Validating Safecast data by comparisons to a U. S. Department of Energy Fukushima Prefecture aerial survey

Publication date: May 2017
Source:Journal of Environmental Radioactivity, Volume 171
Author(s): Mark Coletti, Carolynne Hultquist, William G. Kennedy, Guido Cervone
Safecast is a volunteered geographic information (VGI) project where the lay public uses hand-held sensors to collect radiation measurements that are then made freely available under the Creative Commons CC0 license. However, Safecast data fidelity is uncertain given the sensor kits are hand assembled with various levels of technical proficiency, and the sensors may not be properly deployed. Our objective was to validate Safecast data by comparing Safecast data with authoritative data collected by the U. S. Department of Energy (DOE) and the U. S. National Nuclear Security Administration (NNSA) gathered in the Fukushima Prefecture shortly after the Daiichi nuclear power plant catastrophe. We found that the two data sets were highly correlated, though the DOE/NNSA observations were generally higher than the Safecast measurements. We concluded that this high correlation alone makes Safecast a viable data source for detecting and monitoring radiation.



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Modeling watershed-scale 137Cs transport in a forested catchment affected by the Fukushima Dai-ichi Nuclear Power Plant accident

Publication date: May 2017
Source:Journal of Environmental Radioactivity, Volume 171
Author(s): Lezhang Wei, Tsuyoshi Kinouchi, Kazuya Yoshimura, Mark L. Velleux
The Fukushima nuclear accident in 2011 resulted in ¹³⁷Cs contamination of large areas in northeast Japan. A watershed-scale ¹³⁷Cs transport model was developed and applied to a forested catchment in Fukushima area. This model considers ¹³⁷Cs wash-off from vegetation, movement through soils, and transport of dissolved and particulate ¹³⁷Cs adsorbed to clay, silt and sand. Comparisons between measurements and simulations demonstrated that the model well reproduced ¹³⁷Cs concentrations in the stream fed from the catchment. Simulations estimated that 0.57 TBq of ¹³⁷Cs was exported from the catchment between June, 2011 and December, 2014. Transport largely occurred with eroded sediment particles at a ratio of 17:70:13 of clay, silt, and sand. The overall ¹³⁷Cs reduction ratio by rainfall-runoff wash-off was about 1.6%. Appreciable ¹³⁷Cs remained in the catchment at the end of 2014. The largest rate of ¹³⁷Cs reduction by wash-off was simulated to occur in subwatersheds of the upper catchment. However, despite relatively low initial deposition, middle portions of the watershed exported proportionately more ¹³⁷Cs by rainfall-runoff processes. Simulations indicated that much of the transported ¹³⁷Cs originates from erosion over hillsides and river banks. These results suggested that areas where ¹³⁷Cs accumulates with redeposited sediments can be targeted for decontamination and also provided insight into ¹³⁷Cs transport at the watershed scale to assess risk management and decontamination planning efforts.



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Temporal Stability of Multiple Response Systems to 7.5% Carbon Dioxide Challenge

Publication date: Available online 2 February 2017
Source:Biological Psychology
Author(s): Roxann Roberson-Nay, Eugenia I. Gorlin, Jessica R. Beadel, Therese Cash, Scott Vrana, Bethany A. Teachman
Self-reported anxiety, and potentially physiological response, to maintained inhalation of carbon dioxide (CO2) enriched air shows promise as a putative marker of panic reactivity and vulnerability. Temporal stability of response systems during low-dose, steady-state CO2 breathing challenge is lacking. Outcomes on multiple levels were measured two times, one week apart, in 93 individuals. Stability was highest during the CO2 breathing phase compared to pre-CO2 and recovery phases, with anxiety ratings, respiratory rate, skin conductance level, and heart rate demonstrating good to excellent temporal stability (ICCs ≥ 0.71). Cognitive symptoms tied to panic were somewhat less stable (ICC=0.58) than physical symptoms (ICC=0.74) during CO2 breathing. Escape/avoidance behaviors and DSM-5 panic attacks were not stable. Large effect sizes between task phases also were observed. Overall, results suggest good-excellent levels of temporal stability for multiple outcomes during respiratory stimulation via 7.5% CO2.



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ADAM10-Initiated Release of Notch Intracellular Domain Regulates Microtubule Stability and Radial Migration of Cortical Neurons

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Proper neuronal migration is orchestrated by combined membrane signal paradigms, whereas the role and mechanism of regulated intramembrane proteolysis (RIP) remain to be illustrated. We show here that the disintegrin and metalloprotease-domain containing protein 10 (ADAM10) regulates cortical neurons migration by initiating the RIP of Notch. We found that Notch intracellular domain (NICD) significantly rescued the migration defect of ADAM10-deficient neurons. Moreover, ADAM10 deficiency led to reduced neuronal motility and disrupted microtubule (MT) structure, which were associated with downregulated expression of acetylated tubulin and MT-associated proteins. Specifically, the NICD/RBPJ complex bound directly to the promoter, and regulated the neuronal expression level of doublecortin (DCX), a modulator of the MT cytoskeleton. Functionally, DCX overexpression largely restored neuron motility and reversed migration defect caused by ADAM10 knockout. Taken together, these findings demonstrate the direct requirement of ADAM10 in cortical radial migration and reveal the underlying mechanism by linking ADAM10-initiated RIP of Notch to the regulation of MT cytoskeleton through transcriptional control of <span style="font-style:italic;">Dcx</span> expression.</span>

http://ift.tt/2l1L0l8

Multimodal MRI Imaging of Apoptosis-Triggered Microstructural Alterations in the Postnatal Cerebral Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Prematurely born children often develop neurodevelopmental delay that has been correlated with reduced growth and microstructural alterations in the cerebral cortex. Much research has focused on apoptotic neuronal cell death as a key neuropathological features following preterm brain injuries. How scattered apoptotic death of neurons may contribute to microstructural alterations remains unknown. The present study investigated in a rat model the effects of targeted neuronal apoptosis on cortical microstructure using in vivo MRI imaging combined with neuronal reconstruction and histological analysis. We describe that mild, targeted death of layer IV neurons in the developing rat cortex induces MRI-defined metabolic and microstructural alterations including increased cortical fractional anisotropy. Delayed architectural modifications in cortical gray matter and myelin abnormalities in the subcortical white matter such as hypomyelination and microglia activation follow the acute phase of neuronal death and axonal degeneration. These results establish the link between mild cortical apoptosis and MRI-defined microstructure changes that are reminiscent to those previously observed in preterm babies.</span>

http://ift.tt/2jEi8SM

Regulation of Dendritic Spine Morphology in Hippocampal Neurons by Copine-6

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Dendritic spines compartmentalize information in the brain, and their morphological characteristics are thought to underly synaptic plasticity. Here we identify copine-6 as a novel modulator of dendritic spine morphology. We found that brain-derived neurotrophic factor (BDNF) – a molecule essential for long-term potentiation of synaptic strength – upregulated and recruited copine-6 to dendritic spines in hippocampal neurons. Overexpression of copine-6 increased mushroom spine number and decreased filopodia number, while copine-6 knockdown had the opposite effect and dramatically increased the number of filopodia, which lacked PSD95. Functionally, manipulation of post-synaptic copine-6 levels affected miniature excitatory post-synaptic current (mEPSC) kinetics and evoked synaptic vesicle recycling in contacting boutons, and post-synaptic knockdown of copine-6 reduced hippocampal LTP and increased LTD. Mechanistically, copine-6 promotes BDNF-TrkB signaling and recycling of activated TrkB receptors back to the plasma membrane surface, and is necessary for BDNF-induced increases in mushroom spines in hippocampal neurons. Thus copine-6 regulates BDNF-dependent changes in dendritic spine morphology to promote synaptic plasticity.</span>

http://ift.tt/2jEbGLG

Social Isolation During the Critical Period Reduces Synaptic and Intrinsic Excitability of a Subtype of Pyramidal Cell in Mouse Prefrontal Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Juvenile social experience is crucial for the functional development of forebrain regions, especially the prefrontal cortex (PFC). We previously reported that social isolation for 2 weeks after weaning induces prefrontal cortex dysfunction and hypomyelination. However, the effect of social isolation on physiological properties of PFC neuronal circuit remained unknown. Since hypomyelination due to isolation is prominent in deep-layer of medial PFC (mPFC), we focused on 2 types of Layer-5 pyramidal cells in the mPFC: prominent h-current (PH) cells and nonprominent h-current (non-PH) cells. We found that a 2-week social isolation after weaning leads to a specific deterioration in action potential properties and reduction in excitatory synaptic inputs in PH cells. The effects of social isolation on PH cells, which involve reduction in functional glutamatergic synapses and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/<span style="font-style:italic;">N</span>-methyl-<span style="text-transform:lowercase;font-variant:small-caps;">d</span>-aspartate charge ratio, are specific to the 2 weeks after weaning and to the mPFC. We conclude that juvenile social experience plays crucial roles in the functional development in a subtype of Layer-5 pyramidal cells in the mPFC. Since these neurons project to subcortical structures, a deficit in social experience during the critical period may result in immature neural circuitry between mPFC and subcortical targets.</span>

http://ift.tt/2l1KOC9

Reduced Inhibition within Layer IV of Sert Knockout Rat Barrel Cortex is Associated with Faster Sensory Integration

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Neural activity is essential for the maturation of sensory systems. In the rodent primary somatosensory cortex (S1), high extracellular serotonin (5-HT) levels during development impair neural transmission between the thalamus and cortical input layer IV (LIV). Rodent models of impaired 5-HT transporter (SERT) function show disruption in their topological organization of S1 and in the expression of activity-regulated genes essential for inhibitory cortical network formation. It remains unclear how such alterations affect the sensory information processing within cortical LIV. Using serotonin transporter knockout (<span style="font-style:italic;">Sert</span>^−/−) rats, we demonstrate that high extracellular serotonin levels are associated with impaired feedforward inhibition (FFI), fewer perisomatic inhibitory synapses, a depolarized GABA reversal potential and reduced expression of KCC2 transporters in juvenile animals. At the neural population level, reduced FFI increases the excitatory drive originating from LIV, facilitating evoked representations in the supragranular layers II/III. The behavioral consequence of these changes in network excitability is faster integration of the sensory information during whisker-based tactile navigation, as <span style="font-style:italic;">Sert</span>^−/− rats require fewer whisker contacts with tactile targets and perform object localization with faster reaction times. These results highlight the association of serotonergic homeostasis with formation and excitability of sensory cortical networks, and consequently with sensory perception.</span>

http://ift.tt/2jEoZf4

Variability of skin pH after the use of different collagen gels

Summary

Background

Skin pH is an important parameter indicating the condition of the skin because imbalance can contribute to the development of skin problems and earlier aging. Individual skin pH depends on many factors such as hydration, sweating, sebum excretion, genetics, sex, and age. Additionally, it can be affected by exogenous factors such as cosmetics.

Aims

The aim of the study was to compare different collagen gels and determine whether and to what extent they change the pH of the skin.

Patients/Methods

Baseline skin pH was measured in 49 women aged between 19 and 23. It was measured again 20 and 60 minutes following of the application of four collagen gels.

Results

The mean physiological pH values of the forehead and cheek were 5.67 and 5.76, respectively. The analysis of variance and post hoc test revealed that gel no. 1, gel no. 2, and gel no. 3 (but not 4) significantly changed the skin pH.

Conclusion

Collagen gel should be neutral for the skin barrier; however, most collagen skin care preparations significantly changed skin pH. Methods of processing and stabilizing the collagen may account for the difference in effect between gels, but further research is required.

http://ift.tt/2kvUDe8

Somatic clonal evolution: A selection-centric perspective

Publication date: Available online 2 February 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Jacob Scott, Andriy Marusyk
It is generally accepted that the initiation and progression of cancers is the result of somatic clonal evolution. Despite many peculiarities, evolution within populations of somatic cells should obey the same Darwinian principles as evolution within natural populations, i.e. variability of heritable phenotypes provides the substrate for context-specific selection forces leading to increased population frequencies of phenotypes, which are better adapted to their environment. Yet, within cancer biology, the more prevalent way to view evolution is as being entirely driven by the accumulation of "driver" mutations. Context-specific selection forces are either ignored, or viewed as constraints from which tumor cells liberate themselves during the course of malignant progression. In this review, we will argue that explicitly focusing on selection forces acting on the populations of neoplastic cells as the driving force of somatic clonal evolution might provide for a more accurate conceptual framework compared to the mutation-centric driver gene paradigm. Whereas little can be done to counteract the "bad luck" of stochastic occurrences of cancer-related mutations, changes in selective pressures and the phenotypic adaptations they induce can, in principle, be exploited to limit the incidence of cancers and to increase the efficiency of existing and future therapies. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.



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Effects of Cholecalciferol Supplementation on Serum and Urinary Vitamin D Metabolites and Binding Protein in HIV-infected Youth

Publication date: Available online 1 February 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Allison Ross Eckard, Myrtle Thierry-Palmer, Natalia Silvestrov, Julia C. Rosebush, Ann Mary O'Riordan, Julie E. Daniels, Monika Uribe Leitz, Danielle Labbato, Joshua H. Ruff, Ravinder J. Singh, Vin Tangpricha, Grace A. McComsey
Vitamin D insufficiency is widespread in HIV-infected patients. HIV and/or antiretroviral therapy (ART), particularly efavirenz (EFV), may interfere with vitamin D metabolism. However, few data from randomized, controlled trials exist. Here, we investigate changes in vitamin D metabolites and binding protein (VDBP) after 6 months of supplementation in a randomized, active-control, double-blind trial investigating 2 different monthly cholecalciferol (vitamin D3) doses [60,000 (medium) or 120,000 (high) IU/month] vs. a control arm of 18,000 IU/month in 8–25year old HIV-infected youth on ART with HIV-1 RNA <1000 copies/mL and baseline 25-hydroxycholecalciferol (25(OH)D3) ≤30ng/mL. A matched healthy uninfected group was enrolled in a similar parallel study for comparison. Changes after 6 months were analyzed as intent-to-treat within/between groups [control group (low dose) vs. combined supplementation doses (medium+high)]. At 6 months, 55% vs. 82% of subjects in control and supplementation groups, respectively, reached 25(OH)D3 ≥30ng/mL (P=0.01) with no difference between medium and high doses (both 82% ≥30ng/mL). There were few differences for those on EFV vs. no-EFV, except serum VDBP decreased in EFV-treated subjects (both within- and between-groups P≤0.01). There were no significant differences between the HIV-infected vs. healthy uninfected groups. The major finding of the present study is that cholecalciferol supplementation (60,000 or 120,000 IU/month) effectively raises serum 25(OH)D3 in the majority of HIV-infected subjects, regardless of EFV use. Notably, response to supplementation was similar to that of uninfected subjects.



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Editorial board

Publication date: March 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 167





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Skeletal Muscle Vitamin D in Patients with End Stage Osteoarthritis of the Knee

Publication date: Available online 1 February 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Tara C. Brennan-Speranza, David Mor, Rebecca S. Mason, John R. Bartlett, Gustavo Duque, Itamar Levinger, Pazit Levinger
Muscle function is often impaired in patients with knee osteoarthritis (OA), with reduced strength and increased pain. The role of vitamin D and the vitamin D-endocrine pathway in muscle health has recently been placed in the spotlight, with various groups reporting positive effects on muscle development, function and health. Recently, it has been shown that uptake into muscle of the specialized vitamin D binding protein (DBP) is dependent on the endocytic receptor, megalin. Here we analyze circulating vitamin D, and muscle DBP, megalin and the cognate vitamin D receptor (VDR) in patients with knee OA and compare them to asymptomatic controls.Muscle and blood samples were collected from 19 patients with end-stage OA of the knee and 10 age-matched controls. Muscle biopsies from the OA group were performed during knee replacement surgery and a needle biopsy was used on control volunteers. Immunoblots performed with specific antibodies were used to detect the presence of DBP, megalin, VDR (using the specific D-6 antibody) and albumin in the muscle biopsies. Results were correlated with FoxO1, a key regulator of the ubiquitin-proteasome degradation pathway in muscle.There were no differences in circulating levels of 25 (OH) vitamin D3 between the groups, and no subjects were vitamin D deficient. We found increased VDR, DBP and albumin protein in the muscle from patients with OA compared to controls, with no change in muscle megalin expression. Furthermore, DBP levels in the muscle correlated with FoxO1, suggesting an association between muscle protein breakdown and the activation of the vitamin D-endocrine pathway in muscle surrounding an OA affected joint.We show, for the first time, that the factors involved in the vitamin D-endocrine-pathway are present at higher levels in muscles from OA patients compared to asymptomatic controls. This is despite no differences in circulating 25 (OH) vitamin D levels between the groups. These findings indicate the activation of vitamin D pathway in these muscles that may provide a beneficial compensatory stimulation of the repair process in muscles that are subject to inflammatory and proteolytic processes.



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New PCOS-like phenotype in older infertile women of likely autoimmune adrenal etiology with high AMH but low androgens

Publication date: March 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 167
Author(s): Norbert Gleicher, Vitaly A. Kushnir, Sarah K. Darmon, Qi Wang, Lin Zhang, David F. Albertini, David H. Barad
How anti-Müllerian hormone (AMH) and testosterone (T) interrelate in infertile women is currently largely unknown. We, therefore, in a retrospective cohort study investigated how infertile women with high-AMH (AMH ≥75th quantile; n=144) and with normal-AMH (25th–75th quantile; n=313), stratified for low-T (total testosterone ≤19.0ng/dL), normal-T (19.0–29.0ng/dL) and high-T (>29.0ng/dL) phenotypically behaved. Patient age, follicle stimulating hormone (FSH), dehyroepiandrosterone (DHEA), DHEA sulphate (DHEAS), cortisol (C), adrenocorticotrophic hormone (ACTH), IVF outcomes, as well as inflammatory and immune panels were then compared between groups, with AMH and T as variables. We identified a previously unknown infertile PCOS-like phenotype, characterized by high-AMH but, atypically, low-T, with predisposition toward autoimmunity. It presents with incompatible high-AMH and low-T (<19.0ng/dL), is restricted to lean PCOS-like patients, presenting delayed for tertiary fertility services. Since also characterized by low DHEAS, low-T is likely of adrenal origina, and consequence of autoimmune adrenal insufficiency since also accompanied by low-C and evidence of autoimmunity. DHEA supplementation in such patients equalizes low- to normal-T and normalizes IVF cycle outcomes. Once recognized, this high-AMH/low-T phenotype is surprisingly common in tertiary fertility centers but, currently, goes unrecognized. Its likely adrenal autoimmune etiology offers interesting new directions for investigations of adrenals control over ovarian function via adrenal androgen production.



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Effects of vitamin D status on oral health

Publication date: Available online 1 February 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Anne Marie Uwitonze, Julienne Murererehe, Marie Claire Ineza, Eliane Harelimana, Uziel Nsabimana, Peace Uwambaye, Agnes Gatarayiha, Afrozul Haq, Mohammed S. Razzaque
Normal humans of all ages have the innate ability to produce vitamin D following sunlight exposure. Inadequate vitamin D status has shown to be associated with a wide variety of diseases, including oral health disorders. Insufficient sunlight exposure may accelerate some of these diseases, possibly due to impaired vitamin D synthesis. The beneficial effects of vitamin D on oral health are not only limited to the direct effects on the tooth mineralization, but are also exerted through the anti-inflammatory functions and the ability to stimulate the production of anti-microbial peptides. In this article, we will briefly discuss the effect on the genesis of various oral diseases due to inadequate vitamin D level in the body and explain the potential benefits of safe sunlight exposure for the maintenance of oral and general health.

Graphical abstract

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Role of G-protein-coupled estrogen receptor (GPER/GPR30) in maintenance of meiotic arrest in fish oocytes

Publication date: March 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 167
Author(s): Peter Thomas
An essential role for GPER (formerly known as GPR30) in regulating mammalian reproduction has not been identified to date, although it has shown to be involved in the regulation a broad range of other estrogen-dependent functions. In contrast, an important reproductive role for GPER in the maintenance of oocyte meiotic arrest has been identified in teleost fishes, which is briefly reviewed here. Recent studies have clearly shown that ovarian follicle production of estradiol-17β (E2) maintains meiotic arrest in several teleost species through activation of GPER coupled to a stimulatory G protein (Gs) on oocyte plasma membranes resulting in stimulation of cAMP production and maintenance of elevated cAMP levels. Studies with denuded zebrafish oocytes and with microinjection of GPER antisense oligonucleotides into oocytes have demonstrated the requirement for both ovarian follicle production of estrogens and expression of GPER on the oocyte surface for maintenance of meiotic arrest. This inhibitory action of E2 on the resumption of meiosis is mimicked by the GPER-selective agonist G-1, by the GPER agonists and nuclear ER antagonists, ICI 182,780 and tamoxifen, and also by the xenoestrogen bisphenol-A (BPA) and related alkylphenols. GPER also maintains meiotic arrest of zebrafish oocytes through estrogen- and BPA-dependent GPER activation of epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK) signaling. Interestingly, progesterone receptor component 1 (PGRMC1) is also involved in estrogen maintenance of meiotic arrest through regulation of EGFR expression on the oocyte plasma membrane. The preovulatory surge in LH secretion induces the ovarian synthesis of progestin hormones that activate a membrane progestin receptor alpha (mPRα)/inhibitory G protein (Gi) pathway. It also increases ovarian synthesis of the catecholestrogen, 2-hydroxy-estradiol-17β (2-OHE2) which inhibits the GPER/Gs/adenylyl cyclase pathway. Both of these LH actions cause declines in oocyte cAMP levels resulting in the resumption of meiosis. GPER is also present on murine oocytes but there are no reports of studies investigating its possible involvement in maintaining meiotic arrest in mammals.



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Prevalence, determinants and clinical correlates of vitamin D deficiency in patients with Chronic Obstructive Pulmonary Disease in London, UK

Publication date: Available online 1 February 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): David A. Jolliffe, Wai Yee James, Richard L. Hooper, Neil C. Barnes, Claire L. Greiller, Kamrul Islam, Angshu Bhowmik, Peter M. Timms, Raj K Rajakulasingam, Aklak B. Choudhury, David E. Simcock, Elina Hyppönen, Robert T. Walton, Christopher J. Corrigan, Christopher J. Griffiths, Adrian R. Martineau
Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease (COPD), yet a comprehensive analysis of environmental and genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration in patients with this condition is lacking. We conducted a multi-centre cross-sectional study in 278 COPD patients aged 41–92 years in London, UK. Details of potential environmental determinants of vitamin D status and COPD symptom control and severity were collected by questionnaire, and blood samples were taken for analysis of serum 25(OH)D concentration and DNA extraction. All participants performed spirometry and underwent measurement of weight and height. Quadriceps muscle strength (QS) was measured in 134 participants, and sputum induction with enumeration of lower airway eosinophil and neutrophil counts was performed for 44 participants. Thirty-seven single nucleotide polymorphisms (SNP) in 11 genes in the vitamin D pathway (DBP, DHCR7, CYP2R1, CYP27B1, CYP24A1, CYP27A1, CYP3A4, LRP2, CUBN, RXRA, and VDR) were typed using Taqman allelic discrimination assays. Linear regression was used to identify environmental and genetic factors independently associated with serum 25(OH)D concentration and to determine whether vitamin D status or genetic factors independently associated with % predicted forced expiratory volume in one second (FEV1), % predicted forced vital capacity (FVC), the ratio of FEV1 to FVC (FEV1:FVC), daily inhaled corticosteroid (ICS) dose, respiratory quality of life (QoL), QS, and the percentage of eosinophils and neutrophils in induced sputum. Mean serum 25(OH)D concentration was 45.4 nmol/L (SD 25.3); 171/278 (61.5%) participants were vitamin D deficient (serum 25[OH]D concentration <50nmol/L). Lower vitamin D status was independently associated with higher body mass index (P=0.001), lower socio-economic position (P=0.037), lack of vitamin D supplement consumption (P<0.001), sampling in Winter or Spring (P for trend=0.006) and lack of a recent sunny holiday (P=0.002). Vitamin D deficiency associated with reduced % predicted FEV1 (P for trend=0.060) and % predicted FVC (P for trend=0.003), but it did not associate with FEV1:FVC, ICS dose, QoL, QS, or the percentage of eosinophils or neutrophils in induced sputum. After correction for multiple comparisons testing, genetic variation in the vitamin D pathway was not found to associate with serum 25(OH)D concentration or clinical correlates of COPD severity. Vitamin D deficiency was common in this group of COPD patients in the UK, and it associated independently with reduced % predicted FEV1 and FVC. However, genetic variation in the vitamin D pathway was not associated with vitamin D status or severity of COPD.



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Vitamin D metabolite concentrations in umbilical cord blood serum and associations with clinical characteristics in a large prospective mother-infant cohort in Ireland

Publication date: March 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 167
Author(s): Mairead Kiely, Sinead M. O'Donovan, Louise C. Kenny, Jonathan O'B. Hourihane, Alan D. Irvine, Deirdre M. Murray
Vitamin D deficiency is widespread among mothers and neonates and quality clinical and analytical data are lacking. We used a CDC-accredited LC–MS/MS method to analyze vitamin D metabolites in cord sera from 1050 maternal-infant dyads in the prospective SCOPE Ireland Pregnancy and BASELINE Birth cohort studies, based in Cork, Ireland. The mean±SD total 25(OH)D was 34.9±18.1nmol/L; 35% of cords (50% during winter) had 25(OH)D <25nmol/L, 46% were <30nmol/L and 80% were <50nmol/L. In this predominantly white cohort, the main predictor of cord 25(OH)D [adj. mean difference in nmol/L (95% CI)] was summer delivery [19.2 (17.4, 20.9), P<0.0001]. Maternal smoking during pregnancy (9% prevalence) was negatively associated (P<0.002) with cord 25(OH)D [−4.83 (−7.9, −1.5) nmol/L]. There were no associations between cord 25(OH)D and birth weight or any anthropometric measures at birth. Despite the high prevalence of vitamin D deficiency at birth, there were no documented musculoskeletal complications during infancy, which was likely due to widespread supplementation with vitamin D. The mean±SD concentration of 3-epi-25(OH)D3, detectable in 99.4% of cord samples, was 3.3±1.9nmol/L. The proportion of 25(OH)D as 3-epi-25(OH)D3 was 11.2%. Cord 3-epi-25(OH)D3 concentrations were positively predicted by cord 25(OH)D3 [0.101 (0.099, 0.103) nmol/L, P<0.0001] and negatively by gestational age [−0.104 (−0.131, −0.076) nmol/L, P<0.0001] and maternal age [−0.010 (−0.019, −0.001) nmol/L, P<0.05]. 25(OH)D2 was detected in 98% of cord sera (mean±SD; 2.2±1.9nmol/L) despite low antenatal consumption of vitamin D2 supplements. In conclusion, these first CDC-accredited data of vitamin D metabolites in umbilical cord blood emphasise the high risk of very low vitamin D status in infants born to un-supplemented mothers. Experimental data to define maternal vitamin D requirements for prevention of neonatal deficiency at high latitude are required.



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Potential role for the VDR agonist elocalcitol in metabolic control: Evidences in human skeletal muscle cells

Publication date: March 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 167
Author(s): Cristina Antinozzi, Clarissa Corinaldesi, Carla Giordano, Annalinda Pisano, Bruna Cerbelli, Silvia Migliaccio, Luigi Di Luigi, Katia Stefanantoni, Gabriella Barbara Vannelli, Salvatore Minisola, Guido Valesini, Valeria Riccieri, Andrea Lenzi, Clara Crescioli
Vitamin D plays a pivotal role to maintain skeletal muscle integrity and health. Vitamin D deficiency characterizes inflammatory myopathy (IM) and diabetes, often overlapping diseases involving skeletal muscle damage. Vitamin D receptor (VDR) agonists likely exert beneficial effects in both IM and metabolic disturbances. We aim to evaluate in vitro the effect of elocalcitol, a non-hypercalcemic VDR agonist, on the biomolecular metabolic machinery of human skeletal muscle cells (Hfsmc), vs. insulin (I). We analyzed GLUT4, Flotillin-1, Caveolin-3 and Caveolin-1 cell expression/localization; mTOR, AKT, ERK and 4E-BP1 phosphorylation; IL-6 myokine release; VDR expression. We investigated in vivo vitamin D status in IM subjects, evaluating VDR muscular expression and serum vitamin D with metabolism-related parameters, as glycemia, triglycerides, cholesterol, resistin and adiponectin. In Hfsmc, elocalcitol exerted an I-like effect, promoting GLUT4 re-localization in Flotillin-1, Caveolin-3 and Caveolin-1 positive sites and mTOR, AKT, ERK, 4E-BP1 activation; it enhanced IL-6 myokine release. IM subjects, all normoglycemic, showed VDR/vitamin D deficiency that, together with high lipidemic and resistin profile, possibly increases the risk to develop metabolic diseases. VDR agonists as elocalcitol may be therapeutic tools for skeletal muscle integrity/function maintenance, an indispensable condition for health homeostasis.



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The role of vitamin D and VDR in carcinogenesis: Through epidemiology and basic sciences

Publication date: March 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 167
Author(s): Borja Bandera Merchan, Sonsoles Morcillo, Gracia Martin-Nuñez, Francisco José Tinahones, Manuel Macías-González
In the last two decades vitamin D (VD) research has demonstrated new extraskeletal actions of this pre-hormone, suggesting a protective role of this secosteroid in the onset, progression and prognosis of several chronic noncommunicable diseases, such as cardiovascular disease, diabetes mellitus or cancer.Regarding carcinogenesis, both preclinical and epidemiological evidence available show oncoprotective actions of VD and its receptor, the VDR. However, in late neoplastic stages the VD system (VDS) seems to be less functional, which appears to be due to an epigenetic silencing of the system. In preclinical experimental studies, VD presents oncoprotective actions through modulation of inflammation, cell proliferation, cell differentiation, angiogenesis, invasive and metastatic potential, apoptosis, miRNA expression regulation and modulation of the Hedgehog signalling pathway. Moreover, epidemiological evidence points towards an oncoprotective role of vitamin D and VDR in colorectal cancer. This association is more controversial with breast, ovarian and prostate cancers, although with a few adverse effects. Nonetheless, we should consider other factors to determine the benefit of increased serum concentration of VD. Much of the epidemiological evidence is still inconclusive, and we will have to wait for new, better-designed ongoing RCTs and their results to discern the real effect of vitamin D in cancer risk reduction and therapy.The objective of this literature review is to offer an up-to-date analysis of the role of the VD and VDR, in the onset, progression and prognosis of all types of cancer. We further discuss the available literature and suggest new hypotheses and future challenges in the field of VD research.



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Effect of sex-hormone levels, sex, body mass index and other host factors on human craniofacial bone regeneration with bioactive tricalcium phosphate grafts

Publication date: April 2017
Source:Biomaterials, Volume 123
Author(s): Christine Knabe, Aynur Mele, Peter Herbert Kann, Barbara Peleska, Doaa Adel-Khattab, Harald Renz, Alexander Reuss, Marc Bohner, Michael Stiller
Little is known regarding the associations between sex-hormone levels, sex, body mass index (BMI), age, other host factors and biomaterial stimulated bone regeneration in the human craniofacial skeleton. The aim of this study was to elucidate the associations between these factors and bone formation after sinus floor augmentation procedures (SFA) utilizing a bioactive tricalcium phosphate (TCP) bone grafting material. We conducted a prospective study in a human population in which 60 male and 60 female participants underwent SFA and dental implant placement using a staged approach. BMI as well as levels of serum estradiol (E2), total testosterone (TT), and the free androgen index (FAI) were measured by radioimmunoassay and electrochemoluminescent-immunoassay. At implant placement, 6 months after SFA, bone biopsy specimens were harvested for hard tissue histology, the amount of bone formation was evaluated by histomorphometry and immunohistochemical analysis of osteogenic marker expression. The Wilcoxon rank-sum U test, Spearman correlations and linear regression analysis were used to explore the association between bone formation and BMI, hormonal and other host factors. BMI and log E2 were significantly positively associated with bone formation in male individuals (p < 0.05). Histomorphometry revealed trends toward greater bone formation and osteogenic marker expression with non-smokers compared to smokers. In male patients, higher E2 levels and higher BMI enhanced TCP stimulated craniofacial i.e. intramembranous bone repair.



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Rejuvenation Research , Vol. 0, No. 0.

Rejuvenation Research , Vol. 0, No. 0.


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Effects of Daily Physical Activity Level on Manual Wheelchair Propulsion Technique in Full-Time Manual Wheelchair Users during Steady State Treadmill Propulsion

Publication date: Available online 2 February 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Jennifer Dysterheft, Ian Rice, Yvonne Learmonth, Dominque Kinnett-Hopkins, Robert Motl
ObjectiveTo examine whether differences in propulsion technique as a function of intra-individual variability occur as a result of shoulder pain and physical activity (PA) level in full time manual wheelchair users (MWU).DesignObservational study.SettingResearch laboratory.ParticipantsA sample of 14 MWU completed the study. Participants were 18-64 years old, used a wheelchair for > 80% ambulation, and free of any condition that could be worsened by PA.InterventionsN/AMain Outcome MeasuresPA level was measured using the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD) and shoulder pain was measured using the Wheelchair Users Shoulder Pain Index survey (WUSPI). Mean and intra-individual variability propulsion metrics were measured for propulsion analysis.ResultsWUSPI scores indicated participants experienced low levels of shoulder pain. Results of the Spearman's rank-order correlation revealed PASIPD scores were significantly related to mean Contact Angle (rs=-0.57) and Stroke Frequency (rs=0.60), and coefficient of variability (CV) of Peak Force (rs=0.63), Peak Torque (rs= 0.59), Contact Angle (rs= 0.73), and Stroke Frequency (rs=0.60). WUSPI scores were significantly correlated to only mean Peak Force (p=0.02). No significant correlations were observed between PASIPD, WUSPI, and body mass index (BMI) scores.ConclusionsDifferences in propulsion technique were observed based on PA levels. Participants with higher PASIPD scores used a more injurious stroke technique when propelling at faster speeds. This may indicate active individuals who use injurious stroke, may be at higher risk of injury. A strong relationship was found between peak propulsion forces and shoulder pain. Rehabilitation professionals should emphasize the use of a protective stroke technique in both inactive and active MWU during exercise and faster propulsion.



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How many blinks are necessary for a reliable startle response? A test using the NPU-threat task

Publication date: Available online 2 February 2017
Source:International Journal of Psychophysiology
Author(s): Lynne Lieberman, Elizabeth S. Stevens, Carter J. Funkhouser, Anna Weinberg, Casey Sarapas, Ashley A. Huggins, Stewart A. Shankman
Emotion-modulated startle is a frequently used method in affective science. Although there is a growing literature on the reliability of this measure, it is presently unclear how many startle responses are necessary to obtain a reliable signal. The present study therefore evaluated the reliability of startle responding as a function of number of startle responses (NoS) during a widely used threat-of-shock paradigm, the NPU-threat task, in a clinical (N=205) and non-clinical (N=92) sample. In the clinical sample, internal consistency was also examined independently for healthy controls vs. those with panic disorder and/or major depression and retest reliability was assessed as a function of NoS. Although results varied somewhat by diagnosis and for retest reliability, the overall pattern of results suggested that six startle responses per condition were necessary to obtain acceptable reliability in clinical and non-clinical samples during this threat-of-shock paradigm in the present study.



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Radical polymerization of styrene in presence of poly(2,2,6,6-tetramethylpiperidine-N-oxyl-4-yl methacrylate) - formation of polymer brushes

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Felix Lederle, Eike G. Hübner
The radical polymerization of styrene in presence of poly(2,2,6,6-tetramethylpiperidine-N-oxyl-4-yl methacrylate) (PTMA) is described. PTMA is a well-known polymer for organic radical batteries. Tetramethylpiperidine-N-oxyl (TEMPO) is the common reagent for nitroxide-mediated controlled radical polymerization (NMP). PTMA, as macromolecular counterpart of TEMPO, was found to lead to a partly controlled polymerization process. During the polymerization, large amounts of the graft copolymer PTMA-g-PS are formed via the grafting-to approach. No indication for insoluble gel formation at high conversion rates is observed. The isolated graft copolymers were characterized by dynamic light scattering and revealed hydrodynamic radii in the range of 30–50 nm. The polymerization in presence of PTMA offers a convenient way to the multigram-scale synthesis of bottle-brush polymers.

Graphical abstract

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Synthesis and tailoring the degradation of multi-responsive amphiphilic conetwork gels and hydrogels of poly(β-amino ester) and poly(amido amine)

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Bhingaradiya Nutan, Arvind K.Singh Chandel, Dixit V. Bhalani, Suresh K. Jewrajka
Poly(β-amino esters) and poly(amido amine) are important class of biodegradable polymers useful for biomedical applications. Synthesis of amphiphilic conetwork (APCN) gels and hydrogels of these polymers with controlled composition, degradation, and release behaviour is desirable. Herein, we report a strategy for the synthesis of multi-responsive APCN gels of poly(caprolactone) (PCL) and poly(β-amino esters) or poly(amido amine) with tunable degradability. The APCN gels were synthesized by the sequential nucleophilic substitution reaction between activated halide terminated PCL and poly(ethylene glycol) (PEG)-based poly(β-amino ester) or poly(bis-acrylamide)-based poly(amido amine) prepolymer containing amine moieties in the backbone or side chain. A model APCN gel obtained by reacting halide terminated PCL and mixture of poly(β-amino esters) and di-thiolated poly(amido amine) exhibited triggered degradation and release of drugs in acidic, basic, enzymatic, and slightly reducing environments whereas showed low level of release under normal physiological condition. The properties of this APCN gel were compared with a model hydrogel consisting of PEG and poly(amido amine). These types of gels are hemocompatible and useful for the controlled release and tissue engineering applications.

Graphical abstract

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Nanoporous triptycene based network polyamides (TBPs) for selective CO2 uptake

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Ranajit Bera, Snehasish Mondal, Neeladri Das
In contemporary research, there has been a surge in the efforts to design novel porous materials as adsorbents for CO2 capture. Polyamides are a class of robust polymers that are easy to synthesize from readily available starting materials. These have CO2-philic amide functional groups and hence are being considered as materials for CO2 adsorption and storage. Herein, we report facile and efficient synthesis as well as characterization of a series of triptycene based polyamide networks (TBPs) that are thermally stable and they exhibit reasonably high surface area (SABET upto 80 m² g^-1). The CO2 uptake and CO2/N2 selectivity of these TBPs are noteworthy and these data are comparable to other literature reported polyamides known to demonstrate either highest uptake of carbon dioxide or highest CO2/N2 selectivity. In view of the ease of synthesis, thermal stability, porosity/surface area and CO2 selectivity, TBPs reported herein may be considered as promising adsorbent materials for CO2 contaminated gas purification processes.

Graphical abstract

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Averrhoa bilimbi Linn.: A review of its ethnomedicinal uses, phytochemistry, and pharmacology

Alhassan Muhammad Alhassan, Qamar Uddin Ahmed

Journal of Pharmacy And Bioallied Sciences 2016 8(4):265-271

Averrhoa bilimbi Linn. is principally cultivated for medicinal purposes in many tropical and subtropical countries of the world. Literature survey about this plant shows that A. bilimbi is mainly used as a folk medicine in the treatment of diabetes mellitus, hypertension, and as an antimicrobial agent. The prime objective of this review is to accumulate and organize literature based on traditional claims and correlate those with current findings on the use of A. bilimbi in the management of different ailments. Through interpreting already published scientific manuscripts (1995 through 2015) retrieved from the different scientific search engines, namely Medline, PubMed, EMBASE, and Science Direct databases, published articles and reports covering traditional and scientific literature related to A. bilimbi's potential role against various ailments have been thoroughly evaluated, interpreted, and discussed. Several pharmacological studies have demonstrated the ability of this plant to act as antidiabetic, antihypertensive, thrombolytic, antimicrobial, antioxidant, hepatoprotective, and hypolipidemic agent. A. bilimbi holds great value in the complementary and alternative medicine as evidenced by the substantial amount of research on it. Therefore, we aimed to compile an up-to-date and comprehensive review of A. bilimbi that covers its traditional and folk medicine uses, phytochemistry, and pharmacology. Hence, this paper presents an up-to-date and comprehensive review of the ethnomedicinal uses, different chemical constituents, and pharmacological activities of A. bilimbi. So far, the biologically active agents have not been isolated from this plant and this can be a good scientific study for the future antidiabetic, antihypertensive, and antimicrobial implications. Hence, this review targets at emphasizing the diverse traditional claims and pharmacological activities of A. bilimbi with respect to carrying out more scientific studies to isolate active principles through advanced technology.

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In vitro evaluation of bioremediation capacity of a commercial probiotic, Bacillus coagulans, for chromium (VI) and lead (II) toxicity

Pranoti Belapurkar, Pragya Goyal, Anand Kar

Journal of Pharmacy And Bioallied Sciences 2016 8(4):272-276

Introduction: The bioaccumulation of heavy metals including chromium (VI) (Cr (VI)) and lead (II) (Pb (II)) causes fatal toxicity in humans. Some naturally occurring bacterial genera such as Bacillus and Pseudomonas help in bioremediation of these heavy metals and some of the species of Bacillus are proven probiotics. However, no study has been conducted on Bacillus coagulans, which is a proven probiotic species of genus Bacillus. Objectives: The primary objective of the present study was to assess the potential of a proven probiotic, B. coagulans, marketed as "Sporlac-DS," to survive in the presence of Cr (VI) and Pb (II) and its ability to reduce its concentration in vitro. Materials and Methods: The Minimum inhibitory concentration (MIC) of the organism for Cr (VI) and Pb (II) was determined followed by its biochemical and morphological characterization. Its antibiotic sensitivity and probiotic efficacy were assessed. Further, its bioremediation capacity was observed in vitro by determining the residual Cr (VI) and Pb (II) concentration after 72 h. Results: B. coagulans could tolerate up to 512 ppm concentration of Cr (VI) and had an MIC of 128 ppm for Pb (II). After 72 h, the organism reduced 32 ppm Cr (VI) and 64 ppm Pb (II) by 93% and 89%, respectively. When B. coagulans was studied before and after growing on Cr (VI) and Pb (II) for 24 h, an increase was seen in sensitivity toward the tested antibiotics whereas no change was observed in morphological and biochemical characters. It also showed no change in their bile and acid tolerance, indicating that it retains its probiotic efficacy. Conclusion: The tested probiotic B. coagulans may have a potential role in bioremediation of Cr (VI) and Pb (II), in vivo.

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Prescription patterns and appropriateness of antibiotics in the management of cough/cold and diarrhea in a rural tertiary care teaching hospital

Akram Ahmad, Muhammad Umair Khan, Sadiqa Malik, Guru Prasad Mohanta, S Parimalakrishnan, Isha Patel, Sameer Dhingra

Journal of Pharmacy And Bioallied Sciences 2016 8(4):335-340

Background: Acute gastroenteritis and respiratory illnesses are the major causes of morbidity and mortality in children under 5 years of age. The objective of this study was to evaluate the prescription pattern of antibiotic utilization during the treatment of cough/cold and/or diarrhea in pediatric patients. Methods: A descriptive, cross-sectional study was conducted for 6 months in pediatric units of a tertiary care hospital in South India. Children under 5 years of age presenting with illness related to diarrhea and/or cough/cold were included in this study. Data were collected by reviewing patient files and then assessed for its appropriateness against the criteria developed in view of the Medication Appropriateness Index and Guidelines of the Indian Academy of Pediatrics. The results were expressed in frequencies and percentages. Chi-square test was used to analyze the data. A P < 0.05 was considered statistically significant. Results: A total of 303 patients were studied during the study period. The mean age of the patients was 3.5 ± 0.6 years. The majority of children were admitted mainly due to chief complaint of fever (63%) and cough and cold (56.4%). The appropriateness of antibiotic prescriptions was higher in bloody and watery diarrhea (83.3% and 82.6%; P< 0.05). Cephalosporins (46.2%) and penicillins (39.9%) were the most commonly prescribed antibiotics, though the generic prescriptions of these drugs were the lowest (13.5% and 10%, respectively). The seniority of prescriber was significantly associated with the appropriateness of prescriptions (P < 0.05). Antibiotics prescription was higher in cold/cough and diarrhea (93.5%) in comparison to cough/cold (85%) or diarrhea (75%) alone. Conclusions: The study observed high rates of antibiotic utilization in Chidambaram during the treatment of cough/cold and/or diarrhea in pediatric patients. The findings highlight the need for combined interventions using education and expert counseling, targeted to the clinical conditions and classes of antibiotic for which inappropriate usage is most common.

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Thymol, a monoterpene, inhibits aldose reductase and high-glucose-induced cataract on isolated goat lens

Divya M Kanchan, Smita S Kale, Gauresh S Somani, Aakruti A Kaikini, Sadhana Sathaye

Journal of Pharmacy And Bioallied Sciences 2016 8(4):277-283

Background: Overactivation of aldose reductase (AR) enzyme has been implicated in the development of various diabetic complications. In the present study, the inhibitory effect of thymol was investigated on AR enzyme and its anti-cataract activity was also examined on isolated goat lens. Materials and Methods: Various concentrations of thymol were incubated with AR enzyme prepared from isolated goat lens. Molecular docking studies were carried out using Schrodinger software to verify the binding of thymol with AR as well as to understand their binding pattern. Further, thymol was evaluated for its anti-cataract activity in high-glucose-induced cataract in isolated goat lens in vitro. Quercetin was maintained as standard (positive control) throughout the study. Results: Thymol showed potent inhibitory activity against goat lens AR enzyme with an IC50value of 0.65 μg/ml. Docking studies revealed that thymol binds with AR in similar binding pattern as that of quercetin. The high–glucose-induced cataract in isolated goat lens was also improved by thymol treatment. Thymol was also able to significantly (P < 0.001) reduce the oxidative stress associated with cataract. Conclusion: The results suggest that thymol may be a potential therapeutic approach in the prevention of diabetic complications through its AR inhibitory and antioxidant activities.

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Synthesis of some novel pyrazolo[3,4-d] pyrimidin-4(5H)-one derivatives as potential antimicrobial agent

Dipen K Sureja, Sandip P Dholakia, Kantilal R Vadalia

Journal of Pharmacy And Bioallied Sciences 2016 8(4):321-326

Objectives: The aim of the present work was to synthesize a novel series of pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives and evaluate their in vitro antimicrobial activity. Methods: Cyclization of an ortho-amino ester of 1-(2,4-dinitrophenyl)pyrazole with various aliphatic/aromatic nitriles under different reaction conditions such as conventional and microwave assisted synthesis, provided pyrazolo[3,4-d] pyrimidin-4(5H)-one derivatives. All the synthesized compounds were evaluated in vitro for their antimicrobial activity against selected bacteria and fungi by agar well diffusion method. Results: All newly synthesized compounds were characterized using spectral and elemental analysis. Compounds 2e, 2f, and 2g showed significant antimicrobial activity as compared to standard drugs used. Conclusion: The newly synthesized compounds could be useful templates for the design and optimization of more active analogs as a possible antimicrobial agent.

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A qualitative insight on complementary and alternative medicines used by hypertensive patients

Inas Rifaat Ibrahim, Mohamed Azmi Hassali, Fahad Saleem, Haydar F Al Tukmagi

Journal of Pharmacy And Bioallied Sciences 2016 8(4):284-288

Background: The self-treatment with complementary and alternative medicines (CAMs) in chronic diseases is portraying an expanding trend worldwide. Yet, little is known concerning patients' motives to use CAM in the control of blood pressure. Objective: This study aims to explore the self-use of CAM in the management of hypertension and explore patients' attitudes, perceived benefits, and disclosure to the physician. Materials and Methods: A qualitative technique was adopted and face-to-face interviews, using a validated interview guide, were carried out among twenty hypertensive patients. A purposive sampling method was used to recruit patients at Al-Karama Teaching Hospital in Baghdad; the capital of Iraq; from January to April 2015. All the interviews were audio-recorded, then transcribed verbatim and examined for thematic relationships. Results: Three major themes were identified through thematic content analysis of the interviews. These encompassed patients' understanding of CAM; experience and perceived benefits; and communication with the doctors. The use of CAM was prevalent among the majority of the respondents. The most commonly used therapies were biological-based practices (herbal remedies, special diet, vitamins, and dietary supplements); traditional therapies (Al-Hijama or cupping); and to a less extent of manipulative body-based therapies (reflexology). Factors influencing the use of CAM were traditions, social relationships, religious beliefs, low-cost therapy, and safety of natural products. Conclusion: The use of CAM was common as a practice of self-treatment among hypertensive patients in Iraq. This was underpinned by the cultural effects, social relationships, religious beliefs, and the perception that natural products are effective and safe. Understanding patients' usage of CAM is of great importance as long as patient's safety and interaction with the standard prescribed treatment are major concerns.

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Menopausal symptoms and obesity: Is there a relationship?

Maria Fernanda Naufel, Cristina Frange, Sérgio Tufik, Helena Hachul

Journal of Pharmacy And Bioallied Sciences 2016 8(4):346-347



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Risk factors for developing drug-related problems in patients with cardiovascular diseases attending Gondar University Hospital, Ethiopia

Ousman Abubeker Abdela, Akshaya Srikanth Bhagavathula, Henok Getachew, Yohannes Kelifa

Journal of Pharmacy And Bioallied Sciences 2016 8(4):289-295

Background: Cardiovascular diseases (CVDs) are often accompanied with comoribidities and complications leading to taking multiple drugs and thus are more liable to be exposed to drug-related problems (DRPs). DRPs can occur at any stages of medication process from prescription to follow-up treatment. However, a few studies have assessed the specific risk factors for occurrence of at least one potential DRP per patient with CVDs in sub-Saharan African region. Aim: We aim to assess the risk factors for developing potential DRPs in patients with CVDs attending Gondar University Referral Hospital (GUH). Methodology: This was a cross-sectional study. A structured systematic data review was designed focusing on patients with CVDs (both out and inpatients) with age >18 years of both genders attending GUH from April to June 2015. All DRPs were assessed using drugs.com and Medscape. The causes of DRPs were classified using Pharmaceutical Care Network Europe version 6.2. Risk factors that could cause DRPs were assessed using binary logistic regression showing odds ratio with 95% confidential interval. Statistical significance was set at P< 0.05. Results: A total of 227 patients with CVDs were reviewed with a mean age of 52.0 ± 1.7 years. Majority were females (143, 63%), outpatients (133, 58.6%), and diagnosed with heart failure (71, 31.3%). Diuretics (199, 29.5%) were the most commonly prescribed drugs. A total of 265 DRPs were identified, 63.4% of patients have at least one DRP (1.17 ± 1.1). The most common DRPs were found to be an inappropriate selection of drug (36.1%) and dose (24.8%). The most identified risk factors causing DRPs were: Need of additional drug therapy and lack of therapeutic monitoring. Conclusion: The most identified risk factors for developing DRPs were the need of additional drug therapy and lack of therapeutic monitoring. There is a need for clinical pharmacist interventions to monitor and prevent the risk of developing DRPs and contribute to improve the clinical outcome in patients with CVDs.

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Assessment of cost of illness for diabetic patients in South Indian tertiary care hospital

Leelavathi D Acharya, NR Rau, N Udupa, M Surulivel Rajan, K Vijayanarayana

Journal of Pharmacy And Bioallied Sciences 2016 8(4):314-320

Background: The impact of diabetes on health-care expenditures has been increasingly recognized. To formulate an effective health planning and resource allocation, it is important to determine economic burden. Objective: The objective of this study is to assess the cost of illness (COI) for diabetic inpatients with or without complications. Methodology: The study was conducted in the medicine wards of tertiary care hospital after ethical approval by the Institutional Ethical Committee. A total of 116 each diabetic with or without complications were selected and relevant data were collected using COI questionnaire and data were analyzed using SPSS version 20. Mann–Whitney U test is used to assess the statistical significant difference in the cost of treatment of diabetes alone and with complications'. P ≤ 0.05 was considered statistically significant. Results: Total COI includes the cost of treatment, investigation, consultation fee, intervention cost, transportation, days lost due to work, and hospitalization. The median of total COI for diabetic care without any complication was Rs. 22,456.97/- per patient per annum and with complication was Rs. 30,634.45/-. Patients on dialysis had to spend 7.3 times higher, and patients with cardiac intervention had to spend 7.4 times higher than diabetic patients without any complication. Conclusion: Treatment costs were many times higher in patients with complications and with cardiac and renal interventions. Complications in diabetic patients will increase the economic burden to family and also to the society.

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Therapeutic potential of alpha-ketoglutarate against acetaminophen-induced hepatotoxicity in rats

Lalita Mehra, Yasha Hasija, Gaurav Mittal

Journal of Pharmacy And Bioallied Sciences 2016 8(4):296-299

Objective: Alpha-ketoglutarate (α-KG) is a cellular intermediary metabolite of Krebs cycle, involved in energy metabolism, amino acid synthesis, and nitrogen transport. It is available over-the-counter and marketed as a nutritional supplement. There is a growing body of evidence to suggest that dietary α-KG has the potential to maintain cellular redox status and thus can protect various oxidative stress induced disease states. The aim of the present study was to investigate the hepatoprotective role of α-KG in acetaminophen (APAP) induced toxicity in rats. Materials and Methods: Animals were divided into three groups of six animals each. Group I (Vehicle control): Normal Saline, Group II (APAP): A single intraperitoneal injection of 0.6 g/kg, Group III (APAP + α-KG): APAP as in Group II with α-KG treatment at a dose of 2 g/kg, orally for 5 days. Then the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) with oxidative stress markers including malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and histopathology were analyzed. Results: The results indicate that APAP caused significant elevations in ALT, AST, ALP, and MDA levels, while GSH, SOD, and CAT were significantly depleted while co-administration of α-KG showed a significant (P < 0.05) reduction in the severity of these damages. Histologically, the liver showed inflammation and necrosis after APAP treatment, which were significantly restored with co-administration of α-KG. Conclusion: These results indicate the possible therapeutic potential of α-KG in protecting liver damage by APAP in rats.

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1H NMR-based serum metabolomics reveals erythromycin-induced liver toxicity in albino Wistar rats

Atul Rawat, Durgesh Dubey, Anupam Guleria, Umesh Kumar, Amit K Keshari, Swati Chaturvedi, Anand Prakash, Sudipta Saha, Dinesh Kumar

Journal of Pharmacy And Bioallied Sciences 2016 8(4):327-334

Introduction: Erythromycin (ERY) is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. Objective: To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using 1H NMR based serum metabolomics. Experimental: Fourteen male rats were randomly divided into two groups (n = 7 in each group): control and ERY treated. After 28 days of intervention, the metabolic profiles of sera obtained from ERY and control groups were analyzed using high-resolution 1D 1H CPMG and diffusion-edited nuclear magnetic resonance (NMR) spectra. The histopathological and SEM examinations were employed to evaluate the liver toxicity in ERY treated group. Results: The serum metabolic profiles of control and ERY treated rats were compared using multivariate statistical analysis and the metabolic patterns specific to ERY-induced liver toxicity were established. The toxic response of ERY was characterized with: (a) increased serum levels of Glucose, glutamine, dimethylamine, malonate, choline, phosphocholine and phospholipids and (b) decreased levels of isoleucine, leucine, valine, alanine, glutamate, citrate, glycerol, lactate, threonine, circulating lipoproteins, N-acetyl glycoproteins, and poly-unsaturated lipids. These metabolic alterations were found to be associated with (a) decreased TCA cycle activity and enhanced fatty acid oxidation, (b) dysfunction of lipid and amino acid metabolism and (c) oxidative stress. Conclusion and Recommendations: Erythromycin is often used to produce experimental models of liver toxicity; therefore, the established NMR-based metabolic patterns will form the basis for future studies aiming to evaluate the efficacy of anti-hepatotoxic agents or the hepatotoxicity of new drug-formulations.

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Optimization, characterization, and efficacy evaluation of 2% chitosan scaffold for tissue engineering and wound healing

Priyanka Chhabra, Priyanka Tyagi, Aseem Bhatnagar, Gaurav Mittal, Amit Kumar

Journal of Pharmacy And Bioallied Sciences 2016 8(4):300-308

Objective: To develop a chitosan-based scaffold and carry out a complete comprehensive study encompassing optimization of exact chitosan strength, product characterization, toxicity evaluation, in vitro validation in cell culture experiments, and finally in vivo efficacy in animal excision wound model. Materials and Methods: Developed chitosan scaffolds (CSs) were optimized for tissue engineering and wound healing efficacy by means of microstructure, toxicity, and biocompatibility evaluation. Results: Scanning electron microscope (SEM) studies revealed that porosity of CS decreased with increase in chitosan concentration. Chemical stability and integrity of scaffolds were confirmed by Fourier transform infrared studies. Highest swelling percentage (SP) of 500% was observed in 2%, while lowest (200%) was observed in 1% CS. Reabsorption and noncytotoxic property of optimized scaffold were established by enzymatic degradation and MTT assay. Enzymatic degradation suggested 20–45% of weight loss (WL) within 14 days of incubation. Cytotoxicity analysis showed that scaffolds were noncytotoxic against normal human dermal fibroblast human dermal fibroblast cell lines. Significant cellular adherence over the scaffold surface with normal cellular morphology was confirmed using SEM analysis. In vivo efficacy evaluation was carried out by means of reduction in wound size on Sprague-Dawley rats. Sprague-Dawley rats treated with optimized scaffold showed ~ 100% wound healing in comparison to ~80% healing in betadine-treated animals within 14 days. Histological examination depicted advance re-epithelization with better organization of collagen bundle in wound area treated with 2% CS in comparison to conventional treatment or no treatment. Conclusion: This study, thus, reveals that 2% CSs were found to have a great potential in wound healing.

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Pharmacological evaluation of Apium leptophyllum (Pers.) on bronchial asthma

Himanshu Bhusan Sahoo, Rakesh Sagar, Ganesh Patro, Madhulita Panda, Saroj Kumar Sahoo, D Priyadarshini

Journal of Pharmacy And Bioallied Sciences 2016 8(4):341-345

Objective: The present study was to investigate the antiasthmatic potential from the flavonoid fraction of Apium leptophyllum fruit (FFALF) to validate its traditional claim. Materials and Methods: The antiasthmatic activity of FFALF was evaluated by histamine or acetylcholine-induced bronchospasm model in guinea pigs, compound 48/80 induced mast cell degranulation in albino rats and histamine-induced tracheal contraction in guinea pig. The preconvulsion dyspnea time at 0th and 7th day at the dose of 100 and 200 mg/kg in guinea pig's bronchospasm model, the percentage of granulated and degranulated mast cell at the dose of 500, 750, and 1000 μg/ml in rats and tracheal contraction at the dose of 500, 750, and 1000 μg/ml in guinea pig were measured and compared with respective control groups. Results: The treatments of FFALF were significantly (P < 0.001) decreased the histamine/acetylcholine-induced bronchospasm, mast cell degranulation, and histamine-induced tracheal contraction as compared to inducer group. In addition, FFALF showed dose-dependent antiasthmatic activity in all the animals. Conclusion: Hence, this study suggested that the FFALF showed antiasthmatic activity probably by membrane stabilizing property as well as suppressing antibody production and inhibiting of antigen induced by histamine and acetylcholine.

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Patterns of prescription drugs use among pregnant women at Sultan Qaboos University Hospital and Sultan Qaboos University Hospital Family and Community Medicine Clinic, Oman

JZ Al-Hamimi, KA Al Balushi

Journal of Pharmacy And Bioallied Sciences 2016 8(4):309-313

Objective: This study evaluates the patterns of prescription drugs use among women attending antenatal clinic at Sultan Qaboos University Hospital (SQUH) and SQUH Family and Community Medicine clinic (FAMCO), Oman. Methods: The study was a descriptive retrospective cross-sectional study on pregnant women who attended the antenatal clinic at SQUH and FAMCO from February to April 2014 and received a prescription containing at least one drug. Patients' information was extracted from SQUH electronic records. Results: A total of 105 pregnant women were included in the study. Among the recruited pregnant women, 35 (33.3%) had at least one chronic disease. The average number of drugs prescribed per patient per prescription during the period of pregnancy was 2.33 ± 1.43. Vitamins and minerals were the most frequently prescribed class of drugs (30.60%) followed by analgesics (11.19%) and antidiabetic drugs (10.13%). According to the Food and Drug Administration risk classification, most of the prescribed drugs were from category B (30.0%) and C (27.14%). No drug was prescribed from category X. There was a significant decrease in prescribing category A drugs over the three trimesters (20.7%, 12.7%, and 9.3%, respectively) (P < 0.047). Conclusion: The study gives an overview of the extent of drug prescription during pregnancy and increases the awareness of health-care providers and women about the potential risks of drug use during pregnancy.

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Electronic cigarette experimentation in the Malaysian city of Kuantan: Was there an association with the smoking status?

Konstantinos E Farsalinos, Jacques Le Houezec

Journal of Pharmacy And Bioallied Sciences 2016 8(4):347-348



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Purification and function of two analgesic and anti-inflammatory peptides from coelomic fluid of the earthworm, Eisenia foetida

Publication date: Available online 2 February 2017
Source:Peptides
Author(s): Chunlong Li, Mengrou Chen, Xiaojie Li, Meifeng Yang, Ying Wang, Xinwang Yang
The potential application of anti-inflammatory and analgesic compounds in medication and therapeutic care have become of increasing interest. We purified and characterized two novel analgesic and anti-inflammatory peptides, VQ-5 and AQ-5, from the coelomic fluid of the earthworm (Eisenia foetida). Their primary structures were determined as VSSVQ and AMADQ, respectively. Both peptides, especially AQ-5, exhibited analgesic activity in mouse models of persistent neuropathic pain and inflammation. AQ-5 also inhibited tumor necrosis factor alpha and cyclooxygenase-2 production. The mitogen-activated protein kinase signaling pathway, which is involved in analgesic and anti-inflammatory functions, was inhibited by AQ-5. Thus, the analgesic and anti-inflammatory effects of these peptides, especially AQ-5, demonstrated their potential as candidates for the development of novel analgesic medicines.



http://ift.tt/2kndINh

What nasal endoscope adds in septoplasty

Publication date: Available online 2 February 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Zeyad Mohamed Mandour
A study was conducted to assess the advantages of endoscopic septoplasty over the conventional septoplasty.Sixty patients having symptomatic deviated nasal septal were randomly divided into two groups of 30 patients each. One group underwent conventional septoplasty and the other group underwent endoscopic septoplasty. The groups were compared regarding the relief of symptoms after surgery and complications.The symptoms postoperatively and the objective assessment were significantly less in endoscopic septoplasty group.Endoscopic septoplasty is a fast developing concept and gaining popularity as it provides a direct targeted approach to the septal anatomic deformity, allowing a minimally invasive procedure with limit septal mucosal flap dissection and removal of small cartilaginous and/or bony deformity.



http://ift.tt/2jJf431

Diagnosis of Spinal Lesions Using Heuristic and Pharmacokinetic Parameters Measured by Dynamic Contrast-Enhanced MRI

Publication date: Available online 2 February 2017
Source:Academic Radiology
Author(s): Ning Lang, Huishu Yuan, Hon J. Yu, Min-Ying Su
Rationale and ObjectivesThis study aimed to evaluate the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in differentiation of four spinal lesions by using heuristic and pharmacokinetic parameters analyzed from DCE signal intensity time course.Materials and MethodsDCE-MRI of 62 subjects with confirmed myeloma (n = 9), metastatic cancer (n = 22), lymphoma (n = 7), and inflammatory tuberculosis (TB) (n = 24) in the spine were analyzed retrospectively. The region of interest was placed on strongly enhanced tissues. The DCE time course was categorized as the "wash-out," "plateau," or "persistent enhancement" pattern. The maximum enhancement, steepest wash-in enhancement, and wash-out slope using the signal intensity at 67 seconds after contrast injection as reference were measured. The Tofts 2-compartmental pharmacokinetic model was applied to obtain K^trans and kep. Pearson correlation between heuristic and pharmacokinetic parameters was evaluated, and receiver operating characteristic curve analysis was performed for pairwise group differentiation.ResultsThe mean wash-out slope was −22% ± 10% for myeloma, 1% ± 0.4% for metastatic cancer, 3% ± 3% for lymphoma, and 7% ± 10% for TB, and it could significantly distinguish myeloma from metastasis (area under the curve [AUC] = 0.884), lymphoma (AUC = 1.0), and TB (AUC = 1.0) with P = .001, and distinguish metastasis from TB (AUC = 0.741) with P = .005. The kep and wash-out slope were highly correlated (r = 0.92), and they showed a similar diagnostic performance. The K^trans was significantly correlated with the maximum enhancement (r = 0.71) and the steepest wash-in enhancement (r = 0.85), but they had inferior diagnostic performance compared to the wash-out slope.ConclusionsDCE-MRI may provide additional diagnostic information, and a simple wash-out slope had the best diagnostic performance. The heuristic and pharmacokinetic parameters were highly correlated.



http://ift.tt/2knjUVA

Enzymatic and Non-Enzymatic Detoxification of 4-Hydroxynonenal: Methodological Aspects and Biological Consequences

Publication date: Available online 2 February 2017
Source:Free Radical Biology and Medicine
Author(s): Marco Mol, Luca Regazzoni, Alessandra Altomare, Genny Degani, Marina Carini, Giulio Vistoli, Giancarlo Aldini
4-Hydroxynonenal (HNE), an electrophilic end-product deriving from lipid peroxidation, undergoes a heterogeneous set of biotransformations including enzymatic and non-enzymatic reactions. The former mostly involve red-ox reactions on the HNE oxygenated functions (phase I metabolism) and GSH conjugations (phase II) while the latter are due to the HNE capacity to spontaneously condense with nucleophilic sites within endogenous molecules such as proteins, nucleic acids and phospholipids. The overall metabolic fate of HNE has recently attracted great interest not only because it clearly determines the HNE disposal, but especially because the generated metabolites and adducts are not inactive molecules (as initially believed) but show biological activities even more pronounced than those of the parent compound as exemplified by potent pro-inflammatory stimulus induced by GSH conjugates. Similarly, several studies revealed that the non-enzymatic reactions, initially considered as damaging processes randomly involving all endogenous nucleophilic reactants, are in fact quite selective in terms of both reactivity of the nucleophilic sites and stability of the generated adducts. Even though many formed adducts retain the expected toxic consequences, some adducts exhibit well-defined beneficial roles as documented by the protective effects of sublethal concentrations of HNE against toxic concentrations of HNE. Clearly, future investigations are required to gain a more detailed understanding of the metabolic fate of HNE as well as to identify novel targets involved in the biological activity of the HNE metabolites. These studies are and will be permitted by the continuous progress in the analytical methods for the identification and quantitation of novel HNE metabolites as well as for proteomic analyses able to offer a comprehensive picture of the HNE-induced adducted targets. On these grounds, the present review will focus on the major enzymatic and non-enzymatic HNE biotransformations discussing both the molecular mechanisms involved and the biological effects elicited. The review will also describe the most important analytical enhancements that have permitted the here discussed advancements in our understanding of the HNE metabolic fate and which will permit in a near future an even better knowledge of this enigmatic molecule.

Graphical abstract

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Sensitive detection of DNA oxidation damage induced by nanomaterials

Publication date: Available online 2 February 2017
Source:Free Radical Biology and Medicine
Author(s): Andrew Collins, Naouale El Yamani, Maria Dusinska
From a toxicological point of view, nanomaterials are of interest; because – on account of their great surface area relative to mass - they tend to be more reactive than the bulk chemicals from which they are derived. They might in some cases have the potential to damage DNA directly, or could act via the induction of oxidative stress. The comet assay (single cell gel electrophoresis) is widely used to measure DNA strand breaks and also oxidised bases, by including in the procedure digestion with lesion-specific enzymes such as formamidopyrimidine DNA glycosylase (which converts oxidised purines to breaks) or endonuclease III (recognising oxidised pyrimidines). We summarise reports in which these enzymes have been used to study a variety of nanomaterials in diverse cell types. We also stress that it is important to carry out tests of cell viability alongside the genotoxicity assay, since cytotoxicity can lead to adventitious DNA damage. Different concentrations of nanomaterials should be investigated, concentrating on a non-cytotoxic range; and incubating for short and longer periods can give valuable information about the mode of damage induction. The use of lesion-specific enzymes can substantially enhance the sensitivity of the comet assay in detecting genotoxic effects.



http://ift.tt/2l2kEi2

Transperineal gold marker implantation for image-guided external beam radiotherapy of prostate cancer

Abstract

Purpose

To present the feasibility and complications of transperineal fiducial marker implantation in prostate cancer patients undergoing image-guided radiotherapy (IGRT)

Methods and materials

Between November 2011 and April 2016, three radiopaque, gold-plated markers were transperineally implanted into the prostate of 300 patients under transrectal ultrasound guidance and with local anaesthesia. A week after the procedure patients filled in a questionnaire regarding pain, dysuria, urinary frequency, nocturia, rectal bleeding, hematuria, hematospermia or fever symptoms caused by the implantation. Pain was scored on a 1–10 scale, where score 1 meant very weak and score 10 meant unbearable pain. The implanted gold markers were used for daily verification and online correction of patients' setup during IGRT.

Results

Based on the questionnaires no patient experienced fever, infection, dysuria or rectal bleeding after implantation. Among the 300 patients, 12 (4%) had hematospermia, 43 (14%) hematuria, which lasted for an average of 3.4 and 1.8 days, respectively. The average pain score was 4.6 (range 0–9). Of 300 patients 87 (29%) felt any pain after the intervention, which took an average of 1.5 days. None of the patients needed analgesics after implantation. Overall, 105 patients (35%) reported less, 80 patients (27%) more, and 94 patients (31%) equal amount of pain during marker implantation compared to biopsy. The 21 patients who had a biopsy performed under general anesthesia did not answer this question.

Conclusion

Transperineal gold marker implantation under local anesthesia was well tolerated. Complications were limited; rate and frequency of perioperative pain was comparable to the pain caused by biopsy. The method can be performed safely in clinical practice.

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A Case of T-cell Lymphoprliferative Disorder Associated with Hypereosinophilia with Excellent Response to Mycophenolate Mofetil

Publication date: Available online 1 February 2017
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Amr Hanbali, Marwan Shaheen, Feras Alfraih, Wafa Al-Otaibi, Riad El Fakih, Tarek Owaidah, Syed Ahmed
Hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by a persistent elevation of blood eosinophil count ⩾1.5 × 10⁹/L and clinical manifestations attributable to eosinophilia or tissue hypereosinophilia. Lymphocytic variant of HES (HES-L) is a known subtype according to World Health Organization classification. It is well documented in the literature that patients with HES-L are predisposed to develop T-cell lymphoma. We report a case of T-cell lymphoproliferation associated with hypereosinophilia, which has been successfully treated with mycophenolate mofetil, with resolution of skin lesions and normalization of eosinophil count and immunoglobulin E level. We believe this is a clinically relevant case since this is a rare disease with little known knowledge on its best treatment modality.



http://ift.tt/2k1jUK0

Synovial Sarcoma of the Hard Palate: The Third Case in the Medical Literature

Publication date: Available online 1 February 2017
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Aseel Doubi, Motaz Doubi, Nabil Al Zaher, Asma Tulbah




http://ift.tt/2k1BBJ6

Diagnosis of Variant RARA Translocation Using Standard Dual-Color Dual-Fusion PML/RARA FISH probes: An Illustrative Report

Publication date: Available online 1 February 2017
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Manish K. Singh, Mayur Parihar, Neeraj Arora, D.K. Mishra, Saurabh J. Bhave, Mammen Chandy
Acute promyelocytic leukemia (APML) with variant RARa translocations comprises 1–2% of APML cases. However, the diagnosis of these cases is challenging as the routine practice includes fluorescence in situ hybridization (FISH) reverse transcription polymerase chain reaction targeting the PML and RARA genes to detect PML/RARA fusions. Here, we report a case highlighting the importance of atypical FISH signal patterns in standard dual-color dual-fusion PML/RARa FISH analysis complimented by karyotyping to detect these variant RARA translocations.



http://ift.tt/2k1B89P

Study of CD4+, CD8+, and Natural Killer Cells (CD16+, CD56+) in Children with Immune Thrombocytopenic Purpura

Publication date: Available online 1 February 2017
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Farida Hussein El-Rashedy, Mahmoud Ahmed El-Hawy, Mohamed Ahmed Helwa, Sameh Said Abd-Allah
Objective/BackgroundTo assess the percentage of CD4⁺, CD8⁺, and natural killer cells (CD16⁺, CD56⁺) in children with immune thrombocytopenic purpura (ITP) at presentation and study their impact on disease chronicity.MethodsThis case–control study was conducted at the Pediatric Hematology and Oncology Unit, Menoufia University Hospital (tertiary care center in Egypt). The study was held on 30 children presenting with ITP; they were followed-up and classified into two groups: 15 children with acute ITP; and 15 children with chronic ITP. Patients were compared to a group of 15 healthy children of matched age and sex. Measurements of CD4⁺, CD8⁺, and natural killer cells (CD16⁺, CD56⁺) by flow cytometry were assessed and compared in these groups.ResultsCD4⁺ and CD4⁺/CD8⁺ were significantly lower in acute and chronic patients than the control group (p < .05 and p < .001, respectively), with no significant difference between acute and chronic patients (p > .05). However, CD8⁺ was significantly higher in acute and chronic patients than the control group (p < .05), with no significant difference between acute and chronic patients (p > .05). Natural killer cell percent was significantly lower in acute patients than the control group (p < .001), with no significant difference between chronic and control groups (p > .05).ConclusionITP is associated with immunity dysfunction denoted by the increase in cytotoxic T lymphocytes and the decrease in natural killer cells.



http://ift.tt/2k6CjHr

Relapse of Hodgkin Lymphoma after Autologous Transplantation: Time to Rethink Treatment?

Publication date: Available online 1 February 2017
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Yogesh Jethava, Guru Subramanian Guru Murthy, Mehdi Hamadani
Relapse of Hodgkin lymphoma after autologous hematopoietic cell transplantation (autologous HCT) is a major therapeutic challenge. Its management, at least in younger patients, traditionally involves salvage chemotherapy aiming to achieve disease remission followed by consolidation with allogeneic hematopoietic cell transplantation (allogeneic HCT) in eligible patients. The efficacy of salvage therapy is variable and newer combination chemotherapy regimens have improved the outcomes. Factors such as shorter time to relapse after autologous HCT and poor performance status have been identified as predictors of poor outcome. Newer agents such as immunoconjugate brentuximab vedotin, checkpoint inhibitors (e.g., pembrolizumab, nivolumab), lenalidomide, and everolimus are available for the treatment of patients relapsing after autologous HCT. With the availability of reduced intensity conditioning allogeneic HCT, more patients are eligible for this therapy with lesser toxicity and better efficacy due to graft versus lymphoma effects. Alternative donor sources such as haploidentical stem cell transplantation and umbilical cord blood transplantation are expanding this procedure to patients without HLA-matched donors. However, strategies aimed at reduction of disease relapse after reduced intensity conditioning allogeneic HCT are needed to improve the outcomes of this treatment. This review summarizes the current data on salvage chemotherapy and HCT strategies used to treat patients with relapsed Hodgkin lymphoma after prior autologous HCT.



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Prognosis Biomarkers Evaluation in Chronic Lymphocytic Leukemia

Publication date: Available online 1 February 2017
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Lorena Caixeta Gomes, Fernanda Cristina Gontijo Evangelista, Lirlândia Pires de Sousa, Sergio Schusterschitz da Silva Araujo, Maria das Graças Carvalho, Adriano de Paula Sabino
Objective/BackgroundFrom clinical and biological points of view, chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by a progressive accumulation of lymphocytes in the peripheral blood, bone marrow, and lymphoid organs. New prognostic markers in CLL may be useful to clinicians for predicting outcome and in clinical decision-making. The aim of this study was to evaluate the potential prognostic value of the apoptotic/survival-controlling proteins and protein tyrosine kinase ZAP-70 gene expression in CLL patients and control individuals, correlating such findings with patients' clinical data.MethodsFifty-three patients diagnosed with CLL attending the hematology service of a clinical hospital, and 24 healthy individuals with no history of leukemia (Control group) were enrolled in this study. Analyses of apoptotic/survival-controlling proteins were performed by western blot and ZAP-70 gene expression was evaluated by real-time polymerase chain reaction.ResultsSignificant differences were observed for the p-p38, Mcl-1 long, and Mcl-1 short proteins when patients were compared with CLL and controls. A positive correlation between the results for Mcl-1 short and Mcl-1 long and lymphocyte count was observed, corroborating the hypothesis of an imbalance between proteins of cell survival pathways/apoptosis in CLL.ConclusionZAP-70 gene expression was not detected as a discriminant biomarker in these CLL patients. An imbalance between apoptosis-related proteins was observed in the present study, corroborating the hypothesis of increased survival of lymphocytes in CLL patients.



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Glomangiopericytoma (Hemangiopericytoma) of the Maxillary Sinus and Sinonasal Tract

Publication date: Available online 1 February 2017
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Samaher Al Saad, Razan Al Hadlaq, Nabil Al-Zaher
Glomangiopericytoma of the sinonasal tract (formerly known as hemangiopericytoma) is a rare soft tissue tumor with a perivascular myoid phenotype. It accounts for 1 percent of all vascular tumors. Herein, it is our pleasure to report that in 2006, we, Head & Neck Surgeons at King Faisal Specialist Hospital & Research Center in Riyadh, Saudi Arabia, had the opportunity to contribute to the curative management of a 22-year-old patient, a registered nurse who presented with a 6-month history of recurrent minor spontaneous epistaxis and her clinical, radiological and histopathological assessment confirmed that this was due to a left maxillary glomangiopericytoma. The patient underwent angioembolization followed by left maxillectomy. The patient has been followed up closely until a local recurrence had been discovered and was managed with local surgical resection and adjuvant radiotherapy. Since then, the patient has been free from her malignant disease and is following up regularly with no evidence of metastasis or recurrence.



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Munich anatomy and the distribution of bodies from the Stadelheim execution site during National Socialism

Publication date: Available online 2 February 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Mathias Schütz, Jens Waschke, Georg Marckmann, Florian Steger
During the reign of National Socialism (NS) anatomical institutes regularly received bodies of executed prisoners in steadily increasing numbers. After 1939, the execution site at Stadelheim prison in Munich supplied not only Munich Anatomical Institute but also the institutes in Erlangen, Innsbruck and Würzburg. Due to the disappearance of the Munich body journals, the exact dimension and procedure of body procurement from Stadelheim remained unknown for 70 years. After consultation of a wide range of sources, including rediscovered fragments of the body journals, it is now possible to give an almost comprehensive account of the developments. This article deals with the attempts at recovering information on body procurement from Stadelheim prison during the NS period, having already indicated the significance of Munich Anatomical Institute in organizing the distribution of bodies. Thereafter, it addresses the number and distinct groups of Stadelheim prisoners, executed and delivered to the four anatomical institutes, the differences in the handling of their bodies, and the extent to which in particular the Munich Anatomical Institute profited from the massive increase in executions. Finally, it unveils the role of the Munich Anatomical Institute in distributing those bodies among the anatomical institutes during the Second World War, making it not only the main beneficiary but also the interim center of this process.



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A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: The future is now

Publication date: Available online 2 February 2017
Source:Cancer Treatment Reviews
Author(s): Joaquin Bellmunt, Thomas Powles, Nicholas J. Vogelzang
The treatment of bladder cancer has evolved over time to encompass not only the traditional modalities of chemotherapy and surgery, but has been particularly impacted by the use of immunotherapy. The first immunotherapy was the live, attenuated bacterial Bacillus Calmette–Guérin vaccine, which has been the standard of care non-muscle-invasive bladder cancer since 1990. Modern immunotherapy has focused on inhibitors of checkpoint proteins, which are molecules that impede immune function, thereby allowing tumor cells to grow and proliferate unregulated. Several checkpoint targets (programmed death ligand-1 [PD-L1] programmed cell death protien-1 [PD-1], and cytotoxic T-lymphocyte associated protein 4 [CTLA4]) have received the most attention in the treatment of bladder cancer, and have inhibitor agents either approved or in late-stage development. This review describes the most recent data on agents that inhibit PD-L1, found on the surface of tumor cells, and PD-1 found on activated T and B cells and macrophages. Atezolizumab is the only member of this class currently approved for the treatment of bladder cancer, but nivolumab, pembrolizumab, durvalumab, and avelumab all have positive results for this indication, and approvals are anticipated in the near future. The checkpoint inhibitors offer an effective alternative for patients for whom previously there were few options for durable responses, including those who are ineligible for cisplatin-based regimens or who are at risk of significant toxicity. Research is ongoing to further categorize responses, define ideal patient populations, and investigate combinations of checkpoint inhibitors to address multiple pathways in immune system functioning.



http://ift.tt/2k1Bz45

Immune checkpoint inhibitors and targeted therapies for metastatic melanoma: a network meta-analysis

Publication date: Available online 2 February 2017
Source:Cancer Treatment Reviews
Author(s): Sandro Pasquali, Vanna Chiarion-Sileni, Carlo Riccardo Rossi, Simone Mocellin
BackgroundImmune checkpoint inhibitors and targeted therapies, two new class of drugs for treatment of metastatic melanoma, have not been compared in randomized controlled trials (RCT). We quantitatively summarized the evidence and compared immune and targeted therapies in terms of both efficacy and toxicity.MethodsA comprehensive search for RCTs of immune checkpoint inhibitors and targeted therapies was conducted to August 2016. Using a network meta-analysis approach, treatments were compared with each other and ranked based on their effectiveness (as measured by the impact on progression-free survival [PFS]) and acceptability (the inverse of high grade toxicity).ResultsTwelve RCTs enrolling 6,207 patients were included. Network meta-analysis generated 15 comparisons. Combined BRAF and MEK inhibitors were associated with longer PFS as compared to anti-CTLA4 (HR: 0.22; 95% confidence interval [CI]: 0.12-0.41) and anti-PD1 antibodies alone (HR: 0.38; CI: 0.20-0.72). However, anti-PD1 monoclonal antibodies were less toxic than anti-CTLA4 monoclonal antibodies (RR: 0.65; CI:0.40-0.78) and their combination significantly increased toxicity compared to either single agent anti-CTLA4 (RR: 2.06; CI: 1.45-2.93) or anti-PD1 monoclonal antibodies (RR: 3.67; CI: 2.27-5.96). Consistently, ranking analysis suggested that the combination of targeted therapies is the most effective strategy, whereas single agent anti-PD1 antibodies have the best acceptability. The GRADE level of evidence quality for these findings was moderate to low.ConclusionsThe simultaneous inhibition of BRAF and MEK appears the most effective treatment for melanomas harboring BRAF V600 mutation, although anti-PD1 antibodies appear to be less toxic. Further research is needed to increase the quality of evidence.



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Breast PET/MR Imaging

Publication date: Available online 1 February 2017
Source:Radiologic Clinics of North America
Author(s): Amy Melsaether, Linda Moy

Teaser

Breast and whole-body PET/MR imaging is being used to detect local and metastatic disease and is being investigated for potential imaging biomarkers, which may eventually help personalize treatments and prognoses. This article provides and overview of breast and whole-body PET/MR exam techniques, summarizes PET and MR breast imaging for lesion detection, outlines investigations into multi-parametric breast PET/MR, looks at breast PET/MR in the setting of neo-adjuvant chemotherapy, and reviews the pros and cons of whole-body PET/MR in the setting of metastatic or suspected metastatic breast cancer.


http://ift.tt/2k17Fge

Attentional bias to alcohol stimuli predicts elevated cue-induced craving in young adult social drinkers

Publication date: July 2017
Source:Addictive Behaviors, Volume 70
Author(s): Linda Manchery, Devorah E. Yarmush, Peter Luehring-Jones, Joel Erblich
Considerable evidence has identified biased cognitive processing of alcohol-related stimuli as an important factor in the maintenance of alcohol-seeking and relapse among individuals suffering from alcohol use-disorders (AUDs). In addition, a large body of research has demonstrated that exposure to alcohol cues can elicit powerful alcohol cravings. Little is known, however, about the possible relationship between attentional bias and cue-induced cravings, and even less is known about these processes in social drinkers without a personal history of AUDs. The goal of this study was to examine the possibility that attentional biases toward alcohol-related stimuli would predict elevated cue-induced alcohol craving in this population. Young adult social drinkers (N=30, Mean age=22.8±1.9, 61% female) recruited from an urban university population completed a visual dot probe task in which they were presented with alcohol and neutral stimulus pictures that were immediately followed by a visual probe replacing one of the pictures. Attentional bias was measured by calculating reaction times to probes that replaced alcohol stimuli vs. neutral stimuli. Participants then completed a classic alcohol cue-exposure task and reported cravings immediately before and after alcohol and neutral cue-exposures. Not surprisingly, exposure to alcohol cues elicited significant cravings. Consistent with the study hypothesis, larger attentional biases toward alcohol stimuli predicted higher levels of alcohol craving. Findings demonstrate that heightened attention to alcohol stimuli can significantly impact motivation to consume in healthy young adults, and suggest a possible pathway linking cognitive processes early in the drinking trajectory to the later development of AUDs.



http://ift.tt/2kuLC52

Financial strain and cognitive-based smoking processes: The explanatory role of depressive symptoms among adult daily smokers

Publication date: July 2017
Source:Addictive Behaviors, Volume 70
Author(s): Zuzuky Robles, Sahar Anjum, Lorra Garey, Brooke Y. Kauffman, Rubén Rodríguez-Cano, Kirsten J. Langdon, Clayton Neighbors, Lorraine R. Reitzel, Michael J. Zvolensky
Little work has focused on the underlying mechanisms that may link financial strain and smoking processes. The current study tested the hypothesis that financial strain would exert an indirect effect on cognitive-based smoking processes via depressive symptoms. Three clinically significant dependent variables linked to the maintenance of smoking were evaluated: negative affect reduction motives, negative mood abstinence expectancies, and perceived barriers for quitting. Participants included 102 adult daily smokers (Mage=33.0years, SD=13.60; 35.3% female) recruited from the community to participate in a self-guided (unaided; no psychological or pharmacological intervention) smoking cessation study. Results indicated that depressive symptoms explain, in part, the relation between financial strain and smoking motives for negative affect reduction, negative mood abstinence expectancies, and perceived barriers for quitting. Results indicate that smoking interventions for individuals with high levels of financial strain may potentially benefit from the addition of therapeutic tactics aimed at reducing depression.



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