Internet interventions for treatment of alcohol related problems

This is the protocol for a review and there is no abstract. The objectives are as follows: The primary objective of this review will be to assess the effect of internet and mobile phone alcohol-related interventions on reducing participants' alcohol consumption. Secondary objectives will include assessing the impact of the interventions on symptoms of alcohol-related disorders and degree of alcohol dependence, the effects on functioning, and patient acceptability. The review will also assess whether there are different outcomes for different diagnostic groups, and which intervention approaches or components (including therapeutic support) may be contributing to any positive effects.

Mechanistic details of the membrane perforation and passive translocation of TAT peptides

The trans-activator of transcription (TAT) peptide is regarded as the “gold standard” for cell-penetrating peptides, capable of traversing a mammalian membrane passively into the cytosolic space. This characteristic has been exploited through conjugation of TAT for applications such as drug delivery. However, the process by which TAT achieves membrane penetration remains ambiguous and unresolved. Mechanistic details of TAT peptide action are revealed herein by using three complementary methods: quartz crystal microbalance with dissipation (QCM-D), scanning electrochemical microscopy (SECM) and atomic force microscopy (AFM). When combined, these three scales of measurement define that the membrane uptake of the TAT peptide is by trans-membrane insertion using a “worm-hole” pore that leads to ion permeability across the membrane layer. AFM data provided nanometre-scale visualisation of TAT punctuation using a mammalian-mimetic membrane bilayer. The TAT peptide does not show the same specificity towards a bacterial mimetic membrane and QCM-D and SECM showed that the TAT peptide demonstrates a disruptive action towards these membranes. This investigation supports the energy-independent uptake of the cationic TAT peptide and provides empirical data that clarify the mechanism by which the TAT peptide achieves its membrane activity. The novel use of these three biophysical techniques provides valuable insight into the mechanism for TAT peptide translocation, which is essential for improvements in the cellular delivery of TAT-conjugated cargoes including therapeutic agents required to target specific intracellular locations.

The ASAS criteria for axial spondyloarthritis: Strengths, weaknesses, and proposals for a way forward

Classification criteria should facilitate selection of similar patients for clinical and epidemiologic studies, therapeutic trials, and research on etiopathogenesis to enable comparison of results across studies from different centers. We critically appraise the validity and performance of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA). It is still debatable whether all patients fulfilling these criteria should be considered as having true axSpA. Patients with radiographically evident disease by the ASAS criteria are not necessarily identical with ankylosing spondylitis (AS) as classified by the modified New York criteria. The complex multi-arm selection design of the ASAS criteria induces considerable heterogeneity among patients so classified, and applying them in settings with a low prevalence of axial spondyloarthritis (SpA) greatly increases the proportion of subjects falsely classified as suffering from axial SpA. One of the unmet needs in non-radiographic form of axial SpA is to have reliable markers that can identify individuals at risk for progression to AS and thereby facilitate early intervention trials designed to prevent such progression. We suggest needed improvements of the ASAS criteria for axSpA, as all criteria sets should be regarded as dynamic concepts open to modifications or updates as our knowledge advances.

Narrativas de vida de mulheres alcoolistas: contribuições para a prática da enfermeira no CAPS ad

Estudo de natureza qualitativa utilizou o Método de Narrativa de Vida, cujo objeto foi a motivação da mulher alcoolista para iniciar e aderir ao tratamento no Centro de Atenção Psicossocial de Álcool e outras Drogas (CAPS ad). Os objetivos foram: a) conhecer os motivos que levam a mulher alcoolista a iniciar e aderir ao tratamento; b) descrever o itinerário terapêutico percorrido pela mulher alcoolista; c) identificar os fatores que favorecem a adesão da mulher alcoolista ao tratamento; d) discutir a contribuição das narrativas das mulheres alcoolistas para a prática da enfermeira no CAPS ad. Foram entrevistadas 26 mulheres usuárias de álcool em tratamento no CAPS ad, oriundas de dois cenários distintos no Estado do Rio de Janeiro: um CAPS ad de uma cidade do interior do Estado na região Sul Fluminense no Médio Paraíba e um CAPS ad na cidade do Rio de Janeiro. O arcabouço teórico de sustentação do estudo baseou-se em dois pontos: A Reforma Psiquiátrica no Mundo e no Brasil, a evolução da Política Pública, a Legislação Brasileira para atendimento de usuários de álcool e outras drogas, incluindo Itinerários Terapêuticos, a atuação da Equipe Interdisciplinar no CAPS ad e o papel da Enfermeira e da enfermagem na Saúde Mental e no CAPS ad. O alcoolismo feminino, retratando a evolução do papel da mulher contemporânea na sociedade, questões de gênero e as implicações biológicas, culturais e sociais do alcoolismo onde Edwards e colaboradores discutem as questões biopsicosociais envolvidas na questão. A coleta de dados utilizou a entrevista aberta, com pergunta única: Fale-me a respeito de sua vida que tenha relação com a sua motivação para iniciar e aderir ao tratamento de dependência alcoólica que realiza no CAPS ad. A análise evidenciou: que um dos motivos que caracteriza o alcoolismo feminino refere-se ao prazer proporcionado pelo álcool como escape para as mulheres aliviarem o peso de suas vidas. Estas viveram e experimentaram a solidão, a dor, o sofrimento, a vergonha, a discriminação, as perdas e os agravos físicos e psicológicos decorrentes do uso abusivo de bebida alcoólica. Estas mulheres viveram seus conflitos e suas dores sozinhas com raríssimas exceções, até chegarem ao fim do poço, quando então decidiram procurar e aceitar ajuda. Os itinerários terapêuticos apresentados foram: Hospital Geral; Unidade Básica de Saúde; Pré-natal; Alcoólicos Anônimos (AA); CAPS; CAPS i; Ambulatório de Psiquiatria; Hospital Psiquiátrico e Clínica Especializada de Internação. A motivação para terem iniciado o tratamento foram: desejo de mudarem a realidade que viveram; a perda do poder familiar, ou seja, a perda da guarda dos filhos; a solidão que viveram e a imposição de terceiros para iniciarem o tratamento. Como motivação para adesão ao tratamento foi encontrada na totalidade das narrativas a permanência para conseguir ficar sem uso de bebida alcoólica, e o apoio que receberam da equipe interdisciplinar. Na percepção das mulheres em relação à atuação da equipe interdisciplinar do CAPS ad foi relatada sobre a ajuda que receberam, a escuta, o acolhimento, a paciência, o relacionamento interpessoal entre usuários e profissionais, o cuidado, a força para continuar e a valorização delas como sujeitos essenciais de suas histórias.

Pharmacokinetics of melatonin in preterm infants

Aims: Preterm infants are deprived of the normal intra-uterine exposure to maternal melatonin and may benefit from replacement therapy. We conducted a pharmacokinetic study to guide potential therapeutic trials. Methods: Melatonin was administered to 18 preterm infants in doses ranging from 0.04-0.6μgkg^-1 over 0.5-6h. Pharmacokinetic profiles were analyzed individually and by population methods. Results: Baseline melatonin was largely undetectable. Infants receiving melatonin at 0.1μgkg^-1h^-1 for 2h showed a median half-life of 15.82h and median maximum plasma concentration of 203.3pgml^-1. On population pharmacokinetics, clearance was 0.045lh^-1, volume of distribution 1.098l and elimination half-life 16.91h with gender (P = 0.047) and race (P < 0.0001) as significant covariates. Conclusions: A 2h infusion of 0.1μgkg^-1h^-1 increased blood melatonin from undetectable to approximately peak adult concentrations. Slow clearance makes replacement of a typical maternal circadian rhythm problematic. The pharmacokinetic profile of melatonin in preterm infants differs from that of adults so dosage of melatonin for preterm infants cannot be extrapolated from adult studies. Data from this study can be used to guide therapeutic clinical trials of melatonin in preterm infants. © 2013 The British Pharmacological Society.

Clinical Application of Poly(ADP-Ribose) Polymerase Inhibitors in High-Grade Serous Ovarian Cancer

: High-grade serous ovarian cancer is characterized by genomic instability, with one half of all tumors displaying defects in the important DNA repair pathway of homologous recombination. Given the action of poly(ADP-ribose) polymerase (PARP) inhibitors in targeting tumors with deficiencies in this repair pathway by loss of BRCA1/2, ovarian tumors could be an attractive population for clinical application of this therapy. PARP inhibitors have moved into clinical practice in the past few years, with approval from the Food and Drug Administration (FDA) and European Medicines Agency (EMA) within the past 2 years. The U.S. FDA approval of olaparib applies to fourth line treatment in germline BRCA-mutant ovarian cancer, and European EMA approval to olaparib maintenance in both germline and somatic BRCA-mutant platinum-sensitive ovarian cancer. In order to widen the ovarian cancer patient population that would benefit from PARP inhibitors, predictive biomarkers based on a clear understanding of the mechanism of action are required. Additionally, a better understanding of the toxicity profile is needed if PARP inhibitors are to be used in the curative, rather than the palliative, setting. We reviewed the development of PARP inhibitors in phase I-III clinical trials, including combination trials of PARP inhibitors and chemotherapy/antiangiogenics, the approval for these agents, the mechanisms of resistance, and the outstanding issues, including the development of biomarkers and the rate of long-term hematologic toxicities with these agents.

IMPLICATIONS FOR PRACTICE: The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib has recently received approval from the Food and Drug Administration (FDA) and European Medicines Agency (EMA), with a second agent (rucaparib) likely to be approved in the near future. However, the patient population with potential benefit from PARP inhibitors is likely wider than that of germline BRCA mutation-associated disease, and biomarkers are in development to enable the selection of patients with the potential for clinical benefit from these agents. Questions remain regarding the toxicities of PARP inhibitors, limiting the use of these agents in the prophylactic or adjuvant setting until more information is available. The indications for olaparib as indicated by the FDA and EMA are reviewed.

Non-pain goal pursuit inhibits attentional bias to pain

Although dealing with pain is a vital goal to pursue, most individuals are also engaged in the pursuit of other goals. The aim of the present experiment was to investigate whether attentional bias to pain signals is inhibited when one is pursuing a concurrent salient but nonpain task goal. Attentional bias to pain signals was measured in pain-free volunteers (n=63) using a spatial cueing task with pain cues and neutral cues. The pursuit of a concurrent goal was manipulated by including additional trials in which a digit appeared at the middle of the screen. Half of the participants (goal group) were instructed to name these additional stimuli aloud. In order to increase the affective-motivational value of this non-pain-related goal, monetary reward and punishment were made contingent upon the performance of this task. Participants of the control group did not perform the additional task. As predicted, the results show attentional bias to pain signals in the control group, but not in the goal group. This indicates that attentional bias to signals of impending pain is inhibited when one is engaged in the pursuit of another salient but nonpain goal. The results of this study underscore a motivational view on attention to pain, in which the pursuit of multiple goals, including nonpain goals, is taken into account.

Threat interpretation bias in anxious children and their mothers

The role of parents in the development of anxiety disorders in children is of increasing research and clinical interest. This study investigated interpretation biases of anxious children and their mothers using the ambiguous stimuli task developed by Hadwin, Frost, French, and Richards (1997). Three groups of children (aged 7 to 12 years) and their mothers were recruited; 23 non-clinical controls, 18 children with an anxiety disorder and 15 children with an externalising disorder. Following diagnostic assessments of the children, children and their mothers independently completed the homophone task and self-report measures of anxiety. Mothers of anxious children had significantly higher self-reported anxiety than mothers of non-clinical children. As hypothesised, children in the anxious group had higher threat interpretation scores than the non-clinical group. The hypothesis that mothers of anxious children would make more threat interpretations was not supported. Paired correlations showed no significant association between threat interpretations made by children and their mothers. There was a significant positive correlation between maternal threat interpretation and child anxiety. The results suggest that there is a complex association between mother's anxiety and cognitions and those of their children, which requires further examination in controlled observational and experimental studies, including treatment trials.

Histological assessment of intermediate - and long-term creatine monohydrate supplementation in mice and rats

Creatine monohydrate (CrM) supplementation appears to be relatively safe based on data from short-term and intermediate-term human studies and results from several therapeutic trials. The purpose of the current study was to characterize pathological changes after intermediate-term and long-term CrM supplementation in mice [healthy control and SOD1 (G93A) transgenic] and rats (prednisolone and nonprednisolone treated). Histological assessment (18-20 organs/tissues) was performed on G93A mice after 159 days, and in Sprague-Dawley rats after 365 days, of CrM supplementation (2% wt/wt) compared with control feed. Liver histology was also evaluated in CD-1 mice after 300 days of low-dose CrM supplementation (0.025 and 0.05 g · kg^-1 · day^-1) and in Sprague-Dawley rats after 52 days of CrM supplementation (2% wt/wt) with and without prednisolone. Areas of hepatitis were observed in the livers of the CrM-supplemented G93A mice (P < 0.05), with no significant inflammatory lesions in any of the other 18-20 tissues/organs that were evaluated. The CD-1 mice also showed significant hepatic inflammatory lesions (P < 0.05), yet there was no negative effect of CrM on liver histology in the Sprague-Dawley rats after intermediate-term or long-term supplementation nor was inflammation seen in any other tissues/organs (P = not significant). Dietary CrM supplementation can induce inflammatory changes in the liver of mice, but not rats. The observed inflammatory changes in the murine liver must be considered in the evaluation of hepatic metabolism in CrM-supplemented mice. Species differences must be considered in the evaluation of toxicological and physiological studies.

Disrupting disordered neurocircuitry : treating refractory psychiatric illness with neuromodulation

Despite the premature and somewhat infamous rise and fall of psychosurgery in the mid-20th century, the current era of functional neuromodulation proffers immense opportunity for surgical intervention in treatment-resistant psychiatric disorders. On the basis of recent successes with novel, focused, less invasive, and reversible treatment strategies for movement disorders, several therapeutic trials have been conducted to investigate the effectiveness of deep brain stimulation (DBS) in treatment-resistant depression, obsessive-compulsive disorder (OCD), and Tourette syndrome. The many anatomic targets for these psychiatric disorders are indicative of both the system-wide effects of DBS and the network-level dysfunction mediating the emotional and cognitive disturbances. To gain insight into the application of neuromodulation therapies and their further advancement, we must elucidate neuroanatomic networks involved in refractory psychiatric illness, the neurophysiological anomalies that contribute to disordered information processing therein, and the local and system-wide modulatory effects of DBS. This review discusses the history of psychosurgical procedures, recent DBS clinical data, current anatomic models of psychopathology, and possible therapeutic mechanisms of action of DBS neuromodulation. Our search criteria for PubMed included combinations of the following terms: neuromodulation, DBS, depression, OCD, Tourette syndrome, mechanism of action, and history. Dates were not restricted. As clinical and basic scientific investigations probe the neuromodulatory effects of DBS in the treatment of refractory neuropsychiatric illness, our knowledge of these disorders and our potential to treat them are rapidly expanding. Indeed, this modern era of neuromodulation may provide the key that unlocks many of the mysteries pertaining to the biological basis of disordered emotional neurocircuitry.

Consenso em reumatologia pediátrica: parte II - definição de melhora clínica para o lúpus eritematoso sistêmico e dermatomiosite juvenil

OBJETIVO: avaliar as medidas de atividade e critérios de melhora clínica para o lúpus eritematoso sistêmico juvenil (LESJ) e dermatomiosite juvenil (DMJ), desenvolvidos por meio de consenso entre especialistas. MÉTODOS E RESULTADOS: para o LESJ, as medidas essenciais em cinco domínios e as respectivas variáveis foram: 1) avaliação global pelo médico por escala analógica visual de 0-10 cm; 2) avaliação da qualidade de vida relacionada à saúde (índice Físico - CHQ-PF50); 3) avaliação da atividade pelos pais/paciente por escala analógica visual de 0-10 cm; 4) avaliação renal (proteinúria 24 h); e 5) avaliação global da atividade por instrumento específico (SLEDAI ou ECLAM). A definição preliminar de melhora clínica para o JSLE foi: melhora > 50% em pelo menos 2 das 5 variáveis e não mais que uma com piora > 30%, a qual não pode ser a proteinúria de 24h em casos com envolvimento renal. Os seis domínios e as respectivas variáveis selecionadas para a atividade na DMJ foram: 1) avaliação global pelo médico por escala analógica visual de 0-10 cm; 2) avaliação da força muscular proximal por meio de teste específico - CMAS-Childhood Myositis Assessment Scale 0-52; 3) avaliação da capacidade funcional (CHAQ); 4) avaliação da atividade pelos pais/paciente por escala analógica visual de 0-10 cm; 5) avaliação da qualidade de vida relacionada à saúde (Índice Físico - CHQ-PF50); 6) avaliação global da atividade por meio de instrumento específico (DAS - Disease Activity Score). A definição preliminar de melhora clínica para a DMJ foi: pelo menos 3 de quaisquer das 6 variáveis com melhora > 20% e não mais que uma com piora > 30%, a qual não pode ser o CMAS. CONCLUSÕES: estas variáveis foram testadas em uma casuística representativa e mostraram propriedades estatísticas adequadas de responsividade e validade discriminativa, podendo ser estudadas em ensaios terapêuticos.

Evaluation of the antimutagenic and anticarcinogenic effects of inulin in vivo

The incidence of colorectal cancer is growing worldwide. The characterization of compounds present in the human diet that can prevent the occurrence of colorectal tumors is vital. The oligosaccharide inulin is such a compound. The aim of this study was to evaluate the antigenotoxic, antimutagenic and anticarcinogenic effects of inulin in vivo. Our study is based on 3 assays that are widely used to evaluate chemoprevention (comet assay, micronucleus assay, and aberrant crypt focus assay) and tests 4 protocols of treatment with inulin (pre-treatment, simultaneous, post-treatment, and pre + continuous). Experiments were carried out in Swiss male mice of reproductive age. In order to induce DNA damage, we used the pro-carcinogenic agent 1,2-dimethylhydrazine. Inulin was administered orally at a concentration of 50 mg/kg body weight following the protocols mentioned above. Inulin was not administered to the control groups. Our data from the micronucleus assay reveal antimutagenic effects of inulin in all protocols. The percentage of inulin-induced damage reduction ranged from 47.25 to 141.75% across protocols. These data suggest that inulin could act through desmutagenic and bio-antimutagenic mechanisms. The anticarcinogenic activity (aberrant crypt focus assay) of inulin was observed in all protocols and the percentages of damage reduction ranged from 55.78 to 87.56% across protocols. Further tests, including human trials, will be necessary before this functional food can be proven to be effective in the prevention and treatment of colon cancer. © FUNPEC-RP.

Failures in the rehabilitation treatment with removable partial dentures

Background. Despite being functional and having aesthetic benefits, the acceptance of patients regarding the use of removable partial dentures (RPDs) has been low. In part, this is due to the deleterious effects that causes discomfort to the patient. Success depends not only on the care expended by the patient, including daily care and oral hygiene, but also on common goals set by their professional and clinical staff, aiming beyond aesthetics, to incorporate issues of functionality and the well-being of patients. Methods and results. For rehabilitation treatment with RPDs to reach the desired level of success without damaging the support structure, all the steps (diagnose, cavity preparation, adaptation of the metal structures, functional of distal extension and posterior follow-up) in the rehabilitative treatment should be carefully developed. A literature review was carried out, searching through MEDLINE (PubMed) articles published between 1965 and December 2012 including clinical trials and reviews about the use of RPDs. Conclusions. This study describes factors that lead to failures and complications in oral rehabilitation through the use of RPDs and suggests possible solutions.

Antimicrobial activity of natural products against Helicobacter pylori: a review

Throughout the genetic and physiological evolution of microorganisms, the microbiological sciences have been expanding the introduction of new therapeutic trials against microbial diseases. Special attention has been paid to the bacterium Helicobacter pylori, which induces gastric infections capable of causing damage, ranging from acute and chronic gastritis to the development of gastric cancer and death. The use of compounds with natural origins has gained popularity in scientific research focused on drug innovation against H. pylori because of their broad flexibility and low toxicity. The aim of this study was to describe the use of natural products against H. pylori in order to clarify important parameters for related fields. The study demonstrated the vast therapeutic possibilities for compounds originating from natural sources and revealed the need for innovations from future investigations to expand the therapeutic arsenal in the fight against H. pylori infection.

Syngonanthus nitens (Bong.) Ruhland: caracterização biológica e prospecção terapêutica do extrato metanólico incorporado ou não em sistema nanoestruturado para aplicação no tratamento da candidíase vulvovaginal

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)