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.

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.

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.

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.

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 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.

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.

Smart computer-assisted markets.

The deregulation movement has motivated the experimental study of auction markets designed for interdependent network industries such as natural gas pipelines or electric power systems. Decentralized agents submit bids to buy commodity and offers to sell transportation and commodity to a computerized dispatch center. Computer algorithms determine prices and allocations that maximize the gains from exchange in the system relative to the submitted bids and offers. The problem is important, because traditionally the scale and coordination economies in such industries were thought to require regulation. Laboratory experiments are used to study feasibility, limitations, incentives, and performance of proposed market designs for deregulation, providing motivation for new theory.

Effect of maternal smoking on hemoglobins and hematocrits of the newborn.

PIP: The progeny of smokers had higher 48-hour hemoglobin and hematocrit levels than that of nonsmokers in this study, based on 10,399 clinically-normal term white infants. This effect could not be accounted for by 1) per capita income; 2) maternal pre-pregnancy weight or maternal stature; or 3) placental weight/birth-weight ratio, and was found to be proportionately related to the level of maternal smoking. The response of the progeny in utero to maternal smoking during pregnancy clearly is an increase in 1) red cell volume suggesting oxygen deprivation during gestation, and 2) hemoglobin concentration; consequently the progeny are likely to enter the postnatal period with a larger fetal iron reserve. This result is considered nutritionally relevant.^ieng

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.

Goblet cell carcinoid arising in a mature teratoma of the mediastinum.

Goblet cell carcinoid (GCC) is a rare but distinctive neoplasm with features of both adenocarcinoma and carcinoid tumor. Most cases described in the literature have occurred in the appendix. An additional well-defined location is the ovary, and these tumors have been associated with a mature teratoma of the ovary. GCC arising within a mature teratoma of the mediastinum has not been described in the English-language literature. We report a case of this previously undescribed entity and provide a review of the literature on mediastinal teratomas with malignant transformation. The histologic findings included uniform, smooth-bordered glandular nests lined by goblet cells and admixed endocrine and Paneth cells. Occasional tubular glands were present, as were transitional type glands with both goblet cell and tubular features. Cytologic atypia was minimal, and mitotic activity was rare. Immunohistochemical studies showed positive staining of GCC tumor cells with chromogranin, cytokeratin, neuron-specific enolase, serotonin (focal), and Leu-7 (focal). The GCC component was entirely contained within the mature teratoma.

Midazolam inhibits long-term potentiation through modulation of GABAA receptors.

Benzodiazepine drugs (BZ) are used for anxiety, insomnia, and seizures. They worsen memory, especially in large doses, but the mechanism of this action is uncertain. In micromolar concentrations, benzodiazepines have been shown to reduce long-term potentiation (LTP), which could be a cellular basis for their amnesic action. We have found that the LTP-inhibiting effects of BZ occur in the nanomolar concentrations attained in humans, and that this effect occurs through modulation of GABAA receptor function. We recorded extracellular synaptic input/output (I/O) curves for population spikes (PS) and EPSPs in rat hippocampal slices before and after induction of LTP. LTP increased maximal PS and EPSPs and shifted I/O curves for PS and EPSPs to the left, reflecting increased synaptic responsiveness after LTP. Curves relating EPSPs to PS were also shifted, so that after LTP larger PS were elicited for the same size EPSP (E-S potentiation). Midazolam (0.5 microM) markedly inhibited the left-shift in PS I/O curves due to E-S potentiation but did not significantly affect other parameters. 8-Phenyltheophylline (10 microM), an adenosine receptor antagonist, did not prevent midazolam inhibition of LTP. Bicuculline, a GABAA receptor antagonist, caused a dose-dependent antagonism of midazolam's LTP inhibition. Our results suggest that benzodiazepines reduce LTP primarily through reduction of E-S potentiation, and that this effect occurs through modulation of GABAA receptor function. This could in part account for the ability of benzodiazepines to disturb new memory formation.

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.

Amplification of bacterial DNA using highly conserved sequences: automated analysis and potential for molecular triage of sepsis.

OBJECTIVE: The clinical diagnosis of sepsis remains difficult, particularly in the young child, and would be improved by a rapid and reliable method for identification of bacteria in blood and other body fluids. Polymerase chain reaction (PCR) amplification of highly conserved DNA sequences found in all bacteria would permit fast and sensitive determination of the presence of bacteria in clinical specimens. METHODOLOGY: A primer pair for highly conserved regions of bacterial DNA encoding 16S ribosomal RNA (rDNA) was utilized for PCR amplification. PCR products were analyzed by gel electrophoresis, and, after modification of the primers, by an automated 96-well plate reader. RESULTS: rDNA was amplified from 12 different species of bacteria, including Gram-negative and -positive organisms. No signal was observed when total human DNA was used as template. Colorimetric analysis of amplified sequences using a 96-well format was also successful. CONCLUSIONS: We conclude that a single primer pair designed to anneal to a highly conserved region of bacterial DNA can amplify DNA specimens from a variety of different bacteria, while not amplifying human DNA. Such a molecular genetics approach can be fully automated with existing robotic technology. Because of speed, sensitivity, and cost, molecular triage of patients with signs and symptoms of possible bacterial infection will decrease morbidity and mortality among those with unrecognized bacteremia who are managed as outpatients, and will dramatically reduce hospital expenses from individuals who are admitted and are not bacteremic.

The human L-pipecolic acid oxidase is similar to bacterial monomeric sarcosine oxidases rather than D-amino acid oxidases.

L-Pipecolic acid oxidase activity is deficient in patients with peroxisome biogenesis disorders (PBDs). Because its role, if any, in these disorders is unknown, the authors cloned the human gene to order to further study its functions. BLAST search of the translated sequence showed greatest homology to Bacillus sp. NS-129 monomeric sarcosine oxidase. The purified enzyme could use either L-pipecolic acid or sarcosine as a substrate. No homology was found to the peroxisomal D-amino acid oxidases. A further comparison of L-pipecolic acid oxidase to the two D-amino acid oxidases in peroxisomes showed that the proteins differed in many ways. First, both D-amino acid oxidase and L-pipecolic acid oxidase showed no enzyme activity in liver from Zellweger syndrome patients; D-aspartate oxidase activity was unchanged from control levels. Although all were targeted to peroxisomes, their targeting signals differed. No L-pipecolic acid oxidase was found in brain or other tissues outside of liver and kidney. The D-amino acid oxidases were similarly and more widely distributed. Finally, although D-amino acid degradation is limited to peroxisomes in mammals, L-pipecolic acid can be oxidized in either mitochondria or peroxisomes, or both.

Pulmonary intravascular lymphomatosis: presentation with dyspnea and air trapping.

Intravascular lymphomatosis (IVL) is a rare lymphoid neoplasm that is typically of B-cell lineage and characterized by proliferation of malignant cells within small arterioles, capillaries, and venules. We report a patient with pulmonary IVL who presented clinically with progressive dyspnea, fever, and a dry cough. Pulmonary function tests revealed a marked decrease in diffusion capacity with airflow obstruction and severe air trapping. High-resolution CT (HRCT) of the chest with inspiratory and expiratory images revealed mosaic attenuation consistent with air trapping. Transbronchial biopsies revealed the diagnosis of IVL with capillary expansion in the alveolar and peribronchiolar interstitial tissue. IVL should be considered in the differential diagnosis of a patient with an interstitial lung disease, air trapping on pulmonary function tests, and mosaic attenuation on HRCT. Transbronchial biopsies may be the initial diagnostic procedure of choice.