Publication date: April 2017
Source:Biomedicine & Pharmacotherapy, Volume 88
Author(s): Bei Zhang, Mingze Chang, Juanhong Wang, Yong Liu
Neuroglobin (Ngb) has been reported to be upregulated by hypoxia and plays an anti-apoptotic function. Previous studies have reported that Ngb is expressed in human glioblastoma cells and up-regulated in hypoxic microregions of glioblastoma tumor xenografts. While, the clinical significance of Ngb and its function in human glioma keep unknown. Ngb expression was analyzed in 86 glioma tissues and 20 normal brain tissues. Results showed that Ngb was significantly overexpressed in glioma tissues compared to normal brain tissues. In addition, increased levels of Ngb also observed in glioma cell lines. Clinicopathological analysis verified that the positive expression of Ngb was associated with histological type and world health organization (WHO) grade of glioma. Moreover, Kaplan–Meier analysis found that Ngb overexpression led to a shorter survival. Multivariate Cox regression analysis demonstrated that Ngb expression was an independent prognostic marker. Further experiments illustrated that Ngb knockdown significantly inhibited proliferation and facilitated apoptosis in U251 cells. In vivo experiments further confirmed that Ngb silencing notably prohibited the tumor growth of glioma in nude mice. While, Ngb overexpression prominently promoted proliferation and suppressed apoptosis in U87 cells. Taken together, this work support the first evidence that Ngb can be potentially used as a promising biomarker and target for novel treatment of human glioma.
http://ift.tt/2iDDL07
Τρίτη 17 Ιανουαρίου 2017
Neuroglobin functions as a prognostic marker and promotes the tumor growth of glioma via suppressing apoptosis
Two Phase 1 dose-escalation studies exploring multiple regimens of litronesib (LY2523355), an Eg5 inhibitor, in patients with advanced cancer
Abstract
Purpose
This first-in-human report examined the recommended Phase 2 dose and schedule of litronesib, a selective allosteric kinesin Eg5 inhibitor.
Methods
Two concurrent dose-escalation studies investigated litronesib across the dose range of 0.125–16 mg/m2/day, evaluating the following schedules of administration on a 21-day cycle: Days 1, 2, 3; Days 1, 5, 9; Days 1, 8; Days 1, 5; or Days 1, 4, with or without pegfilgrastim. Best overall response was defined per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0). Pharmacokinetic (PK) evaluations were performed. Exploratory PK/pharmacodynamic analyses investigated the relationship between litronesib plasma exposure and changes in phosphohistone H3 (pHH3) levels.
Results
One hundred and seventeen patients with advanced malignancies were enrolled. Neutropenia was the primary dose-limiting toxicity. Prophylactic pegfilgrastim reduced neutropenia frequency and severity, allowing administration of higher litronesib doses, but increases in the incidences of mucositis and stomatitis were observed. Among 86 response-evaluable patients, 2 patients (2%) achieved partial response, both on the Days 1, 2, 3 regimen (5 and 6 mg/m2/day with pegfilgrastim), and 17 patients (20%) maintained stable disease for ≥6 cycles. Dose-dependent increases in litronesib plasma exposure were observed, with minor intra- and inter-cycle accumulation, along with exposure-dependent increases in pHH3 expression in tumor and skin biopsies.
Conclusions
On the basis of the results of these studies, two regimens were selected for Phase 2 exploration: 6 mg/m2/day on Days 1, 2, 3 plus pegfilgrastim and 8 mg/m2/day on Days 1, 5, 9 plus pegfilgrastim, both on a 21-day cycle.
http://ift.tt/2jFC83X
Does early blindness significantly enhance arithmetic? A statistical comment of a paper by Dormal, Crollen, Baumans, Lepore, and Collignon (2016)
Source:Cortex
Author(s): Jean-Paul Fischer
http://ift.tt/2iDllMS
Genetic defects in PI3Kδ affect B-cell differentiation and maturation leading to hypogammaglobulineamia and recurrent infections
Source:Clinical Immunology
Author(s): Marjolein Wentink, Virgil Dalm, Arjan C. Lankester, Pauline A. van Schouwenburg, Liesbeth Schölvinck, Tomas Kalina, Radana Zachova, Anna Sediva, Annechien Lambeck, Ingrid Pico-Knijnenburg, Jacques J.M. van Dongen, Malgorzata Pac, Ewa Bernatowska, Martin van Hagen, Gertjan Driessen, Mirjam van der Burg
BackgroundMutations in PIK3CD and PIK3R1 cause activated PI3K-δ syndrome (APDS) by dysregulation of the PI3K-AKT pathway.MethodsWe studied precursor and peripheral B-cell differentiation and apoptosis via flowcytometry. Furthermore, we performed AKT-phosphorylation assays and somatic hypermutations (SHM) and class switch recombination (CSR) analysis.ResultsWe identified 13 patients of whom 3 had new mutations in PIK3CD or PIK3R1. Patients had low total B-cell numbers with increased frequencies of transitional B cells and plasmablasts, while the precursor B-cell compartment in bone marrow was relatively normal. Basal AKT phosphorylation was increased in lymphocytes from APDS patients and natural effector B cells where most affected. PI3K mutations resulted in altered SHM and CSR and increased apoptosis.ConclusionsThe B-cell compartment in APDS patients is affected by the mutations in PI3K. There is reduced differentiation beyond the transitional stage, increased AKT phosphorylation and increased apoptosis. This B-cell phenotype contributes to the clinical phenotype.
http://ift.tt/2iJxzqJ
Hypothalamus specific re-introduction of Snord116 into otherwise Snord116 deficient mice increased energy expenditure
Abstract
The Snord116 gene cluster has been recognized as a critical contributor to the Prader-Willi Syndrome (PWS) with mice lacking Snord116 displaying many classical PWS phenotypes including low postnatal body weight, reduced bone mass and increased food intake. However, these mice do not develop obesity due to increased energy expenditure. To understand the physiological function of Snord116 better and potentially rescue the altered metabolism of Snord116-/- mice, we used an adeno-associated viral (AAV) approach to reintroduce the Snord116 gene product into the hypothalamus in Snord116-/- mice at different ages. Our results show that mid-hypothalamic re-introduction of Snord116 in 6-week old Snord116-/- mice leads to significantly reduced body weight and weight gain, associated with elevated energy expenditure. Importantly, when the intervention targets other areas such as the anterior region of the hypothalamus or the reintroduction occurs in older mice the positive effects on energy expenditure are diminished. These data indicate that the metabolic symptoms of PWS develop gradually and the Snord116 gene plays a critical role during this process. Furthermore, when we investigated the consequences of Snord116 re-introduction under conditions of thermo-neutrality where the mild cold stress influences are avoided, we also observed a significant increase in energy expenditure. In conclusion, the rescue of mid-hypothalamic Snord116 deficiency in young Snord116 germline deletion mice increases energy expenditure, providing fundamental information contributing to potential virus-mediated genetic therapy in PWS.
This article is protected by copyright. All rights reserved.
http://ift.tt/2jsvxfU
A Study to Investigate Biomarker Effects of Pre-Surgical Treatment With DNA Damage Repair (DDR) Agents in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC)
Interventions: Drug: AZD6738; Drug: Olaparib
Sponsor: AstraZeneca
Not yet recruiting - verified January 2017
http://ift.tt/2jsp1G1
PET+MR versus PET/CT in the initial staging of head and neck cancer, using a trimodality PET/CT+MR system
Publication date: Available online 17 January 2017
Source:Clinical Imaging
Author(s): Tetsuro Sekine, Felipe Barbosa, Felix P Kuhn, Irene A Burger, Paul Stolzmann, Gerhard F Huber, Spyros S Kollias, Gustav K von Schulthess, Patrick Veit-Haibach, Martin W Huellner
PurposeTo compare the diagnostic accuracy of PET+MR with PET/CT in the initial staging of head and neck cancer.Materials and methodsContrast-enhanced PET/CT+MR was performed in 27 patients with newly diagnosed head and neck cancer. PET/CT and PET+MR were evaluated separately, and the TNM stage and factors influencing treatment were assessed.ResultsThe TNM staging by PET+MR was comparable to PET/CT (T: p=0.331, N: p=0.453, M: p=0.034). The sensitivity/specificity/accuracy of treatment-influencing factors by PET/CT and PET+MR were 0.68/0.99/0.97, and 1.00/1.00/0.99, respectively.ConclusionsWhole-body staging with PET+MR yields at least equal diagnostic accuracy as PET/CT in head and neck cancer.
http://ift.tt/2jUVeSQ
Trial of Nivolumab as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer
Intervention: Drug: Nivolumab
Sponsors: David Neskey; Bristol-Myers Squibb
Not yet recruiting - verified January 2017
http://ift.tt/2jUJb82
Incidental Finding of Single Coronary Artery in a Patient with Alcoholic Cardiomyopathy Presenting as Acute Heart Failure
Publication date: Available online 16 January 2017
Source:Clinical Imaging
Author(s): Patrick McNair, Erica Jones, Quynh Truong, Harsimran Singh
Single coronary artery is a rare clinical finding. Diagnosis is typically made incidentally after the patient presents with symptoms and undergoes coronary angiography, coronary computed tomography angiography (CTA), or post-mortem during autopsy. Several high-risk features of anomalous coronary arteries have been described in the literature. Our paper describes a case of dilated alcoholic cardiomyopathy presenting as heart failure with diagnostic workup incidentally revealing single coronary artery.
http://ift.tt/2jsk3sE
Small bowel volvulus in pregnancy with associated superior mesenteric artery Occlusion
Publication date: Available online 16 January 2017
Source:Clinical Imaging
Author(s): Yonah B. Esterson, Robert Villani, Ronald A. Dela Cruz, Barak Friedman, Gregory M. Grimaldi
Here we report the case of a pregnant 28-year-old who presented with acute upper abdominal pain. CT demonstrated midgut volvulus with short segment occlusion of the superior mesenteric artery (SMA). Emergent detorsion of the small bowel was performed, at which time underlying intestinal malrotation was discovered. Following detorsion, the SMA had a bounding pulse and did not require thrombectomy or revascularization.Fewer than 25 cases of midgut volvulus during pregnancy have been reported over the past 20 years. To our knowledge, this is the first report of maternal midgut volvulus in which imaging captures the resultant occlusion of the SMA.
http://ift.tt/2jUN3pN
Comparison between MR imaging findings of intracranial and extracranial schwannomas
Publication date: Available online 16 January 2017
Source:Clinical Imaging
Author(s): Tomohiro Ando, Hiroki Kato, Masayuki Matsuo
PurposeTo evaluate the differences of MR imaging findings between intracranial and extracranial schwannomas.MethodsWe retrospectively reviewed the MR images of 98 schwannomas and compared the imaging findings between intracranial and extracranial schwannomas.ResultsThe number of intratumoral cysts was greater in intracranial than in extracranial schwannomas (4.8 ± 7.2 vs 1.8 ± 4.1; p < 0.05).ConclusionThe number of intratumoral cysts was different between intracranial and extracranial schwannomas.
http://ift.tt/2jFVtlB
Todd's Paralysis: A Crucial Entity Masquerading Stroke in the Emergency Department
Source:The Journal of Emergency Medicine
Author(s): Halil Onder
http://ift.tt/2jsnKOX
Viral Appendiceal Lymphoid Hyperplasia
Source:The Journal of Emergency Medicine
Author(s): Shorok Hassan, Joshua Greenstein, Jeremy Neuman, Barry J. Hahn
http://ift.tt/2j4C3G9
Spontaneous Valsalva-Associated Right-Sided Diaphragmatic Rupture
Publication date: Available online 16 January 2017
Source:The Journal of Emergency Medicine
Author(s): Ciara J. Barclay-Buchanan, Emily S. Herzog
http://ift.tt/2js8uSr
Brown-Colored Buccal Mucosa Associated with Methemoglobinemia. Cyanosis Appears Different in Varying Ethnic Groups
Source:The Journal of Emergency Medicine
Author(s): Rafiq Kanji, Hank Joseph Schneider, Mark Pontin
http://ift.tt/2j4zp3n
Comments on “Outbreak of Mysterious Illness among Hospital Staff: Poisoning of Iatrogenic Reinforced Mass Psychogenic Illness”
Source:The Journal of Emergency Medicine
Author(s): Tejs Jansen, Eric C. Jansen, Uno B. Haastrup, Kurt Espersen
http://ift.tt/2jsaQkc
Comparison of “Lesion-by-Lesion” and Field Photodynamic Therapy in the Prevention of Actinic Keratoses: A Randomized, Split-Face, Single-Blind Pilot Study
Dermatology
http://ift.tt/2jUCgf0
Biased Opioid Receptor Ligands: Gain without Pain
Publication date: Available online 16 January 2017
Source:Trends in Endocrinology & Metabolism
Author(s): Ravi Ranjan, Shubhi Pandey, Arun K. Shukla
Kappa opioid receptor (κ-OR) agonists are promising therapeutic candidates for pain and itch; however, they also exhibit the adverse effects of sedation and dysphoria. A recent study has demonstrated that a G protein-biased agonist for κ-OR provides effective pain and itch relief without causing sedation or dysphoria, in animal models.
http://ift.tt/2j4FQTH
Photo-pollution stress in skin: traces of pollutants (PAH and particulate matter) impair redox homeostasis in keratinocytes exposed to UVA1
Publication date: Available online 16 January 2017
Source:Journal of Dermatological Science
Author(s): Jérémie Soeur, Jean-Philippe Belaïdi, Christel Chollet, Laurence Denat, Ariane Dimitrov, Christophe Jones, Philippe Perez, Martine Zanini, Olivia Zobiri, Sakina Mezzache, Dominique Erdmann, Guillaume Lereaux, Joan Eilstein, Laurent Marrot
BackgroundIt is likely that skin is exposed to low concentrations of pollutants such as Polycyclic Aromatic Hydrocarbons (PAH) either through topical penetration by ultrafine particles or by systemic distribution. No precise estimation of pollutants in living skin is available, but literature has reported contamination of blood by PAH at concentrations in the nanomolar range. Some pollutants (PAH for example) are photo-reactive and phototoxic: sunlight and pollution might thus synergistically compromise skin health.ObjectiveHere, the biological effects of particulate matter, PM extract and various PAH were compared in normal human epidermal keratinocytes (NHEK) and reconstructed skin model exposed to either daily UV (d-UV 300–400nm) or UVA1 (350–400nm). Impact of pollutants (PM, PAH or PM extract) combined to UV was studied on NHEK by measuring toxicity, redox homeostasis and GSH metabolism in NHEK.MethodsNHEK were exposed to UV from solar simulator (either d-UV or UVA1) combined with pollutants. Viability, clonogenic efficiency, redox homeostasis and GSH metabolism were assessed.ResultsPollutants (PAH, PM or PM extract)±UVA1 irradiation was associated with a significant phototoxic effect that was equal to or greater than that produced by d-UV. This result is interesting considering that UVA1 represents around 80% of daily UV and reaches the dermal-epidermal junction with ease. Moreover, among PAH studied, benzo[a]pyrene and indeno[1,2,3-cd]pyrene were phototoxic at very low concentrations (nanomolar range) on cultured cells or in reconstructed epidermis and also impaired keratinocyte clonogenic potential at sub-toxic doses. ROS generation within cells and in the inner mitochondrial compartment, mitochondrial membrane depolarization and/or reduced ATP production were also noted. Meanwhile, intracellular glutathione concentrations transiently decreased several hours post-treatment and reduction of its synthesis by buthionine sulfoximine potentiated PAH phototoxicity. Consequently, expression of GSH neo-synthesis genes such as SLC7A11 or GCLc was upregulated several hours post-treatment.Conclusionthese results obtained using PAH concentrations in the range of those reported in blood of pollution-exposed people suggest that exposure to such a photo-pollution stress, particularly if chronic, may impair cutaneous homeostasis and aggravate sunlight-induced skin damage.
http://ift.tt/2iCKzLv
The Down syndrome brain in the presence and absence of fibrillar β–amyloidosis
Publication date: Available online 17 January 2017
Source:Neurobiology of Aging
Author(s): Tiina Annus, Liam R. Wilson, Julio Acosta-Cabronero, Arturo Cardenas-Blanco, Young T. Hong, Tim D. Fryer, Jonathan P. Coles, David K. Menon, Shahid H. Zaman, Anthony J. Holland, Peter J. Nestor
People with Down syndrome (DS) have a neurodevelopmentally distinct brain and invariably develop amyloid neuropathology by age 50. This cross-sectional study aimed to provide a detailed account of DS brain morphology and the changes occuring with amyloid neuropathology. Forty-six adults with DS underwent structural and amyloid imaging—the latter using Pittsburgh Compound–B (PIB) to stratify the cohort into PIB–positive (n=19) and PIB–negative (n=27). Age-matched controls (n=30) underwent structural imaging. Group differences in deep grey matter volumetry and cortical thickness were studied. PIB-negative people with DS have neurodevelopmentally atypical brain, characterised by disproportionately thicker frontal and occipitoparietal cortex and thinner motor cortex and temporal pole with larger putamina and smaller hippocampi than controls. In the presence of amyloid neuropathology, the DS brains demonstrated a strikingly similar pattern of posterior dominant cortical thinning and subcortical atrophy in the hippocampus, thalamus and the striatum, to that observed in non-DS Alzheimer's disease. Care must be taken to avoid underestimating amyloid–associated morphological changes in DS due to disproportionate size of some subcortical structures and thickness of the cortex.
http://ift.tt/2jFz9Z5
Krüpple-like factor 10 regulates radio-sensitivity of pancreatic cancer via UV radiation resistance-associated gene
Source:Radiotherapy and Oncology
Author(s): Vincent Hung-Shu Chang, Yi-Chih Tsai, Ya-Li Tsai, Shu-Ling Peng, Su-Liang Chen, Tsung Ming Chang, Winston Chun-Yuan Yu, Hui-Ju Ch'ang
Background and purposeKrüpple-like factor 10 (Klf10), an early response gene of TGFβ, was reported to be a prognostic biomarker for pancreatic cancer survival. The role of Klf10 in predicting tumor response to cancer treatment is unknown.Materials and methodsGenetically manipulated MiaPaCa and Panc-1 cells were established to evaluate clonogenic survival, autophagy, apoptosis and DNA repair after radiation. The interaction between Klf10 and UV radiation resistance-associated gene (UVRAG) was demonstrated by ChiP-PCR and luciferase reporter assay. Orthotopic murine tumor model and clinical specimens were used to evaluate radio-sensitivity of pancreatic cancer.ResultsWe found Klf10 silencing correlates with enhanced pancreatic cancer clonogenic survival and murine tumor growth after radiation. UVRAG was an essential down-stream mediator transcriptionally suppressed by Klf10. Silencing UVRAG mRNA in Klf10 depleted Panc-1 cells reversed the radio-resistant phenotypes including decreased apoptosis and enhanced DNA repair as well as autophagy. Metformin, an anti-diabetic agent, was found to increase Klf10 and suppress UVRAG expression to improve radiation cytotoxicity in pancreatic cancer. The predictive value of Klf10 in radiation response and the inverse correlation with UVRAG were confirmed in cohorts of pancreatic cancer patients.ConclusionsKlf10 is a potential biomarker in predicting and sensitizing radiation effect in pancreatic cancer.
http://ift.tt/2iICZSI
Liquid fiducial marker applicability in proton therapy of locally advanced lung cancer
Source:Radiotherapy and Oncology
Author(s): Jonas Scherman Rydhög, Rosalind Perrin, Rasmus Irming Jølck, Francis Gagnon-Moisan, Klaus Richter Larsen, Paul Clementsen, Steen Riisgaard de Blanck, Gitte Fredberg Persson, Damien Charles Weber, Tony Lomax, Thomas Lars Andresen, Per Munck af Rosenschold
Background and purposeWe investigated the clinical applicability of a novel liquid fiducial marker (LFM) for image-guided pencil beam scanned (PBS) proton therapy (PBSPT) of locally advanced lung cancer (LALC).Materials and methodsThe relative proton stopping power (RSP) of the LFM was calculated and measured. Dose perturbations of the LFM and three solid markers, in a phantom, were measured. PBSPT treatment planning on computer tomography scans of five patients with LALC with the LFM implanted was performed with 1–3 fields.ResultsThe RSP was experimentally determined to be 1.164 for the LFM. Phantom measurements revealed a maximum relative deviation in dose of 4.8% for the LFM in the spread-out Bragg Peak, compared to 12–67% for the solid markers. Using the experimentally determined RSP, the maximum proton range error introduced by the LFM is about 1mm. If the marker was displaced at PBSPT, the maximum dosimetric error was limited to 2 percentage points for 3-field plans.ConclusionThe dose perturbations introduced by the LFM were considerably smaller than the solid markers investigated. The RSP of the fiducial marker should be corrected in the treatment planning system to avoid errors. The investigated LFM introduced clinically acceptable dose perturbations for image-guided PBSPT of LALC.
http://ift.tt/2j4iH3U
Brachytherapy for the palliation of dysphagia owing to esophageal cancer: A systematic review and meta-analysis of prospective studies
Source:Radiotherapy and Oncology
Author(s): Lorenzo Fuccio, Daniele Mandolesi, Andrea Farioli, Cesare Hassan, Leonardo Frazzoni, Alessandra Guido, Nicola de Bortoli, Savino Cilla, Chiara Pierantoni, Francesco Saverio Violante, Franco Bazzoli, Alessandro Repici, Alessio Giuseppe Morganti
BackgroundThe management of dysphagia owing to esophageal cancer is challenging. Brachytherapy has been proposed as an alternative option to stent placement. We performed a systematic review to examine its efficacy and safety in the resolution of dysphagia.MethodsProspective studies recruiting at least 20 patients with malignant dysphagia and published up to April 2016 were eligible. The dysphagia-free survival (DFS) and adverse event rates were pooled by means of a random effect model.ResultsSix studies for a total of 9 treatment arms (623 patients) were eligible for inclusion. After 1month since treatment, the DFS rate was 86.9% [95%CI: 76.0–93.3%]; after 3months, it was 67.2% [95%CI: 56.1–76.7%]; after 6months, it was 47.4% [95%CI: 38.5–56.5%]; after 9months, it was 37.6% [95%CI:30.0–45.9%]; and, finally, after 12months, it was 29.4% [95%CI: 21.6–38.7%]. The heterogeneity between studies was high at 1-, 3- and 6-month assessment; the values of I2 were 86.3%, 80.0% and 57.8%, respectively. The meta-regression analysis showed total radiation dose and number of fractions as the only positively influencing factors. Severe adverse event rate was 22.6% (95%CI 19.4–26.3). The main reported adverse events were brachytherapy-related stenosis (12.2%) and fistula development (8.3%). Two cases (0.3%) of deaths were reported due to esophageal perforation.ConclusionBrachytherapy is a highly effective and relatively safe treatment option therefore its underuse is no longer justified. Further studies should investigate the optimal radiation dose and number of fractions able to achieve the highest DFS rates.
http://ift.tt/2iIIAsx
Challenges and opportunities in primary CNS lymphoma: A systematic review
Source:Radiotherapy and Oncology
Author(s): Mariana N. Kerbauy, Fabio Y. Moraes, Benjamin H. Lok, Jennifer Ma, Lucila N. Kerbauy, Daniel E. Spratt, Fabio P.S. Santos, Guilherme F. Perini, Alejandro Berlin, Caroline Chung, Nelson Hamerschlak, Joachim Yahalom
Background: Historically, high-dose methotrexate (HD-MTX) plus consolidation chemotherapy and/or whole brain radiotherapy (WBRT) has been the gold standard on Primary Central Nervous System Lymphoma (PCNSL) management. We sought to examine and summarize the data, on clinical trial (CT) setting, investigating multi-modality treatment to PCNSL. Methods: We performed a systematic review of electronic databases (Medline, EMBASE, Cochrane Database and clinicaltrials.gov) and a manual search to identify original PCNSL phase 2 and phase 3 CT from the last 10years. After a 4stage Prisma based selection process, 32 published (3 Randomized CT and 29 phases 2 CT) studies ultimately were selected for review. Four ongoing clinical trials found on clinicaltrial.gov were reviewed. Two investigators reviewed titles, abstracts, and articles independently. Two investigators abstracted data sequentially and evaluated each study independently. Findings: Treatment of PCNSL requires a multidisciplinary approach. HD-MTX represents the most accepted standard of care induction therapy for newly diagnosed PCNSL. When HD-MTX is given with WBRT for consolidation delayed neurotoxicity can be an important complication, particularly in elderly patients. Studies have suggested that WBRT may be deferred until relapse without compromising survival and deferring WBRT may be the best approach in elderly patients. Results from dose-reduced WBRT and consolidative HD-Ara-C are encouraging. High-dose chemotherapy in combination with autologous stem cell transplantation (HDC–ASCT) as chemotherapy alone has emerged as an important consolidative treatment for selected population. The optimal salvage therapy is still to be defined. Conclusion: WBRT for consolidation is a well-studied modality; however emerging options to selected population such as HDC–ASCT, dose-reduced WBRT or chemotherapy alone are associated with similar survival outcome and less neurotoxicity in selected series. Ongoing and future clinical trials will better define the best approach on this rare disease.
http://ift.tt/2j4r0Na
Exploring racial influences on flu vaccine attitudes and behavior: Results of a national survey of White and African American adults
Source:Vaccine
Author(s): Sandra Crouse Quinn, Amelia Jamison, Vicki S. Freimuth, Ji An, Gregory R. Hancock, Donald Musa
IntroductionRacial disparities in adult flu vaccination rates persist with African Americans falling below Whites in vaccine acceptance. Although the literature has examined traditional variables including barriers, access, attitudes, among others, there has been virtually no examination of the extent to which racial factors including racial consciousness, fairness, and discrimination may affect vaccine attitudes and behaviors.MethodsWe contracted with GfK to conduct an online, nationally representative survey with 819 African American and 838 White respondents. Measures included risk perception, trust, vaccine attitudes, hesitancy and confidence, novel measures on racial factors, and vaccine behavior.ResultsThere were significant racial differences in vaccine attitudes, risk perception, trust, hesitancy and confidence. For both groups, racial fairness had stronger direct effects on the vaccine-related variables with more positive coefficients associated with more positive vaccine attitudes. Racial consciousness in a health care setting emerged as a more powerful influence on attitudes and beliefs, particularly for African Americans, with higher scores on racial consciousness associated with lower trust in the vaccine and the vaccine process, higher perceived vaccine risk, less knowledge of flu vaccine, greater vaccine hesitancy, and less confidence in the flu vaccine. The effect of racial fairness on vaccine behavior was mediated by trust in the flu vaccine for African Americans only (i.e., higher racial fairness increased trust in the vaccine process and thus the probability of getting a flu vaccine). The effect of racial consciousness and discrimination for African Americans on vaccine uptake was mediated by perceived vaccine risk and flu vaccine knowledge.ConclusionsRacial factors can be a useful new tool for understanding and addressing attitudes toward the flu vaccine and actual vaccine behavior. These new concepts can facilitate more effective tailored and targeted vaccine communications.
http://ift.tt/2jUmeC3
Neural correlates of lexical decisions in Parkinson’s Disease revealed with multivariate extraction of cortico-subthalamic interactions
Source:Clinical Neurophysiology
Author(s): F.U. Hohlefeld, A. Ewald, F. Ehlen, H.O. Tiedt, A. Horn, A.A. Kühn, G. Curio, F. Klostermann, V.V. Nikulin
ObjectiveNeural interactions between cortex and basal ganglia are pivotal for sensorimotor processing. Specifically, coherency between cortex and subthalamic structures is a frequently studied phenomenon in patients with Parkinson's disease. However, it is unknown whether cortico-subthalamic coherency might also relate to cognitive aspects of task performance, e.g., language processing. Furthermore, standard coherency studies are challenged by how to efficiently handle multi-channel recordings.MethodsIn eight patients with Parkinson's disease treated with deep brain stimulation, simultaneous recordings of surface electroencephalography and deep local field potentials were obtained from bilateral subthalamic nuclei, during performing a lexical decision task. A recent multivariate coherency measure (maximized imaginary part of coherency, MIC) was applied, simultaneously accounting for multi-channel recordings.ResultsCortico-subthalamic synchronization (MIC) in 14–35 Hz oscillations positively correlated with accuracy in lexical decisions across patients, but not in 7–13 Hz oscillations. In contrast to multivariate MIC, no significant correlation was obtained when extracting cortico-subthalamic synchronization by "standard" bivariate coherency.ConclusionsCortico-subthalamic synchronization may relate to non-motor aspects of task performance, here reflected in lexical accuracy.SignificanceThe results tentatively suggest the relevance of cortico-subthalamic interactions for lexical decisions. Multivariate coherency might be effective to extract neural synchronization from multi-channel recordings.
http://ift.tt/2k0wFIf
Selective attentional impairment in chronic tinnitus: evidence from an event-related potentials study
Source:Clinical Neurophysiology
Author(s): Daniela Mannarelli, Caterina Pauletti, Patrizia Mancini, Alessandra Fioretti, Antonio Greco, Marco De Vincentiis, Francesco Fattapposta
ObjectiveTinnitus is an auditory phantom sensation experienced in the absence of a sound source. Cognitive dysfunctions, especially in working memory and attention, are frequently reported to be associated with tinnitus. The aim of this study was to investigate attentional functioning in a group of subjects with chronic tinnitus using ERPs, and in particular the P300 components.MethodsWe studied 20 patients with chronic tinnitus and 20 healthy subjects that performed a P300 Novelty task.ResultsP3a amplitude was significantly lower in tinnitus subjects than in controls. P3a latency was comparable in patients and controls. The P3b parameters were similar in the two groups. N1 latency for all the stimuli was significantly longer in tinnitus subjects than in controls.ConclusionThese results point to a general slowing in early stimulus perception in tinnitus subjects. Moreover, a specific difficulty emerged in attentional switching to unexpected events during an orienting response, probably owing to a dysfunction in the ventral attention network.SignificancePsychophysiological approach reveals selective attentional impairment and could provide useful data for rehabilitative strategies in chronic tinnitus.
http://ift.tt/2jUfUKT
Neuromodulation in Response to Electroconvulsive Therapy in Schizophrenia and Major Depression
Source:Brain Stimulation
Author(s): Philipp Arthur Thomann, Robert Christian Wolf, Henrike Maria Nolte, Dusan Hirjak, Stefan Hofer, Ulrich Seidl, Malte Sebastian Depping, Bram Stieltjes, Klaus Maier-Hein, Fabio Sambataro, Torsten Wüstenberg
BackgroundElectroconvulsive therapy (ECT) is one of the most effective treatments in severe and treatment-resistant major depressive disorder (MDD). ECT has been also shown to be effective in schizophrenia (SZ), particularly when rapid symptom reduction is needed or in cases of resistance to drug-treatment. However, its precise mechanisms of action remain largely unknown.Objective/Hypothesis: This study examined whether ECT exerts disorder-specific or unspecific modulation of brain structure and function in SZ and MDD.MethodsWe investigated neuromodulatory effects of right-sided unilateral ECT in pharmacoresistant patients with SZ or MDD. Magnetic resonance imaging was conducted before and after ECT to investigate treatment-related effects on brain structure and function. Imaging data were analyzed by means of Voxel Based Morphometry and Resting State Functional Connectivity (RSFC) methods.ResultsRight unilateral ECT induced transdiagnostic regional increases of limbic gray matter and modulations of neural coupling at rest. Structural effects were accompanied by a decrease in RSFC within temporoparietal, prefrontal and cortical midline structures, and an increase in hypothalamic RSFC. The extent of structural and functional change was partially inversely associated with the baseline measures.ConclusionThe present findings provide first evidence for transdiagnostic changes of brain structure together with modulation of brain function after ECT. The data indicate diagnosis-unspecific mechanisms of action with respect to regional gray matter volume and resting-state functional connectivity.
http://ift.tt/2iCMAHr
Data of ALD Al2O3 rear surface passivation, Al2O3 PERC cell performance, and cell efficiency loss mechanisms of Al2O3 PERC cell
Publication date: April 2017
Source:Data in Brief, Volume 11
Author(s): Haibing Huang, Jun Lv, Yameng Bao, Rongwei Xuan, Shenghua Sun, Sami Sneck, Shuo Li, Chiara Modanese, Hele Savin, Aihua Wang, Jianhua Zhao
This data article is related to the recently published article '20.8% industrial PERC solar cell: ALD Al2O3 rear surface passivation, efficiency loss mechanisms analysis and roadmap to 24%' (Huang et al., 2017) [1]. This paper is about passivated emitter and rear cell (PERC) structures and it describes the quality of the Al2O3 rear-surface passivation layer deposited by atomic layer deposition (ALD), in relation to the processing parameters (e.g. pre-clean treatment, deposition temperature, growth per cycle, and film thickness) and to the cell efficiency loss mechanisms. This dataset is made public in order to contribute to the limited available public data on industrial PERC cells, to be used by other researchers.
http://ift.tt/2iCBBOu
Data of the recombination loss mechanisms analysis on Al2O3 PERC cell using PC1D and PC2D simulations
Publication date: April 2017
Source:Data in Brief, Volume 11
Author(s): Haibing Huang, Jun Lv, Yameng Bao, Rongwei Xuan, Shenghua Sun, Sami Sneck, Shuo Li, Chiara Modanese, Hele Savin, Aihua Wang, Jianhua Zhao
This data article is related to our recently published article ('20.8% industrial PERC solar cell: ALD Al2O3 rear surface passivation, efficiency loss mechanisms analysis and roadmap to 24%', Huang et al., 2017 [1]) where we have presented a systematic evaluation of the overall cell processing and a cost-efficient industrial roadmap for PERC cells. Aside from the information already presented in Huang et al., 2017 [1], here we provide data related to Sectin 3 in Huang et al., 2017 [1] concerning the analysis of the recombination losses׳ mechanisms by PC1D V5.9 and PC2D simulations (Clugston and Basore, 1997, Basore and Cabanas-Holmen, 2011, Cabanas-Holmen and Basore, 2012 and Cabanas-Holmen and Basore, 2012.) [2–5] on our current industrial Al2O3 PERC cell. The data include: i) PC2D simulations on J02, ii) the calculation of series resistance and back surface recombination velocity (BSRV) on the rear side metallization of PERC cell for the case of a point contact, and iii) the PC1D simulation on the cumulative photo-generation and recombination along the distance from the front surface. Finally, the roadmap of the solar cell efficiency for an industrial PERC technology up to 24% is presented, with the aim of providing a potential guideline for industrial researchers.
http://ift.tt/2jv4ikb
E-cigarette specialty retailers: Data to assess the association between retail environment and student e-cigarette use
Publication date: April 2017
Source:Data in Brief, Volume 11
Author(s): Georgiana Bostean, Catherine M. Crespi, Patsornkarn Vorapharuek, William J. McCarthy
The retail environment is a major social determinant of health, yet little is known about the e-cigarette specialty retailer environment. The e-cigarette specialty retail environment may be associated with e-cigarette use by middle and high school students, an issue that was addressed in a recent article entitled, "E-cigarette use among students and e-cigarette specialty retailer presence near schools," by Bostean and colleagues (G. Bostean, C.M. Crespi, P. Vorapharuek, W.J. McCarthy, 2016 [1]). We present data relating to e-cigarette specialty retailers in Orange County, California. We describe the data collection method (including the search methodology to identify e-cigarette specialty retailers), present descriptive retailer data including school proximity, and provide data from multi-level regressions predicting individual-level student use of e-cigarettes based on presence of an e-cigarette specialty retailer in proximity to schools.
http://ift.tt/2iCknAK
Examining the link between cocaine binging and individual, social and behavioral factors among street-based cocaine users
Source:Addictive Behaviors, Volume 68
Author(s): Élise Roy, Nelson Arruda, Didier Jutras-Aswad, Djamal Berbiche, Michel Perreault, Karine Bertrand, Magali Dufour, Julie Bruneau
AimsTo estimate the prevalence of cocaine binging and examine associated factors, to characterize binge episodes and to study the relationship between cocaine binging and HIV and HCV risk behaviors among street-based cocaine users.MethodsA prospective cohort study was conducted in Montréal, Canada. Interviewer-administered questionnaire were carried out at 3-month intervals. Cocaine binging was defined as using large quantities of cocaine, without stopping, over a limited period of time, until resources run out or until being physically incapable of consuming. Generalized Estimation Equations (GEE) analyses were used. Covariates considered included demographic, behavioral, mental health and social risk factors.FindingsIn total, 605 participants were recruited. Prevalence of cocaine binging over the month prior to recruitment was 24.5%. Correlates of cocaine binging were older age (AOR 1.46), homelessness (AOR 1.44), criminal/marginal income strategies (AOR 1.61), high psychological distress (AOR 1.31), high cocaine dependence (AOR 3.71), drug overdoses (AOR 1.56) and smoking as the main route of cocaine administration (AOR 1.38). Additional GEE analyses showed that cocaine binging was significantly associated with the sharing of drug paraphernalia (AOR 1.35) and sexual relations under the influence of cocaine (AOR 1.21).ConclusionCocaine binging is frequent among street-based cocaine users and is associated with markers of vulnerability. It is also associated with increased odds of both sexual and drug use risk behaviors. Interventions need to be tailored in order to help cocaine bingers develop personal strategies that could prevent binging. Harm reduction programs should help cocaine bingers adequately assess their drug equipment needs.
http://ift.tt/2juNnOP
Editorial Board
Source:Addictive Behaviors, Volume 67
http://ift.tt/2juVOKb
Atmospheric nitrogen deposition to China: A model analysis on nitrogen budget and critical load exceedance
Source:Atmospheric Environment, Volume 153
Author(s): Yuanhong Zhao, Lin Zhang, Youfan Chen, Xuejun Liu, Wen Xu, Yuepeng Pan, Lei Duan
We present a national-scale model analysis on the sources and processes of inorganic nitrogen deposition over China using the GEOS-Chem model at 1/2° × 1/3° horizontal resolution. Model results for 2008–2012 are evaluated with an ensemble of surface measurements of wet deposition flux and gaseous ammonia (NH3) concentration, and satellite measurements of tropospheric NO2 columns. Annual total inorganic nitrogen deposition fluxes are simulated to be generally less than 10 kg N ha−1 a−1 in western China (less than 2 kg N ha−1 a−1 over Tibet), 15–50 kg N ha−1 a−1 in eastern China, and 16.4 kg N ha−1 a−1 averaged over China. Annual total deposition to China is 16.4 Tg N, with 10.2 Tg N (62%) from reduced nitrogen (NHx) and 6.2 Tg N from oxidized nitrogen (NOy). Domestic anthropogenic sources contribute 86% of the total deposition; foreign anthropogenic sources 7% and natural sources 7%. Annually 23% of domestically emitted NH3 and 36% for NOx are exported outside the terrestrial land of China. We find that atmospheric nitrogen deposition is about half of the nitrogen input from fertilizer application (29.6 Tg N a−1), and is much higher than that from natural biological fixation (7.3 Tg N a−1) over China. A comparison of nitrogen deposition with critical load estimates for eutrophication indicates that about 15% of the land over China experiences critical load exceedances, demonstrating the necessity of nitrogen emission controls to avoid potential negative ecological effects.
http://ift.tt/2jjqdJ7
In vitro Evaluation of the Cleansing Effect of a Monofilament Fiber Debridement Pad Compared to Gauze Swabs
Skin Pharmacol Physiol 2016;29:318-323
http://ift.tt/2juSBdz
Increasing Fractional Doses Increases the Probability of Benign PSA Bounce in Patients Undergoing Definitive HDR Brachytherapy for Prostate Cancer
Publication date: Available online 16 January 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Carlin R. Hauck, Hong Ye, Peter Y. Chen, Gary S. Gustafson, Amy Limbacher, Daniel J. Krauss
PurposeProstate-specific antigen (PSA) bounce is a temporary elevation of PSA above a prior nadir. The purpose of this study was to determine if the frequency of a PSA bounce following high dose rate (HDR) interstitial brachytherapy for the treatment of prostate cancer is associated with individual treatment fraction size.Materials and MethodsBetween 1999 and 2014, 554 patients were treated for low or intermediate-risk prostate cancer with definitive HDR brachytherapy as monotherapy and had at least 3 subsequent PSA measurements. Four different fraction sizes were used: 950 cGy x 4, 1200 cGy x 2, 1350 cGy x2, 1900 cGy x 1. Four definitions of PSA bounce were applied: ≥0.2, ≥0.5, ≥1.0, and ≥2.0 ng/mL above prior nadir with subsequent return to nadir.ResultsMedian follow-up was 3.7 years. The actuarial 3-year rate of PSA bounce for the entire cohort was 41.3%, 28.4%, 17.4%, and 6.8% for nadir +0.2, +0.5, +1.0, and +2.0 ng/mL, respectively. The 3-year rate of PSA bounce >0.2 ng/mL was 42.2%, 32.1%, 41.0% and 59.1% for the 950, 1200, 1350 and 1900 cGy per fraction levels respectively (p=0.002). The hazard ratio for bounce >0.2 ng/ml for patients receiving a single fraction of 1900 cGy compared to those receiving treatment in multiple fractions was 1.786 (p=0.024). For patients treated with a single 1900 cGy fraction, the 1-, 2-, and 3-year rates of PSA bounce exceeding the Phoenix biochemical failure definition ("nadir + 2"), were 4.5%, 18.7%, and 18.7%, higher than the rates for all other administered dose levels (p=0.025).ConclusionsThe incidence of PSA bounce increases with single-fraction HDR treatment. Knowledge of post-treatment PSA kinetics may aid in decision making regarding management of potential biochemical failures.
Teaser
Following definitive radiation therapy for prostate cancer, benign elevations of prostate serum antigen (PSA), known as bounces, can complicate interpretation of post-treatment PSA values. We reviewed 554 patients treated at a single institution with HDR brachytherapy as monotherapy for the definitive treatment of prostate cancer, and analyzed their post-treatment PSA trends. Patients treated with a high single-fraction dose had a higher rate of experiencing post-treatment PSA bounce, than those treated with lower fractional doses.http://ift.tt/2k0k1ZW
Low Dose Rate Brachytherapy versus Cryotherapy in Low and Intermediate Risk Prostate Cancer
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Matthew M. Gestaut, Wendi Cai, Shilpa Vyas, Belur J. Patel, Salman A. Hasan, Yolanda MunozMaldonado, Niloyjyoti Deb, Gregory Swanson
PurposeCryotherapy and brachytherapy are definitive local treatment options for low- to intermediate-risk prostate cancer. There are both prospective and retrospective data for brachytherapy, but the use of cryotherapy has been limited primarily to single institutional retrospective studies. Currently, no published evidence has compared low-dose rate brachytherapy versus cryotherapy.MaterialsInstitutional Review Board approval was obtained to conduct a retrospective chart review of consecutive patients treated at our institution from 1990-2012. For inclusion, patients must have carried prostate cancer diagnoses and have been considered low- to intermediate-risk according to the National Comprehensive Cancer Network criterion. All patients received brachytherapy or cryotherapy treatment. Disease specifics and failure details were collected for all patients. Failure was defined as prostate-specific antigen nadir +2ng/mL.ResultsA total of 359 patients were analyzed. Groups were comprised of 50 low-risk cryotherapy (LRC), 92 intermediate-risk cryotherapy (IRC), 133 low-risk brachytherapy (LRB), and 84 intermediate-risk brachytherapy (IRB) patients. Median prostate-specific antigen follow-up was 85.6 months (LRC), 59.2 months (IRC), 74.9 months (LRB), and 59.8 months (IRB). The 5-year biochemical progression free survival (bPFS) between the two total groups was 57.9% in cryotherapy versus 89.6% in the brachytherapy group (P<0.0001). The 5-year bPFS was 70.0% (LRC), 51.4% (IRC), 89.4% (LRB) and 89.7% (IRB). The bPFS was significantly different between brachytherapy and cryotherapy for low and intermediate risk groups (p<0.05). The mean nadir temperature reached for cryotherapy patients was -35 (range: -6 to -96) degrees Celsius. Cryotherapy utilized a median of 2 (range: 2-4) freeze thaw cycles.ConclusionsResults from this study suggest that cryotherapy is inferior to brachytherapy for patients with low- to intermediate-risk prostate cancer. Patient selection criterion for consideration of cryotherapy and brachytherapy is similar in terms of anesthesia candidacy. Therefore, cryotherapy would not be recommended as a first-line local therapy for this particular patient subset.
Teaser
Currently no published evidence has compared clinical outcomes in prostate cancer for low-dose rate brachytherapy versus cryotherapy. A retrospective review was completed for these two modalities in low and intermediate risk localized prostate cancer. Brachytherapy was found to have significantly better biochemical progression free survival.http://ift.tt/2j3WCm1
Nature of Medical Malpractice Claims Against Radiation Oncologists
Publication date: Available online 16 January 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Deborah Marshall, Kathryn Tringale, Michael Connor, Rinaa Punglia, Abram Recht, Jona Hattangadi-Gluth
Purpose/Objective(s)We examined characteristics of medical malpractice claims involving radiation oncologists closed during a 10-year period.Methods and MaterialsMalpractice claims filed against radiation oncologists from 2003 to 2012 collected by a nationwide liability insurance trade association were analyzed. Outcomes included the nature of claims and indemnity payments, including associated presenting diagnoses, procedures, alleged medical errors, and injury severity. We compared the likelihood of a claim resulting in payment in relation to injury severity categories (death as referent) using binomial logistic regression.ResultsThere were 362 closed claims involving radiation oncology, 102 (28%) of which were paid, resulting in $38 million in indemnity payments. The most common alleged errors included: 'improper performance' (38% of closed claims, 18% were paid; 29% [$11 million] of total indemnity); 'errors in diagnosis' (25% of closed claims, 46% were paid; 44% [$17 million] of total indemnity); and, 'no medical misadventure' (14% of closed claims, 8% were paid; less than 1% [$148,000] of total indemnity). Another physician was named in 32% of claims, and consent issues/breach of contract were cited in 18%. Claims for injury resulting in death represented 39% of closed claims and 25% of total indemnity. 'Improper performance' was the primary alleged error associated with injury resulting in death. Compared to claims involving death, major temporary injury (OR 2.8, 95% CI 1.29-5.85, P=0.009), significant permanent injury (OR 3.1, 1.48-6.46, P =0.003) and major permanent injury (OR 5.5, 1.89-16.15, P =0.002) had higher likelihood of a claim resulting in indemnity payment.ConclusionsImproper performance was the most common alleged malpractice error. Claims involving significant or major injury were more likely to be paid than those involving death. Insights into the nature of liability claims against radiation oncologists may help direct efforts to improve quality of care and minimize the risk of being sued.
Teaser
This study is the first systematic analysis on the nature of medical malpractice claims against radiation oncologists. We analyzed 10 years of such claims using a nationwide data-base. We describe the nature of malpractice claims and indemnity payments, associated presenting diagnoses, procedures, alleged medical errors, and injury severity. We then discuss the implications of these claims for improving the quality of care and patient safety, and minimizing the risk of being sued.http://ift.tt/2k0fB53
Radiation-specific clinical data should be included in existing large-scale genomic datasets
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): William Chen, Jeffrey P. Townsend, James B. Yu
http://ift.tt/2j3Qk62
Intracoerulear microinjection of orexin-A induces morphine withdrawal-like signs in rats
Publication date: Available online 16 January 2017
Source:Brain Research Bulletin
Author(s): Masoumeh Ghaemi-Jandabi, Hossein Azizi, S.Mohammad Ahmadi-Soleimani, Saeed Semnanian
Orexin (hypocretin) neuropeptides play a pivotal role in expression of opioid withdrawal signs. Hypothalamic orexinergic neurons provide dense afferents for the nucleus locus coeruleus (LC). Somatic signs of opioid withdrawal are associated with the enhanced activity of LC neurons. In addition, intra-LC administration of orexin-A leads to the hyperactivity of LC neurons. The present study was an attempt to investigate whether intra-LC microinjection of orexin-A induces morphine withdrawal-like signs in both morphine dependent and control rats. To end this, adult male Wistar rats weighing 250–300g were used. For induction of morphine dependence, animals received morphine sulfate subcutaneously (10mg/kg,s.c.) at an interval of 12h for 9 days. On day 10, intra-LC orexin injection (100μM, 200 nl) was carried out two hours after last morphine administration. Morphine withdrawal-like signs were assessed in a transparent Plexiglas test chamber (30cm diameter, 50cm height) for 25minutes. Orexin-A microinjection induced some morphine withdrawal-like signs in both morphine dependent (chewing, scratching, rearing, teeth chattering, wet-dog shake and paw tremor) and control (chewing, scratching, rearing, sniffing, wet-dog shake and head tremor) rats. Furthermore, microinjection of SB-334867, a selective orexin type-1 receptor antagonist before orexin-A significantly suppressed orexin-induced morphine withdrawal-like signs. It seems that orexin-A, via increasing the activity of LC neurons, mediates the induction of some morphine withdrawal-like signs independent of morphine dependence.
Graphical abstract
http://ift.tt/2iwPO46
Peripheral nerve injury potentiates excitatory synaptic transmission in locus coeruleus neurons
Source:Brain Research Bulletin
Author(s): Kambiz Rohampour, Hossein Azizi, Yaghoub Fathollahi, Saeed Semnanian
Peripheral nerve injury (PNI) is believed to cause maladaptive changes at synaptic level, leading to neuropathic pain which is difficult to treat with common analgesic drugs. Noradrenergic locus coeruleus (LC) neurons have a crucial role in neuropathic pain modulation. In this study we examined whether chronic constriction injury (CCI) could affect glutamatergic synaptic transmission in LC neurons.CCI was performed on P10 to P12 Sprague Dawley pups. Seven days after CCI, horizontal slices of brainstem (300μm thick) were prepared and whole-cell patch clamp recording was performed. Evoked and spontaneous excitatory postsynaptic currents (eEPSC and sEPSC) were recorded from LC neurons at a holding potential of −70mV, in the presence of bicuculline (20μM).The sEPSCs recorded from LC neurons of neuropathic rats showed a significant increase in amplitude, but not in frequency. The eEPSC amplitude in neurons of rats under gone CCI was significantly increased compared to the control group (P<0.05). The paired pulse ratio (PPR) elicited with different inter-stimulus intervals (50–250ms) did not show any difference between neurons of CCI and control pups.This study shows that PNI increases excitatory synaptic transmission in LC neurons 7days after chronic constriction injury. The observed synaptic potentiation is mainly due to postsynaptic mechanisms.
http://ift.tt/2iwMbeo
Weapon carrying in and out of school among pure bullies, pure victims and bully-victims: A systematic review and meta-analysis of cross-sectional and longitudinal studies
Source:Aggression and Violent Behavior
Author(s): Sara Valdebenito, Maria M. Ttofi, Manuel Eisner, Hannah Gaffney
Weapon carrying has detrimental effects for perpetrators and victims alike. It is therefore imperative that research efforts are invested into establishing those contextual factors that are associated with this antisocial behavior. This systematic and meta-analytic review investigates the association of weapon carrying with bullying perpetration and victimization inside and outside the school context. Results on pure bullies, pure victims and bully-victims are also presented.Further to extensive searches, across 20 databases and 46 journals, and careful screening of reports, in line with pre-established methodological criteria, a total of 35 manuscripts are included in the meta-analysis. Narrative results based on longitudinal studies are also presented but not meta-analyzed given the variability in study characteristics and the small number of studies.Weapon carrying is significantly associated with both bullying perpetration (adjusted OR=2.64; p<0.001) and victimization (adjusted OR=1.58; p<0.05). Effect sizes are larger when looking at discrete categories of pure bullies (adjusted OR=3.24; p<0.01), pure victims (adjusted OR=1.79; p<0.05) and bully-victims (adjusted OR=5.66; p<0.001) when compared with non-involved school children. Subgroup analyses suggest that pure victims (Q=6.77; p<0.01) and bully-victims (Q=8.01; p<0.01) are significantly more likely to carry a weapon inside than outside the school, thus rendering support to the 'vulnerability/self-protection' hypothesis. Pure bullies have the same odds of carrying a weapon inside and outside the school context (Q=0.60; p=0.44), supporting a persistent antisocial personality theoretical framework.Implications for policy and practice arising from our results are discussed.
http://ift.tt/2jELRra
Emotion socialization and internalizing behavior problems in diverse youth: A bidirectional relationship across childhood
Publication date: March 2017
Source:Research in Developmental Disabilities, Volume 62
Author(s): Naomi V. Rodas, Denise A. Chavira, Bruce L. Baker
Mothers' and fathers' emotion socialization (ES) practices have been widely associated with child socioemotional outcomes. To extend this research, we examined the bidirectional relationship between parent ES practices (supportive and non-supportive parenting) and internalizing behavior problems in children of Anglo and Latino parents. Participants were 182 mothers and 162 fathers and their children with or without intellectual disability (ID). We compared the stability of mother and father ES practices across child ages 4–8. We utilized cross-lagged panel modeling to examine the bidirectional relationship between parents' ES and child internalizing behavior problems. Emotion socialization practices differed across time by parent gender, with mothers displaying higher levels of supportive parenting and lower levels of non-supportive parenting than fathers. Cross-lagged panel models revealed differential relationships between child internalizing behaviors and emotion socialization practices by parent gender and by ethnicity. Implications for intervening with culturally diverse families of children with ID are discussed.
http://ift.tt/2jjidb9
Factors associated with meeting physical activity guidelines by adults with intellectual and developmental disabilities
Publication date: March 2017
Source:Research in Developmental Disabilities, Volume 62
Author(s): Roger J. Stancliffe, Lynda L. Anderson
BackgroundMany individuals with intellectual and developmental disabilities (IDD) have sedentary lifestyles.Aims(a) compare adults with IDD with the general adult population on adherence to U.S. physical activity (PA) guidelines, and (b) determine what factors predict adherence to PA guidelines by adults with IDD.MethodsWe compared adults with IDD from the 2011–2012 National Core Indicators Adult Consumer Survey (NCI-ACS) with the general U.S. population on meeting PA guidelines. We examined the association of demographic, diagnostic, mobility, health and community participation variables with meeting PA guidelines by adults with IDD.ResultsThe rate for adults with IDD meeting PA guidelines (13.5%) was less than half that of the general population (30.8%). Among adults with IDD, at-risk groups included those with more severe disability, Down syndrome, mobility impairments, obesity, poor health, mental illness, no independent access to community exercise, and less frequent participation in community exercise. Going out for exercise was the only form of community participation associated with meeting PA guidelines. People who accessed the community for exercise independently (i.e., alone) were more likely to meet PA guidelines.ConclusionsInterventions aimed at increasing PA for people with IDD should consider these factors in their design.
http://ift.tt/2iwMYMs
Fiber laser welding of thick AISI 304 plate in a horizontal (2G) butt joint configuration
Publication date: 15 March 2017
Source:Materials & Design, Volume 118
Author(s): Junhao Sun, Kai Feng, Ke Zhang, Baochao Guo, En Jiang, Pulin Nie, Jian Huang, Zhuguo Li
An innovative laser technique has been developed for welding 16mm thick 304L stainless steel in the horizontal (2G) butt joint configuration. Autogenous laser welding (ALW) was applied to join the thick plate with a square groove and zero air gap, and laser welding assisted with a cold wire (LWACW) was used to fill the unfilled joint. The dimension of the square groove was optimized to achieve full penetration joint with smooth reinforcement at the back side. The wire feed process was also optimized to produce a sound weld appearance. The microstructure and mechanical properties were observed and evaluated by optical microscope, electron backscatter diffraction, microhardness measurement and tensile test. The results showed that the square groove contributed to produce a joint with deeper penetration and narrower width. The relative position of weld wire with respect to the laser spot had a great influence on the weld appearance. Sound appearance with defect-free joint was successfully produced for the 16mm thick plate in the horizontal position. The microstructure and microhardness of the top and middle samples are different, resulting in the different tensile strength and fractured location.
Graphical abstract
http://ift.tt/2jETduA
Characteristics of 7055Al alloy powders manufactured by gas-solid two-phase atomization: A comparison with gas atomization process
Publication date: 15 March 2017
Source:Materials & Design, Volume 118
Author(s): Chaorun Si, Xingling Tang, Xianjie Zhang, Junbiao Wang, Weichao Wu
In this paper, the principle of gas-solid two-phase atomization methodology for metal powder is demonstrated. A cost-effective production technology for high-quality metal powder was proposed. The morphology, size distribution, microstructure and cooling rate of two-phase atomized 7055Al powder were examined. The experimental results have demonstrated a number of advantages and unique features of gas-solid two-phase atomization in the preparation of metal powders. When the Argon gas pressure P=0.6MPa and iron particle feed rate M′=235.6g·min−1, the mass median diameter (d50) of the 7055Al powder manufactured by two-phase atomization process was 22.8μm, which is reduced by 52.7% compared with gas atomized powders with d50=48.2μm under the same atomization parameters. Experimental results also showed that the gas-solid two-phase atomized powders exhibited more irregular shapes than gas atomized powders. The cooling rate of most powders was in the range of 104–105K/s, and for some extra checked fine powders the cooling rate can even reach 106K/s. The two-phase atomized powders had larger cooling rate and presented obvious rapid solidification characteristics than gas atomized powder with the same diameter. Moreover, this study indicates that gas-solid two-phase atomization could be a promising high-quality and low-cost metal powder preparation technology.
Graphical abstract
http://ift.tt/2jEOUQc
Thermal and magnetic properties of nanostructured densified ferrimagnetic composites with graphene - graphite fillers
Publication date: 15 March 2017
Source:Materials & Design, Volume 118
Author(s): S. Ramirez, K. Chan, R. Hernandez, E. Recinos, E. Hernandez, R. Salgado, A.G. Khitun, J.E. Garay, A.A. Balandin
We report the results of an experimental study of thermal and magnetic properties of nanostructured ferrimagnetic iron oxide composites with graphene and graphite fillers synthesized via the current activated pressure assisted densification. The thermal conductivity was measured using the laser-flash and transient plane source techniques. It was demonstrated that addition of 5wt.% of equal mixture of graphene and graphite flakes to the composite results in a factor of ×2.6 enhancement of the thermal conductivity without significant degradation of the saturation magnetization. The microscopy and spectroscopic characterization reveal that sp2 carbon fillers preserve their crystal structure and morphology during the composite processing. The strong increase in the thermal conductivity was attributed to the excellent phonon heat conduction properties of graphene and graphite. The results are important for energy and electronic applications of the nanostructured permanent magnets.
Graphical abstract
http://ift.tt/2juJlpU
Potential to design magnesium potassium phosphate cement paste based on an optimal magnesia-to-phosphate ratio
Publication date: 15 March 2017
Source:Materials & Design, Volume 118
Author(s): Hongyan Ma, Biwan Xu
Magnesium potassium phosphate cement (MKPC) is an important engineering material, and it has been attracting increasing attention. Properties of MKPC based materials depend largely on the magnesia-to-phosphate molar ratio (M/P) and the water-to-cement mass ratio (W/C). While the effect of W/C has been clear, experimental results of the effect of M/P in the literature seem to be inconsistent. In this paper, a model is developed to unify these experimental findings. The model hypothesizes that the strength of MKPC based materials is dominated by the volume ratio of magnesium potassium phosphate hexahydrate and space (MKP/space ratio), and the ultimate MKP/space ratio can be limited by the availabilities of the three reactants, i.e. magnesia, phosphate and water. It proves that, if the W/C of MKPC-based material is kept constant, there exists an optimal M/P that results in the highest compressive strength. It appears that the higher the W/C is, the smaller this optimal M/P will be.
Graphical abstract
http://ift.tt/2juFLf5
The normal vaginal and uterine bacterial microbiome in giant pandas (Ailuropoda melanoleuca)
Source:Microbiological Research
Author(s): Xin Yang, Guangyang Cheng, Caiwu Li, Jiang Yang, Jianan Li, Danyu Chen, Wencheng Zou, SenYan Jin, Hemin Zhang, Desheng Li, Yongguo He, Chengdong Wang, Min Wang, Hongning Wang
While the health effects of the colonization of the reproductive tracts of mammals by bacterial communities are widely known, there is a dearth of knowledge specifically in relation to giant panda microbiomes. In order to investigate the vaginal and uterine bacterial diversity of healthy giant pandas, we used high-throughput sequence analysis of portions of the 16S rRNA gene, based on samples taken from the vaginas (GPV group) and uteri (GPU group) of these animals. Results showed that the four most abundant phyla, which contained in excess of 98% of the total sequences, were Proteobacteria (59.2% for GPV and 51.4% for GPU), Firmicutes (34.4% for GPV and 23.3% for GPU), Actinobacteria (5.2% for GPV and 14.0% for GPU) and Bacteroidetes (0.3% for GPV and 10.3% for GPU). At the genus level, Escherichia was most abundant (11.0%) in the GPV, followed by Leuconostoc (8.7%), Pseudomonas (8.0%), Acinetobacter (7.3%), Streptococcus (6.3%) and Lactococcus (6.0%). In relation to the uterine samples, Janthinobacterium had the highest prevalence rate (20.2%), followed by Corynebacterium (13.2%), Streptococcus (19.6%), Psychrobacter (9.3%), Escherichia (7.5%) and Bacteroides (6.2%). Moreover, both Chao1 and abundance-based coverage estimator (ACE) species richness indices, which were operating at the same sequencing depth for each sample, demonstrated that GPV had more species richness than GPU, while Simpson and Shannon indices of diversity indicated that GPV had the higher bacterial diversity. These findings contribute to our understanding of the potential influence abnormal reproductive tract microbial communities have on negative pregnancy outcomes in giant pandas.
http://ift.tt/2juEUuT
Antifungal activity of ionic liquids based on (−)-menthol: A mechanism study
Publication date: Available online 16 January 2017
Source:Microbiological Research
Author(s): Jakub Suchodolski, Joanna Feder-Kubis, Anna Krasowska
The mechanism of toxicity of chiral ionic liquids with (1R,2S,5R)-(−)-menthol [Cn-Am-Men][Cl] (n=10, 11 or 12) in the fungus Candida albicans is reported here. Ionic liquids were more toxic towards Candida strain lacking all identified multidrug resistance efflux pumps. Moreover, the compounds tested inhibited C. albicans filamentation at the concentration at which detached fungal cells also adhered to the plastic surface. Our results showed the high activity of all the tested chiral ionic liquids in the permeabilization of C. albicans' membranes and in the digestion and interruption of the cell wall. The investigated ionic liquids thus have potential as disinfectants because besides their antifungal and antiadhesive action these compounds do not cause hemolysis.
Graphical abstract
http://ift.tt/2jEPFbV
Molecular assessment of the bacterial community associated with Cassava (Manihot esculenta Crantz) cultivation in Cameroon
Source:Microbiological Research
Author(s): Papa Saliou Sarr, Akifumi Sugiyama, Aime Didier Boyogueno Begoude, Kazufumi Yazaki, Shigeru Araki, Eiji Nawata
Bacterial communities play an important role in nutrient cycles and plant development. Their distribution and activity may depend on location and environmental heterogeneity. This study characterized soil bacterial communities in cassava fields of Eastern (Andom) and Southern (Bityili) Cameroon using molecular tools. In both sites, two improved varieties (TMS-96/1414; TMS-92/0326) and a local variety (Local) were grown in a randomized block design. Composite bulk soils were collected at 10 months after planting from cassava plots. The 16S rDNA region was amplified, MiSeq was performed and sequence data analyzed. The same 17 bacterial phyla were present in both Andom and Bityili, while Chlorobi and Deinococcus-Thermus were only specific to Andom. The phyla Proteobacteria, Planctomycetes, Actinobacteria and Acidobacteria were dominant. Although both sites shared similar phyla, the principal coordinate analysis revealed significant variations in their composition, suggesting that the functions of the bacteria in nutrients cycling are likely to differ between Andom and Bityili. Cassava yields were generally higher in Andom which also displayed a higher diversity of bacterial communities. This study provides useful information on the composition of bacterial communities in cassava fields in two agro-ecologies of Cameroon. It constitutes to our knowledge the first report describing soil bacterial communities in association with cassava growth in the country, using molecular tools.
http://ift.tt/2jEPEVp
Estimating the Reliability of Nontechnical Skills in Medical Teams
Publication date: Available online 16 January 2017
Source:Journal of Surgical Education
Author(s): Ipek Mete, Michael T. Brannick
ObjectiveTo assess the reliability of measurement of assessments of nontechnical skills in medical teams.BackgroundThere are several scales for assessing nontechnical skills in medical teams. In this critique, we describe the reliability of such assessments and discuss factors that may influence the obtained estimate of reliability for such scales.MethodA review of the literature yielded 28 reliability estimates, mostly intraclass correlations. We analyzed the methods of scale development and reliability estimation for factors that are likely to influence the resulting estimate, including aspects of the judges, the targets, what is observed, and the kind of reliability coefficient.ResultsTypical reliability was approximately 0.7, but estimates were quite varied in magnitude, from quite low (0.3) to quite high (0.9). Thus, highly reliable assessment is possible, but rarely achieved. Factors that are likely to influence the magnitude of reliability include the number of assessors, the participants' range in skill level, and the observational process. Most studies do not present enough information to make the estimates comparable from one study to the next.ConclusionsAlthough nontechnical skills can be measured reliably under some circumstances, it is not clear from the existing literature that one scale provides more reliable data than another. We recommend several practices that would help readers to make informed decisions about which scales are most useful for their purposes.
http://ift.tt/2iHbw3M
Training in Cerebral Aneurysm Clipping Using Self-Made 3-Dimensional Models
Publication date: Available online 16 January 2017
Source:Journal of Surgical Education
Author(s): Toshihiro Mashiko, Naoki Kaneko, Takehiko Konno, Keisuke Otani, Rie Nagayama, Eiju Watanabe
IntroductionRecently, there have been increasingly fewer opportunities for junior surgeons to receive on-the-job training. Therefore, we created custom-built three-dimensional (3D) surgical simulators for training in connection with cerebral aneurysm clipping.MethodsThree patient-specific models were composed of a trimmed skull, retractable brain, and a hollow elastic aneurysm with its parent artery. The brain models were created using 3D printers via a casting technique. The artery models were made by 3D printing and a lost-wax technique. Four residents and 2 junior neurosurgeons attended the training courses. The trainees retracted the brain, observed the parent arteries and aneurysmal neck, selected the clip(s), and clipped the neck of an aneurysm. The duration of simulation was recorded. A senior neurosurgeon then assessed the trainee's technical skill and explained how to improve his/her performance for the procedure using a video of the actual surgery. Subsequently, the trainee attempted the clipping simulation again, using the same model. After the course, the senior neurosurgeon assessed each trainee's technical skill. The trainee critiqued the usefulness of the model and the effectiveness of the training course.ResultsTrainees succeeded in performing the simulation in line with an actual surgery. Their skills tended to improve upon completion of the training.ConclusionThese simulation models are easy to create, and we believe that they are very useful for training junior neurosurgeons in the surgical techniques needed for cerebral aneurysm clipping.
http://ift.tt/2iBV9lX
Is Enhanced Recovery the New Standard of Care in Microsurgical Breast Reconstruction?.
http://ift.tt/2iwDu3S
Distribution Pattern of the Superior and the Inferior Labial Arteries -Impact for Safe Upper and Lower Lip Augmentation Procedures.
http://ift.tt/2jjdPsx
The construction of expanded prefabricated adipose tissue (EPAT) using an external volume expansion (EVE) device.
http://ift.tt/2iwz6BP
Anatomical Basis and Clinical Application of Synovial Flaps in the Wrist and Distal Forearm.
http://ift.tt/2jjlMhE
The effect of parathyroid hormone on the uptake and retention of 25-hydroxyvitamin D in skeletal muscle cells
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): M. Abboud, M.S. Rybchyn, J Liu, Y Ning, C. Gordon-Thomson, T.C. Brennan-Speranza, L. Cole, H. Greenfield, D.R. Fraser, R.S. Mason
Data from our studies, and those of others, support the proposal that there is a role for skeletal muscle in the maintenance of vitamin D status. We demonstrated that skeletal muscle is able to internalise extracellular vitamin D binding protein, which then binds to actin in the cytoplasm, to provide high affinity binding sites which accumulate 25-hydroxyvitamin D3 (25(OH)D3) [1]. This study investigated the concentration- and time-dependent effects of parathyroid hormone (PTH) on the capacity of muscle cells to take up and release 3H-25(OH)D3. Uptake and retention studies for 3H-25(OH)D3 were carried out with C2C12 cells differentiated into myotubes and with primary mouse muscle fibers as described [1]. The presence of PTH receptors on mouse muscle fibers was demonstrated by immunohistochemistry and PTH receptors were detected in differentiated myotubes, but not myoblasts, and on muscle fibers by Western blot. Addition of low concentrations of vitamin D binding protein to the incubation media did not alter uptake of 25(OH)D3. Pre-incubation of C2 myotubes or primary mouse muscle fibers with PTH (0.1 to 100 pM) for 3h resulted in a concentration-dependent decrease in 25(OH)D3 uptake after 4 or 16h. These effects were significant at 0.1 or 1pM PTH (p <0.001) and plateaued at 10 pM, with 25(OH)D3 uptake reduced by over 60% (p <0.001) in both cell types. In C2 myotubes, retention of 25(OH)D3 was decreased after addition of PTH (0.1 to 100pM) in a concentration-dependent manner by up to 80% (p<0.001) compared to non-PTH treated-C2 myotubes. These data show that muscle uptake and retention of 25(OH)D3 are modulated by PTH, a physiological regulator of mineral homeostasis, but the cell culture model may not be a comprehensive reflection of vitamin D homeostatic mechanisms in whole animals.
http://ift.tt/2iH0z2o
Constitutively active RAS signaling reduces 1,25 dihydroxyvitamin D-mediated gene transcription in intestinal epithelial cells by reducing vitamin D receptor expression
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Marsha L. DeSmet, James C. Fleet
High vitamin D status is associated with reduced colon cancer risk but these studies ignore the diversity in the molecular etiology of colon cancer. RAS activating mutations are common in colon cancer and they activate pro-proliferative signaling pathways. We examined the impact of RAS activating mutations on 1,25 dihydroxyvitamin D (1,25(OH)2D)-mediated gene expression in cultured colon and intestinal cell lines. Transient transfection of Caco-2 cells with a constitutively active mutant K-RAS (G12 V) significantly reduced 1,25(OH)2D-induced activity of both a human 25-hydroxyvitamin D, 24 hydroxyase (CYP24A1) promoter-luciferase and an artificial 3X vitamin D response element (VDRE) promoter-luciferase reporter gene. Young Adult Mouse Colon (YAMC) and Rat Intestinal Epithelial (RIE) cell lines with stable expression of mutant H-RAS had suppressed 1,25(OH)2D-mediated induction of CYP24A1 mRNA. The RAS effects were associated with lower Vitamin D receptor (VDR) mRNA and protein levels in YAMC and RIE cells and they could be partially reversed by VDR overexpression. RAS-mediated suppression of VDR levels was not due to either reduced VDR mRNA stability or increased VDR gene methylation. However, chromatin accessibility to the VDR gene at the proximal promoter (−300bp), an enhancer region at −6kb, and an enhancer region located in exon 3 was significantly reduced in RAS transformed YAMC cells (YAMC-RAS). These data show that constitutively active RAS signaling suppresses 1,25(OH)2D-mediated gene transcription in colon epithelial cells by reducing VDR gene transcription but the mechanism for this suppression is not yet known. These data suggest that cancers with RAS-activating mutations may be less responsive to vitamin D mediated treatment or chemoprevention.
http://ift.tt/2iBIWh4
Thoughts on interactions between PGRMC1 and diverse attested and potential hydrophobic ligands
Publication date: Available online 16 January 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Michael A. Cahill, Amy E. Medlock
Progesterone Receptor Membrane Component 1 (PGRMC1) is located in many different subcellular locations with many different attested and probably location-specific functions. PGRMC1 was recently identified in the mitochondrial outer membrane where it interacts with ferrochelatase, the last enzyme in the heme synthetic pathway. It has been proposed that PGRMC1 may act as a chaperone to shuttle newly synthesized heme from the mitochondrion to cytochrome P450 (cyP450) enzymes. Here we consider potential roles that PGRMC1 may play in transferring heme, and other small hydrophobic ligands such as cholesterol and steroids, between the hydrophobic compartment of the membrane lipid bilayer interior to aqueous proteins, and perhaps to the membranes of other organelles. We review the synthesis and roles of especially PGRMC1- and cyP450-bound heme, the sources and transport of cholesterol, the involvement of PGRMC1 in cholesterol regulation, and the production of the first progestogen pregnenolone from cholesterol. We also show by clustering by inferred models of evolution (CLIME) analysis that PGRMC1 and related proteins exhibit co-evolution with a series of cyP450 enzymes, as well as a group of mitochondrial proteins lacking in several parasitic protist groups. The blood fluke Schistosoma mansoni also lacks a PGRMC1 homolog as well as cyP450s involved in cholesterol synthesis, suggesting co-evolution of the combined loss of PGRMC1-like and sterologenic cyP450 proteins by distinct uni- and multi-cellular parasites. Altogether, PGRMC1 is implicated with important roles in sterol synthesis and energy regulation that are dispensable in certain parasites. Some novel hypothetical models for PGRMC1 function are proposed to direct future investigative research.
Graphical abstract
http://ift.tt/2iH3XtS
Vitamin D metabolites in captivity? Should we measure free or total 25(OH)D to assess vitamin D status?
Publication date: Available online 16 January 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Daniel Bikle, Roger Bouillon, Ravi Thadhani, Inez Schoenmakers
There is general consensus that serum 25(OH)D is the best biochemical marker for nutritional vitamin D status. Whether free 25(OH)D would be a better marker than total 25(OH)D is so far unclear. Free 25(OH)D can either be calculated based on the measurement of the serum concentrations of total 25(OH)D, vitamin D-binding protein (DBP), albumin, and the affinity between 25(OH)D and its binding proteins in physiological situations. Free 25(OH)D can also be measured directly by equilibrium dialysis, ultrafitration or immunoassays. During the vitamin D workshop held in Boston in March 2016, a debate was organized about the measurements and clinical value of free 25(OH)D, and this debate is summarized in the present manuscript. Overall there is consensus that most cells apart from the renal tubular cells are exposed to free rather than to total 25(OH)D. Therefore free 25(OH)D may be highly relevant for the local production and action of 1,25(OH)2D. During the debate it became clear that there is a need for standardization of measurements of serum DBP and of direct measurements of free 25(OH)D. There seems to be very limited genetic or racial differences in DBP concentrations or (probably) in the affinity of DBP for its major ligands. Therefore, free 25(OH)D is strongly correlated to total 25(OH)D in most normal populations. Appropriate studies are needed to define the clinical implications of free rather than total 25(OH)D in normal subjects and in disease states. Special attention is needed for such studies in cases of abnormal DBP concentrations or when one could expect changes in its affinity for its ligands.
http://ift.tt/2iHc1uV
CYP24A1 LOSS OF FUNCTION: CLINICAL PHENOTYPE OF MONOALLELIC AND BIALLELIC MUTATIONS
Publication date: Available online 16 January 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Thomas O. Carpenter
CYP24A1, encoding the vitamin D-24-hydroxylase, is of major clinical and physiologic importance, serving to regulate the catabolism of 1,25-(OH)2D, the physiologically active vitamin D metabolite. In addition to facilitating catabolism of 1,25-(OH)2D, CYP24A1 also enhances the turnover and elimination of 25-OHD, the abundant precursor metabolite and storage form of the vitamin. CYP24A1 can be stimulated hormonally by 1,25-(OH)2D and by FGF23, whereas CYP27B1, encoding the vitamin D-1α–hydroxylase, is stimulated hormonally by parathyroid hormone (PTH) and downregulated by FGF23. Thus CYP24A1 and CYP27B1, together, provide for alternate and regulated fates of 25-OHD, and control the availability of the active metabolite, 1,25-(OH)2D depending upon physiologic needs. These two enzymes, are therefore central to the homeostatic control of vitamin D metabolism, and as a result affect calcium metabolism in critical ways. Disruption of CYP24A1 in mice results in elevated circulating 1,25-(OH)2D, substantiating the importance of the enzyme in the maintenance of vitamin D metabolism. The consequential skeletal phenotype in these mice further demonstrates the biologic sequelae of the disruption of the vitamin D pathway, and illustrates a specific developmental pathology mediated largely by oversupply of 1,25-(OH)2D. More recent evidence has identified loss of function mutations in CYP24A1 in association with hypercalcemia, hypercalciuria and nephrolithiasis in humans. Initial reports described certain variant mutations in CYP24A1 as an unrecognized cause of "Idiopathic Infantile Hypercalcemia," and more recently older children and adults have been identified with a similar phenotype. Over 25 likely disease-causing variants are described. Homozygous and compound heterozygote mutations account for the overwhelming majority of cases, however the heterozygous loss-of-function mutations of CYP24A1 do not appear to consistently result in symptomatic hypercalcemia. Considerations ripe for exploration include the potential role for such mutations in the tolerance to challenges to the calcium homeostatic system, such as changes in dietary calcium intake, vitamin D supplementation, sunlight exposure or pregnancy.
http://ift.tt/2iBPFro
Detection of Somatic Variants in Peripheral Blood Lymphocytes Using a Next Generation Sequencing Multigene Pan Cancer Panel
Source:Cancer Genetics
Author(s): Bradford Coffee, Hannah C. Cox, John Kidd, Scott Sizemore, Krystal Brown, Susan Manley, Debora Mancini-DiNardo
Next Generation Sequencing (NGS) multigene panels, which are routinely used to assess hereditary cancer risk, can detect both inherited germline variants and somatic variants in cancer-risk genes. We evaluated the frequency and distribution of likely somatic pathogenic and likely pathogenic variants (PVs) detected in >220,000 individuals who underwent clinical testing with a 25-gene panel between September 2013 and March 2016. Likely somatic PVs are defined as variants with NGS read frequencies from 10%-30%. Overall, 137 (0.06%) individuals were identified as carrying likely somatic PVs, most commonly in TP53 (73), CHEK2 (27), and ATM (20). Among this group, a second PV with a NGS read frequency consistent with a germline variant within the same gene or a different gene on the panel was detected in 21 individuals (15.3%), which is similar to the detection rate in our general testing population. Likely somatic PVs accounted for 38.8% of all PVs in TP53. In comparison, likely somatic PVs accounted for <1% of PVs in most other genes. Likely somatic PVs were more frequently identified in older individuals (p<0.001). Additional studies are ongoing to further investigate the incidence and clinical implications of somatic variants, enabling the appropriate medical management for these patients.
http://ift.tt/2iH3bgt
Biology and Patterns of Response to EGFR-Inhibition in Squamous Cell Cancers of the Lung and Head & Neck
Source:Cancer Treatment Reviews
Author(s): Rosalyn A. Juergens, Scott V. Bratman, Ming-Sound Tsao, Scott A. Laurie, M. Sara Kuruvilla, Albiruni R.A. Razak, Aaron R. Hansen
The identification of common molecular aberrations that drive cancer progression has led to targeted therapies that improve treatment efficacy in many tumor types. Epidermal growth factor receptor (EGFR) inhibitors have been used to treat both lung and head and neck cancers with squamous cell histology. These tumors often show high EGFR expression and/or increased gene copy number, but low incidence of the activating kinase domain mutations common to adenocarcinomas of the lung. In this manuscript, we review clinical trial data on EGFR-inhibitors in the treatment of squamous cell carcinoma (SqCC) of the lung and head and neck (SCCHN), including both efficacy and biomarker analyses. Although some efficacy with use of EGFR inhibitors is observed, the level of benefit varies within and across tumor types, and the predictive capacity of high EGFR protein expression and/or gene amplification, if any, is limited. Due to the lack of candidate biomarkers that consistently predict response to EGFR-inhibitor therapy across treatment setting and class of agent in SqCC of the lung and SCCHN, we explore the biology, genomics and patterns of response to EGFR-inhibitors to inform identification of potential biomarkers, highlighting several key molecules that have shown promise in preclinical studies and clinical trials across multiple cancer sites.
http://ift.tt/2jr62vb
Δευτέρα 16 Ιανουαρίου 2017
Adaptive cone-beam CT planning improves long-term biochemical disease-free survival for 125I prostate brachytherapy
Source:Brachytherapy
Author(s): M. Peters, D.A. Smit Duijzentkunst, H. Westendorp, S.M.G. van de Pol, R. Kattevilder, A. Schellekens, J.R.N. van der Voort van Zyp, M.A. Moerland, M. van Vulpen, C.J. Hoekstra
PurposeDetermining the independent effect of additional intraoperative adaptive C-arm cone-beam CT (CBCT) planning vs. transrectal ultrasound (TRUS)-guided interactive planning alone in 125I brachytherapy for prostate cancer (PCa) on biochemical disease-free survival (BDFS).Methods and materialsT1/T2-stage PCa patients receiving TRUS-guided brachytherapy from 2000 to 2014 were analyzed. From October 2006, patients received additional intraoperative adaptive CBCT planning for dosimetric evaluation and subsequent remedial seed placement in underdosed areas. Patients were stratified according to the National Comprehensive Cancer Network (NCCN) risk classification. Kaplan–Meier analysis was used to estimate BDFS (primary outcome), overall survival, and PCa-specific survival (secondary outcomes). Cox regression was used to assess the relation between CBCT use and biochemical failure (BF) and overall mortality.ResultsIn all, 1623 patients were included. Median followup was 99 months (interquartile range 70–115) for TRUS patients (n = 613) and 51 months (interquartile range 29–70) for CBCT patients (n = 1010). BF occurred 203 times and 206 patients died, 26 from PCa. For TRUS and CBCT patients, 7-year BDFS was 87.2% vs. 93.5% (log rank: p = 0.04) for low, 75.9% vs. 88.5% (p < 0.001) for intermediate, and 57.1% vs. 85.0% for high-risk patients (p < 0.001). For TRUS and CBCT patients, 7-year PCa-specific survival was 96.0% vs. 100% (p < 0.0001). After Cox regression, CBCT patients had lower hazard of BF: hazard ratio (HR) 0.25 (95% confidence interval [CI]: 0.18–0.33; p < 0.0001). Corrected for confounders, CBCT remained a predictor of BF: HR 0.51 (95% CI: 0.31–0.86; p = 0.01) but not for overall mortality: HR 0.66 (95% CI: 0.40–1.07; p = 0.09).ConclusionsAdditional intraoperative adaptive CBCT planning in 125I prostate brachytherapy leads to a significant increase in BDFS in all NCCN risk groups.
http://ift.tt/2jut6c9
-
Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
-
Abstract Noise pollution is a major factor of environmental complaints in many cities, which has significant impacts on human health. As a...
