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Sleep disturbances have been linked to suicidal ideation and behaviors in adolescents. Specifically, insomnia and nightmares are associated with current suicide risk and predict future ideation. Associations between hypersomnia, sleep apnea, and suicide remain inconclusive. Potential biological mechanisms underlying these relationships include executive functioning deficits and hyperarousal. Related psychological factors may include thwarted belongingness, perceived burdensomeness, and negative appraisals. Assessing suicide risk in patients with sleep disturbances, and vice versa, is needed. Therapeutic interventions such as cognitive behavior therapy for insomnia and imagery rehearsal treatment, as well as pharmacologic treatments, show promise in treating sleep disorders and suicidal behavior.

Background To investigate the longitudinal relationship between physical frailty, the clinical representation of accelerated biological aging, and antidepressant medication response in older adults with depressive illness. Methods An 8-week randomized placebo-controlled trial (escitalopram or duloxetine) followed by 10 months of open antidepressant medication treatment (augmentation, switch strategies) was conducted in an outpatient research clinic. 121 adults aged 60 years or older with major depressive disorder (MDD) or persistent depressive disorder and a 24-item Hamilton Rating Scale for Depression (HRSD) ≥16 were enrolled. Primary measures assessed serially over 12 months include response (50% reduction from baseline HRSD score), remission (HRSD score Results A 2-class model best fit the data, identifying a consistently low frailty risk (63% of the sample) and consistently high frailty risk (37% of the sample) trajectory. Response and remission rates (ps ≤ .002) for adults in the high-risk frailty class were at least 21 percentage points worse than those in the low-risk class over 12 months. Furthermore, subsequent frailty was associated with previous frailty (ps ≤ .01) but not previous response or remission (ps ≥ .10). Conclusions Antidepressant medication is poorly effective for MDD occurring in the context of frailty in older adults. Furthermore, even when an antidepressant response is achieved, this response does little to improve their frailty. These data suggest that standard psychiatric assessment of depressed older adults should include frailty measures and that novel therapeutic strategies to address comorbid frailty and depression are needed.

Funding: We wish to thank all the collaborators (administrative staff, nurses, etc.) of the surgery block, as well as the doctors of the vascular surgery and transplantation departments of the Hospital of Santa Maria for the availability and assistance in the collection of the samples. We also thank Sociedade Portuguesa de Reumatologia for funding with two fellowships: Fundo de Apoio à Investigação 2014 and SPR/MSD 2015. DC-F received funding from a PhD grant from Fundação para a Ciência e a Tecnologia (SFRH/BD/80940/2011). Background and Aims: Atherosclerosis and osteoporosis share common risk factors, as well as inflammatory mechanisms. Our aim was to understand how atherosclerotic lesions are related with disturbances in bone. Methods: Gene expression of pro-inflammatory and bone metabolism related proteins (IL-1β, IL-6, IL-17A, TNF, RANKL, OPG, COL1, CTSK, OCL, TRAP, CBFA1, DKK1, SOST, ADIPOQ, and ADIPOR1) were analyzed in arteries and bones from 45 deceased donors and adipose tissue was used as control. Additionally, in 139 patients with advanced atherosclerosis submitted to carotid endarterectomy we compared calcium content (Alizarin red) and plaque inflammatory scores (CD3+, CD68+, and adiponectin) of patients with normal bone mineral density (BMD) with those with low BMD and explored the associations between gene expression in atherosclerotic plaques and BMD. Serum levels of pro-inflammatory and bone related proteins were measured both in donors and patients. Associations were investigated by the Pearson or Spearman correlation tests, and multivariate regression analyzes were performed when justified. Results: Gene expression of bone remodeling and pro-inflammatory proteins correlated positively in bone and aorta, independently of age and sex of donors, but not in adipose tissue. The expression of bone formation genes was significantly higher in atheroma plaques from endarterectomized patients with normal vs. low BMD as well as inflammatory CD68+ scores, regardless of patients' age and sex, but not of body mass index. No relationship was observed between serum levels and gene expression levels of pro-inflammatory or bone remodeling proteins. Conclusions: Our results suggest that the relationship between bones and vessels in the context of atherosclerotic disease and osteoporosis may rely on the intrinsic connection between the tissues involved, independently of disease stage. Serum measurements of pro-inflammatory and bone-remodeling proteins do not accurately translate tissue pathologic processes. publishersversion published

BackgroundExisting diagnostic methods for the parasitic gastrointestinal nematode,Haemonchus contortus, are time consuming and require specialised expertise, limiting their utility in the field. A practical, on-farm diagnostic tool could facilitate timely treatment decisions, thereby preventing losses in production and flock welfare. We previously demonstrated the ability of visible–near-infrared (Vis–NIR) spectroscopy to detect and quantify blood in sheep faeces with high accuracy. Here we report our investigation of whether variation in sheep type and environment affect the prediction accuracy of Vis–NIR spectroscopy in quantifying blood in faeces.MethodsVisible–NIR spectra were obtained from worm-free sheep faeces collected from different environments and sheep types in South Australia (SA) and New South Wales, Australia and spiked with various sheep blood concentrations. Spectra were analysed using principal component analysis (PCA), and calibration models were built around the haemoglobin (Hb) wavelength region (387–609 nm) using partial least squares regression. Models were used to predict Hb concentrations in spiked faeces from SA and naturally infected sheep faeces from Queensland (QLD). Samples from QLD were quantified using Hemastix® test strip and FAMACHA© diagnostic test scores.ResultsPrincipal component analysis showed that location, class of sheep and pooled versus individual samples were factors affecting the Hb predictions. The models successfully differentiated ‘healthy’ SA samples from those requiring anthelmintic treatment with moderate to good prediction accuracy (sensitivity 57–94%, specificity 44–79%). The models were not predictive for blood in the naturally infected QLD samples, which may be due in part to variability of faecal background and blood chemistry between samples, or the difference in validation methods used for blood quantification. PCA of the QLD samples, however, identified a difference between samples containing high and low quantities of blood.ConclusionThis study demonstrates the potential of Vis–NIR spectroscopy for estimating blood concentration in faeces from various types of sheep and environmental backgrounds. However, the calibration models developed here did not capture sufficient environmental variation to accurately predict Hb in faeces collected from environments different to those used in the calibration model. Consequently, it will be necessary to establish models that incorporate samples that are more representative of areas whereH. contortusis endemic.Graphical Abstract

Resumo Fundamento A prevalência da obesidade vem aumentando sistematicamente na população, inclusive nas crianças e adolescentes, ao redor do mundo. Objetivos Descrever curvas percentílicas de referência para a circunferência abdominal (CA) nas crianças brasileiras e fornecer pontos de corte da CA para identificar crianças com risco de obesidade. Métodos Um estudo multicêntrico, prospectivo, tranversal foi realizado em crianças com idades entre 6 e 10 anos, matriculadas no ensino fundamental de escolas públicas e particulares de 13 cidades do estado de São Paulo. A estatura, o peso e a CA foram medidos em duplicata em 22.000 crianças (11.199 meninos). Para estabelecer o melhor ponto de corte da CA para o diagnóstico da obesidade, foram calculadas curvas ROC com crianças classificadas como com peso normal e obesas, de acordo com as curvas do IMC, estratificadas por gênero e idade, e o índice Youden foi utilizado como a eficácia potencial máxima desse biomarcador. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados Os valores da CA aumentaram com a idade, tanto nos meninos quanto nas meninas. A prevalência de obesidade em cada grupo variou de 17% (6 anos de idade) a 21,6 % (9 anos de idade), dentre os meninos, e de 14,1% (7 anos de idade) a 17,3 % (9 anos de idade), dentre as meninas. As análises ROC mostraram o percentil 75 como ponto de corte para o risco de obesidade, e o diagnóstico de obesidade está classificado no percentil 85 ou acima. Conclusão Curvas de referência da CA específicas para idade e sexo em crianças brasileiras e pontos de corte para o risco de obesidade podem ser usados em triagem nacional e estudos intervencionais para reduzir a carga da obesidade no Brasil. (Arq Bras Cardiol. 2020; 114(3):530-537) Abstract Backgroud The prevalence of obesity has systematically been increased in the population, including children and adolescents, around the world. Objectives To describe reference percentile curves for waist circumference (WC) in Brazilian children and provide cut-off values of WC to identify children at risk for obesity. Methods A multicenter, prospective, cross-sectional study was performed with children aged from 6 to 10 years old, enrolled in public and private elementary schools from 13 cities of the São Paulo State. Height, weight, and WC were measured in duplicate in 22,000 children (11,199 boys). To establish the WC best cut-off value for obesity diagnosis, ROC curves with children classified as normal weight and obese were calculated, according to BMI curves, stratified by gender and age, and the Youden Index was utilized as the maximum potential effectiveness of this biomarker. A p < 0.05 was considered statistically significant. Results WC values increased with age in both boys and girls. The prevalence of obesity in each age group varied from 17% (6 years old) to 21.6% (9 years old) among boys, and from 14.1% (7 years old) to 17.3 % (9 years old) among girls. ROC analyses have shown the 75th percentile as a cut-off for obesity risk, and the diagnosis of obesity is classified on the 85th percentile or more. Conclusion Age and gender specific reference curves of WC for Brazilian children and cut-off values for obesity risk may be used for national screening and interventional studies to reduce the obesity burden in Brazil. (Arq Bras Cardiol. 2020; 114(3):530-537)

Made available in DSpace on 2020-12-12T01:58:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-02-19 Background: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. Methods: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. Discussion: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM. Department of Gynecology and Obstetrics Botucatu Medical School (FMB) São Paulo State University (UNESP) Physics Department Institute of Biosciences Letters and Exact Sciences Multiuser Center for Biomolecular Innovation UNESP-São Paulo State University Physiotherapy Department Faculdades Integradas de Bauru FIB Universidade Do Sagrado Coração (USC), Jardim Brasil Department of Health Research Methods Evidence and Impact McMaster University Biostatistics Unit Father Sean o'Sullivan Research Centre St Joseph's Healthcare-Hamilton Department of Obstetrics and Gynecology Weill Cornell Medicine Institute of Tropical Medicine University of Sao Paulo Medical School School of Philosophy and Sciences Department of Physiotherapy and Occupational Therapy UNESP-São Paulo State University Department of Gynecology and Obstetrics Botucatu Medical School (FMB) São Paulo State University (UNESP) Physics Department Institute of Biosciences Letters and Exact Sciences Multiuser Center for Biomolecular Innovation UNESP-São Paulo State University School of Philosophy and Sciences Department of Physiotherapy and Occupational Therapy UNESP-São Paulo State University

Nutrition education is one of the factors that may help to promote behavior change and therefore may improve the dietary habits of adolescent soccer players. However, information about the relationship between nutrition knowledge (NK) and the dietary behavior of these athletes is scarce. The purpose of this study was to evaluate the eating habits of adolescent soccer players and analyse the correlations among dietary intake and NK. Seventy-three Brazilian adolescent soccer players (aged 14–19 years), from four professional clubs, underwent anthropometric evaluation and completed 3-day food records. Misreporting of energy intake was evaluated and the dietary intake data were energy-adjusted and compared with recommendations for athletes and dietary reference intakes. The athletes also answered a questionnaire about barriers for healthy eating and a nutrition knowledge test divided into three sections: Basic Nutrition Knowledge (BNK), Sports Nutrition Knowledge (SNK), and Food Pyramid Nutrition Knowledge (FPNK). The participants showed a low NK (54.6%) and an inadequate intake of fruits, vegetables, dairy, carbohydrates, and micronutrients. A positive correlation was found between the ingestion of phosphorus and FPNK as well as among calcium and both SNK and Total NK (p<0.05). Sodium intake was negatively correlated with all categories of the NK test (p<0.05). The adolescents reported that the principal barriers for adopting a healthy diet were the lack of willpower and a busy lifestyle. In this context, nutrition education is recommended and should also provide practicable healthy eating goals according to athletes´ lifestyle as well as target motivational barriers to increase adherence.

IntroductionSkin-Picking Disorder (SPD) is psychiatric condition characterized by recurrent and excessive picking of the skin. There are several attempts to stop the behavior and it causes negative consequences such as dermatological complications and functional impairment.ObjectivesThe aim of this study is to describe a case report of SPD.MethodsData was collected retrospectively from case notes.ResultsA 30 year-old male, married with 2 children, currently on sick leave, was admitted to the Day Hospital at Centro Hospitalar Psiquiátrico de Lisboa (CHPL) with worsen skin-picking behaviour and functional impairment. During childhood the patient would “cut my toe nails the wrong way so that I could fix them”. By adolescence the patient suffered from acne and felt the need to “solve” them and take out the pus. Over the years the skin-picking behaviour spread to other areas of the body, mainly dorsal and chest areas. Before being admitted to the Day Hospital the episodes were daily and had 2-3 hours duration, using scissors and tweezers and evolving his family, asking his wife’s help with picking. He is being treated with fluoxetine 80 mg, risperidone 2 mg and N-acetylcysteine 1200 mg and Cognitive Behavioural Therapy. He is also participating in the Day Hospital activities that include occupational therapy, movement therapy, psychoeducation. After 2 months he has a few 20 minutes episodes per week, spends more time with his children and thinks about coming back to work.ConclusionsSPD is a severe and debilitating illness that benefits from a multidisciplinary approach.DisclosureNo significant relationships.

As áreas verdes urbanas são percebidas de diferentes formas pelas pessoas, a depender de fatores culturais, sociais e sensoriais. Uma Instituição de Ensino Superior (IES) reunindo uma heterogeneidade de classes sociais e descendências étnicas torna-se um local de pesquisa que pode refletir diferentes percepções ambientais. O conhecimento de tal heterogeneidade serve de base para a construção de programas específicos de educação ambiental. Desta forma, o objetivo deste trabalho foi analisar a percepção e conhecimento de alunos de graduação presencial e funcionários da IES em relação às espécies de flora e áreas naturais do campus universitário. O método adotado foi a aplicação de entrevistas estruturadas contando questões abertas e fechadas. Os dados foram analisados quali e quantitativas. Foram 40 participantes, sendo 55% alunos e 45% funcionários. O número de espécies citadas pelos participantes variou entre 1 e 11 (± 2.93). Sobre as áreas naturais do campus a maioria dos entrevistados (73%) a declarou como "regular" segundo sua percepção, sendo alguma forma de utilidade ao homem as mais citadas, ficando as funções ecológicas com menor importância. Baseando-se no conceito da “cegueira botânica” os resultados mostram que os entrevistados apresentam dificuldade em perceber as plantas em seu cotidiano. Tendo a referida IES a divulgação de uma postura sustentável, esperamos que os resultados possam servir de base para o planejamento de projetos de Educação Ambiental envolvendo alunos e funcionários da instituição e comunidade externa em projetos de extensão universitária que contribuam para o alcance de uma comunidade acadêmica que contribua com seu pilar ambiental.

Adolfo Lutz Institute in Sao Paolo State performs mycobacterial identification for many healthcare units, and in 2008 identified a possible outbreak involving patients submitted to bronchoscopy at the same hospital. This study aimed to analyse the clonality of isolates. Mycobacterium abscessus subsp. massiliense isolated from 28 patients, water from one bronchoscope and water from four automated endoscope reprocessing machines presented high similarity by pulsed-field gel electrophoresis. This strain was not found in the water supply, and it was hypothesized that an infected patient contaminated the bronchoscope, with further false-positive cultures from subsequent patients.

We report the first use of near-infrared spectroscopy for rapid, low-cost, noninvasive detection of Zika virus in Aedes aegypti., The accelerating global spread of arboviruses, such as Zika virus (ZIKV), highlights the need for more proactive mosquito surveillance. However, a major challenge during arbovirus outbreaks has been the lack of rapid and affordable tests for pathogen detection in mosquitoes. We show for the first time that near-infrared spectroscopy (NIRS) is a rapid, reagent-free, and cost-effective tool that can be used to noninvasively detect ZIKV in heads and thoraces of intact Aedes aegypti mosquitoes with prediction accuracies of 94.2 to 99.3% relative to quantitative reverse transcription polymerase chain reaction (RT-qPCR). NIRS involves simply shining a beam of light on a mosquito to collect a diagnostic spectrum. We estimated in this study that NIRS is 18 times faster and 110 times cheaper than RT-qPCR. We anticipate that NIRS will be expanded upon for identifying potential arbovirus hotspots to guide the spatial prioritization of vector control.

The search for antiprion compounds has been encouraged by the fact that transmissible spongiform encephalopathies (TSEs) share molecular mechanisms with more prevalent neurodegenerative pathologies, such as Parkinson's and Alzheimer's diseases. Cellular prion protein (PrP C ) conversion into protease-resistant forms (protease-resistant PrP [PrP Res ] or the scrapie form of PrP [PrP Sc ]) is a critical step in the development of TSEs and is thus one of the main targets in the screening for antiprion compounds. In this work, three trimethoxychalcones (compounds J1, J8, and J20) and one oxadiazole (compound Y17), previously identified in vitro to be potential antiprion compounds, were evaluated through different approaches in order to gain inferences about their mechanisms of action. None of them changed PrP C mRNA levels in N2a cells, as shown by reverse transcription-quantitative real-time PCR. Among them, J8 and Y17 were effective in real-time quaking-induced conversion reactions using rodent recombinant PrP (rPrP) from residues 23 to 231 (rPrP 23–231 ) as the substrate and PrP Sc seeds from hamster and human brain. However, when rPrP from residues 90 to 231 (rPrP 90–231 ), which lacks the N-terminal domain, was used as the substrate, only J8 remained effective, indicating that this region is important for Y17 activity, while J8 seems to interact with the PrP C globular domain. J8 also reduced the fibrillation of mouse rPrP 23–231 seeded with in vitro -produced fibrils. Furthermore, most of the compounds decreased the amount of PrP C on the N2a cell surface by trapping this protein in the endoplasmic reticulum. On the basis of these results, we hypothesize that J8, a nontoxic compound previously shown to be a promising antiprion agent, may act by different mechanisms, since its efficacy is attributable not only to PrP conversion inhibition but also to a reduction of the PrP C content on the cell surface.

The global approach to mosquito-borne diseases (MBDs) is in need of critical re-evaluation. Although there have been dramatic reductions in malaria incidence since 2000, malaria elimination from high-transmission settings remains problematic. At the same time, arbovirus outbreaks have increased in their frequency and impact. The 2015-2016 Zika virus epidemic exposed the dire state of MBD control in many countries, calling for united global action. Despite international resolve to prevent future epidemics, current practices in MBD control are mostly reactive and of limited efficacy. In this Opinion article, we summarize the views of 25 international mosquito experts about the current state of MBD control and highlight the issues that must be addressed in order to tackle emerging threats on the horizon.

Cellulose is the main constituent of plant cell walls and can be converted into a wide range of derivatives. The derivatives are produced by a chemical reaction of the primary and two secondary hydroxyl groups available in β-d-glucopyranose units, often in heterogeneous conditions, yielding, in many cases

Within the Organic Analysis Working Group (OAWG) of the Comité Consultatif pour la Quantitè de Matiére (CCQM), key comparison CCQM-K141 and associated pilot study CCQM-P178 were coordinated by the National Research Council Canada (NRC). This comparison was a Track A key comparison that formed part of the OAWG 10-year strategic plan. The comparison demonstrated capabilities for measuring high-polarity analytes in a high-fat and high-protein matrix. The measurand chosen as the model system was enrofloxacin and sulfadiazine in bovine tissue. Thirteen National Metrology Institutes or Designated Institutes participated in the CCQM-K141, while two National Metrology Institutes participated in CCQM-P178. The bovine muscle tissue study material was derived from a single live animal that was administered with chemical based pharmaceutical agents prior to processing. Therefore, the study material was naturally incurred, providing a true test of extraction procedures relative to more commonly encountered spiked materials. NRC confirmed excellent homogeneity and stability of the material prior to shipping. Three 10 g bottles of freeze dried powdered muscle tissue were supplied. NRC also provided isotopically labelled solutions of the two measurands, 13C6-sulfadiazine and enrofloxacin-d5 (HI Salt), to those interested in using isotope dilution mass spectrometry (IDMS) methodologies. Procurement and purity assignment with appropriate metrological traceability of native calibrants were the responsibility of individual participants. The study required extraction, clean-up, analytical separation, and selective detection of the analytes. The level of agreement was reasonable given the measurands and matrix were new for most laboratories. The KCRV values and their uncertainties at the 95% confidence level of 57.81 ± 2.57 μg/kg for enrofloxacin and 2285 ± 68 μg/kg for sulfadiazine were calculated using the DSL means. While one participant's value was voluntarily excluded from the KCRV calculations for enrofloxacin, all other participants demonstrated equivalence for both measurands. Significant effort was undertaken post-study to identify the major sources of variability between results. In particular, the various extraction conditions used by participants were investigated thoroughly. While there appeared to be a correlation between highly acidic conditions and higher recovery, this was not definitive and could not be confirmed. The form of standards employed (i.e. free base vs salts) and potential differential solubility between forms was also a suspected source of variability. Biases could also have been introduced with the choice of solvents used for standard preparation, with some solvents better able to minimize adsorption of the analytes to glass surfaces. KEY WORDS FOR SEARCH enrofloxacin, sulfadiazine, bovine tissue, incurred, key comparison Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

The present study investigated the structural changes in the rat calcaneal tendon (CT), superficial flexor tendon (SFT), and deep flexor tendon (DFT) in response to jump exercises and anabolic androgenic steroids (AAS). Animals were divided into four groups: sedentary, trained, AAS-treated sedentary rats, and AAS-treated trained animals. Training increased the volume density (Vv%) of blood vessels in all regions of the CT and DFT, cell Vv% in the peritendinous sheath of the proximal and distal regions of the SFT and proximal region of DFT, and cell Vv% in the tendon proper of the proximal and distal regions of the SFT and DFT. The combination of AAS and load exercises showed little increased blood vessel Vv% at the proximal region of the CT, intermediate region of the SFT, and all regions of the DFT as opposed to an increase in adipose cell Vv% in the CT proximal region. The AAS reduced the levels of hydroxyproline in the proximal region of the DFT and in the distal region of the STF. In conclusion, exercise promoted benefits to the adaptation of the tendons to overload. These effects were absent when load exercise was combined with AAS. The abusive consumption of AAS contributes to tendon inertness and rigidity, and increases the potential risk of injury.

Summary Objectives We constructed age- and gender-specific norms for healthy adults on a large number of speech and voice measures using standardized recording procedures. Study design Participants were 159 younger (mean=19.1 years, standard deviation [SD]=1.4) and 133 older (mean=72.0 years, SD=4.8) healthy native English male and female speakers who did not currently smoke and had typical hearing for their age group. Methods Participants phonated the vowel [a] under various instructions and read an abbreviated version of the Rainbow Passage. Voice measures based on the productions of [a] included fundamental frequency ( F 0 ), jitter, shimmer, harmonics-to-noise ratio, noise-to-harmonics ratio, maximum phonation time, minimum phonation intensity, maximum pitch, and the Dysphonia Severity Index (DSI). Mean speaking fundamental frequency (SF 0 ), SF 0 standard deviation (SF 0 SD), and signal intensity were measured from the reading passage. Results Noteworthy age-related differences were found for males and females. Older females had a lower F 0 and SF 0 and smaller SF 0 SD than younger females, but younger and older males did not differ. Shimmer increased with age for males, but neither jitter nor shimmer increased with age for females, whereas noise measures were similar for both ages. Younger and older males had a similar DSI, whereas older females had a higher DSI than younger females. Conclusions This study provides a unique database containing a wide variety of voice measures collected from a large sample of adults in good health using standardized recording procedures. Males and females differed on the type and extent of age-related vocal changes, but overall age-related differences were limited.

Treatment of metastatic melanoma still remains a challenge, since in advanced stage it is refractory to conventional treatments. Most patients with melanoma have either B-RAF or N-RAS mutations, and these oncogenes lead to activation of the RAS-RAF-MEK-ERK and AKT signal pathway, keeping active the proliferation and survival pathways in the cell. Therefore, the identification of small molecules that block metastatic cell proliferation and induce cell death is needed. Violacein, a pigment produced by Chromobacterium violaceum found in Amazon River, has been used by our group as a biotool for scrutinizing signaling pathways associated with proliferation, survival, aggressiveness, and resistance of cancer cells. In the present study, we demonstrate that violacein diminished the viability of RAS- and RAF-mutated melanoma cells (IC50 value ∼500 nM), and more important, this effect was not abolished after treatment medium removal. Furthermore, violacein was able to reduce significantly the invasion capacity of metastatic melanoma cells in 3D culture. In the molecular context, we have shown for the first time that violacein causes a strong drop on histone deacetylase 6 expression, a proliferating activator, in melanoma cells. Besides, an inhibition of AXL and AKT was detected. All these molecular events propitiate an inhibition of autophagy, and consequently, melanoma cell death by apoptosis.

Electrocoagulation has recently attracted attention as a potential technique for treating toxic effluents due to its versatility and environmental compatibility, generating a residue chemically suitable to be used as a soil additive. In the present study, landfill leachate sludge hazardous effects were investigated prior and after electrocoagulation process using in vitro assays with the mammalian cells CHO-k1. An integrated strategy for risk assessment was used to correctly estimate the possible adverse landfill leachate sludge effects on human health and ecosystem. Electrocoagulation process proved to be an effective treatment due to possibility to improve effluent adverse characteristics and produce sludge with potential to be used as soil additive. Despite low cytoxicity, the residue presented genotoxic and mutagenic effects, indicating a capacity to induce genetic damages, probably due to induction of polyploidization process in cells. The observed effects demand an improvement of waste management methods for reduce negative risks of landfill leachate sludge application.

The purpose of this study was to verify the inter-rater agreement level as a means of obtaining an efficiency measure of a standard mastication evaluation through video recordings. The studied population included oral breathing children and teenagers with maxillary atresia. The chewing aspects studied were mode of chewing and preferential chewing side. A white tag was placed on half the subjects´ chins while the recordings were made. Two expert evaluators analyzed 54 video recordings at regular viewing speed. The lead author analyzed the same video recordings both at reduced speed and at reduced speed linked through graphical computing techniques. The analysis was conducted on chewing cycles with the viewing angle of the frontal plane. Findings indicated that when comparing the data for the three manners of watching the video recordings, the agreement level was higher for videos with the tag on the chin watched at reduced speed. It was also determined that alternating and bilateral mastication modes were prevalent (64.7%) in this sample.

The mechanisms by which dietary sodium modulates cardiovascular risk are not fully understood. This study investigated whether sodium intake is related to carotid structure and hemodynamics and to plasma matrix metalloproteinase (MMP) activity in hypertensive adults. One hundred thirty-four participants were cross-sectionally evaluated by clinical history, anthropometry, carotid ultrasound, and analysis of hemodynamic, inflammatory, and metabolic variables. Daily sodium intake (DSI) was estimated by 24-h recall, discretionary sodium, and a FFQ. In 42 patients, plasma MMP-2 and MMP-9 activities were also analyzed. The mean DSI was 5.52 ± 0.29 g/d. Univariate analysis showed that DSI correlated with common carotid artery systolic and diastolic diameter (r = 0.36 and 0.34; both P < 0.001), peak and mean circumferential tension (r = 0.44 and 0.39; both P < 0.001), Young's Elastic Modulus (r = 0.40; P < 0.001), intima-media thickness (r = 0.19; P < 0.05), and internal carotid artery resistive index (r = 0.20; P < 0.05). Multivariate analyses revealed that only artery diameter, circumferential wall tension, and Young's Elastic Modulus were independently associated with DSI. Conversely, plasma MMP-9 activity was associated with DSI (r = 0.53; P < 0.001) as well as with common carotid systolic diameter (r = 0.33; P < 0.05) and Young's Elastic Modulus (r = 0.38; P < 0.01). In conclusion, sodium intake is associated with carotid alterations in hypertensive adults independently of systemic hemodynamic variables. The present findings also suggest that increased MMP-9 activity might play a role in sodium-induced vascular remodeling.

Background This study investigated the impact of a putative functional TLR4 polymorphism (Asp299Gly) on left ventricular (LV) structure in hypertensive subjects. Methods A sample of 443 patients (266 women and 177 men) was evaluated by clinical history, physical examination, anthropometry, analysis of inflammatory and metabolic parameters, echocardiography and TLR4 Asp299Gly genotyping. In addition, the relationship between the polymorphism and in vitro lipopolysaccharide responsiveness of peripheral blood monocytic cells was also assessed. Results Women carrying the 299Gly allele presented lower posterior wall thickness (p = 0.01), interventricular septum thickness (p = 0.04), LV mass (p = 0.01) and LV mass index (p = 0.03), as well as a reduced prevalence of LV hypertrophy (p = 0.002), in comparison to women with the wild-type genotype. These results were confirmed by stepwise and logistic regression analyses adjusted for potential confounders. Conversely, the 299Gly allele did not influence LV structure in men. Furthermore, in vitro assays revealed that monocytes of either men or women heterozygous for the 299Gly allele presented a lower lipopolysaccharide-induced production of interleukin-6, compared to non-carriers. Conclusions The functional TLR4 Asp299Gly polymorphism is associated with lower LV mass in hypertensive women. These findings suggest that interactions among gender, LV remodeling and TLR4 gene variants may occur in hypertensive subjects.

The present study aims at understanding the changes in the channel conveyance and in the turbulent flow structure due to the presence of both submerged vegetation in the floodplains and riparian vegetation. An experimental campaign was carried out comprising uniform compound channels flows (i) without any kind of vegetation, (ii) with synthetic grass in the floodplains, (iii) with synthetic grass in the floodplains and rods in the interface between main channel and the floodplain and (iv) with synthetic grass in the floodplains and artificial shrubs in the interface between main channel and the floodplain. For comparison, the water depth in all flow cases was kept constant. Accurate acoustic Doppler velocimetry was used to evaluate the 3d velocity field and the turbulence structures characteristics.

The developmental requirements of ovarian follicles are dependent on the maturation stage of the follicle; in particular, elegant studies with genetic models have indicated that FSH is required for antral, but not preantral, follicle growth and maturation. To elucidate further the role of FSH and other regulatory molecules in preantral follicle development, in vitro culture systems are needed. We employed a biomaterials-based approach to follicle culture, in which follicles were encapsulated within matrices that were tailored to the specific developmental needs of the follicle. This three-dimensional system was used to examine the impact of increasing doses of FSH on follicle development for two-layered secondary (100-130 microm; two layers of granulosa cells surrounding the oocyte) and multilayered secondary (150-180 microm, several layers of granulosa cells surrounding the oocyte) follicles isolated from mice. Two-layered secondary follicles were FSH responsive when cultured in alginate-collagen I matrices, exhibiting FSH dose-dependent increases in follicle growth, lactate production, and steroid secretion. Multilayered secondary follicles were FSH dependent, with follicle survival, growth, steroid secretion, metabolism, and oocyte maturation all regulated by FSH. However, doses greater than 25 mIU/ml of FSH negatively impacted multilayered secondary follicle development (reduced follicle survival). The present results indicate that the hormonal and environmental needs of the follicular complex change during the maturation process. The culture system can be adapted to each stage of development, which will be especially critical for translation to human follicles that have a longer developmental period.

The structural organization of the interbranchial septum of the gill arch of the air-breathing loricariid fish Hypostomus plecostomus was examined using light and electron microscopy. In the middle of the interbranchial septum, an extensive interconnection was found between the afferent primary arteries from successive and opposing primary lamellae. The blood circulates among numerous trabeculae consisting of connective tissue, smooth muscle cells, and collagen fibres. A sheet of smooth muscle cells is localized at the borders of these interconnected primary arteries and joins the cartilage rod from one primary lamella to the adjacent one on the same hemibranch. The adductor muscles are restricted to the distal end of the interbranchial septum and consist of transverse and oblique striated muscle fibres fixed to the cartilage rod from the primary lamella of opposite hemibranchs. The arrangement of these muscle fibres suggests a double movement of adduction: approximation of the tips of the primary lamellae of opposing hemibranchs and reduction of the space between adjacent primary lamellae of the same hemibranch. The action of both smooth and striated muscles reduces the interconnecting vascular septal space between the primary arteries, which may allow fine adjustment of vascular perfusion of the distal part of the filaments as an adaptation for better blood flow under hypoxic conditions.

OBJECTIVE: To evaluate the onset of analgesic effect for a new formulation of ibuprofen sodium dihydrate versus conventional ibuprofen (ibuprofen acid). MATERIALS AND METHODS: In this randomized, double-blind, double-dummy, crossover trial, patients requiring surgical removal of two impacted or partially impacted mandibular third molars received: ibuprofen sodium dihydrate 400 mg plus conventional ibuprofen placebo (Group 1); or conventional ibuprofen 400 mg plus ibuprofen sodium dihydrate placebo (Group 2) following the first surgery. Patients were then crossed over to the alternative treatment. RESULTS: 72 patients were enrolled in Group 1 and 72 patients in Group 2. Ibuprofen sodium dihydrate produced faster initial pain relief than conventional ibuprofen as assessed by time to first pain relief (24.6 vs. 30.5 minutes; p = 0.004), and patient-assessed pain relief at 15 minutes ("some" to "complete" pain relief: 43% vs. 29%; p < 0.001) and 30 minutes (82% vs. 63%; p < 0.001) and pain intensity at 30 minutes (p < 0.001). Substantial pain relief with ibuprofen sodium dihydrate was twice that of conventional ibuprofen at 30 minutes (11% vs. 5%; not significant); 29% and 33% of patients did not reach substantial pain relief at 120 minutes. There were no adverse events leading to treatment discontinuation and only two serious adverse events (oral abscess and facial paresis with conventional ibuprofen) considered unrelated to treatment. CONCLUSIONS: Ibuprofen sodium dihydrate was as effective as conventional ibuprofen, but had a faster onset of initial pain relief and significantly reduced pain intensity within the first 30 minutes after administration, providing rapid clinically meaningful pain relief for patients.

Aim: The main purpose of this study was to determine whether general practitioners (GPs) in the Cape Town metropole have sufficient knowledge to diagnose and treat primary care ophthalmic conditions correctly, and to assess their own perceptions of their levels of knowledge. Secondary objectives included identifying the need for courses to improve the ophthalmic knowledge of GPs and assessing whether there is a need to revise the undergraduate curriculum in ophthalmology in general.Method: A cross-sectional survey was done. A questionnaire of 10 primary care level ophthalmology questions, including a self-assessment section, was sent to each of 140 randomly chosen GPs in Cape Town.Results: A response rate of 79.2% was obtained. Respondents included graduates from all eight medical schools in South Africa. Most of the responding GPs were practising for more than 10 years (78.2%). The mean test score was 52.5% (standard deviation [SD]: 22.2). The mean self-rating was 51.9% (SD: 14.5). There was no statistically significant difference between the test score and the self-rating score (p = 0.5840). Responding GPs felt that there is a need for ophthalmology up-skilling courses and 99.9% of them would attend such courses. Also, 82% of GPs felt that primary care doctors, not optometrists, should deliver primary eye care. Conclusion: GPs appear to lack sufficient knowledge to manage primary health eye care problems, presumably due to a lack of adequate training in the field. Clinical up-skilling courses are needed to improve core knowledge in ophthalmology.Keywords: survey; ophthalmology; general practitioners

Summary. Background: Protein S (PS) has direct anticoagulant activity, independently of activated protein C (APC). The mechanisms underlying this activity remain unclear, because PS preparations differ in activity, giving rise to conflicting results. Some purification procedures result in loss of intramolecular Zn2+, which is essential for inhibition of prothrombinase. Objective: To investigate the inhibition of extrinsic factor (F)Xase by Zn2+-containing PS. Methods: Purified component extrinsic FXase assays were used to determine FXa generation in the presence and absence of PS and/or tissue factor pathway inhibitor (TFPI). Binding assays, immunoblots and thrombin generation assays in plasma supported the FXase data. Results: Zn2+-containing PS potently inhibited extrinsic FXase in the presence of saturating phospholipids, independently of TFPI, whereas inhibition of extrinsic FXase by Zn2+-deficient PS required TFPI. Immunoblots for FXa and functional assays showed that Zn2+-containing PS inhibited primarily the quantity of FXa formed by tissue factor (TF)–FVIIa, rather than FXa amidolytic activity. Zn2+-containing PS, but not Zn2+-deficient PS, bound to TF with high affinity (Kd app = 41 nm) and targeted TF function. Binding of PS to FVIIa was negligible, whereas PS showed appreciable binding to FX. Increasing FX concentrations 10-fold reduced PS inhibition five-fold, suggesting that PS inhibition of FXase is FX-dependent. PS also exhibited TFPI-independent and APC-independent anticoagulant activity during TF-initiated thrombin generation in plasma. Conclusions: PS that retains native Zn2+ also retains anticoagulant functions independently of APC and TFPI. Inhibition of extrinsic FXase by PS at saturating levels of phospholipids depends on PS retention of intramolecular Zn2+, interaction with FX, and, particularly, interaction with TF.

BACKGROUND Experimental data demonstrated that inactivation of toll-like receptor (TLR) pathway components attenuated left ventricular (LV) remodeling induced by pressure overload. This study investigated the impact of TLR6 Ser249Pro polymorphism on LV structure in hypertensive subjects. METHODS A sample of 443 patients (266 women and 177 men) was evaluated by clinical history, physical examination, analysis of inflammatory and metabolic parameters, echocardiography, and genotyping of the TLR6 variant. Moreover, the relationship between genotypes and in vitro responsiveness of peripheral blood monocytic cells to TLR agonists was also assessed. RESULTS Homozygous women for the TLR6 249Ser allele had lower LV posterior wall thickness (9.4 + or - 0.4 vs. 10.5 + or - 0.1 mm; P = 0.02), interventricular septum thickness (9.7 + or - 0.3 vs. 10.7 + or - 0.1 mm; P = 0.03), and LV relative wall thickness (0.39 + or - 0.02 vs. 0.44 + or - 0.01; P = 0.02) than women with other genotypes. These results were confirmed by stepwise regression analyses adjusted by potential confounders. Conversely, homozygous men for the 249Ser variant showed no differences in LV structure in comparison to males carrying the 249Pro allele. In addition, monocytes from hypertensive women homozygous for the 249Ser allele showed a lower release of tumor necrosis factor-alpha and interleukin-6 in response to zymosan (TLR6 agonist), but not to lipopolysaccharide (TLR4 agonist). CONCLUSION These data suggest that hypertensive women homozygous for the TLR6 249Ser polymorphism might exhibit lower LV wall thickness and reduced TLR6-mediated inflammatory response than females carrying the major allele.

Background: At the admission in rehabilitation program, some patients with chronic respiratory disease were asked by a health professional to to answer a questionnaire about their sexuality. The objectives of the study were 1) to determine if sexual problems occurred in patients with respiratory chronic disease ; 2) to assess if these survey problems were linked to respiratory disease; 3) to explore the motivation to speak about sexuality during rehabilitation program. Methods: 52 consecutive respiratory disease subjects (58.3 ± 9 yr; FEV1 = 65.5 ± 21 % predicted, mean ± SD) answered a sexuality questionnaire survey with rehabilitation team (psychologists, nurses, physiotherapists). This group comprised 26 men and 26 women. Results: 70% of patients estimated that respiratory disease had an impact on their sexuality. A visual analog scale showed that 62% of patients were not satisfied. The severity of obstruction (FEV1) was not correlated to satisfaction (r=.017, P=0.90), or frequency (r=.08, P=0.55). Breathlessness was the most important factor of discomfort in sexual activity (61.5%). Tiredness and cough came second (32% and 21% respectively). 63% of respiratory patients never spoke about their sexuality with a health professional. 60% would like the health professional to begin to talk about their sexuality. 36% of patients spoke about it with a professional. In this group, 94% of patients told the professional about their sexual activity on their own initiative. Conclusion: More than one of two chronic respiratory disease patients (77%) participating in a rehabilitation program want sexuality to be taken into consideration during their program.

The psychiatric conditions secondary to substance use (whether legal or illegal drugs) are well characterized and include psychosis, mania, depression and behavior changes. We present a case of metformin-induced psychosis in a 79 years-old patient without any previous psychiatric history. She was brought to emergency room after suicide attempt by hanging. She had a one-month history of altered behavioral and presented paranoid delusional though. Hallucinations were excluded. A detailed clinical evaluation excluded dementia, late-onset chronic psychosis and primary mood disorders with psychotic symptoms and revealed that symptoms initiate few days after the introduction of metformin to treat her diabetes. After Metformin suspension, total remission of psychotic symptoms was obtained in one week and patient return to previous functionality. Psychosis secondary to metformin use is a very rare complication of oral antidiabetic drugs use but the awareness of this condition can lead to an earlier recognition and diagnosis.

FEBRUARY 2015 AB40 Abstracts S A T U R D A Y 123 Adult Eosinophilic Oesophagitis: A UK Based Case Series Efrem Eren, MBBS, MRCP, FRCPath, PhD, Tak Chin, William Rae, BSc, BM, MRCP, Syed H. Arshad, DM, FRCP, Peter H. Howarth, MD, Anthony Williams, Elena Salagean, SpR, Bryan N. Fernandes, MD, Ramesh Kurukulaaratchy, Carina Venter, PhD, RD; Southampton General Hospital, UK, Southampton, United Kingdom, Southampton, University Hospital Southampton, Southampton, United Kingdom, The David Hide Asthma and Allergy Research Centre, United Kingdom, University of Southampton, United Kingdom, Southampton General Hospital, Southampton, United Kingdom, University of Southampton, University Hospital of NHS Foundation Trust, United Kingdom, University of Southampton, Southampton, United Kingdom, University of Portsmouth, United Kingdom. RATIONALE: Adult onset Eosinophilic Oesophagitis (EoE) presents frequently to the allergy clinics in the UK. However, no study to date has attempted to describe these patients. . This case series set out to clinically characterise adults patients with EoE seen over the past four years in a tertiary care center in the UK. METHODS: We screened Allergy/Immunology clinic lists and the edocument systems at Southampton General Hospital (SGH) for patients given a diagnosis of EoE since 2010. RESULTS: Thirty six patients were identified with a diagnostic label of EoE. They were predominantly male (77.8%; 28/36) with an age range of 19 – 71 years. The majority (61%, 22/36) suffered from other atopic conditions/or showed a positive total IgE level and suspected a wide range of potential foods triggers. Interestingly, patients often considered food that are difficult to swallow such as meat, chicken and starchy food as the cause of their problems. SPT and specific IgE tests were not helpful in identifying offending foods. As expected the majority (58.3%; 21/36) were sensitised to aero-allergens with 14 being sensitised to tree/birch pollen. Dietary interventions varied widely between these patients, ranging from elemental diets, 6 food elimination diets to test directed diets. CONCLUSIONS: Male sex and atopy were found to be primary characteristics, but age did not influence the diagnosis. A wide range of foods are suspected to trigger EoE pathology in adults, and dietarymeasure seems to vary greatly. Studies are needed to identify which foods are implicated in adult EoE in the UK.

7 pages, 1 table.-- PMID: 16762114 [PubMed]., An epidemiological survey was undertaken to explore human exposure to Rickettsia slovaca in two provinces of northern Spain. When IFAT were used to test 200 members of the general population for antibodies to rickettsiae of the spotted-fever group, six (3.3%) were found positive, presumably, since Dermacentor is one of the most common genera of human-biting tick in the study area, for antibodies to R. slovaca. Thirty-one (16.9%) of an additional 183 subjects who presented shortly after being bitten by ticks were also found seropositive. The difference in seroprevalence between the general and the tick-bitten populations was significant. Subject gender had no influence on seroprevalence in either population, although, in the tick-bitten group, age and occupation did have a significant influence on the prevalence recorded. Immunoblotting was used to confirm the presence of antibodies in the five subjects, all from the tick-bitten group, found to have acute infections. Three D. marginatus ticks obtained from three of these acute cases were found PCR-positive for R. slovaca DNA., The authors would like to thank all the physicians who provided serum samples, and the members of the EBATRAG (Enfermedades Bacterianas Transmitidas por Garrapatas) network in Castilla-León (G03/057).

In this work, anthers isolated from male flowers of carob tree (Ceratonia siliqua L.) at developmental phase II were cryopreserved by vitrification, using a fast freezing method. Different types of carbohydrates at different concentrations, namely sorbitol (0.5 M, 1 M, and 2 M), mannitol (0.5 M and 1 M), sucrose (0.5 M, 1 M, and 2 M), and glucose (0.5 M, 1 M, and 2 M), namely sorbitol, mannitol, sucrose and glucose, were compared with respect to their capacity of inducing freeze tolerance in pollen of carob tree. Carbohydrates were applied as a pre-treatment to anthers before cryostorage. It was also assessed if the presence of the cryoprotectant during the storage period was beneficial for pollen viability. The viability of cryopreserved pollen was evaluated after 5 and 8 months of storage. The application of the cryoprotectants generally increased pollen viability as compared with the control. The best results were obtained after 5 months storage, in the presence of the cryo-protector, with pollen pre-treated with sucrose 0.5 M. The viability of pollen decreased with increasing the duration of storage period.

Laminin-5, the major extracellular matrix protein produced by mammary epithelial cells, is composed of three chains (designated alpha3A, beta3, and gamma2), each encoded by a separate gene. Laminin-5 is markedly down-regulated in breast cancer cells. Little is known about the regulation of laminin gene transcription in normal breast cells, nor about the mechanism underlying the down-regulation seen in cancer. In the present study, we cloned the promoter of the gene for the human laminin alpha3A chain (LAMA3A) and investigated its regulation in functionally normal MCF10A breast epithelial cells and several breast cancer cell lines. Using site-directed mutagenesis of promoter-reporter constructs in transient transfection assays in MCF10A cells, we find that two binding sites for Kruppel-like factor 4 (KLF4/GKLF/EZF) are required for expression driven by the LAMA3A promoter. Electrophoretic mobility shift assays reveal absence of KLF4 binding activity in extracts from T47D, MDA-MB 231, ZR75-1, MDA-MB 436, and MCF7 breast cancer cells. Transient transfection of a plasmid expressing KLF4 activates transcription from the LAMA3A promoter in breast cancer cells. A reporter vector containing duplicate KLF4-binding sites in its promoter is expressed at high levels in MCF10A cells but at negligible levels in breast cancer cells. Thus, KLF4 is required for LAMA3A expression and absence of laminin alpha3A in breast cancer cells appears, at least in part, attributable to the lack of KLF4 activity.