Sociodemographic and behavioural correlates of social jetlag in Australian adults: results from the 2016 National Sleep Health Foundation Study.

Social jetlag is a term used to describe misalignment between biological and social time. Measured as the difference in sleep midpoints between work and free days, social jetlag has been associated with unhealthy lifestyle behaviours and adverse health outcomes. This study aimed to identify the prevalence of social jetlag, and its sociodemographic and behavioural correlates in 837 respondents who completed the Sleep Health Foundation Australia 2016 online survey. Binomial logistic regression models determined associations between social jetlag and self-reported lifestyle and work outcomes, excluding night, evening or rotating shift workers. One third (31.1%) of respondents experienced >1h of social jetlag. In analyses adjusted for sociodemographic variables associated with social jetlag (age, marital status, work status and metropolitan living plus the significant interaction term for age by metro living), social jetlag was associated with longer sleep duration on free days (OR = 2.8, CI = 1.9-4.1), evening preference (OR = 2.0, CI = 1.4-2.4), often staying up later than planned on work days (OR 1.9, CI = 1.3-2.9), and having a computer (OR = 1.7, CI = 1.2-2.4) or phone (OR = 1.6, CI = 1.1-2.4) in the bedroom and internet use in the hour before bed (OR = 1.7, CI 1.2-2.5). Almost twice as many working respondents with social jetlag reported going to work when they should have taken sick leave due to their state of health (OR = 1.9, CI = 1.3-3.0). In conclusion, social jetlag is prevalent in the Australian community and associated with bedtime technology use. Work attendance when in poor health is cause for concern in Australian day workers and requires further investigation.

Prevalence and comorbidity of sleep conditions in Australian adults: 2016 Sleep Health Foundation national survey.

OBJECTIVE: To determine the prevalence of sleep conditions (obstructive sleep apnea [OSA], insomnia symptoms, simple snoring, and restless legs) and their associated burden of chronic conditions in a community sample. DESIGN: Cross-sectional national adult online survey. SETTING: Community-based sample. PARTICIPANTS: Australian adults ≥18 years, N = 1011. MEASUREMENTS: A cross-sectional national online survey assessed diagnosed OSA, OSA symptoms, insomnia symptoms, sleep problems, excessive daytime sleepiness (Epworth Sleepiness Scale ≥11), and physician-diagnosed health conditions (heart disease, diabetes, hypertension, reflux disease, lung disease, depression, anxiety/panic disorder, arthritis). Possible undiagnosed OSA was estimated using self-reported frequent loud snoring and witness apneas. International Criteria for Sleep Disorders-3 criteria identified insomnia symptoms. Logistic regression models adjusted for age, sex, obesity, and smoking determined correlates of sleep disorders. RESULTS: Comorbid sleep conditions were common, with 56% of participants demonstrating ≥1 condition. Reporting ≥1 mental health condition (depression and/or anxiety) was independently associated with diagnosed OSA (odds ratio [95% confidence interval {CI}]: 6.6 [3.2-13.6]), undiagnosed OSA (3.2 [1.8-5.8]), simple snoring (2.4 [1.2-4.5]), insomnia symptoms (4.3 [2.5-7.3]), and restless legs (1.9 [1.2-3.1]). Diagnosed OSA was significantly associated with ≥1 cardiometabolic condition (2.9 [1.4-6.0]) and arthritis (3.6 [1.8-7.2]). ESS ≥11 was associated with diagnosed (3.1 [1.4-6.8]) and undiagnosed OSA (6.2 [3.4-11.4]), insomnia symptoms (2.6 [1.4-4.9]), and restless legs (2.3 [1.4-4.0]), and these sleep conditions were also significantly associated with ≥2 diagnosed medical problems. CONCLUSION: Strategies to facilitate the diagnosis and management of often comorbid sleep disorders in primary care are required to reduce the significant sleep-related disparities in cardiometabolic and mental health.

Co-morbid OSA and insomnia increases depression prevalence and severity in men.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) and insomnia coexist in clinical populations but prevalence in the community and risk factors remain largely unknown. We examined the prevalence and profile of previously undiagnosed co-morbid OSA and insomnia symptoms (COMISA) in community-dwelling men. METHODS: Men (n = 700, aged 58.5 ± 11.0 (mean ± SD) years) without a prior diagnosis of OSA completed full at-home unattended polysomnography, the Pittsburgh Sleep Quality Index and 36-item short form (SF-36) survey (2007-2012). Insomnia symptoms included difficulty initiating/maintaining sleep in the presence of daytime fatigue (DIMS-F). Depressive symptoms were assessed using the Beck Depression Inventory-1A, Centre for Epidemiological Studies Depression Scale and Patient Health Questionnaire-9 (PHQ-9) (2007-2010). Univariate (χ2 and analysis of variance (ANOVA)) and multiple linear regressions were used to compare data from four groups of individuals: neither disorder; previously undiagnosed OSA (apnoea-hypopnoea index ≥ 10) or DIMS-F alone; and COMISA. RESULTS: COMISA prevalence was 6.7%. Depression prevalence (COMISA, 42.6%; DIMS-F, 21.6%; OSA, 8.4%, χ2 = 71.6, P < 0.00) and symptom scale scores (e.g. PHQ-9 mean ± SD: 16.1 ± 5.5 c.f. DIMS-F: 14.0 ± 4.9, P < 0.01 and OSA: 11.4 ± 3.0, P = 0.01) were highest in men with COMISA. In COMISA, respiratory and arousal indices were similar to those observed in OSA whilst reductions in subjective sleep and day dysfunction scores were similar to DIMS-F. After adjustment, predicted mean depression scores were all higher in DIMS-F and COMISA using linear regression (e.g. PHQ-9 ß (95% CI): DIMS-F: 2.3 (1.2, 3.5); COMISA: 4.1 (3.0, 5.1)). CONCLUSION: Men with COMISA have a greater prevalence, and severity, of depression than men with only one disorder.

Chronic Kidney Disease and Sleep Apnea Association of Kidney Disease With Obstructive Sleep Apnea in a Population Study of Men.

Study Objectives: To determine the relationship between obstructive sleep apnea (OSA) and chronic kidney disease (CKD). Previous population studies of the association are sparse, conflicting and confined largely to studies of administrative data. Methods: Cross-sectional analysis in unselected participants of the Men Androgens Inflammation Lifestyle Environment and Stress (MAILES) study, aged >40 years. Renal data were available for 812 men without a prior OSA diagnosis who underwent full in-home polysomnography (Embletta X100) in 2010-2011. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 or eGFR≥60 and albuminuria (albumin-creatinine ratio ≥3.0 mg/mmol). Results: CKD (10.5%, n = 85 [Stage 1-3, 9.7%; Stage 4-5, 0.7%]) of predominantly mild severity showed significant associations with OSA (apnea-hypoapnea index [AHI] ≥ 10): odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.02-3.5; severe OSA (AHI ≥ 30/h): OR = 2.6, 95% CI: 1.1-6.2; and respiratory-related arousal index: ≥7.6/h, OR = 2.3, 95%CI: 1.1-4.7; but not measures of hypoxemia after adjustment for age, hypertension, diabetes, smoking, obesity, and NSAID use. There was no association of CKD with daytime sleepiness. In men with CKD, those with OSA were not significantly more likely to report symptoms (sleepiness, snoring, and apneas) or be identified with the STOP OSA screening questionnaire, compared to men without OSA. Conclusions: Predominantly mild CKD is associated with severe OSA and arousals. Further population studies examining the longitudinal relationship between CKD and OSA are warranted. Better methods are needed to identify OSA in CKD which may have few symptoms.

Sleep health of Australian adults in 2016: results of the 2016 Sleep Health Foundation national survey.

OBJECTIVE: To measure the prevalence and social impacts of sleep problems in Australia. DESIGN: Cross-sectional national adult online survey. SETTING: Community-based sample. PARTICIPANTS: Australian adults ≥18 years, n=1011. RESULTS: Self-reported inadequate sleep, of either duration or quality, and its daytime consequences affect 33%-45% of adults. Diagnosed sleep apnea is reported by 8%, significant insomnia by 20%, and restless legs by18% of adults. Besides specific clinical sleep disorders, poor sleep habits were common. Average reported sleep time is 7 hours, although 12% sleep less than 5½hours and 8% over 9 hours. Three-quarters (76%) of those who sleep less than 5½hours report frequent daytime impairment or sleep-related symptoms. Frequent, loud snoring is reported by 24% of men and 17% of women. Among these, 70% report daytime impairment or other sleep-related symptoms. Twenty-six percent report Internet use most or every night just before bed and frequent sleep difficulties or daytime impairments. Similarly, 16% of working adults do work just before bed and also have frequent sleep difficulties or daytime sleep-related symptoms. Younger adults (18-34 years) sleep around 1 hour longer before non-work days than working days compared with 18 minutes in older age groups. In the past 3 months, 29% of adults report making errors at work due to sleepiness or sleep problems. Driving while drowsy at least every month is reported by 29% of people, 20% have nodded off while driving, and 5% have had an accident in the past year because they dozed off. CONCLUSION: Sleep problems and daytime consequences are endemic among Australian adults. A focus on healthy sleep at a policy level as well as increased clinician and public awareness may be warranted.

Associations of Undiagnosed Obstructive Sleep Apnea and Excessive Daytime Sleepiness With Depression: An Australian Population Study.

STUDY OBJECTIVES: To determine whether undiagnosed obstructive sleep apnea (OSA) and/or excessive daytime sleepiness are associated with symptomatic depression in Australian men. METHODS: Participants were randomly selected, urban community dwelling men aged 40 to 88 years without a prior diagnosis of OSA. Clinically significant depressive symptoms were assessed using the Beck Depression Inventory-1A or Centre for Epidemiological Studies Depression Scale (2007-2010). A random sample of men (n = 788) undertook full at-home unattended polysomnography (Embletta X100, Broomfield, Colorado, United States) and completed the Epworth Sleepiness Scale questionnaire (2010-2012). RESULTS: Undiagnosed severe obstructive sleep apnea (apnea-hypopnea index ≥ 30 events/h) was associated with depressive symptoms (adjusted odds ratio = 1.98; 95% confidence interval [CI] 1.05-3.73; P = .036). However, a significant interaction was observed between obstructive sleep apnea and excessive daytime sleepiness (P = .03) such that individuals with OSA and excessive daytime sleepiness (Epworth Sleepiness Scale score of 10 or higher) exhibited the strongest associations with depression (mild-moderate apnea: adjusted odd ratio = 3.86; 95% CI 1.87-7.95; severe apnea: adjusted odd ratio = 4.82; 95% CI 1.42-16.35) when compared to individuals without apnea. CONCLUSIONS: Depressive symptoms in men were associated with undiagnosed OSA in the community. It is important that clinicians and primary care practitioners consider screening for depression in men with severe OSA and for OSA in men with depression. Screening for depression should also be considered in men with excessive daytime sleepiness regardless of OSA severity.

Association of daytime sleepiness with obstructive sleep apnoea and comorbidities varies by sleepiness definition in a population cohort of men.

BACKGROUND AND OBJECTIVE: To determine correlates of excessive daytime sleepiness (EDS) identified with the Epworth Sleepiness Scale (ESS) and a more broad definition, while accounting for obstructive sleep apnoea (OSA) in community dwelling men. METHODS: Participants of the Men Androgens Inflammation Lifestyle Environment and Stress (MAILES) Study (n = 837, ≥ 40 years) without a prior OSA diagnosis, underwent in-home full unattended polysomnography (PSG, Embletta X100), completed the ESS, STOP questionnaire and Pittsburgh Sleep Quality Index in 2010-2011. In 2007-2010, questionnaires and biomedical assessment (in South Australian public hospital-based clinics) identified medical conditions. An alternate EDS definition (EDSAlt ) consisted of ≥ 2 of 3 problems (feeling sleepy sitting quietly; feeling tired/fatigued/sleepy; trouble staying awake). RESULTS: EDSAlt (30.4%, n = 253), but not ESS ≥ 11 (EDSESS , 12.6%, n = 104), increased significantly across OSA severity and body mass index categories. In adjusted analyses, EDSESS was significantly associated with depression: odds ratio (OR), 95%CI: 2.2 (1.3-3.8) and nocturia: 2.0 (1.3-3.2). EDSAlt was associated with depression, financial stress, relationship, work-life balance problems and associations with nocturia and diabetes were borderline. After excluding men with EDSESS , EDSAlt was associated with oxygen desaturation index (3%) ≥ 16 and the highest arousal index quartile but not with comorbidities. CONCLUSION: Sleepiness not necessarily leading to dozing, but not ESS ≥ 11, was related to sleep disordered breathing. Clinicians should be alert to (1) differing perspectives of sleepiness for investigation and treatment of OSA, and (2) the presence of depression and nocturia in men presenting with significant Epworth sleepiness regardless of the presence of OSA.

Hypertension Is Associated With Undiagnosed OSA During Rapid Eye Movement Sleep.

BACKGROUND: Evidence linking OSA with hypertension in population studies is conflicting. We examined longitudinal and cross-sectional associations of previously unrecognized OSA, including OSA occurring in rapid eye movement (REM) sleep, with hypertension. METHODS: The Men Androgens Inflammation Lifestyle Environment and Stress (MAILES) study is a longitudinal study of community-dwelling men in Adelaide, South Australia. Biomedical assessments at baseline (2002-2006) and follow-up (2007-2010) identified hypertension (systolic ≥ 140 mm Hg and/or diastolic ≥ 90 mm Hg, or medication) and risk factors. In 2010 to 2011, 837 men without a prior diagnosis of OSA underwent full in-home unattended polysomnography of whom 739 recorded ≥ 30 min of REM sleep. Hypertension at follow-up (concomitant with OSA status) was defined as prevalent hypertension. Recent-onset hypertension was defined as hypertension at biomedical follow-up (56 months mean follow-up [range, 48-74]) in men free of hypertension at baseline. RESULTS: Severe REM OSA (apnea hypopnea index ≥30/h) showed independent adjusted associations with prevalent (OR, 2.40, 95% CI, 1.42-4.06), and recent-onset hypertension (2.24 [1.04-4.81]). Significant associations with non-REM AHI were not seen. In men with AHI < 10, REM OSA (apnea hypopnea index) ≥ 20/h was significantly associated with prevalent hypertension (2.67 [1.33-5.38]) and the relationship with recent-onset hypertension was positive but not statistically significant (2.32 [0.79-6.84]). Similar results were seen when analyses were confined to men with non-REM AHI < 10. CONCLUSIONS: In men not considered to have OSA (AHI < 10), hypertension was associated with OSA during REM sleep. REM OSA may need consideration as an important clinical entity requiring treatment but further systematic assessment and evidence is needed.

Weight Gain and Its Correlates Among Forensic Inpatients.

OBJECTIVE: We investigated changes in weight, body mass index (BMI), and other indices of the metabolic syndrome in forensic inpatients. Weight gain associated with newer antipsychotics (APs) is well established in the general psychiatric population. METHODS: We examined the medical records of 291 men admitted to a forensic hospital at admission and again at discharge or 365 days later if still in hospital. We also recorded diagnosis and smoker status on admission and quantified psychotropic treatment and adherence, physical activity, and daytime occupation during the hospitalization. RESULTS: On admission, 33% were obese and 22% of the 106 patients for whom sufficient data were available met criteria for metabolic syndrome. Among patients staying at least 30 days, 60% were weighed again before discharge but repeated blood pressure and waist circumference measures were uncommon, even among those at greatest risk. The 122 forensic inpatients with sufficient information gained an average of 12% of their body weight and 40% increased by at least 1 BMI category, gaining an average of 3.67 kg per month. Weight gain was associated with duration of time and was not attributable to being underweight on admission, diagnosis of schizophrenia, atypical AP treatment, medication adherence, or having been a smoker. CONCLUSIONS: Patients gained weight during forensic hospitalization independent of medication use. We recommend further research using consistent measurement and wider sampling of both metabolic syndrome indicators and its individual and systemic causes in forensic populations.

Zinc and zinc transporters in macrophages and their roles in efferocytosis in COPD.

Our previous studies have shown that nutritional zinc restriction exacerbates airway inflammation accompanied by an increase in caspase-3 activation and an accumulation of apoptotic epithelial cells in the bronchioles of the mice. Normally, apoptotic cells are rapidly cleared by macrophage efferocytosis, limiting any secondary necrosis and inflammation. We therefore hypothesized that zinc deficiency is not only pro-apoptotic but also impairs macrophage efferocytosis. Impaired efferocytic clearance of apoptotic epithelial cells by alveolar macrophages occurs in chronic obstructive pulmonary disease (COPD), cigarette-smoking and other lung inflammatory diseases. We now show that zinc is a factor in impaired macrophage efferocytosis in COPD. Concentrations of zinc were significantly reduced in the supernatant of bronchoalveolar lavage fluid of patients with COPD who were current smokers, compared to healthy controls, smokers or COPD patients not actively smoking. Lavage zinc was positively correlated with AM efferocytosis and there was decreased efferocytosis in macrophages depleted of Zn in vitro by treatment with the membrane-permeable zinc chelator TPEN. Organ and cell Zn homeostasis are mediated by two families of membrane ZIP and ZnT proteins. Macrophages of mice null for ZIP1 had significantly lower intracellular zinc and efferocytosis capability, suggesting ZIP1 may play an important role. We investigated further using the human THP-1 derived macrophage cell line, with and without zinc chelation by TPEN to mimic zinc deficiency. There was no change in ZIP1 mRNA levels by TPEN but a significant 3-fold increase in expression of another influx transporter ZIP2, consistent with a role for ZIP2 in maintaining macrophage Zn levels. Both ZIP1 and ZIP2 proteins were localized to the plasma membrane and cytoplasm in normal human lung alveolar macrophages. We propose that zinc homeostasis in macrophages involves the coordinated action of ZIP1 and ZIP2 transporters responding differently to zinc deficiency signals and that these play important roles in macrophage efferocytosis.

Validation of and revision to the VRAG and SORAG: the Violence Risk Appraisal Guide-Revised (VRAG-R).

The violence risk appraisal guide (VRAG) was developed in the early 1990s, and approximately 60 replications around the world have shown its utility for the appraisal of violence risk among correctional and psychiatric populations. At the same time, authorities (e.g., Dawes, Faust, & Meehl, 1989) have argued that tools should be periodically evaluated to see if they need to be revised. In the present study, we evaluated the accuracy of the VRAG in a sample of 1,261 offenders, fewer than half of whom were participants in the development sample, then developed and validated a revised and easier-to-score instrument (the VRAG-R). We examined the accuracy of both instruments over fixed durations of opportunity ranging from 6 months to 49 years and examined outcome measures pertaining to the overall number, severity, and imminence of violent recidivism. Both instruments were found to predict dichotomous violent recidivism overall and at various fixed follow-ups with high levels of predictive accuracy (receiver operating characteristic areas of approximately .75) and to significantly predict other violent outcomes.

BLAST model: an innovative approach to prepare second-degree accelerated BSN students for inpatient psychiatric clinical experiences.

This article describes the design, development, and implementation of an innovative teaching/learning model involving integration of classroom teaching, clinical simulation, and debriefing/critical thinking to prepare accelerated baccalaureate nursing students for clinical practice experiences in the inpatient psychiatric setting. Lessons learned and future directions for simulation experiences involving standardized patient scenarios in undergraduate psychiatric nursing education are shared.

Immunolocalization of NLRP3 Inflammasome in Normal Murine Airway Epithelium and Changes following Induction of Ovalbumin-Induced Airway Inflammation.

Little is known about innate immunity and components of inflammasomes in airway epithelium. This study evaluated immunohistological evidence for NLRP3 inflammasomes in normal and inflamed murine (Balb/c) airway epithelium in a model of ovalbumin (OVA) induced allergic airway inflammation. The airway epithelium of control mice exhibited strong cytoplasmic staining for total caspase-1, ASC, and NLRP3, whereas the OVA mice exhibited strong staining for active caspase-1, with redistribution of caspase-1, IL-1ß and IL-18, indicating possible activation of the NLRP3 inflammasome. Active caspase-1, NLRP3, and other inflammasome components were also detected in tissue eosinophils from OVA mice, and may potentially contribute to IL-1ß and IL-18 production. In whole lung, inRNA expression of NAIP and procaspase-1 was increased in OVA mice, whereas NLRP3, IL-1ß and IL-18 decreased. Some OVA-treated mice also had significantly elevated and tightly correlated serum levels of IL-1ß and TNFα. In cultured normal human bronchial epithelial cells, LPS priming resulted in a significant increase in NLRP3 and II-lp protein expression. This study is the first to demonstrate NLRP3 inflammasome components in normal airway epithelium and changes with inflammation. We propose activation and/or luminal release of the inflammasome is a feature of allergic airway inflammation which may contribute to disease pathogenesis.

Adolescents who have sexually offended: is phallometry valid?

It is unclear whether deviant sexual preferences distinguish adolescents who commit sex offenses in the same way that such deviance characterizes adult sex offenders. We compared male adolescents (mean age = 15 at the time of a referral sex offense), matched adult sex offenders, and normal men (adult nonoffenders or nonsex offenders). We hypothesized the following: phallometric responses of the adolescents would be similar to those of adult sex offenders and would differ from normals; adolescents with male child victims would exhibit greater evidence of sexual deviance than those whose only victims were female children; among adolescents who had molested children, those with a history of sexual abuse would exhibit more evidence of sexual deviance than those with no such history; and phallometric measures would predict recidivism. With some notable exceptions or qualifications, results confirmed the hypotheses. Phallometry has valid clinical and research uses with adolescent males who commit serious sex offenses.

Ultrastructural analysis, zinc transporters, glucose transporters and hormones expression in New world primate (Callithrix jacchus) and human pancreatic islets.

The New world primates (NWP) Callithrix jacchus separated from man approximately 50 million years ago and is a potential alternative small non-human primate model for diabetes research. Ultrastructure, and gene expression of pancreatic islets and the recently described diabetes auto antigenic zinc transporters families in human, NWP and pig pancreas were studied. Morphologically NWP islets were larger than pig islets and similar in size to human islets. NWP islets alpha cells had high dense core surrounded by a limiting membrane, beta cells by the mixed morphology of the granule core, and delta cells by moderate opaque core. Antibody staining for insulin, glucagon, somatostatin and Glucagon-like peptide-1 (GLP-1) showed that the distribution pattern of the different cell types within islets was comparable to pig and human islets. In all three species protein expression of zinc transporter ZnT8 was detected in most of the insulin producing beta cells whereas Zip14 expression was widely expressed in alpha and beta cells. In both human and NWP little or no expression of Glut2 was observed compared to Glut1 and glucokinase at the protein level, however the messenger RNA level of Glut2 was greater than Glut1 and glucokinase. In contrast all three glucose transporters were expressed in pig islets at the protein level. The expression of Zip14 in islets is reported for the first time. In conclusion NWP pancreatic islets express comparable islet cell types and distribution to humans and pigs. Importantly, marmosets have a similar glucose transporter profile to humans, making this non-endangered primate species a useful animal model for pancreatic biology.

Dietary zinc mediates inflammation and protects against wasting and metabolic derangement caused by sustained cigarette smoke exposure in mice.

In mouse asthma models, inflammation can be modulated by zinc (Zn). Given that appetite loss, muscle wasting and poor nutrition are features of chronic obstructive pulmonary disease (COPD) and that poor dietary Zn intake is in itself accompanied by growth retardation and appetite loss, we hypothesised that dietary Zn limitation would not only worsen airway inflammation but also exaggerate metabolic effects of cigarette smoke (CS) exposure in mice. Conversely, Zn supplementation would lessen inflammation. Mice were exposed to CS [2× 2RF, 3×/day; 15 min/cigarette] and fed diets containing 2, 20 or 140 mg/kg Zn ad libitum. Airway cells were collected by bronchoalveolar lavage (BAL). Plasma Zn was measured by fluorometric assay. Inflammatory, metabolic and Zn transport markers were measured by real-time RT-PCR. Mice fed low Zn diets had less plasma labile zinc (0-0.18 µM) than mice fed moderate (0.61-0.98 µM) or high (0.77-1.1 µM) Zn diets (SDs 0.1-0.4, n = 8-10). Smoke exposure increased plasma and BAL labile Zn (1.5-2.5 fold, P < 0.001), bronchoalveolar macrophages (2.0 fold, P < 0.0001) and MT-1 (1.5 fold), MIP-2 (2.3 fold) and MMP-12 (3.5 fold) mRNA. Zn supplementation reduced alveolar macrophage numbers by 62 and 52% in sham and smoke-exposed mice, respectively (Zn effect: P = 0.011). Gastrocnemius, soleus and tibialis anterior muscle mass were affected by both smoke and dietary Zn in the order of 3-7%. The 50-60% reduction in alveolar macrophages in Zn-supplemented mice supports our evolving hypothesis that Zn is an important anti-inflammatory mediator of airway inflammation. Restoring airway Zn levels through dietary supplementation may lessen the severity of lung inflammation when Zn intake is low.

Apical localization of zinc transporter ZnT4 in human airway epithelial cells and its loss in a murine model of allergic airway inflammation.

The apical cytoplasm of airway epithelium (AE) contains abundant labile zinc (Zn) ions that are involved in the protection of AE from oxidants and inhaled noxious substances. A major question is how dietary Zn traffics to this compartment. In rat airways, in vivo selenite autometallographic (Se-AMG)-electron microscopy revealed labile Zn-selenium nanocrystals in structures resembling secretory vesicles in the apical cytoplasm. This observation was consistent with the starry-sky Zinquin fluorescence staining of labile Zn ions confined to the same region. The vesicular Zn transporter ZnT4 was likewise prominent in both the apical and basal parts of the epithelium both in rodent and human AE, although the apical pools were more obvious. Expression of ZnT4 mRNA was unaffected by changes in the extracellular Zn concentration. However, levels increased 3-fold during growth of cells in air liquid interface cultures and decreased sharply in the presence of retinoic acid. When comparing nasal versus bronchial human AE cells, there were significant positive correlations between levels of ZnT4 from the same subject, suggesting that nasal brushings may allow monitoring of airway Zn transporter expression. Finally, there were marked losses of both basally-located ZnT4 protein and labile Zn in the bronchial epithelium of mice with allergic airway inflammation. This study is the first to describe co-localization of zinc vesicles with the specific zinc transporter ZnT4 in airway epithelium and loss of ZnT4 protein in inflamed airways. Direct evidence that ZnT4 regulates Zn levels in the epithelium still needs to be provided. We speculate that ZnT4 is an important regulator of zinc ion accumulation in secretory apical vesicles and that the loss of labile Zn and ZnT4 in airway inflammation contributes to AE vulnerability in diseases such as asthma.

Zinc and zinc transporter regulation in pancreatic islets and the potential role of zinc in islet transplantation.

The critical trace element zinc is essential for normal insulin production, and plays a central role in cellular protection against apoptosis and oxidative stress. The regulation of zinc within the pancreas and ß-cells is controlled by the zinc transporter families ZnT and ZIP. Pancreatic islets display wide variability in the occurrence of these molecules. The zinc transporter, ZnT8 is an important target for autoimmunity in type 1 diabetes. Gene polymorphisms of this transporter confer sensitivity for immunosuppressive drugs used in islet transplantation. Understanding the biology of zinc transport within pancreatic islets will provide insight into the mechanisms of ß-cell death, and may well reveal new pathways for improvement of diabetes therapy, including islet transplantation. This review discusses the possible roles of zinc in ß-cell physiology with a special focus on islet transplantation.

Sexual preferences and recidivism of sex offenders with mental retardation.

By some accounts, sex offenders with mental retardation commit sex offenses against children because the offenders lack sexual knowledge or are socially and intellectually immature rather than because of sexually deviant interests. By other accounts, these offenders exhibit pedophilic sexual interests. In this study, phallometrically determined sexual interests, recidivism, and choices of victims of 69 sex offenders with mental retardation are examined and compared with those of 69 sex offenders of average or higher IQ. Consistent with hypotheses, sex offenders with mental retardation exhibit more deviant preferences for prepubertal children, male children, and young children than do the comparison offenders. They are also more likely to have had a prepubertal victim, a prepubertal male victim, and a very young victim. They are no more likely than the comparison offenders to exhibit preferences for extremely coercive sex with children or to exhibit deviant adult activity preferences, nor are they more likely to recidivate violently. Results support the idea that pedophilia is a disorder of neurodevelopment and point to the importance of risk assessments that include assessing sexual preferences among sex offenders with mental retardation.