SS Participants Research Articles

Testicular Volume in Children with Sickle Cell Anaemia in Uyo, a South-South Nigerian City.

Sickle cell anaemia (SCA) often presents in early childhood with repeated vaso-occlusive crisis that leads to ischaemia, infarction and fibrosis which may result in a reduction in expected testicular volume (TV) at puberty. This was a cross-sectional study of 95 children with SCA aged 1-18 years compared with 95 age-matched controls. Participants responded to an interviewer-administered questionnaire, with their anthropometric measurements taken, pubertal maturity assessed by Tanner staging and testicular ultrasonography done. Changes in TV across the ages were compared graphically and regression analyses were used to determine the factors independently associated with TV. A p-value of <0.05 was considered statistically significant. In the prepubertal period, the haemoglobin SS (HbSS) participants had larger median ultrasound TV (MUSTV) compared to the haemoglobin AA (HbAA) controls (p = 0.001). This trend reversed in the pubertal period. On regression analysis, the frequency of testicular pain (p = 0.04), weight (p = 0.02) and pubic hair rating (p = 0.03) of the HbSS participants were significant predictors of increased TVs in the HbSS participants, irrespective of pubertal status. The prepubertal MUSTV of the HbSS participants were higher than those of the HbAA controls, while the HbAA controls had higher MUSTV at puberty and beyond. The frequency of testicular pain episodes, pubic hair rating and weight were independent predictors of TV changes in the HbSS participants. Prevention of repeated vaso-occlusive crisis in the prepubertal period may help prevent the reduction in TV and possible hypogonadism. Lay summarySickle cell anaemia (SCA) causes repeated episodes of painful crisis and in boys, these may affect the way their testes grow. The study set out to document testicular sizes on a one-time basis in boys aged 1-18 years with SCA compared with controls of similar ages. The participants responded to structured questions assisted by the researchers and their body measurements were appropriately taken. Their level of sexual maturation was assessed according to the method by Tanner and the sizes of their testes were measured using an ultrasound machine. The research information was analysed and a statistical value less than 0.05 was taken to mean that there was a difference between the measured variables. The mid-testicular sizes of the SCA participants were noted to be higher than that of their controls during the prepubertal period while the non-SCA boys had higher sizes from puberty onwards. The frequency of testicular pain, weight and pubic hair stage of the SCA boys were important contributors to their increased testes sizes, irrespective of pubertal status. Efforts aimed at preventing painful crisis should start during early childhood to forestall future sexual challenges in adulthood.

Structural brain alterations in older adults exposed to early-life adversity

BackgroundAdverse childhood events may have differential effects on the brain that persist into adulthood. Findings on structural brain alterations in older adults exposed to early-life adversity are inconsistent notably due to heterogeneity in imaging studies, population, psychiatric comorbidities, nature of adverse events, and genetic vulnerability. This study examines whether exposure related to physical or sexual maltreatment, emotional maltreatment, and global adverse environment during childhood are associated with specific alterations in grey matter volumes and if this varies according to sex and serotonin transporter-linked promoter region (5-HTTLPR) genotype. MethodStructural MRI was used to acquire anatomical scans from 398 community-dwelling older adults. Quantitative regional estimates of 23 subregional volumes were derived using FreeSurfer software. Retrospective reporting of childhood adversity was collected using structured self-reported questionnaire. Analyses adjusted for age, sex, brain volume, head injury, lifetime depression and anxiety disorder, psychiatric medication, and cardiovascular ischemic pathologies. ResultsExposure to adverse family environment was associated with smaller volumes of several frontal, cingulate, and parietal subregions and larger amygdala in the 5-HTTLPR SS genotype participants specifically but larger volumes of caudate, putamen, pallidum, and nucleus accumbens in the SL genotype participants. Highly significant differences were found with excessive sharing of parent problems with children, associated with larger grey-matter volumes in the thalamus and several frontal and parietal regions in 5-HTTLPR SL male participants specifically. ConclusionsEarly-life adversity is associated with grey-matter volume alterations in older adults and this varies according to the type of adversity experienced, sex, and serotonergic genetic vulnerability; 5-HTTLPR SS participants appearing most vulnerable and SL individuals most resilient.

Baseline and Disease-Induced Transcriptional Profiles in Children with Sickle Cell Disease

Acute chest syndrome (ACS) is a significant cause of morbidity and mortality in sickle cell disease (SCD), but preventive, diagnostic, and therapeutic options are limited. Further, ACS and acute vasoccclusive pain crises (VOC) have overlapping features, which causes diagnostic dilemmas. We explored changes in gene expression profiles among patients with SCD hospitalized for VOC and ACS episodes to better understand ACS disease pathogenesis. Whole blood RNA-Seq was performed for 20 samples from children with SCD at baseline and during a hospitalization for either an ACS (n = 10) or a VOC episode (n = 10). Respiratory viruses were identified from nasopharyngeal swabs. Functional gene analyses were performed using modular repertoires, IPA, Gene Ontology, and NetworkAnalyst 3.0. The VOC group had a numerically higher percentage of female, older, and hemoglobin SS participants compared to the ACS group. Viruses were detected in 50% of ACS cases and 20% of VOC cases. We identified 3004 transcripts that were differentially expressed during ACS episodes, and 1802 transcripts during VOC episodes. Top canonical pathways during ACS episodes were related to interferon signaling, neuro-inflammation, pattern recognition receptors, and macrophages. Top canonical pathways in patients with VOC included IL-10 signaling, iNOS signaling, IL-6 signaling, and B cell signaling. Several genes related to antimicrobial function were down-regulated during ACS compared to VOC. Gene enrichment nodal interactions demonstrated significantly altered pathways during ACS and VOC. A complex network of changes in innate and adaptive immune gene expression were identified during both ACS and VOC episodes. These results provide unique insights into changes during acute events in children with SCD.

First examination of varying health outcomes of the chronically homeless according to Housing First configuration

Objective:To determine whether two Housing First configurations (scattered site [SS] versus congregated site [CS]) are associated with different health‐related outcomes. Methods:This ecological study employed a longitudinal, quantitative design to compare the outcomes from 63 individuals (SS: n=37; CS: n=26) in Sydney, Australia, over 12 months. Results:Both configurations showed similar improvements in quality of life and psychological distress. While recent use of substances remained stable across the two configurations over time, a marginally greater increase in the proportion of CS individuals injecting more than weekly was found. For health service utilisation, CS participants had notably higher service utilisation rates for mental health specialists and the emergency department for mental health reasons at follow‐up than SS participants. Conclusion:Preliminary evidence of differential injecting and health service utilisation outcomes between configurations emerged within this small‐scale study over the 12‐month period. Implications for public health:Given the rapid expansion of both SS and CS Housing First configurations across Western countries and the indications from this initial study that outcomes may differ according to configuration, there remains a need for robust evaluative evidence on the efficacy of various supported housing models on long‐term individual outcomes.

The effect of an adverse psychological environment on salivary cortisol levels in the elderly differs by 5-HTTLPR genotype

BackgroundAn adverse psychological environment (e.g. stressful events or depression) has been shown to influence basal cortisol levels and cortisol response to stress. This differs depending on the adverse stimuli, but also varies across individuals and may be influenced by genetic predisposition. An insertion/deletion polymorphism in the serotonin transporter gene (5-HTTLPR) is a strong candidate in this regard. ObjectiveTo investigate how stressful life events and depression are associated with diurnal cortisol levels in community-dwelling elderly and determine whether this varies according to genetic variability in the 5-HTTLPR. MethodsThis population-based study included 334 subjects aged 65 and older (mean (SD) = 76.5 (6.3)). Diurnal cortisol was measured on two separate days, under quiet (basal) and stressful conditions. The number of recent major stressful events experienced during the past year was assessed from a 12-item validated questionnaire as an index of cumulative recent stressful events. Lifetime trauma was evaluated using the validated Watson's PTSD inventory, which evaluates the most severe traumatic or frightening experience according to DSM criteria. Depression was defined as having a Mini-International Neuropsychiatric Interview (MINI) diagnosis of current major depressive disorder or high levels of depressive symptoms (Center for Epidemiologic Studies-Depression Scale ≥16). 5-HTTLPR genotyping was performed on blood samples. ResultsExposure to stressful life events was associated with lower basal evening cortisol levels overall, and in the participants with the 5-HTTLPR L allele but not the SS genotype. The greatest effects (over 50% decrease, p < 0.001) were observed for the LL participants having experienced multiple recent stressful events or severe lifetime traumas. Participants with the L allele also had higher evening cortisol stress response. Conversely, depression tended to be associated with a 42% higher basal morning cortisol in the SS participants specifically, but did not modify the association between stressful events and cortisol levels. ConclusionAn adverse psychological environment is associated with basal cortisol levels and cortisol stress response, but this differs according to 5-HTTLPR genotype.

Associations of Housing First Configuration and Crime and Social Connectedness Among Persons With Chronic Homelessness Histories.

This study compared changes in criminal justice contact, quality of life, and social connectedness over a 12-month follow-up period between participants in two Housing First configurations (scattered site [SS] and congregate site [CS]). A longitudinal, quantitative design was utilized for this ecological study. Changes in individual outcomes over time were compared for SS and CS participants who completed both baseline and 12-month follow-up surveys (N=63). The number of contacts with various types of criminal justice system channels differed significantly between SS and CS participants, decreasing significantly among SS participants and increasing significantly among CS participants. The two groups did not differ on quality-of-life outcomes or social-connectedness measures, with the exception of case management engagement, whereby a greater proportion of SS participants disengaged from this service over time compared with CS participants. At follow-up, significant within-group changes over time emerged, with increased boredom reported among SS participants, whereas CS participants reported improvements in social relationships, with fewer reporting losing their temper. The findings supported the notion that the Housing First approach has the potential to significantly improve the lives of persons who have experienced chronic homelessness, a traditionally marginalized and vulnerable group. Over time, this may result in a reduction in the use of acute services, thereby reducing societal costs. The challenge remains to identify the suitability of particular configurations of housing and support and how service delivery can optimize individual outcomes so positive outcomes are maintained in the longer term.

Effects of the Young Adolescent Sleep Smart Program on sleep hygiene practices, sleep health efficacy, and behavioral well-being

ObjectivesUsing a social learning model, the aim of the Sleep Smart Program was to primarily improve sleep health behaviors and secondarily improve academic performance and behavioral well-being. DesignRandomized control trial for a social learning-based preventive intervention program. ParticipantsA diverse group of seventh graders from 2 urban, middle schools were randomly assigned, according to school, to an 8-session Sleep Smart Program (SS = 70) or a comparison group (comparison = 73). MeasurementsSleep patterns, sleep hygiene, and sleep health efficacy; academic performance; and behavioral well-being were assessed at 4 times of measure (baseline, postintervention, 2 follow-up times in eighth grade). ResultsSS seventh graders experienced significantly greater sleep health efficacy, improved physiological and emotional sleep hygiene, more time in bed, and earlier bedtimes vs comparison group. SS (vs comparison) participants also reported a significant decrease in internalizing behavior problems and sustained academic performance. Finally, although not maintained at time 4, SS participants continued to report improved sleep health efficacy at time 3, whereas the comparison group participants' sleep health efficacy declined. ConclusionThe Sleep Smart preventive intervention was effective in improving sleep health efficacy, sleep hygiene, time in bed, and bedtimes; in maintaining grades; and in reducing internalizing behavior problems, yet these changes were not sustained at follow-up.

Randomized controlled effectiveness trial of executive function intervention for children on the autism spectrum

Unstuck and On Target (UOT) is an executive function (EF) intervention for children with autism spectrum disorders (ASD) targeting insistence on sameness, flexibility, goal-setting, and planning through a cognitive-behavioral program of self-regulatory scripts, guided/faded practice, and visual/verbal cueing. UOT is contextually-based because it is implemented in school and at home, the contexts in which a child uses EF skills. To evaluate the effectiveness of UOT compared with a social skills intervention (SS), 3rd-5th graders with ASD (mean IQ=108; UOT n=47; SS n=20) received interventions delivered by school staff in small group sessions. Students were matched for gender, age, race, IQ, ASD symptomotolgy, medication status, and parents' education. Interventions were matched for 'dose' of intervention and training. Measures of pre-post change included classroom observations, parent/teacher report, and direct child measures of problem-solving, EF, and social skills. Schools were randomized and evaluators, but not parents or teachers, were blinded to intervention type. Interventions were administered with high fidelity. Children in both groups improved with intervention, but mean change scores from pre- to postintervention indicated significantly greater improvements for UOT than SS groups in: problem-solving, flexibility, and planning/organizing. Also, classroom observations revealed that participants in UOT made greater improvements than SS participants in their ability to follow rules, make transitions, and be flexible. Children in both groups made equivalent improvements in social skills. These data support the effectiveness of the first contextually-based EF intervention for children with ASD. UOT improved classroom behavior, flexibility, and problem-solving in children with ASD. Individuals with variable background/training in ASD successfully implemented UOT in mainstream educational settings.

Results of Community Deliberation About Social Impacts of Ecological Restoration: Comparing Public Input of Self-Selected Versus Actively Engaged Community Members

Participatory processes for obtaining residents' input about community impacts of proposed environmental management actions have long raised concerns about who participates in public involvement efforts and whose interests they represent. This study explored methods of broad-based involvement and the role of deliberation in social impact assessment. Interactive community forums were conducted in 27 communities to solicit public input on proposed alternatives for recovering wild salmon in the Pacific Northwest US. Individuals identified by fellow residents as most active and involved in community affairs ("AE residents") were invited to participate in deliberations about likely social impacts of proposed engineering and ecological actions such as dam removal. Judgments of these AE participants about community impacts were compared with the judgments of residents motivated to attend a forum out of personal interest, who were designated as self-selected ("SS") participants. While the magnitude of impacts rated by SS participants across all communities differed significantly from AE participants' ratings, in-depth analysis of results from two community case studies found that both AE and SS participants identified a large and diverse set of unique impacts, as well as many of the same kinds of impacts. Thus, inclusion of both kinds of residents resulted in a greater range of impacts for consideration in the environmental impact study. The case study results also found that the extent to which similar kinds of impacts are specified by AE and SS group members can differ by type of community. Study results caution against simplistic conclusions drawn from this approach to community-wide public participation. Nonetheless, the results affirm that deliberative methods for community-based impact assessment involving both AE and SS residents can provide a more complete picture of perceived impacts of proposed restoration activities.

Evaluation of Stepping Stones as a tool for changing knowledge, attitudes and behaviours associated with gender, relationships and HIV risk in Karnataka, India

BackgroundStepping Stones training aims to help individuals explore sexual relationships and recognize gender inequalities, the structural drivers of the HIV epidemic, in order to understand risk behaviours and to seek solutions to factors that increase HIV vulnerability. Despite earlier studies suggesting the success of Stepping Stones, little data exist to show diffusion to trainees' social networks or the wider community.MethodsA mixed-methods evaluation of this approach was undertaken using in-depth interviews of trainees and friends, and polling booth surveys in 20 villages where Stepping Stones training took place and in another 20 villages with no Stepping Stones intervention.ResultsThe interview respondents and their friends reported significant changes in their relationships after training, and benefit from discussion of gender, sexuality, condom use and HIV vulnerability issues. However, though diffusion of this knowledge at the level of personal contacts was strong, the evaluation revealed that diffusion to the community level was limited.ConclusionsThe qualitative part of this study reflects other studies in different settings, in that SS participants gained immensely from the training. Wider behaviour change is a challenging goal that many programmes fail to attain, with most interventions too limited in scope and intensity to produce larger community effects. This may have contributed to the fact that we observed few differences between interventions and non-intervention villages in this study. However, it is also possible that we had excessive expectations of individual change at the community level, and that it might have been more appropriate to have had broader community level rather than individual behavioural change indicators. We suggest that SS could be enhanced by efforts to better engage existing community opinion leaders, to empower and train participants as community change agents, and to support the development of village-level action plans that combat sexual stereotyping and risky behaviours that lead to unhealthy sexual relationships.

A Genetically Mediated Bias in Decision Making Driven by Failure of Amygdala Control

Genetic variation at the serotonin transporter-linked polymorphic region (5-HTTLPR) is associated with altered amygdala reactivity and lack of prefrontal regulatory control. Similar regions mediate decision-making biases driven by contextual cues and ambiguity, for example the "framing effect." We hypothesized that individuals hemozygous for the short (s) allele at the 5-HTTLPR would be more susceptible to framing. Participants, selected as homozygous for either the long (la) or s allele, performed a decision-making task where they made choices between receiving an amount of money for certain and taking a gamble. A strong bias was evident toward choosing the certain option when the option was phrased in terms of gains and toward gambling when the decision was phrased in terms of losses (the frame effect). Critically, this bias was significantly greater in the ss group compared with the lala group. In simultaneously acquired functional magnetic resonance imaging data, the ss group showed greater amygdala during choices made in accord, compared with those made counter to the frame, an effect not seen in the lala group. These differences were also mirrored by differences in anterior cingulate-amygdala coupling between the genotype groups during decision making. Specifically, lala participants showed increased coupling during choices made counter to, relative to those made in accord with, the frame, with no such effect evident in ss participants. These data suggest that genetically mediated differences in prefrontal-amygdala interactions underpin interindividual differences in economic decision making.

Randomized Controlled Pilot Study of Cognitive-Behavioral Therapy in a Sample of Incarcerated Women With Substance Use Disorder and PTSD

This randomized controlled pilot study compared a cognitive-behavioral therapy (Seeking Safety; SS) plus treatment-as-usual (TAU) to TAU-alone in 49 incarcerated women with substance use disorder (SUD) and posttraumatic stress disorder (PTSD; full or subthreshold). Seeking Safety consisted of a voluntary group treatment during incarceration and individual treatment after prison release. TAU was required in the prison and comprised 180 to 240 hours of individual and group treatment over 6 to 8 weeks. Assessments occurred at intake, 12 weeks after intake, and 3 and 6 months after release from prison. There were no significant differences between conditions on all key domains (PTSD, SUD, psychopathology, and legal problems); but both conditions showed significant improvements from intake to later time points on all of these outcomes across time. Secondary analyses at follow-up found trends for SS participants improving on clinician-rated PTSD symptoms and TAU participants worsening on self-reported PTSD symptoms. Also, SS demonstrated continued improvement on psychopathology at 3 and 6 months, whereas TAU did not. However, alcohol use improved more for TAU during follow-up. Satisfaction with SS was high, and a greater number of SS sessions was associated with greater improvement on PTSD and drug use. Six months after release from prison, 53% of the women in both conditions reported a remission in PTSD. Study limitations include lack of assessment of SS outcomes at end of group treatment; lack of blind assessment; omission of the SS case management component; and possible contamination between the two conditions. The complex needs of this population are discussed.

Health Care Use and Costs Associated With Use of a Health Club Membership Benefit in Older Adults with Diabetes

OBJECTIVE—The purpose of this study was to determine whether elective use of a health plan–sponsored health club membership had an impact on health care use and costs among older adults with diabetes.RESEARCH DESIGN AND METHODS—Administrative claims for 2,031 older adults with diabetes enrolled in a Medicare Advantage plan were obtained for this retrospective cohort study. Participants (n = 618) in the plan-sponsored health club benefit (Silver Sneakers [SS]) and control subjects (n = 1,413) matched on SS enrollment index date were enrolled in the plan for at least 1 year before the index date. Two-year health care use and costs of SS participants and control subjects were estimated in regressions adjusting for baseline differences.RESULTS—SS participants were more likely to be male, had a lower chronic disease burden, used more preventive services, and had a lower prevalence of arthritis (P ≤ 05). SS participants had lower adjusted total health care costs than control subjects in the first year after enrollment (−$1,633 [95% CI −$2,620 to −$646], P = 0.001), and adjusted total costs in year 2 trended lower (−$1,230 [−$2,494 to $33], P = 0.06). Participants who made on average ≥2 SS visits/week in year 1 had lower total costs in year 2 ($2,141 [−$3,877 to −$405], P = 0.02) than participants who made <2 visits/week.CONCLUSIONS—Use of a health club benefit by older adults with diabetes was associated with slower growth in total health care costs over 2 years; greater use of the benefit was actually associated with declines in total costs.

Fluorescence measurements of the labile iron pool of sickle erythrocytes

AbstractSickle erythrocytes have increased ferritin and increased molecular iron on the inner membrane leaflet, and we postulated that cytosolic labile iron is also elevated. We used the fluorescent metal-losensor, calcein, and a permeant Fe2+ chelator to estimate labile cytoslic Fe2+, and calcein plus an Fe3+ chelator to estimate total cytosolic labile iron (Fe2+ + Fe3+). We measured membrane nonheme iron by its reactivity with ferrozine. As estimated by calcein and Fe2+ chelator, the mean ± SD labile Fe2+ concentration was significantly lower in hemoglobin (Hb) SS (n = 29) than hemoglobin AA (n = 17) erythrocytes (0.56 ± 0.35 μM versus 1.25 ± 0.65 μM; P < .001). In contrast, as estimated by calcein and Fe3+ chelator, total erythrocyte labile iron was similar in hemoglobin SS (n = 12) and hemoglobin AA (n = 10) participants (1.75 ± 0.41 μM versus 2.14 ± 0.93 μM; P = .2). Mean membrane nonheme iron levels were higher in hemoglobin SS cells than hemoglobin AA cells (0.0016 × 10-4 versus 0.0004 × 10-4 fmol/cell; P = .01), but much lower than the mean amounts of total labile iron (1.6-1.8 × 10-4 fmol/cell) or hemoglobin iron (18 000-19 000 × 10-4 fmol/cell). Both membrane iron and total labile iron were much less than the mean amount of iron potentially present in erythrocyte ferritin as calculated from results of other investigators (15 × 10-4 versus 34 × 10-4 fmol/cell in HbAA versus HbSS erythrocytes). We conclude that cytosolic labile iron is not elevated in hemoglobin SS erythrocytes and that elemental membrane iron is present in only trace amounts. (Blood. 2003;102:357-364)