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Combat-exposed veterans risk encountering events that disrupt beliefs. To facilitate reduced discrepancy between prior beliefs and current trauma appraisals, veterans may engage in a process of meaning-making. Meaning-making can lead to positive outcomes, such as integrating the traumatic event into one's life narrative or adapting global meaning (meaning made) or elicit distress. Given these potentially different outcomes, this study examined potential correlates of posttraumatic stress symptom (PTSS) severity and meaning made, including relationship attachment dimensions of anxiety and avoidance, and difficulties with emotion regulation, while controlling for combat exposure.Veterans receiving mental health services at a Veterans Affairs (VA) Medical Center and a VA community-based outpatient clinic (N = 130) completed measures through a paper-and-pencil survey. Almost all participants (92%) were male, with a mean age of 55.92 years.In terms of meaning made, lower levels of attachment anxiety and emotional clarity (an aspect of emotion regulation) predicted higher meaning made. In terms of PTSS severity, higher attachment avoidance, attachment anxiety, and difficulties engaging in goal-directed behavior (an aspect of emotion regulation) significantly predicted higher PTSS severity.Aspects of both attachment style and emotion regulation difficulties affect meaning made and PTSS severity. These constructs may be especially relevant for clinicians working with veterans to help PTSS and support meaning made postcombat.

Community participation in occupational, social, recreational, and other domains is critically important during young adulthood. Coordinated Specialty Care (CSC) programs provide developmentally tailored care to young adults experiencing early psychosis within the United States, but little is known about the breadth of efforts to promote community participation. This study aimed to develop and evaluate indicators of these efforts based on the perspectives of a national multi-stakeholder group.Seventeen stakeholders (i.e., young adults with early psychosis, family members, experts by profession) participated in a modified e-Delphi study, conducted in two rounds. The purpose of round one was to generate a comprehensive list of community participation-promoting indicators. During round two, stakeholders rated the importance and feasibility of the implementation of each indicator. Descriptive statistics and percentage of agreement regarding round two ratings were assessed.During round one, 186 indicators of activities and/or practices designed to promote community participation were identified; this list was reduced to 44 by eliminating redundancies or indicators not related to community participation. In round two, we found broad agreement regarding the importance, but significant variation in perceived feasibility of indicators. The highest-rated indicators in both categories pertained to staff knowledge (regarding barriers and supports to participation and the importance of participation to health) and strategies for addressing participation barriers.This study is expected to facilitate the identification and development of promising CSC activities and practices designed to promote community participation among young adults while potentially also enhancing engagement in services and improving clinical outcomes.

Occupational therapy plays an important role in fostering community participation in areas such as education, employment, leisure, and social relationships, yet its added value within early intervention in psychosis services, especially in the United States, remains poorly understood. The purpose of this research was to conduct a national survey of early intervention in psychosis programs to: (1) understand the role and unique contributions of occupational therapists to early intervention teams, and (2) identify barriers and supports to the implementation of occupational therapy services within these programs.Fifty-one senior leaders from U.S.-based early intervention in psychosis programs participated in the national survey. The survey consisted of a series of closed and open-ended questions related to program staffing, the presence of specific services that fall within the occupational therapy scope of practice, and implementation barriers and supports.Despite there being strong interest in employing occupational therapists, a small proportion of programs (31%) reported having them on staff. Occupational therapists supported clients across multiple life areas and were significantly more likely than other team members to promote daily living activities (e.g., cooking) and to address sensory processing needs and challenges. Implementation was influenced by environmental/organizational and staff factors; the primary barrier was funding.Findings support the role occupational therapists may play in facilitating the community participation of clients of early intervention services, but significant barriers to implementation of occupational therapy services remain. Additional research is needed to further identify the impact of occupational therapy services within the early intervention model.

METHODS Adults seeking behavioral health or medical treatment (N = 158) were recruited from a community healthcare agency and a residential support program in the southeastern United States. RESULTS Individuals who reported interpersonal trauma had significantly higher total PTS severity and symptom clusters. No significant difference was found in perceived PTG based on trauma type. No significant curvilinear relationship between PTS and perceived PTG was found. A significant negative linear relationship was observed between PTS and perceived PTG for non-interpersonal trauma, but not interpersonal trauma. CONCLUSION Trauma type may influence the PTS and perceived PTG relationship and, while associated with PTS, seems less important to reporting of perceived PTG.

Although telomere attrition is associated with the process of normal ageing, shorter telomere length (TL) has been associated with acute and chronic stressors. A neurobiological factor hypothesised to be responsible for this accelerated attrition is the dysregulation of the cortisol stress response, which can induce DNA damage affecting DNA telomeric caps. Marked sex differences are reported in both the cortisol stress response and telomere dynamics, yet no explicit investigation of sex specificity on the relationship between cortisol and TL exists. This study used mathematical equation modelling to describe the relationship between diurnal cortisol levels and telomere length within the context of sex, in a healthy population. Cortisol awakening responses (CAR) were measured via ELISA methodology in fifty-one healthy participants (28 males, 23 females). qPCRs determined TL from genomic DNA extracted from saliva. To assess the effect of free cortisol on relative TL ratio, a semi-log regression plot of the two variables trended for sex were fitted using spline curves. Results demonstrated significant differences between males and females in the relationship defining CAR and TL association (p = 0.03). These results suggest the relationship is not linear and can be represented as a complex arcsin function, and that the patterns are opposite in males and females. Males demonstrate a positive correlation, with higher levels of CAR being associated with longer telomere sequences. Females demonstrated a negative correlation. Future studies must carefully take into consideration moderating factors such as sex, and sex hormones across the lifespan when investigating telomere length.

The Cholera-Hospital-Based Intervention for 7-days (CHoBI7) mobile health (mHealth) program delivers mobile messages to diarrhoea patient households promoting water treatment and handwashing with soap. The randomised controlled trial (RCT) of the CHoBI7 mHealth program demonstrated this intervention was effective in significantly reducing diarrhoea and stunting amoung young children. The objective of this study was to assess the implementation of the CHoBI7 mHealth program in delivering mHealth messages during this RCT.517 diarrhoea patient households with 1777 participants received weekly text, voice and interactive voice response (IVR) messages from the CHoBI7 mHealth program over the 12-month program period. The program process evaluation indicators were the following: the percentage of CHoBI7 mHealth messages received and fully listened to by program households (program fidelity and dose), and household members reporting receiving and sharing an mHealth message from the program in the past two weeks (program reach).Ninety two percent of text messages were received by program households. Eighty three percent of voice and 86% of IVR messages sent were fully listened to by at least one household member. Eighty one percent of IVR quiz responses from households were answered correctly. Program households reported receiving a CHoBI7 mHealth message in the past two weeks at 79% of monthly household visits during the 12-month program. Seventy seven percent of participants reported sharing a program message with a spouse, 55% with a neighbour and 49% with a child during the program period.There was high fidelity, dose and reach of mobile messages delivered for the CHoBI7 mHealth program. This study presents an approach for process evaluation that can be implemented to evaluate future mHealth programs.Le programme CHoBI7 (Cholera-Hospital-Based-Intervention-for-7-days) de santé mobile (mHealth) délivre des messages mobiles aux ménages avec patients atteints de diarrhée pour promouvoir le traitement de l'eau et le lavage des mains au savon. L'essai contrôlé randomisé (ECR) du programme mHealth CHoBI7 a démontré que cette intervention était efficace pour réduire de manière significative la diarrhée et le retard de croissance chez les jeunes enfants. L'objectif de cette étude était d'évaluer la mise en œuvre du programme CHoBI7 mHealth dans la diffusion des messages mHealth au cours de cet ECR. MÉTHODES: 517 ménages avec des patients atteints de diarrhée ont reçu chaque semaine des messages SMS, vocaux et de réponse vocale interactive (RVI) du programme mHealth de CHoBI7 pendant les 12 mois du programme. Les indicateurs d'évaluation du processus du programme étaient les suivants: le pourcentage de messages mHealth du programme CHoBI7 reçus (fidélité au programme et dose) et entièrement écoutés par les ménages participant au programme (fidélité au programme et dose) et les bénéficiaires déclarant avoir reçu et partagé un message mHealth du programme (portée du programme) au cours des deux dernières semaines. RÉSULTATS: 92% des SMS ont été reçus par les ménages participant au programme. 83% des messages vocaux et 86% des messages RVI envoyés ont été entièrement écoutés par au moins un membre du ménage. 81% des réponses aux quiz RVI des ménages ont été correctement répondues. Les ménages du programme ont déclaré avoir reçu un message CHoBI7 mHealth au cours des deux dernières semaines dans 79% des visites mensuelles des ménages pendant les 12 mois du programme. 77% des participants ont déclaré avoir partagé un message du programme avec un conjoint, 55% avec un voisin et 49% avec un enfant pendant la durée du programme.La dose et les messages délivrés dans le cadre du programme mHealth de CHoBI7 l’ont été avec une fidélité élevée. Cette étude présente une approche d'évaluation des processus qui peut être mise en œuvre pour évaluer les futurs programmes mHealth.

The objective of this study was to investigate the association between dietary diversity, child growth and child developmental outcomes. This was a prospective cohort study. Developmental outcomes were assessed by communication, fine motor, gross motor, personal social, problem solving and combined developmental scores measured by the Extended Ages and Stages Questionnaire (EASQ) at a 6-month follow-up visit. Height and weight were measured at baseline and a 6-month follow-up. Baseline minimum dietary diversity (MDD) for children 6-23 months old was defined by consumption of five or more of the following food groups: (1) breast milk; (2) grains, roots and tubers; (3) legumes and nuts; (4) dairy products; (5) flesh foods; (6) eggs; (7) vitamin A-rich fruits and vegetables and (8) other fruits and vegetables. Participants were 117 children 6-23 months of age. Linear growth faltering was defined as a significant decline (p 0.05) in length-for-age Z-scores (LAZ) between baseline and follow-up. Regression models were performed. The study was conducted in rural eastern Democratic Republic of the Congo (DRC). MDD was positively associated with change in LAZ (coefficient: 0.87 [95% confidence interval [CI]: 0.33, 1.40]), and a reduced odds of stunting (LAZ -2) (odds ratio: 0.21 [95% CI: 0.07, 0.61]). MDD was also associated with a significantly higher combined EASQ-Z-scores (coefficient: 0.34 [95% CI: 0.003, 0.68], higher communication EASQ-Z-scores [0.50 {95% CI: 0.14, 0.85}], and higher personal social EASQ-Z-scores [0.46 {95% CI: 0.11, 0.82}]). This study provides further evidence demonstrating the need for interventions to improve dietary diversity among young children.

Objectives The study aims to evaluate the long-term results of the extraperitoneal uterosacral ligament suspension (bilateral) technique in women with apical prolapse following hysterectomy. Design Longitudinal clinical follow up conducted between June 2002 and December 2017. Setting Tertiary urogynaecology centre in Melbourne, Australia. Population A total of 472 women with symptomatic vault prolapse who underwent bilateral extraperitoneal uterosacral ligament suspension (EPUSLS). Of these patients, 61% (287/472) had previously had a procedure for pelvic organ prolapse (POP). Methods Follow up using structured, standardised questionnaires and examination by POP-Q and Baden-Walker system pre- and postoperatively. Main outcome measures Functional and anatomical results and surgical complications. Results Mean follow-up duration was approximately 5 years. The objective success rate at vaginal cuff support was 89% (420/472). Only 4% needed revision surgery for vault recurrence. There was improvement in bladder, bowel, and sexual symptoms after the procedure. Mesh exposure rate was 17% (of the 138 having mesh augmentation), with the majority of cases managed conservatively or with minor interventions. The ureteric injury rate was 1% and mainly occurred in patients operated early on in the series. No women had buttock pain. Conclusion EPUSLS is an effective, suture-based procedure for vault prolapse with few complications even on long-term follow up. This technique avoids the need to open the peritoneum vaginally and has a low risk of ureteric injury and gluteal pain. Tweetable abstract Bilateral extraperitoneal USL suspension of vault is effective with low morbidity and a high success rate.

By their ability to shatter quality of life for both patients and caregivers, neurodegenerative diseases are the most devastating of human disorders. Unfortunately, there are no effective or long-terms treatments capable of slowing down the relentless loss of neurons in any of these diseases. One impediment is the lack of detailed knowledge of the molecular mechanisms underlying the processes of neurodegeneration. While some neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are mostly sporadic in nature, driven by both environment and genetic susceptibility, many others, including Huntington's disease, spinocerebellar ataxias, and spinal-bulbar muscular atrophy, are genetically inherited disorders. Surprisingly, given their different roots and etiologies, both sporadic and genetic neurodegenerative disorders have been linked to disease mechanisms involving histone deacetylase (HDAC) proteins, which consists of 18 family members with diverse functions. While most studies have implicated certain HDAC subtypes in promoting neurodegeneration, a substantial body of literature suggests that other HDAC proteins can preserve neuronal viability. Of particular interest, however, is the recent realization that a single HDAC subtype can have both neuroprotective and neurotoxic effects. Diverse mechanisms, beyond transcriptional regulation have been linked to these effects, including deacetylation of non-histone proteins, protein-protein interactions, post-translational modifications of the HDAC proteins themselves and direct interactions with disease proteins. The roles of these HDACs in both sporadic and genetic neurodegenerative diseases will be discussed in the current review.

OBJECTIVE The current study aimed to identify how sex influences neurobiological responses to food cues, particularly those related to hedonic eating, and how this relates to obesity propensity, using functional magnetic resonance imaging (fMRI). METHODS Adult men and women who were either obesity resistant (OR) or obesity prone (OP) underwent fMRI while viewing visual food cues (hedonic foods, neutral foods, and nonfood objects) in both fasted and fed states. RESULTS When fasted, a significant sex effect on the response to hedonic vs. neutral foods was observed, with greater responses in women than men in the nucleus accumbens (P = 0.0002) and insula (P = 0.010). Sex-based differences were not observed in the fed state. No significant group effects (OP vs. OR) or group-by-sex interactions were observed in fasted or fed states. CONCLUSIONS Greater fasted responses to hedonic food cues in reward-related brain regions were observed in women compared with men, suggesting that women may be more sensitive to the reward value of hedonic foods than men when fasted. This may indicate sex-dependent neurophysiology underlying eating behaviors.

Background The occupational justice framework was established in the late 1990s with an agenda to spur occupational therapists to take action against injustices pertaining to occupation. Methods A critical interpretive synthesis of 23 texts was undertaken to examine how the occupational justice framework has been utilised in research, with a particular focus on how such research is located on a knowledge to action continuum and the extent to which it enacts the call to remediate occupational injustices. Results Within the texts reviewed, the occupational justice framework was predominantly used to interpret research findings, and only four studies explicitly used an action research approach. There was also a dominant tendency to individualise situations of occupational justice, but with some examples attending to the social and political production of injustices. Absences and silences related to the locations of the research in developed regions and a focus on conceptualisations of justice commensurate with a Western worldview were evident. Conclusions Full realisation of the potential contributions of the occupational justice framework requires challenging traditional modes of research that focus primarily on knowledge generation, and expanding into modes of research that embrace a knowledge to action continuum. This expansion, which will enable occupational justice research to more fully embrace action-oriented work, requires practicing epistemological reflexivity, adopting a critical stance, incorporating a participatory action research approach and collaborating with scholars from different disciplines.

Aims and objectives Pelvic organ prolapse is a common condition, with reported incidence of up to 50%. We aimed to assess whether written information, in addition to face-to-face consultation, improved happiness with information, confidence to self-manage and prolapse knowledge in women attending a pessary clinic. Background Little is known about the effect of adding a written information brochure on clinical outcomes of patients using pessaries. Design This prospective study used a pretest posttest method, conducted following Ethical approval. Methods Between February and December 2013 all women attending Pessary Clinic were eligible for participation. A questionnaire was developed assessing happiness with information, confidence regarding self-management (using a visual analogue scale, 1-10) and prolapse knowledge (using eight multiple-choice questions). Data were collected in person at baseline prior to distribution of a patient brochure and thereafter by telephone at one-week and three-months. Paired analysis was conducted using the McNemar test and Related Samples Wilcoxon Signed Rank Test for VAS items with p.05), first language(p>.05) or previous clinic visits(p>.05). Conclusion A written information brochure, in addition to face-to-face consultation, improves happiness with information, confidence to self-manage and knowledge about pessaries compared to verbal instruction alone and does make patients better able to understand their care. The written brochure was equally effective in women with low education and advanced age, and occurred regardless of number of clinic visits. This article is protected by copyright. All rights reserved.

Background Research indicates that dispositional mindfulness is associated with positive psychological functioning. Although this disposition has been linked with beneficial outcomes in the broader mental health literature, less is known about dispositional mindfulness in cancer survivors and how it may be linked with indices of psychological and physical health relevant to cancer survivorship. Methods We conducted a multivariate path analysis of data from a heterogeneous sample of cancer patients (N = 97) to test the Mindfulness-to-Meaning Theory, an extended process model of emotion regulation linking dispositional mindfulness with cancer-related quality of life via positive psychological processes. Results We found that patients endorsing higher levels of dispositional mindfulness were more likely to pay attention to positive experiences (β = .56), a tendency which was associated with positive reappraisal of stressful life events (β = .51). Patients who engaged in more frequent positive reappraisal had a greater sense of meaning in life (β = .43) and tended to savor rewarding or life affirming events (β = .50). In turn, those who engaged in high levels of savoring had better quality of life (β = .33) and suffered less from emotional distress (β = −.54). Conclusions Findings provide support for the Mindfulness-to-Meaning Theory and help explicate the processes by which mindfulness promotes psychological flourishing in the face of cancer. Implications for Cancer Survivorship Cancer survivors may benefit from enhancing mindfulness, reappraisal, and savoring. Copyright © 2016 John Wiley & Sons, Ltd.

Objective Phentermine is thought to cause weight loss through a reduction in hunger. We hypothesized that higher hunger ratings would predict greater weight loss with phentermine.

Objective To determine the effect of mode of delivery and perineal injury on sexual function at 6 and 12 months postpartum. Design Prospective cohort study. Setting Tertiary women's hospital in Melbourne, Australia. Population A cohort of 440 primigravid women. Methods The Female Sexual Function Index (FSFI) was completed at first visit (7–19 weeks of gestation), and at 6 and 12 months postpartum. Main outcome measures A statistically significant difference in total FSFI or domain scores over time according to mode of delivery or perineal injury. Results In this cohort 54% of women had a normal vaginal delivery, 21% had an instrumental delivery, and 25% gave birth by caesarean section. No difference was found in total FSFI or domain scores according to mode of delivery over time between antenatal assessment and 12 months postpartum. Pain was decreased in the caesarean group only at 6 months postpartum. All groups showed pain scores at 12 months that were comparable with antenatal levels. For those who gave birth vaginally, 27% had an intact perineum, 50% had an episiotomy, and 6%, 14%, and 3% had first, second, and third-degree tears, respectively. The only differences between groups were found over time according to perineal injury at 6 months in the arousal domain. At 12 months, total FSFI and domain scores were no different to initial scores. Conclusions At 12 months postpartum sexual function has returned to early pregnancy levels, irrespective of mode of delivery or perineal injury.

Objective This randomized, cross-over trial was designed to investigate the metabolic and appetitive responses to skipping breakfast in overweight women who were habitual breakfast Eaters or Skippers. Methods Nine Eaters and nine Skippers were studied on two separate days during which subjects ate breakfast (B) or had no breakfast (NB), followed by a standard lunch meal 4 h later. Blood sampling for hormones and metabolites was performed after lunch, and appetite was rated throughout the day. Results Interactions between day and habitual breakfast pattern were seen for area under the curve (AUC) for insulin and free fatty acids (FFA). Both insulin (P = 0.020) and FFA (P = 0.023) AUC were higher on the NB day for Eaters but similar on both days for Skippers. Eaters had higher pre lunch hunger AUC on the NB day (P = 0.015) as well as lower pre lunch satiety AUC under both conditions (P = 0.019). Conclusions Overall, this study showed that the adverse effects of skipping breakfast (higher insulin and FFA responses to lunch, increased hunger, and decreased satiety) were found primarily in habitual breakfast eaters. This suggests that meal skipping may have enhanced effects in habitual Eaters due to entrainment of metabolic and appetitive regulatory systems.

Three loci that modify β-amyloid (Aβ) accumulation and deposition in the brains of a mouse model of Alzheimer's disease have been previously described. One encompasses the Psen2 gene encoding presenilin 2, a component of the γ-secretase activity responsible for generating Aβ by proteolysis. We show that the activity of mouse Psen2, as measured by levels of mRNA accumulation, unexpectedly is heritable in the liver but not the brain, suggesting liver as the origin of brain Aβ deposits. Administration of STI571, a cancer therapeutic that does not cross the blood-brain barrier, reduced accumulation of Aβ in both the blood and the brain, confirming brain Aβ's peripheral origin and suggesting that STI571 and related compounds might have therapeutic/prophylactic value in human Alzheimer's disease. The genes Cib1 and Zfhx1b reside within the other modifier loci and also exhibit heritable expression in the liver, suggesting that they too contribute to Aβ accumulation.

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor, psychiatric, and cognitive abnormalities. In this present study, we tested whether abnormal motor behavior in a mouse model of HD, the R6/1 transgenic (Tg) mice, was associated with changes in cerebellar lipid composition and gene expression. We report altered motor behavior, which was associated with abnormal expression of glycosyltransferase genes in the cerebellum of R6/1 Tg mice. Cerebellar wet weight and total ganglioside concentration was significantly lower in R6/1 Tg mice than in wild-type (Wt) mice. Furthermore, the Purkinje cell-enriched ganglioside LD1 and the granule cell-enriched ganglioside GD1a were significantly lower in R6/1 Tg mice than in Wt mice. The myelin-enriched lipid sulfatides was also reduced in the cerebellum of R6/1 Tg mice. In contrast to the R6/1 Tg mice, total cerebellar ganglioside concentration did not differ between HD and control subjects. However, expression of several cerebellar glycosyltransferases genes was significantly less in HD subjects than in control subjects. Our findings indicate that the R6/1 Tg mice have severe cerebellar glycosphingolipid (GSL) abnormalities that may account, in part, for their abnormal motor behavior. Although the cerebellar lipid abnormalities found in the R6/1 Tg mice were not found in these HD subjects, the R6/1 Tg mice may be useful for evaluating the role of GSLs in cerebellar development.

With accelerated melting of alpine glaciers, understanding the future state of the cryosphere is critical. Because the observational record of glacier response to climate change is short, palaeo-records of glacier change are needed. Using proglacial lake sediments, which contain continuousanddatablerecordsofpastglacieractivity,weinvestigateHoloceneglacierfluctuationson northeastern Baffin Island. Basal radiocarbon ages from three lakes constrain Laurentide Ice Sheet retreat by ca. 10.5ka. High sedimentation rates (0.03cma ! 1 ) and continuous minerogenic sedimen- tation throughout the Holocene in proglacial lakes, in contrast to organic-rich sediments and low sedimentation rates (0.005cma ! 1 ) in neighbouring non-glacial lakes, suggest that glaciers may have persisted in proglacial lake catchments since regional deglaciation. The presence of varves and relatively high magnetic susceptibility from 10 to 6ka and since 2ka in one proglacial lake suggest minimum Holocene glacier extent ca. 6-2ka. Moraine evidence and proglacial and threshold lake sediments indicate that the maximum Holocene glacier extent occurred during the Little Ice Age. The finding that glaciers likely persisted through the Holocene is surprising, given that regional proxy records reveal summer temperatures several degrees warmer than today, and may be due to shorter ablation seasons and greater accumulation-season precipitation. Copyright # 2009 John Wiley & Sons, Ltd.

We examined genome-wide expression datasets from human prefrontal cortex of normal and schizophrenic individuals ranging from 19 to 81 years of age. We found that changes in gene expression that are correlated with aging in normal subjects differ dramatically from those observed with aging in schizophrenic subjects. Only 2.5% of genes were correlated with age in both groups. Surprisingly, we also found a significant overlap (29-34%) between those genes whose expression was correlated with aging in normal subjects and those significantly altered in subjects with early-stage schizophrenia (within 4 years of diagnosis). This suggests that schizophrenia onset anticipates the normal aging process, and further, that some symptoms of aging, i.e. dementia and psychosis, might be explained by these common molecular profiles.

As the field of glycobiology grows, important roles for glycolipids and glycoproteins in neurological disorders are being increasingly appreciated. However, few studies have explored the involvement of these molecules in the pathology of psychiatric illnesses. We investigated molecular differences related to glycobiology in subjects with schizophrenia by analyzing gene expression profiles using a focused glycogene chip, a custom-designed oligonucleotide array containing genes encoding proteins related to glycobiology, including glycosyltransferases, carbohydrate-binding proteins, proteoglycans, and adhesion molecules. We measured expression profiles in prefrontal cortical (BA46) samples from schizophrenic subjects and matched controls. We find differential expression of genes particularly related to glycosphingolipid/sphingolipid metabolism and N- and O-linked glycan biosynthesis in subjects with schizophrenia. Expression decreases of seven genes associated with these pathways, UGT8, SGPP1, GALC, B4GALT6, SPTLC2, ASAH1, and GAL3ST1, were validated by quantitative PCR in schizophrenic subjects with short-term illness. Only one of these genes, SPTLC2, showed differential expression in chronic schizophrenic subjects, although an increase in expression was observed. Covariate analysis showed that the expression of five of these genes was significantly positively correlated with age in schizophrenic, but not control, subjects. These changing patterns of expression could represent an adaptive response to pathology with disease progression or a compensatory effect of antipsychotic medication, although no significant correlations between gene expression levels and drug doses were observed. Disruption of sphingolipid metabolism early in illness could result in widespread downstream effects encompassing diverse pathological deficits already described in schizophrenia, especially those involving myelination and oligodendrocyte function; hence, this system may represent an important link in schizophrenia pathology.

In contrast to typical neuroleptic drugs, which have high affinities for dopamine D2 receptors, clozapine binds to multiple neurotransmitter receptors. The mechanisms responsible for its superior clinical efficacy over typical neuroleptics remain unknown. Using an automated genomics approach, total gene expression analysis (TOGA), we found an approximately threefold increase in the accumulation of the mRNA encoding apolipoprotein D (apoD) in mouse striatum in response to chronic treatment with clozapine. While in control animals, apoD is expressed predominantly in astrocytes, in situ hybridization and immunohistochemical studies indicated a substantial increase in apoD expression in neurons of the striatum, globus pallidus and thalamus after 2 weeks of clozapine treatment. Clozapine-induced increases in apoD expression were also observed in some white matter regions. These results suggest that apoD is a mediator in the mechanisms of clozapine and thus that deficiencies in aspects of lipid metabolism may be responsible for psychoses.

Apolipoprotein D (apoD) expression is known to be elevated in select regions of rodent and human brain in association with different types of CNS pathology. To investigate a potential role for apoD in the neuropathology of Alzheimer's disease, we have measured apoD mRNA expression in transgenic mice expressing mutated human amyloid precursor protein under control of platelet-derived growth factor promoter (PDAPP mice). In situ hybridization analysis revealed increased apoD mRNA expression in brains of aged (26 months) PDAPP transgenic mice compared to aged littermate controls. These increases were most prominent in the hippocampal fimbria, corpus callosum and other white matter tracts. No substantial increases in expression were observed in white matter regions in young (6 months) PDAPP transgenic mice compared to young controls. Comparison between aged and young control mice revealed increased apoD expression in similar white matter regions of the aged animals. These findings suggest that, although increases in apoD expression are a normal feature of brain aging, super-increases may represent a glial cell compensatory response to beta-amyloid deposition in Alzheimer's disease.

Schizophrenia is a complex psychiatric illness that manifests as a combination of positive symptoms, negative symptoms, and cognitive deficits. Antipsychotic drugs, such as haloperidol, attenuate dopamine receptor signaling in neurons and constitute the frontline treatment for the positive symptoms of schizophrenia. However, haloperidol treatment has also been reported to exacerbate preexisting negative symptoms/cognitive deficits and the severity of these deficits has been correlated with white matter pathology in schizophrenia. Indeed, several studies implicate oligodendrocyte function in the pathophysiology of schizophrenia, but it is unknown whether these effects are related to drug treatment. It is well established that haloperidol alters gene expression in neurons. However, its effect on oligodendrocytes is unknown. In this study, we investigate the effects of chronic haloperidol treatment on the expression of eight genes known to play critical roles in myelin/oligodendrocyte function. We treated male mice with haloperidol (2 mg/kg/day) for 30 days and measured gene expression changes by using in situ hybridization analysis and quantitative densitometry. Haloperidol caused a decrease in the expression of these genes in several white matter regions of the mouse CNS. In contrast, clozapine (10 mg/kg/day) had no effect on the expression of a subset of these genes. This has important implications for both disease pathology and the consideration of treatment options for patients.

BackgroundBronchiectasis is characterised by a widening of the airways, leading to excess mucus production and recurrent infection. It is more prevalent in women and those in middle age. Many patients with bronchiectasis do not adhere to treatments (medications, exercise and airway clearance) prescribed for their condition. The best methods to change these adherence behaviours have not been identified.ObjectivesTo assess the effects of interventions to enhance adherence to any aspect of treatment in adults with bronchiectasis in terms of adherence and health outcomes, such as pulmonary exacerbations, health-related quality of life and healthcare costs.Search methodsWe searched the Cochrane Airways Group Specialised Register (CAGR), which contains trial reports identified through systematic searches of CENTRAL, MEDLINE, EMBASE, CINAHL, AMED and PsycINFO, from inception to October 2015.Selection criteriaWe planned to include randomised controlled trials (RCTs) of adults with bronchiectasis that compared any intervention aimed at enhancing adherence versus no intervention, usual care or another adherence intervention. We excluded studies of those who had bronchiectasis due to cystic fibrosis.Data collection and analysisTwo review authors (AMcC and ET) independently screened titles, abstracts and full-texts of identified studies.Main resultsSearches retrieved 36 studies reported in 37 articles; no eligible studies were identified.Authors' conclusionsWe did not identify any studies that assessed the effect of interventions to enhance adherence to treatment in bronchiectasis. Adequately powered, well-designed trials of adherence interventions for bronchiectasis are needed.

We have identified and cataloged 54 genes that exhibit predominant expression in the striatum. Our hypothesis is that such mRNA molecules are likely to encode proteins that are preferentially associated with particular physiological processes intrinsic to striatal neurons, and therefore might contribute to the regional specificity of neurodegeneration observed in striatal disorders such as Huntington's disease (HD). Expression of these genes was measured simultaneously in the striatum of HD R6/1 transgenic mice using Affymetrix oligonucleotide arrays. We found a decrease in expression of 81% of striatum-enriched genes in HD transgenic mice. Changes in expression of genes associated with G-protein signaling and calcium homeostasis were highlighted. The most striking decrement was observed for a newly identified subunit of the sodium channel, beta 4, with dramatic decreases in expression beginning at 8 weeks of age. A subset of striatal genes was tested by real-time PCR in caudate samples from human HD patients. Similar alterations in expression were observed in human HD and the R6/1 model for the striatal genes tested. Expression of 15 of the striatum-enriched genes was measured in 6-hydroxydopamine-lesioned rats to determine their dependence on dopamine innervation. No changes in expression were observed for any of these genes. These findings demonstrate that mutant huntingtin protein causes selective deficits in the expression of mRNAs responsible for striatum-specific physiology and these may contribute to the regional specificity of degeneration observed in HD.

We have investigated the functional coupling of the rat 5HT(5a) receptor subtype to adenylate cyclase in a rat C6 glioma cell line. In 5HT(5a) receptor-transfected cells, 5HT caused a concentration-dependent inhibition of forskolin-stimulated cAMP accumulation, with an EC(50) value of 41 nM and a maximal effect of 57% inhibition. This effect was dependent on the concentration of forskolin used to elevate cAMP levels. Methiothepin (1 mcM), which has high affinity for the 5HT(5a) receptor, antagonized the 5HT(5a) receptor-mediated inhibition, and unmasked a stimulation of cAMP formation similar to that observed in untransfected cells, whereas ketanserin (0.1 mcM) enhanced the inhibitory effect of 5HT. Pertussis toxin treatment (0.5 mcg/ml) completely blocked the inhibitory effect of 5HT on cAMP formation, also revealing increase in cAMP accumulation. Pretreatment of the transfected membranes with pertussis toxin abolished subsequent ADP-ribosylation of a 41 kDa protein, correlating the cAMP effect with a functional uncoupling of an inhibitory G protein from its receptor. These results demonstrate an efficient functional coupling of the rat 5HT(5a) receptor to the inhibition of adenylate cyclase via a pertussis toxin-sensitive G[alpha(i)], inhibitory G-protein.

Comparison of high-resolution core-level spectra from simple long-chain aliphatic hydrocarbons and hydrocarbon polymers show minor differences between ideal, specially prepared samples and samples of ‘as-received’ materials. Asymmetric peaks whose structure may be attributed to vibrational-level excitation can be resolved easily under conditions that do not cause damage. This asymmetric structure is independent of sample morphology and sampling depth. © 1998 John Wiley & Sons, Ltd.

A clone of the regulator of G-protein signalling, RGS9, was isolated from a rat striatum-minus-cerebellum-minus-hippocampus subtracted library generated by directional tag polymerase chain reaction subtraction. The full-length cDNA clone encodes a 444 amino acid protein containing an 118 amino acid RGS domain, which corresponds to an evolutionarily conserved domain that is present in all members of the RGS family of proteins. Outside of the homology domain, RGS9 shows more extended similarity to human RGS6 and RGS7, rat RGS12, and the C. elegans protein EGL-10. During embryonic and early postnatal stages of development, two RGS9 transcripts of approximately 1.4 Kb and 1.8 Kb were detected in whole brain. After postnatal day 10, accumulation of the larger transcript increased progressively until adulthood at the expense of the smaller transcript, which was undetectable in the adult. In adult rat brain, the 1.8-Kb RGS9 transcript was detected in the striatum but not in other brain regions or peripheral tissues. In situ hybridization in rat and mouse demonstrates that RGS9 mRNA is expressed predominantly in medium-sized, spiny neurons of the neostriatum and in neurons of the nucleus accumbens and olfactory tubercle. Relatively strong signals were also detected in some hypothalamic nuclei. Its selective expression suggests that RGS9 may play an important role in modulation of the complex signalling pathways of the basal ganglia.

Fatty acid amide hydrolase (FAAH) is a membrane-bound enzyme activity that degrades neuromodulatory fatty acid amides, including oleamide and anandamide. A single 2.5-kb FAAH mRNA is distributed throughout the rat CNS and accumulates progressively between embryonic day 14 and postnatal day 10, remains high until postnatal day 30, then decreases into adulthood. FAAH enzymatic activity, as measured in dissected brain regions, was well correlated with the distribution of its messenger RNA. In situ hybridization revealed profound distribution of FAAH mRNA in neuronal cells throughout the CNS. The most prominent signals were detected in the neocortex, hippocampal formation, amygdala, and cerebellum. The FAAH distribution in the CNS suggests that degradation of neuromodulatory fatty acid amides at their sites of action influences their effects on sleep, euphoria, and analgesia.

The mRNA for the 5-hydroxytryptamine receptor 5-HT5A was detected at embryonic day 18 in the rat central nervous system and peaked by postnatal day 20. At all time points examined, 5-HT5A immunoreactivity observed on astrocyte cell bodies and in the stellate processes not only colocalized with the astrocyte-specific marker glial fibrillary acidic protein (GFAP) but was coordinately regulated with GFAP, increasing during development and during gliosis. Transfection of 5-HT5A into glioma cells prevented the 5-HT-induced increase in cAMP observed in untransfected cells and decreased the relative forskolin response by approximately 20%, suggesting that the 5-HT5A receptor couples negatively to adenylyl cyclase in astrocytes. Together, these results indicate a neuron-to-astrocyte serotonergic signaling pathway mediating cAMP concentrations, which could provide a neuronally driven mechanism for regulating astrocyte physiology with relevance to gliosis.

Chemical stabilization of {beta}-cristobalite has been achieved using two methods: (1) incorporating ``stuffing`` cations Na, Ca, Cu, and Sr into the cavities in the tectosilicate framework, as previously reported, and (2) without ``stuffing`` cations, by substituting AIPO{sub 4} into the framework. XRD, TEM, FTIR, DSC, and solid-state variable-temperature {sup 29}Si NMR confirm that stabilization occurs by both methods. Dynamic disorder, characteristic of the {beta}-cristobalite structure above the {alpha} {leftrightarrow} {beta} phase transition, was observed via TEM in the NaAlO{sub 2}-, CaAl{sub 2}O{sub 4}-, and CuAl{sub 2}O{sub 4}-stabilized cristobalites at room temperature. For AIPO{sub 4}-stabilized material intergrowths of AIPO{sub 4} regions with a tridymite-type structure suppress the {beta}- {yields} {alpha}-cristobalite phase transition.

The author analyzes international migration patterns of Caribbean populations with particular attention to the persistence of significant return flows. A typology of migration in the region is presented which includes categories of transients or shuttle migrants and settlers or long-stay migrants. Skill or occupational changes principal remittances and migration objectives of each group are summarized. The social economic and policy implications of international circulation in the Caribbean are considered. (SUMMARY IN FRE AND SPA) (ANNOTATION)

To study type and amount of training in geropsychology available to students in APA-approved doctoral programs in clinical and counseling psychology, a questionnaire was mailed to all such programs in 1984. Response rate was 71 of 132 (59%) for clinical programs and 27 of 37 (73%) for counseling programs. Very little difference was found between responses of clinical and counseling programs and between this 1984 survey and one conducted in 1975-76. There seems to be a very small increase in training opportunities for psychology students in geropsychology in 1984 at the doctoral level.