Positive autoantibodies to ZnT8 indicate elevated risk for additional autoimmune conditions in patients with Addison’s disease

Abstract

Autoimmune Addison's disease (AAD) associates with exceptional susceptibility to develop other autoimmune conditions, including type 1 diabetes (T1D), marked by positive serum autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and insulinoma-associated protein 2 (IA-2A). Zinc transporter 8 (ZnT8) is a new T1D autoantigen, encoded by the SLC30A8 gene. Its polymorphic variant rs13266634C/T seems associated with the occurrence of serum ZnT8 antibodies (ZnT8A). This study was designed to determine the prevalence of serum ZnT8A and their clinical implication in 140 AAD patients. Other beta cell and thyroid-specific autoantibodies were also investigated, and ZnT8A results were confronted with the rs13266634 genotype. ZnT8A were detectable in 8.5 %, GADA in 20.7 %, IA-2A in 5.7 %, IAA in 1.6 % and various anti-thyroid antibodies in 7.1–67.8 % individuals. Type 1 diabetes was found in 10 % AAD patients. ZnT8A were positive in 57.1 % of T1D patients and 3.4 % non-diabetic AAD. Analysis of ZnT8A enabled to identify autoimmunity in two (14.3 %) T1D individuals previously classified as autoantibody-negative. ZnT8A-positive patients revealed significantly higher number of autoimmune conditions (p < 0.001), increased prevalence of T1D (p < 0.001) and other beta cell-specific autoantibodies. Carriers of the rs13266634 T-allele displayed increased frequency (p = 0.006) and higher titres of ZnT8A (p = 0.002). Our study demonstrates high incidence of ZnT8A in AAD patients. ZnT8A are associated with coexisting T1D and predictive of T1D in non-diabetic subjects. Moreover, positive ZnT8A in AAD indicate elevated risk for additional autoimmune conditions. Autoantibodies to beta cell antigens, comprising ZnT8, could be included in routine screening panels in AAD.

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An uncommon response to metronomic therapy in a heavily pretreated patient with metastatic carcinosarcoma: a case report

Background: Uterine carcinosarcoma is well known for its aggressive behavior. There is little evidence regarding the gold standard combination chemotherapy in metastatic or locally advanced carcinosarcoma, due to poor survival outcomes obtained with conventional scheduled chemotherapy. This case report represents the first-ever reported objective response to a metronomic chemotherapy regimen and adds to the current literature.Case presentationWe describe a case of a Caucasian woman diagnosed with metastatic carcinosarcoma that had already been treated with multiple lines of conventional chemotherapy, with progressive disease. This patient had a surprising clinical and imaging response when treated with oral metronomic cyclophosphamide. Conclusions: We reviewed the mechanism of action implicated in metronomic chemotherapy, and correlated it with the biology of disease in carcinosarcoma. This information may add to the current literature, providing important insights to future clinical trials in this patient population.

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Akt3 knockdown induces mitochondrial dysfunction in human cancer cells

Akt/PKB plays a pivotal role in cell proliferation and survival. However, the isotype-specific roles of Akt in mitochondrial function have not been fully addressed. In this study, we explored the role of Akt in mitochondrial function after stable knockdown of the Akt isoforms in EJ human bladder cancer cells. We found that the mitochondrial mass was significantly increased in the Akt1- and Akt3-knockdown cells, and this increase was accompanied by an increase in TFAM and NRF1. Akt2 knockdown did not cause a similar effect. Interestingly, Akt3 knockdown also led to severe structural defects in the mitochondria, an increase in doxorubicin-induced senescence, and impairment of cell proliferation in galactose medium. Consistent with these observations, the mitochondrial oxygen consumption rate was significantly reduced in the Akt3-knockdown cells. An Akt3 deficiency-induced decrease in mitochondrial respiration was also observed in A549 lung cancer cells. Collectively, these results suggest that the Akt isoforms play distinct roles in mitochondrial function and that Akt3 is critical for proper mitochondrial respiration in human cancer cells.

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Relationship between Chronic Periodontitis and Erectile Dysfunction: A Narrative Review

Objective. To conduct a descriptive literature review on research studies investigating the association between chronic periodontitis (CP) and erectile dysfunction (ED). Methods. Cohort studies, case-control studies, cross-sectional studies, randomized control trials, and animal studies up to July 2015 that studied the relationship between CP and ED were reviewed and reported. Data sources included PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov. The themes "periodontal disease" and "erectile dysfunction" and the role of periodontal therapy were identified and discussed throughout the narrative review. Results. After reviewing the literature, it was found that an association between CP and vasculogenic ED likely exists. Inflammation resulting from CP promotes endothelial dysfunction by increasing the systemic levels of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α). Periodontal therapy attempts to decrease the release of TNF-α and could act to restore endothelial function, particularly in the penile vasculature. Conclusion. Although the literature reported a positive association between CP and ED, the studies were few and possess several methodological limitations. Large-scale cohort studies and confounder analysis are recommended. Dentists and physicians should collaborate to manage patients with either CP or ED because of their potential association not only with each other but also with other serious systemic comorbidities.

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Comparative study of occurrence of postpartum low back and pelvic pain (LBPP) after normal delivery versus caesarean section (CS) following spinal anaesthesia and its rehabilitative management

2016-03-13T18-22-34Z
Source: International Journal of Therapies and Rehabilitation Research
ANIL KUMAR JOSHI, CHITRA JOSHI.
Introduction and hypothesis: Low back and pelvic pain is very commonly encountered ailment in pregnancy and post-partum in women of childbearing age group. It can account for around half of the women of childbearing age. The pathophysiology of low back pain during pregnancy and postpartum is still poorly understood. Methods: The study was to compare low backache after normal delivery and after caesarean section following spinal anaesthesia, and its persistence after pregnancy. Moreover women were educated to regain the pre-pregnancy state uneventfully. Results: Postpartum backache at 1 month incidence in our study was 49%. Remission of pain occurred in 51% at 1 month and 78% at 6 months in caesarean section group, while in the normal vaginal delivery group 55% at 1 month and 85% in the 6th month had remission of pain. Conclusions: Women who had caesarean section with spinal anaesthesia had more chances to develop low back pain than women with normal vaginal delivery. Pre-pregnancy state can be achieved by supervised exercise regime.


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Ironing PDT for AMD

Otsuji T, Sho K, Tsumura A, Koike N, Nishimura T, Takahashi K

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International GWAS Consortium Identifies Novel Loci Associated with Blood Pressure in Children and Adolescents.

Related Articles

International GWAS Consortium Identifies Novel Loci Associated with Blood Pressure in Children and Adolescents.

Circ Cardiovasc Genet. 2016 Mar 11;

Authors: Parmar PG, Taal HR, Timpson NJ, Thiering E, Lehtimäki T, Marinelli M, Lind PA, Howe LD, Verwoert G, Aalto V, Uitterlinden AG, Briollais L, Evans DM, Wright MJ, Newnham JP, Whitfield JB, Lyytikäinen LP, Rivadeneira F, Boomsma DI, Viikari J, Gillman MW, St Pourcain B, Hottenga JJ, Montgomery GW, Hofman A, Kähönen M, Martin NG, Tobin MD, Raitakari O, Vioque J, Jaddoe VW, Jarvelin MR, Beilin LJ, Heinrich J, van Duijn CM, Pennell CE, EArly Genetics and Lifecourse Epidemiology Consortium, Lawlor DA, Palmer LJ

Abstract
BACKGROUND: -Our aim was to identify genetic variants associated with blood pressure (BP) in childhood and adolescence.
METHODS AND RESULTS: -Genome-wide association study data from participating European ancestry cohorts of the EAGLE ( EA: rly G: enetics and L: ifecourse E: pidemiology) Consortium was meta-analysed across three 'epochs'; pre-puberty [4-7 years], puberty [8-12 years] and post-puberty [13-20 years]. Two novel loci were identified as having genome-wide associations with systolic blood pressure across specific age epochs; rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor CHiP and CpG methylation site) during pre-puberty (p = 2.86 × 10(-8)) and rs872256 during puberty (p = 8.67 × 10(-9)). Several SNP 'clusters' were also associated with childhood BP at p < 5 × 10(-3). Using a p-value threshold of < 5 × 10(-3) we found some overlap in variants across the different age epochs within our study, and between several SNPs in any of the three epochs and adult BP related SNPs.
CONCLUSIONS: -Our results suggest that genetic determinants of blood pressure act from childhood, develop over the lifecourse, and show some evidence of age-specific effects.

PMID: 26969751 [PubMed - as supplied by publisher]

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"Int J Pediatr Otorhinolaryngol"[jour]; +38 new citations

38 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Int J Pediatr Otorhinolaryngol"[jour]

These pubmed results were generated on 2016/03/13

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Blunted angiogenesis and hypertrophy are associated with increased fatigue resistance and unchanged aerobic capacity in old overloaded mouse muscle

Abstract

We hypothesize that the attenuated hypertrophic response in old mouse muscle is (1) partly due to a reduced capillarization and angiogenesis, which is (2) accompanied by a reduced oxidative capacity and fatigue resistance in old control and overloaded muscles, that (3) can be rescued by the antioxidant resveratrol. To investigate this, the hypertrophic response, capillarization, oxidative capacity, and fatigue resistance of m. plantaris were compared in 9- and 25-month-old non-treated and 25-month-old resveratrol-treated mice. Overload increased the local capillary-to-fiber ratio less in old (15 %) than in adult (59 %) muscle (P < 0.05). Although muscles of old mice had a higher succinate dehydrogenase (SDH) activity (P < 0.05) and a slower fiber type profile (P < 0.05), the isometric fatigue resistance was similar in 9- and 25-month-old mice. In both age groups, the fatigue resistance was increased to the same extent after overload (P < 0.01), without a significant change in SDH activity, but an increased capillary density (P < 0.05). Attenuated angiogenesis during overload may contribute to the attenuated hypertrophic response in old age. Neither was rescued by resveratrol supplementation. Changes in fatigue resistance with overload and aging were dissociated from changes in SDH activity, but paralleled those in capillarization. This suggests that capillarization plays a more important role in fatigue resistance than oxidative capacity.

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Droplets on Mold

Droplets due to respiration or possible antibiotic production seen in the center of a mold colony. Mold grew pink in the center with green spore formation around the edges and a white non spore forming "apron" This is a fairly common environmental contaminant seen in our lab , presumably airbo...

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Creating Sub-50 Nm Nanofluidic Junctions in PDMS Microfluidic Chip via Self-Assembly Process of Colloidal Particles

We propose a simple self-assembly technique of silica colloidal nanoparticles to create a nanofluidic junction between two microchannels in polydimethylsiloxane (PDMS). Using this technique, a nanoporous bead membrane with a pore size down to ~45 nm was built inside a microchannel and applied to electrokinetic preconcentration of DNA samples.

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Simultaneous Two-photon In Vivo Imaging of Synaptic Inputs and Postsynaptic Targets in the Mouse Retrosplenial Cortex

This video shows the craniotomy procedure that allows chronic imaging of neurons in mouse retrosplenial cortex using in vivo two photon microscopy in Thy1-GFP transgenic line. This approach is combined with injection of mCherry-expressing adeno-associated virus into dorsal hippocampus. These techniques allow long-term monitoring of experience-dependent structural plasticity in RSC.

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Allergen extracts and recombinant proteins: comparison of efficiency of in vitro allergy diagnostics using multiplex assay on a biological microchip

Immunological test systems for diagnostics of type I hypersensitivity involve the following types of antigens: whole allergen extracts, individual highly purified proteins and their recombinant analogues. The ...

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Medical Robotics textbook

 Last year a great textbook was published, summarizing the key engineering knowledge required to understand medical/surgical robotics: Achim Schweikard, Floris Ernst: Medical Robotics (Springer, Oct 8, 2015). The authors belong to the Robotics Laboratory at University of Lübeck.
It is also available as a google book.



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The inflammatory inception of gallbladder cancer

Publication date: Available online 12 March 2016
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Jaime A. Espinoza, Carolina Bizama, Patricia García, Catterina Ferreccio, Milind Javle, Juan F. Miquel, Jill Koshiol, Juan C. Roa
Gallbladder cancer is a lethal disease with notable geographical variations worldwide and a predilection towards women. Its main risk factor is prolonged exposure to gallstones, although bacterial infections and other inflammatory conditions are also associated. The recurrent cycles of gallbladder epithelium damage and repair enable a chronic inflammatory environment that promotes progressive morphological impairment through a metaplasia-dysplasia-carcinoma, along with cumulative genome instability. Inactivation of TP53, which is mutated in over 50% of GBC cases, seems to be the earliest and one of the most important carcinogenic pathways involved. Increased cell turnover and oxidative stress promote early alteration of TP53, cell cycle deregulation, apoptosis and replicative senescence. In this review, we will discuss evidence for the role of inflammation in gallbladder carcinogenesis obtained through epidemiological studies, genome-wide association studies, experimental carcinogenesis, morphogenetic studies and comparative studies with other inflammation-driven malignancies. The evidence strongly supports chronic, unresolved inflammation as the main carcinogenic mechanism of gallbladder cancer, regardless of the initial etiologic trigger. Given this central role of inflammation, evaluation of the potential for GBC prevention removing causes of inflammation or using anti-inflammatory drugs in high-risk populations may be warranted.

Graphical abstract

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Increased 5-hydroxymethylcytosine in CD4+ T cells in systemic lupus erythematosus

Publication date: Available online 13 March 2016
Source:Journal of Autoimmunity
Author(s): Ming Zhao, Jing Wang, Wei Liao, Duo Li, Mengying Li, Haijing Wu, Yiqun Zhang, M. Eric Gershwin, Qianjin Lu
One of the major disappointments in autoimmunity has been the relative lack of informative data when genomewide associations (GWAS) have been applied to patients with systemic lupus erythematosus (SLE). Indeed, there is increasing evidence that SLE is characterized by widespread epigenetic changes. 5-Hydroxymethylcytosine (5-hmC) is a newly discovered modified form of cytosine suspected to be an important epigenetic modification in embryonic development, cell differentiation and cancer. DNA methylation dynamics have already been implicated in the pathogenesis of SLE, while little is known about hydroxymethylation in this process. Here, we show an increased 5-hmC level in genomic DNA in CD4⁺ T cells of patients with SLE compared with healthy controls, accompanied by the up-regulated expression of the Ten-eleven translocation TET2 and TET3, which can enzymatically convert 5-methylcytosine (5-mC) to 5-hmC. Moreover, we present the differential patterns of DNA hydroxymethylation in genome-wide promoter regions in SLE CD4⁺ T cells compared with healthy controls. We identified 2748 genes with increased 5-hmC levels in promoter regions in SLE CD4⁺ T cells, which were enriched in critical pathways, including neurotrophin signaling, WNT signaling, MAPK signaling, calcium signaling and the mTOR signaling pathway. Through a combined analysis of differential DNA hydroxymethylation profile and gene expression profile in SLE CD4⁺ T cells, we found 131 genes with the increased 5-hmC in promoter regions and up-regulated expression in SLE CD4⁺ T cells compared with healthy controls, including selected immune-related genes, i.e. SOCS1, NR2F6 and IL15RA, which were also confirmed by ChIP-qPCR. Furthermore, we demonstrate that CTCF, as a transcription factor, can mediate DNA hydroxymethylation and contribute to overexpression of SOCS1 in CD4⁺ T cells through binding to the promoter region of SOCS1. Taken together, our study reveals a critical differential 5-hmC in the genome-wide promoter regions of SLE CD4⁺ T cells and provides a novel mechanism that suggests that DNA hydroxymethylation contributes to the aberrant regulation of genes transcription in the pathogenesis of SLE.



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Is low level laser therapy effective in management of pain and swelling after mandibular third molar surgery

Publication date: Available online 12 March 2016
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Majid Eshghpour, Farzaneh Ahrari, Mohammad Takallu
PurposeThis study was conducted to evaluate the effect of low level laser therapy (LLLT) on reducing pain and swelling following removal of impacted third molars.MethodsThis randomized, double blind, split-mouth designed study included patients presenting two symmetrically impacted mandibular third molars. One side of each participant was randomly assigned to laser treatment and the other side served as placebo. LLLT was performed by intraoral application of a 660 nm laser (200 mW, 6 J/point, 4 points) followed by extraoral application of an 810 nm laser (200 mW, 6 J/point, 3 points). Irradiation from the 810 nm wavelength was repeated on days 2 and 4 after operation. On the placebo side, the treatment protocol was similar to the experimental side but with laser simulation. The main outcomes were measuring the degree of pain over 7 days and calculating the edema coefficients on days 2, 4 and 7 after operation. The data were analyzed using generalized linear models to determine the effect of group and time on pain level and edema coefficients.ResultsThe final sample consisted of 40 patients. Pain level was significantly lower in the laser than the placebo side at all time points over the experiment (p<0.05). Swelling was significantly lower in the laser than the placebo group on days 2, 4 and 7 after operation (p<0.05).ConclusionLLLT proved to be effective in reducing the intensity of pain and swelling after removal of impacted third molars and could be recommended to alleviate patients' symptoms following operation.



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Pediatric Maxillofacial Trauma: a Review of 156 Patients

Publication date: Available online 12 March 2016
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Al Haitham Al Shetawi, C. Anthoney Lim, Yash K. Singh, Jason E. Portnof, Stephen M. Blumberg
PurposeTo review the epidemiology and management of facial fractures in a pediatric population.Materials and MethodsRetrospective review of patients under 18 years old presenting to a pediatric emergency department over a 5-year period in an urban, academic, Level-1 designated trauma center.Results156 patients were identified. Most were male (87%), and the mean age was 13.5 years (SD+/-4.9, IQR 12-17). The most common mechanism of injury (MOI) was assault (48.1%). Mandibular fractures (40.7%) were most common. Multiple fractures occurred in 26.9% of patients. Concomitant injuries occurred in 73.7% of patients, most commonly concussions (39.1%). Intracranial hemorrhages were associated with pan-facial (p=0.005), frontal (p=0.001), and orbital fractures (p=0.04). Most patients (91.7%) were admitted, and non-operative repair was undertaken in 57.1%. There was an independent association between surgical intervention and age >14 years and mandibular fractures (p<0.01).ConclusionsAssault was the most common MOI and mandibular fracture was the most commonly encountered. Concomitant non-facial injuries occurred in a majority of patients. Patients sustaining pan-facial, frontal, and orbital fractures should provoke evaluation for other intracranial injuries. Children >14 years old and those with mandibular fractures may prompt mobilization of resources for operative repair.



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Internal Jugular Vein Duplication: Anatomic Relationship With The Spinal Accessory Nerve

Publication date: Available online 12 March 2016
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Badr Ibrahim, Ilyes Berania, Sami P. Moubayed, Apostolos Christopoulos, Tareck Ayad
Level II neck dissection is a commonly performed procedure in head and neck surgery. It carries the risk of injury to the spinal accessory nerve (SAN) and the internal jugular vein (IJV). Injury to any of these structures leads to increased intraoperative and post-operative complications and morbidity. Knowledge of the anatomic relationship – and possible variations from the norm- is vital to decrease the morbidity of this frequently practiced procedure. We report on the two rare different variations of SAN to IJV relations with IJV: 1) IJV splitting with SAN passage through the IJV window; 2) IJV splitting without SAN passage through the IJV window. We also review pre-operative imaging and pertinent literature regarding the variability in the relations of these structures.



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Gelam Honey Attenuates the Oxidative Stress-Induced Inflammatory Pathways in Pancreatic Hamster Cells

Purpose. Type 2 diabetes consists of progressive hyperglycemia and insulin resistance, which could result from glucose toxicity, inflammatory cytokines, and oxidative stress. In the present study we investigated the effect of Gelam honey and quercetin on the oxidative stress-induced inflammatory pathways and the proinflammatory cytokines. Methods. HIT-T15 cells were cultured and preincubated with the extract of Gelam honey (20, 40, 60, and 80 μg/mL), as well as quercetin (20, 40, 60, and 80 μM), prior to stimulation by 20 and 50 mM glucose. Results. HIT-T15 cells cultured under hyperglycemic condition showed a significant increase in the inflammatory pathways by phosphorylating JNK, IKK-β, and IRS-1 at Ser307 (). There was a significant decrease in the phosphorylation of Akt at Ser473 (). Pretreatment with Gelam honey and quercetin reduced the expression of phosphorylated JNK, IKK-β, and IRS-1, thereby significantly reducing the expression of proinflammatory cytokines like TNF-α, IL-6, and IL-1β (). At the same time there was a significant increase in the phosphorylated Akt showing the protective effects against inflammation and insulin resistance (). In conclusion, our data suggest the potential use of the extract from Gelam honey and quercetin in modulating the inflammation induced insulin signaling pathways.

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Transient Creatine Kinase Elevation Followed by Hypocomplementemia in a Case of Rotavirus Myositis

We report an infant case of rotavirus myositis, a rare complication of rotavirus infection. Complement levels of the patient were normal when serum creatine kinase (CK) level was at its peak and then decreased when the CK level became normalized. In a previous case report of rotavirus myositis, transient decrease of serum albumin, immunoglobulin, and complement levels was reported. The authors speculated that intravascular complement activation was caused by rotavirus and resulted in the pathogenesis of myositis, although complement levels at onset were not measured by the authors. In this report, however, we demonstrate that the complement activation of our patient is a result of, rather than the cause of, skeletal muscle damage.

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Leaf Proteome Analysis Reveals Prospective Drought and Heat Stress Response Mechanisms in Soybean

Drought and heat are among the major abiotic stresses that affect soybean crops worldwide. During the current investigation, the effect of drought, heat, and drought plus heat stresses was compared in the leaves of two soybean varieties, Surge and Davison, combining 2D-DIGE proteomic data with physiology and biochemical analyses. We demonstrated how 25 differentially expressed photosynthesis-related proteins affect RuBisCO regulation, electron transport, Calvin cycle, and carbon fixation during drought and heat stress. We also observed higher abundance of heat stress-induced EF-Tu protein in Surge. It is possible that EF-Tu might have activated heat tolerance mechanisms in the soybean. Higher level expressions of heat shock-related protein seem to be regulating the heat tolerance mechanisms. This study identifies the differential expression of various abiotic stress-responsive proteins that regulate various molecular processes and signaling cascades. One inevitable outcome from the biochemical and proteomics assays of this study is that increase of ROS levels during drought stress does not show significant changes at the phenotypic level in Davison and this seems to be due to a higher amount of carbonic anhydrase accumulation in the cell which aids the cell to become more resistant to cytotoxic concentrations of H2O2.

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Lower Order Krawtchouk Moment-Based Feature-Set for Hand Gesture Recognition

The capability of lower order Krawtchouk moment-based shape features has been analyzed. The behaviour of 1D and 2D Krawtchouk polynomials at lower orders is observed by varying Region of Interest (ROI). The paper measures the effectiveness of shape recognition capability of 2D Krawtchouk features at lower orders on the basis of Jochen-Triesch's database and hand gesture database of 10 Indian Sign Language (ISL) alphabets. Comparison of original and reduced feature-set is also done. Experimental results demonstrate that the reduced feature dimensionality gives competent accuracy as compared to the original feature-set for all the proposed classifiers. Thus, the Krawtchouk moment-based features prove to be effective in terms of shape recognition capability at lower orders.

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Comparing a number line and audio prompts in supporting price comparison by students with intellectual disability

Publication date: June–July 2016
Source:Research in Developmental Disabilities, Volumes 53–54
Author(s): Emily C. Bouck, Rajiv Satsangi, Whitney Bartlett
Background/aims/methodsPrice comparison is an important and complex skill, but it lacks sufficient research attention in terms of educating secondary students with intellectual disability and/or autism spectrum disorder. This alternating treatment design study compared the use of a paper-based number line and audio prompts delivered via an audio recorder to support three secondary students with intellectual disability to independently and accuracy compare the price of three separate grocery items.Procedures/outcomesThe study consisted of 22 sessions, spread across baseline, intervention, best treatment, and two different generalization phases. Data were collected on the percent of task analysis steps completed independently, the type of prompts needed, students' accuracy selecting the lowest priced item, and task completion time.Results/conclusionsWith both intervention conditions, students were able to independently complete the task analysis steps as well as accurately select the lowest priced item and decrease their taskcompletion time. For two of the students, the audio recorder condition resulted in the greatest independence and for one the number line. For only one student was the condition with the greatest independence also the condition for the highest rate of accuracy. Implications: The results suggest both tools can support students with price comparison. Yet, audio recorders offer students and teachers an age-appropriate and setting-appropriate option.



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Effect of Inhalation of Aromatherapy Oil on Patients with Perennial Allergic Rhinitis: A Randomized Controlled Trial

This study aimed to investigate the effects of aromatherapy oil inhalation on symptoms, quality of life, sleep quality, and fatigue level among adults with perennial allergic rhinitis (PAR). Fifty-four men and women aged between 20 and 60 were randomized to inhale aromatherapy oil containing essential oil from sandalwood, geranium, and Ravensara or almond oil (the placebo) for 5 minutes twice daily for 7 days. PAR symptoms determined by Total Nasal Symptom Score (TNSS), the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), sleep quality by Verran Synder-Halpern (VSH) scale, and fatigue level by Chalder Fatigue Scale (CFS) were assessed before and after intervention period. Compared with the placebo, the experimental group showed significant improvement in TNSS, especially in nasal obstruction. The aromatherapy group also showed significantly higher improvements in total score of RQLQ and CFS. These findings indicate that inhalation of certain aromatherapy oil helps relieve PAR symptoms, improve rhinitis-specific quality of life, and reduce fatigue in patients with PAR. In conclusion, inhalation of aromatherapy essential oil may have potential as an effective intervention to alleviate PAR.

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Effects of neuromuscular electrical stimulation combined with effortful swallowing on post-stroke oropharyngeal dysphagia: a randomised controlled trial.

Effects of neuromuscular electrical stimulation combined with effortful swallowing on post-stroke oropharyngeal dysphagia: a randomised controlled trial.

J Oral Rehabil. 2016 Mar 9;

Authors: Park JS, Oh DH, Hwang NK, Lee JH

Abstract
Neuromuscular electrical stimulation (NMES) has been used as a therapeutic intervention for dysphagia. However, the therapeutic effects of NMES lack supporting evidence. In recent years, NMES combined with traditional swallowing therapy has been used to improve functional recovery in patients with post-stroke dysphagia. This study aimed to investigate the effects of effortful swallowing combined with neuromuscular electrical stimulation on hyoid bone movement and swallowing function in stroke patients. Fifty stroke patients with mild dysphagia who were able to swallow against the resistance applied by using NMES and cooperate actively in training were included. This study was designed as a 6-week single-blind, randomised, controlled study. In the experimental group, two pairs of electrodes were placed horizontally in the infrahyoid region to depress the hyoid bone. The NMES intensity was increased gradually until the participants felt a grabbing sensation in their neck and performed an effortful swallow during the stimulation. In the placebo group, the same procedure was followed except for the intensity, which was increased gradually until the participants felt an electrical sensation. All participants underwent this intervention for 30 min per session, 5 sessions per week, for 6 weeks. Videofluoroscopic swallowing studies (VFSS) were carried out before and after the intervention and kinematics of the hyoid bone and swallowing function were analysed based on the VFSS. The experimental group revealed a significant increase in anterior and superior hyoid bone movement and the pharyngeal phase of the swallowing function. This intervention can be used as a novel remedial approach in dysphagic stroke patients.

PMID: 26969528 [PubMed - as supplied by publisher]

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Periostin Facilitates the Epithelial-Mesenchymal Transition of Endometrial Epithelial Cells through ILK-Akt Signaling Pathway

Although periostin was confirmed to facilitate the pathogenesis of endometriosis by enhancing the migration, invasion, and adhesion of human endometrial stromal cells (ESCs), its effect on the endometrial epithelial cells (EECs) is still unknown. The current study aimed to determine whether periostin enhanced the epithelial-mesenchymal transition (EMT) of EECs. EECs were isolated from 12 women with endometriosis. The migration and invasion abilities of EECs were evaluated by transwell assays. Expressions of proteins were detected by western blot. After treatment with periostin, the migration and invasion abilities of EECs were enhanced. Additionally, E-cadherin and keratin were downregulated while N-cadherin and vimentin were upregulated in EECs. Simultaneously, levels of ILK, p-Akt, slug, and Zeb1 were all upregulated in EECs. After silencing the expression of ILK in EECs, levels of p-Akt, slug, Zeb1, N-cadherin, and vimentin were downregulated while E-cadherin and keratin were upregulated. Although periostin weakened the above effects in EECs after silencing the expression of ILK, it failed to induce the EMT of EECs. Thus, periostin enhanced invasion and migration abilities of EECs and facilitated the EMT of EECs through ILK-Akt signaling pathway. Playing a pivotal role in the pathogenesis of endometriosis, periostin may be a new clinical therapy target for endometriosis.

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Effects of high intensity noise on the vestibular system in rats.

Related Articles

Effects of high intensity noise on the vestibular system in rats.

Hear Res. 2016 Mar 9;

Authors: Stewart C, Yu Y, Huang J, Maklad A, Tang X, Allison J, Mustain W, Zhou W, Zhu H

Abstract
Some individuals with noise-induced hearing loss (NIHL) also report balance problems. These accompanying vestibular complaints are not well understood. The present study used a rat model to examine the effects of noise exposure on the vestibular system. Rats were exposed to continuous broadband white noise (0-24kHz) at an intensity of 116dB sound pressure level (SPL) via insert ear phones in one ear for three hours under isoflurane anesthesia. Seven days after the exposure, a significant increase in ABR threshold (43.3+1.9dB) was observed in the noise-exposed ears, indicating hearing loss. Effects of noise exposure on vestibular function were assessed by three approaches. First, fluorescein-conjugated phalloidin staining was used to assess vestibular stereocilia following noise exposure. This analysis revealed substantial sensory stereocilia bundle loss in the saccular and utricular maculae as well as in the anterior and horizontal semicircular canal cristae, but not in the posterior semicircular canal cristae. Second, single unit recording of vestibular afferent activity was performed under pentobarbital anesthesia. A total of 548 afferents were recorded from 10 noise-treated rats and 12 control rats. Noise exposure produced a moderate reduction in baseline firing rates of regular otolith afferents and anterior semicircular canal afferents. Also a moderate change was noted in the gain and phase of the horizontal and anterior semicircular canal afferent's response to sinusoidal head rotation (1 and 2Hz, 45 degrees/s peak velocity). Third, noise exposure did not result in significant changes in gain or phase of the horizontal rotational and translational vestibular-ocular reflex (VOR). These results suggest that noise exposure not only causes hearing loss, but also causes substantial damage in the peripheral vestibular system in the absence of immediate clinically measurable vestibular signs. These peripheral deficits, however, may lead to vestibular disorders over time.

PMID: 26970474 [PubMed - as supplied by publisher]

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Quantitative ELISA-Like Immunohistochemistry of Fibroblast Growth Factor 23 in Diagnosis of Tumor-Induced Osteomalacia and Clinical Characteristics of the Disease

Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic disorder and fibroblast growth factor 23 (FGF23) plays a key role in its pathogenesis. This study was conducted to describe a novel FGF23 detecting procedure and describe clinical features of the disease. Fourteen TIO cases were retrieved and FGF23 expression was measured by quantitative ELISA-like immunohistochemistry using formalin-fixed and paraffin-embedded tissues. As summarized from 14 TIO cases, clinical features of TIO were long-standing history of osteomalacia, hypophosphatemia, and urinary phosphate wasting. The associated tumors were mostly benign phosphaturic mesenchymal tumors mixed connective tissue variant (PMTMCT) which could be located anywhere on the body, and most of them could be localized by conventional examinations and octreotide scanning. By quantitative ELISA-like immunohistochemistry, all the 14 TIO cases had high FGF23 expression (median 0.69, 25%–75% interquartile 0.57–1.10, compared with 26 non-TIO tumors of median 0.07, 25%–75% interquartile 0.05–0.11, ). The quantitative ELISA-like immunohistochemistry was a feasible and reproducible procedure to detect the high FGF23 expression in formalin-fixed and paraffin-embedded biopsies or specimens. Since TIO was often delay-diagnosed or misdiagnosed, clinicians and pathologists should be aware of TIO and PMTMCT, respectively.

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Human Hemochromatosis Protein (HFE) Immunoperoxidase Stain Highlights Choriocarcinoma within Mixed Germ Cell Tumors

Identification of choriocarcinoma within a germ cell tumor can have major implications for the subsequent staging and treatment of testicular neoplasms. Immunoperoxidase staining greatly enhances the speed and sensitivity of identifying occult, though clinically significant, tumor components. In mixed germ cell tumors, staining for beta-human chorionic gonadotropin (β-hCG) has been historically used to assess for the presence and burden of choriocarcinoma. However, current β-hCG stains produce variable, intense staining of trophoblastic elements and surrounding tissues, clouding the assessment of true-positive staining. Human hemochromatosis protein (HFE) is a membrane bound mediator of iron transport expressed at high levels within placenta. Additionally, previous reports have demonstrated that choriocarcinoma cell lines express HFE, although in vivo expression had not been examined. To address whether HFE can stain trophoblastic elements, HFE immunohistochemistry was conducted in choriocarcinoma (), mixed germ cell tumors (), seminoma (), and placenta (). HFE consistently demonstrated cytoplasmic and membranous staining, highlighting both syncytiotrophoblasts and cytotrophoblasts within choriocarcinoma and placenta. Staining of intratumoral white blood cells was observed within seminomas and mixed germ cell tumors, corroborating prior reports stating that HFE highlights monocytes and macrophages. Taken together, HFE may serve as an alternative target from β-hCG for immunoperoxidase studies when highlighting choriocarcinoma.

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TWiV 380: Viruses visible in le microscope photonique

Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, 

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Medical Undergraduates' Contributions to Publication Output of World's Top Universities in 2013.

Medical Undergraduates' Contributions to Publication Output of World's Top Universities in 2013.

QJM. 2016 Mar 11;

Authors: Gouda MA, Zidan HS, Marey AA, Gameal MG, Elmahrook RG, Saleh A, Nasr AA, Seifelnasr O, Radwan AE, Shahen A, Elgayar MM, Elabd AA, Mohamed KS, Hammad MF, Badr MM

Abstract
BACKGROUND: Medical undergraduates' involvement in research activities is thought to be mutually beneficial to students, their mentors, and the scholarly productivity of their universities. However, most evidence in favor of such assumption relies on subjective measures such as the self-reported gains in skills or knowledge rather than robust objective estimates for assessing impact.
AIM: We aimed to objectively track and describe publications with undergraduate co-authors - their proportion to the total publication output of world's top universities, their characteristics, and their potential impact on biomedical literature.
METHODS: We contacted the corresponding authors of the 2013's Medline-indexed publications affiliated to world's top ten universities to investigate if any of their co-authors was an undergraduate. Articles with undergraduate co-authors were further assessed to determine, along with other variables: the type of study design, field of the article, publishing journal and its impact factor (IF), and number of received citations.
RESULTS: Out of 25,152 publications, 2,537 articles (10.1%) contained at least one undergraduate co-author who was the first author in 635 papers (25%). Articles with undergraduate co-authors were published in 1,114 journals with a median IF of 3.661. Most undergraduates' co-authored publications (82.7%, n = 2098) were cited at least once within one year, for a median of three citations per article.
CONCLUSION: Undergraduates contributed to one in every ten publications affiliated to top universities. Their papers were published in journals with good IFs and received a fair number of citations, which would reflect the relatively good quality and impact of these articles.

PMID: 26970608 [PubMed - as supplied by publisher]

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How Evolution May Work Through Curiosity-Driven Developmental Process.

How Evolution May Work Through Curiosity-Driven Developmental Process.

Top Cogn Sci. 2016 Mar 11;

Authors: Oudeyer PY, Smith LB

Abstract
Infants' own activities create and actively select their learning experiences. Here we review recent models of embodied information seeking and curiosity-driven learning and show that these mechanisms have deep implications for development and evolution. We discuss how these mechanisms yield self-organized epigenesis with emergent ordered behavioral and cognitive developmental stages. We describe a robotic experiment that explored the hypothesis that progress in learning, in and for itself, generates intrinsic rewards: The robot learners probabilistically selected experiences according to their potential for reducing uncertainty. In these experiments, curiosity-driven learning led the robot learner to successively discover object affordances and vocal interaction with its peers. We explain how a learning curriculum adapted to the current constraints of the learning system automatically formed, constraining learning and shaping the developmental trajectory. The observed trajectories in the robot experiment share many properties with those in infant development, including a mixture of regularities and diversities in the developmental patterns. Finally, we argue that such emergent developmental structures can guide and constrain evolution, in particular with regard to the origins of language.

PMID: 26969919 [PubMed - as supplied by publisher]

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Language Evolution: Constraints and Opportunities From Modern Genetics.

Language Evolution: Constraints and Opportunities From Modern Genetics.

Top Cogn Sci. 2016 Mar 10;

Authors: Dediu D, Christiansen MH

Abstract
Our understanding of language, its origins and subsequent evolution (including language change), is shaped not only by data and theories from the language sciences, but also fundamentally by the biological sciences. Recent developments in genetics and evolutionary theory offer both very strong constraints on what scenarios of language evolution are possible and probable, but also offer exciting opportunities for understanding otherwise puzzling phenomena. Due to the intrinsic breathtaking rate of advancement in these fields, and the complexity, subtlety, and sometimes apparent non-intuitiveness of the phenomena discovered, some of these recent developments have either being completely missed by language scientists or misperceived and misrepresented. In this short paper, we offer an update on some of these findings and theoretical developments through a selection of illustrative examples and discussions that cast new light on current debates in the language sciences. The main message of our paper is that life is much more complex and nuanced than anybody could have predicted even a few decades ago, and that we need to be flexible in our theorizing instead of embracing a priori dogmas and trying to patch paradigms that are no longer satisfactory.

PMID: 26969626 [PubMed - as supplied by publisher]

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Risk and Protective Factors for Late Talking: An Epidemiologic Investigation.

Risk and Protective Factors for Late Talking: An Epidemiologic Investigation.

J Pediatr. 2016 Mar 8;

Authors: Collisson BA, Graham SA, Preston JL, Rose MS, McDonald S, Tough S

Abstract
OBJECTIVE: To identify risk and protective factors for late talking in toddlers between 24 and 30 months of age in a large community-based cohort.
STUDY DESIGN: A prospective, longitudinal pregnancy cohort of 1023 mother-infant pairs in metropolitan Calgary, Canada, were followed across 5 time points: before 25 weeks gestation, between 34-36 weeks gestation, and at 4, 12, and 24 months postpartum. Toddlers who scored ≤10th percentile on The MacArthur-Bates Communicative Development Inventories: Words and Sentences between 24 and 30 months of age were identified as late talkers. Thirty-four candidate characteristics theoretically and/or empirically linked to language development and/or language impairment were collected using survey methodology.
RESULTS: The prevalence of late talking was 12.6%. Risk factors for late talking in the multivariable model included: male sex (P = .017) and a family history of late talking and/or diagnosed speech or language delay (P = .002). Toddlers were significantly less likely to be late talkers if they engaged in informal play opportunities (P = .013), were read to or shown picture books daily (P < .001), or cared for primarily in child care centers (P = .001).
CONCLUSIONS: Both biological and environmental factors were associated with the development of late talking. Biological factors placed toddlers at risk for late talking, and facets of the environment played a protective role. Enveloping infants and toddlers in language-rich milieus that promote opportunities for playing, reading, and sharing books daily may decrease risk for delayed early vocabulary.

PMID: 26968834 [PubMed - as supplied by publisher]

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An examination of the language construct in NIMH's research domain criteria: Time for reconceptualization!

An examination of the language construct in NIMH's research domain criteria: Time for reconceptualization!

Am J Med Genet B Neuropsychiatr Genet. 2016 Mar 10;

Authors: Elvevåg B, Cohen AS, Wolters MK, Whalley HC, Gountouna VE, Kuznetsova KA, Watson AR, Nicodemus KK

Abstract
The National Institute of Mental Health's Research Domain Criteria (RDoC) Initiative "calls for the development of new ways of classifying psychopathology based on dimensions of observable behavior." As a result of this ambitious initiative, language has been identified as an independent construct in the RDoC matrix. In this article, we frame language within an evolutionary and neuropsychological context and discuss some of the limitations to the current measurements of language. Findings from genomics and the neuroimaging of performance during language tasks are discussed in relation to serious mental illness and within the context of caveats regarding measuring language. Indeed, the data collection and analysis methods employed to assay language have been both aided and constrained by the available technologies, methodologies, and conceptual definitions. Consequently, different fields of language research show inconsistent definitions of language that have become increasingly broad over time. Individually, they have also shown significant improvements in conceptual resolution, as well as in experimental and analytic techniques. More recently, language research has embraced collaborations across disciplines, notably neuroscience, cognitive science, and computational linguistics and has ultimately re-defined classical ideas of language. As we move forward, the new models of language with their remarkably multifaceted constructs force a re-examination of the NIMH RDoC conceptualization of language and thus the neuroscience and genetics underlying this concept. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

PMID: 26968151 [PubMed - as supplied by publisher]

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Auditory training program for Arabic-speaking children with auditory figure-ground deficits.

Auditory training program for Arabic-speaking children with auditory figure-ground deficits.

Int J Pediatr Otorhinolaryngol. 2016 Apr;83:160-7

Authors: Hassaan MR, Ibraheem OA

Abstract
OBJECTIVE: Listening to speech in noise makes up a great challenge for school children with auditory processing disorders mainly those with deficit in auditory figure ground (AFG) ability. These children are candidates for auditory training programs targeting AFG such as noise-desensitization programs. This work aimed to develop a new training material in Arabic language targeting this ability.
METHODS: A noise-desensitization semi-formal training program was developed and standardized on normal children in a pilot study preceding the main one. Seventeen school children with AFG deficit were submitted to the program for eight weeks then reevaluated.
RESULTS: The paired sample t-test revealed significant improvement of all trained children after training period in their psychophysical and electrophysiological results. The electrophysiological threshold of signal to noise ratio decreased from -5.3dB to -11.3dB after training.
CONCLUSION: The newly developed training material revealed efficacy in managing children with AFG deficit. The other affected auditory abilities improved also because of the multi-ability tapping character of the program.

PMID: 26968071 [PubMed - in process]

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Adaptation and validation of Common Object Token (COT) test into the Sinhalese language.

Adaptation and validation of Common Object Token (COT) test into the Sinhalese language.

Int J Pediatr Otorhinolaryngol. 2016 Apr;83:143-7

Authors: Jeyaraman J, Kumarasinghe C, Mohamed Rafi SF, Mendis TL, Abdul Rasheed FS

Abstract
OBJECTIVES: This manuscript presents a translation and adaptation of the Common Object Token (COT) test, which assesses speech perception, into the Sinhalese language and an attempt to validate it for use on children with normal hearing (NH) and children with a cochlear implant (CI).
METHODS: Ninety-five children (70 with NH, 25 with a CI) participated in the study. The COT test was translated, back-translated, and evaluated by a team of experts until the Sinhalese translation was deemed acceptable. Data of Sinhalese children with NH and values of children with a CI were analysed. Internal reliability and consistency of the COT total score were determined. Lastly, a quick version of the COT test was created.
RESULTS: The total mean scores and subtest mean scores improved with age for children with NH. For children with a CI, a strong relationship between the COT total score and device experience, i.e. hearing age, was found. A Quick Sinhalese COT test version, suitable for children with a CI, could be created from Subtests 2, 3, and 4.
CONCLUSION: The Sinhalese COT test is valid for assessing the age-related development of speech perception and identification skills of children with NH. Results suggest that the COT is valid for use in children with a CI.

PMID: 26968068 [PubMed - in process]

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Postoperative pain in patients undergoing a transcutaneous active bone conduction implant (Bonebridge).

Postoperative pain in patients undergoing a transcutaneous active bone conduction implant (Bonebridge).

Eur Arch Otorhinolaryngol. 2016 Mar 11;

Authors: Lassaletta L, Calvino M, Zernotti M, Gavilán J

Abstract
The objective of the study was to evaluate postoperative pain following a transcutaneous active conductive hearing implant. 27 patients undergoing Bonebridge (BB) bone conduction implantation were evaluated with two pain-related questionnaires. The Headache Impact Test (HIT-6) was used to measure the degree of disability including none or little impact (≤49), mild (50-55), moderate (56-59), and severe (≥60). The Brief Pain Inventory (BPI) was used to assess pain severity score and function interference (0 = no pain to 10 = worst pain); meaningful pain was considered to be ≥3. The impact of surgical factors on postoperative pain was analyzed. Postoperative BB pain results were compared with 11 Vibrant Soundbridge™ (VSB) and 103 cochlear implant (CI) users. The mean pre- and postoperative HIT-6 scores for BB implantation were 42.6 and 41.8, respectively and the mean preoperative BPI pain severity score changed from 0.6 to 0.9 postoperatively, whereas the preoperative interference score changed from 0.1 to 0.3. None of the mean postoperative values revealed significant pain. The retrosigmoid approach, the need for dural or sinus compression, and the use of bone conduction implant lifts had no significant impact on pain scores. The mean postoperative HIT-6 pain scores for patients with BB, VSB, and CI were 41.8, 46.4, and 42.8, respectively, with the differences not being significant. BB implantation causes no significant postoperative pain irrespective of sinus or dura compression. Pain scores were similar to those experienced by patients with other transcutaneous auditory implants such as middle ear or CIs.

PMID: 26968179 [PubMed - as supplied by publisher]

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Usefulness of Preoperative Plasma Fibrinogen Versus Other Prognostic Markers for Predicting Gastric Cancer Recurrence.

Usefulness of Preoperative Plasma Fibrinogen Versus Other Prognostic Markers for Predicting Gastric Cancer Recurrence.

World J Surg. 2016 Mar 11;

Authors: Yamamoto M, Kurokawa Y, Miyazaki Y, Makino T, Takahashi T, Yamasaki M, Nakajima K, Takiguchi S, Mori M, Doki Y

Abstract
BACKGROUND: Hypercoagulation is associated with tumor progression and metastasis in various types of malignancy. We compared the prognostic value of preoperative plasma fibrinogen level with those of other prognostic markers in patients with gastric cancer and assessed whether fibrinogen level was an independent prognostic indicator.
METHODS: We collected preoperative data from 609 consecutive patients with gastric cancer who underwent curative gastrectomy. A receiver operating curve (ROC) was used to compare the sensitivity and specificity of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), C-reactive protein (CRP), platelet count, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and fibrinogen level in predicting recurrence. Recurrence-free survival (RFS) and overall survival (OS) were compared between the normal and high fibrinogen groups.
RESULTS: In the ROC analysis, the area under the curve (AUC) was 0.534 for CEA, 0.552 for CA19-9, 0.587 for CRP, 0.565 for platelet count, 0.567 for PLR, 0.522 for NLR, and 0.692 for fibrinogen. Plasma fibrinogen level increased with tumor stage. The high fibrinogen (≥350 mg/dl) group had significantly worse RFS (p < 0.001) and OS (p < 0.001) than the normal fibrinogen (<350 mg/dl) group. Cox multivariate analysis of RFS revealed that fibrinogen level was an independent prognostic factor (p < 0.001) in addition to sex, pT stage, and pN stage.
CONCLUSIONS: Preoperative plasma fibrinogen level had the highest predictive value for recurrence among seven known prognostic markers. Since fibrinogen level is an independent factor for RFS, it would be useful for predicting prognosis after gastric cancer surgery.

PMID: 26969673 [PubMed - as supplied by publisher]

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Mometasone furoate in the treatment of mild, moderate, or severe persistent allergic rhinitis: a non-inferiority study (PUMA).

Mometasone furoate in the treatment of mild, moderate, or severe persistent allergic rhinitis: a non-inferiority study (PUMA).

Braz J Otorhinolaryngol. 2016 Feb 15;

Authors: Antila MA, Castro FM, Sano F, Machado A, Fernandes F, Rosário Filho NA, Stelmach R

Abstract
INTRODUCTION: Allergic rhinitis is considered the most prevalent respiratory disease in Brazil and worldwide, with great impact on quality of life, affecting social life, sleep, and also performance at school and at work.
OBJECTIVE: To compare the efficacy and safety of two formulations containing mometasone furoate in the treatment of mild, moderate, or severe persistent allergic rhinitis after four weeks of treatment.
METHODS: Phase III, randomized, non-inferiority, national, open study comparing mometasone furoate in two presentations (control drug and investigational drug). The primary endpoint was the percentage of patients with reduction of at least 0.55 in nasal index score (NIS) after four weeks of treatment. Secondary outcomes included total nasal index score score after four and 12 weeks of treatment; individual scores for symptoms of nasal obstruction, rhinorrhea, sneezing, and nasal pruritus; as well as score for pruritus, lacrimation, and ocular redness after four and 12 weeks of treatment. The study was registered at clinicaltrials.gov with the reference number NCT01372865.
RESULTS: The efficacy primary analysis demonstrated non-inferiority of the investigational drug in relation to the control drug, since the upper limit of the confidence interval (CI) of 95% for the difference between the success rates after four weeks of treatment (12.6%) was below the non-inferiority margin provided during the determination of the sample size (13.7%). Adverse events were infrequent and with mild intensity in most cases.
CONCLUSION: The efficacy and safety of investigational drug in the treatment of persistent allergic rhinitis were similar to the reference product, demonstrating its non-inferiority.

PMID: 26968623 [PubMed - as supplied by publisher]

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Cross-cultural adaptation and validation of the Sinus and Nasal Quality of Life Survey (SN-5) into Brazilian Portuguese.

Cross-cultural adaptation and validation of the Sinus and Nasal Quality of Life Survey (SN-5) into Brazilian Portuguese.

Braz J Otorhinolaryngol. 2016 Feb 13;

Authors: Uchoa PR, Bezerra TF, Lima ÉD, Fornazieri MA, Pinna FR, Sperandio FA, Voegels RL

Abstract
INTRODUCTION: The concept of quality of life is subjective and variable definition, which depends on the individual's perception of their state of health. Quality of life questionnaires are instruments designed to measure quality of life, but most are developed in a language other than Portuguese. Questionnaires can identify the most important symptoms, focus on consultation, and assist in defining the goals of treatment. Some of these have been validated for the Portuguese language, but none in children.
OBJECTIVE: To validate the translation with cross-cultural adaptation and validation of the Sinus and Nasal Quality of Life Survey (SN-5) into Portuguese.
METHODS: Prospective study of children aged 2-12 years with sinonasal symptoms of over 30 days. The study comprised two stages: (I) translation and cross-cultural adaptation of the SN-5 into Portuguese (SN-5p); and (II) validation of the SN5-p. Statistical analysis was performed to assess internal consistency, test-retest reliability, and sensitivity, as well as construct and discriminant validity and standardization.
RESULTS: The SN-5 was translated and adapted into Portuguese (SN-5p) and the author of the original version approved the process. Validation was carried out by administration of the SN-5p to 51 pediatric patients with sinonasal complaints (mean age, 5.8±2.5 years; range, 2-12 years). The questionnaire exhibited adequate construct validity (0.62, p<0.01), internal consistency (Cronbach's alpha=0.73), and discriminant validity (p<0.01), as well as good test-retest reproducibility (Goodman-Kruskal gamma=0.957, p<0.001), good correlation with a visual analog scale (r=0.62, p<0.01), and sensitivity to change.
CONCLUSION: This study reports the successful translation and cross-cultural adaptation of the SN-5 instrument into Brazilian Portuguese. The translated version exhibited adequate psychometric properties for assessment of disease-specific quality of life in pediatric patients with sinonasal complaints.

PMID: 26968622 [PubMed - as supplied by publisher]

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Significance of Interleukin-6 in Papillary Thyroid Carcinoma

This study sought to reveal the significance of IL-6 in papillary thyroid carcinoma by determining its circulating levels, tumoral protein, and mRNA expressions. As compared to the healthy individuals, serum IL-6 was significantly higher in patients with benign thyroid diseases and PTC. Further, its level was significantly higher in PTC patients as compared to patients with benign thyroid diseases. ROC curves also confirmed a good discriminatory efficacy of serum IL-6 between healthy individuals and patients with benign thyroid diseases and PTC. The circulating IL-6 was significantly associated with poor overall survival in PTC patients. IL-6 immunoreactivity was significantly high in PTC patients as compared to the benign thyroid disease patients. Significantly higher IL-6 mRNA expression was also observed in the primary tumour tissues of PTC patients than the adjacent normal tissues. The protein expression of IL-6 at both the circulating and tissue level correlated with disease aggressiveness in PTC patients. Moreover, a significant positive correlation was observed between the IL-6 protein and mRNA expression in the primary tumours of PTC patients. Finally in conclusion, IL-6 has an important role in thyroid cancer progression. Thus targeting IL-6 signalling can help in clinical management of thyroid carcinoma patients.

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Effect of Preoperative Nerve Block on Postthyroidectomy Headache and Cervical Pain: A Randomized Prospective Study

The aim of the current study was to investigate the efficacy of greater occipital nerve (GON) block and bilateral superficial cervical plexuses (BSCP) blocks in alleviating postoperative occipital headache and posterior neck pain after thyroidectomy. This randomized prospective study consisted of 75 women undergoing total thyroidectomy. Patients were randomized into three groups: Group I (): patients receiving GON, Group II (): patients receiving bilateral (BSCP) blocks, and Group III (): patients receiving no block. Assessment of occipital headache, posterior neck, and incision site pains was made at 12 hours and 24 hours after extubation by Visual Analogue Scale (VAS). In comparison to Group III significantly fewer patients in Groups I and II experienced occipital headache at 12 () and 24 hours () and also posterior neck pain at 24 hours (). Mean VAS scores at 12 and 24 hours for occipital headache ( and ) and posterior neck pain ( and ) were significantly lower in Group I. The differences between Groups II and III were not significant except for the occipital headache at 12 hours. The efficacy of GON block is superior to BSCP blocks in alleviating postthyroidectomy occipital headache and posterior cervical pain.

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Alternate dosing schedules for cancer chemopreventive agents.

Alternate dosing schedules for cancer chemopreventive agents.

Semin Oncol. 2016 Feb;43(1):116-122

Authors: Lazzeroni M, DeCensi A

Abstract
Pharmacologic interventions for cancer risk reduction involve the chronic administration of synthetic or natural agents to reduce or delay the occurrence of malignancy. Despite the strong evidence for a favorable risk-benefit ratio for a number of agents in several common malignancies such as breast and prostate cancer, the public's attitude toward cancer chemoprevention remains ambivalent, with the issue of toxicity associated with drugs being perceived as the main barrier to widespread use of preventive therapy by high-risk subjects. Among the strategies to overcome such obstacles to preventive therapies, two novel and potentially safer modes of administering agents are discussed in this paper. The first strategy is to lower the dose of drugs that are in common use in the adjuvant setting based on the notion that prevention of cancer cells from developing should require a lower dose than eradicating established tumor cells. A second approach is to adopt an intermittent administration similar to what is used in the chemotherapy setting in an attempt to minimize risks while retaining benefits. This article provides a detailed discussion of the principles and future development of these two approaches in the direction of a precision preventive medicine.

PMID: 26970130 [PubMed - as supplied by publisher]

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Looking to the future in an unprecedented time for cancer drug development.

Looking to the future in an unprecedented time for cancer drug development.

Semin Oncol. 2016 Feb;43(1):2-3

Authors: Kluetz PG, Pazdur R

Abstract
Basic research in cancer biology, genetics and immunology has resulted in improved insights into mechanisms that drive tumor initiation and growth. This improved biologic understanding of the diseases we treat has led to unprecedented therapeutic breakthroughs across multiple tumor types. In this article, we discuss opportunities and challenges in contemporary cancer drug development, highlighting efficacy endpoints, clinical trial design and the thoughtful inclusion of the patient perspective. As the field re-examines old practices and explores new opportunities, we must continue to efficiently utilize the human and scientific resources at our disposal to foster the development and delivery of safe and effective therapies to cancer patients.

PMID: 26970117 [PubMed - as supplied by publisher]

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Molecular genetics of childhood, adolescent and young adult non-Hodgkin lymphoma.

Molecular genetics of childhood, adolescent and young adult non-Hodgkin lymphoma.

Br J Haematol. 2016 Mar 11;

Authors: Miles RR, Shah RK, Frazer JK

Abstract
Molecular genetic abnormalities are ubiquitous in non-Hodgkin lymphoma (NHL), but genetic changes are not yet used to define specific lymphoma subtypes. Certain recurrent molecular genetic abnormalities in NHL underlie molecular pathogenesis and/or are associated with prognosis or represent potential therapeutic targets. Most molecular genetic studies of B- and T-NHL have been performed on adult patient samples, and the relevance of many of these findings for childhood, adolescent and young adult NHL remains to be demonstrated. In this review, we focus on NHL subtypes that are most common in young patients and emphasize features actually studied in younger NHL patients. This approach highlights what is known about NHL genetics in young patients but also points to gaps that remain, which will require cooperative efforts to collect and share biological specimens for genomic and genetic analyses in order to help predict outcomes and guide therapy in the future.

PMID: 26969846 [PubMed - as supplied by publisher]

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The Metabolism, Analysis, and Targeting of Steroid Hormones in Breast and Prostate Cancer.

The Metabolism, Analysis, and Targeting of Steroid Hormones in Breast and Prostate Cancer.

Horm Cancer. 2016 Mar 11;

Authors: Capper CP, Rae JM, Auchus RJ

Abstract
Breast and prostate cancers are malignancies in which steroid hormones drive cellular proliferation. Over the past century, this understanding has led to successful treatment strategies aimed to inhibit hormone-mediated tumor growth. Nonetheless, disease relapse and progression still pose significant clinical problems, with recurrent and metastatic tumors often exhibiting resistance to current drug therapies. The central role of androgens and estrogens in prostate and breast cancer etiology explains not only why endocrine therapies are often initially successful but also why many tumors ultimately become resistant. It is hypothesized that reducing the concentration of active hormones in the systemic circulation may be insufficient to block cancer progression, as this action selects for tumor cells that can generate active steroids from circulating precursors. This review aims to highlight the currently known differences of steroid biosynthesis in normal physiology versus hormone-dependent cancers, modern approaches to the assessment and targeting of these pathways, and priorities for future research.

PMID: 26969590 [PubMed - as supplied by publisher]

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Treatment cost and life expectancy of diffuse large B-cell lymphoma (DLBCL): a discrete event simulation model on a UK population-based observational cohort.

Treatment cost and life expectancy of diffuse large B-cell lymphoma (DLBCL): a discrete event simulation model on a UK population-based observational cohort.

Eur J Health Econ. 2016 Mar 11;

Authors: Wang HI, Smith A, Aas E, Roman E, Crouch S, Burton C, Patmore R

Abstract
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma. Previous studies examining the cost of treating DLBCL have generally focused on a specific first-line therapy alone; meaning that their findings can neither be extrapolated to the general patient population nor to other points along the treatment pathway. Based on empirical data from a representative population-based patient cohort, the objective of this study was to develop a simulation model that could predict costs and life expectancy of treating DLBCL.
METHODS: All patients newly diagnosed with DLBCL in the UK's population-based Haematological Malignancy Research Network ( www.hmrn.org ) in 2007 were followed until 2013 (n = 271). Mapped treatment pathways, alongside cost information derived from the National Tariff 2013/14, were incorporated into a patient-level simulation model in order to reflect the heterogeneities of patient characteristics and treatment options. The NHS and social services perspective was adopted, and all outcomes were discounted at 3.5 % per annum.
RESULTS: Overall, the expected total medical costs were £22,122 for those treated with curative intent, and £2930 for those managed palliatively. For curative chemotherapy, the predicted medical costs were £14,966, £23,449 and £7376 for first-, second- and third-line treatments, respectively. The estimated annual cost for treating DLBCL across the UK was around £88-92 million.
CONCLUSIONS: This is the first cost modelling study using empirical data to provide 'real world' evidence throughout the DLBCL treatment pathway. Future application of the model could include evaluation of new technologies/treatments to support healthcare decision makers, especially in the era of personalised medicine.

PMID: 26969332 [PubMed - as supplied by publisher]

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Knockdown of cullin 4A inhibits growth and increases chemosensitivity in lung cancer cells.

Knockdown of cullin 4A inhibits growth and increases chemosensitivity in lung cancer cells.

J Cell Mol Med. 2016 Mar 10;

Authors: Hung MS, Chen IC, You L, Jablons DM, Li YC, Mao JH, Xu Z, Lung JH, Yang CT, Liu ST

Abstract
Cullin 4A (Cul4A) has been observed to be overexpressed in various cancers. In this study, the role of Cul4A in the growth and chemosensitivity in lung cancer cells were studied. We showed that Cul4A is overexpressed in lung cancer cells and tissues. Knockdown of the Cul4A expression by shRNA in lung cancer cells resulted in decreased cellular proliferation and growth in lung cancer cells. Increased sensitivity to gemcitabine, a chemotherapy drug, was also noted in those Cul4A knockdown lung cancer cells. Moreover, increased expression of p21, transforming growth factor (TGF)-β inducible early gene-1 (TIEG1) and TGF beta-induced (TGFBI) was observed in lung cancer cells after Cul4A knockdown, which may be partially related to increased chemosensitivity to gemcitabine. G0/G1 cell cycle arrest was also noted after Cul4A knockdown. Notably, decreased tumour growth and increased chemosensitivity to gemcitabine were also noted after Cul4A knockdown in lung cancer xenograft nude mice models. In summary, our study showed that targeting Cul4A with RNAi or other techniques may provide a possible insight to the development of lung cancer therapy in the future.

PMID: 26969027 [PubMed - as supplied by publisher]

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