Circulating and Endometrial Regulatory T Cell and Related Populations in Endometriosis and Infertility: Endometriosis Is Associated with Blunting of Endometrial Cyclical Effects and Reduced Proportions in Moderate-Severe Disease.

Evidence to date supports regulatory T cell (Treg) alterations in endometriosis; however, the relationship remains unclear, and Tregs have not previously been investigated with respect to infertility in endometriosis. This prospective cross-sectional cohort study details circulating and endometrial tissue-specific disturbances in Tregs and broader gated populations in women of reproductive age with and without endometriosis (n = 57 and 29, respectively) using flow cytometry and immunohistochemistry. Participants were characterised by menstrual cycle phase, r-ASRM endometriosis disease stage and fertility status.In the endometrium of women with endometriosis, endometrial Tregs and CD4+ lymphocyte proportions did not change between the proliferative and secretory phases, while in women without the disease, they significantly decreased (p = 0.045 and p = 0.039, respectively). In women with endometriosis, endometrial Tregs were lower than in women without endometriosis overall (p = 0.050 as a proportion of all CD45+ immune cells). We have shown for the first time that proportions of CD4+ lymphocytes (p = 0.021), overall lymphocytes (p = 0.034) and non-granulocytes (p = 0.027) were significantly decreased in the endometrium of women with moderate-severe (r-ASRM stages III and IV) compared to minimal-mild (r-ASRM stages I and II) endometriosis. During the secretory phase, circulating Treg proportions were significantly increased in infertile compared to fertile women (p = 0.049). This study confirms differences in endometrial Tregs in women with endometriosis, with blunting of normal menstrual cyclical variations, reduced proportions during the proliferative phase and disease stage-specific relationships.

Comprehensive analysis utilizing flow cytometry and immunohistochemistry reveals inflammatory changes in local endometrial and systemic dendritic cell populations in endometriosis.

STUDY QUESTION: What are the detailed endometrial tissue specific and systemic dendritic cell (DC) subset disturbances in endometriosis? SUMMARY ANSWER: This study confirms myeloid DC (mDC) and plasmacytoid DC subsets are readily identified in endometrial tissue and shows both endometrial and circulating differences in DC populations in women with endometriosis, with disease stage-specific relationships evident locally in the endometrium. WHAT IS KNOWN ALREADY: Immune factors in the uterus, the peritoneal environment and systemically are implicated in the pathogenesis and progression of both endometriosis and infertility. While there is some evidence that endometrial DC populations are altered in endometriosis, DC subset involvement in both the endometrium and peripheral blood have not been comprehensively investigated so the functional consequences have been unknown. STUDY DESIGN, SIZE, DURATION: This prospective cross-sectional cohort study compares circulating and endometrial DC populations in women of reproductive age with and without endometriosis (n = 55 and 30, respectively), wherein each participant donated samples at a single time point. Study participants were surveyed for menstrual cycle phase, American Society for Reproductive Medicine (ASRM) endometriosis disease stage and fertility status (where possible). PARTICIPANTS/MATERIALS, SETTING, METHODS: Peripheral blood samples were processed into mononuclear cells for analysis by flow cytometry, and endometrial samples were analysed by immunohistochemistry and dissociated into single-cell suspension for flow cytometry. MAIN RESULTS AND THE ROLE OF CHANCE: In the endometrium of women with endometriosis, IRF-8+ cells were increased during the proliferative phase (P = 0.014), total DC proportions increased in the secretory phase (P = 0.038) and normal menstrual cyclical fluctuations in CD1c+ and IRF-8+ cells blunted; indicative of a consistently inflammatory tissue environment. The inflammatory changes in CD141+ and IRF-8+ populations in the endometrium of women with endometriosis were particularly evident in more advanced ASRM stages of the disease (respective P-values 0.032 and 0.045). There was also evidence of systemic inflammation in women with endometriosis, with increased circulating CD141+ mDC proportions (overall P = 0.040, secretory phase P = 0.021). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: As is common in this type of study, one of the main limitations was small sample numbers, particularly during the menstrual phase of the cycle. WIDER IMPLICATIONS OF THE FINDINGS: Further phenotyping of local and circulating immune cell subtypes is critical to improving understanding of endometriosis pathogenesis and immune contributions to infertility associated with the disease. STUDY FUNDING/COMPETING INTEREST(S): This research was financially supported by a Sydney Medical School and Balnaves Foundation Kick Start Grant and the Department of Obstetrics, Gynaecology and Neonatology at The University of Sydney. The authors have no conflicts of interest to declare.

Age distribution and metabolic disorders in people with Type 1 diabetes in Beijing and Shantou, China: a cross-sectional study.

AIMS: To examine whether the age profile of people with Type 1 diabetes differs from that of the general population and in what manner, and to study the clinical characteristics related to metabolic disorders among people with Type 1 diabetes in China. METHODS: We sequentially enrolled 849 people with Type 1 diabetes from hospital records review, inpatient wards and outpatient clinics. Data were collected via face-to-face interviews, medical records and venous blood samples. Beijing census data for 2011 were used to provide the general population statistics. Descriptive analysis of the results and tests for differences were performed. RESULTS: The median (interquartile range) age at diagnosis of diabetes was 16 (9-28) years and the duration of diabetes was 4 (1-8) years. The mean ± sd HbA1c concentration was 76±28 mmol/mol (9.1±2.5%). Compared with the general population, the population with Type 1 diabetes comprised more young individuals and fewer elderly individuals. The overall prevalence of metabolic syndrome among those with Type 1 diabetes was 10.1% (95% CI 7.9-12.2). People with metabolic syndrome were older and were diagnosed with diabetes at an older age. Hypertension and dyslipidaemia were more common in obese individuals with Type 1 diabetes than in their non-obese counterparts. CONCLUSIONS: Compared with the general population, people with Type 1 diabetes comprised more young and fewer elderly individuals. The prevalence of metabolic syndrome in the Type 1 diabetes population was 10.1%. Hypertension and dyslipidaemia were more prevalent in obese than non-obese individuals.

New screening technologies for type 2 diabetes mellitus appropriate for use in tuberculosis patients.

Type 2 diabetes mellitus (DM), which is epidemic in low- and middle-income countries (LMICs), may threaten gains made in tuberculosis (TB) control, as DM is both a major risk factor for developing active TB and it can lead to adverse TB treatment outcomes. Despite World Health Organization guidance that all TB patients should be screened for DM, most facilities in LMICs that manage TB patients do not currently perform screening for DM, due in part to the cost and complexity involved. DM screening is further complicated by the presentation of transient hyperglycemia in many TB patients, as well as differences in diabetes risk factors (e.g., body mass index) between TB patients and the general public. In this article, we review existing and new technologies for DM screening that may be more suitable for TB patients in LMICs. Such methods should be rapid, they should not require fasting, and they should allow the provider to differentiate between transient and longer-term hyperglycemia, using inexpensive tools that require little training and no specialized infrastructure. Several methods that are currently under development, such as point-of-care glycated hemoglobin and glycated albumin assays, non-invasive advanced glycation end-product readers, and sudomotor function-based screening devices, offer interesting performance characteristics and warrant evaluation in populations with TB.

L'épidémie de diabète sucré (DM) de type 2 dans les pays à revenus faibles et moyens (LMIC) peut constituer une menace pour les progrès de la lutte contre la tuberculose (TB), car le DM est à la fois un facteur majeur de risque et de développement d'une TB active et peut aussi entrainer des résultats défavorables du traitement de la TB. En dépit de la directive de l'Organisation mondiale de la Santé selon laquelle tous les patients TB devraient faire l'objet d'un dépistage pour le DM, la plupart des services des LMIC qui traitent les patients TB ne réalisent pas actuellement le dépistage du DM, en partie en raison du coût et de la complexité qu'il implique. Le dépistage du DM est par ailleurs compliqué par l'existence d'une hyperglycémie transitoire chez beaucoup de patients TB ainsi que par les différences de facteurs de risque de DM (par exemple l'indice de masse corporelle) entre les patients TB et la population générale. Dans cet article, nous révisons les technologies existantes et nouvelles pour le dépistage du DM qui pourraient être les plus applicables aux patients TB dans les LMIC. De telles méthodes devraient être rapides, elles devraient ne pas exiger le jeûne et elles devraient permettre aux pourvoyeurs de soins de distinguer entre des hyperglycémies transitoires et de plus longue durée au moyen d'outils peu coûteux, n'exigeant que peu de formation et aucune infrastructure spécialisée. Différentes méthodes sont actuellement en cours de développement, tels que les tests sur l'hémoglobine glycosylée aux lieux de soins et sur l'albumine glycosylée, les lecteurs des produits finaux d'une glycation avancée non-invasive et les outils de dépistage basés sur la fonction sudomotrice ; elles offrent des caractéristiques intéressantes de performance et méritent une évaluation dans les populations TB.

La diabetes (DM) de tipo 2 presenta características epidémicas en los países con ingresos bajos e intermedios (LMIC) y puede poner en peligro los avances alcanzados en materia de control de la tuberculosis (TB); la DM constituye un factor de riesgo importante de padecer la enfermedad TB activa y también puede tener consecuencias desfavorables en el desenlace del tratamiento antituberculoso. Pese a la recomendación de la Organización Mundial de la Salud de realizar la detección sistemática de la DM en todos los pacientes TB, la mayoría de los establecimientos que atienden a estos pacientes en los LMIC no cumplen con esta práctica, en parte debido a los costos y a la complejidad de la misma. La detección de la DM se complica además por la hiperglucemia transitoria que suele observarse en muchos pacientes TB y por las diferencias en los factores de riesgo de DM, presentes en los pacientes con TB y la población general, por ejemplo el índice de masa corporal. En el presente artículo se analizan las técnicas existentes y los nuevos métodos de detección sistemática de la DM que pueden ser más adaptados a los pacientes con TB de los LMIC. Estos métodos deben ser rápidos, no deben precisar el estado de ayuno y deben permitir al profesional de salud diferenciar entre la hiperglucemia transitoria y la hiperglucemia de largo plazo, mediante la utilización instrumentos de bajo costo, que exijan poco entrenamiento y no necesiten infraestructuras especializadas. En la actualidad, se encuentran en curso de desarrollo varios métodos como las pruebas de hemoglobina glucosilada y albúmina glucosilada realizadas en el punto de atención, los lectores no invasivos de productos finales de la glucosilación avanzada y los dispositivos de detección basados en la función sudomotora; estos métodos ofrecen características de rendimiento interesantes y merecen una evaluación en las poblaciones de pacientes con diagnóstico de TB.

Efficacy, tolerability and side-effect profile of fluvoxamine for major depression: meta-analysis.

Fluvoxamine, one of the oldest selective serotonin reuptaking inhibitors, is commonly prescribed to patients with major depression. Several studies have reviewed the efficacy and tolerability of fluvoxamine for the treatment of major depression. However, these reviews are outdated, have not been systematic and/or suffered from several methodological weaknesses. We conducted a systematic review to synthesize the best available evidence on the efficacy of fluvoxamine for adult patients suffering from major depression in comparison with other active antidepressive agents. Relevant randomized controlled trials were identified through a comprehensive search. The primary outcome was a relative risk of response, and the secondary outcome was a relative risk of remission. Tolerability and side-effect profile were also examined. Fifty-three trials were included. There were no large differences between fluvoxamine and any other antidepressants in terms of efficacy and tolerability. There is evidence of differing side effect profiles, especially when comparing gastrointestinal side effects between fluvoxamine and tricyclics. Clinicians should focus on practically or clinically relevant differences including those in side-effect profiles.

Psychological treatments versus treatment as usual for obsessive compulsive disorder (OCD).

BACKGROUND: Obsessive compulsive disorder (OCD) is a chronic anxiety disorder associated with significant morbidity, social impairment and lower quality of life. Psychological treatments are a frequently used approach for OCD. OBJECTIVES: To perform a systematic review of randomised trials of psychological treatments for obsessive compulsive disorder in comparison with treatment as usual. SEARCH STRATEGY: We conducted an electronic search of CCDANCTR-Studies (31/10/2006), and other databases. We searched reference lists, and contacted experts in the field. SELECTION CRITERIA: Published and unpublished randomised trials of psychological treatments versus treatment as usual for adults with a diagnosis of OCD DATA COLLECTION AND ANALYSIS: Two review authors worked independently throughout the selection of trials and data extraction. Findings were compared and disagreements were discussed with a third review author. Full data extraction, using a standardised data extraction sheet, was performed on all studies included in the review. Results were synthesised using Review Manager software. For dichotomous data, odds ratios were calculated. For continuous data, effect sizes were obtained and the standardised mean difference, with 95% confidence intervals, was calculated. Fixed and random effects models were used to pool the data. Reasons for heterogeneity in studies were explored and sensitivity analyses were performed by excluding trials of lower quality. MAIN RESULTS: Eight studies (11 study comparisons) were identified, all of which compared cognitive and/or behavioural treatments versus treatment as usual control groups. Seven studies (ten comparisons) had usable data for meta-analyses. These studies demonstrated that patients receiving any variant of cognitive behavioural treatment exhibited significantly fewer symptoms post-treatment than those receiving treatment as usual (SMD -1.24, 95% CI -1.61 to -0.87, I(2) test for heterogeneity 33.4%). Different types of cognitive and/or behavioural treatments showed similar differences in effect when compared with treatment as usual. The overall treatment effect appeared to be influenced by differences in baseline severity. AUTHORS' CONCLUSIONS: The findings of this review suggest that psychological treatments derived from cognitive behavioural models are an effective treatment for adult patients with obsessive compulsive disorder. Larger high quality randomised controlled trials involving longer follow up periods are needed, to further test cognitive behavioural treatments, and other psychological approaches, in comparison to each other and control conditions. Future trials should examine the predictors of response to each treatment, and also conduct cost-effectiveness evaluations.

Exercise therapy for chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is an illness characterised by persistent medically unexplained fatigue. CFS is a serious health-care problem with a prevalence of up to 3%. Treatment strategies for CFS include psychological, physical and pharmacological interventions. OBJECTIVES: To investigate the relative effectiveness of exercise therapy and control treatments for CFS. SEARCH STRATEGY: CCDANCTR-Studies and CENTRAL were searched using "Chronic Fatigue" and Exercise. The Journal of Chronic Fatigue Syndrome and CFS conferences were handsearched. Experts in the field were contacted. Clinicaltrials.gov and controlled-trials.com were searched. SELECTION CRITERIA: Only Randomised Controlled Trials (RCT) including participants with a clinical diagnosis of CFS and of any age were included. DATA COLLECTION AND ANALYSIS: The full articles of studies identified were inspected by two reviewers (ME and HMG). Continuous measures of outcome were combined using standardised mean differences. An overall effect size was calculated for each outcome with 95% confidence intervals. One sensitivity analysis was undertaken to test the robustness of the results. MAIN RESULTS: Nine studies were identified for possible inclusion in this review, and five of those studies were included. At 12 weeks, those receiving exercise therapy were less fatigued than the control participants (SMD -0.77, 95% CIs -1.26 to -0.28). Physical functioning was significantly improved with exercise therapy group (SMD -0.64, CIs -0.96 to -0.33) but there were more dropouts with exercise therapy (RR 1.73, CIs 0.92 to 3.24). Depression was non-significantly improved in the exercise therapy group compared to the control group at 12 weeks (WMD -0.58, 95% CIs -2.08 to 0.92). Participants receiving exercise therapy were less fatigued than those receiving the antidepressant fluoxetine at 12 weeks (WMD -1.24, 95% CIs -5.31 to 2.83). Participants receiving the combination of the two interventions, exercise + fluoxetine, were less fatigued than those receiving exercise therapy alone at 12 weeks, although again the difference did not reach significance (WMD 3.74, 95% CIs -2.16 to 9.64). When exercise therapy was combined with patient education, those receiving the combination were less fatigued than those receiving exercise therapy alone at 12 weeks (WMD 0.70, 95% CIs -1.48 to 2.88). REVIEWERS' CONCLUSIONS: There is encouraging evidence that some patients may benefit from exercise therapy and no evidence that exercise therapy may worsen outcomes on average. However the treatment may be less acceptable to patients than other management approaches, such as rest or pacing. Patients with CFS who are similar to those in these trials should be offered exercise therapy, and their progress monitored Further high quality randomised studies are needed.

Low dosage tricyclic antidepressants for depression.

BACKGROUND: Tricyclic antidepressants are still extensively prescribed worldwide. Evidence for the recommended dosage of tricyclics, however, is poor. OBJECTIVES: To compare the effects and side effects of low dosage tricyclic antidepressants with placebo and with standard dosage tricyclics in acute phase treatment of depression. SEARCH STRATEGY: Electronic search of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), incorporating results of group searches of MEDLINE (1966-), EMBASE (1980-), CINAHL (1982-), PsycLIT (1974-), PSYNDEX (1977-) and LILACS (1982-1999) and hand searches of major psychiatric and medical journals. Reference search and SciSearch of the identified studies. Personal contact with authors of significant papers. SELECTION CRITERIA: All randomised controlled trials 1) comparing low dosage TCA (=< 100 mg/d on average at the end of trial) with placebo or 2) comparing low and standard dosages of the same TCA, in acute phase treatment of depressive disorder DATA COLLECTION AND ANALYSIS: Two independent reviewers examined eligibility of the identified studies, and extracted data for outcomes at 1 week, 2 weeks, 4 weeks, 6-8 weeks and later. Main outcome measures were relative risk of response in depression (random effects model), according to the original authors' definition but usually defined as 50% or greater reduction in severity of depression according to the last-observation-carried-forward intention-to-treat method, and relative risks of overall dropouts and dropouts due to side effects. Other outcome measures included worst-case-scenario intention-to-treat analysis of response as defined above (in which dropouts were considered non-responders in the active treatment group and as responders in the comparison group), and standardised weighted mean scores of continuous depression severity scales (usually calculated by last-observation-carried-forward method). MAIN RESULTS: 35 studies (2013 participants) compared low dosage tricyclics with placebo, and six studies (551 participants) compared low dosage tricyclics with standard dosage tricyclics. Low dosage tricyclics, mostly between 75 and 100 mg/day, were 1.65 (95% confidence interval 1.36 to 2.0) and 1.47 (1.12 to 1.94) times more likely than placebo to bring about response at 4 weeks and 6-8 weeks, respectively. Standard dosage tricyclics failed, however, to bring about more response but produced more dropouts due to side effects than low dosage tricyclics. REVIEWER'S CONCLUSIONS: Treatment of depression in adults with low dose tricyclics is justified. However, more rigorous studies are needed to definitively establish the relative benefits and harms of varying dosages.

Interventions for vaginismus.

BACKGROUND: Vaginismus is involuntary vaginal muscle contraction which makes sexual intercourse difficult or impossible. It is one of the more common female psychosexual problems. Various therapeutic strategies for vaginismus, such as sex therapy and desensitization, have been considered in uncontrolled studies. OBJECTIVES: The aim of this review is to determine the clinical effectiveness of treatments for vaginismus and also to examine the role of partner participation in the effectiveness of the treatment. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety & Neurosis Controlled Trials Register (Issue 3, 2000), the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), MEDLINE (1966 to Nov 2002), EMBASE (1980 to Nov 2002), PsycINFO (1967 to Nov 2002) and CINAHL (1982 to Nov 2002) were searched. The Journal of Sex Research (1974 to 1999), Sexual & Marital Therapy (1986 to 1999), Sexual Dysfunction (1998 to 1999) and the Journal of Sex and Marital Therapy (1974 to 1999) were handsearched. Reference lists and conference abstracts were searched. Experts in the field were contacted regarding unpublished material. SELECTION CRITERIA: Controlled trials comparing treatments for vaginismus with another treatment, a placebo treatment, treatment as usual or waiting list control. DATA COLLECTION AND ANALYSIS: The reviewers extracted data which were verified with the trial investigator. MAIN RESULTS: Two controlled trials were identified although data were only available from one trial. The second trial compared two forms of systematic desensitization and reported no discernible differences between them. REVIEWER'S CONCLUSIONS: In spite of encouraging results reported from uncontrolled series of patients there is very limited evidence from controlled trials concerning the effectiveness treatments for vaginismus. Further trials are need to compare therapies with waiting list control and with other therapies.

Interventions for vaginismus.

BACKGROUND: Vaginismus is involuntary vaginal muscle contraction which makes sexual intercourse difficult or impossible. It is one of the more common female psychosexual problems. Various therapeutic strategies for vaginismus, such as sex therapy and desensitization, have been considered in uncontrolled studies. OBJECTIVES: The aim of this review is to determine the clinical effectiveness of treatments for vaginismus and also to examine the role of partner participation in the effectiveness of the treatment. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety & Neurosis Controlled Trials Register (Issue 3, 2000), the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2000), MEDLINE (1966 to Apr 2000), EMBASE (1980 to Apr 2000), PsycINFO (1967 to April 2000) and CINAHL (1982 to Mar 2000) were searched. The Journal of Sex Research (1974 to 1999), Sexual & Marital Therapy (1986 to 1999), Sexual Dysfunction (1998 to 1999) and the Journal of Sex and Marital Therapy (1974 to 1999) were handsearched. Reference lists and conference abstracts were searched. Experts in the field were contacted regarding unpublished material. SELECTION CRITERIA: Controlled trials comparing treatments for vaginismus with another treatment, a placebo treatment, treatment as usual or waiting list control. DATA COLLECTION AND ANALYSIS: The reviewers extracted data which were verified with the trial investigator. MAIN RESULTS: Two controlled trials were identified although data were only available from one trial. The second trial compared two forms of systematic desensitization and reported no discernible differences between them. REVIEWER'S CONCLUSIONS: In spite of encouraging results reported from uncontrolled series of patients there is very limited evidence from controlled trials concerning the effectiveness treatments for vaginismus. Further trials are need to compare therapies with waiting list control and with other therapies.

Effects of amygdala lesions on body weight, conditioned taste aversion, and neophobia.

Female rats with posterodorsal amygdala (PDA), basolateral amygdala (BLA), or sham lesions were compared regarding ad libitum food intake, weight gain, consumption of a novel food, and acquisition of a conditioned taste aversion (CTA). While only the rats with PDA lesions evidenced substantial weight gains at 10 days after surgery eating standard lab chow (25-45 g more than the other groups), only the rats with BLA lesions demonstrated significant deficits in the CTA and neophobia paradigms. Rats with basolateral lesions, on average, took less than 30 s to begin drinking the novel sweetened condensed milk after pairing with illness while the other groups took approximately 15 min to begin drinking. Also, rats with basolateral lesions ate, on average, 5 g of the novel Froot Loops while the other groups ate approximately 2 g. It is concluded that the changes in food-motivated behavioral tests frequently observed in animals with amygdala lesions do not coexist with the hyperphagia and weight gain of animals with PDA lesions.

Sex differences in body weight gains following amygdaloid lesions in rats.

Lesions of the most posterodorsal aspects of the amygdala resulted in equal weight gains (mean = 58 g) in male and female rats during a 22-day observation period. However, the absolute weight gains in the first 5 days after lesions were greater in females (+41.4 g) than in males (+18.8 g), as were the longer-term gains relative to their respective control groups. In a second study with female rats, it was found that amygdaloid lesions had little effect on the estrous cycle and that ovariectomy resulted in additional excessive weight gains in both rats with sham lesions and those with amygdaloid lesions. The weight gains produced by amygdaloid lesions and ovariectomy were additive. It is concluded that there is a sex difference in weight gains after amygdaloid lesions, but that the lesion-induced obesity is independent of estrogen levels. Similarities to lesions of the ventromedial hypothalamus are noted, and an amygdaloid-ventromedial hypothalamic pathway for the regulation of feeding behavior is proposed.