Psychiatric Diagnoses and Psychosocial Needs of Outpatient Deaf Children and Adolescents

Deaf youth may be more vulnerable to psychiatric disorders but very little research data is available. The current study identified prevalence rates of psychiatric disorders and examined the psychosocial needs and strengths of deaf youth aged 4–17 receiving specialized outpatient mental health services for the deaf. Compared to hearing peers, deaf youth had greater rates of attention deficit hyperactivity disorder, conduct, autism-spectrum and bipolar disorders and spent three times longer in treatment than their hearing peers. In the deaf subsample, moderate-severe risk was found in social functioning (33.3 %) and suicidal behavior (14 %). Deaf youth had moderate to severe impairment in social relationships (54.8 %), school functioning (42.9 %). Over one-third of deaf youth had impaired family relationships, living situation, communication, judgment and physical health. Deaf youth present with higher rates of certain clinical disorders and have deficits in multiple life domains that may impact functioning and create a longer treatment course.     

Enzyme functional evolution through improved catalysis of ancestrally nonpreferred substrates

In this study, we investigated the role for ancestral functional variation that may be selected upon to generate protein functional shifts using ancestral protein resurrection, statistical tests for positive selection, forward and reverse evolutionary genetics, and enzyme functional assays. Data are presented for three instances of protein functional change in the salicylic acid/benzoic acid/theobromine (SABATH) lineage of plant secondary metabolite-producing enzymes. In each case, we demonstrate that ancestral nonpreferred activities were improved upon in a daughter enzyme after gene duplication, and that these functional shifts were likely coincident with positive selection. Both forward and reverse mutagenesis studies validate the impact of one or a few sites toward increasing activity with ancestrally nonpreferred substrates. In one case, we document the occurrence of an evolutionary reversal of an active site residue that reversed enzyme properties. Furthermore, these studies show that functionally important amino acid replacements result in substrate discrimination as reflected in evolutionary changes in the specificity constant (k(cat)/K(M)) for competing substrates, even though adaptive substitutions may affect K(M) and k(cat) separately. In total, these results indicate that nonpreferred, or even latent, ancestral protein activities may be coopted at later times to become the primary or preferred protein activities.     

Skeletal Muscle Triacylglycerol Hydrolysis Does Not Influence Metabolic Complications of Obesity

Intramyocellular triacylglycerol (IMTG) accumulation is highly associated with insulin resistance and metabolic complications of obesity (lipotoxicity), whereas comparable IMTG accumulation in endurance-trained athletes is associated with insulin sensitivity (the athlete’s paradox). Despite these findings, it remains unclear whether changes in IMTG accumulation and metabolism per se influence muscle-specific and systemic metabolic homeostasis and insulin responsiveness. By mediating the rate-limiting step in triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL) has been proposed to influence the storage/production of deleterious as well as essential lipid metabolites. However, the physiological relevance of ATGL-mediated triacylglycerol hydrolysis in skeletal muscle remains unknown. To determine the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes in the context of obesity, we generated mice with targeted deletion or transgenic overexpression of ATGL exclusively in skeletal muscle. Despite dramatic changes in IMTG content on both chow and high-fat diets, modulation of ATGL-mediated IMTG hydrolysis did not significantly influence systemic energy, lipid, or glucose homeostasis, nor did it influence insulin responsiveness or mitochondrial function. These data argue against a role for altered IMTG accumulation and lipolysis in muscle insulin resistance and metabolic complications of obesity.Obesity is a global public health problem and a major risk factor for insulin resistance and type 2 diabetes. These disorders are characterized by excess lipid accumulation in multiple tissues, primarily as triacylglycerols (TAGs). The lipotoxicity hypothesis suggests that this lipid excess promotes cellular dysfunction and cell death, which ultimately contribute to insulin resistance and metabolic disease (1). However, intracellular TAG accumulation is not always associated with adverse metabolic outcomes, suggesting that TAGs themselves are not pathogenic (2). In contrast, other non-TAG lipid metabolites such as fatty acids (FAs), diacylglycerols (DAGs), and ceramides have been shown to influence glucose homeostasis and insulin action by interfering with insulin signaling and glucose transport, promoting endoplasmic reticulum stress and mitochondrial dysfunction, and activating inflammatory and apoptotic pathways (reviewed in ref. 3). Nevertheless, the precise identities and sources of these bioactive lipid intermediates remain elusive (4,5). Furthermore, whether intracellular TAGs serve as a protective sink or a toxic source of deleterious lipid metabolites that contribute to insulin resistance remains unclear (6).Since skeletal muscle is the major contributor to insulin-mediated glucose disposal, lipid excess in this tissue could have serious implications for systemic glucose homeostasis and insulin responsiveness (7). Indeed, numerous studies have demonstrated a strong association between intramyocellular triacylglycerol (IMTG) accumulation and insulin resistance (reviewed in ref. 8). In contrast, endurance exercise training is characterized by IMTG accumulation and insulin sensitivity (the athlete’s paradox) (2). This variable association between IMTG accumulation and insulin responsiveness has largely been attributed to differences in the balance between lipid delivery and muscle oxidative capacity (8–10). Not surprisingly then, most studies have focused on the impact of muscle FA uptake and/or oxidation on glucose homeostasis and insulin action (11). However, experimental manipulations of these parameters cannot distinguish among the effects of IMTGs, IMTG metabolism, and other lipid intermediates. Furthermore, accumulating evidence suggests that muscle oxidative capacity cannot entirely explain differences in IMTGs or insulin responsiveness (12). These findings have led to speculation that dynamic IMTG metabolism (i.e., TAG synthesis or hydrolysis) may be critically involved in lipid-induced insulin resistance (6). However, few studies have specifically addressed the contribution of IMTG metabolism per se to this process.The regulated storage and release of IMTGs remain poorly understood, but require the coordinated action of synthetic enzymes (i.e., diacylglycerol acyltransferases [DGATs]), hydrolytic enzymes (i.e., adipose triglyceride lipase [ATGL] and hormone sensitive lipase [HSL]), and other lipid droplet proteins (6). Specifically, modulating IMTG synthesis in murine skeletal muscle alters IMTG content and systemic glucose homeostasis, supporting a role for IMTG metabolism in metabolic disease (13–15). However, the metabolic impact of modulating IMTG hydrolysis in vivo remains unclear. Global deletion of either ATGL (16–19) or HSL (20) has produced variable results. The former, but not the latter, results in massive IMTG accumulation with improvement in systemic glucose homeostasis, suggesting that inhibition of ATGL-mediated TAG hydrolysis protects against insulin resistance. In contrast, recent studies in cardiac muscle (21) and other tissues (22,23) indicate that ATGL-mediated TAG hydrolysis is required for mitochondrial function such that enhancing, rather than inhibiting, ATGL action may improve metabolic outcomes. Nevertheless, the autonomous role of skeletal muscle TAG catabolism in influencing muscle-specific and systemic metabolic phenotypes remains unknown.The goal of the current study was to understand the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes, particularly glucose homeostasis and insulin action, in the context of obesity. We therefore generated animal models with decreased (skeletal muscle-specific ATGL knockout [SMAKO] mice) and increased (muscle creatine kinase [Ckm]-ATGL transgenic [Tg] mice) ATGL action exclusively in skeletal muscle, and assessed the metabolic consequences at baseline and in response to chronic high-fat feeding. Interestingly, modulation of IMTG hydrolysis via ATGL action did not significantly influence glucose homeostasis, insulin action, or other metabolic phenotypes in the context of obesity despite dramatic changes in IMTG content.     

High HIV-1 prevalence,risk behaviours,and willingness to participate in HIV vaccine trials in fishing communities on Lake Victoria,Uganda

Introduction

HIV epidemics in sub-Saharan Africa are generalized, but high-risk subgroups exist within these epidemics. A recent study among fisher-folk communities (FFC) in Uganda showed high HIV prevalence (28.8%) and incidence (4.9/100 person-years). However, those findings may not reflect population-wide HIV rates in FFC since the study population was selected for high-risk behaviour.

Methods

Between September 2011 and March 2013, we conducted a community-based cohort study to determine the population representative HIV rates and willingness to participate (WTP) in hypothetical vaccine trials among FFC, Uganda. At baseline (September 2011–January 2012), a household enumeration census was done in eight fishing communities (one lakeshore and seven islands), after which a random sample of 2200 participants aged 18–49 years was selected from 5360 individuals. Interviewer-administered questionnaire data were collected on HIV risk behaviours and WTP, and venous blood was collected for HIV testing using rapid HIV tests with enzyme-linked immunosorbent assay (EIA) confirmation. Adjusted prevalence proportion ratios (adj.PPRs) of HIV prevalence were determined using log-binomial regression models.

Results

Overall baseline HIV prevalence was 26.7% and was higher in women than men (32.6% vs. 20.8%, p<0.0001). Prevalence was lower among fishermen (22.4%) than housewives (32.1%), farmers (33.1%) and bar/lodge/restaurant workers (37%). The adj.PPR of HIV was higher among women than men (adj.PPR =1.50, 95%; 1.20, 1.87) and participants aged 30–39 years (adj.PPR=1.40, 95%; 1.10, 1.79) and 40–49 years (adj.PPR=1.41, 95%; 1.04, 1.92) compared to those aged 18–24 years. Other factors associated with HIV prevalence included low education, previous marriage, polygamous marriage, alcohol and marijuana use before sex. WTP in hypothetical vaccine trials was 89.3% and was higher in men than women (91.2% vs. 87.3%, p=0.004) and among island communities compared to lakeshore ones (90.4% vs. 85.8%, p=0.004).

Conclusions

The HIV prevalence in the general fisher-folk population in Uganda is similar to that observed in the “high-risk” fisher folk. FFC have very high levels of willingness to participate in future HIV vaccine trials.     

Clients' perspectives on therapy termination

Abstract

We used consensual qualitative research to analyze interviews with 12 clients about their termination from psychotherapy. Those who had positive termination experiences reported a strong therapeutic relationship and positive outcomes of therapy. They terminated primarily for logistical or financial reasons; their termination, post-termination plans, and feelings about termination were discussed in advance with their therapist, as was their growth in therapy, leading to mostly positive effects of the termination. In contrast, those who had problematic terminations reported a mixed therapeutic relationship and mixed outcomes of therapy. They usually terminated abruptly because of a therapeutic rupture, and thus termination was rarely planned and discussed in advance, rendering it a negative experience. Implications of these findings are addressed.     

Concerns About ABA-Based Intervention: An Evaluation and Recommendations

Journal of Autism and Developmental Disorders - For over 50&nbsp;years, intervention methods informed by the principles of applied behavior analysis (ABA) have been empirically researched and...