Understanding male circumcision: insights from a peri-urban community in Maputo City, Mozambique.

BACKGROUND: Circumcision is a protective measure against sexually transmitted infections (STIs), reducing the risk of HIV infection. This study reported coverage of male circumcision and assessed the factors associated with male uncircumcision in a peri-urban area in Maputo City, Mozambique. METHODS: This cross-sectional study of the Health Demographic Surveillance System in the Polana Caniço neighborhood investigated the sociodemographic and behavioral factors associated with uncircumcised males aged 15-49 y from October 2019 to June 2021. Data were collected from an HIV risk factors questionnaire and descriptive analyses conducted comparing self-reported male circumcision status by sociodemographic factors and sexual behaviors. The association was assessed via χ2 tests, and a multivariable logistic regression model was constructed. Adjusted ORs and 95% CIs were reported for factors associated with uncircumcised status. RESULTS: Of the 3481 males aged 15-49 y who responded to the questionnaire, 79.5% (2766) self-reported being circumcised. The percentage of uncircumcised men steadily increased with age, ranging from 12.4% (95) among males aged 15-19 y to 34.5% (148) of men aged 40-49 y. Men without education or with primary education, as well as those not practicing Islam, were 3-4 times more likely to be uncircumcised. Uncircumcised men were more likely to self-report an STI and a lack of condom use. CONCLUSIONS: Being uncircumcised was associated with not using condoms and having STIs, highlighting the need to further emphasize combination HIV-prevention programs and regular HIV/STI screening. Targeting males with lower education and across religions can help reach those with lower coverage of this effective prevention intervention.

Spine apparatus modulates Ca 2+ in spines through spatial localization of sources and sinks.

Dendritic spines are small protrusions on dendrites in neurons and serve as sites of postsynaptic activity. Some of these spines contain smooth endoplasmic reticulum (SER), and sometimes an even further specialized SER known as the spine apparatus (SA). In this work, we developed a stochastic spatial model to investigate the role of the SER and the SA in modulating Ca 2+ dynamics. Using this model, we investigated how ryanodine receptor (RyR) localization, spine membrane geometry, and SER geometry can impact Ca 2+ transients in the spine and in the dendrite. Our simulations found that RyR opening is dependent on where it is localized in the SER and on the SER geometry. In order to maximize Ca 2+ in the dendrites (for activating clusters of spines and spine-spine communication), a laminar SA was favorable with RyRs localized in the neck region, closer to the dendrite. We also found that the presence of the SER without the laminar structure, coupled with RyR localization at the head, leads to higher Ca 2+ presence in the spine. These predictions serve as design principles for understanding how spines with an ER can regulate Ca 2+ dynamics differently from spines without ER through a combination of geometry and receptor localization. Highlights: 1RyR opening in dendritic spine ER is location dependent and spine geometry dependent. Ca 2+ buffers and SERCA can buffer against runaway potentiation of spines even when CICR is activated. RyRs located towards the ER neck allow for more Ca 2+ to reach the dendrites. RyRs located towards the spine head are favorable for increased Ca 2+ in spines.

The process of adapting a sexual health intervention for Black early adolescents: a stakeholder engagement approach.

Young Black women are disproportionately affected by sexually transmitted infections (STIs) and HIV. Notably, few sexual health interventions for Black girls have documented the process of utilizing stakeholder input from the Black community to culturally tailor content. We conducted formative work in Chicago to adapt a mother-daughter HIV/STI prevention intervention originally designed for Black adolescent girls aged 14-18 years to meet the needs of early adolescent girls aged 11-13 years. Our iterative process involved three phases: (i) soliciting feedback from an expert panel and community advisory board; (ii) conducting focus groups with experienced research participants; and (iii) theater testing a new curriculum in the target population. Key findings of this process indicate the importance of sophisticated community engagement strategies to shape research design and program implementation. Findings may be used to inform processes for future adaptation work, especially in sexual health programs for young Black girls and their mothers.

The Importance of Understanding Individual Differences of Emotion Regulation Abilities in 22q11.2 Deletion Syndrome.

Chromosome 22q11.2 deletion syndrome (22q11DS) is characterised by a complex behavioural phenotype including anxiety, attention-deficit/hyperactivity disorder and psychosis. In the current study, we aimed at improving our understanding of the heterogeneity of behavioural characteristics in a group of 129 young people (aged 4-22) with a confirmed 22q11.2 microdeletion and 116 age and gender matched typically developing controls. Half the participants with 22q11DS had behaviour characterised by emotion dysregulation. A cluster analyses, of the participants with 22q11DS, revealed four groups characterised by intact emotion regulation; predominantly internalizing problems; both internalizing and externalizing problems; and predominantly externalizing difficulties. Importantly, it was found that young people with 22q11DS whose emotion dysregulation was characterised by externalizing problems had the poorest levels of functioning. As our understanding of 22q11DS improves, it is becoming increasingly clear that we need a better understanding of how individual differences and psychosocial factors contribute to, and interact with one another, to result in the observable individual differences in the 22q11DS behavioural phenotype.

Environmental stress in the Gulf of Mexico and its potential impact on public health.

The Deepwater Horizon (DWH) oil spill in the Gulf of Mexico was the largest maritime oil spill in history resulting in the accumulation of genotoxic substances in the air, soil, and water. This has potential far-reaching health impacts on cleanup field workers and on the populations living in the contaminated coastal areas. We have employed portable airborne particulate matter samplers (SKC Biosampler Impinger) and a genetically engineered bacterial reporter system (umu-ChromoTest from EBPI) to determine levels of genotoxicity of air samples collected from highly contaminated areas of coastal Louisiana including Grand Isle, Port Fourchon, and Elmer's Island in the spring, summer and fall of 2011, 2012, 2013 and 2014. Air samples collected from a non-contaminated area, Sea Rim State Park, Texas, served as a control for background airborne genotoxic particles. In comparison to controls, air samples from the contaminated areas demonstrated highly significant increases in genotoxicity with the highest values registered during the month of July in 2011, 2013, and 2014, in all three locations. This seasonal trend was disrupted in 2012, when the highest genotoxicity values were detected in October, which correlated with hurricane Isaac landfall in late August of 2012, about five weeks before a routine collection of fall air samples. Our data demonstrate: (i) high levels of air genotoxicity in the monitored areas over last four years post DWH oil spill; (ii) airborne particulate genotoxicity peaks in summers and correlates with high temperatures and high humidity; and (iii) this seasonal trend was disrupted by the hurricane Isaac landfall, which further supports the concept of a continuous negative impact of the oil spill in this region.

Social cognition dysfunction in adolescents with 22q11.2 deletion syndrome (velo-cardio-facial syndrome): relationship with executive functioning and social competence/functioning.

BACKGROUND: Social difficulties are often noted among people with intellectual disabilities. Children and adults with 22q.11.2 deletion syndrome (22q11DS) often have poorer social competence as well as poorer performance on measures of executive and social-cognitive skills compared with typically developing young people. However, the relationship between social functioning and more basic processes of social cognition and executive functioning are not well understood in 22q11DS. The present study examined the relationship between social-cognitive measures of emotion attribution and theory of mind with executive functioning and their contribution to social competence in 22q11DS. METHOD: The present cross-sectional study measured social cognition and executive performance of 24 adolescents with 22q11DS compared with 27 age-matched typically developing controls. Social cognition was tested using the emotion attribution task (EAT) and a picture sequencing task (PST), which tested mentalising (false-belief), sequencing, cause and effect, and inhibition. Executive functioning was assessed using computerised versions of the Tower of London task and working memory measures of spatial and non-spatial ability. Social competence was also assessed using the parent-reported Strengths and Difficulties Questionnaire. RESULTS: Adolescents with 22q11DS showed impaired false-belief, emotion attribution and executive functioning compared with typically developing control participants. Poorer performance was reported on all story types in the PST, although, patterns of errors and response times across story types were similar in both groups. General sequencing ability was the strongest predictor of false-belief, and performance on the false-belief task predicted emotion attribution accuracy. Intellectual functioning, rather than theory of mind or executive functioning, predicted social competence in 22q11DS. CONCLUSIONS: Performance on social-cognitive tasks of theory of mind indicate evidence of a general underlying dysfunction in 22q11DS that includes executive ability to understand cause and effect, to logically reason about social scenarios and also to inhibit responses to salient, but misleading cues. However, general intellectual ability is closely related to actual social competence suggesting that a generalised intellectual deficit coupled with more specific executive impairments may best explain poor social cognition in 22q11DS.

Triggering necroptosis in cisplatin and IAP antagonist-resistant ovarian carcinoma.

Ovarian cancer patients are typically treated with carboplatin and paclitaxel, but suffer a high rate of relapse with recalcitrant disease. This challenge has fostered the development of novel approaches to treatment, including antagonists of the 'inhibitor of apoptosis proteins' (IAPs), also called SMAC mimetics, as apoptosis-inducing agents whose action is opposed by caspase inhibitors. Surprisingly, IAP antagonist plus caspase inhibitor (IZ) treatment selectively induced a tumor necrosis factor-α (TNFα)-dependent death among several apoptosis-resistant cell lines and patient xenografts. The induction of necroptosis was common in ovarian cancer, with expression of catalytically active receptor-interacting protein kinase-3 (RIPK3) necessary for death, and in fact sufficient to compromise survival of RIPK3-negative, necroptosis-resistant ovarian cancer cells. The formation of a necrosome-like complex with a second critical effector, receptor-interacting serine-threonine kinase-1 (RIPK1), was observed. RIPK1, RIPK3 and TNFα were required for the induction of death, as agents that inhibit the function of any of these targets prevented cell death. Abundant RIPK3 transcript is common in serous ovarian cancers, suggesting that further evaluation and targeting of this RIPK3-dependent pathway may be of clinical benefit.

Key workers in cancer care: patient and staff attitudes and implications for role development in cancer services.

The role of the key worker in cancer services was developed in the UK and is now being adopted more widely. Although this role arose out of national guidance, little is known about how it has been implemented, and there been no systematic attempt to investigate how the role is viewed by either patients or staff. This study used a qualitative approach to explore views of the impact of the key worker role in cancer care. Interviews were conducted with 15 staff and 15 patients. Generally, patients were very positive about the role, while staff felt it was just a renaming of their role, which they thought unnecessary. Several differences in the views of staff and patients emerged from the interviews. For example, staff felt the role should transfer to other members of the care team while patients wanted to keep the same worker. Potential reasons for this divergence in attitudes are discussed, and suggestions for the future development of the role made.

LacI(Ts)-regulated expression as an in situ intracellular biomolecular thermometer.

In response to needs for in situ thermometry, a temperature-sensitive vector was adapted to report changes in the intracellular heat content of Escherichia coli in near-real time. This model system utilized vectors expressing increasing quantities of ß-galactosidase in response to stepwise temperature increases through a biologically relevant range (22 to 45°C). As judged by calibrated fluorometric and colorimetric reporters, both whole E. coli cells and lysates expressed significant repeatable changes in ß-galactosidase activity that were sensitive to temperature changes of less than 1°C (35 to 45°C). This model system suggests that changes in cellular heat content can be detected independently of the medium in which cells are maintained, a feature of particular importance where the medium is heterogeneous or nonaqueous, or otherwise has a low heat transfer capacity. We report here that the intracellular temperature can be reliably obtained in near-real time using reliable fluorescent reporting systems from cellular scales, with a 20°C range of detection and at least 0.7°C sensitivity between 35 and 45°C.

Clinical and acquired immunologic responses to West Nile virus infection of domestic chickens (Gallus gallus domesticus).

Numerous bird species are highly susceptible to North American strains of West Nile virus (WNV), and although domestic chickens are relatively resistant to WNV-associated disease, this species currently represents the most practical avian model for immune responses to WNV infection. Knowledge of the immunomodulation of susceptibility to WNV in birds is important for understanding taxonomic differences in infection outcomes. While focusing on immunophenotyping of CD3(+), CD4(+), CD8(+), and CD45(+) lymphocyte subpopulations, we compared lymphocyte subpopulations, blood chemistries, cloacal temperatures, IgM and IgG antibody titers, and differential whole-blood cell counts of WNV-infected and uninfected hens. Total blood calcium and lymphocyte numbers were lower in WNV-infected chickens compared with uninfected chickens. The heterophil-to-lymphocyte ratio increased over time from 2 to 22 d postinoculation (DPI) in uninfected chickens and from 2 to 8 DPI in WNV-infected chickens, although levels declined from 8 to 22 DPI in the latter group. No significant differences were found in the remaining immunological and hematological variables of the WNV-infected and uninfected groups. Our results reaffirm that chickens are resistant to WNV infection, and demonstrated that the heterophil-to-lymphocyte ratio differed between groups, allowing for sorting of infection status. Similar patterns in immune responses over time in both infected and uninfected hens may be related to age (i.e., 10 wk) and associated immune development.

Incidence and diagnostic diversity in first-episode psychosis.

OBJECTIVE: To investigate the incidence and range of diagnostic groups in patients with first-episode psychosis (FEP) in a defined geographical area. METHOD: An observational database was set up on all patients aged 16 years and over presenting with FEP living in a county in Northern England between 1998 and 2005. RESULTS: The incidence of all FEP was 30.95/100,000. The largest diagnostic groups were psychotic depression (19%) and acute and transient psychotic disorder (19%). Fifty-four per cent of patients were aged 36 years and over. Patients with schizophrenia spectrum disorder only accounted for 55% of cases. CONCLUSION: This clinical database revealed marked diversity in age and diagnostic groups in FEP with implications for services and guidelines. These common presentations of psychoses are grossly under researched, and no treatment guidelines currently exist for them.

A functional imaging study of cooperation in two-person reciprocal exchange.

Cooperation between individuals requires the ability to infer each other's mental states to form shared expectations over mutual gains and make cooperative choices that realize these gains. From evidence that the ability for mental state attribution involves the use of prefrontal cortex, we hypothesize that this area is involved in integrating theory-of-mind processing with cooperative actions. We report data from a functional MRI experiment designed to test this hypothesis. Subjects in a scanner played standard two-person "trust and reciprocity" games with both human and computer counterparts for cash rewards. Behavioral data shows that seven subjects consistently attempted cooperation with their human counterpart. Within this group prefrontal regions are more active when subjects are playing a human than when they are playing a computer following a fixed (and known) probabilistic strategy. Within the group of five noncooperators, there are no significant differences in prefrontal activation between computer and human conditions.

Childhood and adolescent onset conduct disorder: a test of the developmental taxonomy.

Hypotheses generated by a developmental taxonomy that distinguishes between childhood and adolescent onset conduct disorders were tested. Hypotheses predicted that (1) individual and familial factors would be more strongly related to childhood onset conduct disorder, whereas ethnic minority status and exposure to deviant peers would be more strongly related to adolescent onset conduct disorder and (2) individuals with childhood onset disorder would be more likely to commit violent and victim oriented offenses than individuals with adolescent onset conduct disorder. The first hypothesis was strongly supported and the second hypothesis was partially supported. Implications for early identification of youth at risk for chronic offending are discussed.

Bradykinin metabolism in the isolated perfused rabbit heart.

BACKGROUND: Bradykinin is a potent cardioprotective hormone, the beneficial role of which in vivo appears to be limited by its rapid metabolism. Inhibitors of peptidases that degrade endogenously formed bradykinin are themselves cardioprotective, presumably by increasing local bradykinin concentrations. As bradykinin-degrading peptidases are potential therapeutic targets, it is important to identify these enzymes in different animal models of cardiac function. OBJECTIVE: To determine the mechanism of bradykinin degradation in the coronary circulation of the rabbit, using an isolated perfused heart preparation. DESIGN AND METHODS: [3H]Bradykinin (16 nmol/l) was perfused as a bolus through the isolated rabbit heart in the presence and absence of specific peptidase inhibitors. The effluent was collected and the radiolabeled metabolites of [3H]bradykinin were separated by high performance liquid chromatography, identified, and quantified. RESULTS: [3H]Bradykinin was metabolized to the extent of 62 +/- 3% in a single passage through the rabbit coronary circulation at a physiological flow rate. The metabolites were identified as [3H]bradykinin(1-5) and [3H]bradykinin(1-7),accounting for 50 +/- 4 and 12 +/- 2% of the radioactivity, respectively. Co-perfusion with the angiotensin converting enzyme inhibitor, ramiprilat, completely blocked formation of these metabolites. CONCLUSIONS: Angiotensin-converting enzyme fully accounts for the metabolism of [3H]bradykinin in the rabbit coronary circulation. This result contrasts with data obtained using rat heart, which demonstrated a prominent role for aminopeptidase P in bradykinin metabolism in this species.

Prevalence of psychiatric disorders in youths across five sectors of care.

OBJECTIVE: To examine the prevalence of psychiatric disorders among youths from the following five public sectors of care: alcohol and drug services (AD), child welfare (CW), juvenile justice (JJ), mental health (MH), and public school services for youths with serious emotional disturbance (SED) in San Diego, California. METHOD: The Diagnostic Interview Schedule for Children was administered between October 1997 and January 1999 for 1,618 randomly selected youths aged 6-18 years who were active in at least one of the five sectors. RESULTS: Fifty-four percent of the participants met criteria for at least one study disorder. Attention-deficit/hyperactivity disorder (ADHD) and disruptive behavior disorders (50%) were much more common than anxiety (10%) or mood (7%) disorders. Youths who were active in the MH and SED sectors were more likely than those not in these sectors to meet criteria for a disorder; youths in the CW sector were least likely. CONCLUSIONS: Rates of psychiatric disorders, specifically ADHD and disruptive behavior disorders, are extremely high for youths in public sectors of care. Rates are generally higher in sectors designed to serve youths with psychiatric needs, but the prevalence of disorders was also high in sectors not specifically designed for this need (e.g., CW and JJ).

A longitudinal study of T1 hypointense lesions in relapsing MS: MSCRG trial of interferon beta-1a. Multiple Sclerosis Collaborative Research Group.

BACKGROUND: T1 hypointense lesions (T1 black holes) are focal areas of relatively severe CNS tissue damage detected by MRI in patients with MS. OBJECTIVE: To determine the natural history of T1 hypointense lesions in relapsing MS and the utility of T1 hypointense lesions as outcome measures in MS clinical trials. METHODS: MR studies were from the Multiple Sclerosis Collaborative Research Group trial. Longitudinal results are reported in 80 placebo- and 80 interferon beta-1a (IFNbeta-1a)-treated patients with mild to moderate disability relapsing-remitting MS. RESULTS: There was a small but significant correlation between T1 hypointense lesion volume and disability at baseline and on trial (r = 0.22, r = 0.28). In placebo patients there was a 29.2% increase in the mean volume of T1 hypointense lesions (median 124.5 mm3) over 2 years (p < 0.001 for change from baseline), as compared to an 11.8% increase (median 40 mm3) in the IFNbeta-1a-treated patients (change from baseline not significant). These treatment group comparisons did not quite reach significance. The most significant contributor to change in T1 hypointense lesions was the baseline number of enhancing lesions (model r2 = 0.554). Placebo patients with more active disease, defined by enhancing lesions at baseline, were the only group to show a significant increase in T1 hypointense lesion volume from baseline. CONCLUSION: The development of T1 hypointense lesions is strongly influenced by prior inflammatory disease activity, as indicated by enhancing lesions. These results suggest that treatment with once weekly IM IFNbeta-1a (30 mcg) slows the 2-year accumulation of these lesions in the brain.

Characteristics of hormone-treated prostate carcinoma: stressing the need for clinician-pathologist communication.

OBJECTIVE: Patients scheduled for prostatectomy often receive androgen deprivation therapy to make malignant tumors more amenable to resection and improve the postoperative course. These hormonal therapies may significantly alter the histomorphology of carcinoma of the prostate detected on subsequent needle biopsies. METHODS: Needle specimens were obtained from resected prostates harboring biopsy-proven carcinoma previously treated with leuprolide. The tissue was examined by light microscopy to note architectural and cytologic characteristics. RESULTS: A high proportion of treated carcinomas had an atrophic, infiltrative appearance. Nuclear and nucleolar enlargement were consistently observed. Macronucleoli, blue-tinged mucin, and intraluminal pink amorphous material was frequently identified. CONCLUSIONS: The markedly atrophic nature of the cells and glands may result in either overgrading of prostate carcinoma or failure to recognize the more subtle patterns of this malignant neoplasm. It is imperative that clinicians convey a history of hormone treatment to pathologists when core biopsies of the prostate are submitted for histologic evaluation.