A comparison of sex offenders and other types of offenders referred to intellectual disability forensic services

This study compared 131 sex offenders with ID and 346 other types of offenders with ID using case file records. All the females in the study were non sexual offenders. Significantly more sexual offenders were referred from court and criminal justice services while significantly fewer were referred from secondary healthcare. A higher percentage of sex offenders had some form of legal status at time of referral. Greater proportions of non sexual offenders were referred for aggression, damage to property, substance abuse and fire setting while only the sex offenders had an index sex offence. For previous offending, the non sexual offenders had higher rates of aggression, cruelty and neglect of children, property damage and substance abuse while the sexual offenders had higher rates of previous sexual offending. For psychiatric disturbance and adversity in childhood, only ADHD showed a significant difference between groups with the non sexual offenders recording higher rates

Vaginal Microbicide Preferences Among Midwestern Urban Adolescent Women

Purpose The purpose of this study was to assess adolescent women's preferences for specific microbicide characteristics including pregnancy prevention, timing of application, potential for side effects, and whether it targeted human immunodeficiency virus (HIV) or other sexually transmitted infections (STI). Potential differences in microbicide preferences by adolescent age group and behavioral patterns including engaging in sexual intercourse and use of hormonal contraception were examined, as it was hypothesized that as adolescents progress into adulthood and gain sexual experience their preferences in microbicide characteristics may shift. Method Adolescent and young women (N = 405, 56.0% African American; 24.0% Euro-American) between the ages of 14 and 20 (mean = 17.0, SD = 1.8) were recruited from urban community-based clinics. Video-Audio Computer-Assisted Self-Interviews were conducted with the young women, during which they were asked about their preferences regarding the characteristics of hypothetical vaginal microbicides. Conjoint analysis was utilized to determine adolescent women's relative preferences for each microbicide characteristic and intent-to-purchase microbicides based upon a combination of the selected properties. Results Overall, the results suggest adolescent and young women had an ordered preference for a microbicide with (1) no side effects, (2) pregnancy prevention, (3) postcoital application, and (4) protection against HIV. Age and behavioral group conjoint analyses resulted in the same pattern of preferences as those reported for the entire group. However, women having sex and not using hormonal contraception had a stronger preference for postcoital application. Conclusion The findings suggest that young women's ratings of microbicides were sensitive to characteristics such as side effects, pregnancy prevention, and timing of application and should be considered in microbicide development. The conjoint analysis approach is useful in understanding microbicide preferences, and should be utilized with other populations to assess preferences for specific microbicide characteristics

Gender-specific effects of HIV protease inhibitors on body mass in mice

Protease inhibitors, as part of highly active anti-retroviral therapy (HAART), have significantly increased the lifespan of human immunodeficiency virus (HIV) infected patients. Several deleterious side effects including dyslipidemia and lipodystrophy, however, have been observed with HAART. Women are at a higher risk of developing adipose tissue alterations and these alterations have different characteristics as compared to men. We have previously demonstrated that in mice the HIV protease inhibitor, ritonavir, caused a reduction in weight gain in females, but had no effect on male mice. In the present study, we examined the potential causes of this difference in weight gain. Low-density lipoprotein receptor (LDL-R) null mice or wild-type C57BL/6 mice, were administered 15 mug/ml ritonavir or vehicle (0.01% ethanol) in the drinking water for 6 weeks. The percent of total body weight gained during the treatment period was measured and confirmed that female LDL-R gained significantly less weight with ritonavir treatment than males. In wild type mice, however, there was no effect of ritonavir treatment in either sex. Despite the weight loss in LDL-R null mice, ritonavir increased food intake, but no difference was observed in gonadal fat weight. Serum leptin levels were significantly lower in females. Ritonavir further suppressed leptin levels in (p \u3c 0.05). Ritonavir did not alter serum adiponectin levels in either gender. To determine the source of these differences, female mice were ovariectomized remove the gonadal sex hormones. Ovariectomy prevented the weight loss induced by ritonavir (p \u3c 0.05). Furthermore, leptin levels were no longer suppressed by ritonavir (p \u3c 0.05). This study demonstrates that gonadal factors in females influence the hormonal control of weight gain changes induced by HIV protease inhibitors in an environment of elevated cholesterol

Facial coloration tracks changes in women’s estradiol

Red facial coloration is an important social cue in many primate species, including humans. In such species, the vasodilatory effects ofestradiolmay cause red facial coloration to change systematically during females’ ovarian cycle. Although increased red facial coloration during estrus has been observed in female mandrills (Mandrillus sphinx) and rhesus macaques (Macaca mulatta), evidence linking primate facial color changes directly to changes in measured estradiol is lacking. Addressing this issue, we used alongitudinal designto demonstrate that red facial coloration tracks within-subject changes in women's estradiol, but not within-subject changes in women'sprogesteroneor estradiol-to-progesterone ratio. Moreover, the relationship between estradiol and facial redness was observed in two independent samples of women (N=50 andN=65). Our results suggest that changes in facial coloration may provide cues of women's fertility and present the first evidence for a direct link between estradiol and female facial redness in a primate species

Ion atmosphere relaxation controlled electron transfers in cobaltocenium polyether molten salts

A room-temperature redox molten salt for the study of electron transfers in semisolid media, based on combining bis(cyclopentadienyl)cobalt with oligomeric polyether counterions, [Cp2Co](MePEG350SO3), is reported. The transport properties of the new molten salt can be varied (plasticized) by varying the polyether content. The charge transport rate during voltammetric reduction of the ionically conductive [Cp2Co](MePEG350SO3) molten salt exceeds the actual physical diffusivity of [Cp2Co]+ because of rapid [Cp2Co]+/0 electron self-exchanges. The measured [Cp2Co]+/0 electron self-exchange rate constants (kEX) are proportional to the diffusion coefficients (DCION) of the counterions in the melt. The electron-transfer activation barrier energies are also close to those of ionic diffusion but are larger than those derived from optical intervalent charge-transfer results. Additionally, the [Cp2Co]+/0 rate constant results are close to those of dissimilar redox moieties in molten salts where DCION values are similar. All of these characteristics are consistent with the rates of electron transfers of [Cp2Co]+/0 (and the other donor−acceptor pairs) being controlled not by the intrinsic electron-transfer rates but by the rate of relaxation of the ion atmosphere around the reacting pair. In the low driving force regime of mixed-valent concentration gradients, the ion atmosphere relaxation is competitive with electron transfer. The results support the generality of the recently proposed model of ionic atmosphere relaxation control of electron transfers in ionically conductive, semisolid materials

Hybrid Theory: Creation of a Faculty Position That Allows Half-Time Hospice Employment Alongside Academic Palliative Care

BACKGROUND: The specialty of hospice and palliative medicine struggles to merge the fast-paced technological consultative work of acute hospital palliative care with slower paced and home-based hospice. Each has equal if different merits. Here, we describe creation of a position that allowed half-time hospice employment, alongside academic hospital-based palliative care. METHODS: Johns Hopkins Medicine and Gilchrist, Inc., a large nonprofit hospice, partnered to form a joint position with time spent equally between the two locations. RESULTS: Created as a university position with leasing to the hospice, specific attention has been paid to mentoring at both sites to allow professional advancement. Both organizations have benefited in terms of recruitment, and more physicians have chosen this dual pathway suggesting that it is working well. DISCUSSION: Hybrid positions are possible and may be desired by those who wish to practice both palliative medicine and hospice. Creation of one successful position helped recruit a second and a third candidate a year later. The original recipient has been promoted within Gilchrist to direct the inpatient unit. Such positions require careful mentoring and coordination to allow success at both sites and this can be done with foresight

Rescue of the MERTK phagocytic defect in a human iPSC disease model using translational read-through inducing drugs.

Inherited retinal dystrophies are an important cause of blindness, for which currently there are no effective treatments. In order to study this heterogeneous group of diseases, adequate disease models are required in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer a new way to recapitulate patient specific diseases in vitro, providing an almost limitless amount of material to study. We used fibroblast-derived induced pluripotent stem cells to generate retinal pigment epithelium (RPE) from an individual suffering from retinitis pigmentosa associated with biallelic variants in MERTK. MERTK has an essential role in phagocytosis, one of the major functions of the RPE. The MERTK deficiency in this individual results from a nonsense variant and so the MERTK-RPE cells were subsequently treated with two translational readthrough inducing drugs (G418 & PTC124) to investigate potential restoration of expression of the affected gene and production of a full-length protein. The data show that PTC124 was able to reinstate phagocytosis of labeled photoreceptor outer segments at a reduced, but significant level. These findings represent a confirmation of the usefulness of iPSC derived disease specific models in investigating the pathogenesis and screening potential treatments for these rare blinding disorders

Selection of Metastatic Breast Cancer Cells Based on Adaptability of Their Metabolic State

A small subpopulation of highly adaptable breast cancer cells within a vastly heterogeneous population drives cancer metastasis. Here we describe a function-based strategy for selecting rare cancer cells that are highly adaptable and drive malignancy. Although cancer cells are dependent on certain nutrients, e.g., glucose and glutamine, we hypothesized that the adaptable cancer cells that drive malignancy must possess an adaptable metabolic state and that such cells could be identified using a robust selection strategy. As expected, more than 99.99% of cells died upon glutamine withdrawal from the aggressive breast cancer cell line SUM149. The rare cells that survived and proliferated without glutamine were highly adaptable, as judged by additional robust adaptability assays involving prolonged cell culture without glucose or serum. We were successful in isolating rare metabolically plastic glutamine-independent (Gln-ind) variants from several aggressive breast cancer cell lines that we tested. The Gln-ind cells overexpressed cyclooxygenase-2, an indicator of tumor aggressiveness, and they were able to adjust their glutaminase level to suit glutamine availability. The Gln-ind cells were anchorage-independent, resistant to chemotherapeutic drugs doxorubicin and paclitaxel, and resistant to a high concentration of a COX-2 inhibitor celecoxib. The number of cells being able to adapt to non-availability of glutamine increased upon prior selection of cells for resistance to chemotherapy drugs or resistance to celecoxib, further supporting a linkage between cellular adaptability and therapeutic resistance. Gln-ind cells showed indications of oxidative stress, and they produced cadherin11 and vimentin, indicators of mesenchymal phenotype. Gln-ind cells were more tumorigenic and more metastatic in nude mice than the parental cell line as judged by incidence and time of occurrence. As we decreased the number of cancer cells in xenografts, lung metastasis and then primary tumor growth was impaired in mice injected with parental cell line, but not in mice injected with Gln-ind cells

Casein kinase 2-mediated phosphorylation of Brahma-related gene 1 controls myoblast proliferation and contributes to SWI/SNF complex composition

Transcriptional regulation is modulated in part by chromatin-remodeling enzymes that control gene accessibility by altering chromatin compaction or nucleosome positioning. Brahma-related gene 1 (Brg1), a catalytic subunit of the mammalian SWI/SNF chromatin-remodeling enzymes, is required for both myoblast proliferation and differentiation, and the control of Brg1 phosphorylation by calcineurin, PKCbeta1, and p38 regulates the transition to differentiation. However, we hypothesized that Brg1 activity might be regulated by additional kinases. Here, we report that Brg1 is also a target of casein kinase 2 (CK2), a serine/threonine kinase, in proliferating myoblasts. We found that CK2 interacts with Brg1, and mutation of putative phosphorylation sites to non-phosphorylatable (Ser to Ala, SA) or phosphomimetic residues (Ser to Glu, SE) reduced Brg1 phosphorylation by CK2. Although BRG1-deleted myoblasts that ectopically express the SA-Brg1 mutant proliferated similarly to the parental cells or cells ectopically expressing wild-type (WT) Brg1, ectopic expression of the SE-Brg1 mutant reduced proliferation and increased cell death, similar to observations from cells lacking Brg1. Moreover, pharmacological inhibition of CK2 increased myoblast proliferation. Furthermore, the Pax7 promoter, which controls expression of a key transcription factor required for myoblast proliferation, was in an inaccessible chromatin state in the SE-Brg1 mutant, suggesting that hyperphosphorylated Brg1 cannot remodel chromatin. WT-, SA-, and SE-Brg1 exhibited distinct differences in interacting with and affecting expression of the SWI/SNF subunits Baf155 and Baf170 and displayed differential sub-nuclear localization. Our results indicate that CK2-mediated phosphorylation of Brg1 regulates myoblast proliferation and provides insight into one mechanism by which composition of the mammalian SWI/SNF enzyme complex is regulated