Manifestations of affective disturbance in sub-Saharan Africa: key themes

BACKGROUND: Affective disorder, once seen as rare in sub-Saharan Africa, is now viewed as more common. There are however challenges in assessing rates of depression, exploring manifestations of depression, and understanding risk factors for depression, especially those related to gender. AIM: To identify key themes and new directions for research on affective disorder in sub-Saharan Africa, with particular reference to gender issues. METHODS: Interpretive review of selected literature, and theoretical analysis. RESULTS: There are gender differences in manifestations and rates of depression in sub-Saharan Africa, and there are forms of presentation (largely somatic, based on interpersonal relationships, or spiritual in nature) which may obscure the detection of depression. Studies are consistent however that when depressive symptoms are sought and are present, these are reasonably easy to elicit. LIMITATIONS: This was not a systematic review, and the substantial grey literature from sub-Saharan Africa was not reviewed. For many countries, there are no data available. CONCLUSIONS: Affective disorder, when properly sought for through both qualitative and quantitative methods, has been found to be common in sub-Saharan Africa. There is a paucity of research on interventions with affective disorder in this region.     

Antagonizing the αvβ3 Integrin Inhibits Angiogenesis and Impairs Woven but Not Lamellar Bone Formation Induced by Mechanical Loading

Angiogenesis and osteogenesis are critically linked, although the role of angiogenesis is not well understood in osteogenic mechanical loading. In this study, either damaging or non‐damaging cyclic axial compression was used to generate woven bone formation (WBF) or lamellar bone formation (LBF), respectively, at the mid‐diaphysis of the adult rat forelimb. α_vβ₃ integrin–targeted nanoparticles or vehicle was injected intravenously after mechanical loading. β₃ integrin subunit expression on vasculature was maximal 7 days after damaging mechanical loading, but was still robustly expressed 14 days after loading. Accordingly, targeted nanoparticle delivery in WBF‐loaded limbs was increased compared with non‐loaded limbs. Vascularity was dramatically increased after WBF loading (+700% on day 14) and modestly increased after LBF loading (+50% on day 14). This increase in vascularity was inhibited by nanoparticle treatment in both WBF‐ and LBF‐loaded limbs at days 7 and 14 after loading. Decreased vascularity led to diminished woven, but not lamellar, bone formation. Decreased woven bone formation resulted in impaired structural properties of the skeletal repair, particularly in post‐yield behavior. These results demonstrate that α_vβ₃ integrin–mediated angiogenesis is critical for recovering fracture resistance after bone injury but is not required for bone modeling after modest mechanical strain. © 2014 American Society for Bone and Mineral Research.     

Effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine on appetite,food intake and emotional processing in healthy volunteers

Rationale

The treatment of obesity is an increasing global health priority, yet few effective drug treatments are currently available. The discovery of novel anti-obesity therapies could be assisted by the validation of experimental (translational) medicine models in healthy volunteers that assess efficacy and safety at an early stage of drug development.

Objectives

The aim of this study was to examine the effects of the 5-HT_2C receptor agonist meta-chlorophenylpiperazine (mCPP) in an experimental medicine model assessing both appetite and mood.

Methods

Using a between-subjects, double-blind, placebo-controlled design, 24 male and 24 female participants were randomly assigned to either placebo, 15- or 30-mg mCPP treatment groups. Lunch was eaten from a Universal Eating Monitor (UEM) that measured eating rate, and the participants completed the P1vital® Oxford Emotional Test Battery (ETB) and a series of appetite and mood ratings.

Results

mCPP reduced appetite and, in women, enhanced measures of satiation. The drug also enhanced memory for emotional material in the word recall and recognition memory tasks of the ETB.

Conclusions

The results provide new insight into the effects of mCPP on appetite, satiety and memory in humans. In addition, our data provide an illustration of the value of measuring changes in appetite and mood in healthy volunteers to determine the potential efficacy and safety of novel anti-obesity drugs.     

Androgen generation in adipose tissue in women with simple obesity--a site-specific role for 17beta-hydroxysteroid dehydrogenase type 5

Women with polycystic ovary syndrome (PCOS) have high circulating androgens, thought to originate from ovaries and adrenals, and frequently suffer from the metabolic syndrome including obesity. However, serum androgens are positively associated with body mass index (BMI) not only in PCOS, but also in simple obesity, suggesting androgen synthesis within adipose tissue. Thus we investigated androgen generation in human adipose tissue, including expression of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes, important regulators of sex steroid metabolism. Paired omental and subcutaneous fat biopsies were obtained from 27 healthy women undergoing elective abdominal surgery (age range 30-50 years; BMI 19.7-39.2 kg/m(2)). Enzymatic activity assays in preadipocyte proliferation cultures revealed effcient conversion of androstenedione to testosterone in both subcutaneous and omental fat. RT-PCR of whole fat and preadipocytes of subcutaneous and omental origin showed expression of 17beta-HSD types 4 and 5, but no relevant expression of 17beta-HSD types 1, 2, or 3. Microarray analysis confirmed this expression pattern (17beta-HSD5>17beta-HSD4) and suggested a higher expression of 17beta-HSD5 in subcutaneous fat. Accordingly, quantitative real-time RT-PCR showed significantly higher expression of 17beta-HSD5 in subcutaneous compared with omental fat (P<0.05). 17beta-HSD5 expression in subcutaneous, but not omental, whole fat correlated significantly with BMI (r=0.51, P<0.05). In keeping with these findings, 17beta-HSD5 expression in subcutaneous fat biopsies from six women taking part in a weight loss study decreased significantly with weight loss (P<0.05). A role for 17beta-HSD5 in adipocyte differentiation was further supported by the observed increase in 17beta-HSD5 expression upon differentiation of stromal preadipocytes to mature adipocytes (n=5; P<0.005), which again was higher in cells of subcutaneous origin. Functional activity of 17beta-HSD5 also significantly increased with differentiation, revealing a net gain in androgen activation (androstenedione to testosterone) in subcutaneous cultures, contrasting with a net gain in androgen inactivation (testosterone to androstenedione) in omental cultures. Thus, human adipose tissue is capable of active androgen synthesis catalysed by 17beta-HSD5, and increased expression in obesity may contribute to circulating androgen excess.     

SMAD4 mutations in colorectal cancer probably occur before chromosomal instability, but after divergence of the microsatellite instability pathway

Loss of chromosome 18q21 is well documented in colorectal cancer, and it has been suggested that this loss targets the DCC, DPC4/SMAD4, and SMAD2 genes. Recently, the importance of SMAD4, a downstream regulator in the TGF-beta signaling pathway, in colorectal cancer has been highlighted, although the frequency of SMAD4 mutations appears much lower than that of 18q21 loss. We set out to investigate allele loss, mutations, protein expression, and cytogenetics of chromosome 18 copy number in a collection of 44 colorectal cancer cell lines of known status with respect to microsatellite instability (MSI). Fourteen of thirty-two MSI(-) lines showed loss of SMAD4 protein expression; usually, one allele was lost and the other was mutated in one of a number of ways, including deletions of various sizes, splice site changes, and missense and nonsense point mutations (although no frameshifts). Of the 18 MSI(-) cancers with retained SMAD4 expression, four harbored missense mutations in the 3' part of the gene and showed allele loss. The remaining 14 MSI(-) lines had no detectable SMAD4 mutation, but all showed allele loss at SMAD4 and/or DCC. SMAD4 mutations can therefore account for about 50-60% of the 18q21 allele loss in colorectal cancer. No MSI(+) cancer showed loss of SMAD4 protein or SMAD4 mutation, and very few had allelic loss at SMAD4 or DCC, although many of these MSI(+) lines did carry TGFBIIR changes. Although SMAD4 mutations have been associated with late-stage or metastatic disease, our combined molecular and cytogenetic data best fit a model in which SMAD4 mutations occur before colorectal cancers become aneuploid/polyploid, but after the MSI(+) and MSI(-) pathways diverge. Thus, MSI(+) cancers may diverge first, followed by CIN(+) (chromosomal instability) cancers, leaving other cancers to follow a CIN(-)MSI(-) pathway.     

Incorporating Couples-Based Approaches into HIV Prevention for Gay and Bisexual Men: Opportunities and Challenges

Thirty years after the beginning of the HIV epidemic, gay, bisexual, and other men who have sex with men (collectively called MSM) bear a disproportionate burden of HIV in the United States and continue to acquire a distressingly high number and proportion of new infections. Historically, HIV prevention for MSM has been focused on individual-level behavior change, rarely intervening with MSM as part of a couple. Yet, an estimated 33–67 % of HIV infections among MSM are acquired from primary sexual partners, suggesting that work with MSM as couples could be an important contributor to prevention. Given the emergence of high impact combination HIV prevention, it is timely to consider how work with the broad variety of male couples can improve both personal and community health. Couples HIV testing and counseling for MSM is an important advance for identifying men who are unaware that they are HIV-positive, identifying HIV-discordant couples, and supporting men who want to learn their HIV status with their partner. Once men know their HIV status, new advances in biomedical prevention, which can dramatically reduce risk of HIV transmission or acquisition, allow men to make prevention decisions that can protect themselves and their partners. This paper highlights the present-day challenges and benefits of using a couples-based approach with MSM in the era of combination prevention to increase knowledge of HIV status, increase identification of HIV discordant couples to improve targeting prevention services, and support mutual disclosure of HIV status.     

The use of mobile phones as a data collection tool: A report from a household survey in South Africa

Background  

To investigate the feasibility, the ease of implementation, and the extent to which community health workers with little experience of data collection could be trained and successfully supervised to collect data using mobile phones in a large baseline survey