Sexuality Among Adults with Congenital Deafblindness: A Cross-Sectional Survey Study Among Primary Carers

Research investigating the sexuality of individuals with physical or intellectual disabilities is increasing. However, little is known about the sexuality of people with congenital deafblindness (CDB). The aim of the current study was to create a profile of the sexuality of adults with CDB in Denmark. Data was collected from the primary carers of 95 adults with CDB by use of a survey with questions about sexual behavior, the object of sexual behavior, level of sexual frustration, and pedagogical support for sexual satisfaction. The data were analyzed with regard to gender, age, severity of deafblindness, communication, activities of daily living (ADL), cognitive abilities, and carer characteristics. The results revealed that approximately half the number of participants showed sexual behavior while the other half did not. In the majority of cases, sexual behavior was self-stimulation, while, for the rest, sexual behavior was directed toward other people and/or objects. Around one out of ten participants was provided with pedagogical support to help satisfy their sexual needs. Sexual behavior was significantly associated with high scores for communication skills, ADL, and cognitive abilities. Further, high ADL and cognitive abilities were associated with the provision of pedagogical support for sexual satisfaction. Around one out of ten participants, all of whom were men, experienced sexual frustrations. The findings of the current study—the first quantitative study on sexuality among individuals with CDB—are comparable to the findings of studies among individuals with developmental disorders and underline the need for sexuality-related support for individuals with disabilities including those with CDB.

     

A novel knock-in prostate cancer model demonstrates biology similar to that of human prostate cancer and suitable for preclinical studies.

Preclinical studies of prostate cancer (CaP) have employed a genetically engineered mouse model, since there is no naturally occurring CaP in rodents. We have previously reported a new knock-in mouse adenocarcinoma prostate (KIMAP) model. In this study, we demonstrate that the new model possesses a tumor architecture of heterogeneity and multifocality similar to that of human CaP, by utilizing a new compound scoring system to compare with the PSP94 (approved gene symbol Msmb) gene-directed transgenic mouse CaP model (TGMAP). KIMAP mice showed a balanced distribution of tumor extent, which penetrated the prostate gland. Comparative studies on cDNA microarrays demonstrated that KIMAP tumors were upregulated with higher contents of immunoresponse genes, whereas PSP-TGMAP tumors had neuroendocrine (NE) differentiation. The majority of KIMAP mice did not progress to NE CaP, which was observed only at a very late stage and a low frequency. Several tumor marker genes characteristic of human CaP were uniquely identified in KIMAP tumors, including hepsin, maspin, Nkx3.1, CD10 and PSP94 (similar to PSA), etc. The differences between these two CaP models are attributed to the introduction of a single endogenous knock-in mutation. Due to the similarities between human CaP tumors and the PSP-KIMAP tumors, this preclinical model may supplement the current transgenic models to study CaP more accurately.     

U.K. utility weights for the EORTC QLU‐C10D

The EORTC QLU‐C10D is a new multi‐attribute utility instrument derived from the widely used cancer‐specific quality of life questionnaire, EORTC QLQ‐C30. It contains 10 dimensions (physical functioning, role functioning, social functioning, emotional functioning, pain, fatigue, sleep, appetite, nausea, bowel problems), each with four levels. The aim of this study was to provide U.K. general population utility weights for the QLU‐C10D. A U.K. online panel was quota‐sampled to align the sample to the general population proportions of sex and age (≥18 years). The online valuation survey included a discrete choice experiment (DCE). Each participant was asked to complete 16 choice‐pairs, each comprising two QLU‐C10D health states plus duration. DCE data were analysed using conditional logistic regression to generate utility weights. Data from 2,187 respondents who completed at least one choice set were included in the DCE analysis. The final U.K. QLU‐C10D utility weights comprised decrements for each level of each health dimension. For nine of the 10 dimensions (all except appetite), the expected monotonic pattern was observed across levels: Utility decreased as severity increased. For the final model, consistent monotonicity was achieved by merging inconsistent adjacent levels for appetite. The largest utility decrements were associated with physical functioning and pain. The worst possible health state (the worst level of each dimension) is ?0.083, which is considered slightly worse than being dead. The U.K.‐specific utility weights will enable cost–utility analysis (CUA) for the economic evaluation of new oncology therapies and technologies in the United Kingdom, where CUA is commonly used to inform resource allocation.     

Unexpectedly low pulse oximetry measurements associated with variant hemoglobins: a systematic review

Pulse oximetry estimates arterial blood oxygen saturation based on light absorbance of oxy‐ and deoxy‐hemoglobin at 660 and 940 nm wavelengths. Patients with unexpectedly low SpO₂ often undergo cardio‐pulmonary testing to ascertain the cause of their hypoxemia. However, in a subset of patients, a variant hemoglobin is responsible for low SpO₂ measurements. The extent of this problem is unclear. We performed a systematic literature review for reports of low SpO₂ associated with variant hemoglobins. We also reviewed unpublished cases from an academic hemoglobin diagnostic reference laboratory. Twenty‐five publications and four unpublished cases were identified, representing 45 patients with low SpO₂ and confirmed variant hemoglobin. Fifty‐seven family members of patients had confirmed or suspected variant hemoglobin. Three low oxygen affinity variant hemoglobins had concordantly low SpO₂ and SaO₂. Eleven variant hemoglobins were associated with unexpectedly low SpO₂ measurements but normal SaO₂. Hemoglobin light absorbance testing was reported in three cases, all of which showed abnormal absorption spectra between 600 and 900 nm. Seven other variant hemoglobins had decreased SpO₂, with unreported or uncertain SaO₂. Twenty‐one variant hemoglobins were found to be associated with low SpO₂. Most variant hemoglobins were associated with spuriously low SpO₂. Abnormal absorption spectra explain the discrepancy between SpO₂ and SaO₂ for some variants. The differential diagnosis of possible variant hemoglobin ought to be considered in asymptomatic patients found to have unexpectedly low SpO₂. The correct diagnosis will help to spare patients from unnecessary investigations and anxiety. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.     

Examination of Association with Candidate Genes for Diabetic Nephropathy in a Mexican American Population

Background and objectives: Diabetic nephropathy (DN) is a multifactorial complication characterized by persistent proteinuria in susceptible individuals with type 1 and type 2 diabetes. Disease burden in people of Mexican-American descent is particularly high, but there are only a few studies that characterize genes for DN in this ethnic group. Two genes, carnosine dipeptidase 1 (CNDP1) and engulfment and cell motility 1 (ELMO1) previously showed association with DN in other ethnic groups. CNDP1 and ELMO1 were examined along with eight other genes that are less well characterized for DN in a new study of Mexican-Americans.Design, setting, participants, & measurements: The target sample was patients of Mexican-American ancestry collected from three centers: 455 patients with DN and 437 controls with long-term diabetes but no incident nephropathy. Forty-two, 227, and 401 single nucleotide polymorphisms (SNPs) in CNDP1, ELMO1, and the other eight genes, respectively, were examined.Results: No region in CNDP1 or ELMO1 showed significant P values. Of the other eight candidate genes, an association of DN with a SNP pair, rs2146098 and rs6659783, was found in hemicentin 1 (HMCN1) (unadjusted P = 6.1 × 10⁻⁵). Association with a rare haplotype in this region was subsequently identified.Conclusions: The associations in CNDP1 or ELMO1 were not replicable; however, an association of DN with HMCN1 was found. Additional work at this and other loci will enable refinement of the genetic hypotheses regarding DN in the Mexican-American population to find therapies for this debilitating disease.Diabetic nephropathy (DN) is the main cause of ESRD in the United States (1). The disease burden in people of Mexican-American descent is particularly high (1), but there are only a limited number of studies that have characterized genes for DN in this ethnic group. Recently, two genes, carnosine dipeptidase 1 (CNDP1) and engulfment and cell motility 1 (ELMO1), were reported to be associated with DN (2–5). Janssen et al. (4) reported an association between DN and a microsatellite marker, D18S880, in CNDP1 among type 1 and type 2 diabetic patients from four different countries, and Freedman et al. (2) reported its replication among type 2 diabetic Caucasian patients. Shimazaki et al. (5) reported an association in the Japanese population between DN and ELMO1, which includes rs741301 as the most significant single nucleotide polymorphism (SNP).Here, we study ten candidate genes for their association with DN in the Mexican-American population. We attempt to replicate the previous associations of CNDP1 and ELMO1 with a sample size that is similar or greater than previously used (2–5). In addition, we study the following eight genes, which are good biologic candidates but have not been studied extensively: hemicentin 1 (HMCN1), complement factor H (CFH), α-2Heremans-Schmid-glycoprotein (AHSG), caspase 3 (CASP3), heat shock 70-kD protein 1A (HSPA1A), heat shock 27-kD protein 1 (HSPB1), caspase 12 (CASP12), and heme oxygenase (decycling) 1 (HMOX1).HMCN1 was shown to be associated with change in calculated GFR (6), but its role in DN has never been examined. CFH is long known to play a role in atypical hemolytic uremia and membranoproliferative GN, but its involvement in DN has not been evaluated. AHSG is reported to be associated with type 2 diabetes and dyslipidemia, it inhibits insulin-induced tyrosine phosphorylation of insulin receptor substrate-1 (7), and it has been identified as a marker of acute kidney injury (8). Its serum concentration is increased in nondialyzed patients with DN (9) and is low in patients with ESRD (10). High serum levels are associated with insulin resistance (11). HSPB1, also known as HSP27, is involved in the regulation of cell adhesion and invasion (12), regulates actin cytoskeleton turnover, and has anti-apoptotic and antioxidant properties in a wide variety of cells and tissues (13). A mutation in HSPB1 causing a variant of Charcot-Marie-Tooth disease is associated with the development of focal and segmental glomerulosclerosis (14). HMOX1, also known as HO-1, provides antioxidant adaptive functions in response to renal injury (15) and is associated with the degree of renal failure in DN (16). CASP3 and CASP12 mediate apoptotic cell death and were chosen as candidate genes because of their relevance to DN (17,18). Finally, HSPA1A was chosen because of its cellular protectant role in the unfolded protein response (19).Our study aimed to replicate the previous association of the two genes with DN and/or discover new associations at the other eight genes of biologic importance by contrasting the genotype frequencies of SNPs in these ten genes between cases and controls after allowing for relevant covariates.     

Behavioral,Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders

Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders.     

Lack of effect of menthol level and type on smokers’ estimated mouth level exposures to tar and nicotine and perceived sensory characteristics of cigarette smoke

Menthol can reduce sensory irritation and it has been hypothesised that this could result in smokers of mentholated cigarettes taking larger puffs and deeper post-puff inhalations thereby obtaining higher exposures to smoke constituents than smokers of non-mentholated cigarettes. The aim of our study was to use part-filter analysis methodology to assess the effects of cigarette menthol loading on regular and occasional smokers of mentholated cigarettes. We measured mouth level exposure to tar and nicotine and investigated the effects of mentholation on smokers’ sensory perceptions such as cooling and irritation. Test cigarettes were produced containing no menthol and different loadings of synthetic and natural l-menthol at 1 and 4 mg ISO tar yields. A target of 100 smokers of menthol cigarettes and 100 smokers who predominantly smoked non-menthol cigarettes from both 1 and 4 mg ISO tar yield categories were recruited in Poland and Japan. Each subject was required to smoke the test cigarette types of their usual ISO tar yield. There were positive relationships between menthol loading and the perceived ‘strength of menthol taste’ and ‘cooling’ effect. However, we did not see marked menthol-induced reductions in perceived irritation or menthol-induced increases in mouth level exposure to tar and nicotine.     

Face ethnicity and measurement reliability affect face recognition performance in developmental prosopagnosia: evidence from the Cambridge Face Memory Test-Australian

The Cambridge Face Memory Test (CFMT, Duchaine & Nakayama, 2006) provides a validated format for testing novel face learning and has been a crucial instrument in the diagnosis of developmental prosopagnosia. Yet, some individuals who report everyday face recognition symptoms consistent with prosopagnosia, and are impaired on famous face tasks, perform normally on the CFMT. Possible reasons include measurement error, CFMT assessment of memory only at short delays, and a face set whose ethnicity is matched to only some Caucasian groups. We develop the "CFMT-Australian" (CFMT-Aus), which complements the CFMT-original by using ethnicity better matched to a different European subpopulation. Results confirm reliability (.88) and validity (convergent, divergent using cars, inversion effects). We show that face ethnicity within a race has subtle but clear effects on face processing even in normal participants (includes cross-over interaction for face ethnicity by perceiver country of origin in distinctiveness ratings). We show that CFMT-Aus clarifies diagnosis of prosopagnosia in 6 previously ambiguous cases. In 3 cases, this appears due to the better ethnic match to prosopagnosics. We also show that face memory at short (<3-min), 20-min, and 24-hr delays taps overlapping processes in normal participants. There is some suggestion that a form of prosopagnosia may exist that is long delay only and/or reflects failure to benefit from face repetition.