Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 2, Page 60-64, March 2018.
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Παρασκευή 16 Μαρτίου 2018
PTPN12 Affects Nasopharyngeal Carcinoma Cell Proliferation and Migration Through Regulating EGFR
Samsum Ant Venom Exerts Anticancer Activity Through Immunomodulation In Vitro and In Vivo
Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 2, Page 65-73, March 2018.
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Current and Future Approaches for Effective Cancer Imaging and Treatment
Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 2, Page 39-51, March 2018.
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64Cu-Labeled Phosphonate Cross-Bridged Chelator Conjugates of c(RGDyK) for PET/CT Imaging of Osteolytic Bone Metastases
Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 2, Page 74-83, March 2018.
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Evaluation of the in vitro Chemosensitivity and Correlation with Clinical Outcomes in Lung Cancer using the ATP-TCA
Background and Objective: Multiple drug resistance (MDR) to chemotherapeutic agents often leads to a failure to respond to chemotherapy. We utilized an in vitro chemosensitivity test to identify sensitive and effective chemotherapeutic drugs and further elucidated the correlation between the in vivo chemosensitivity and clinical outcomes.
Methods: Here, we evaluated the in vitro chemosensitivity and MDR of 120 lung cancer patients to eight singledrug chemotherapies and of 291 lung cancer patients to seven chemotherapy regimens using an ATP-based tumor chemosensitivity assay (ATP-TCA). Additionally, the chemosensitivity profiles of lung adenocarcinoma patients (284 cases) and lung squamous cell carcinoma patients (90 cases) to these single-drug and chemotherapy regimens were compared. Furthermore, the correlations between the chemosensitivity and clinical outcomes were investigated in 16 stage III squamous cell carcinoma patients.
Results and Conclusion: PTX (51.7%), TXT (43.3%), GEM (12.5%), PTX+DDP (62.5%), TXT+L-OHP (54.3%) and VP-16+DDP (16.2%) had the highest in vitro chemosensitivity rates. Approximately 31.7% of patients developed resistance to all eight single-drug chemotherapies, and 25.8% of patients displayed resistance to all seven chemotherapy regimens. In addition, lung squamous cell carcinoma was significantly more sensitive to GEM and MTA+DDP than lung adenocarcinoma (P
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Tumor-Targeting Peptides: Ligands for Molecular Imaging and Therapy
The aberrant proliferation of tumor cells and abundant vasculature in tumor tissues are closely correlated with receptors that are specifically dysregulated in tumor cells. These tumor-associated targets are critical in early diagnosis and therapy selection. Ligands such as antibodies, proteins, polypeptides and polysaccharides that specifically bind to these targets can significantly improve the detection and cure rate when used as tumor imaging probes or anti-tumor agents. Compared to other targeting ligands, peptides have attracted increasingly more attention in tumor diagnostics and therapeutics because of their small sizes, high affinity, stability, ease of modification and low immunogenicity. Several peptide-based imaging probes and therapeutic agents have already been used in clinical trials. This review summarizes some of the tumor-associated targets and their corresponding peptides, as well as the potential of these peptides in cancer treatment.
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Synthesis, Characterization, and Inducing Tumor Cell Apoptosis of Two Ru(II) Complexes Containing Guanidinium as Ligands
Description: Two new ruthenium(II) complexes containing guanidinium as ligands, [Ru(dip)2 (L1)]3+ (Ru1) and [Ru(dip)2(L2)]3+ (Ru2) (dip=4,7-diphenyl-1,10-phenanthroline; L1=1-(4-(1H-imidazo[4,5- f][1,10]phenanthrolin-2-yl)phenyl)guanidine cation; L2 = 1-(3-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl) phenyl)guanidine cation) have been synthesized and characterized. Both complexes display higher cytotoxicity against several cancer cell lines compared to cisplatin and are less cytotoxic on the nontumorigenic cell line LO2. Intracellular distribution studies show that these complexes are selectively localized in the cytoplasm.
Findings: Further analysis revealed that Ru1 and Ru2 had no obvious effects on the cell cycle and induced apoptosis in HeLa cells via the mitochondrial pathway, which involved reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and Bcl-2 family member activation. Taken together, the two complexes have the potential to be utilized as anticancer agents.
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4-aryl/heteroaryl-4H-fused Pyrans as Anti-proliferative Agents: Design, Synthesis and Biological Evaluation
Aims: The current study is focused on the design and synthesis of 4-aryl/heteroaryl-4H-fused pyrans as anti-proliferative agents. All the synthesized molecules were screened against a panel of human carcinoma cell lines.
Description: Significant inhibition was exhibited by the compounds against HCT-116 (Colon) and PC-3 (Prostate) cell lines while A-549 (Lung) cell lines, MiaPaCa-2 (Pancreatic) cell lines and HL-60 (Leukemia Cancer) cell lines were almost resistant to the exposure of the test compounds. Compound FP-(v)n displayed noteworthy cytotoxicity towards HCT-116 malignant cells with the IC50 value of 0.67 µM. It induces apoptosis as revealed by several biological endpoints like apoptotic body formation, through DAPI staining, phase contrast microscopy and mitochondrial membrane potential loss. Moreover FP-(v)n is a potent apoptotic inducer confirmed by cell cycle arrest and ROS generation. The cell phase distribution studies indicate an augment from 4.94 % (control sample) to 39.68 % (sample treated with 1.5 µM compound FP-(v)n) in the apoptotic population. Compound FP-(v)n inhibits the tumor growth in Ehrlich ascites carcinoma (EAC), Ehrlich Tumor (ET, solid) and sarcoma-180 (solid) mice models. Additionally, it was established to be non-toxic at maximum tolerated dose of 1000 mg/kg in acute oral toxicity in Swiss-albino mice.
Conclusion: The current study provides an insight into anti-cancer potential of FP-(v)n, which might be valuable in the treatment of tumor.
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Histamine and Histaminergic Receptors in Colorectal Cancer: From Basic Science to Evidence-based Medicine
Background: Histamine is an imidazolic compound performing a crucial function in the pathogenesis of inflammation. Several studies have also emphasized its pro-carcinogenic effect in colorectal cancer (CRC).
Object: In fact, increased histamine levels have been observed in CRC and a decreased catabolism of this molecule is typical of colorectal adenomas. Additional data have demonstrated that CRC is characterized by an altered balance of histamine receptors (HRs); in fact, HR1 and HR4 are down-regulated in CRC, while HR2 is overexpressed.
Method: Based on this evidence, we reviewed several studies investigating the role of HR2 antagonists (HR2A), such as cimetidine in CRC.
Results: From a clinical point of view, HR2A may prolong the survival rates of patients with CRC, and a recent meta-analysis seems to confirm this finding. From a biological perspective, it has been demonstrated that HR2A could have a beneficial effect on CRC for many reasons: i) promotion of peri-tumoral lymphocyte growth and improvement of immune response against the tumor, ii) suppression of adhesion molecules which might favor metastasis, iii) anti-angiogenetic activity (reduction of VEGF), iv) increased production of some cytokines which may counteract tumor growth, such as tumor necrosis factor (TNF) alpha, interleukin (IL)-10 and IL-15. On the contrary, HR1 antagonists did not demonstrate any beneficial effect on CRC. Therefore, it is presumable that histamine could be a relevant player in the development of CRC, but its effect might be mediated by an imperfect homeostasis of its receptors.
Conclusion: In this scenario, HR2A could inhibit carcinogenesis whereas HR2 might act as a pro-carcinogenetic, while HR1 and HR4, being suppressed in CRC, may antagonize neoplastic development.
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Volatile Inhibitors of Phosphatidylinositol-3-Kinase (PI3K) Pathway: Anticancer Potential of Aroma Compounds of Plant Essential Oils
Background: Cancer is a grave health problem for the world as the global cancer burden rises to 14 million new cases with 8.2 million deaths every year which is expected to rise by 70% in the next 2 decades as reported by the WHO.These steady rises in death demand for rapid developments in anti-cancer agents. Essential oils, being natural and multi-component complex systems have recently attracted a lot of attention in this search for novel anti-cancer agents.
Materials and Methods: The pharmaceutical attributes of essential oil components, specifically focusing on their affinity towards COX, 5-LOX, AKT, MDM2, PDK1 and mTOR which defines the phosphatidylinositol-3- kinase (PI3K) pathway, were assessed. 123 compounds present in essential oils of different plants were analyzed for their drug like attributes which were then allowed to dock with PI3K dependent receptors crucial for the development of cancer malignancies. Among them, 21 compounds were filtered possessing high druglikeness with favourable metabolism offered by major cytochromeP450 isoforms. Finally, the best docked compounds with highest binding affinities were employed for building a ligand based pharmacophore. Being inhibitors of P-glycoproteins, these molecules also exhibited good absorption profiles and noncarcinogenic properties. Further from these 21, six compounds were evaluated against A549 lung cancer cells.
Results: The pharmacophoric feature obtained can be applied for both designing and screening moieties for active inhibitors of the phosphatidylinositol-3-kinase pathway specifically from essential oil compounds and these final 21 compounds can be further promoted to studies for anti-cancer drug development. Among these, six compounds exhibited promising inhibitory results against A549 lung cancer cells. Furthermore, immunoblotting assay confirmed the efficacy of the compounds for inhibiting mTOR and AKT enzymes which are bandmasters for downstream signaling of thePI3K pathway.
Conclusion: Methyl nonanoate, (R)-citronellol, cis-carveol (L-carveol), 3-methyl-Cyclohexanone, 4-carene and thujopsene were finally screened for PI3K targeted anti-cancer therapies which may find direct application as inhalers or sprays against lung cancer as these compounds are highly volatile.
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Recent Advancements in 1,4-Disubstituted 1H-1,2,3-Triazoles as Potential Anticancer Agents
Cancer is a class of formidable disease with high degree of mortality. Despite much progress in chemotherapy, the problem of drug resistance has led to the search for newer leads with superior efficacy. 1,2,3- Triazoles are among a vast number of nitrogen containing heterocycles studied extensively as pharmacologically important scaffolds. Recently developed copper(I)-catalyzed cycloaddition reaction between organic azides and terminal alkynes yielding 1,4-disubstituted 1,2,3-triazoles has attracted considerable attention because it allows the construction of a vast array of 1,2,3-triazoles with significant potential in pharmaceutical chemistry. In this article, an attempt to summarize the wide range of anticancer agents derived from copper(I)-catalyzed azide alkyne cycloaddition reported by the authors worldwide, has been made. This review includes articles published from 2010 onwards and summarizes the recent progress on the development of 1,4-disubstituted 1H-1,2,3-triazoles as novel anticancer chemotypes with high therapeutic indices.
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Rationale Design, Synthesis, Cytotoxicity Evaluation, and Molecular Docking Studies of 1,3,4-oxadiazole Analogues
Background: 1,3,4-Oxadiazole heterocycles possess a broad spectrum of biological activities. They were reported as potent cytotoxic agents and tubulin inhibitors; hence it is of great interest to explore new oxadiazoles as cytotoxic agents targeting tubulin polymerization.
Objective: Two new series of oxadiazoles (5a-h and 12a-h) were synthesized, structurally related to the heterocyclic linked aryl core of IMC-038525, NSC 776715, and NSC 776716, with further modification by incorporating methylene linker.
Method: The 2,5-disubstituted-1,3,4-oxadiazoles (5a-h and 12a-h) were synthesized by refluxing an equimolar mixture of the intermediates [(4) and (8a-d)] and aromatic aldehydes in water-ethanol system using sodium bisulphite catalyst. The cytotoxicity evaluation was carried out according to the National Cancer Institute (NCI US) Protocol, while the tubulin polymerization assay kits from Cytoskeleton ™(bk011p) was used to perform an in vitro tubulin polymerization assay.
Results: 2-(5-{[(4-Chlorophenyl)amino]methyl}-1,3,4-oxadiazol-2-yl)phenol (5f) and 2-[(2,4-dichlorophenoxy) methyl]-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole (12c) showed maximum cytotoxicity with the mean percent growth inhibitions (GIs) of 71.56 and 72.68 respectively at 10 µM drug concentrations. Both the compounds (5f and 12c) showed superior cytotoxicity than clinically prevalent anticancer drugs, Imatinib and Gefitinib in one dose assay. The compound 12c showed promising results in five dose assay, with GI50 values varies between 1.61 and >100 µM. Furthermore, the compounds, 5f and 12c also inhibited the polymerization of tubulin with, an IC50 of 2.8 and 2.2 µM, respectively.
Conclusion: The oxadiazoles reported herein are tubulin inhibitors and cytotoxic agents. These findings will be helpful in future drug design of more potent tubulin inhibitor cytotoxic agents..
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Double Edge Sword Behavior of Carbendazim: A Potent Fungicide With Anticancer Therapeutic Properties
Background: A number of benzimidazole derivatives such as benomyl and carbendazim have been known for their potential role as agricultural fungicides. Simultaneously carbendazim has also been found to inhibit proliferation of mammalian tumor cells specifically drug and multidrug resistant cell lines.
Objective: To understand the dual role of Carbendazim as a fungicide and an anticancer agent, the study has been planned referring to the earlier studies in literature.
Results: Studies carried out with fungal and mammalian cells have highlighted the potential role of carbendazim in inhibiting proliferation of cells, thereby exhibiting therapeutic implications against cancer. Because of its promising preclinical antitumor activity, Carbendazim had undergone phase I clinical trials and is under further clinical investigations for the treatment of cancer. A number of theoretical interactions have been pinpointed. There are many anticancer drugs in the market, but their usefulness is limited because of drug resistance in a significant proportion of patients. The hunger for newer drugs drives anticancer drug discovery research on a global platform and requires innovations to ensure a sustainable pipeline of lead compounds.
Conclusion: Current review highlights the dual role of carbendazim as a fungicide and an anticancer agent. Further, the harmful effects of carbendazim and emphasis upon the need for more pharmacokinetic studies and pharmacovigilance data to ascertain its clinical significance, have also been discussed.
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Effect of Number of Bifunctional Chelating Agents on the Pharmacokinetics and Immunoreactivity of 177Lu-labeled Rituximab: A Systemic Study
Objective: Monoclonal antibodies (mAbs) have been radiolabeled with a variety of radioisotopes utilizing various kinds of bi-functional chelating agents (BFCAs) with an aim to develop suitable agents for radioimmunotherapy. The number of BFCA moieties present per antibody molecule plays a significant role in determining the pharmacokinetics and immunoreactivity exhibited by the radiolabeled antibodies. The objective of the present study is to evaluate the effect of the number of BFCA moieties present per antibody molecule on the pharmacokinetics and immunoreactivity of the 177Lu-labeled Rituximab.
Methods: Three different mAb-BFCA conjugates were prepared using different molar ratios of Rituximab (mAb) to p-NCS-benzyl-DOTA (BFCA) viz. 1:5, 1:10 and 1:50 employing different reaction conditions. Studies were carried out to determine the average number of BFCAs attached per mAb molecule. All the three mAb-BFCA conjugates were labeled with 177Lu(III) and were subsequently evaluated in normal Swiss mice to ascertain their respective pharmacokinetic behavior. In-vitro studies were also performed in Raji cell lines (human burkitt's lymphoma) for determining the effect of increasing number of BFCAs attached per mAb molecule on the immunoreactivity of the resultant 177Lu-labeled mAb-BFCA complexes.
Results: 177Lu-labeled mAb-BFCA complex prepared corresponding to 1:50 mAb to BFCA ratio exhibited the least non-specific uptake and rapid clearance from majority of the organs, but also exhibited least immunoreactive fraction (IRF = 19.37%). On the other hand, 177Lu-labeled mAb-BFCA complex prepared corresponding to 1:5 mAb to BFCA ratio exhibited the highest non-specific uptake and slower clearance pattern, but highest IRF (71.17%). 177Lu-labeled mAb-BFCA complex prepared corresponding to 1:10 mAb:BFCA ratio exhibited intermediate pharmacokinetic behaviour with moderate IRF (53.05%).
Conclusions: The present study indicates that antibody to BFCA ratio plays a crucial role in determining the immunoreactivity and pharmacokinetic behavior of the radiolabeled antibodies and must be prudently chosen for their successful therapeutic application.
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Castleman’s Disease: a Suprarenal Surprise!
Abstract
Castleman's disease is a distinct form of lymph node hyperplasia. It commonly presents as a mediastinal mass and rarely as a solitary retroperitoneal mass. We narrate a case of Castleman's disease presenting as a right suprarenal mass emphasising the usefulness of robot-assisted retroperitoneoscopy in surgical management of retroperitoneal masses in close relation to vital structures.
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Fatty acid addition and thermotolerance of Kluyveromyces marxianus
Abstract
Membrane fatty acid composition has an important role in yeast stress resistance, particularly in temperature tolerance. Most studies investigating temperature and membrane fatty acids use the yeast Saccharomyces cerevisiae without considering other yeasts, such as Kluyveromyces marxianus, which has physiological differences and industrial advantages with respect to S. cerevisiae. One of the primary traits of K. marxianus is its thermotolerance. The effect of fatty acid addition (oleic acid, linoleic acid, linolenic acid and araquidic acid) on the thermotolerance of the K. marxianus strain SLP1 was evaluated. SLP1 yeast exhibited temperature tolerance of up to 50°C; at 55°C, viability was reduced significantly, probably due to an increase in the generation of reactive oxygen chemical species. Externally added fatty acids were incorporated in the yeast membrane, increasing their proportion to approximately 70%, thereby changing membrane fluidity. SLP1 cells supplemented with polyunsaturated fatty acids decreased cell thermotolerance and increased the degree of lipoperoxidation, while arachidic acid addition exhibited a tendency to increase yeast thermotolerance.http://ift.tt/2pj8iqh
Overexpression of the periplasmic nitrate reductase supports anaerobic growth by Ensifer meliloti
Abstract
The alfalfa endosymbiont Ensifer meliloti strain1021 is known to be an incomplete denitrifier due to its inability to grow anoxically using nitrate as respiratory substrate to produce ATP and grow under anoxic conditions. Although this bacterium contains and expresses the complete set of denitrification genes napEFDABC, nirK, norECBQD and nosRZDFYLX encoding the periplasmic nitrate reductase (Nap), Cu-containing nitrite reductase (NirK), c-type nitric oxide (cNor) and nitrous oxide reductase (Nos), respectively, the reasons of its inability to grow under anoxic conditions are still very poorly understood. In the present study, we have constructed an E. meliloti strain overexpressing napEFDABC genes (Nap+) and demonstrated that this strain is able to grow through anaerobic nitrate respiration. Furthermore, Nap+ showed increased NapC levels as well as Nap, Nir and cNor activities and higher capacity to produce NO and N2O compared to wild-type cells. These results suggest that the inability of E. meliloti to grow under anaerobic conditions using nitrate as electron acceptor is attributable to a limitation in the expression of the periplasmic nitrate reductase.http://ift.tt/2piL8Af
The Evidence for Dietary Interventions and Nutritional Supplements as Treatment Options in Multiple Sclerosis: a Review
Abstract
Purpose of review
This review aims to critically evaluate published studies examining diets and nutritional supplements (excepting vitamin D) for the impact on prevention and prognosis of multiple sclerosis (MS).
Recent findings
There is a negative relationship between the Mediterranean diet and vascular disease, and vascular co-morbidities are associated with a worse MS prognosis. Low-fat, fish-based diets, sodium-restricted diets, calorie restriction, the paleo diet, and gluten-free diets have been examined, mostly in observational studies; results are inconclusive. With regard to nutritional supplements, pilot data show a possible benefit of biotin with respect to disability worsening in people with progressive MS (PMS). The best designed randomized controlled trials (RCTs) for PUFA supplementation have not shown significant impact, but several weaker RCTs have. Many other nutritional supplements have been tested, including several anti-oxidants. While some early studies show positive results, no result has been definitive.
Summary
Unfortunately, there is no strong evidence for a direct benefit of any given dietary intervention on MS risk or prognosis. However, due to its relationship with vascular co-morbidities, the Mediterranean diet has the strongest rationale for employment in PwMS. Higher-quality clinical trials are needed to ascertain the possible benefits of nutritional supplements.
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Transducing Airway Basal Cells with a Helper-Dependent Adenoviral Vector for Lung Gene Therapy
Human Gene Therapy, Ahead of Print.
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Therapeutic DNA Vaccines for Human Papillomavirus and Associated Diseases
Human Gene Therapy, Ahead of Print.
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Correction to: Recent Progress on Genetic Diagnosis and Therapy for β-Thalassemia in China and Around the World, by Zhang J, Yan J, and Zeng F.; Hum Gene Ther 2018;29(2):197–203.; DOI: 10.1089/hum.2017.228
Human Gene Therapy, Volume 29, Issue 3, Page 400-400, March 2018.
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Immune signatures predicting responses to immunomodulatory antibody therapy
Graham Pawelec
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Haplotype-Based Genome-Wide Prediction Models Exploit Local Epistatic Interactions Among Markers
Genome-wide prediction approaches represent versatile tools for the analysis and prediction of complex traits. Mostly they rely on marker-based information, but scenarios have been reported in which models capitalizing on closely-linked markers that were combined into haplotypes outperformed marker-based models. Detailed comparisons were undertaken to reveal under which circumstances haplotype-based genome-wide prediction models are superior to marker-based models. Specifically, it was of interest to analyze whether and how haplotype-based models may take local epistatic effects between markers into account. Assuming that populations consisted of fully homozygous individuals, a marker-based model in which local epistatic effects inside haplotype blocks were exploited (LEGBLUP) was linearly transformable into a haplotype-based model (HGBLUP). This theoretical derivation formally revealed that haplotype-based genome-wide prediction models capitalize on local epistatic effects among markers. Simulation studies corroborated this finding. Due to its computational efficiency the HGBLUP model promises to be an interesting tool for studies in which ultra-high-density SNP data sets are studied. Applying the HGBLUP model to empirical data sets revealed higher prediction accuracies than for marker-based models for both traits studied using a mouse panel. In contrast, only a small subset of the traits analyzed in crop populations showed such a benefit. Cases in which higher prediction accuracies are observed for HGBLUP than for marker-based models are expected to be of immediate relevance for breeders, due to the tight linkage a beneficial haplotype will be preserved for many generations. In this respect the inheritance of local epistatic effects very much resembles the one of additive effects.
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Bivalent chromatin domains in glioblastoma reveal a subtype-specific signature of glioma stem cells
Glioblastoma multiforme (GBM) can be clustered by gene expression into four main subtypes associated with prognosis and survival, but enhancers and other gene regulatory elements have not yet been identified in primary tumors. Here, we profiled six histone modifications and CTCF binding as well as gene expression in primary gliomas, and identified chromatin states that define distinct regulatory elements across the tumor genome. Enhancers in mesenchymal and classical tumor subtypes drove gene expression associated with cell migration and invasion, while enhancers in proneural tumors controlled genes associated with a less aggressive phenotype in GBM. We identified bivalent domains marked by activating and repressive chromatin modifications. Interestingly, the gene interaction network from common (subtype-independent) bivalent domains was highly enriched for homeobox genes and transcription factors, and dominated by SHH and Wnt signaling pathways. This subtype-independent signature of early neural development may be indicative of poised de-differentiation capacity in glioblastoma, and could provide potential targets for therapy.
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The Kyn-AhR Pathway Upregulates PD-1 to Promote Tumor Immune Escape [Research Watch]
Tumor-repopulating cells release Kyn, which activates AhR on T cells to promote PD-1 upregulation.
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LKB1-Salt-Inducible Kinase Signaling Is Essential in MEF2C+ Leukemia [Research Watch]
MEF2C activity in acute myeloid leukemia is dependent upon salt-inducible kinase (SIK) signaling.
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Ewing Sarcomas Phenocopy BRCA1-Deficient Tumors [Research Watch]
Transcriptional dysregulation promotes R-loops and impairs homologous recombination in Ewing sarcoma.
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Firefly Otoscope Travels with Friend Ships Unlimited on their Mission to Syria
On their current mission to Syria, Friend Ships Unlimited (a.k.a. Park West Children's Fund) will be taking a Firefly Otoscope to aid those in need.
Headquartered in Louisiana, Friend Ships Unlimited has worked in over forty nations since their foundation in 1983. We hope their mission is a success and that our Otoscope can play a supporting role
To learn more about Friend Ships Unlimited and their mission, you can find their latest activities HERE.
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The relationship between mismatch response and the acoustic change complex in normal hearing infants
The importance of exposure to quality spoken language during the first year of life has been highlighted in studies of normal hearing (NH) infants and toddlers (Kuhl, 1991; Strange and Jenkins, 1978; Werker and Tees, 1984) and in studies of the later implications of this exposure on word learning and syntactic abilities (Graf Estes et al., 2007; van Leeuwen et al., 2008; Mueller et al., 2012). Research in infants with hearing loss (HL) has shown improved language outcomes when infants are fit with amplification and enrolled in early intervention by six months of age (Yoshinaga-Itano et al., 1998).
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Luminally-polarized mural and vascular remodeling in ileal strictures of Crohn's Disease
Intestinal stricture, a major complication of Crohn's disease (CD), results from fibromuscular remodeling and expansion of the intestinal wall. The corresponding microanatomical alterations have not been fully described, hindering progress toward understanding their pathogenesis and devising appropriate treatments. We used tissue-specific staining and quantitative digital histomorphometry for this purpose. Serial histological sections from 37 surgically-resected ileal strictures and adjacent non-strictured controls from patients with CD were evaluated after staining for smooth muscle actin, collagen (Sirius red) and collagen types I, III and V.
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Proving cortical death after vascular coma: Evoked potentials, EEG and neuroimaging
Prognostication of coma outcome is a key factor for the management of critically ill patients. The self-fulfilling prophecy related to treatment limitation is likely to appear after neurological insults with tragic consequences in case of erroneous prognostication, especially if a bad outcome is expected (Murray et al., 1993). With this caveat in mind, it is important to consider that clinical judgment appears frequently more severe than the objective assessment 6 months after traumatic brain injury (Bonds et al., 2015) and could conduce to inappropriate early care withdrawal in anoxic coma (Elmer et al., 2016; Gobert et al., 2016).
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Frailty and the gut
Frailty, which is a syndrome that encompasses losses in physical, psychological and social domains, is responsible for enhanced vulnerability to endogenous and/or exogenous stressors. Frailty is a public health problem for an ageing society; however, it is poorly understood and often under-recognised in clinical settings. In particular, the impact of frailty on either intestinal functions, i.e. immune response, permeability, and absorption, or gut microbiota composition is as yet mostly unexplored.
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Spectrum of Findings in Orchiectomy Specimens of Persons Undergoing Gender Confirmation Surgery
Gender confirmation surgery (GCS) is increasingly common in persons with gender dysphoria. We describe changes seen in gonads from individuals seeking male to female physical adaptation. We studied 99 orchiectomies from 50 persons. The average age was 33years (range: 21–63). Eighty six of 99 (86.8%) testes were normal in size with an average size of 3.87cm (range: 3.0–5.5). Thirteen of 99 (13.1%) testes were hypotrophic and measured up to 2.5cm. Seminiferous tubules were reduced in diameter compared to controls (0.237 mm vs.
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Analysis of cancer-associated fibroblasts and the epithelial-mesenchymal transition in cutaneous basal cell carcinoma, squamous cell carcinoma and malignant melanoma
Activated cancer-associated fibroblasts (CAFs) and fibroblasts that have undergone the epithelial-mesenchymal transition (EMT) in cancer stroma contribute to tumor progression and metastasis. However, no reports have investigated the CAF phenotype and its clinicopathological relevance in cutaneous malignant tumors, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM). Here, we investigated the CAF phenotype in cutaneous malignant tumors based on their histology and immunohistochemical expression of CAF-related markers, including adipocyte enhancer-binding protein 1 (AEBP1), podoplanin, platelet derived growth factor receptor α (PDGFRα), PDGFRβ, fibroblast activating protein (FAP), CD10, S100A4, α-smooth muscle actin (α-SMA), and EMT-related markers (Zeb1, Slug and Twist).
http://ift.tt/2FP3iQy
P16-positive cystic squamous cell carcinoma in midline neck: metastasis from oropharynx or primary carcinoma arising from thyroglossal duct cyst?
Cystic squamous cell carcinoma (SCC) of the lateral neck is considered metastatic human papilloma virus (HPV)-related oropharyngeal SCC (HPV-OPSCC) until proven otherwise. P16 immunohistochemistry is diffusely positive in those carcinomas and is used as a surrogate marker of active human papillomavirus (HPV) infection.Thyroglossal duct cysts (TDC) are one of the differential diagnoses for cystic neck lesions. SCC arising from TDC is extremely rare. In this study, we report a p16-positive cystic SCC located in the midline neck.
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Aberrant high expression level of MORC2 is a common character in multiple cancers
Microrchidia 2 (MORC2) plays important roles in DNA damage repair and lipogenesis, but the clinical and functional role of MORC2 in cancer remains largely unexplored. In this study, we showed that MORC2 was widely expressed in human tissues while significantly up-regulated in most cancer types employing immunohistochemical staining and analysis of mRNA expression profile of more than 2000 human tissue samples from 15 different organs (lung, prostate, liver, breast, brain, stomach, colon/rectum, pancreas, ovary, endometrium, skin, nasopharynx, kidney, oesophagus and bladder).
http://ift.tt/2GAfTIm
Guidelines to Practice: Identifying Barriers to Cardiovascular Health Management in Pediatric Type 1 Diabetes
Great progress has been made in the clinical care and health outcomes for children, adolescents, and adults with type 1 diabetes (T1D) since the discovery of insulin almost a century ago. Despite this progress, commonly accepted metrics of care such as severe hypoglycemia,1 diabetic ketoacidosis,2 and hemoglobin A1c3,4 remain much too high. Multiple international registry studies suggest that, on average, people with T1D have lifespans that are 7-13 years shorter than the general population and that cardiovascular disease remains the leading cause of death in people with T1D.
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Neuroinflammation-Related Encephalopathy in an Infant Born Preterm Following Exposure to Maternal Diabetic Ketoacidosis
A pregnant woman with new-onset type 1 diabetes and ketoacidosis delivered an infant at 28 weeks of gestation who died with multiple organ failure and severe cerebral vasculopathy with extensive hemorrhage, diffuse microgliosis, and edema. This illustrates that antenatal metabolic and inflammatory stressors may be associated with neonatal encephalopathy and cerebral hemorrhage.
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Health Related Quality of Life and Neurocognitive Outcomes in the First Year after Pediatric Acute Liver Failure
To determine health-related quality of life (HRQoL) and neurocognitive impairment in survivors of pediatric acute liver failure (PALF).
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Bronchopulmonary Dysplasia: Executive Summary of a Workshop
Despite significant advances in perinatal care, bronchopulmonary dysplasia (BPD) remains one of the most common, complex, and intriguing diseases in perinatal medicine. The pathogenesis of BPD remains to be elucidated fully. Defining this disease continues to be imprecise and varies across institutions, and evidence-based guidelines addressing management are lacking. To address these and other knowledge gaps, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) held a workshop on BPD in October 2016.
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Pneumococcal and Meningococcal Vaccination among Michigan Children with Sickle Cell Disease
To determine the proportion of Michigan children with sickle cell disease (SCD) who were vaccinated according to pneumococcal vaccination recommendations and, secondarily, to examine uptake of meningococcal vaccine, and to compare up-to-date (UTD) vaccination status between children with and without SCD.
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The Impact of Maternal Antibiotics on Neonatal Disease
We examined the impact of prenatal exposure to maternal antibiotics on risk of necrotizing enterocolitis (NEC), late onset sepsis (LOS), and death in infants born preterm.
http://ift.tt/2DCfa6A
Radiation for Treatment of Painful Bone Metastases
Several variables may be considered when deciding on optimal modality of radiation therapy for each cancer patient with bone pain, including prognosis, tumor histology, location and extent of metastases, and association with cord compression. Hypofractionated external beam radiation therapy is as effective as a multiple fraction radiotherapy course in most cases, although retreatment rates are higher after a single dose of radiation. Stereotactic body radiation may be used in cases of oligometastatic disease, repeat irradiation, and radiation-resistant tumors. Radiopharmaceuticals may be used for pain from diffuse bone metastases and have an overall survival benefit in patients with castrate-resistant prostate cancer.
http://ift.tt/2FZVs9T
Rehabilitation Medicine Approaches to Pain Management
Rehabilitation medicine offers strategies that reduce musculoskeletal pain, targeted approaches to alleviate movement-related pain, and interventions to optimize patients' function despite the persistence of pain. These approaches fall into four categories: modulating nociception, stabilizing and unloading painful structures, influencing pain perception, and alleviating soft tissue musculotendinous pain. Incorporating these interventions into individualized, comprehensive pain management programs offers the potential to empower patients and limit pain associated with mobility and required daily activities. Rehabilitative approach may be particularly helpful for patients with refractory movement-associated pain and functional vulnerability, and for those who do not wish for, or cannot, tolerate pharmacoanalgesia.
http://ift.tt/2tWYEyc
Pain, a Complex Challenge
Despite the many diagnostic and therapeutic advances in the 26 years since the last Hematology/Oncology Clinics of North America issue on Pain, control of pain in our patients remains a complex challenge.
http://ift.tt/2GzKYM9
Alka-Seltzer Plus Products: Recall - Ingredients on Front Sticker May Not Match Product in Carton
Audience: Consumer, Pharmacy [Posted 03/16/2018] ISSUE: Bayer is voluntarily recalling Alka-Seltzer Plus packages that: Were sold only in the U.S. at Walmart, CVS, Walgreens and Kroger (including Dillons Food Stores, Fred Meyer, Fry's Food...
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How EMS agencies can prepare their communities to 'Stop the Bleed'
Prehospital care experts stress the importance of the Stop the Bleed initiative, preparing bystanders to control severe hemorrhage and securing funding for a statewide program
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Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites
http://ift.tt/2pi1bOX
A Technology Intervention for Nurses Engaged in Preventing Catheter-Associated Urinary Tract Infections
Catheter-associated urinary tract infections account for 40% of healthcare-acquired infections. This study explored the addition of cloud-based software technology to an established nursing quality improvement program to reduce catheter-associated urinary tract infections. Unit-based nurse champions evaluated peers' evidence-based catheter-associated urinary tract infection prevention practices using manual, paper-based feedback. That process achieved reduced rates of catheter-associated urinary tract infection over 18 months. However, it was resource intensive. Cloud-based software technology was introduced to replace the paper. Nurse champions' satisfaction, catheter-associated urinary tract infection and indwelling urinary catheter utilization, and prevention practices were compared before and after the technology intervention. Compliance with the provision of a chlorhexidine bath demonstrated improvement (P = .003), while other practice measures did not significantly change. The indwelling urinary catheter utilization ratio was lower (P = .01), yet the intervention yielded no change in catheter-associated urinary tract infection rates. The short time interval of the intervention was potentially a contributing factor in no significant rate change. Nurse champions (N = 14) were more satisfied with the cloud-based technology (P = .004), the clarity of improvement targets (P = .004), and the speed of sharing data (P = .001). Their time to share data decreased from 4 days or more to 1 hour or less. Nurse champions readily adopted the cloud-based technology. These findings suggest additional research on technology innovations for nursing quality improvement is needed. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Corresponding author: Kathleen Rea, DNP, RN, ACNS-BC, PCCN, CNL, University of Virginia Health System, Box 801442, 1215 Lee St, Charlottesville, VA 22908 (kmj6d@virginia.edu). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2tTNg6n
http://ift.tt/2tTNg6n
Predicting mucositis risk associated with cytotoxic cancer treatment regimens: rationale, complexity, and challenges
Purpose of review The goals of this review are to describe the complexity of factors influencing the risk of cancer regimen-related mucosal injury (CRRMI), to evaluate the contribution of the innate immune response to CRRMI risk, to compare the concordance of genome analytics in describing mechanism and risk, and to determine if common biological pathways are noted when CRRMI is compared to a disease with a similar phenotype. Recent findings The pathogenesis of and risk for CRRMI are complex and influenced by multiple intrinsic and extrinsic factors. It is incumbent on analyses to recognize the likelihood that the interplay and cross-talk of synergistically expressed factors is critical and that the contributing weights of these factors is not uniform from patient to patient. Genomically derived analyses imply final common pathways are implicit in phenotype expression. Summary The identification of specific factors (both genomic and otherwise) which contribute to CRRMI risk represents an important opportunity to apply principles of precision medicine to the management of regimen-related toxicities. Correspondence to Stephen T. Sonis, Division of Oral Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. E-mail: ssonis@bwh.harvard.edu Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://ift.tt/2FWWEea). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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http://ift.tt/2Dz8zcJ
Prophylactic probiotics for cancer therapy-induced diarrhoea: a meta-analysis
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Methods of Pairing and Pair Maintenance of New Zealand White Rabbits (Oryctolagus Cuniculus) Via Behavioral Ethogram, Monitoring, and Interventions
Though European rabbits are a social species, socially housing them can be challenging. Therefore, there must be a thorough understanding of behaviors and social structures of pair-housed laboratory rabbits. Here we present a protocol to identify pairing methods, species-typical hierarchy establishment behaviors and behaviors that warrant appropriate intervention.
http://ift.tt/2IsfgkN
On the Preparation and Testing of Fuel Cell Catalysts Using the Thin Film Rotating Disk Electrode Method
http://ift.tt/2pj8DIN
Primary Cell Cultures from the Mouse Retinal Pigment Epithelium
The retinal pigment epithelium (RPE) is a multi-functional epithelium of the eye. Here we present a protocol to establish primary cell cultures derived from the murine RPE.
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In Vivo EPR Assessment of pH, pO2, Redox Status, and Concentrations of Phosphate and Glutathione in the Tumor Microenvironment
http://ift.tt/2HGiT58
Diagnosis of hepatocellular carcinoma with MRI
In most cases, hepatocellular carcinoma (HCC) is associated with a known underlying risk factor like chronic viral hepatitis type B and C or alcoholic cirrhosis.1 Patients with chronic liver disease that are at risk for HCC should undergo surveillance ultrasound examinations every 6 months and dynamic cross-sectional imaging like CT and MRI if a detected hepatic nodule exceeds 1 cm in size.2 The established radiological hallmarks for diagnosing HCC non-invasively by imaging—strong contrast uptake in the arterial phase in conjunction with washout in the venous or later phases of dynamic contrast-enhanced studies—as proposed in practice guidelines of different specialised societies (eg, American Association for the Study of the Liver (AASLD) and European Association for the Study of the Liver (EASL) have not been changed for many years.3
Although these imaging features have proven to be very robust with specificities close to 100% even in detecting HCC lesions...
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Hypertriglyceridaemia delays pancreatic regeneration after acute pancreatitis in mice and patients
We read with great interest the recent publication by Barlass et al in which morphine was demonstrated to aggravate the severity of acute pancreatitis (AP) and delay pancreatic regeneration. These results indicated the risk of morphine use in AP-associated pain treatment.1 Similar to their observation, we found another interesting phenomenon that hypertriglyceridaemia (HTG), a prevalent metabolic disorder, delayed pancreatic regeneration after AP in mice and patients. Moreover, the delayed regeneration process could be ameliorated by lipid-lowering therapy.
Two models of HTG (drug induced: poloxamer 407 (P407) and gene modified: glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) deficiency) were employed to explore the effect of HTG on AP repair. AP induced by caerulein infusion in both normal triglyceride (NTG) mice and HTG mice caused pancreatic acinar cell necrosis. The injured pancreas was reconstructed in 3 days and recovered its normal architecture in 7 days in the NTG mice (figure 1A–C)....
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An Acute Bout of Aquatic Treadmill Exercise Induces Greater Improvements in Endothelial Function and Post-Exercise Hypotension than Land Treadmill Exercise: A Crossover Study
Objective The purpose of the study was to compare acute bouts of aquatic treadmill (ATM) and land treadmill (LTM) exercise on flow-mediated dilation (FMD), post-exercise blood pressure (BP), plasma nitrate/nitrite (PN), and atrial natriuretic peptide (ANP) in untrained, pre-hypertensive men. Design In a counterbalanced, crossover design, 19 untrained, pre-hypertensive men completed bouts of ATM and LTM on separate days. FMD was measured pre-exercise and 1-hour post-exercise. Blood samples were obtained pre-exercise and immediately post-exercise and analyzed for PN and ANP. A magnitude-based inference approach to inference was used for statistical analysis. Results A possible clinically beneficial increase in FMD (1.2%; 90% confidence interval (CI), -0.07% to 2.5%) was observed 1-hour post ATM. In contrast, a possible clinically harmful decrease in FMD (-1.3%; 90% CI, -2.7% to 0.2%) was observed 1-hour post LTM. The magnitude of the post-exercise systolic BP reduction was greater following ATM (-4.9, SD 2.9 mmHg) than LTM (-2.6, SD 2.5 mmHg). ANP increased 34.3 (SD 47.0) % following ATM and decreased -9.0 (SD 40.0) % following LTM. Conclusion An acute bout of ATM induced a more favorable endothelial response and greater post-exercise hypotensive response than LTM. These changes were associated with increased ANP levels following ATM. Address for correspondence: Dustin P. Joubert, Ph.D., Department of Kinesiology and Health Science, Stephen F. Austin State University, P.O. Box 13015, SFA Station, Nacogdoches, TX 75962-3015; ; E-mail: joubertd@sfasu.edu Disclosures: The authors declare no conflict of interest. This study was partially funded by the Sydney and J.L. Huffines Institute for Sports Medicine and Human Performance and the Texas – American College of Sports Medicine. Partial findings from the present study were previously presented at the 2016 and 2017 American College of Sports Medicine Annual Meeting. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2FJcSZa
http://ift.tt/2FJcSZa
Facilitating weight shifting during treadmill training improves walking function in humans with SCI: a randomized controlled pilot study
Objective To determine whether the integration of dynamic weight shifting into treadmill training would improve the efficacy of treadmill training in humans with spinal cord injury (SCI). Design Sixteen humans with SCI were randomly assigned to receive robotic or treadmill only training, and underwent 6 weeks of training. A force was applied to the pelvis for facilitating weight shifting and to the legs for assisting with leg swing for participants in the robotic group. No assistance force was applied for participants in the treadmill only group. Outcome measures consisted of overground walking speed, 6-minute walking distance, and other clinical measures, and were assessed pre, post 6 weeks of training, and 8 weeks after the end of training. Results A greater improvement in 6-minute walking distance was observed after robotic training than that after treadmill only training (p = 0.03), but there was not a significant difference between the two groups in improvements in walking speed. However, a greater improvement was observed for the participants who underwent robotic training than those who underwent treadmill only training (i.e., 15% vs. 2%). Conclusion Applying a pelvis assistance force for facilitating weight shifting during treadmill training may improve locomotor function in humans with SCI. Correspondence to: Ming Wu Ph.D., Legs and walking lab, Shirley Ryan Abilitylab, 355 East Erie Street, 23 floor, Chicago, IL, USA, 60611, E_mail: w-ming@Northwestern.edu Acknowledgement: This work is supported by the Davee Foundation, in partial by NIH (NIH/NICHD R01HD082216). We thank Dr. Sheng-Che Yen, Mrs. Jillian MacDonald, and Ms. Pooja Arora for their assistance during data collection. We thank Ms. Jill Landry for her suggestions and comments. Suppliers: GaitRite, CIR Systems Inc. 12 Cork Hill Road, Bldg #2, Franklin, NJ, 07416 Woodway, WOODWAY USA, Inc. W229 N591 Foster Ct., Waukesha, WI, 53186 Highlights: Humans with SCI underwent 6 weeks (3/week) of robotic or treadmill only training. Pelvis assistance was applied for facilitating weight shifting for robotic group. A greater improvement in endurance was obtained through robotic training. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2FN5qIn
http://ift.tt/2FN5qIn
Trajectories of quality of life and associated risk factors in patients with knee osteoarthritis: findings from the Osteoarthritis Initiative
Objective Knee osteoarthritis (OA) has a significant impact on quality of life (QOL). Although QOL is generally thought to diminish over time, it is unknown if different patient groups demonstrate unique patterns of change in QOL. We sought to identify and characterize QOL trajectories in knee OA. Design This prospective cohort study included 1013 individuals with symptomatic knee OA from the Osteoarthritis Initiative. We used group-based trajectory modeling to identify distinct temporal patterns of change in the Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL subscale over 8 years. Baseline covariates included age, gender, ethnicity, education, comorbidities, body mass index (BMI), substance use, depression, knee pain, and functional tests. Results Group-based trajectory modeling revealed three distinct QOL trajectories: a high QOL trajectory (32% of the cohort) experiencing improvement over 8 years, and moderate (49%) and low QOL (20%) trajectories maintaining similar levels over time. Low QOL trajectory membership was significantly associated with younger age (p
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http://ift.tt/2phwOYF
Long-term Retention of Musculoskeletal Ultrasound Training During Residency
The Accreditation Council for Graduate Medical Education (ACGME) and the American Board of Physical Medicine and Rehabilitation (ABPMR) developed milestones for evaluation of resident physicians that include proper musculoskeletal ultrasound (MSUS) examination of major joints. To date, there have been no published data demonstrating acquisition and retention of these skills and correlation with the milestone evaluation. The investigators developed and implemented a curriculum in musculoskeletal ultrasound examination for Physical Medicine and Rehabilitation (PM&R) residents at a large academic medical center. The investigators chose six joints for training and evaluation: ankle, elbow, hip, knee, shoulder and wrist/hand. The program included: 1) didactic lectures on anatomy and ultrasound technique; 2) peer-led demonstrations of the procedure on a standardized patient (SP); 3) individual practice on SPs; 4) faculty observation and feedback; 5) review sessions and additional practice; and, 6) assessment of skills in an objective structured clinical examination (OSCE). From 2013-2017, 30 PM&R residents were trained and evaluated. The results, based on OSCE scores, showed that the majority of residents achieved the appropriate level of competency for their year. A blended, standardized curriculum in MSUS instruction with assessment by an OSCE, can be used to evaluate MSUS skills, and can help align this education with residency milestones. Correspondence should be addressed to Dr. Irwin, Professor and Interim Chairman, Department of Physical Medicine and Rehabilitation, University of Miami Miller School of Medicine; PO Box 016960 (C206), Miami, FL 33101; Email: RIrwin@med.miami.edu. Disclosures: Ultrasound machines were supplied by FUJIFILM SonoSite, Inc., Bothell, WA Funding: No funding was received for this project Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2pjbKAu
http://ift.tt/2pjbKAu
Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
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EMS agency debuts St. Patrick's Day-themed ambulance
The Chatham Emergency Services ambulance is decked out in shamrocks and will make its first public debut in the St. Patrick's Day parade
http://ift.tt/2Gzr5oL
Endogenous c-Jun N-terminal kinase (JNK) activity marks the boundary between normal and malignant granulosa cells
Endogenous c-Jun N-terminal kinase (JNK) activity marks the boundary between normal and malignant granulosa cells
Endogenous c-Jun N-terminal kinase (JNK) activity marks the boundary between normal and malignant granulosa cells, Published online: 16 March 2018; doi:10.1038/s41419-018-0459-3
Endogenous c-Jun N-terminal kinase (JNK) activity marks the boundary between normal and malignant granulosa cellshttp://ift.tt/2phIQRU
Increased autophagy in EOC re-ascites cells can inhibit cell death and promote drug resistance
Increased autophagy in EOC re-ascites cells can inhibit cell death and promote drug resistance
Increased autophagy in EOC re-ascites cells can inhibit cell death and promote drug resistance, Published online: 16 March 2018; doi:10.1038/s41419-018-0449-5
Increased autophagy in EOC re-ascites cells can inhibit cell death and promote drug resistancehttp://ift.tt/2HCkF7G
Downregulation of lumican accelerates lung cancer cell invasion through p120 catenin
Downregulation of lumican accelerates lung cancer cell invasion through p120 catenin
Downregulation of lumican accelerates lung cancer cell invasion through p120 catenin, Published online: 16 March 2018; doi:10.1038/s41419-017-0212-3
Downregulation of lumican accelerates lung cancer cell invasion through p120 cateninhttp://ift.tt/2FFiFik
Nuclear galectin-1-FOXP3 interaction dampens the tumor-suppressive properties of FOXP3 in breast cancer
Nuclear galectin-1-FOXP3 interaction dampens the tumor-suppressive properties of FOXP3 in breast cancer
Nuclear galectin-1-FOXP3 interaction dampens the tumor-suppressive properties of FOXP3 in breast cancer, Published online: 16 March 2018; doi:10.1038/s41419-018-0448-6
Nuclear galectin-1-FOXP3 interaction dampens the tumor-suppressive properties of FOXP3 in breast cancerhttp://ift.tt/2HBigtN
Use of the XRCC2 promoter for in vivo cancer diagnosis and therapy
Use of the XRCC2 promoter for in vivo cancer diagnosis and therapy
Use of the XRCC2 promoter for in vivo cancer diagnosis and therapy, Published online: 16 March 2018; doi:10.1038/s41419-018-0453-9
Use of the XRCC2 promoter for in vivo cancer diagnosis and therapyhttp://ift.tt/2FIKdmT
Astrocytic metabolic switch is a novel etiology for Cocaine and HIV-1 Tat-mediated neurotoxicity
Astrocytic metabolic switch is a novel etiology for Cocaine and HIV-1 Tat-mediated neurotoxicity
Astrocytic metabolic switch is a novel etiology for Cocaine and HIV-1 Tat-mediated neurotoxicity, Published online: 16 March 2018; doi:10.1038/s41419-018-0422-3
Astrocytic metabolic switch is a novel etiology for Cocaine and HIV-1 Tat-mediated neurotoxicityhttp://ift.tt/2HEhY5s
Mitochondria-associated membranes (MAMs) and pathologies
Mitochondria-associated membranes (MAMs) and pathologies
Mitochondria-associated membranes (MAMs) and pathologies, Published online: 16 March 2018; doi:10.1038/s41419-018-0424-1
Mitochondria-associated membranes (MAMs) and pathologieshttp://ift.tt/2FHE3Ug
NF-κB-driven improvement of EHD1 contributes to erlotinib resistance in EGFR-mutant lung cancers
NF-κB-driven improvement of EHD1 contributes to erlotinib resistance in EGFR-mutant lung cancers
NF-κB-driven improvement of EHD1 contributes to erlotinib resistance in EGFR-mutant lung cancers, Published online: 16 March 2018; doi:10.1038/s41419-018-0447-7
NF-κB-driven improvement of EHD1 contributes to erlotinib resistance in EGFR-mutant lung cancershttp://ift.tt/2FOfJvY
Sero-epidemiological study of peste des petits ruminants in small ruminants in Amahara region, Ethiopia
Abstract
Peste des petits ruminants (PPR) is an acute, highly contagious, and economically important transboundary viral disease of sheep and goats. It is among the major infectious diseases that affect the production and productivity of small ruminants in Ethiopia. Cross-sectional and retrospective studies were undertaken to estimate the sero-prevalence, risk factors, and distribution of PPR in Amhara region. A total of 672 (329 sheep and 343 goats) sera were collected from 30 kebeles in 10 districts. Of the 672 sheep and goat sera samples tested using c-ELISA, 123 were positive for PPR antibodies, with the overall prevalence of 18.30% (95%CI 15.37, 21.24). The sero-prevalence of PPR was 21.57% (95%CI 17.15, 25.86) in goats and 14.89% (95%CI 10.96–18.65) in sheep. The variation of sero-prevalence among study zones was statistically significant (p < 0.05). The highest sero-prevalence was reported in Awi zone (55.34%) followed by South Gondar (15.89%), North Gondar (13.64%), East Gojjam (7.93%), and West Gojjam (6.62%) zones. Among host- and environment-related risk factors, species, sex, agro-ecology, and location of the study were significantly associated with PPR sero-positivity. The analysis of 5-year retrospective data (2010–2014) revealed high occurrence of PPR in the Amhara region with a total occurrence of 63 outbreaks (3978 cases and 919 deaths). In conclusion, the study revealed that PPR is an important and widely distributed disease of small ruminants in Amhara region. Appropriate control strategy including regular surveillance and vaccination is recommended to mitigate the challenge of PPR.
http://ift.tt/2tWzEaq
Intimate partner violence during pregnancy and use of antenatal care among rural women in southern Terai of Nepal
Publication date: April 2018
Source:Women and Birth, Volume 31, Issue 2
Author(s): Jitendra Kumar Singh, Sara Evans-Lacko, Dilaram Acharya, Rajendra Kadel, Salila Gautam
BackgroundUnderutilisation of antenatal care services due to intimate partner violence during pregnancy has been well documented elsewhere, but it is understudied in Nepal. Our study aimed at exploring the impact of intimate partner violence on antenatal care service utilisation in southern Terai of Nepal.MethodA community-based cross-sectional study was performed in 6 village development committees in Dhanusha district, Nepal. A total of 426 pregnant women in their second trimester were selected using a multistage cluster sampling method. Multivariable regression analyses were used to examine the association between exposure to intimate partner violence and selected antenatal care services, adjusting for covariates.ResultsAmong 426 pregnant women, almost three out of ten women (28.9%) were exposed to intimate partner violence at some point during their pregnancy. Pregnant women who were exposed to intimate partner violence were less likely to: register for antenatal care (OR 0.31; 95% CI (0.08–0.50)), take iron and folic acid (OR 0.55; 95% CI (0.12–0.90)), report dietary diversity (middle vs low: OR 0.34; 95% CI (0.11–0.58) and high vs low: OR 0.18; 95% CI (0.08–0.37)), have rest and sleep during day time (OR 0.47; 95% CI (0.61–0.58)), and attend mother's group meetings (OR 0.29; 95% CI (0.10–0.83)).ConclusionsIntimate partner violence during pregnancy is associated with low utilisation of antenatal care services. Therefore, effective strategies to prevent or reduce intimate partner violence during pregnancy is needed, which may lead to improved antenatal care service utilization in Nepal with healthier mothers and children's outcome.
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Aims and scope
Publication date: April 2018
Source:Women and Birth, Volume 31, Issue 2
http://ift.tt/2HDBP4E
Oral, systemic and socioeconomic factors associated with preterm birth
Publication date: Available online 16 March 2018
Source:Women and Birth
Author(s): Anna Clara F. Vieira, Cláudia M. Alves, Vandilson P. Rodrigues, Cecília C. Ribeiro, Isaac S. Gomes-Filho, Fernanda F. Lopes
BackgroundThe rates of preterm births have been increasing worldwide. Complications related to preterm births are associated with increased costs of care, and have a direct impact on the health system of the countries. Therefore, it is important to address factors associated with preterm birth in order to provide prevention strategies.ObjectiveThis case–control study investigated oral, systemic, and socioeconomic factors associated with preterm birth in postpartum women. Participants were 279 postpartum women that gave birth to a singleton live-born infant. Cases were women giving birth before 37 completed weeks of gestation (preterm birth). Controls were women giving birth at term (≥37weeks). Data were collected through questionnaires, medical records and intra-oral clinical examinations, which included dental caries registration according to World Health Organization criteria and oral biofilm evaluation through visible plaque index.ResultsNinety-one women had preterm birth (cases) and 188 women had birth at term (controls), ratio 1:2. Caries lesions were present in 62.3% of the cases and in 62.5% of the controls. The univariate analysis showed no association between dental caries and preterm birth (Odds Ratio=1.08, p=0.90). The multivariate analysis showed that maternal educational level (Odds Ratio=2.56, p=0.01) and arterial hypertension (Odds Ratio=2.32, p=0.01) were associated with prematurity.ConclusionThis study demonstrated that dental caries is frequent in postpartum women, but it does not appear to be associated with preterm birth. Meanwhile, maternal education level and arterial hypertension were associated with prematurity in this population.
http://ift.tt/2phmYGq
Mediastinoscopy-assisted esophagectomy for T2 middle and lower thoracic esophageal squamous cell carcinoma patients
Abstract
Background
We aimed to compare mediastinoscopy-assisted esophagectomy (MAE) with the Ivor Lewis procedure in T2 middle and lower thoracic esophageal carcinoma patients in fields of perioperative complications and overall survival (OS).
Methods
The clinical data of 112 T2 esophageal cancer patients who received MAE (n = 31) or Ivor Lewis procedure (n = 81) from January 2010 to December 2015 were retrospectively analyzed in propensity score analysis. Thirty-eight T2 esophageal cancer patients who underwent MAE (n = 19) and Ivor Lewis procedure (n = 19) were included in this study. The perioperative conditions and OS were analyzed.
Results
The MAE group showed shorter operation time (143.2 ± 20.6 vs 176.8 ± 31.1 min, P = 0.001), less drainage in 24 h (119.2 ± 235.1 vs 626.3 ± 396.3 mL, P < 0.001), less retention time of thoracic tube (27.8 ± 24.0 vs 101.2 ± 54.6 h, P < 0.001), and less hemorrhage during operation (255.4 ± 159.8 vs 367.4 ± 150.9 mL, P = 0.059) compared with the Ivor Lewis group. Less dissected lymph nodes were detected in the MAE group (12.2 ± 5.4 vs 16.8 ± 5.8, P = 0.044) than in the Ivor Lewis group, especially in the upper mediastinum (1.8 ± 2.1 vs 3.5 ± 2.3, P < 0.001) and middle mediastinum (2.5 ± 2.0 vs 5.3 ± 3.2, P = 0.027). The mean survival time was 59.1 and 53.3 months for the MAE group and Ivor Lewis group, respectively (P = 0.635). The results of Cox regression indicated that the nodal stage (P = 0.016) was an independent prognostic factor and the surgical method was not an independent prognostic factor for these patients (P = 0.290).
Conclusions
MAE procedure showed less surgical trauma compared with the Ivor Lewis procedure. The mediastinal lymphadenectomy of T2 esophageal carcinoma patients who underwent MAE was inferior to those who underwent Ivor Lewis procedure. The perioperative complications and OS of the MAE group were no worse than that of the Ivor Lewis group.
http://ift.tt/2IxSo3q
Unusual bilateral ovarian metastases from ileal gastrointestinal stromal tumor (GIST): a case report
Abstract
Background
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract and liver and peritoneum are the main sites of recurrence. Ovarian metastases from GIST are very rare.
Case Presentation
A 50 years-old woman was found to have a pelvic mass on transvaginal ultrasound (TV-US) and computed tomography (CT)-scan, considered as a right ovarian mass. The patient underwent surgical abdominal exploration that showed an ileal mass, a normal right ovary and an irregular and vascularized surface of the left ovary. A segmental ileal resection and an ileal anastomosis were performed. Frozen section showed a GIST and surgery was completed with hysterectomy, bilateral salpingo-oophorectomy, pelvic peritonectomy, peritoneal washing and Burch procedure. The histological examination confirmed an ileal GIST with ovarian metastases, harboring in both sites of disease a KIT exon 11 deletion.
Conclusions
Ovarian localizations, as far as rare, can be a clinical finding in case of ileal GIST patients, and both gynecologists, pathologists and medical oncologists should be able to recognize them.
http://ift.tt/2pgU8VK
EMS Strong honors first responders with ‘Stronger Together’ campaign
By EMS1 Staff WASHINGTON — A campaign to honor EMS providers was recently announced by the American College of Emergency Physicians and the National Association of Emergency Medical Technicians in an effort to raise National EMS Week awareness. According to a press release, this year's EMS Strong campaign will be "Stronger Together" and will bring together organizations and other ...
http://ift.tt/2tUmieM
NCI Launches the Intramural Continuing Umbrella of Research Experiences (iCURE) Program!
The NCI Intramural Research Program and CRCHD announce the new Intramural Continuing Umbrella of Research Experiences (iCURE) program! iCURE supports mentored research experiences within the NCI research community and encourages participation by underrepresented individuals.
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Quality indicators for in-hospital geriatric co-management programmes: a systematic literature review and international Delphi study
Objective
To find consensus on appropriate and feasible structure, process and outcome indicators for the evaluation of in-hospital geriatric co-management programmes.
DesignAn international two-round Delphi study based on a systematic literature review (searching databases, reference lists, prospective citations and trial registers).
SettingWestern Europe and the USA.
ParticipantsThirty-three people with at least 2 years of clinical experience in geriatric co-management were recruited. Twenty-eight experts (16 from the USA and 12 from Europe) participated in both Delphi rounds (85% response rate).
MeasuresParticipants rated the indicators on a nine-point scale for their (1) appropriateness and (2) feasibility to use the indicator for the evaluation of geriatric co-management programmes. Indicators were considered appropriate and feasible based on a median score of seven or higher. Consensus was based on the level of agreement using the RAND/UCLA Appropriateness Method.
ResultsIn the first round containing 37 indicators, there was consensus on 14 indicators. In the second round containing 44 indicators, there was consensus on 31 indicators (structure=8, process=7, outcome=16). Experts indicated that co-management should start within 24 hours of hospital admission using defined criteria for selecting appropriate patients. Programmes should focus on the prevention and management of geriatric syndromes and complications. Key areas for comprehensive geriatric assessment included cognition/delirium, functionality/mobility, falls, pain, medication and pressure ulcers. Key outcomes for evaluating the programme included length of stay, time to surgery and the incidence of complications.
ConclusionThe indicators can be used to assess the performance of geriatric co-management programmes and identify areas for improvement. Furthermore, the indicators can be used to monitor the implementation and effect of these programmes.
http://ift.tt/2HFfOCA
Impact of adolescent age on maternal and neonatal outcomes in the Born in Bradford cohort
Objectives
Explore associations between maternal and neonatal outcomes and maternal age, with particular reference to adolescent women.
DesignPopulation-based cohort study.
SettingMaternity department of a large hospital in Northern England.
ParticipantsPrimiparous women delivering a singleton at Bradford Royal Infirmary between March 2007 and December 2010 aged ≤19 years (n=640) or 20–34 years (n=3951). Subgroup analysis was performed using women aged ≤16 years (n=68). Women aged 20–34 years were used as the reference group.
Primary outcome measuresMaternal and neonatal outcomes.
ResultsThe odds of extremely low birth weight (<1000 g) were significantly higher in the adolescent group (≤19 years) compared with the reference group (adjusted OR (aOR) 4.13, 95% CI 1.41 to 12.11). The odds of very (<32 weeks) and extremely (<28 weeks) preterm delivery were also higher in the adolescent group (aOR 2.12, 95% CI 1.06 to 4.25 and aOR 5.06, 95% CI 1.23 to 20.78, respectively).
Women in the adolescent group had lower odds of gestational diabetes (aOR 0.35, 95% CI 0.20 to 0.62), caesarean delivery (aOR 0.53, 95% CI 0.42 to 0.67 and instrumental delivery (aOR 0.53, 95% CI 0.41 to 0.67).
ConclusionsThis study identifies important differences in maternal and neonatal outcomes between women by age group. These findings could help in identifying at-risk groups for additional support and tailored interventions to minimise the risk of adverse outcomes for these vulnerable groups. Further work is needed to identify the causal mechanisms linking age with outcomes in adolescent women where significant gaps in the literature exist.
http://ift.tt/2FF0IQW
Effectiveness of serious games and impact of design elements on engagement and educational outcomes in healthcare professionals and students: a systematic review and meta-analysis protocol
Introduction
Serious games (SGs) are interactive and entertaining digital software with an educational purpose. They engage the learner by proposing challenges and through various design elements (DEs; eg, points, difficulty adaptation, story). Recent reviews suggest the effectiveness of SGs in healthcare professionals' and students' education is mixed. This could be explained by the variability in their DEs, which has been shown to be highly variable across studies. The aim of this systematic review is to identify, appraise and synthesise the best available evidence regarding the effectiveness of SGs and the impact of DEs on engagement and educational outcomes of healthcare professionals and students.
Methods and analysisA systematic search of the literature will be conducted using a combination of medical subject headings terms and keywords in Cumulative Index of Nursing and Allied Health, Embase, Education Resources Information Center, PsycInFO, PubMed and Web of Science. Studies assessing SGs on engagement and educational outcomes will be included. Two independent reviewers will conduct the screening as well as the data extraction process. The risk of bias of included studies will also be assessed by two reviewers using the Effective Practice and Organisation of Care criteria. Data regarding DEs in SGs will first be synthesised qualitatively. A meta-analysis will then be performed, if the data allow it. Finally, the quality of the evidence regarding the effectiveness of SGs on each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.
Ethics and disseminationAs this systematic review only uses already collected data, no Institutional Review Board approval is required. Its results will be submitted in a peer-reviewed journal by the end of 2018.
PROSPERO registration numberhttp://ift.tt/2FLs83D
Reappraisal of previously reported meta-analyses on antibiotic prophylaxis for low-risk laparoscopic cholecystectomy: an overview of systematic reviews
Introduction
Many researchers have addressed overdosage and inappropriate use of antibiotics. Many meta-analyses have investigated antibiotic prophylaxis for low-risk laparoscopic cholecystectomy with the aim of reducing unnecessary antibiotic use. Most of these meta-analyses have concluded that prophylactic antibiotics are not required for low-risk laparoscopic cholecystectomies. This study aimed to assess the validity of this conclusion by systematically reviewing these meta-analyses.
MethodsA systematic review was undertaken. Searches were limited to meta-analyses and systematic reviews. PubMed and Cochrane Library electronic databases were searched from inception until March 2016 using the following keyword combinations: 'antibiotic prophylaxis', 'laparoscopic cholecystectomy' and 'systematic review or meta-analysis'. Two independent reviewers selected meta-analyses or systematic reviews evaluating prophylactic antibiotics for laparoscopic cholecystectomy. All of the randomised controlled trials (RCTs) analysed in these meta-analyses were also reviewed.
ResultsSeven meta-analyses regarding prophylactic antibiotics for low-risk laparoscopic cholecystectomy that had examined a total of 28 RCTs were included. Review of these meta-analyses revealed 48 miscounts of the number of outcomes. Six RCTs were inappropriate for the meta-analyses; one targeted patients with acute cholecystitis, another measured inappropriate outcomes, the original source of a third was not found and the study protocols of the remaining three were not appropriate for the meta-analyses. After correcting the above miscounts and excluding the six inappropriate RCTs, pooled risk ratios (RRs) were recalculated. These showed that, contrary to what had previously been concluded, antibiotics significantly reduced the risk of postoperative infections. The rates of surgical site, distant and overall infections were all significantly reduced by antibiotic administration (RR (95% CI); 0.71 (0.51 to 0.99), 0.37 (0.19 to 0.73), 0.50 (0.34 to 0.75), respectively).
ConclusionsProphylactic antibiotics reduce the incidence of postoperative infections after elective laparoscopic cholecystectomy.
http://ift.tt/2pgZlxz
Does a prostate cancer diagnosis affect management of pre-existing diabetes? Results from PCBaSe Sweden: a nationwide cohort study
Objectives
Both prostate cancer (PCa) and type 2 diabetes mellitus (T2DM) are increasingly prevalent conditions, which frequently coexist in men. Here, we set out to specifically examine the impact of a PCa diagnosis and its treatment on T2DM treatment.
SettingThis study uses observational data from Prostate Cancer database Sweden Traject.
ParticipantsThe study was undertaken in a cohort of 16 778 men with T2DM, of whom 962 were diagnosed with PCa during mean follow-up of 2.5 years.
Primary and secondary outcome measuresWe investigated the association between PCa diagnosis and escalation in T2DM treatment in this cohort. A treatment escalation was defined as a new or change in anti-T2DM prescription, as recorded in the prescribed drug register (ie, change from diet to metformin or sulphonylurea or insulin). We also investigated how PCa diagnosis was associated with two treatment escalations. Multivariate Cox proportional hazards regression with age as a time scale was used while adjusting for educational level and initial T2DM treatment.
ResultsWe found no association between PCa diagnosis and risk of a single treatment escalation (HR 0.99, 95% CI 0.87 to 1.13). However, PCa diagnosis was associated with an increased risk of receiving two consecutive T2DM treatment escalations (HR 1.75, 95% CI 1.38 to 2.22). This increase was strongest for men on gonadotropin-releasing hormone (GnRH) agonists (HR 3.08, 95% CI 2.14 to 4.40). The corresponding HR for men with PCa not on hormonal treatment was 1.40 (95% CI 1.03 to 1.92) and for men with PCa on antiandrogens 0.91 (95% CI 0.29 to 2.82).
ConclusionsMen with T2DM who are diagnosed with PCa, particularly those treated with GnRH agonists, were more likely to have two consecutive escalations in T2DM treatment. This suggests a need for closer monitoring of men with both PCa and T2DM, as coexistence of PCa and its subsequent treatments could potentially worsen T2DM control.
http://ift.tt/2HFzTc7
Targeted social care for highly vulnerable pregnant women: protocol of the Mothers of Rotterdam cohort study
Introduction
Social vulnerability is known to be related to ill health. When a pregnant woman is socially vulnerable, the ill health does not only affect herself, but also the health and development of her (unborn) child. To optimise care for highly vulnerable pregnant women, in Rotterdam, a holistic programme was developed in close collaboration between the university hospital, the local government and a non-profit organisation. This programme aims to organise social and medical care from pregnancy until the second birthday of the child, while targeting adult and child issues simultaneously. In 2014, a pilot in the municipality of Rotterdam demonstrated the significance of this holistic approach for highly vulnerable pregnant women. In the 'Mothers of Rotterdam' study, we aim to prospectively evaluate the effectiveness of the holistic approach, referred to as targeted social care.
Methods and analysisThe Mothers of Rotterdam study is a pragmatic prospective cohort study planning to include 1200 highly vulnerable pregnant women for the comparison between targeted social care and care as usual. Effectiveness will be compared on the following outcomes: (1) child development (does the child show adaptive development at year 1?) and (2) maternal mental health (is maternal distress reduced at the end of the social care programme?). Propensity scores will be used to correct for baseline differences between both social care programmes.
Ethics and disseminationThe prospective cohort study was approved by the Erasmus Medical Centre Ethics Committee (ref. no. MEC-2016–012) and the first results of the study are expected to be available in the second half of 2019 through publication in peer-reviewed international journals.
Trial registration numberNTR6271; Pre-results.
http://ift.tt/2FQN8pu
Effectiveness of pneumococcal and influenza vaccines to prevent serious health complications in adults with chronic liver disease: a protocol for a systematic review
Introduction
In advanced chronic liver disease, diseases caused by common bacteria Streptococcus pneumoniae or influenza virus put people at an increased risk of serious health complications and death. The effectiveness of the available vaccines in reducing the risk of poor health outcomes, however, is less clear.
Methods and analysisWe will search Medline (Ovid), Embase (Ovid), PubMed and Cochrane Central Register of Controlled Trials for published reports on randomised controlled trials and observational studies on the effectiveness of pneumococcal and influenza vaccines in people with chronic liver disease. Two independent reviewers will screen the studies for eligibility, extract data and assess study quality and risk of bias. Random effects meta-analyses will be performed as appropriate.
Ethics and disseminationFormal ethical approval is not required, as no primary data will be collected for this study. We will publish results of this study in relevant peer-reviewed medical journal or journals. Where possible, the study results will also be presented as posters or talks at relevant medical conferences and meetings.
PROSPERO registration numberhttp://ift.tt/2pg2Owe
Protocol for a 1-year prospective, longitudinal cohort study of patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy: the BARI-LIFESTYLE observational study
Introduction
Roux-en-Y gastric bypass and sleeve gastrectomy are the two most common bariatric surgery performed in the UK that result in comparable weight loss and remission of obesity-associated comorbidities. However, there is a paucity of studies examining the impact of these procedures on body composition, physical activity levels, sedentary behaviour, physical function and strength, dietary intake, health-related quality of life and costs.
Methods and analysisThe BARI-LIFESTYLE observational study is a 1-year prospective, longitudinal cohort study within a real-world routine clinical care setting aiming to recruit 100 patients with severe obesity undergoing either primary Roux-en-Y gastric bypass or sleeve gastrectomy from two bariatric centres in London, UK. Participants will be followed up four times during the study period; presurgery baseline (T0) and at 3 (T1), 6 (T2) and 12 months (T3) postsurgery. In addition to the standard follow-up investigations, assessments including dual-energy X-ray absorptiometry scan, bioelectric impedance analysis, 6 min walk test, sit-to-stand test and handgrip test will be undertaken together with completion of questionnaires. Physical activity levels and sedentary behaviour will be assessed using accelerometer, and dietary intake will be recorded using a 3-day food diary. Outcome measures will include body weight, body fat mass, lean muscle mass, bone mineral density, physical activity levels, sedentary behaviour, physical function and strength, dietary intake, health-related quality of life, remission of comorbidities, healthcare resource utilisation and costs.
Ethics and disseminationThis study has been reviewed and given a favourable ethical opinion by London-Dulwich Research Ethics Committee (17/LO/0950). The results will be presented to stakeholder groups locally, nationally and internationally and published in peer-reviewed medical journals. The lay-person summary of the findings will be published on the Centre for Obesity Research, University College London website (http://www.ucl.ac.uk/obesity).
http://ift.tt/2HFar6x
Associations between healthcare worker participation in workplace wellness activities and job satisfaction, occupational stress and burnout: a cross-sectional study in Botswana
Objectives
Healthcare workers (HWs) are prone to high levels of stress and burnout, particularly when caring for people with HIV/AIDS. This study assessed whether participation in Botswana's Workplace Wellness Programme (WWP) for HWs was associated with job satisfaction, occupational stress, well-being and burnout.
MethodsUsing multistage sampling, a paper-based questionnaire was distributed to 1856 randomly selected HWs at 135 public facilities across Botswana. Well-validated scales assessed key outcomes. Analysis of covariance models were built for psychosocial factors associated with WWP participation, controlling for associated demographics.
ResultsResponse rate was 73% (n=1348). The majority of respondents were female (62%), not married (65%) and had children (84%). Mean age was 40.0 years (SD±9.9). Respondents were roughly split between participation in no WWP activities (29.4%), 1–6 WWP activities (38.9%) and seven or more WWP activities (31.7%) in the past year. High participation was associated with older age, being a doctor or other professional, working at hospitals or District Health Management Teams, working longer in health services or working longer at a facility. In unadjusted analyses, high participation was significantly associated (P<0.05) with higher satisfaction with overall job, work, supervision, promotion, pay and professional efficacy and lower stress, exhaustion and cynicism. All associations remained significant in controlled analyses except cynicism.
ConclusionsResults from this study suggest that participation in workplace wellness activities is associated with higher satisfaction with multiple job facets and lower stress, exhaustion and cynicism. Introduction of these activities may help ameliorate high occupational stress levels among HWs.
http://ift.tt/2FF9tKS
A Service evaluation of a hospital child death review process to elucidate understanding of contributory factors to child mortality and inform practice in the English National Health Service
Objective
To describe a novel approach to hospital mortality meetings to elucidate understanding of contributory factors to child death and inform practice in the National Health Service.
DesignAll child deaths were separately reviewed at a meeting attended by professionals across the healthcare pathway, and an assessment was made of contributory factors to death across domains intrinsic to the child, family and environment, parenting capacity and service delivery. Data were analysed from a centrally held database of records.
SettingAll child deaths in a tertiary children's hospital between 1 April 2010 and 1 April 2013.
Main outcome measuresDescriptive data summarising contributory factors to child deaths.
Results95 deaths were reviewed. In 85% cases, factors intrinsic to the child provided complete explanation for death. In 11% cases, factors in the family and environment and, in 5% cases, factors in parenting capacity, contributed to patient vulnerability. In 33% cases, factors in service provision contributed to patient vulnerability and in two patients provided complete explanation for death. 26% deaths were classified as potentially preventable and in those cases factors in service provision were more commonly identified than factors across other domains (OR: 4.89; 95% CI 1.26 to 18.9).
ConclusionsHospital child death review meetings attended by professionals involved in patient management across the healthcare pathway inform understanding of events leading to a child's death. Using a bioecological approach to scrutinise contributory factors the multidisciplinary team concluded most deaths occurred as a consequence of underlying illness. Although factors relating to service provision were commonly identified, they rarely provided a complete explanation for death. Efforts to reduce child mortality should be driven by an understanding of modifiable risk factors. Systematic data collection arising from a standardised approach to hospital reviews should be the basis for national mortality review processes and database development.
http://ift.tt/2HFaj73
Efficacy and moderators of psychological interventions in treating subclinical symptoms of depression and preventing major depressive disorder onsets: protocol for an individual patient data meta-analysis of randomised controlled trials
Introduction
The long-term effectiveness of psychological interventions for the treatment of subthreshold depression and the prevention of depression is unclear and effects vary among subgroups of patients, indicating that not all patients profit from such interventions. Randomised clinical trials are mostly underpowered to examine adequately subgroups and moderator effects. The aim of the present study is, therefore, to examine the short-term and long-term as well as moderator effects of psychological interventions compared with control groups in adults with subthreshold depression on depressive symptom severity, treatment response, remission, symptom deterioration, quality of life, anxiety and the prevention of major depressive disorder (MDD) onsets on individual patient level and study level using an individual patient data meta-analysis approach.
Methods and analysisSystematic searches in PubMed, PsycINFO, Embase and the Cochrane Central Register of Controlled Trials were conducted. We will use the following types of outcome criteria: (A) onset of major depression; (B) time to major depression onset; (C) observer-reported and self-reported depressive symptom severity; (D) response; (E) remission; (F) symptom deterioration; (G) quality of life, (H) anxiety; and (I) suicidal thoughts and behaviours. Multilevel models with participants nested within studies will be used. Missing data will be handled using a joint modelling approach to multiple imputation. A number of sensitivity analyses will be conducted in order test the robustness of our findings.
Ethics and disseminationThe investigators of the primary trials have obtained ethical approval for the data used in the present study and for sharing the data, if this was necessary, according to local requirements and was not covered from the initial ethic assessment.
This study will summarise the available evidence on the short-term and long-term effectiveness of preventive psychological interventions for the treatment of subthreshold depression and prevention of MDD onset. Identification of subgroups of patients in which those interventions are most effective will guide the development of evidence-based personalised interventions for patients with subthreshold depression.
PROSPERO registration numberhttp://ift.tt/2FF9luS
Forgone care among middle aged and elderly with chronic diseases in China: evidence from the China Health and Retirement Longitudinal Study Baseline Survey
Objective
In general, published studies analyse healthcare utilisation, rather than foregone care, among different population groups. The assessment of forgone care as an aspect of healthcare system performance is important because it indicates the gap between perceived need and actual utilisation of healthcare services. This study focused on a specific vulnerable group, middle-aged and elderly people with chronic diseases, and evaluated the prevalence of foregone care and associated factors among this population in China.
MethodsData were obtained from a nationally representative household survey of middle-aged and elderly individuals (≥45 years), the China Health and Retirement Longitudinal Study, which was conducted by the National School of Development of Peking University in 2013. Descriptive statistics were used to analyse sample characteristics and the prevalence of foregone care. Andersen's healthcare utilisation and binary logistic models were used to evaluate the determinants of foregone care among middle-aged and elderly individuals with chronic diseases.
ResultsThe prevalence of foregone outpatient and inpatient care among middle-aged and elderly people was 10.21% and 6.84%, respectively, whereas the prevalence of foregone care for physical examinations was relatively high (57.88%). Predisposing factors, including age, marital status, employment, education and family size, significantly affected foregone care in this population. Regarding enabling factors, individuals in the highest income group reported less foregone inpatient care or physical examinations compared with those in the lowest income group. Social healthcare insurance could significantly reduce foregone care in outpatient and inpatient situations; however, these schemes (except for urban employee medical insurance) did not appear to have a significant impact on foregone care involving physical examinations.
ConclusionIn China, policy-makers may need to further adjust healthcare policies, such as health insurance schemes, and improve the hierarchical medical system, to promote reduction in foregone care and effective utilisation of health services.
http://ift.tt/2FOf5hP
Can virtual autopsy with postmortem CT improve clinical diagnosis of cause of death? A retrospective observational cohort study in a Dutch tertiary referral centre
Objective
To investigate whether virtual autopsy with postmortem CT (PMCT) improves clinical diagnosis of the immediate cause of death.
DesignRetrospective observational cohort study. Inclusion criteria: inhospital and out-of-hospital deaths over the age of 1 year in whom virtual autopsy with PMCT and conventional autopsy were performed. Exclusion criteria: forensic cases, postmortal organ donors and cases with incomplete scanning procedures. Cadavers were examined by virtual autopsy with PMCT prior to conventional autopsy. The clinically determined cause of death was recorded before virtual autopsy and was then adjusted with the findings of virtual autopsy. Using conventional autopsy as reference standard, we investigated the increase in sensitivity for immediate cause of death, type of pathology and anatomical system involved before and after virtual autopsy.
SettingTertiary referral centre.
Participants86 cadavers that underwent conventional and virtual autopsy between July 2012 and June 2016.
InterventionPMCT consisted of brain, cervical spine and chest–abdomen–pelvis imaging. Conventional autopsy consisted of thoracoabdominal examination with/without brain autopsy.
Primary and secondary outcome measuresIncrease in sensitivity for the immediate cause of death, type of pathology (infection, haemorrhage, perfusion disorder, other or not assigned) and anatomical system (pulmonary, cardiovascular, gastrointestinal, other or not assigned) involved, before and after virtual autopsy.
ResultsUsing PMCT, the sensitivity for immediate cause of death increased with 12% (95% CI 2% to 22%) from 53% (41% to 64%) to 64% (53% to 75%), with 18% (9% to 27%) from 65% (54% to 76%) to 83% (73% to 91%) for type of pathology and with 19% (9% to 30%) from 65% (54% to 76%) to 85% (75% to 92%) for anatomical system.
ConclusionWhile unenhanced PMCT is an insufficient substitute for conventional autopsy, it can improve diagnosis of cause of death over clinical diagnosis alone and should therefore be considered whenever autopsy is not performed.
http://ift.tt/2pgNuzt
Awareness of the role of general practitioners in primary care among outpatient populations: evidence from a cross-sectional survey of tertiary hospitals in China
Objective
General practitioners (GPs) are highly underutilised in China with many patients going directly to hospitals when seeking routine care. Multiple countries around the world have successfully used GPs in routine care, and as such, China may benefit from the use of GPs. This study examines the status of, and factors associated with, knowledge related to GPs among outpatient populations from China's tertiary hospitals.
DesignThis is a cross-sectional survey study.
Study setting and participantsThe questionnaires were completed by 565 outpatients from four tertiary hospitals in China during 2016. Convenience sampling on different floors and throughout the outpatient building was carried out.
Primary outcome measuresWe used the logistic regression models to identify GP-related knowledge among different populations.
ResultsOverall, 50.27% of respondents said they had never heard of GPs. This was also true among females (adjusted OR (AOR)=1.57, 95% CI 1.43 to 2.71), older adults (AOR46–65=1.61, 95% CI 1.39 to 2.98; AOR>65=2.01, 95% CI 1.62 to 3.59), those with lower education level (AORBachelor's degree=0.61, 95% CI 0.20 to 0.81; AOR≥Master's degree=0.49, 95% CI 0.23 to 0.76), rural residents (AOR=1.51, 95% CI 1.35 to 2.82) and those with chronic disease (AORwithout chronic disease=0.61, 95% CI 0.22 to 0.71). What is more, less than one-in-ten (9.03%) outpatients were able to accurately describe what a GP was, with less than 30% accurately describing a GP among those receiving GPs' services.
ConclusionsOutpatients who could have received less costly health services from GPs in primary medical institutions were more likely to choose costlier specialist physicians in tertiary hospitals, which is likely linked to limited knowledge about GPs. Policy makers should invest in outreach efforts to improve public awareness of GPs, while at the same time conducting continued surveillance of these efforts to evaluate progress towards this goal.
http://ift.tt/2FQFhZq
Patient confidence regarding secondary lifestyle modification and knowledge of 'heart attack symptoms following percutaneous revascularisation in Japan: a cross-sectional study
Objective
To assess patient perspectives on secondary lifestyle modification and knowledge of 'heart attack' after percutaneous coronary intervention (PCI) for coronary artery disease (CAD).
DesignObservational cross-sectional study.
SettingA single university-based hospital centre in Japan.
ParticipantsIn total, 236 consecutive patients with CAD who underwent PCI completed a questionnaire (age, 67.4±10.1 years; women, 14.8%; elective PCI, 75.4%). The survey questionnaire included questions related to confidence levels about (1) lifestyle modification at the time of discharge and (2) appropriate recognition of heart attack symptoms and reactions to these symptoms on a four-point Likert scale (1=not confident to 4=completely confident).
Primary outcome measureThe primary outcome assessed was the patients' confidence level regarding lifestyle modification and the recognition of heart attack symptoms.
ResultsOverall, patients had a high level of confidence (confident or completely confident,>75%) about smoking cessation, alcohol restriction and medication adherence. However, they had a relatively low level of confidence (<50%) about the maintenance of blood pressure control, healthy diet, body weight and routine exercise (≥3 times/week). After adjustment, male sex (OR 3.61, 95% CI 1.11 to 11.8) and lower educational level (OR 3.25; 95% CI 1.70 to 6.23) were identified as factors associated with lower confidence levels. In terms of confidence in the recognition of heart attack, almost all respondents answered 'yes' to the item 'I should go to the hospital as soon as possible when I have a heart attack'; however, only 28% of the responders were confident in their ability to distinguish between heart attack symptoms and other conditions.
ConclusionsThere were substantial disparities in the confidence levels associated with lifestyle modification and recognition/response to heart attack. These gaps need to be studied further and disseminated to improve cardiovascular care.
http://ift.tt/2FHK4QE
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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