Sexuality and mental health: Issues and what next?

Abstract

Human sexuality plays a major role in an individual's existence and functioning. In addition, rightly or wrongly sexuality often defines people and also affects social attitudes. These attitudes, if negative, can contribute to stigma and prevent people from help seeking if they are suffering from mental health problems. Recent changes in policy towards same-sex relationships have been positive in many countries including the UK and the USA, whereas in others such as Russia and Uganda attitudes have become more negative and punitive. Sexual activity is seen as having both pleasurable and procreational functions which contribute to society's attitudes to homosexual behaviour. Inevitably, individual responses to their own sexuality and sexual behaviour will be influenced by social attitudes. To ensure that those with various sexual variations can access psychiatric services without discrimination, various levels of interventions are needed. Here we discuss different levels of intervention and organizational change that may make it possible. Social organization and institutional organization of services need to be sensitive, especially as rates of many mental disorders are high in individuals who may be sexually variant. Those providing services need to understand their own negative attitudes as well as prejudices to ensure that services are emotionally accessible.     

Impact of human mobility on the emergence of dengue epidemics in Pakistan

The recent emergence of dengue viruses into new susceptible human populations throughout Asia and the Middle East, driven in part by human travel on both local and global scales, represents a significant global health risk, particularly in areas with changing climatic suitability for the mosquito vector. In Pakistan, dengue has been endemic for decades in the southern port city of Karachi, but large epidemics in the northeast have emerged only since 2011. Pakistan is therefore representative of many countries on the verge of countrywide endemic dengue transmission, where prevention, surveillance, and preparedness are key priorities in previously dengue-free regions. We analyze spatially explicit dengue case data from a large outbreak in Pakistan in 2013 and compare the dynamics of the epidemic to an epidemiological model of dengue virus transmission based on climate and mobility data from ∼40 million mobile phone subscribers. We find that mobile phone-based mobility estimates predict the geographic spread and timing of epidemics in both recently epidemic and emerging locations. We combine transmission suitability maps with estimates of seasonal dengue virus importation to generate fine-scale dynamic risk maps with direct application to dengue containment and epidemic preparedness.Dengue is the most rapidly spreading mosquito-borne disease worldwide (1, 2). Half the global population now lives in at-risk regions for dengue virus transmission, due to the wide distribution of the mosquito vector, Aedes aegypti, which thrives in peri-urban areas and transmits the virus between humans (3). Dengue virus can cause acute febrile illness and carries the risk of severe disease, hospitalization, and shock syndrome, especially in clinical settings with little experience treating dengue patients. There is currently no specific therapeutic protocol for, or vaccine against, infection (1). Current control measures focus on vector control, although these measures are often logistically difficult and have shown varying efficacy in controlling epidemics (4). In the absence of effective prevention and treatment, public health system preparedness remains the single most important tool for minimizing morbidity and mortality as dengue epidemics spread beyond endemic areas (5, 6).The introduction of dengue into new populations is mediated by travel of infected individuals to areas that can support transmission, because mosquito vectors move only short distances during their lifespans (3, 7–12). International travel to endemic countries has resulted in imported cases and outbreaks in Europe and the Americas (2, 8, 10, 13). Local variation in transmission, within a single city for example, is also driven by mobility patterns of individuals on short timescales (7). Forecasting methods are needed to spatially target interventions and epidemic preparedness measures that reflect both the changing temporal risks of importation and environmental suitability that go beyond solely climate-based methods (14).Dengue has long been endemic in most Southeast Asian countries (1), but has more recently emerged in parts of the Middle East and South Asia, including Pakistan (15, 16). In Pakistan, the transmission of dengue viruses was largely confined to the southern city of Karachi until 2011 when a large dengue epidemic with over 20,000 cases occurred in the northeastern city of Lahore (16), causing significant morbidity and mortality. In 2013, a second large epidemic occurred in northeastern Pakistan in Punjab and Khyber-Pakhtunkhwa (KP) provinces, establishing the region as an emerging focus of seasonal dengue epidemics. It has been hypothesized that the recent geographic expansion of A. aegypti mosquito vectors, changing environmental suitability, and human importation of dengue from endemic regions all contributed to the emergence of dengue in northern areas (17). Pakistan is therefore representative of many countries that are on the verge of countrywide endemic dengue transmission and are struggling to contain its emergence into previously dengue-free regions.Measuring changing risks of importation events that spark epidemics has been extremely challenging on the refined temporal and spatial scales necessary to inform local policies (18). Being able to predict when to prepare surveillance systems and health facilities for dengue outbreaks could dramatically reduce the morbidity and mortality associated with epidemics and would allow policy makers to pinpoint regions that are particularly vulnerable to imported cases, for vector control. Mobile phone data offer direct measures of human aggregation and movement and represent a unique source of information on the human determinants of the geographic expansion of emerging epidemic diseases like dengue. Here, we conduct a retrospective epidemiological analysis of large dengue outbreaks in Pakistan in 2013, to examine the predictive ability of an epidemiological model that integrates human mobility from the largest mobile phone dataset analyzed to date with climate information. We show that within-country human mobility predicts emerging epidemics in Pakistan, and epidemiological models incorporating this type of data can predict the spatial extent and timing of outbreaks, providing a new approach to forecasting.     

Antisense inhibition of pig α1,3galactosyl-transferase leads to a reduction in expression of the major target for human natural antibodies on pig vascular endothelial cells

Abstract: The expression of epitopes on pig cells for human natural antibodies (NAb) currently constitutes a major barrier to the use of pig organs and tissues in clinical transplantation. This is of particular significance to vascularized organs where the presence of carbohydrate antigens invariably leads to a hyperacute rejection when exposed to human blood or serum. It has been strongly suggested that the major antigen in this context consists of a terminal Galα1,3Galβ1,4GlcNAc trisaccharide. We have previously proposed that decreased expression of this epitope for human NAb may lead to elimination of hyperacute rejection. We have now used mRNA targeted antisense oligonucleotides to decrease the expression of the α1,3galactosyltransferase directing the terminal synthesis of this epitope on pig vascular endothelial cells. This mRNA antisense targeting leads to a decreased expression of the Galα1,3Galβ1,4GlcNAc structure as detected by epitope specific lectin. Moreover, a very similar reduction in mean fluorescence was seen when staining the same cells with human Galα1,3Galα1,4GlcNAc-specific IgM NAb. We feel these findings constitute an important step in the process of providing conclusive evidence that reduction of or complete elimination of this epitope will overcome the hyperacute response in this species combination. In addition, such pig tissues may be less susceptible to further antibody rejection once the hyperacute phase has been overcome.     

Parafibromin and APC as Screening Markers for Malignant Potential in Atypical Parathyroid Adenomas

The identification of parathyroid carcinomas is based upon histopathological criteria in which an invasive growth pattern or distant metastasis is demonstrated. A dilemma arises when tumours present with atypical histopathological features but lack direct evidence of malignancy. Recently, reduced expression or loss of the tumour suppressor proteins parafibromin and adenomatous polyposis coli (APC) has been associated with parathyroid malignancy. We report results from APC and parafibromin expression analyses by immunohistochemistry and Western blot in five cases of atypical adenoma, a single case of carcinoma and 54 adenomas without atypical features. Complete loss of APC immunoreactivity and reduced expression of parafibromin was evident in two of the atypical adenomas and in the parathyroid carcinoma. By contrast, all adenomas displayed APC expression, including two cases with hyperparathyroidism 2 gene (HRPT2) mutations and loss of parafibromin expression. We conclude that loss of APC is a frequent molecular event in atypical adenomas and carcinomas, but not in adenomas. Following verification in an independent material, APC could become a valuable tool when assessing parathyroid tumours in the clinical setting. Furthermore, the molecular resemblance of atypical adenomas with carcinoma concerning parafibromin and APC expression indicates that atypical adenomas should be subjects to watchful follow-up.     

Tumor necrosis factor-associated susceptibility to type 1 diabetes is caused by linkage disequilibrium with HLA-DR3 haplotypes

Tumor necrosis factor-α (TNF-α) is an important proinflammatory cytokine involved in the pathogenesis of autoimmune type 1 diabetes (T1D). The TNF gene locus is located in the major histocompatibility complex (MHC) class III region and its genetic polymorphisms have been reported to be associated with T1D. However, it is not clear whether these associations are primary or caused by their linkage disequilibrium with other predisposing genes within the MHC. We have tested 2 TNF-α single nucleotide polymorphisms at positions -308G/A and -238G/A in the 5' untranslated region and a (GT)n microsatellite TNFa in the North Indian healthy population and T1D patients with known HLA-A-B-DR-DQ haplotypes. The allele frequencies of TNFa5, -308A, and -238G were determined to be significantly increased among patients compared with controls. Although the observed positive association of -238G was caused by its presence on all 3 DR3(+) groups, namely, B8-DR3-DQ2, B50-DR3-DQ2, and B58-DR3-DQ2 haplotypes associated with T1D in this population, the increase of the -308A allele was caused by its association with the latter 2 haplotypes. On the other hand, TNF -308G occurred on B8-DR3 haplotypes along with -238G and TNFa5 alleles, particularly in T1D patients with late disease onset (at >20 years of age). These results indicate that TNF associations with T1D are caused by their linkage disequilibrium with specific HLA-DR3-DQ2 haplotypes in the Indian population. Because polymorphisms in the promoter region regulate TNF expression levels (e.g., -308A), they retain crucial immunological significance in the development of T1D and its management.