An NHS review of transvaginal mesh implants released this week has been branded a "whitewash" after failing to order a safety review of the devices, which patients say carry unacceptable risks of...
"Earlier this month we published our latest annual report on adverse incidents related to transfusion.1 Our organisation is 20 years old and has had a significant impact on transfusion safety."All...
Another day of discount shopping? Fantastic!No, you fool—this is Black Wednesday, not Black Friday. It's the first Wednesday in August, when a new cohort of junior doctors start working at NHS...
A report from RAND Europe, a non-profit research institute based in Cambridge, has sparked a debate about whether community hospitals can deliver integrated care in England.The report,1 commissioned...
Almost 63 000 people in England will die over the next five years from liver problems linked to heavy drinking, researchers have predicted, prompting doctors to call for the government to introduce...
Viruses, Vol. 9, Pages 196: Perspectives on the Evolution of Porcine Parvovirus
Viruses doi: 10.3390/v9080196
Authors: Woo-Taek Oh Ri-Yeon Kim Van-Giap Nguyen Hee-Chun Chung Bong-Kyun Park
Porcine parvovirus (PPV) is one of the main causes of porcine reproductive failure. It is important for swine industries to understand the recent trends in PPV evolution. Previous data show that PPV has two genetic lineages originating in Germany. In this study, two more genetic lineages were defined, one of which was distinctly Asian. Additionally, amino acid substitutions in European strains and Asian strains showed distinct differences in several regions of the VP2 gene. The VP1 gene of the recent PPV isolate (T142_South Korea) was identical to that of Kresse strain isolated in the USA in 1985, indicating that modern PPV strains now resemble the original strains (Kresse and NADL-2). In this study, we compared strains isolated in the 20th century to recent isolates and confirmed the trend that modern strains are becoming more similar to previous strains.
Vaccinium bracteatum Thunb, have been widely used in various traditional medicines and food products. The narrow and uniform particle size distribution in V. bracteatum Thunb leaves (VBTL) can be achieved through a new emerging type of foodstuff processing and superfine grinding. The VBTL powders were subjected to four particle sizes as followed: 300–125, 125–75, 75–40, and <40 μm. The VBTL powders were observed to be with smaller size and bulk density, greater surface area, tapped density and the angle of repose. Water solubility index, water holding capacity and total flavonoid extraction increased slightly with the decrease in particle size. Differential scanning calorimetry showed that the VBTL exhibiting particle size of <40 μm had the lowest peak temperature; whereas, powder with a particle size of 125–300 μm displayed the largest endothermic enthalpy. Our results of the properties of VBTL superfine powder supplied the basis for VBTL in potential industrial applications of foods.
Dr Santos talks with ecancer at NOSCM 2017 about the New Orleans Summer Cancer Meeting 2017 and his talk about how immunotherapy has moved to the frontline in treatment of lung cancer. He goes on to discus the treatment of lung cancer using carboplatin...
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Dr Klemp talks with ecancer at NOSCM 2017 about the unmet needs of cancer survivors and how this is becoming an imperative part of cancer care delivery. She goes on to outline how important it is to address the physical and psychological consequences of...
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Prof Petrylak talks with ecancer at NOSCM 2017 about the management and treatment of advanced prostate cancer and new drug approvals for prostate cancer. He goes on to discuss new FDA drug approvals and the benefit on survival rates for patients with...
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Adrienne Vazquez talks to ecancer at NOSCM 2017 about precision medicine from a nurses perspective. She goes on to discuss the ways in which the University of Miami operates in relation to precision medicine. She outlines the next generation sequencing...
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Urticaria is a common, mast cell-driven disease presenting with wheals or angioedema or both. In the last years, urticaria has increasingly attracted notice to clinicians and researchers, last but not least inspired by the approval of omalizumab, an anti-IgE antibody, for urticaria treatment. There is wide consensus on the clinical classification based on duration and elicitation. However, the pathogenesis is incompletely understood. This review summarizes current guidelines for the management and novel insights in the pathogenesis of urticaria with special focus on their impact on clinical praxis. The classification of urticaria subgroups is mainly based on clinical criteria: acute and chronic urticaria (CU). Chronic urticaria comprises both chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU) that includes physical and non-physical urticarias. Recent research focused on characterizing the role of cells and mediators involved in the pathogenesis of urticaria, identifying the mechanisms of mast cell activation, and investigating underlying autoimmune processes in chronic spontaneous urticarial. Currently, non-sedating antihistamines and omalizumab, an antiimmunoglobulin E antibody, are recommended for the therapy of chronic urticaria, as both exhibit a favorable efficacy and safety profile. Novel therapeutic strategies aim at specifically targeting cells and mediators involved in the pathogenesis of urticaria.
Fibrin has excellent biocompatibility and biological properties to support tissue regeneration and promote wound healing. However, the role of diluted fibrin in wound healing has yet to be elucidated as it is commonly used in high concentration. This study was aimed to examine the effects of diluted plasma-derived fibrin (PDF) on keratinocyte and fibroblast wound healing in term of cell proliferation, migration, extracellular matrix (ECM) production and soluble factor secretion. Two PDF concentrations, 10 and 20% (v/v) were tested on keratinocytes and fibroblasts indirectly co-cultured in the transwell system. The control group was cultured with 5% FBS. Results showed that PDF reduced the keratinocyte growth rate and fibroblast migration, and increased the fibroblast ECM gene expression whereby significant differences were found between the 20% PDF group and the 5% FBS group. Similar trend was seen for the 10% PDF group but the differences were not significant. Comparison of the soluble factors between the PDF groups demonstrated that the level of growth-related oncogene alpha, interleukin-8 and epithelial neutrophil-activating peptide-78 were significantly higher in the 10% PDF group, whilst interleukin-1 alpha and granulocyte–macrophage colony stimulating factor were significantly more concentrated in the 20% PDF group. Our results suggested that PDF selectively elevated the expression of collagen type 1 and collagen type 3 in fibroblasts but slowed down the migration in concentration-dependent manner. These novel findings provide new insight into the role of PDF in wound healing and may have important implications for the use of fibrin in skin tissue engineering.
É morta a soli 45 anni a causa del melanoma Elisa Busato, originaria di San Bellino in provincia di Rovigo, ma residente da qualche tempo a Vigodarzere con...
Optimal therapy for infections with carbapenem resistant GNB is not well established due to the weakness of data. Patients presenting with bloodstream infections caused by multidrug resistant Klebsiella pneumoniae were treated with a combination treatment. Optimal therapy for infections with carbapenem resistant Gram-negative bacteria is a serious problem in pediatric patients. We presented three cases who were successfully treated with addition of ertapenem to the combination treatment for bacteremia with multidrug resistant Klebsiella pneumoniae. Dual carbapenem treatment approach is a new approach for these infections and requires more data in children.
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Pancreaticoduodenal artery aneurysms (PDA) are rare visceral aneurysms. Celiac trunk stenosis represents a common attributable aetiology for those aneurysms. Therefore, an alternative treatment approach, which differs from those isolated aneurysms, is recommended. We hereby present a 77-year-old male patient who was admitted with sudden onset of severe abdominal pain and significant drop in haemoglobin, occurring within a 24-hour interval. Contrast-enhanced computed tomography revealed a ruptured visceral aneurysm arising from the anterior branch of the inferior pancreaticoduodenal artery. A severe stenosis was also noted at the take-off of the celiac trunk. Selective catheterization of the supplying branch of the superior mesenteric artery, followed by coil embolization of the aneurysm, was performed, resulting in cessation of flow within the aneurysm, with preservation of the posterior branch, supplying the celiac territory. PDAs are usually asymptomatic and discovered incidentally at rupture. The risk of rupture is independent of the aneurysmal size and is associated with a 50% mortality rate. The consensus on coping with aneurysms is to treat them whenever they are discovered. Selective angiography followed by coil embolization represents a less invasive, and frequently definitive, approach than surgery. The risk for ischemia mandates that the celiac territory must not be compromised after embolization.
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Background. Studies on treatment modalities for primary hepatic neoplasms (PHN) in Canada are lacking. Our primary aim was to analyze the age-standardized incidence of hepatic resection, ablation, transplantation, and embolization for PHN between 2002 and 2013. Secondary aim was to evaluate temporal trends for these treatment modalities. Study Design. National Canadian Cancer Registries were accessed for relevant epidemiological data. Age-standardized incidence of treatment ratios (SIRs) was calculated and comparisons were performed for Atlantic Canada, Ontario, the Prairies, and British Columbia. Results. British Columbia recorded the highest SIRs for ablation (1.9; 95% CI 1.8–2.0), hepatic resection (1.2; 95% CI 1.1–1.3), and transarterial locoregional therapies (2.8; 95% CI 2.4–3.2). For hepatic resection, the lowest SIR was found in Atlantic Canada (0.7; 95% CI 0.6–0.9), while the Prairies recorded the lowest estimate for transarterial therapies (0.2; 95% CI 0.1–0.4). Liver transplantation had the highest SIR in Ontario (1.5; 95% CI 1.3–1.6) and the lowest SIR in British Columbia. No significant temporal changes in SIRs were observed for any of the treatments except for transarterial therapies. Conclusions. Treatment of PHN in Canada differs by geography. Variations might be due to differences in expertise or access to therapeutic modalities.
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Background. Breast cancer is the most common cancer in women. Disparities in some characteristics of breast cancer patients and their survival data for six randomly selected states in the US were examined. Materials and Methods. A probability random sampling method was used to select the records of 2,000 patients from each of six randomly selected states. Demographic and disease characteristics were extracted from the Surveillance Epidemiology and End Results (SEER) database. To evaluate relationships between variables, we employed a Cox Proportional Regression to compare survival times in the different states. Results. Iowa had the highest mean age of diagnosis at 64.14 years () and Georgia had the lowest at 57.97 years (). New Mexico had the longest mean survival time of 189.09 months () and Hawaii the shortest at 119.01 () months, a 70.08-month difference (5.84 years). Analysis of stage of diagnosis showed that the highest survival times for Whites and American Indians/Alaska Natives were for stage I cancers. The highest survival times for Blacks varied. Stage IV cancer consistently showed the lowest survival times. Conclusions. Differences in breast cancer characteristics across states highlight the need to understand differences between the states that result in variances in breast cancer survival.
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Background and Aims. Plenty of studies were conducted to explore the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) in ovarian cancer with contradictory results. This study aims to summarize the prognostic significance of NLR in patients with ovarian cancer. Methods. A literature search in PubMed, Cochrane Library, and Embase was conducted. The endpoints were progression-free survival (PFS) and overall survival (OS). Results. Eleven studies involving a total of 2,892 patients were identified. The results indicated that patients with high NLR had shorter PFS compared to patients with low NLR in ovarian cancer (HR = 1.55, 95% CI = 1.15–2.08, , and ). Similarly, high NLR was related to shorter OS (HR = 1.51, 95% CI = 1.03–2.23, , and ). Moreover, high NLR was significantly associated with shorter PFS when the NLR cut-off was less than 3.3 () or when treatment is operation (). In addition, high NLR was distinctly related to worse OS in Asian people (p = 0.04) or operation (p = 0.04). Conclusion. High NLR was associated with shorter PFS and shorter OS in ovarian cancer. NLR is potentially a promising prognostic biomarker in patients with ovarian cancer.
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Large bone defects and nonunions are serious complications that are caused by extensive trauma or tumour. As traditional therapies fail to repair these critical-sized defects, tissue engineering scaffolds can be used to regenerate the damaged tissue. Highly porous titanium scaffolds, produced by selective laser sintering with mechanical properties in range of trabecular bone (compressive strength 35 MPa and modulus 73 MPa), can be used in these orthopaedic applications, if a stable mechanical fixation is provided. Hydroxyapatite coatings are generally considered essential and/or beneficial for bone formation; however, debonding of the coatings is one of the main concerns. We hypothesised that the titanium scaffolds have an intrinsic potential to induce bone formation without the need for a hydroxyapatite coating. In this paper, titanium scaffolds coated with hydroxyapatite using electrochemical method were fabricated and osteoinductivity of coated and noncoated scaffolds was compared in vitro. Alizarin Red quantification confirmed osteogenesis independent of coating. Bone formation and ingrowth into the titanium scaffolds were evaluated in sheep stifle joints. The examinations after 3 months revealed 70% bone ingrowth into the scaffold confirming its osteoinductive capacity. It is shown that the developed titanium scaffold has an intrinsic capacity for bone formation and is a suitable scaffold for bone tissue engineering.
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to evaluate the influence of cerebral venous drainage on the pathogenesis of idiopathic sudden sensorineural hearing loss (ISSHL) and Ménière syndrome (MD).
we enrolled 59 consecutive patients (32 males, mean age 53.05+15.37 years): 40 ISSHL and 19 MD. All underwent physical examination, biochemical evaluation (glycemic and lipid profile, viral serology, C reactive protein, etc), audiometric (tonal, vocal, vestibular evoked myogenic potentials and auditory brainstem response test) and impedentiometric examination. The pure tone average (PTA) was calculated for the following frequencies: 250, 500, 1000, 2000, 3000, 4000, 8000. An echo-color Doppler evaluation of the venous cerebral veins, internal jugular (IJV) and vertebral veins (VV) at supine and 90° position was performed.
no morphological alterations were found both in patients and controls. There were no signs of stenosis, blocked flow, membranes, etc. We found lower minimum, mean and maximum velocities in distal IJVs (p=0.019; p=0.013; p=0.022; respectively) and left VVs (p=0.027; p=0.008; p=0.001; respectively) in supine (0°) position in both MD and ISSHL patients as compared to controls. The same was for orthostatic position (90°). We found negative correlations between the velocities in extracranial veins and PTA values: therefore, the worst the audiometric performance of the subjects, the lower the velocities in the venous cerebral drainage.
ISSHL and MD patients showed altered venous flow in IJVs and VVs as compared to controls, independently from posture. This different behavior of venous tone control can influence the ear performance and may have a role in the pathogenesis of both diseases.
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Since the genomic region containing the Bcl-2-related ovarian killer (BOK) locus is frequently deleted in certain human cancers, BOK is hypothesized to have a tumor suppressor function. In the present study, we analyzed primary non-small cell lung carcinoma (NSCLC) tumors and matched lung tissues from 102 surgically treated patients. We show that BOK protein levels are significantly downregulated in NSCLC tumors as compared to lung tissues (P<0.001). In particular, we found BOK downregulation in NSCLC tumors of grades two (P=0.004, n=35) and three (P=0.031, n=39) as well as in tumors with metastases to hilar (pN1) (P=0.047, n=31) and mediastinal/subcarinal lymph nodes (pN2) (P=0.021, n=18) as opposed to grade one tumors (P=0.688, n=7) and tumors without lymph node metastases (P=0.112, n=51). Importantly, in lymph node positive patients, BOK expression greater than the median value was associated with longer survival (P=0.002, Mantel test). Using in vitro approaches, we provide evidence that BOK overexpression is inefficient in inducing apoptosis but that it inhibits TGFβ-induced migration and epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma-derived A549 cells. We have identified epigenetic mechanisms, in particular BOK promoter methylation, as an important means to silence BOK expression in NSCLC cells. Taken together, our data point toward a novel mechanism by which BOK acts as a tumor suppressor in NSCLC by inhibiting EMT. Consequently, the restoration of BOK levels in low-BOK-expressing tumors might favor the overall survival of NSCLC patients. This article is protected by copyright. All rights reserved.
The anatomic site-dependent expression of hematopoietic progenitor cell antigen CD34 is a feature of gastrointestinal stromal tumours (GISTs). The basis for the differential CD34 expression is only incompletely understood. This study aimed at understanding the regulation of CD34 in GISTs and clarification of its site-dependent expression. Two sample sets of primary GISTs were interrogated including 52 fresh-frozen and 134 paraffin-embedded and formalin-fixed specimens. DNA methylation analysis was performed by HumanMethylation450 BeadChip array in three cell lines derived from gastric and intestinal GISTs, and differentially methylated CpG sites were established upstream of CD34. The methylation degree was further quantified by pyrosequencing and inversely correlated with CD34 mRNA and protein abundance. The gene's expression could be activated upon induction of DNA hypomethylation with 5-aza-2'-deoxycytidine in GIST-T1 cells. In patient samples, a strong inverse correlation of DNA methylation degree with immunohistochemically evaluated CD34 expression was documented. Both CD34 expression and DNA methylation levels were specific to the tumours' anatomic location and mutation status. A constant decrease in methylation levels was observed ranging from almost 100% hypermethylation in intestinal GISTs from duodenum to hypomethylation in rectum. CD34 was heavily methylated in gastric PDGFRA-mutant GISTs in comparison to hypomethylated KIT-mutant counterparts. Next to CD34 hypermethylation, miR-665 was predicted and experimentally confirmed to target CD34 mRNA in GIST-T1 cells. Our results suggest that CD34 expression in GISTs may undergo a complex control by DNA methylation and miR-665. Differential methylation and expression of CD34 in GISTs along the gastrointestinal tract axis and in tumours that harbour different gain-of-function mutations suggest the origin from different cell populations in the gastrointestinal tract. This article is protected by copyright. All rights reserved.
The complexes cis-[Ru(quin)(dppm)2]PF6 and cis-[Ru(kynu)(dppm)2]PF6 (quin = quinaldate; kynu = kynurenate; dppm = bis(diphenylphosphino)methane) were prepared and characterized by elemental analysis, electronic, FTIR, 1H, and 31P NMR spectroscopies. Characterization data were consistent with a cis arrangement for the dppm ligands and a bidentate coordination through carboxylate oxygens of the quin and kynu anions. These complexes were not able to intercalate CT-DNA as shown by circular dichroism spectroscopy. On the other hand, bovine serum albumin (BSA) binding constants and thermodynamic parameters suggest spontaneous interactions with this protein by hydrogen bonds and van der Waals forces. Cytotoxicity assays were carried out on a panel of human cancer cell lines including HepG2, MCF-7, and MO59J and one normal cell line GM07492A. In general, the new ruthenium(II) complexes displayed a moderate to high cytotoxicity in all the assayed cell lines with IC50 ranging from 10.1 to 36 µM and were more cytotoxic than the precursor cis-[RuCl2(dppm)2]. The cis-[Ru(quin)(dppm)2]PF6 were two to three times more active than the reference metallodrug cisplatin in the MCF-7 and MO59J cell lines.
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Marijuana is the most widely abused "recreational" substance in the United States, with highest prevalence in young adults. It is reported to cause ischemic strokes, hepatitis, anxiety, and psychosis. Although it is associated with dose dependent tachycardia and can lead to coronary vasospasm, it has not been directly related to acute myocardial infarction (AMI). Marijuana induced coronary vasospasm can result in endothelial denudation at the site of a vulnerable atherosclerotic plaque in response to hemodynamic stressors, potentially causing an AMI. Spice refers to herbal mixture with composition and effects similar to that of marijuana and therefore is referred to as "synthetic marijuana." Herein, we report 3 cases of spice induced ST-segment elevation myocardial infarction. All patients were relatively young and had few or absolutely no risk factors for cardiovascular disease. All patients underwent emergent coronary angiography, with two needing stent placement and the third requiring only aspiration thrombectomy. Our case series emphasizes the importance of suspecting and investigating synthetic marijuana use in low risk young adults presenting with AMI.
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Design. The social, cultural, and economic context can be an important variable in the perception and adoption of risk behaviors in adolescents. Objective. The purpose of this study was to identify the prevalence of simultaneous health risk behaviors and associated socioeconomic factors in adolescents living in the metropolitan region of Aracaju, State of Sergipe, Brazil. Methods. The sample consisted of 2,207 high school students aged 13–18 years. The risk behaviors measured were "low levels of physical activity," "excessive daily TV time," "high consumption of alcoholic beverages on a single occasion," "involvement in fights," "smoking cigarettes," "carrying firearms," and "marijuana consumption." Information was obtained through self-administered questionnaire. Results. Considering the results, it was observed that female adolescents and those aged up to 16 years were less likely to have two or more health risk behaviors compared to males and those aged 17 years or more, respectively. It was also found that both high- and middle-income level adolescents had higher prevalence of having two or more health risk behaviors. Conclusions. It was concluded that male adolescents older than 16 years with better socioeconomic level were more exposed to the simultaneous presence of several health risk behaviors.
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For advanced atomic force microscopy (AFM) investigation of chemical surface modifications or very soft organic sample surfaces, the AFM probe tip needs to be operated in a liquid environment because any attractive or repulsive forces influenced by the measurement environment could obscure molecular forces. Due to fluid properties, the mechanical behavior of the AFM cantilever is influenced by the hydrodynamic drag force due to viscous friction with the liquid. This study provides a numerical model based on computational fluid dynamics (CFD) and investigates the hydrodynamic drag forces for different cantilever geometries and varying fluid conditions for Peakforce Tapping (PFT) in liquids. The developed model was verified by comparing the predicted values with published results of other researchers and the findings confirmed that drag force dependence on tip speed is essentially linear in nature. We observed that triangular cantilever geometry provides significant lower drag forces than rectangular geometry and that short cantilever offers reduced flow resistance. The influence of different liquids such as ultrapure water or an ethanol-water mixture as well as a temperature induced variation of the drag force could be demonstrated. The acting forces are lowest in ultrapure water, whereas with increasing ethanol concentrations the drag forces increase.
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Candida glabrata is a facultative intracellular opportunistic fungal pathogen in human infections. Several virulence-associated attributes are involved in its pathogenesis, host-pathogen interactions, modulation of host immune defenses, and regulation of antifungal drug resistance. This study evaluated the in vitro antifungal susceptibility profile to five antifungal agents, the production of seven hydrolytic enzymes related to virulence, and the relationship between these phenotypes in 91 clinical strains of C. glabrata. All C. glabrata strains were susceptible to flucytosine. However, some of these strains showed resistance to amphotericin B (9.9%), fluconazole (15.4%), itraconazole (5.5%), or micafungin (15.4%). Overall, C. glabrata strains were good producers of catalase, aspartic protease, esterase, phytase, and hemolysin. However, caseinase and phospholipase in vitro activities were not detected. Statistically significant correlations were identified between micafungin minimum inhibitory concentration (MIC) and esterase production, between fluconazole and micafungin MIC and hemolytic activity, and between amphotericin B MIC and phytase production. These results contribute to clarify some of the C. glabrata mechanisms of pathogenicity. Moreover, the association between some virulence attributes and the regulation of antifungal resistance encourage the development of new therapeutic strategies involving virulence mechanisms as potential targets for effective antifungal drug development for the treatment of C. glabrata infections.
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In childhood acute lymphoblastic leukemia, treatment failure is associated with resistance to glucocorticoid agents. Resistance to this class of drugs represents one of the strongest indicators of poor clinical outcome. We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells. Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner. Unlike solid tumors, where 2-deoxy-D-glucose promotes inhibition of glycolysis by hexokinase II exclusively under hypoxic conditions, we were able to show that the antileukemic effects of 2-deoxy-D-glucose are far more complex in leukemia. We demonstrate a hexokinase II-independent cell viability decrease and apoptosis induction of the glucose analog in leukemia. Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response.
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Purpose. To analyze the risk factors associated with a series of ectasia cases following photorefractive keratectomy (PRK) and all published cases. Methods. In a retrospective study on post-PRK ectasia patients, 9 eyes of 7 patients were included, in addition to 20 eyes of 13 patients from the literature. Risk of post-PRK ectasia was calculated using the ectasia risk score system (ERSS) for laser in situ keratomileusis (LASIK) patients. The percent tissue altered (PTA) was also evaluated. Results. ERSS scoring of zero for age, RSB, and spherical equivalent was found in 66%, 86%, and 86% of the eyes, respectively. Pachymetry risk score was 2 in 60% of the eyes and 3 or 4 in 16% of the eyes. Topography risk score was 3 in 41% of the eyes and 4 in 21% of the eyes. Cumulative ectasia risk score was ≥4 (high risk) in 77% of the eyes and ≥3 (medium and high risk) in 86% of the eyes. Average PTA was 23.2 ± 7.0%. All eyes but one had a PTA
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Scope. Several reports in the literature have suggested the renoprotective effects of ketone bodies and green tea polyphenols (GTPs). Our previous study found that GTP consumption could elevate the renal expression of the ketogenic rate-limiting enzyme, which was decreased by a high-fat diet (HFD) in rats. Here, we investigated whether ketogenesis can mediate renoprotection by GTPs against an HFD. Methods and Results. Wistar rats were fed a standard or HFD with or without GTPs for 18 weeks. The renal oxidative stress level, kidney function, renal expression, and activity levels of mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2) and sirtuin 3(SIRT3) were detected. The increased renal oxidative stress and the loss of renal function induced by the HFD were ameliorated by GTPs. Renal ketogenesis and SIRT3 expression and activity levels, which were reduced by the HFD, were restored by GTPs. In vitro, HEK293 cells were transfected with the eukaryotic expression plasmid pcDNA HMGCS2. GTP treatment could upregulate HMGCS2 and SIRT3 expression. Although SIRT3 expression was not affected by HMGCS2 transfection, the 4-hydroxy-2-nonenal (4-HNE) level and the acetyl-MnSOD (K122)/MnSOD ratio were reduced in HMGCS2-transfected cells in the context of H2O2. Conclusion. The ketogenesis/SIRT3 pathway mediates the renoprotection of GTPs against the oxidative stress induced by an HFD.
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Liver enzymes alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) are markers for type 2 diabetes mellitus (T2DM); alkaline phosphatase is a marker of liver disease. Mexican-American adolescents are disproportionately affected by T2DM, while in Mexico its prevalence is emerging. We assessed liver biomarkers and lipid profiles among Mexican and Mexican-American adolescents 10–14 years old with high/low risk of T2DM through a cross-sectional, descriptive study (Texas ; Mexico ). We included family medical histories, anthropometry, and blood pressure. Obesity was present in one-third of subjects in both sites. ALT (UL) was higher () in high-risk adolescents (23.5 ± 19.5 versus 17.2 ± 13.4 for males, 19.7 ± 11.6 versus 15.1 ± 5.5 for females), in Toluca and in Texas (26.0 ± 14.7 versus 20.0 ± 13.2 for males, 18.2 ± 13.4 versus 14.6 ± 10.1 for females), as well as GGT (UL) () (18.7 ± 11.1 versus 12.4 ± 2.3 for males, 13.6 ± 5.8 versus 11.5 ± 3.9 for Mexican females; 21.0 ± 6.8 versus 15.4 ± 5.5 for males, 14.3 ± 5.0 versus 13.8 ± 5.3 for females in Texas). We found no differences by sex or BMI. Total cholesterol and HDL were higher among Mexican-Americans (). In conclusion, multiple risk factors were present in the sample. We found differences by gender and between high and low risk for T2DM adolescents in all liver enzymes in both sites.
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This study updates information on mortality and cancer morbidity in a cohort of Norwegian talc workers.
Follow-up was extended with 24 years, covering 1953-2011. Comparisons were made with the general population and between subgroups within the cohort.
Standardized mortality ratio for non-malignant respiratory disease (NMRD) was 0.38 (95%CI: 0.18, 0.69) and for diseases of the circulatory system (CVD) 0.98 (95%CI: 0.82, 1.16). A non-significantly increased NMRD risk was observed at high dust exposures. There were no deaths from pneumoconiosis.
With the clear limitations of a small cohort, our results do hint at an effect of talc dust on mortality from NMRD other than pneumoconiosis, covered by a strong and persisting healthy worker effect. Also, an effect on CVD mortality, masked by a healthy worker selection into the cohort cannot be ruled out. Excess mortality from pneumoconiosis seen in other studies, may reflect exposure to quartz and, possibly, bias due to comparability problems.
The carcinogenicity of short tremolite fibers in human has not been cleared and has been argued hitherto. A lung cancer patient had worked at a gabbro quarry. Particles isolated from the excised lung parenchyma of the patient were measured for asbestos bodies (ABs) and asbestos fibers (AFs). The concentrations of ABs were 3964 AB/g dry lung, and AFs were 5.60 × 106 fibers/g dry lung (>5 um in length) and 22.5 × 106 fibers/g dry lung (>1 um in length). AFs were mostly tremolite fibers and under 7 um in length (mean length 4.0 um, standard deviation 2.8 um). Almost all fibers were <10 um in length and an aspect ratio (AR) of <20:1 and ≥3:1. The patient had never smoked. His wife, who had worked with him in the quarry, had died of pleural mesothelioma. This study strongly indicates that such short tremolite fibers will induce lung cancer and possibly mesothelioma in human.
Napping has known benefits for fatigue mitigation and improved alertness. However the Accreditation Council for Graduate Medical Education (ACGME) New Common Program Requirements recently removed the 16 h work limit for PGY1 residents and removed any suggestions of napping.
We utilized a cross-sectional study design to administer a 44-item questionnaire in June 2016 to 858 residents and fellows at one large urban academic medical center. We assessed: 1) resident physician sentiment of work environment supportiveness for napping at work; and 2) agreement with 2011 ACGME guidelines on workweek hour limitations and strategic napping recommendations.
While 89% of residents reported access to an on-call room at work, only 20% felt their work environment supported a culture of napping while at work. Over 76% expressed agreement with the 2011 ACGME work-hour restrictions.
Strategies to support napping and well-being within the resident physician workforce and organizational setting are warranted.
A rate-based understanding of home care aides' adverse occupational outcomes related to their work location and care tasks is lacking.
Within a 30-month, dynamic cohort of 43 394 home care aides in Washington State, injury rates were calculated by aides' demographic and work characteristics. Injury narratives and focus groups provided contextual detail.
Injury rates were higher for home care aides categorized as female, white, 50 to <65 years old, less experienced, with a primary language of English, and working through an agency (versus individual providers). In addition to direct occupational hazards, variability in workload, income, and supervisory/social support is of concern.
Policies should address the roles and training of home care aides, consumers, and managers/supervisors. Home care aides' improved access to often-existing resources to identify, manage, and eliminate occupational hazards is called for to prevent injuries and address concerns related to the vulnerability of this needed workforce.
Publication date: October 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 101
Author(s): Casey Means, Mark A. Aldape, Ericka King
ContextPrimary Sjögren syndrome is uncommon in children, and the standard clinical criteria used in diagnosis of adult Sjögren syndrome will miss many children with the disease. Floor of mouth ranulas have not been described in Sjögren syndrome.ObjectiveThis study aims to describe a novel presentation of juvenile primary Sjögren syndrome, and to present a comprehensive systematic review of the literature regarding the presentation and diagnosis of Sjögren syndrome in children.Data sourcesOvid MEDLINE.Study selectionA MEDLINE literature search was performed using the following search terms: primary, Sjögren, disease, and children. Results were limited to human subjects and articles written in English between 1981 and 2014. Applicable articles were reviewed and qualitatively summarized.Data extractionPreferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRIMA).ResultsInitial MEDLINE search yielded 146 articles, 80 of which were excluded as not clinically pertaining to Sjögren syndrome. An additional 25 were excluded due to lack of pediatric-specific data. Systematic review of the literature revealed no reports of ranula in association with Sjögren syndrome. 6 papers were manually included from review of reference lists of included articles. Our review indicated that recurrent parotitis is the most commonly reported presenting symptom in children, followed by ocular and oral symptoms, musculoskeletal, and renal symptoms. Compared to adults, children are less likely to present with dry eyes and mouth.LimitationsAll studies were retrospective chart reviews, case series or case reports.ConclusionThis is the first report of a child presenting with floor of mouth ranulas in association with Sjögren syndrome. While recurrent parotitis is the most common presentation in children, other salivary gland and extra-salivary manifestations may be seen, and the clinician must maintain a high index of suspicion for underlying Sjögren syndrome.
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To develop an antibacterial treatment for acne vulgaris using natural substance with few side effects, we investigated the antibacterial activities of oligochitosan against acne-related bacteria, particularly Propionibacterium acnes. Oligochitosan showed potent antibacterial effect on P. acnes. Especially, 10 kDa oligochitosan presented the highest antimicrobial effect with minimum inhibitory concentration values of 32–64 μg/mL on P. acnes. In addition, oligochitosan clearly reversed the antibacterial effect of tetracycline and erythromycin on P. acnes in the combination mode. The combination of tetracycline- or erythromycine-10 kDa oligochitosan resulted in a median ΣFIC range of 0.02–0.56, suggesting that the antibiotics–oligochitosan combination resulted in an antibacterial synergy against P. acnes. Thus, the results obtained in this research strongly supported that erythromycin and tetracycline will restore the antibacterial activity against P. acnes in the combination mode with 10 kDa oligochitosan.
Inhibitory effects of soy-protein edible coatings incorporated with 1, 2, or 3% of thyme or oregano essential oils (EOs) were determined against Escherichia coli O157:H7 (EC), Listeria monocytogenes (LM), and Staphylococcus aureus (SA) in vitro and on fresh beef during refrigerated storage for 14 days. The soy-protein coatings with oregano and thyme EOs exhibited similar antimicrobial activity against the test bacteria. Greater antimicrobial activity of soy edible coatings was demonstrated against SA when 3% of EOs were added. Coatings with 3% thyme and oregano EOs exhibited 2.86 and 2.59, 1.97 and 1.90, and 1.87 and 1.83 log CFU/g reductions in SA, LM, and EC populations, respectively, as compared with the control by Day 14. This study demonstrated that application of edible coatings containing oregano and thyme EOs on fresh beef cuts could have a potential for controlling pathogenic bacteria and enhancing color stability with acceptable sensory characteristics.
Publication date: 25 July 2017
Source:Cell Reports, Volume 20, Issue 4
Author(s): Pedro Réu, Azadeh Khosravi, Samuel Bernard, Jeff E. Mold, Mehran Salehpour, Kanar Alkass, Shira Perl, John Tisdale, Göran Possnert, Henrik Druid, Jonas Frisén
The hematopoietic system seeds the CNS with microglial progenitor cells during the fetal period, but the subsequent cell generation dynamics and maintenance of this population have been poorly understood. We report that microglia, unlike most other hematopoietic lineages, renew slowly at a median rate of 28% per year, and some microglia last for more than two decades. Furthermore, we find no evidence for the existence of a substantial population of quiescent long-lived cells, meaning that the microglia population in the human brain is sustained by continuous slow turnover throughout adult life.
Publication date: 25 July 2017
Source:Cell Reports, Volume 20, Issue 4
Author(s): Georgina Berrozpe, Gene O. Bryant, Katherine Warpinski, Dan Spagna, Santosh Narayan, Shivangi Shah, Mark Ptashne
How is Polycomb (Pc), a eukaryotic negative regulator of transcription, targeted to specific mammalian genes? Our genome-wide analysis of the Pc mark H3K27me3 in murine cells revealed that Pc is preferentially associated with CpG island promoters of genes that are transcribed at a low level and less so with promoters of genes that are either silent or more highly expressed. Studies of the CpG island promoter of the Kit gene demonstrate that Pc is largely absent when the gene is silent in myeloid cells, as well as when the gene is highly expressed in mast cells. Manipulations that increase transcription in the former case, and reduce it in the latter, increase Pc occupancy. The average negative effect of Pc, we infer, is about 2-fold. We suggest possible biological roles for such negative effects and propose a mechanism by which Pc might be recruited to weakly transcribed genes.
Publication date: 25 July 2017
Source:Cell Reports, Volume 20, Issue 4
Author(s): Larissa D. Cunha, Alexandre L.N. Silva, Juliana M. Ribeiro, Danielle P.A. Mascarenhas, Gustavo F.S. Quirino, Leonardo L. Santos, Richard A. Flavell, Dario S. Zamboni
Inflammasomes are multimeric protein complexes that initiate inflammatory cascades. Their activation is a hallmark of many infectious or inflammatory diseases. Their composition and activity are specified by proinflammatory stimuli. For example, the NLRP3 inflammasome is activated in response to cell damage and K+ efflux, whereas the AIM2 inflammasome is activated in response to cytosolic DNA. We used Legionella pneumophila, an intracellular bacterial pathogen that activates multiple inflammasomes, to elucidate the molecular mechanisms regulating inflammasome activation during infection. Upon infection, the AIM2 inflammasome engaged caspase-1 to induce pore formation in the cell membrane, which then caused K+-efflux-mediated activation of NLRP3. Thus, the AIM2 inflammasome amplifies signals of infection, triggering noncanonical activation of NLRP3. During infection, AIM2 and caspase-11 induced membrane damage, which was sufficient and essential for activating the NLRP3 inflammasome. Our data reveal that different inflammasomes regulate one another's activity to ensure an effective immune response to infection.
Publication date: 25 July 2017
Source:Cell Reports, Volume 20, Issue 4
Author(s): Yi-Li Cho, Michael Flossdorf, Lorenz Kretschmer, Thomas Höfer, Dirk H. Busch, Veit R. Buchholz
To what extent the lineage decisions of activated CD4+ T cells are determined by the quality of T cell receptor (TCR) ligation is incompletely understood. Here, we show that individual T cells expressing identical TCRs take highly variable fate decisions despite binding the same ligand. We identify a mathematical model that correctly captures this probabilistic behavior and allows one to formalize changes in TCR signal quality—due to cognate versus altered peptide ligation—as changes of lineage-specific proliferation and differentiation rates. We show that recall responses also adhere to this probabilistic framework requiring recruitment of multiple memory clones to provide reliable differentiation patterns. By extending our framework to simulate hypothetical TCRs of distinct binding strength, we reconstruct primary and secondary response patterns emerging from a polyclonal TCR repertoire in silico. Collectively, these data suggest that individual T cells harboring distinct TCRs generate overlapping primary differentiation patterns that segregate only upon repetitive immunization.
(Natural News) An opioid that is 50 times stronger than pure heroin (and 100 times more potent than morphine) is being over-prescribed by physicians nationwide as the delineation between medical ethics and personal gain fades even further. Fentanyl, a powerful prescription pain medication, is an entirely synthetic opioid initially meant to ease cancer patients to... (Source: NaturalNews.com)
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US Senate Republicans overcame their 1st hurdle as they aim to begin repealing and replacing Obamacare, narrowly passing a procedural motion to open debate on a bill to begin the dismantling. The Senate deadlocked at 50-50 on whether to move forward on the healthcare debate, with VP Mike Pence casting the tie-braking vote to open debate on a bill to repeal and replace the ACA. Senators Susan Collins (R-Maine) and Lisa Murkowski (R-Alaska) were the only Republicans to oppose the measure. Former opponents, including John McCain who was recently diagnosed with brain cancer and returned today to vote on the measure, tilted towards opening the bill for debate. President Trump praised the motion, saying that it was "a giant step to end the Obamacare nightmare." "As this vote shows, inactio...
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