Transcranial direct current stimulation during a prolonged cognitive task: the effect on cognitive and shooting performances in professional female basketball players.

The negative effect of prolonged cognitive demands on psychomotor skills in athletes has been demonstrated. Transcranial direct current stimulation (tDCS) could be used to mitigate this effect. This study examined the effects of tDCS over the left dorsolateral prefrontal cortex (DLPFC) during a 30-min inhibitory Stroop task on cognitive and shooting performances of professional female basketball players. Following a randomised, double-blinded, sham-controlled, cross-over design, players were assigned to receive anodal tDCS (a-tDCS, 2 mA for 20 min) or sham-tDCS in two different sessions. Data from 8 players were retained for analysis. Response Time decreased significantly over time (p < 0.001; partial η2 = 0.44; no effect of condition, or condition vs. time interaction). No difference in mean accuracy and shooting performance was observed between tDCS conditions. The results suggest that a-tDCS exert no additional benefits in reducing the negative effects of prolonged cognitive demands on technical performance compared to sham (placebo).Practitioner summary: Prolonged cognitive demands can negatively affect the athletes' performance. We tested whether transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) could attenuate these effects on cognitive and shooting performance in professional female basketball players. However, tDCS did not exert any additional benefits compared to sham.Abbreviations: tDCS: transcranial direct current stimulation; a-tDCS: anodal transcranial direct current stimulation; PFC: prefrontal cortex; DLPFC: dorsolateral prefrontal cortex; PCT: prolonged cognitive task; TT: time trial; RT: response time; NASA-TLX: National Aeronautics and Space Administration Task Load Index; RPE: ratings of perceived exertion; CR-10 scale: category rating scale; EEG: electroencephalogram; AU: arbitrary units.

Comparative Bioavailability of Two Diosmin Formulations after Oral Administration to Healthy Volunteers.

Diosmin is a flavonoid commonly found in citrus fruits, largely used as adjuvant treatment for circulatory disorders, including chronic venous insufficiency (CVI) and hemorrhoids. Following oral administration, diosmin is not directly absorbed but must first be hydrolyzed into its aglycone, diosmetin, which is then absorbed into the systemic circulation. The aim of the current cross-over clinical study was to assess the pharmacokinetic profile of µSmin® Plus, a micronized diosmin flavonoid complex standardized in diosmin and formulated with a buffering agent (tested formulation). The study compared this to unformulated micronized diosmin (reference), in 16 healthy volunteers. Plasma samples were analyzed by HPLC-MS and plasma diosmetin concentration was measured after deconjugation with ß-glucuronidase. For the tested formulation area under the curve (AUC0-t), and maximum plasma and time concentration (Cmax; tmax) were found to be 298.4 ± 163.7, 50.3 ± 22.6 and 2.2 ± 2.9, respectively. AUC0-t and Cmax of the reference were 31.9 ± 100.4 and 2.4 ± 1.9, respectively. The tested formulation showed higher plasmatic concentrations of diosmetin in comparison to those obtained after the administration of unformulated micronized diosmin. The relative bioavailability was 9.4 greater for the tested formulation than in micronized diosmin. In conclusion, our data indicate that µSmin® Plus was rapidly and well absorbed into systemic circulation and may therefore be ideally suitable to deliver diosmin in human interventional trials.

[The evaluation of unsaturation of blood lipids using methods of physical chemistry and clinical biochemistry. The insulin regulation of metabolism of fatty acids, number of double binds and cell absorption of glucose].

It is supposed that the main cause of insulin synthesis at late stages of phylogenesis became discrepancy between increase in vivo need in energy and physical chemical parameters of palmitic saturated fatty acid; its transportation to cells in composition of lipoproteins in optimal quantity (more than 15% of all fatty acids) became in vivo unfeasible. The biological role of insulin consists in supporting of insulin-dependent cells (skeletal miocytes in the first place) with substrates for gaining energy. The hormone transforms all palmitic saturated fatty acid endogenously synthesized from glucose into specific for animal cells rn-9 C18:1 oleic mono unsaturated fatty acid. The endogenous mono unsaturated fatty acid is oxidized by mitohondria with the highest constant of reaction velocity gaining for cells optimal quantity of biotransforming energy in the form of ATP. The insulin expresses in hepatocytes synthesis of oleic triglycerides and formation of oleic lipoproteins of very low density that only insulin-dependent cells absorb using apoE/B-100-endocytosis. The insulin expresses synthesis of Palmitoyl-KoA-elongase, stearyl-KoA-desaturase and glucose transporters 4, activates glucose absorption by cells with the purpose of synthesis endogenous oleic saturated fatty acid. The insulin substitutes in vivo ineffective palmitic alternative of metabolism of fatty acids for potentially more effective oleic metabolism of fatty acids. The insulin increases unsaturation of fatty acids and number of double binds in them. This can be established by direct titration of double binds by ozone on the basis of quantitative detection of fatty acids using technique of gas chromatography and calculating ratio C16:1/C16:0, C18:1/C18:0 and C18:1/C16:0. The diabetes mellitus is a disorder of metabolism of mono unsaturated fatty acid in the first place and only in the second place pathology of glucose absorption by cells.

An 8-week course of 45 mg of carbonyl iron daily reduces iron deficiency in female whole blood donors aged 18 to 45 years: results of a prospective randomized controlled trial.

BACKGROUND: Blood donation is known to contribute to iron deficiency in regular blood donors. This study investigated the safety and efficacy of postdonation iron replacement to mitigate iron deficiency in blood donors. STUDY DESIGN AND METHODS: A total of 282 female whole blood donors aged 18 to 45 were prospectively randomized in a double-blinded placebo controlled trial to receive an 8-week postdonation course of carbonyl iron (45 mg daily) or placebo. The primary endpoint was prevalence of iron deficiency (ferritin < 15 ng/mL) at 12 weeks postdonation. Secondary endpoints were eligibility to donate based on capillary hemoglobin (Hb) and incidence of gastrointestinal (GI) complaints. RESULTS: Ferritin levels at Week 12 were significantly higher in donors receiving carbonyl iron (17.0 ± 10.9 ng/mL) compared with those receiving placebo (10.6 ± 8.4 ng/mL; p < 0.001). The proportion of iron-deficient donors was significantly lower in the carbonyl iron group (51.9%) compared to the placebo (80.5%; p < 0.001). The mean Hb level in the carbonyl iron group (134.6 ± 8.7 g/L) was significantly higher than in the placebo arm (130.0 ± 9.9 g/L; p < 0.001), significantly improving eligibility to donate at Week 12. Significantly more donors receiving carbonyl iron had at least one GI side effect (p < 0.001). Importantly, 86.7% of donors receiving carbonyl iron indicated that they would take iron on an ongoing basis. CONCLUSION: An 8-week postdonation course of 45 mg of carbonyl iron significantly reduced iron deficiency and was well tolerated in female whole blood donors. Postdonation iron replacement may have a role in a broader strategy to optimize donor iron status.

Bioavailability and systemic transport of oleanolic acid in humans, formulated as a functional olive oil.

Evidence of the pharmacological activity of oleanolic acid (OA) suggests its potential therapeutic application. However, its use in functional foods, dietary supplements, or nutraceuticals is hindered by limited human bioavailability studies. The BIO-OLTRAD trial is a double-blind, randomized controlled study with 22 participants that received a single dose of 30 mg OA formulated as a functional olive oil. The study revealed that the maximum serum concentration of OA ranged from 500 to 600 ng mL-1, with an AUC0-∞ value of 2862.50 ± 174.50 ng h mL-1. Furthermore, we discovered a physiological association of OA with serum albumin and triglyceride-rich lipoproteins (TRL). UV absorption spectra showed conformational changes in serum albumin due to the formation of an adduct with OA. Additionally, we demonstrated that TRL incorporate OA, reaching a maximum concentration of 140 ng mL-1 after 2-4 hours. We conjecture that both are efficient carriers to reach target tissues and to yield high bioavailability.

Explaining elevated social anxiety among Asian Americans: emotional attunement and a cultural double bind.

Previous research has documented elevated levels of social anxiety in Asian American college students when compared with their European American peers. The authors hypothesized that higher symptoms among Asians could be explained by cultural differences in attunement to the emotional states of others. Socialization within interdependent cultures may cultivate concerns about accurately perceiving other's emotional responses, yet at the same time, norms governing emotional control may limit competencies in emotion recognition. A sample of 264 Asian American and European American college students completed measures of social anxiety, attunement concerns (shame socialization and loss of face), and attunement competencies (self-reported sensitivity and performance on emotion recognition tasks). Results confirmed that ethnic differences in social anxiety symptoms were mediated by differences in attunement concerns and competencies in emotion recognition. Asian American college students may find themselves in a double bind that leads to social unease because of a cultural emphasis on sensitivity to others' emotions in the midst of barriers to developing this attunement skill set.

A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57.

BACKGROUND: Maternal blood folate concentrations during pregnancy have been previously linked with DNA methylation patterns, but this has been done predominantly through observational studies. We showed recently in an epigenetic analysis of the first randomized controlled trial (RCT) of folic acid supplementation specifically in the second and third trimesters (the EpiFASSTT trial) that methylation at some imprinted genes was altered in cord blood samples in response to treatment. Here, we report on epigenome-wide screening using the Illumina EPIC array (~ 850,000 sites) in these same samples (n = 86). RESULTS: The top-ranked differentially methylated promoter region (DMR) showed a gain in methylation with folic acid (FA) and was located upstream of the imprint regulator ZFP57. Differences in methylation in cord blood between placebo and folic acid treatment groups at this DMR were verified using pyrosequencing. The DMR also gains methylation in maternal blood in response to FA supplementation. We also found evidence of differential methylation at this region in an independent RCT cohort, the AFAST trial. By altering methylation at this region in two model systems in vitro, we further demonstrated that it was associated with ZFP57 transcription levels. CONCLUSIONS: These results strengthen the link between folic acid supplementation during later pregnancy and epigenetic changes and identify a novel mechanism for regulation of ZFP57. This trial was registered 15 May 2013 at www.isrctn.com as ISRCTN19917787.

Hepatic triglyceride content does not affect circulating CETP: lessons from a liraglutide intervention trial and a population-based cohort.

Cholesteryl ester transfer protein (CETP) is mainly expressed by Kupffer cells in the liver. A reduction of hepatic triglyceride content (HTGC) by pioglitazone or caloric restriction is accompanied by a decrease in circulating CETP. Since GLP-1 analogues also reduce HTGC, we assessed whether liraglutide decreases CETP. Furthermore, we investigated the association between HTGC and CETP in a population-based cohort. In a placebo-controlled trial, 50 patients with type 2 diabetes were randomly assigned to treatment with liraglutide or placebo added to standard care. In this trial and in 1,611 participants of the Netherlands Epidemiology of Obesity (NEO) study, we measured HTGC and circulating CETP by proton magnetic resonance spectroscopy and ELISA, respectively. The HTGC was decreased in the liraglutide group (-6.3%; 95%CI of difference [-9.5, -3.0]) but also in the placebo group (-4.0%; 95%CI[-6.0, -2.0]), without between-group differences. CETP was not decreased by liraglutide (-0.05 µg/mL; 95%CI[-0.13, 0.04]) or placebo (-0.04 µg/mL; 95%CI[-0.12, 0.04]). No association was present between HTGC and CETP at baseline (ß: 0.002 µg/mL per %TG, 95%CI[-0.005, 0.009]) and between the changes after treatment with liraglutide (ß: 0.003 µg/mL per %TG, 95%CI[-0.010, 0.017]) or placebo (ß: 0.006 µg/mL per %TG, 95%CI[-0.012,0.024]). Also, in the cohort n o association between HTGC and CETP was present (ß: -0.001 µg/mL per SD TG, 95%CI[-0.005, 0.003]). A reduction of HTGC after treatment with liraglutide or placebo does not decrease circulating CETP. Also, no association between HTGC and CETP was present in a large cohort. These findings indicate that circulating CETP is not determined by HTGC.Clinical Trial Registration: Clinicaltrials.gov (NCT01761318).

The antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacodynamic interaction with aspirin in healthy volunteers.

Patients with cardiovascular disease taking aspirin and some nonsteroidal anti-inflammatory drugs (NSAIDs) appear to have increased vascular events. This study was conducted to compare the ex vivo antiplatelet effects of 6 commonly used NSAIDs and to determine whether these agents antagonize the effect of aspirin. Platelet function was assessed by Platelet Function Analyzer 100 closure time in normal subjects in a randomized, blinded, multiple-crossover study. Platelet function was measured 12 hours after the administration of each NSAID. The NSAID was then given 2 hours before aspirin 300 mg, and platelet function was reassessed 24 hours later. At 12 hours after the administration of naproxen and tiaprofenic acid, closure time was significantly prolonged, whereas the other NSAIDs did not cause significant prolongations. Compared with placebo plus aspirin, closure time was significantly reduced when ibuprofen, indomethacin, naproxen, or tiaprofenic acid was given before aspirin. In conclusion, ibuprofen, indomethacin, naproxen, and tiaprofenic acid all block the antiplatelet effect of aspirin. Sulindac and celecoxib did not demonstrate any significant antiplatelet effect or reduce the antiplatelet of aspirin and, therefore, of the NSAIDs evaluated may be the drugs of choice for patients requiring aspirin and NSAIDs.

Reflexo e sombra: o duplo e o narcisismo em hoffmann e chamisso / Reflection and shadow: the double and the narcissism in hoffmann and chamisso / Reflejo y penumbra: el doble y el narcisismo en hoffman y chamisso

Esta é uma pesquisa qualitativa, em formato de ensaio, que realiza o estudo comparado de duas obras literárias, de A. Von Chamisso e E. T. A. Hoffmann, e de uma anotação do diário deste último para problematizar a repercussão de algumas formas de desestabilizações do Eu na dinâmica psíquica da neurose. O foco dos textos referidos está no fenômeno do duplo na sua forma negativizada, isto é, como o desaparecimento da imagem exterior que dá suporte ao Eu. As ausências da sombra e do reflexo são entendidas como representações metafóricas de uma alteração do Eu que engendra repercussões importantes na homeostase psíquica, sobretudo nas relações sociais de troca. Explora-se daí a menção no diário de Hoffmann de instrumentos ópticos para interrogar o uso desses aparelhos como modelos metapsicológicos na psicanálise. Salienta-se, ainda, a participação de processos de natureza estética na dinâmica psíquica do infamiliar, tomando como referência a ligação entre o conto de Hoffmann e o relato de Stendhal sobre a sua estadia em Florença.(AU)

This is a qualitative research, in essay format, which performs the comparative study of two literary works, by A. Von Chamisso and E. T. A. Hoffmann, and an annotation in the latter's diary to problematize the repercussion of some forms of destabilization of the Ego's in the psychic dynamics of neurosis. The focus of the referred texts is on the phenomenon of the double in its negative form, that is, as the disappearance of the outer image that supports the Ego. The absences of the shadow and the reflection are understood as metaphorical representations of an alteration of the Ego that generates important repercussions on psychic homeostasis, above all in social relationships of exchange. Thus, we analyze the mention of optical instruments in Hoffmann's diary to question the use of these devices as metapsychological models in psychoanalysis. Note, also, the participation of processes of aesthetic nature in the psychic dynamics of the uncanny, taking as reference the connection between Hoffmann's short story and Stendhal's account of his stay in Florence.(AU)

Este ensayo cualitativo realiza un estudio comparativo de dos obras literarias de A. Von Chamisso y de E. T. A. Hoffmann, junto con una anotación en el diario de este último para problematizar la repercusión de algunas formas de desestabilizaciones de la función del Yo en la dinámica psíquica de la neurosis. Los textos se centran en el fenómeno del doble en su forma negativa, como la desaparición de la imagen exterior que sostiene el Yo. Se entienden las ausencias de la penumbra y el reflejo como una representación metafórica de una alteración de la función del Yo que genera importantes repercusiones en la regulación psíquica, sobre todo en las relaciones de intercambio social. Se analiza la presencia en el diario de Hoffmann de instrumentos ópticos para discutir el uso de estos dispositivos como modelos metapsicológicos en psicoanálisis. Se destaca la reverberación de procesos de naturaleza estética en la dinámica psíquica de lo ominoso, tomando como referencia la conexión entre el cuento de Hoffmann y el relato de Stendhal sobre su estancia en Florencia.(AU)

A hyaluronic acid- and chondroitin sulfate-based medical device improves gastritis pain, discomfort, and endoscopic features.

Gastritis is an inflammation of the gastric mucosa. In this study, we investigated the efficacy of a medical device, Esoxx®, based on hyaluronic acid and chondroitin sulfate on gastritis-related upper abdominal pain/discomfort and endoscopic features. Fifty patients, affected by gastritis, were randomised to receive the medical device or placebo. The primary endpoint was the medical device efficacy on upper abdominal pain/discomfort associated with gastritis and measured by Visual Analogue Scale (VAS). The secondary endpoints were the efficacy of the medical device on gastritis-related mucosal erosions, blood oozing, and hyperemia (redness)/edema, as assessed by endoscopy, and the patients' rating of their compliance with the treatments. A significant reduction in VAS pain was observed in the treatment group after a 5-week treatment, if compared with placebo (p < 0.001). In summary, administration of a medical device, based on hyaluronic acid and chondroitin sulfate, improves gastritis-related upper abdominal pain/discomfort and decreases mucosal erosions, blood oozing, and hyperemia (redness)/edema at 5-week follow-up in patients affected by gastritis.

Falsa acusação de abuso sexual na alienação parental: luto ou melancolia? / False accusation of sexual abuse in parental alienation: mourning or melancholia? / Falsa acusación de abuso sexual en la alienación parental: ¿luto o melancolía?

Este artigo apresenta como principal objeto de estudo a falsa acusação de abuso sexual no contexto da alienação parental para, diante dela, estabelecer a seguinte problemática: será possível propor uma eventual correlação entre si e os processos psíquicos do luto e da melancolia? Neste sentido, a partir do recurso teórico ao referencial psicanalítico de Freud e de Laplanche, debate as circunstâncias que norteiam o discurso levado ao Judiciário pelo genitor alienante valorizando em tal movimento não apenas a realidade material da prova, tão importante no campo jurídico, mas também a realidade psíquica ditada pelo inconsciente, a qual se pauta em uma noção de verdade que, na sua vinculação direta com a particularidade de cada sujeito e com o dinamismo das relações específicas que ele estabelece consigo mesmo e com os outros, coloca em xeque as certezas positivistas da norma. Em termos conclusivos, destaca o quanto, a despeito da atual literatura existente sobre alienação parental no Brasil a correlacionar, em regra, a um luto mal elaborado por parte do alienante, é possível e mesmo desejável cogitar também a presença da melancolia - ou, mais especificamente, de traços melancólicos intermediários - na formação e desenvolvimento desse fenômeno.(AU)

This article presents as the main object of study the false accusation of sexual abuse in the context of parental alienation, to establish the following problem: would it be possible to propose a probable correlation between parental alienation and the psychic processes of mourning and melancholia? In this sense, based on the psychoanalytic theoretical framework of Freud and Laplanche, the article discusses the circumstances that guide the discourse taken to the judiciary branch by the alienating parent, valuing in such action not only the material reality of the evidence, which is very important in the legal field, but also the psychic reality dictated by the unconscious, which is guided by a notion of truth that, in its direct connection with the particularity of each subject and with the dynamism of the specific relations that they establish with themselves and others, threatens the positivist certainties of the norm. In conclusive terms, it highlights how, despite the current existing literature on parental alienation in Brazil generally correlates it to a poorly elaborated mourning by the alienating person, it is possible and even desirable to also consider the presence of melancholia-or, more specifically, of intermediate melancholic traits-in the formation and development of this phenomenon.(AU)

Este artículo presenta como principal objeto de estudio la falsa acusación de abuso sexual en el contexto de alienación parental, con el fin de responder al siguiente planteamiento: ¿Es posible proponer una posible correlación entre la alienación parental y los procesos psíquicos de duelo y melancolía? Para ello, desde el marco psicoanalítico de Freud y de Laplanche, se discuten las circunstancias del discurso llevado al Poder Judicial por el padre alienante, que valora en tal movimiento no solo la realidad material de la prueba, tan importante en el campo jurídico, sino también la realidad psíquica dictada por el inconsciente, el cual se guía por una noción de verdad que, en su conexión directa con la particularidad de cada sujeto y con el dinamismo de las relaciones específicas que establece consigo mismo y con otros, pone en jaque las certezas positivistas de la norma. En la conclusión, destaca cómo, a pesar de la literatura actual existente sobre la alienación parental en Brasil, en general, la correlaciona con un duelo mal diseñado por parte de la persona alienante, es posible e incluso deseable considerar la presencia de la melancolía -más específicamente, de rasgos melancólicos intermediarios- en la formación y desarrollo de este fenómeno.(AU)

Losing a training analyst for ethical violations: a candidate's perspective.

The author presents her experience as the analysand of a training analyst who was investigated and expelled for ethical violations with another patient, including sexual-boundary violations, during her analytic training. While boundary violations by training analysts are not uncommon, the particular trauma experienced by 'bystanders' such as candidates and supervisees is not discussed in the literature, nor the response of institutes to the educational problems that are generated. The author illustrates the complications for candidates that arise from the dual roles of training analyst as educator and analyst when he or she faces investigation or censure, including isolation and secrecy, which promote various splits in the candidate, analytic dyad and group, as well as loyalty conflicts. The discussion covers three phases of the author's experience as a candidate-analysand, namely the period encompassing the institute's ethics investigation, the announcement of findings to her and to the institute as a group, and the ensuing individual and group dynamics generated by her analyst's expulsion from the institute and revocation of his medical license. Theoretical perspectives are utilized to understand the group regression, including contamination and contagion fears, which occurred in the wake of the training analyst's expulsion, and the impact of these processes on the candidate, including the pressure to function as a 'container' for projections of the group. Implications and recommendations for candidates and institutes are made for dealing helpfully with trainees who are affected by the process of dealing with a training analyst's ethical violations. Short-term and longer-term outcomes of the experience are considered.

Azilsartan in Patients With Mild to Moderate Hypertension Using Clinic and Ambulatory Blood Pressure Measurements.

This was a phase 2, multicenter, randomized, parallel-group, double-blind dose-ranging study. Hypertensive adults (n=555) received one of five doses of azilsartan (AZL; 2.5, 5, 10, 20, 40 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. Compared with placebo, all AZL doses (except 2.5 mg) provided statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) based on both clinic blood pressure (BP) and 24-hour ambulatory BP monitoring (ABPM). AZL 40 mg was statistically superior vs OLM. Clinic BP was associated with a pronounced placebo effect (-6 mm Hg), whereas this was negligible with ABPM (±0.5 mm Hg). Adverse event frequency was similar in the AZL and placebo groups. Based on these and other findings, subsequent trials investigated the commercial AZL medoxomil tablet at doses 20 to 80 mg/d using 24-hour ABPM.

Plasma bikunin as a favorable prognostic factor in ovarian cancer.

PURPOSE: Bikunin is a multifunctional glycoprotein, which mediates suppression of tumor cell invasion and metastasis. The measurement of bikunin levels in the tissue of patients with malignant diseases has been introduced as a new and simple diagnostic tool for the evaluation of prognosis. The high bikunin expression in ovarian cancer tissue would enable the use of soluble bikunin protein present in the circulation of ovarian cancer patients as a biomarker of disease. PATIENTS AND METHODS: We developed a double-antibody immunoassay for bikunin and detected its presence in normal human circulation. We quantified, by enzyme-linked immunosorbent assay and/or immunoblot assay bikunin in sera from 200 healthy women (controls), 200 patients with benign gynecologic diseases, and 327 patients with ovarian cancer before surgical removal of the tumor. RESULTS: When the values of bikunin corresponding to the median were used as the cutoff value (11.5 microg/mL), low plasma bikunin was strongly associated with late-stage, suboptimal debulking with large residual tumor (> 2 cm) and low response to chemotherapy. The median survival time of the patients with a high bikunin level was more than 60 months as compared with 26 months among those with low bikunin level (P = .002). This difference corresponded to a 2.2-fold increased risk of dying for the lower plasma bikunin patients (hazard ratio, 0.45; P = .023) and remained significant in multivariate analysis (hazard ratio, 0.63; P = .041). CONCLUSION: Preoperative plasma bikunin concentration is a strong and independent favorable prognostic marker for ovarian cancer.

Effects of sibutramine on thermogenesis in obese patients assessed via immersion calorimetry.

Glucose utilization studies show that sibutramine-induced thermogenesis is mediated via selective sympathetic activation of brown adipose tissue. The goal of the present study was to use a new calorimetry method in which resting metabolic rate is enhanced to evaluate the effects of sibutramine treatment on thermogenesis. Sixty obese women were included in the study. Subjects were divided into 2 equal groups-the placebo and sibutramine treatment groups. The sibutramine group was given sibutramine 10 mg daily for 12 wk. At baseline and at the end of the 12-wk treatment period, thermogenic measurements were taken with the use of water immersion calorimetry. Subjects were examined at weeks 4, 8, and 12 of treatment to identify adverse effects. Body mass index, measured at 31.5+/-2.05 kg/m2 in the placebo group, decreased to 30.4+/-2.94 kg/m(2) after 12 wk (P=.07). In the sibutramine group, it decreased from 33.5+/-4.1 kg/m(2) to 30.9+/-4.8 kg/m(2) (P<.05). In the sibutramine group, mean thermogenic response changed from a baseline value of 1.27+/-0.29 kcal/kg/h to 1.44+/-0.13 kcal/kg/h after 12 wk of treatment. In the placebo group, the baseline value was 1.56+/-0.27 kcal/kg/h; it changed to 1.33+/-0.36 kcal/kg/h at the end of 12 wk. The findings of this study suggest that sibutramine treatment promotes thermogenesis, thus facilitating weight loss. Calorimetry enhances resting metabolism through more efficient heat transfer from the body.

Double binding, abusive intimate partner relationships, and pregnancy.

The purpose of this study was to extend and integrate the process theories of abuse and becoming a mother in order to provide a contextually appropriate perspective for understanding women's behavioural responses to intimate partner abuse during pregnancy. Double binding is proposed as a construct for understanding intimate partner abuse during pregnancy. Double binding refers to the simultaneous and often conflicting psychological and social processes of binding-in to the unborn child and to the abusive intimate partner that women engage in as they perform the developmental tasks associated with becoming a mother while living with an abusive partner. This construct was developed through an inductive-deductive process using clinical experience, a literature review, and qualitative data from 2 studies of abuse during pregnancy. The authors conclude that double binding is a suitable lens through which to interpret pregnant women's behavioural responses to abuse. They offer suggestions regarding clinical practice and research to further develop appropriate interventions incorporating this construct.

Measurement of red blood cell eicosapentaenoic acid (EPA) levels in a randomised trial of EPA in patients with colorectal cancer liver metastases.

We investigated red blood cell (RBC) PUFA profiles, and the predictive value of RBC EPA content for tumour EPA exposure and clinical outcomes, in the EMT study, a randomised trial of EPA in patients awaiting colorectal cancer (CRC) liver metastasis surgery (Cockbain et al., 2014) [8]. There was a significant increase in RBC EPA in the EPA group (n=43; median intervention 30 days; mean absolute 1.26[±0.14]% increase; P<0.001), but not in the placebo arm (n=45). EPA incorporation varied widely in EPA users and was not explained by treatment duration or compliance. There was little evidence of 'contamination' in the placebo group. The EPA level predicted tumour EPA content (r=0.36; P=0.03). Participants with post-treatment EPA≥1.22% (n=49) had improved OS compared with EPA <1.22% (n=29; HR 0.42[95%CI 0.16-0.95]). RBC EPA content should be evaluated as a biomarker of tumour exposure and clinical outcomes in future EPA trials in CRC patients.

Population Pharmacokinetics of Bedaquiline and Metabolite M2 in Patients With Drug-Resistant Tuberculosis: The Effect of Time-Varying Weight and Albumin.

Albumin concentration and body weight are altered in patients with multidrug-resistant tuberculosis (MDR-TB) and change during the long treatment period, potentially affecting drug disposition. We here describe the pharmacokinetics (PKs) of the novel anti-TB drug bedaquiline and its metabolite M2 in 335 patients with MDR-TB receiving 24 weeks of bedaquiline on top of a longer individualized background regimen. Semiphysiological models were developed to characterize the changes in weight and albumin over time. Bedaquiline and M2 disposition were well described by three and one-compartment models, respectively. Weight and albumin were correlated, typically increasing after the start of treatment, and significantly affected bedaquiline and M2 plasma disposition. Additionally, age and race were significant covariates, whereas concomitant human immunodeficiency virus (HIV) infection, sex, or having extensively drug-resistant TB was not. This is the first population model simultaneously characterizing bedaquiline and M2 PKs in its intended use population. The developed model will be used for efficacy and safety exposure-response analyses.

Overall Survival Analysis From a Randomized Phase II Study of Axitinib With or Without Dose Titration in First-Line Metastatic Renal Cell Carcinoma.

BACKGROUND: In a randomized phase II trial in metastatic renal cell carcinoma (mRCC), objective response rate was significantly higher with axitinib versus placebo titration (54% vs. 34%; 1-sided P = .019). PATIENTS AND METHODS: Treatment-naive patients with mRCC (n = 213) received axitinib 5 mg twice per day (b.i.d.) for 4 weeks. Patients meeting dose titration criteria were randomized to receive axitinib 5 mg b.i.d. with axitinib or placebo titration (n = 56 each); 91 patients ineligible for randomization continued axitinib 5 mg b.i.d.; 10 discontinued before randomization. RESULTS: Median overall survival (95% confidence interval [CI]) was 42.7 months (24.7-not estimable) with axitinib titration versus 30.4 months (23.7-45.0) with placebo titration (stratified hazard ratio, 0.785; 95% CI, 0.485-1.272; 1-sided P = .162), and 41.6 months (95% CI, 33.0-not estimable) in nonrandomized patients. Safety data were consistent with previous reports. CONCLUSION: Median overall survival was numerically longer in patients with first-line mRCC who received axitinib versus placebo titration. No new safety signal was observed after long-term axitinib treatment in first-line mRCC.