney transplant recipients
Background Urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP7) have been validated as biomarkers for acute kidney injury. We investigated the performance of both markers in predicting the occurrence and duration of functionally defined delayed graft function (fDGF) in donation after circulatory death (DCD) kidney transplant recipients. Methods Urine samples of 74 DCD recipients were analyzed. TIMP-2 and IGFBP7 were measured with ELISA on postoperative day 1 to 7, day 10, week 6 and month 6 and values were corrected for osmolality (mOsm). Immunosuppression consisted of anti-CD25 antibody induction and triple maintenance therapy (steroids, MMF and CNI). Statistical analysis included receiver operating characteristic curves and multivariate logistic regression. Results Fifty-one renal transplant recipients had fDGF (69%), of which 14 experienced prolonged fDGF (≥21 days). TIMP-2/mOsm on day-1 and day-10 adequately identified patients with fDGF (AUC 0.91) and prolonged fDGF (AUC 0.80), respectively, whereas IGFBP7/mOsm did not (AUC 0.63 and 0.60). Multivariate analysis on day-1 identified 24-hour urinary creatinine excretion and TIMP-2/mOsm as significant predictors of fDGF (AUC 0.90, 95% CI 0.80-0.98). The best predictors of prolonged fDGF on day-10 were 24-hour urinary creatinine excretion, TIMP-2/mOsm and total warm ischemia time with an AUC of 0.85 (95% CI: 0.72-0.95). Consecutive TIMP-2/mOsm values showed a decrease in TIMP-2/mOsm prior to an increase in eGFR, enabling us to monitor fDGF and predict resolution of fDGF. Conclusion Urinary TIMP-2, but not IGFBP7, is a promising biomarker to predict the occurrence and duration of fDGF in DCD kidney transplant recipients. Corresponding author: Prof.dr. J.W. de Fijter, Leiden University Medical Center, Department of Nephrology, PO Box 9600, 2300 RC Leiden, the Netherlands. E-mail: jwdefijter@lumc.nl, Phone: +31-71-5262218, Fax: +31-71-5266868 AUTHORS CONTRIBUTION JRB participated in the study design, data collection and interpretation, analysis, and writing of the paper. RH participated in study design, data collection and interpretation (ELISAs). DS participated in study design and writing of the paper. OM participated in data analysis (clinical data). FPR participated in data interpretation and conducting ELISAs. CvK participated in study design, data interpretation and writing of the paper. CMC participated in the study design and data interpretation. JWdF participated in study design, data interpretation and writing of the paper. DISCLOSURES The authors of this manuscript declare no funding or conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2Oicu8j
https://ift.tt/2Oicu8j
Importance of Hematopoietic Mixed Chimerism for Induction of Renal Allograft Tolerance in Nonhuman Primates
BACKGROUND Although induction of durable mixed chimerism is required for murine skin allograft tolerance, renal allograft tolerance has been achieved after induction of only transient mixed chimerism in nonhuman primates (NHPs) and humans. To better define the level/duration of chimerism required for stable renal allograft tolerance, we retrospectively analyzed these parameters and compared them with transplant outcomes in NHP combined kidney and bone marrow transplant (CKBMT) recipients. METHODS Peripheral blood levels and duration of myeloid or lymphoid chimerism were retrospectively analyzed in 34 NHP CKBMT recipients which were divided into 3 groups: Tolerance (TOL), n=10; chronic antibody-mediated rejection (CAMR), n=12; and T cell-mediated rejection (TCMR), n=12. RESULTS All 4 of the recipients that failed to develop any chimerism lost their allografts due to TCMR after discontinuation of immunosuppression (56 ± 3 days). Among 30 recipients who successfully developed multilineage chimerism, 10 achieved immunosuppression-free survival (1258 ± 388 days), 12 eventually developed CAMR (932 ± 155 days), and 8 developed TCMR (82 ± 10 days). The maximum level but not duration of lymphoid chimerism was significantly higher in TOL recipients compared with both CAMR (p=0.0159) and TCMR (p=0.0074). Conversely, the maximum myeloid chimerism was significantly higher in TOL than in TCMR (p=0.0469), but not in CAMR. ROC analyses revealed that lymphoid chimerism levels of 3.1% or greater could reliably predict long-term immunosuppression-free renal allograft survival (p
https://ift.tt/2yvnuUS
https://ift.tt/2yvnuUS
Establishing a Core Outcome Measure for Life Participation: a Standardized Outcomes in Nephrology – Kidney Transplantation (SONG-Tx) Consensus Workshop Report
Background Kidney transplantation confers substantial survival and quality of life benefits for many patients with end-stage kidney disease compared with dialysis, but complications and side-effects of immunosuppression can impair participation in daily life activities. Life participation is a critically important patient-reported outcome for kidney transplant recipients but is infrequently and inconsistently measured in trials. We convened a consensus workshop on establishing an outcome measure for life participation for use in all trials in kidney transplantation. Methods Twenty-five (43%) kidney transplant recipients/caregivers and 33 (57%) health professionals from 8 countries participated in 6 facilitated breakout group discussions. Transcripts were analyzed thematically. Results Four themes were identified. Returning to normality conveyed the patients' goals to fulfill their roles (ie, in their family, work, and community) and reestablish a normal lifestyle after transplant. Recognizing the diverse meaning and activities of 'life' explicitly acknowledged life participation as a subjective concept that could refer to different activities (eg, employment, recreation, family duties) for each individual patient. Capturing vulnerability and fluctuations posttransplant (eg, due to complications and side-effects) distinguished between experiences in the first year posttransplant and the long-term impact of transplantation. Having a scientifically rigorous, feasible and meaningful measure was expected to enable consistent and frequent assessment of life participation in trials in kidney transplantation. Conclusions A feasible and validated core outcome measure for life participation is needed so that this critically important patient-reported outcome can be consistently and meaningfully assessed in trials in kidney transplantation to inform decision-making and care of recipients. *A complete list of the SONG-Tx Life Participation Workshop Investigators is provided in SDC, Materials and Methods 1, https://ift.tt/2OhZAak Address for correspondence: Angela Ju, Centre for Kidney Research. The Children's Hospital at Westmead, Westmead, NSW 2145, Sydney, Australia, Phone: +61 2 9845 1486 Fax: +61 2 9845 1491; Email: angela.ju@sydney.edu.au Authors' specific contributions: AJ participated in the research design, data collection, data analysis, and drafted the manuscript. MAJ participated in the research design, data collection, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. ZB participated in participated in the research design, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. SJG participated in the research design, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. JT participated in the research design, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. QT participated in the research design, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. KF participated in the research design, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. FD participated in the research design, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. FC participated in the research design, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. VJ participated in the research design, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. JL participated in the research design, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. GK participated in the research design, data collection, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. CA participated in the research design, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. CSH participated in the research design, data collection, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. BS participated in the research design, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. KM participated in the research design, data collection, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. JCC participated in the research design, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. MH participated in the research design, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. CR participated in the research design, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. AT participated in the research design, data collection, data analysis, and provided intellectual input on the manuscript and contributed to manuscript writing. Disclosure: The authors declare no conflicts of interest. Funding: This project is supported by a National Health and Medical Research Council Project Grant 1128564 and Program Grant 1092597. Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (https://ift.tt/2EZJQTY). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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https://ift.tt/2OfbPUR
Temporal Trends Associated with the Rise in Alcoholic Liver Disease Related Liver Transplantation in the United States
Background In the United States, alcoholic liver disease (ALD) has recently become the leading indication for liver transplantation (LT). Methods Using the United Network for Organ Sharing registry, we examined temporal trends in adult liver transplant waitlist registrants and recipients with chronic liver disease (CLD) due to ALD from 2007 to 2016. Results From 2007 to 2016, ALD accounted for 20.4% (18 399) of all CLD waitlist (WL) additions. The age-standardized ALD WL addition rate was 0.459 per 100 000 US population in 2007; nearly doubled to 0.872 per 100 000 US population in 2016 and increased with an average annual percent change of 47.56% (95% CI: 30.33% to 64.72%).The ALD WL addition rate increased over twofold among young (18-39 years) and middle-aged (40-59 years) adults during the study period. Young adult ALD WL additions presented with a higher severity of liver disease including Model for End-Stage Liver Disease score compared to middle aged and older adults (> 60 years). The number of annual ALD WL deaths readily rose from 2014 to 2016, despite an overall annual decline in all CLD WL deaths. Severe hepatic encephalopathy, low BMI (
https://ift.tt/2yAxDzZ
https://ift.tt/2yAxDzZ
Nonalcoholic fatty liver disease: basic pathogenetic mechanisms in the progression from NAFLD to NASH
Nonalcoholic fatty liver disease (NAFLD) represents a growing cause of chronic liver injury, especially in Western Countries, where it is becoming the most frequent indication for liver transplantation (OLTx). NAFLD encompasses a spectrum of diseases that from simple steatosis (pure NAFLD) can progress to Nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of NAFLD and the mechanisms behind its progression to NASH have been extensively studied. However, while the processes that determine fat accumulation are mostly clear, the mechanisms associated with the progression of the disease are not fully characterized. In predisposed patients, lipid accumulation can promote lipotoxicity and mitochondrial dysfunction, thus triggering hepatocyte death, inflammation and fibrosis. The specific role of different lipids has been identified and free fatty acids as well as free cholesterol have been identified as toxic species. To make the picture more complex, the pathogenesis of NAFLD involves pathological connections between several organs, including the adipose tissue and the gut, with the liver. The "inflamed" adipose tissue plays a key role in the release of toxic lipids, while alterations in the gut-liver axis have been associated with the progression from NAFLD to NASH mediated by dysbiosis, alteration of intestinal barrier, and finally bacterial translocation, that can trigger proinflammatory and profibrogenetic pathways, finally leading to cirrhosis development. CORRESPONDING AUTHOR: Prof. Gianluca Svegliati-Baroni, Department of Gastroenterology, Università Politecnica delle Marche, Via Tronto 10, 60126 Ancona, Italy, phone: +39 071-2206043, fax: +39 071-2206044, e-mail: gsvegliati@gmail.com. DISCLOSURE The authors disclose no conflict of interest. AUTHORSHIP Both authors contributed to the writing of the manuscript. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2yrFQpV
https://ift.tt/2yrFQpV
The Transplant Index (TI): A Novel Method To Predict Adult Liver Transplant Waitlist Outcomes
Background The field of transplantation is shifting outcome priorities from 1-year survival to more comprehensive metrics including transplant rate and waitlist mortality. Identifying disenfranchised candidates (high waitlist death risk, low transplantation chance) can be a focus to improve outcomes. Methods Given waitlist outcomes, (continued waiting, death, and transplantation), we aimed to identify factors predicting the likelihood candidates would undergo transplant or death by performing multivariate competing risk analyses of 121 198 candidates in the United Network for Organ Sharing database. We incorporated these probabilities (likelihood of transplantation and waitlist death) into the transplant index (TI) to identify disenfranchised candidates (high likelihood of death, low likelihood of transplantation). Results Half of the patients had low incidences of death and transplantation within 90 days (TI-inactive). The remaining were stratified into 10 groups within a predictive index, the TI. Low-TI groups (TI-10, 20, 30) had 90-day transplant rates of 50.8%, 41.6%, and 39.8% respectively, and their respective 90-day death rates were 22.8%, 15.1%, and 10.9%. High-TI groups (TI 80, 90, >90) had 90-day transplantation rates of 53.7%, 64.3%, and 73.9% respectively, and 90-day death rates of 5.9%, 6.5%, and 6.7% respectively. As TI increased, the likelihood of transplantation increased and that of death decreased. Low-TI groups represent the disenfranchised candidates. Conclusions The TI identifies disenfranchised candidates on the adult liver transplant waitlist. This is the subgroup that would benefit the most from efforts to increase access to transplantation. CORRESPONDING AUTHOR CONTACT INFORMATION: Abbas Rana, MD, Michael E. DeBakey Department of Surgery, Division of Abdominal Transplantation and Division of Hepatobiliary Surgery, Baylor College of Medicine, One Baylor Plaza, MS:BCM 390, Houston, Texas 77030, USA. (713) 321-8423. abbas.rana@bcm.edu AUTHORSHIP STATEMENT Abbas Rana participated in conceptualization of the study, data analysis and drafting the initial manuscript. Jessie Wu and Hao Liu participated in the conceptualization of the study and the data analysis. Michael Kueht, Syed Shahyan Bakhtiyar, John Goss, Warren H. Chan, Ronald Cotton, Nhu Thao Galvan, Christine O'Mahony, Henrik Petrowsky, Irbaz B. Riaz, Abbas Rana, Jessie Wu, and Hao Liu reviewed, revised, and approved the final manuscript. FUNDING SOURCE No funding was secured for this study. FINANCIAL DISCLOSURE The authors have no financial relationships relevant to this article to disclose. CONFLICT OF INTEREST The authors have no conflicts of interest to disclose Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2Og5OHO
https://ift.tt/2Og5OHO
Recommendations for management and treatment of nonalcoholic steatohepatitis
The prevalence of nonalcoholic liver disease (NAFLD) is increasing worldwide in conjunction with the epidemic increase in obesity and metabolic risk factors. Consequently, NAFLD has become a leading indication for liver transplantation. While genetic factors play an important role in the pathogenesis of NAFLD, detrimental lifestyle trends favoring a calorically unrestricted diet rich in carbohydrates and unsaturated fat, prolonged sedentary periods or limited physical activity have major metabolic implications. In aggregate these physiological dysregulations constitute the main risk factors for the metabolic syndrome and NAFLD. The cornerstone of the treatment of NAFLD, is lifestyle changes, including modifications to diet and physical activity, to reduce body weight and liver fat, however adherence is notoriously poor and the epidemic of NAFLD continues to grow unimpeded. In the face of this unmet clinical need, the pharmacologic therapy of NAFLD has been expanding as the varied mechanistic pathways of NAFLD are elucidated. Beyond these approaches to treating NAFLD, the prevention of other liver diseases is additionally important. Chief among these is alcoholic liver disease, and heavy use is detrimental irrespective of underlying NAFLD. However, the impact of mild to moderate alcohol use in patients with mild or nonadvanced forms NAFLD is undefined. This article summarizes the results of the International Liver Transplant Society consensus meeting on NAFLD in liver transplantation. It describes the available evidence and provides consensus guidance on the lifestyle and pharmacologic therapies of NAFLD, and the consensus position on alcohol use in patients with NAFLD. Corresponding author: Prof V Ratziu, vlad.ratziu@inserm.fr Conflicts of Interest: Vlad Ratziu: consultancy or advisory board meetings for Allergan, Boehringer, Galmed, Genfit, Intercept, Novartis, Novo-Nordisk. Marwan Ghabril: Research support Salix Pharmaceutical. Manuel Romero-Gomez: consultancy or advisory board meetings for Allergan, Intercept, Medimmune, Gilead, Novo-Nordisk. Gianluca Svegliati-Baroni: Advisory board meetings for Gilead Authorship contributions: All authors took part in the meeting, the discussions and provided input on the grading of recommendations. Specific contributions include: Marwan Ghabril, text on physical exercise, Manuel Romero-Gomez, text on dietary interventions, Gianluca Svegliati-Baroni, text on alcohol consumption, Vlad Ratziu, text on pharmacological therapy. Vlad Ratziu was responsible for editing of the whole document and all authors approved the final version. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2yrFOyj
https://ift.tt/2yrFOyj
Emerging Ethical Challenges Raised by the Evolution of Vascularized Composite Allotransplantation
Background Despite early skepticism, the field of vascularized composite allotransplantation (VCA) has demonstrated feasibility. The ethics of VCA have moved past doubts about the morality of attempting such transplant to how to conduct them ethically. Methods Leaders of each program performing and/or evaluating VCA in the United States were invited to participate in a working group to assess the state and future of VCA ethics and policy. Four meetings were held over the course of 1 year to describe key challenges and potential solutions. Results Working group participants concluded that VCA holds great promise as treatment for patients with particular injuries or deficits, but the field faces unique challenges to adoption as standard of care, which can only be overcome by data sharing and standardization of evaluation and outcome metrics. Conclusions Adequate attention must be given to concerns including managing the uniquely intense physician-patient relationship, ethical patient selection, ensuring patients have adequate representation, informing and earning the trust of the public for donation, standardizing metrics for success, and fostering an environment of data sharing. These steps are critical to transitioning VCA from research to standard of care, and to its insurance coverage inclusion. Corresponding Author: Brendan Parent. brendan.parent@nyu.edu; 7 East 12th Street Suite 825b NY NY 10003 *List of members/contributors to NYU/Hopkins VCA ethics working group: Arthur L. Caplan, Jeffrey Kahn, Brendan Parent, WP Andrew Lee, Wendy Dean, Laura L. Kimberly, Bruce Gelb, James F. Childress, Eduardo D. Rodriguez, James McCartney, Nomi Levy-Carrick, Gerard MaGill, Hatem Amer, Rolph N Barth, Leslie Bernstein, Rosamond Rhodes, David B. Sarwer, Helen Irving, Simon Talbot, Kevin I Reid, Elisa J Gordon, Benjamin Chang, Lisa Kearns, James Benedict, Linda C. Cendales, Jeremy Sugarman Authorship All authors participated in working group meetings and drafting documents on assigned relevant topics. BP wrote the initial draft of this paper based on literature review, notes from working group meetings, and content in assigned documents. AC revised with significant feedback from LK, JK, WD, and BG. WPAL and EDR contributed to design and final revisions. Disclosure The authors of this manuscript declare no conflicts of interests. Funding Working group hosts received a gift from United Therapeutics to support travel and lodging for participants of working group meetings. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2OdttbC
https://ift.tt/2OdttbC
Fatal iatrogenic vinorelbine poisoning: a case report
The paper describes the case of a 69-year-old man with non-small-cell lung cancer who, owing to a mistake, received intravenously 500 mg of vinorelbine. Within 3 days of intoxication, the bone marrow of the patient was damaged with subsequent pancytopenia that did not respond to treatment. On the fifth day after the poisoning, features of intestinal obstruction appeared. The patient died on the sixth day after the drug overdose. The case presented by us constitutes the first description of a fatal iatrogenic poisoning with this drug. Correspondence to Marcin Zawadzki, MD, PhD, Department of Forensic Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 4, PL 50-345 Wroclaw, Poland Tel: +48 717 841 480; fax: +48 717 575 006; e-mail: marcin.zawadzki@umed.wroc.pl Received June 23, 2018 Accepted September 27, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2A1udbq
https://ift.tt/2A1udbq
Micron-scale Phenotyping Techniques of Maize Vascular Bundles Based on X-ray Microcomputed Tomography
https://ift.tt/2CyoX15
Effect of reducing acid‐etching duration time on compressive strength and bonding of a universal adhesive to calcium silicate cements
International Endodontic Journal, Volume 0, Issue ja, -Not available-.
https://ift.tt/2pJPWOU
Patients with MELAS not only require treatment of stroke‐like episodes but a comprehensive individual and family management
Acta Neurologica Scandinavica, Volume 0, Issue ja, -Not available-.
https://ift.tt/2y5SUlx
Target identification for the diagnosis and intervention of vulnerable atherosclerotic plaques beyond 18 F-fluorodeoxyglucose positron emission tomography imaging: promising tracers on the horizon
Abstract
Cardiovascular disease is the major cause of morbidity and mortality in developed countries and atherosclerosis is the major cause of cardiovascular disease. Atherosclerotic lesions obstruct blood flow in the arterial vessel wall and can rupture leading to the formation of occlusive thrombi. Conventional diagnostic tools are still of limited value for identifying the vulnerable arterial plaque and for predicting its risk of rupture and of releasing thromboembolic material. Knowledge of the molecular and biological processes implicated in the process of atherosclerosis will advance the development of imaging probes to differentiate the vulnerable plaque. The development of imaging probes with high sensitivity and specificity in identifying high-risk atherosclerotic vessel wall changes and plaques is crucial for improving knowledge-based decisions and tailored individual interventions. Arterial PET imaging with 18F-FDG has shown promising results in identifying inflammatory vessel wall changes in numerous studies and clinical trials. However, due to its limited specificity in general and its intense physiological uptake in the left ventricular myocardium that impair imaging of the coronary arteries, different PET tracers for the molecular imaging of atherosclerosis have been evaluated. This review describes biological, chemical and medical expertise supporting a translational approach that will enable the development of new or the evaluation of existing PET tracers for the identification of vulnerable atherosclerotic plaques for better risk prediction and benefit to patients.
https://ift.tt/2IKEJGt
Culturing and Manipulation of O9-1 Neural Crest Cells
O9-1 is a multipotent mouse neural crest cell line. Here we describe detailed step-by-step protocols for culturing O9-1 cells, differentiating O9-1 cells into specific cell types, and genetically manipulating O9-1 cells by using siRNA-mediated knockdown or CRISPR-Cas9 genome editing.
https://ift.tt/2IKGxPL
The Morphogenesis of the Renal Plexus: Renal Artery and Sympathetic Fibers
Clinical Anatomy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2E8GE9l
Technology for improving accessibility of end-of-life care: Extension for Community Healthcare Outcomes Project
Purpose of review To describe how Project ECHO works and to analyze what has been published on Project ECHO Palliative Care (Project ECHO PC) over the last 18 months. Recent findings Only two articles on Project ECHO PC have been published over the last 18 months: a descriptive study of experiences in seven health centers of the United States, the United Kingdom, Uruguay and India; and a quantitative and qualitative study of the impact of the teleECHO clinic on physicians and nurses in Northern Ireland, which reports a significant boost in knowledge acquisition and self-efficacy. Summary Project ECHO is an innovative telemedicine strategy, which creates learning communities, which use a standardized methodology and benefits healthcare professionals, particularly primary care providers or practitioners based on remote or rural areas. Since 2011, Project ECHO PC has been implemented in 12 health centers in 4 different countries, with greater growth in 2017. It has facilitated a wider access to professional education, improvements in clinical practice and knowledge acquisition, the development of professional curricula and more confidence and self-efficacy among healthcare professionals. Project ECHO PC is engaged in several international initiatives to aid countries with different degrees of palliative care development. Correspondence to Gabriela Píriz Alvarez, Internal Medicine and Palliative Care Specialist, Adult Palliative Care teleECHO Clinic Coordinator, Hospital Maciel Palliative Care Service – Medical School, Universidad de la República, Montevideo, Uruguay. Tel: +598 99665618; e-mail: gpirizalvarez@gmail.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2y9x1lc
https://ift.tt/2y9x1lc
Compassion in palliative care: a review
Purpose of review Compassion has been recognized as a key aspect of high-quality healthcare, particularly in palliative care. This article provides a general review of the current understanding of compassion in palliative care and summarizes emergent compassionate initiatives in palliative care at three interdependent levels: compassion for patients, compassion in healthcare professionals, and compassionate communities at the end of life. Recent findings Compassion is a constructive response to suffering that enhances treatment outcomes, fosters the dignity of the recipient, and provides self-care for the giver. Patients and healthcare professionals value compassion and perceive a general lack of compassion in healthcare systems. Compassion for patients and for professionals' self-care can be trained and implemented top-down (institutional policies) and bottom-up (compassion training). 'Compassionate communities' is an important emerging movement that complements regular healthcare and social services with a community-level approach to offer compassionate care for people at the end of life. Summary Compassion can be enhanced through diverse methodologies at the organizational, professional, and community levels. This enhancement of compassion has the potential to improve quality of palliative care treatments, enhance healthcare providers' satisfaction, and reduce healthcare costs. Correspondence to Gonzalo Brito-Pons, PhD, Nirakara Institute, Centro Superior de Estudios de Gestión, Campus de Somosaguas, 28223 Somosaguas, Madrid, Spain. Tel: +34 655 60 59 11; e-mail: gonzalo@nirakara.org Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2Pk7X1j
https://ift.tt/2Pk7X1j
Palliative care teaching shapes medical undergraduate students’ professional development: a scoping review
Purpose of review The aim of this review is to understand how palliative care teaching (PCT) as a patient-centered learning model, influences medical undergraduate students' professional development. Recent findings To study PCT medical undergraduate students' learning experiences, we have employed the medical teaching concept, 'hidden curriculum,' as a way of describing attitudes and behavior conveyed implicitly by palliative care educators. Fifteen studies were selected: ten of those studies used a qualitative approach; two are theoretical explanations of the topic explored, one guideline, one review and just one quantitative study, made up the review. Medical undergraduate students reported that after PCT, they felt they had acquired better attitudes for effective integration with the patient, such as empathy or holistic care; ethical principles, such as respect or humanization of their clinical practice; and commitment to an improvement in competences, such as self-awareness or self-esteem. They also reported improved behavior in effective integration with patients, such as communication, caring for patients' families, and when addressing psychosocial, cultural and spiritual aspects; their commitment to improvement in competences, such as dealing with emotions and uncertainty; they learned team work as an effective way to interact within the health system; and to become more reliable, making themselves more available and dedicating enough time to each patient. Summary PCT seems to be an effective way of fostering medical undergraduate students' patient-centered professional development. Correspondence to Antonio Noguera, MD, PhD, Edificio Bibliotecas, Campus Universitario sn. 31009 Pamplona, Navarra, Spain. Tel. +34 948 425600; fax. +34 948 425636. e-mail: anoguera@unav.es Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2y9wZK6
https://ift.tt/2y9wZK6
The role of day care in supporting older people living with long-term conditions
Purpose of review For older people with long-term conditions, regular structured activities within a community setting meeting others are thought to improve well being and quality of life. Historically local authority-run day care centres were widely available, but austerity measures have meant that in many areas, such provision has been markedly reduced and different models of day care services are being developed. There is little known about outcomes of day care provision for older people with long-term conditions. Recent findings This review has critically examined the recent evidence on outcomes of day care provision for older people with long-term conditions and will focus on three areas – physical functioning, intergenerational provision and measurement of outcomes. In terms of interventions to improve physical functioning for older people with long-term conditions attending day care, there are few studies and it is difficult to generalize but there appears to be a trend for positive impact on physical functioning when activities are incorporated into a day care programme. There is a paucity of research on intergenerational provision, however, the small number of studies suggest positive benefits. Studies measuring outcomes for older people with long-term conditions attending day care services are very limited in terms of outcome data with the exception of a Canadian study, which suggested that attendance at day care could reduce hospital attendance and admissions. Summary This review reveals a lack of research of day care provision for older people with long-term conditions. There is a suggestion in the small number of articles included in this review that there can be benefits both in terms of global outcomes of attendance and in improved physical functioning; there is limited evidence of the value of intergenerational provision. Robust research with collection of meaningful outcomes is required to ensure that the increasing number of older people with long-term conditions are enabled to access high-quality day care provision. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://ift.tt/1eRPUFd Correspondence to Mari Lloyd-Williams, Professor/Honorary Consultant in Palliative Medicine, Academic Palliative and Supportive Care Studies Group (APSCSG), Block B Waterhouse Building, University of Liverpool, Brownlow Hill, Liverpool L69 3GB, England. E-mail: mlw@liv.ac.uk; mlw@liverpool.ac.uk Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2PpR9WK
https://ift.tt/2PpR9WK
Targeting IL-1α in cancer cachexia: a narrative review
Purpose of review Cachexia is defined as ongoing loss of skeletal muscle mass, with or without depletion of adipose tissue and is a common syndrome in cancer patients, affecting 50% of those diagnosed. Cachexia, which cannot be fully reversed and causes significant functional impairment is caused by various mechanisms such as an altered energy balance and disruption of homeostatic control by the central nervous system. This central nervous system deregulation involves hypothalamic pituitary adrenal (HPA) axis stimulation, which can be triggered by IL-1R1 engagement on neuronal processes and endothelium in the microvasculature of the hypothalamus. This review will explore current evidence regarding both the importance of IL-1α in the various components of cancer cachexia and its potential as a therapeutic target. Recent findings IL-1α, which signals through IL-1R1, has been identified as a key agonist in the IL-1 pathway. As such, IL-1α has been explored as a therapeutic target in cancer cachexia, leading to the development of bermekimab, a mAb which neutralizes IL-1α. With a limited array of medication currently available to treat cancer cachexia, bermekimab represents a possible therapy. Summary IL-1α is a key mediator in cachexia development and targeting this may be a viable therapeutic target. Correspondence to Barry J. Laird, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XR, UK. Tel: +00 44 131 651 8611; e-mail: barry.laird@ed.ac.uk Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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https://ift.tt/2PtZDfS
Predictors of reliably high-value end-of-life care
Purpose of the review Care near the end of life is expensive and frequently not aligned with the expressed preferences of decedents, creating an opportunity to improve value, or increase quality while lowering cost. This review examines publications from 2017 and 2018 on interventions and policies associated with high-value end-of-life care. Innovations in video and web-based advance care planning are promising to improve preference-congruent care at low cost. Recent findings The patterns of care within hospice and in particular increased investment in patient care in hospice are shown to improve value. A meta-analysis demonstrated the role of inpatient palliative care consultations in decreasing hospitalization costs, as did several studies on inpatient palliative care units. Internationally, a range of home-based palliative care programs, implemented at the population level, demonstrated cost savings and reduced intensive care near the end of life. Finally, public policies that funded medical and long-term care and address broader inequalities were demonstrated to decrease low-value care near the end of life. Summary This review demonstrates the efficacy of a range of approaches to improve value of care at the end of life, both within the health system and across public policy sectors. Correspondence to Claire K. Ankuda, MD, MPH, Department of Geriatrics and Palliative Medicine, One Gustave L. Levy Place, Box 1070, New York, NY 10029, USA. Tel: +1 212 241 0635; e-mail: claire.ankuda@mssm.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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https://ift.tt/2y9uSGl
Intravenous and Intra-amniotic In Utero Transplantation in the Murine Model
https://ift.tt/2IMs2uX
Risk of Opioid-Benzodiazepine Overlap Up for Dual Prescribing
TUESDAY, Oct. 9, 2018 -- Receiving prescriptions from both the U.S. Department of Veterans Affairs (VA) and Medicare Part D is associated with increased risk for overlapping of opioid and benzodiazepine prescriptions, according to a study published...
https://ift.tt/2PmKIDV
Mechanical Ventilation May Alter Diaphragm Muscle Fibers
TUESDAY, Oct. 9, 2018 -- In critically ill patients, mechanical ventilation with positive end-expiratory pressure (PEEP) results in reduced diaphragm fiber length that may make it more difficult to wean patients from mechanical ventilation,...
https://ift.tt/2PozAql
Integrated Classifier Identifies Benign Lung Nodules
TUESDAY, Oct. 9, 2018 -- An integrated plasma proteomics classifier, which integrates the relative abundance of two plasma proteins with a clinical risk prediction model, can distinguish benign from malignant lung nodules in those at...
https://ift.tt/2y8Dn4w
FDA Approves Marketing of First User-Fitted Hearing Aid
TUESDAY, Oct. 9, 2018 -- The first hearing aid that does not require the assistance of an audiologist or other health care provider has been approved by the U.S. Food and Drug Administration. The Bose Hearing Aid is a user-fitted device for people...
https://ift.tt/2ybjYQ9
Application of Blood Pressure Guidelines Ups Treatment
TUESDAY, Oct. 9, 2018 -- Implementation of the 2017 American College of Cardiology/American Heart Association (ACC/AHA) blood pressure guideline would direct initiation and intensification of antihypertensive medication treatment to adults at high...
https://ift.tt/2Pozzmh
Weight Loss May Cut Breast CA Risk in Postmenopausal Women
TUESDAY, Oct. 9, 2018 -- Postmenopausal women with weight loss have a reduced risk for breast cancer, according to a study published online Oct. 8 in Cancer. Rowan T. Chlebowski, M.D., Ph.D., from the City of Hope National Medical Center in Duarte,...
https://ift.tt/2ybjXf3
ZICO premix container holders now available in black
YARDLEY, Pa. — Responding to popular demand, Zico has expanded their line of premix and bar oil container storage options and is now offering each model in black as well as yellow. The Single Premix/Bar Container Holder – Black, Model QM-PMH-1-B, accommodates your choice of one cylindrical 32 oz. (3-3/8″ dia.) can or one rectangular 32 oz. (2-5/8″ x 4-1/4″) quart...
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The use of STarT back screening tool to predict functional disability outcomes in patients receiving physical therapy for low back pain
Publication date: Available online 9 October 2018
Source: The Spine Journal
Author(s): Irene L. Katzan, Nicolas R. Thompson, Steven Z. George, Sandi Passek, Frederick Frost, Mary Stilphen
ABSTRACT
Background Context
The STarT Back Screening Tool (SBST) categorizes risk of future disability in patients with low back pain (LBP). Previous studies evaluating the use of SBST in physical therapy populations do not reflect the ethnic and socioeconomic diversity occurring in clinical practice and lack statistical power to evaluate factors associated with outcomes within each SBST risk category.
Purpose
The purpose of this study is to further refine SBST risk categorization for predicting improvements in functional disability with attention towards patient level factors that might guide SBST use in routine outpatient physical therapy practice.
Study Design/Setting
This was a retrospective cohort study that took place within a large academic, tertiary-care health system
Patient Sample
The study cohort consisted of 1,169 patients with low back pain who completed a course of outpatient physical therapy from June 1, 2014 and May 31, 2015 and who completed the patient-reported SBST and Modified Low Back Pain Disability Questionnaire (MDQ) questionnaires as part of standard of care.
Outcome Measures
Improvement in functional disability defined as decrease in 10 or more points in the MDQ.
Methods
Multivariable logistic regression was performed to evaluate independent predictors of improvement after PT, which included SBST risk category, baseline MDQ, a 2-way interaction term between SBST category and baseline MDQ, prior level of function (independent vs required assistance), demographic characteristics, number of completed PT visits and duration of PT episode of care. In exploratory analyses, additional 2-way interaction terms between SBST category and the significant predictors were added to the regression model.
Results
Mean age of patients in the study cohort was 55.1 years (SD 16.1); 657 (56.2%) were female, 117 (10.0%) were black race, 127 (10.9%) had Medicaid insurance, and 353 (30.2%) had previously received PT for back pain. In all, 35.8% (n=419) patients categorized as low risk SBST category, 40.7% (n= 476) medium risk SBST category, and 23.4% (n=274) high risk SBST category. There was an interaction between baseline MDQ and SBST risk category and improvement with PT. For all 3 SBST categories, higher baseline MDQ was associated with higher probability of improvement, but the effect was less pronounced as SBST risk category increased. Additional factors independently associated with reduced odds of improvement after PT included black race (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.28 – 0.72), Medicaid insurance (OR = 0.58, 95% CI 0.36 – 0.95), and prior PT (OR = 0.48, 95% CI 0.34 – 0.67). In exploratory analyses, there was a significant interaction between insurance type and SBST risk category in predicting functional improvement after PT. Patients with Medicare and Medicaid insurance had similar rates of improvement in low and high risk SBST categories but different rates of improvement in the medium risk categories.
Conclusions
The SBST tool predicts outcomes of PT in a cohort of patients receiving outpatient PT for LBP. The odds of improvement varied according to baseline disability and SBST risk status. Race, insurance type, and history of previous PT influenced prediction independent of SBST risk status. Incorporating these variables and the interaction between SBST and baseline disability in outcome models has the potential to refine prediction of outcomes after PT.
https://ift.tt/2C8oylk
2019 NAEMSP/AMR Foundation Professional Member Scholarship
AUSTIN, Texas — The NAEMSP/AMR Foundation scholarship provides reimbursement of up to $2,000 for expenses to attend the 2019 Annual Meeting in Austin. Who is eligible: Any non-physician, non-student EMS professional who is interested in becoming (or currently is) a professional member of NAEMSP® and would be a first time attendee of the NAEMSP® Annual Meeting in Austin, January...
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How an unexpectedly fast stroke recovery is possible, according to a stroke survivor
Quick action by family, paramedics and doctors combined with innovative procedure made a huge difference
https://ift.tt/2PoqhGV
Postoperative Complications Independently Predict Cancer-Related Survival in Peritoneal Malignancies
Abstract
Background
The authors hypothesized that postoperative complications after cytoreductive surgery–hyperthermic intraperitoneal chemoperfusion (CRS–HIPEC) have a negative impact on perioperative and oncologic outcomes and that the novel Comprehensive Comorbidity Index (CCI) would be a better predictor of such outcomes than the traditional Clavien–Dindo classification (CDC).
Methods
The study used a prospective database of 1296 patients with peritoneal metastases (PM) undergoing CRS–HIPEC between 2001 and 2016. The Kaplan–Meier method was used to estimate survival. Multivariate analyses identified associations with perioperative and oncologic outcomes. The Akaike information criterion and the Schwarz (Bayesian information) criterion were used to compare model fitting for CCI versus CDC.
Results
In this study, CRS–HIPEC was performed for malignant mesothelioma (12%) and PM from appendix (50%), colorectal (30%), and ovarian (8%) cancers. Major postoperative in-hospital complications (CDC grades 3–4) occurred for 24% of the patients. However, a range of CCI scores was calculated for each CDC grade because 36% of the patients experienced multiple complications. After a median follow-up period of 55 months, the median progression-free survival was 15 months, and the median overall survival was 39 months. In the multivariate Cox proportional hazards models, postoperative in-hospital complications (measured by CDC or CCI) were independent prognostic factors for 30-day post-discharge morbidity and readmission, as well as for survival. The CCI scores demonstrated higher prognostic sensitivity for these outcomes than CDC grades.
Conclusions
Reduction of postoperative complications after CRS–HIPEC is essential for optimal short- and long-term outcomes. For assessing total burden of postoperative complications per patient, CCI is superior to CDC and more sensitive for assessing surgery- and cancer-related outcomes after CRS–HIPEC.
https://ift.tt/2CxDiuU
Antidiabetic Effect of Abextide, a Long‐Acting Exendin‐4 Analogue in Cynomolgus Monkeys
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2OeO27v
Single LAMS versus multigate plastic stent drainage of WON; fair comparison or apples versus oranges?
In the recent edition of Gut, Bang et al present an important randomised trial comparing lumen-apposing metal stents (LAMS) versus plastic endoprostheses for the drainage of walled-off pancreatic necrosis (WON).1 The authors demonstrate that caution needs to be exercised when using LAMS for this indication given that they may induce pseudoaneurysm formation and severe haemorrhage.
Interestingly, they also showed that there was no difference in the number of procedures required for the management of WON for LAMS versus plastic stents which contradicted prior cohort studies suggesting that the larger drainage pathway of LAMS presented an advantage.2 3
Nevertheless, in their methods section Bang et al indicate that multiple transluminal gateway technique, in which multiple drainage tracts are created, was reserved for patients with WON diameter >12 cm.1 The median diameter of WOPN among patients managed with LAMS was 8 cm compared with 6 cm for those who underwent...
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Quantification of HBV core antibodies may help revisit infectious occult hepatitis B virus
We read with great interest the paper by Candotti et al and the commentary by Locarnini and Raimondo.1 2 Occult hepatitis B virus (HBV) infection (OBI) poses a potential risk of viral reactivation and transmission in several aspects of clinical practices.3–7 Candotti et al confirmed the HBV transfusion transmission from OBI patients who had undetectable HBV DNA measured by the very sensitive nucleic acid testing (NAT). The infectious HBV produced from the intrahepatic persistent and replication-competent covalently closed circular (ccc) DNA is probably beyond the detection limit (3.4 IU/mL) of current NAT. The authors estimated the HBV infectious dose by transfusion could be as low as 3 IU of HBV DNA. They, thus, suggested that the development of ultrasensitive NAT (detection limit of 0.15 IU/mL) and exclusion of anti-HBc-positive blood donors may be required to reduce the risk of HBV...
https://ift.tt/2yoescp
Towards optimal pancreatic cyst fluid management: the need for standardisation
We read with interest the paper by Singhi et al.1 The authors prospectively assessed using targeted next-generation sequencing (NGS) 626 pancreatic cyst fluid (PCF) samples from 595 patients. They found that compared with Sanger sequencing, cytology and CEA, preoperative NGS for KRAS/GNAS mutations is highly sensitive for intraductal papillary mucinous neoplasms (IPMNs) and specific for mucinous pancreatic cysts (PCs).
Moreover, alterations in TP53/PIK3/PTEN are significantly associated with advanced neoplasia facilitating decision-making for the management of these lesions.
Despite the evidence that NGS outperforms complementary techniques, we remain puzzled by several features related to the methodology used.
The Results section of the paper shows that the majority of the cases (93%) were satisfactory for molecular testing.
On the contrary, the amount of cyst fluid was insufficient for CEA analysis in 28% of cases, and 60% of specimens were either less than optimal (47%) or unsatisfactory (13%) for cytopathological diagnosis. The proposed primary reason for specimen...
https://ift.tt/2OfyHnl
Inhibition of monoacylglycerol lipase, an anti-inflammatory and antifibrogenic strategy in the liver
Objective
Sustained inflammation originating from macrophages is a driving force of fibrosis progression and resolution. Monoacylglycerol lipase (MAGL) is the rate-limiting enzyme in the degradation of monoacylglycerols. It is a proinflammatory enzyme that metabolises 2-arachidonoylglycerol, an endocannabinoid receptor ligand, into arachidonic acid. Here, we investigated the impact of MAGL on inflammation and fibrosis during chronic liver injury.
DesignC57BL/6J mice and mice with global invalidation of MAGL (MAGL-/-), or myeloid-specific deletion of either MAGL (MAGLMye-/-), ATG5 (ATGMye-/-) or CB2 (CB2Mye-/-), were used. Fibrosis was induced by repeated carbon tetrachloride (CCl4) injections or bile duct ligation (BDL). Studies were performed on peritoneal or bone marrow-derived macrophages and Kupffer cells.
ResultsMAGL-/- or MAGLMye-/- mice exposed to CCl4 or subjected to BDL were more resistant to inflammation and fibrosis than wild-type counterparts. Therapeutic intervention with MJN110, an MAGL inhibitor, reduced hepatic macrophage number and inflammatory gene expression and slowed down fibrosis progression. MAGL inhibitors also accelerated fibrosis regression and increased Ly-6Clow macrophage number. Antifibrogenic effects exclusively relied on MAGL inhibition in macrophages, since MJN110 treatment of MAGLMye-/- BDL mice did not further decrease liver fibrosis. Cultured macrophages exposed to MJN110 or from MAGLMye-/- mice displayed reduced cytokine secretion. These effects were independent of the cannabinoid receptor 2, as they were preserved in CB2Mye-/- mice. They relied on macrophage autophagy, since anti-inflammatory and antifibrogenic effects of MJN110 were lost in ATG5Mye-/- BDL mice, and were associated with increased autophagic flux and autophagosome biosynthesis in macrophages when MAGL was pharmacologically or genetically inhibited.
ConclusionMAGL is an immunometabolic target in the liver. MAGL inhibitors may show promising antifibrogenic effects during chronic liver injury.
https://ift.tt/2OiGRvr
TGF‐β suppresses RasGRP1 expression and supports regulatory T cell resistance against p53‐induced CD28‐dependent T cell apoptosis
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2EcIO7N
Immunophenotyping of Orthotopic Homograft (Syngeneic) of Murine Primary KPC Pancreatic Ductal Adenocarcinoma by Flow Cytometry
The experimental procedure on the immunophenotyping of murine orthotopic PDAC homografts aims at profiling the tumor immuno-microenvironment. Tumors are orthotopically implanted via surgery. Tumors of 200–600 mm3 in size were harvested and dissociated to prepare single-cell suspensions, followed by multi-immune marker FACS analysis using different fluorescently-labeled antibodies.
https://ift.tt/2QyzVXm
MPV17 mutations in juvenile‐ and adult‐onset axonal sensorimotor polyneuropathy
Clinical Genetics, Volume 0, Issue ja, -Not available-.
https://ift.tt/2ILMpbr
Ventilatory constraints influence physiologic dead space in heart failure
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Pqle8W
Extracellular Hsp70 modulates the inflammatory response of CSE in NCI‐H292 cells
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2y9mZRf
Impact of carbohydrate substrate complexity on the diversity of the human colonic microbiota
Abstract
The diversity of the colonic microbial community has been linked with health in adults and diet composition is one possible determinant of diversity. We used carefully controlled conditions in vitro to determine how the complexity and multiplicity of growth substrates influence species diversity of the human colonic microbiota. In each experiment, five parallel anaerobic fermentors that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources. Inulin supported less microbial diversity over the first six days than the other two single substrates or the 3- and 6-mixes, showing that substrate complexity is key to influencing microbiota diversity. The communities enriched in these fermentors did not differ greatly at the phylum and family level, but were markedly different at the species level. Certain species were promoted by single substrates, whilst others (such as Bacteroides ovatus, LEfSe p = 0.001) showed significantly greater success with the mixed substrate. The complex polysaccharides such as pectin and arabinoxylan-oligosaccharides promoted greater diversity than simple homopolymers, such as inulin. These findings suggest that dietary strategies intended to achieve health benefits by increasing gut microbiota diversity should employ complex non-digestible substrates and substrate mixtures.https://ift.tt/2ILdxaR
EGFR promotes glioma progression by regulating xCT and GluN2B‐containing NMDA receptor signaling
Cancer Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2yslJYD
Tox and Hound – Toxicology’s Shapeshifter: Synthetic Cannabinoids
by Jeff Lapoint July, 2010. 3:14 am. "Jeff, I got a liddle case for ya", said the voice of Lou (named changed), the very New York C-SPI from the Poison Center. "917-555-. . ." He continued to rattle off a phone number. "Dude, give me more than that", I begged. I was a new fellow, […]
EMCrit Project by Tox & Hound.
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
