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In a sample of 140 HIV-positive immigrant Latino gay men, we tested a mediational model of the impact of sociocultural factors (i.e., poverty, discrimination, and U.S. acculturation) on active engagement of health-promoting behaviors (i.e., practicing good health habits). The role of coping as a mediator was examined. We proposed that the experience of social discrimination, together with acculturation, has a negative influence on active coping, which in turn would impact health behaviors. Regression analyses supported the role of coping as a mediator between sociocultural factors (specifically discrimination based on race or ethnicity and acculturation to the U.S.) and health-promoting behaviors. Findings from this study contribute to explaining the way in which sociocultural factors impact health among those who are HIV-positive and most vulnerable in our society. [ABSTRACT FROM AUTHOR]

Short term treatment with low doses of glucocorticoid analogues has been shown to ameliorate neurological symptoms in Ataxia-Telangiectasia (A-T), a rare autosomal recessive multisystem disease that mainly affects the cerebellum, immune system, and lungs. Molecular mechanisms underlying this clinical observation are unclear. We aimed at evaluating the effect of dexamethasone on the induction of alternative ATM transcripts (ATMdexa1). We showed that dexamethasone cannot induce an alternative ATM transcript in control and A-T lymphoblasts and primary fibroblasts, or in an ATM-knockout HeLa cell line. We also demonstrated that some of the reported readouts associated with ATMdexa1 are due to cellular artifacts and the direct induction of γH2AX by dexamethasone via DNA-PK. Finally, we suggest caution in interpreting dexamethasone effects in vitro for the results to be translated into a rational use of the drug in A-T patients.

The Citron protein was originally identified for its capability to specifically bind the active form of RhoA small GTPase, leading to the simplistic hypothesis that it may work as a RhoA downstream effector in actin remodeling. More than two decades later, a much more complex picture has emerged. In particular, it has become clear that in animals, and especially in mammals, the functions of the Citron gene ( CIT ) are intimately linked to many aspects of central nervous system (CNS) development and function, although the gene is broadly expressed. More specifically, CIT encodes two main isoforms, Citron-kinase (CIT-K) and Citron-N (CIT-N), characterized by complementary expression pattern and different functions. Moreover, in many of their activities, CIT proteins act more as upstream regulators than as downstream effectors of RhoA. Finally it has been found that, besides working through actin, CIT proteins have many crucial functional interactions with the microtubule cytoskeleton and may directly affect genome stability. In this review, we will summarize these advances and illustrate their actual or potential relevance for CNS diseases, including microcephaly and psychiatric disorders.

Neuroblastoma is the most common extra-cranial pediatric solid tumor, responsible for 13-15% of pediatric cancer death. Its intrinsic heterogeneity makes it difficult to target for successful therapy. The adaptor protein p140Cap/SRCIN1 negatively regulates tumor cell features and limits breast cancer progression. This study wish to assess if p140Cap is a key biological determinant of neuroblastoma outcome. RNAseq profiles of a large cohort of neuroblastoma patients show that SRCIN1 mRNA levels are an independent risk factor inversely correlated to disease aggressiveness. In high-risk patients, CGH+SNP microarray analysis of primary neuroblastoma identifies SRCIN1 as frequently altered by hemizygous deletion, copy-neutral loss of heterozygosity, or disruption. Functional experiments show that p140Cap negatively regulates Src and STAT3 signaling, affects anchorage-independent growth and migration, in vivo tumor growth and spontaneous lung metastasis formation. p140Cap also increases sensitivity of neuroblastoma cells to doxorubicin and etoposide treatment, as well as to a combined treatment with chemotherapy drugs and Src inhibitors. Our functional findings point to a causal role of p140Cap in curbing the aggressiveness of neuroblastoma, due to its ability to impinge on specific molecular pathways, and to sensitize cells to therapeutic treatment. This study provides the first evidence that the SRCIN1/p140Cap adaptor protein is a key player in neuroblastoma as a new independent prognostic marker for patient outcome and treatment. Altogether, these data highlight the potential clinical impact of SRCIN1/p140Cap expression in neuroblastoma tumors, in terms of reducing cytotoxic effects of chemotherapy, one of the main issues for pediatric tumor treatment.

Down Syndrome (DS) is the most common genetic disorder associated with intellectual disability (ID). Excitatory neurons of DS patients and mouse models show decreased size of dendritic field and reduction of spine density. Whether these defects are caused by cell autonomous alterations or by abnormal multicellular circuitry is still unknown. In this work, we explored this issue by culturing cortical neurons obtained from two mouse models of DS: the widely used Ts65Dn and the less characterized Ts2Cje. We observed that, in the in vitro conditions, axon specification and elongation, as well as dendritogenesis, take place without evident abnormalities, indicating that the initial phases of neuronal differentiation do not suffer from the presence of an imbalanced genetic dosage. Conversely, our analysis highlighted differences between trisomic and euploid neurons in terms of reduction of spine density, in accordance with in vivo data obtained by other groups, proposing the presence of a cell-intrinsic malfunction. This work suggests that the characteristic morphological defects of DS neurons are likely to be caused by the possible combination of cell-intrinsic defects together with cell-extrinsic cues. Additionally, our data support the possibility of using the more sustainable line Ts2Cje as a standard model for the study of DS., (Copyright © 2019 Chiotto, Migliorero, Pallavicini, Bianchi, Gai, Di Cunto and Berto.)

Key Points: Tymothy syndrome (TS) is a multisystem disorder featuring cardiac arrhythmias, autism and adrenal gland dysfunction that originates from a de novo point mutation in the gene encoding the Cav1.2 (CACNA1C) L-type channel. To study the role of Cav1.2 channel signals in autism, the autistic TS2-neo mouse has been generated bearing the G406R point-mutation associated with TS type-2. Using heterozygous TS2-neo mice, we report that the G406R mutation reduces the rate of inactivation and shifts leftward the activation and inactivation of L-type channels, causing marked increase of resting Ca 2+ influx ('window' Ca 2+ current). The increased 'window current' causes marked reduction of Na V channel density, switches normal tonic firing to abnormal burst firing, reduces mitochondrial metabolism, induces cell swelling and decreases catecholamine release. Overnight incubations with nifedipine rescue Na V channel density, normal firing and the quantity of catecholamine released. We provide evidence that chromaffin cell malfunction derives from altered Cav1.2 channel gating., Abstract: L-type voltage-gated calcium (Cav1) channels have a key role in long-term synaptic plasticity, sensory transduction, muscle contraction and hormone release. A point mutation in the gene encoding Cav1.2 (CACNA1C) causes Tymothy syndrome (TS), a multisystem disorder featuring cardiac arrhythmias, autism spectrum disorder (ASD) and adrenal gland dysfunction. In the more severe type-2 form (TS2), the missense mutation G406R is on exon 8 coding for the IS6-helix of the Cav1.2 channel. The mutation causes reduced inactivation and induces autism. How this occurs and how Cav1.2 gating-changes alter cell excitability, neuronal firing and hormone release on a molecular basis is still largely unknown. Here, using the TS2-neo mouse model of TS we show that the G406R mutation altered excitability and reduced secretory activity in adrenal chromaffin cells (CCs). Specifically, the TS2 mutation reduced the rate of voltage-dependent inactivation and shifted leftward the activation and steady-state inactivation of L-type channels. This markedly increased the resting 'window' Ca 2+ current that caused an increased percentage of CCs undergoing abnormal action potential (AP) burst firing, cell swelling, reduced mitochondrial metabolism and decreased catecholamine release. The increased 'window' Ca 2+ current caused also decreased Na V channel density and increased steady-state inactivation, which contributed to the increased abnormal burst firing. Overnight incubation with the L-type channel blocker nifedipine rescued the normal AP firing of CCs, the density of functioning Na V channels and their steady-state inactivation. We provide evidence that CC malfunction derives from the altered Cav1.2 channel gating and that dihydropyridines are potential therapeutics for ASD., (© 2019 University of Torino. The Journal of Physiology © 2019 The Physiological Society.)

The neuronal scaffold protein p140Cap was investigated during hippocampal network formation. p140Cap is present in presynaptic GABAergic terminals and its genetic depletion results in a marked alteration of inhibitory synaptic activity. p140Cap-/- cultured neurons display higher frequency of miniature inhibitory postsynaptic currents (mIPSCs) with no changes of their mean amplitude. Consistent with a potential presynaptic alteration of basal GABA release, p140Cap-/- neurons exhibit a larger synaptic vesicle readily releasable pool, without any variation of single GABAA receptor unitary currents and number of postsynaptic channels. Furthermore, p140Cap-/- neurons show a premature and enhanced network synchronization and appear more susceptible to 4-aminopyridine-induced seizures in vitro and to kainate-induced seizures in vivo. The hippocampus of p140Cap-/- mice showed a significant increase in the number of both inhibitory synapses and of parvalbumin- and somatostatin-expressing interneurons. Specific deletion of p140Cap in forebrain interneurons resulted in increased susceptibility to in vitro epileptic events and increased inhibitory synaptogenesis, comparable to those observed in p140Cap-/- mice. Altogether, our data demonstrate that p140Cap finely tunes inhibitory synaptogenesis and GABAergic neurotransmission, thus regulating the establishment and maintenance of the proper hippocampal excitatory/inhibitory balance.

Maintenance of genome stability is a crucial cellular function for normal mammalian development and physiology. However, despite the general relevance of this process, genome stability alteration due to genetic or non-genetic conditions has a particularly profound impact on the developing cerebral cortex. In this review, we will analyze the main pathways involved in maintenance of genome stability, the consequences of their alterations with regard to central nervous system development, as well as the possible molecular and cellular basis of this specificity.

Medulloblastoma is the most common malignant brain tumor in children. Current treatment for medulloblastoma consists of surgery followed by irradiation of the whole neuraxis and high-dose multiagent chemotherapy, a partially effective strategy associated with highly invalidating side effects. Therefore, identification and validation of novel target molecules capable of contrasting medulloblastoma growth without disturbing brain development is needed. Citron kinase protein (CITK), encoded by primary microcephaly gene MCPH17 , is required for normal proliferation and survival of neural progenitors. Constitutive loss of CITK leads to cytokinesis failure, chromosome instability, and apoptosis in the developing brain, but has limited effects on other tissues. On this basis, we hypothesized that CITK could be an effective target for medulloblastoma treatment. In medulloblastoma cell lines DAOY and ONS-76, CITK knockdown increased both cytokinesis failure and DNA damage, impairing proliferation and inducing cell senescence and apoptosis via TP53 or TP73. Similar effects were obtained in the NeuroD-SmoA1 transgenic mouse model, in which CITK deletion increased apoptotic cells and senescence markers such as P21 CIP1 , P27 KIP1 , and P16 INK4A Most importantly, CITK deletion decreased tumor growth and increased overall survival in these mice, with no apparent side effects. These results suggest that CITK can be a useful molecular target for medulloblastoma treatment. Significance: In vitro and in vivo proof of concept identifies citron kinase protein as a suitable target for medulloblastoma treatment. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4599/F1.large.jpg Cancer Res; 78(16); 4599-612. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Abscission is the final step of cytokinesis whereby the intercellular bridge (ICB) linking the two daughter cells is cut. The ICB contains a structure called the midbody, required for the recruitment and organization of the abscission machinery. Final midbody severing is mediated by formation of secondary midbody ingression sites, where the ESCRT III component CHMP4B is recruited to mediate membrane fusion. It is presently unknown how cytoskeletal elements cooperate with CHMP4B to mediate abscission. Here, we show that F-actin is associated with midbody secondary sites and is necessary for abscission. F-actin localization at secondary sites depends on the activity of RhoA and on the abscission regulator citron kinase (CITK). CITK depletion accelerates loss of F-actin proteins at the midbody and subsequent cytokinesis defects are reversed by restoring actin polymerization. Conversely, midbody hyperstabilization produced by overexpression of CITK and ANLN is reversed by actin depolymerization. CITK is required for localization of F-actin and ANLN at the abscission sites, as well as for CHMP4B recruitment. These results indicate that control of actin dynamics downstream of CITK prepares the abscission site for the final cut., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Mutations in citron (CIT), leading to loss or inactivation of the citron kinase protein (CITK), cause primary microcephaly in humans and rodents, associated with cytokinesis failure and apoptosis in neural progenitors. We show that CITK loss induces DNA damage accumulation and chromosomal instability in both mammals and Drosophila. CITK-deficient cells display "spontaneous" DNA damage, increased sensitivity to ionizing radiation, and defective recovery from radiation-induced DNA lesions. In CITK-deficient cells, DNA double-strand breaks increase independently of cytokinesis failure. Recruitment of RAD51 to DNA damage foci is compromised by CITK loss, and CITK physically interacts with RAD51, suggesting an involvement of CITK in homologous recombination. Consistent with this scenario, in doubly CitK and Trp53 mutant mice, neural progenitor cell death is dramatically reduced; moreover, clinical and neuroanatomical phenotypes are remarkably improved. Our results underscore a crucial role of CIT in the maintenance of genomic integrity during brain development., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Epidemiological evidence from the current outbreak of Zika virus (ZIKV) and recent studies in animal models indicate a strong causal link between ZIKV and microcephaly. ZIKV infection induces cell-cycle arrest and apoptosis in proliferating neural progenitors. However, the mechanisms leading to these phenotypes are still largely obscure. In this report, we explored the possible similarities between transcriptional responses induced by ZIKV in human neural progenitors and those elicited by three different genetic mutations leading to severe forms of microcephaly in mice. We found that the strongest similarity between all these conditions is the activation of common P53 downstream genes. In agreement with these observations, we report that ZIKV infection increases total P53 levels and nuclear accumulation, as well as P53 Ser15 phosphorylation, correlated with genotoxic stress and apoptosis induction. Interestingly, increased P53 activation and apoptosis are induced not only in cells expressing high levels of viral antigens but also in cells showing low or undetectable levels of the same proteins. These results indicate that P53 activation is an early and specific event in ZIKV-infected cells, which could result from cell-autonomous and/or non-cell-autonomous mechanisms. Moreover, we highlight a small group of P53 effector proteins that could act as critical mediators, not only in ZIKV-induced microcephaly but also in many genetic microcephaly syndromes.

Correct orientation of cell division is considered an important factor for the achievement of normal brain size, as mutations in genes that affect this process are among the leading causes of microcephaly. Abnormal spindle orientation is associated with reduction of the neuronal progenitor symmetric divisions, premature cell cycle exit, and reduced neurogenesis. This mechanism has been involved in microcephaly resulting from mutation of ASPM, the most frequently affected gene in autosomal recessive human primary microcephaly (MCPH), but it is presently unknown how ASPM regulates spindle orientation. In this report, we show that ASPM may control spindle positioning by interacting with citron kinase (CITK), a protein whose loss is also responsible for severe microcephaly in mammals. We show that the absence of CITK leads to abnormal spindle orientation in mammals and insects. In mouse cortical development, this phenotype correlates with increased production of basal progenitors. ASPM is required to recruit CITK at the spindle, and CITK overexpression rescues ASPM phenotype. ASPM and CITK affect the organization of astral microtubules (MT), and low doses of MT-stabilizing drug revert the spindle orientation phenotype produced by their knockdown. Finally, CITK regulates both astral-MT nucleation and stability. Our results provide a functional link between two established microcephaly proteins., (© 2016 The Authors.)

Cytokinesis, the physical separation of daughter cells at the end of cell cycle, is commonly considered a highly stereotyped phenomenon. However, in some specialized cells this process may involve specific molecular events that are still largely unknown. In mammals, loss of Citron-kinase (CIT-K) leads to massive cytokinesis failure and apoptosis only in neuronal progenitors and in male germ cells, resulting in severe microcephaly and testicular hypoplasia, but the reasons for this specificity are unknown. In this report we show that CIT-K modulates the stability of midbody microtubules and that the expression of tubulin β-III (TUBB3) is crucial for this phenotype. We observed that TUBB3 is expressed in proliferating CNS progenitors, with a pattern correlating with the susceptibility to CIT-K loss. More importantly, depletion of TUBB3 in CIT-K-dependent cells makes them resistant to CIT-K loss, whereas TUBB3 overexpression increases their sensitivity to CIT-K knockdown. The loss of CIT-K leads to a strong decrease in the phosphorylation of S444 on TUBB3, a post-translational modification associated with microtubule stabilization. CIT-K may promote this event by interacting with TUBB3 and by recruiting at the midbody casein kinase-2α (CK2α) that has previously been reported to phosphorylate the S444 residue. Indeed, CK2α is lost from the midbody in CIT-K-depleted cells. Moreover, expression of the nonphosphorylatable TUBB3 mutant S444A induces cytokinesis failure, whereas expression of the phospho-mimetic mutant S444D rescues the cytokinesis failure induced by both CIT-K and CK2α loss. Altogether, our findings reveal that expression of relatively low levels of TUBB3 in mitotic cells can be detrimental for their cytokinesis and underscore the importance of CIT-K in counteracting this event.

Objectives: We estimated HIV prevalence among men who have sex with men (MSM) and transgender women in Bogotá, Colombia, and explored differences between HIV-positive individuals who are aware and unaware of their serostatus., Methods: In this cross-sectional 2011 study, we used respondent-driven sampling (RDS) to recruit 1000 MSM and transgender women, who completed a computerized questionnaire and received an HIV test., Results: The RDS-adjusted prevalence was 12.1% (95% confidence interval [CI] = 8.7, 15.8), comparable to a previous RDS-derived estimate. Among HIV-positive participants, 39.7% (95% CI = 25.0, 54.8) were aware of their serostatus and 60.3% (95% CI = 45.2, 75.5) were unaware before this study. HIV-positive-unaware individuals were more likely to report inadequate insurance coverage, exchange sex (i.e., sexual intercourse in exchange for money, goods, or services), and substance use than other participants. HIV-positive-aware participants were least likely to have had condomless anal intercourse in the previous 3 months. Regardless of awareness, HIV-positive participants reported more violence and forced relocation experiences than HIV-negative participants., Conclusions: There is an urgent need to increase HIV detection among MSM and transgender women in Bogotá. HIV-positive-unaware group characteristics suggest an important role for structural, social, and individual interventions.

This paper examined structural, social, and personal characteristics that shape the processes of gender affirmation and body modification among transgender persons (assigned male at birth) in Bogotá, Colombia. Qualitative data from life-history interviews (N=14) and a focus group (N=11) explored research questions concerning the ways in which the internal psychological and external contextual processes influence individuals' decisions and behaviors concerning hormonal treatment, injections, or surgery. Research questions concerning practices and consequences of treatment performed without medical supervision were addressed through qualitative data, as well as quantitative data from 58 transgender participants. Findings indicated variation in ways participants conceptualized gender (e.g., binary or fluid), but an increased feminine presentation was a strong personal desire expressed by many and often encouraged by romantic partners and transgender friends. Transgender individuals within participants' social networks were frequently instrumental not only in providing information about hormones and contouring injections, but also in carrying out procedures-sometimes with negative consequences. Body modification procedures occurred primarily outside the health care system, due to limited access to or awareness of medical care, societal stigma, social norms within the transgender community, and personal decision-making. Public health approaches to protect the health of transgender persons undergoing body modification were suggested.

This qualitative study examined sex work among internally displaced male and transgender female sex workers in Bogotá, Colombia. Internal displacement has occurred in Colombia as a result of decades of conflict among armed groups and has created large-scale migration from rural to urban areas. Informed by the polymorphous model of sex work, which posits that contextual conditions shape the experience of sex work, we examined three main research questions. The first dealt with how internal displacement was related to the initiation of sex work; the second concerned the effect of agency on sex worker satisfaction; and the third examined how sex work in this context was related to HIV and other risks. Life history interviews were conducted with 26 displaced individuals who had done sex work: 14 were men who have sex with men and 12 were transgender women (natal males). Findings revealed that many participants began doing sex work in the period immediately after displacement, because of a lack of money, housing, and social support. HIV risk was greater during this time due to limited knowledge of HIV and inexperience negotiating safer sex with clients. Other findings indicated that sex workers who exerted more control and choice in the circumstances of their work reported greater satisfaction. In addition, we found that although many sex workers insisted on condom use with clients, several noted that they would sometimes have unprotected sex for additional money. Specific characteristics affecting the experience of sex work among the transgender women were also discussed.

This study used mixed methods to examine characteristics related to HIV testing among men who have sex with men (MSM) in Bogotá, Colombia. A sample of 890 MSM responded to a computerized quantitative survey. Follow-up qualitative data included 20 in-depth interviews with MSM and 12 key informant interviews. Hierarchical logistic set regression indicated that sequential sets of variables reflecting demographic characteristics, insurance coverage, risk appraisal, and social context each added to the explanation of HIV testing. Follow-up logistic regression showed that individuals who were older, had higher income, paid for their own insurance, had had a sexually transmitted infection, knew more people living with HIV, and had greater social support were more likely to have been tested for HIV at least once. Qualitative findings provided details of personal and structural barriers to testing, as well as inter-relationships among these factors. Recommendations to increase HIV testing among Colombian MSM are offered.

Background and Aim: We identified a balanced de novo translocation involving chromosomes Xq25 and 8q24 in an eight year-old girl with a non-progressive form of congenital ataxia, cognitive impairment and cerebellar hypoplasia., Methods and Results: Breakpoint definition showed that the promoter of the Protein Tyrosine Kinase 2 (PTK2, also known as Focal Adhesion Kinase, FAK) gene on chromosome 8q24.3 is translocated 2 kb upstream of the THO complex subunit 2 (THOC2) gene on chromosome Xq25. PTK2 is a well-known non-receptor tyrosine kinase whereas THOC2 encodes a component of the evolutionarily conserved multiprotein THO complex, involved in mRNA export from nucleus. The translocation generated a sterile fusion transcript under the control of the PTK2 promoter, affecting expression of both PTK2 and THOC2 genes. PTK2 is involved in cell adhesion and, in neurons, plays a role in axonal guidance, and neurite growth and attraction. However, PTK2 haploinsufficiency alone is unlikely to be associated with human disease. Therefore, we studied the role of THOC2 in the CNS using three models: 1) THOC2 ortholog knockout in C.elegans which produced functional defects in specific sensory neurons; 2) Thoc2 knockdown in primary rat hippocampal neurons which increased neurite extension; 3) Thoc2 knockdown in neuronal stem cells (LC1) which increased their in vitro growth rate without modifying apoptosis levels., Conclusion: We suggest that THOC2 can play specific roles in neuronal cells and, possibly in combination with PTK2 reduction, may affect normal neural network formation, leading to cognitive impairment and cerebellar congenital hypoplasia.

Using the structural-environmental conceptual framework, this study employed mixed methods to address the question of whether sex with female sex workers contributes to HIV risk among male immigrant Latino day laborers in suburban Maryland. Because contextual factors can greatly affect HIV risk for both sex workers and their clients, this study investigated the organizational structure of sex work, factors that predicted men's hiring of sex workers, sexual behaviors performed with sex workers, and the use of condoms. Qualitative research was conducted to inform the development of a quantitative survey, but also provided crucial descriptions about the motivations, locations, arrangements, and sexual activities related to sex work. Key informant interviews (N = 10), in-depth interviews with day laborers (N = 10) and Latina female sex workers (N = 4), and two focus groups with day laborers (N = 11) were conducted, and a quantitative survey administered via Audio-enhanced Computer-assisted Self-interviewing (N = 174). Condom use was nearly universal in encounters with female sex workers, thus indicating that the sex workers were not an important source of HIV transmission in this context. Logistic regression was performed to test a model predicting sex with sex workers. Latino day laborers who reported more immigrant stress and who did not have a partner in the U.S. were more likely to have had sex with a sex worker, as were men who reported binge drinking. Structural and social conditions influenced the hiring of sex workers. Further research is warranted to better understand the interrelationships among these circumstances and to inform the development of programs to address them.

The current study investigated a methodological question of whether traditional, additive, quantitative data can be used to address intersectional issues, and illustrated such an approach with a sample of 301 HIV-positive, Latino gay men in the United States. Participants were surveyed using A-CASI. Hierarchical logistic set regression investigated the role of sets of variables reflecting demographic characteristics, gender nonconformity, and gay and ethnic discrimination in relation to depression and gay collective identity. Results showed the discrimination set was related to depression and to gay collective identity, as was gender nonconformity. Follow-up logistic regression showed that both types of discrimination were associated with greater depression, but gender nonconformity was not. Gay discrimination and gender nonconformity were positively associated with gay collective identity, whereas ethnic discrimination was negatively associated. Results are discussed in terms of the use of traditional quantitative data as a potential means of understanding intersectional issues, as well as of contributing to knowledge about individuals facing multiple structural inequalities.

Colombia has endured six decades of civil unrest, population displacement and violence. We examined the relationships between contextual conditions, displacement and HIV among gay, bisexual and transgender individuals in Bogotá, Colombia. A total of 19 key informants provided information about internal displacement of sexual minorities. Life-history interviews were conducted with 42 participants aged 18 to 48 years and included questions about displacement experiences, sexual behaviour, life prior to displacement and participants' economic and social situation in Bogotá. The interplay of a variety of factors - including internal conflict and violence, homonegativity and 'social cleansing', gender and sexual identity and poverty - strongly shaped the varied experiences of displacement. Migration, sexual violence, exchange sex and low rates of HIV testing were risk factors that increased vulnerability for HIV in this displaced sample. Although displacement and HIV in Colombia are major problems, both are understudied.

Male circumcision has received increased attention for its potential to reduce sexual transmission of HIV. Research on the acceptability of circumcision as a means of HIV prevention among men who have sex with men is limited. Men who have sex with men in Bogotá, Colombia, either participated in a focus group in which they shared information regarding their perceptions of circumcision or completed a survey that assessed circumcision experiences, attitudes, beliefs and willingness. Few participants reported they were circumcised, yet most participants reported knowing something about the procedure. Overall, attitudes towards circumcision were mixed: although circumcision was viewed as safe, it was also viewed as unnatural and cruel to babies. Beliefs that circumcision could improve sexual functioning and protect against STIs and HIV were not widely endorsed by survey participants, although focus-group participants discussed the potential impacts of circumcision on the availability of sexual partners and sexual performance. Some focus-group participants and many survey participants reported a hypothetical willingness to get circumcised if strong evidence of its effectiveness could be provided, barriers removed and recovery time minimised.

Sexual pleasure has been identified as an important consideration in decision-making surrounding condom use. We examined the impact of perceived pleasure loss associated with condom use on recent history of insertive and receptive unprotected anal intercourse (UAI) among Latino men who have sex with men (MSM) living in the United States. A total of 482 Dominican, Colombian, and Brazilian immigrant MSM were surveyed regarding sexual attitudes and practices via computer-assisted self-interviewing technology with audio enhancement (ACASI). Participants rated the pleasure they derived from protected and unprotected anal intercourse in each position (insertive and receptive) and also reported their HIV status, relationship status, and recent sexual history. Men who had engaged in both positions, with and without condoms (n=268), perceived a greater pleasure loss associated with condoms during anal intercourse in the insertive versus receptive position. Logistic regression analyses controlling for HIV status, relationship status, and age revealed that men who perceived greater pleasure loss from condoms were more likely to have engaged in UAI over the past 3 months (n[insertive]=297; n[receptive]=284). Findings indicate that the pleasure loss associated with condoms may be a key deterrent for their use in either sex position among Latino MSM. Therefore, pleasure needs to be prioritized in the development of condoms and other sexual safety measures as well as in the promotion of their use.

Introduction: Cigarette smoking has become an important influence of morbidity and mortality for HIV-positive individuals in the era of highly active antiretroviral therapy. Although smoking is common among military personnel and veterans, the lasting impact of military service on smoking at a later stage of life has not been examined. The current study investigated present and past influences on current smoking among HIV-positive male veterans., Methods: Participants were 200 HIV-positive men served by the Veterans Affairs Medical Center. A survey was administered via audio-enhanced computer-assisted self-interview, and additional information was extracted from the computerized patient record system., Results: Logistic regression was performed to test hypotheses concerning the participants' current situations as well as characteristics of their past military service. Having smokers in one's environment, being more depressed, and having used alcohol or drugs were associated with having smoked in the previous 30 days, whereas stronger endorsement of attitudes stating adverse effects of smoking was linked to lower likelihood of smoking. Neither having been in a military conflict nor the length of the military service was significantly related to current smoking., Conclusions: Remote experiences in the military did not have a sustained effect on smoking behavior years later. Implications of this study for the development of smoking cessation programs targeting HIV-positive veterans include the importance of altering attitudes about tobacco, treating underlying depression, addressing social influence, decreasing substance use, and increasing awareness of the heightened vulnerability to a variety of negative consequences of smoking among infected individuals.

This study examined factors associated with communication about condom use and unprotected anal intercourse (UAI) in a U.S. sample of immigrant Latino MSM (N = 356), with a focus on culturally based beliefs. Logistic regression analysis revealed that communication about condom use at participants' most recent encounter was associated with a lower likelihood of UAI during that encounter. UAI was more likely when the partner was a main partner and there was seroconcordance. A separate logistic regression indicated that communication about condom use was less likely when the most recent encounter involved a main partner, greater sexual desire, and intoxication due to substance use. Although cultural beliefs were not predictive of communication about condom use or UAI at the most recent encounter, they were related to the occurrence of UAI in the previous three months. There is a need for more research on the interplay of culture, safer sex communication, and sexual risk.

Many men who have sex with men (MSM) have sexual encounters in public places, and some data suggest that this behavior is more common among Latino than non-Hispanic white MSM in the USA. In a sample of 482 Latino MSM born in Brazil, Colombia, and the Dominican Republic, and living in the New York City metropolitan area, we examined how demographic and psychosocial characteristics are related to having sex in public venues. Logistic regression was performed with the dichotomous outcome of sex in a public place in the previous six months. Demographic variables included education, HIV-positive serostatus, unknown HIV serostatus, and years in the USA; psychosocial variables included self-efficacy for safer sex, depression, and gay community involvement. Results indicated that those individuals with unknown serostatus were more likely than those with HIV-negative serostatus to have had sex in a public setting, as were men with lower self-efficacy for safer sex. These findings suggest that the partner pool may pose some risk to men who have sex in public sex venues, and therefore, low-risk sexual practices and condom use should be promoted in such settings. Contrary to expectations, higher education was related to sex in public settings, but neither depression nor more recent immigration was. Greater involvement in the gay community was also associated with having sex in public places, which may reflect the larger social function served by gay venues such as bathhouses and bars.

Myelin formation and maintenance are crucial for the proper function of the CNS and are orchestrated by a plethora of factors including growth factors, extracellular matrix components, metalloproteases and protease inhibitors. Hemopexin (Hx) is a plasma protein with high heme binding affinity, which is also locally produced in the CNS by ependymal cells, neurons and glial cells. We have recently reported that oligodendrocytes (OLs) are the type of cells in the brain that are most susceptible to lack of Hx, as the number of iron-overloaded OLs increases in Hx-null brain, leading to oxidative tissue damage. In the current study, we found that the expression of the Myelin Basic Protein along with the density of myelinated fibers in the basal ganglia and in the motor and somatosensory cortex of Hx-null mice were strongly reduced starting at 2 months and progressively decreased with age. Myelin abnormalities were confirmed by electron microscopy and, at the functional level, resulted in the inability of Hx-null mice to perform efficiently on the Rotarod. It is likely that the poor myelination in the brain of Hx-null mice was a consequence of defective maturation of OLs as we demonstrated that the number of mature OLs was significantly reduced in mutant mice whereas that of precursor cells was normal. Finally, in vitro experiments showed that Hx promotes OL differentiation. Thus, Hx may be considered a novel OL differentiation factor and the modulation of its expression in CNS may be an important factor in the pathogenesis of human neurodegenerative disorders.

Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive decline of cognitive function that represents one of the most dramatic medical challenges for the aging population. Aβ peptides, generated by processing of the Amyloid Precursor Protein (APP), are thought to play a central role in the pathogenesis of AD. However, the network of physical and functional interactions that may affect their production and deposition is still poorly understood. The use of a bioinformatic approach based on human/mouse conserved coexpression allowed us to identify a group of genes that display an expression profile strongly correlated with APP. Among the most prominent candidates, we investigated whether the collagen chaperone HSP47 could be functionally correlated with APP. We found that HSP47 accumulates in amyloid deposits of two different mouse models and of some AD patients, is capable to physically interact with APP and can be relocalized by APP overexpression. Notably, we found that it is possible to reduce the levels of secreted Aβ peptides by reducing the expression of HSP47 or by interfering with its activity via chemical inhibitors. Our data unveil HSP47 as a new functional interactor of APP and imply it as a potential target for preventing the formation and/or growth amyloid plaques.

This qualitative study explored partner selection in a sample of immigrant Latino men who have sex with men (MSM). In-depth interviews were conducted with men living in the greater New York metropolitan area who had been born in Brazil (n = 10), Colombia (n = 14), or the Dominican Republic (n = 9). One focus group was conducted with MSM from each of the three countries (9 Brazilian, 11 Colombian, and 5 Dominican participants). A grounded theory approach revealed three main themes relating to partner selection. The first concerned stereotypes of how Latino and Anglo-American men tend to behave in their sexual encounters and relationships. The participants perceived Latinos to be more affectionate and passionate, whereas they saw Anglo-American men as more independent and practical. These cultural discrepancies sometimes resulted in a preference for Latino partners. A second theme concerned stereotypes of the national groups, including expectations that Brazilians would be sexy and sensual and that Dominicans would have large penises. As found in other research on MSM of color, ethnic and national stereotypes were associated with experiences of sexual objectification. The third theme addressed the importance of masculine characteristics in sexual attraction and partner selection. Negative feelings towards effeminate men who did not conform to normative male physical or behavioral presentation reflect a stigma found inside and outside of the gay community. These findings suggest that gender and ethnic stereotypes play an important role in shaping partner choice and have implications for sexual risk and relationship formation.

Latino men who have sex with men (MSM) constitute a group at high risk for HIV. Recent approaches to understanding sexual risk have emphasized the role that contextual factors can play in shaping behavior. This study examined sexual behavior of Latino MSM in private and public settings. First, a within-person comparison of behaviors performed in sexual encounters that occurred in public and private settings was conducted. Unprotected anal intercourse (UAI) and other sexual behaviors involving anal stimulation were more common in private settings; group sex was more likely in public settings. Second, a between-person analysis compared sexual behaviors of MSM who went to three different types of public sex settings during the past six months. The types were: (1) commercial sex venues (CSVs), which were defined as businesses with the function of providing a space where MSM can go to have sexual encounters, such as gay bathhouses; (2) commercial sex environments (CSEs), which were defined as businesses with another apparent function, but in which MSM sometimes have sexual encounters, such as gay bars or pornographic movie houses; and (3) public sex environments (PSEs), which were defined as free public areas where MSM can go to find partners for anonymous sex, such as parks or public restrooms. Results indicated that anal sexual behavior was most likely to occur in CSVs and least likely in PSEs, but the probability of UAI was not found to differ among the three types of settings. Behavioral differences were discussed in terms of structural conditions related to privacy and safety, and psychological factors related to intimacy.

This study investigated relationships between Latino gay-identified men in metropolitan New York City and their non-gay-identified male partners. Phase 1 consisted of in-depth interviews (N = 33), and Phase 2 consisted of quantitative surveys (N = 120) with Brazilian, Colombian, and Dominican men who have sex with men (MSM). A majority of participants reported having had sex with heterosexually identified men, and in many cases, the relationship was sustained over time. We found mixed results concerning an attitude sometimes attributed to Latinos that sexual orientation is defined by sexual role, with receptive MSM seen as gay and insertive MSM seen as straight. Although there were no significant associations between partner sexual orientation and unprotected anal intercourse, gay men were less likely to take the insertive role in oral or anal sex with straight-identified male partners than with gay partners.

Theoretical models of sexual risk-taking have traditionally focused on personal characteristics, but conceptual approaches emphasizing the social and situational context have also been proposed. This study examined the impact of characteristics of the person and of the sexual encounter on unprotected anal intercourse (UAI) among 482 immigrant Latino MSM. Analyses included logistic regression and hierarchical linear modeling. The personal characteristic of self-efficacy for safer sex was negatively associated with UAI over the previous three months, at the most recent encounter, and over multiple encounters reported by each participant. In addition, a cross-level interaction of self-efficacy at the person-level and sexual desire at the encounter-level showed that increased sexual desire was associated with greater likelihood of UAI for those with low self-efficacy, but not those with high self-efficacy. Likelihood of UAI was also linked to the situational characteristics of closeness to the partner, seroconcordance, and concern about STIs in the encounter.

To test a theoretical approach to disclosure of human immunovirus (HIV) status, 301 HIV-positive Latino gay men were interviewed using Audio-CASI (Computer Assisted Self-Interview technology with Audio enhancement). Consequence theory and social influence theory were combined to create a model of antecedents of disclosure. Results provided support for both theories. Perceived positive consequences were associated with greater disclosure to casual partners, families, and friends, whereas perceived negative consequences were associated with less disclosure to friends and family members. Social influence of peer behavioral norms was predictive of disclosure to all three target groups. Gay community social influence produced different effects on disclosure of HIV-positive status: a negative association for casual partners, a positive association for close friends, and no relationship for family members. Time since diagnosis was also predictive of disclosure., (2007 APA)

Key informant interviews, in-depth interviews and focus groups were conducted to examine ways in which social context influenced the behavior of Brazilian, Colombian and Dominican men who have sex with men. First, we investigated how the social context in the home country affected motivation for migration. Findings suggest that Latino men who have sex with men frequently reported coming to the USA to escape homo-negativity and to achieve greater sexual freedom. The study also examined how the social context encountered in the early years after migration shaped sexual behavior and risk. A majority of the participants reported easy access to sex partners and frequent sexual encounters. The anonymity of living in a gay epicentre such as New York City, often without social connections from the past, was experienced as liberating and conducive to sexual exploration. Moreover, sex in public venues, such as parks and sex cabins, was readily available to those who do not speak English. The tendency to engage in high levels of sexual activity during the early period after arrival in New York City was particularly evident among younger men. Implications for future programme development are discussed alongside prevention efforts targeting migrants during this critical period.

This study investigated protective effects of circumcision in a sample of immigrant Latino men who have sex with men (MSM). A survey in Portuguese, Spanish, or English was administered with computer-assisted self-interview technology with audio enhancement (A-CASI) to 482 MSM from Brazil (n=146), Colombia (n=169), and the Dominican Republic (n=167), living in the New York metropolitan area. Logistic regression revealed that after controlling for age, income, education, having had syphilis, having done sex work, and preferring the receptive role in anal intercourse, uncircumcised men were almost twice as likely to be HIV-positive as circumcised men. Follow-up analyses revealed, however, that the protective effects occurred only among the group of Colombian men.

This article examined, in a sample of 219 HIV-positive Latino men who have sex with men (MSM), a set of three variables that can shape the context of sexual encounters between men and influence sexual risk behaviors: disclosure of positive HIV serostatus, seroconcordance of partners, and relationship between partners. Participants from Boston, New York, and Washington completed a survey in English or Spanish using computer-assisted self-interview technology with audio enhancement. At the bivariate level, disclosure, seroconcordance, and partner relationship were all interrelated, as well as associated with the likelihood of unprotected intercourse. Unprotected anal intercourse with the most recent partner was more likely when the partner (a) knew that the participant was HIV-positive, (b) was the participant's main partner, and (c) was himself also HIV-positive. A logistic set regression revealed that the set of three variables added significantly to the prediction of unprotected anal intercourse, beyond demographic variables of income, education, and age. In the multivariate model, however, of the three, only seroconcordance achieved significance. The importance of a contextual approach to understanding sexual risk behavior was discussed.

This study examined disclosure of HIV-positive serostatus by 301 Latino gay and bisexual men to members of their social networks and the mental health consequences of such disclosure. The sample was recruited from clinics, hospitals, and community agencies in New York City, Washington, DC, and Boston. Proportions disclosing differed depending on the target, with 85% having disclosed to closest friend, 78% to male main partner, 37% to mother, and 23% to father. Although there were differences depending on the target, disclosure was related to greater quality of social support, greater self-esteem, and lower levels of depression. Moreover, findings indicated that social support mediated the relationship between disclosure of serostatus and both self-esteem and depression. Thus, disclosure resulted in greater social support, which in turn had positive effects on psychological well-being. Findings demonstrate that generally Latino gay men are selective in choosing people to whom they disclose their serostatus and that disclosure tends to be associated with positive outcomes.

This study examined sexual behaviors in a sample of 155 HIV-positive Latino gay and bisexual men. Nearly half the sample had engaged in unprotected anal intercourse in the past 12 months; unprotected anal intercourse was more likely when the partner was also HIV-positive. Separate regression models predicted the number of receptive and insertive partners for unprotected anal intercourse. Participants reported both more unprotected insertive and receptive partners if they had sex under the influence of alcohol or drugs. Older participants and those with lower levels of Latino acculturation reported having more partners with whom they took the receptive role during unprotected anal intercourse, whereas those with higher levels of depression reported having more partners with whom they took the insertive role. Hierarchical set logistic regression revealed that the dyadic variable of seroconcordance added to the prediction of unprotected anal sex with the most recent male partner, beyond the individual characteristics. Results show the importance of examining both individual and dyadic characteristics in the study of sexual behavior.

This study explored disclosure of serostatus in a sample of 155 HIV-positive Latino gay men from New York City and Washington, DC. We examined rates of disclosure to different members of the social network: mothers, fathers, close friends, and primary sexual partners. There were high rates of disclosure of HIV-positive serostatus to main partners and closest friends and lower rates to fathers and mothers. We examined the role of 3 contextual target-dependent factors (emotional closeness to target, anticipated reactions from target, and target's knowledge of sexual orientation), as well as acculturation and time since diagnosis. Three separate logistic regression models were performed to predict disclosure of HIV-positive status to 3 targets: mothers, fathers, and closest friends. We found that disclosure was not a generalized tendency, but rather different factors were influential depending on the target. Whether the target was aware of participant's sexual orientation was associated with disclosure in all 3 models. Greater emotional closeness also predicted disclosure to mother and father; greater U.S. acculturation was associated with disclosure to father and marginally to mother. A longer time since diagnosis was associated with disclosure to the closest friend. These findings highlight the importance of taking into account roles and relationships, and their effect on disclosure.

The contribution of J. E. Helms's (1990) people of color racial identity model to the collective and individual self-esteem of Black Brazilian men (N = 203) was explored. The relationships between racial identity attitudes and other racial constructs such as skin color, racial group self-designation, and racial mistrust were also examined. Hierarchical regression analyses revealed that the set of racial identity attitudes (conformity, dissonance, resistance, and internalization) was significant in predicting self-esteem (collective and individual). Results from a multivariate analysis of variance showed an effect for skin color on racial attitudes. In addition, racial identity was significantly related to mistrust of Whites by Black Brazilian men. The implications of these findings are discussed in the context of racial relations in Brazil.