Detection of persistent high risk human papillomavirus infections with hybrid capture II and SPF10/LiPA.

BACKGROUND: HPV infection in young women is common. However only a certain number of HPV genotypes are oncogenic. It is necessary for high risk HPV infection to persist at the cervix for a considerable time before oncogenesis occurs. OBJECTIVES: To look for persistence of high risk HPV in women attending a colposcopy clinic. Two DNA detection methods were used and the results compared to determine the rates of persistent, resolved and acquired infections over a 6-month period. HPV genotyping was used to determine type specific persistence. STUDY DESIGN: One hundred and thirty-eight women were tested for HPV infection when attending the colposcopy clinic at UCLH and then tested again at a subsequent visit approximately 6 months later. HPV DNA was detected by the Digene HC II assay using the high risk probes only and by PCR with the SPF10 primer set. All SPF10 PCR-positive samples were then specifically genotyped by a Line Probe Assay (LiPA) [Kleter et al. 1999. J. Clin. Microbiol. 1999;37:2508]. RESULTS: At entry of the study high risk HPV was detected in 43% of the samples by Digene HC II and in 60% of the samples by SPF10/LiPA. Thirty-eight (28%) of the women had a true persistent infection with the same high risk HPV genotype over a median period of 6.3 months. Nine (7%) women resolved one HR HPV infection after their first colposcopy visit, but obtained a different high risk HPV infection by the time they were tested at their second visit as identified by LiPA. Thirty-seven (27%) of the 138 women had mixed HPV infections, representing 45% of all those infected. CONCLUSIONS: The SPF10/LiPA assay detected more high risk infections than the Digene HC II assay. The Digene HC II assay was unable to distinguish between persistent infections with the same high risk genotype and those where the genotype had changed between visits.     

The patients’ perspective: Results of a survey assessing knowledge about and attitudes toward depression in PD

We report results of a survey assessing patients’ knowledge about and attitudes towards depression in Parkinson’s disease (PD). 345 patients from 8 tertiary care centers responded (43% response rate). Overall, patients were relatively knowledgeable about depression and its occurrence in PD. However, many patients believed that depression is a normal reaction to the illness. While many respondents would be reluctant to initiate a discussion of depression during a clinical evaluation, most would feel comfortable talking about depression with their physician if he or she asked them questions about their mood. Based on the results of this survey, we recommend the following approach for physicians: (1) inform PD patients that, although a frequent occurrence, depression need not be accepted as a “normal reaction” to PD; and (2) routinely inquire about depressive symptoms rather than waiting for the patient to spontaneously report them.     

Comparison of the behavior of neural stem cells in the brain of normal and twitcher mice after neonatal transplantation

The twitcher mouse is a model of human Krabbe's disease caused by a mutation in the galacto-cerebrosidase gene. As a result of deficient catabolism of myelin, death of oligodendrocytes and demyelination occur widely in the central and peripheral nervous system, making it an ideal model for investigation of myelin repair strategies. Here we describe the use of mouse neural stem cells (NSCs) expressing enhanced green fluorescence protein (eGFP) for transplantation in neonatal normal and twitcher mice. Normal and twitcher mice in all age groups (20, 30, and 45 days old) showed engraftment and differentiation of injected cells. The engrafted cells were found in the ventricles and a wide range of regions in the brain parenchyma. There was no significant difference in the total number of cells engrafted and the pattern of engraftment between 30-day-old normal and twitcher mice. The average number of engrafted cells in the brain of a 30-day-old mouse was 964 +/- 281 (n = 8). Engrafted cells with the morphology of neurons, astrocytes, and oligodendrocytes were identified. Differentiation into oligodendrocytes was confirmed by immunohistochemical staining using a cell-type-specific marker. There was a higher percentage of cells engrafted in the grey matter than in the white matter (p < 0.01) in both normal and twitcher mouse brain. This study indicates that the environment of demyelination in 30-day-old twitcher mouse brain has not significantly altered the engraftment and distribution patterns of NSCs after neonatal transplantation.     

IL-21 signaling is critical for the development of type I diabetes in the NOD mouse

IL-21 is a pleiotropic type I cytokine that shares the common cytokine receptor γ chain and plays important roles for normal Ig production, terminal B cell differentiation to plasma cells, and Th17 differentiation. IL-21 is elevated in several autoimmune diseases, and blocking its action has attenuated disease in MRL/lpr mice and in collagen-induced arthritis. The diabetes-associated Idd3 locus is at the Il2/Il21 locus, and elevated IL-21 was observed in the nonobese diabetic (NOD) mouse and suggested to contribute to diabetes by augmenting T cell homeostatic proliferation. To determine the role of IL-21 in diabetes, Il21r-knockout (KO) mice were backcrossed to NOD mice. These mice were devoid of lymphocytic infiltration into the pancreas, and only 1 of 20 animals had an elevated glucose compared with 60% of NOD mice on a wild-type (WT) background. Although TCR and Treg-related responses were normal, these mice had reduced Th17 cells and significantly higher levels of mRNAs encoding members of the Reg (regenerating) gene family whose transgenic expression protects against diabetes. Our studies establish a critical role for IL-21 in the development of type I diabetes in the NOD mouse, with obvious potential implications for type I diabetes in humans.     

Genetics of hand grip strength in mid to late life

Hand grip strength (GS) is a predictor of mortality in older adults and is moderately to highly heritable, but no genetic variants have been consistently identified. We aimed to identify single nucleotide polymorphisms (SNPs) associated with GS in middle-aged to older adults using a genome-wide association study (GWAS). GS was measured using handheld dynamometry in community-dwelling men and women aged 55–85 from the Hunter Community Study (HCS, N = 2088) and the Sydney Memory and Ageing Study (Sydney MAS, N = 541). Genotyping was undertaken using Affymetrix microarrays with imputation to HapMap2. Analyses were performed using linear regression. No genome-wide significant results were observed in HCS nor were any of the top signals replicated in Sydney MAS. Gene-based analyses in HCS identified two significant genes (ZNF295, C2CD2), but these results were not replicated in Sydney MAS. One out of eight SNPs previously associated with GS, rs550942, located near the CNTF gene, was significantly associated with GS (p = 0.005) in the HCS cohort only. Study differences may explain the lack of consistent results between the studies, including the smaller sample size of the Sydney MAS cohort. Our modest sample size also had limited power to identify variants of small effect. Our results suggest that similar to various other complex traits, many genetic variants of small effect size may influence GS. Future GWAS using larger samples and consistent measures may prove more fruitful at identifying genetic contributors for GS in middle-aged to older adults.

Electronic supplementary material

The online version of this article (doi:10.1007/s11357-015-9745-5) contains supplementary material, which is available to authorized users.     

Prevalence of obstructive sleep apnoea and periodic limb movement in 45 subjects with heart transplantation.

BACKGROUND: Obesity, a major risk factor for obstructive sleep apnoea, is common after cardiac transplantation. Case reports have shown development of obstructive sleep apnoea in cardiac transplantation recipients. The present study represents the first systematic evaluation of sleep disorders after cardiac transplantation. OBJECTIVE: To determine the prevalence and clinical impact of sleep disorders in a cohort of cardiac transplant recipients. METHODS: This was a cross-sectional study at the Veterans Affairs Medical Center. Forty-five of 60 eligible subjects agreed to take part in the study. Polysomnography, sleep and health survey questionnaires, and laboratory tests were recorded. RESULTS: Thirty-six percent had obstructive sleep apnoea-hypopnoea with an index of 15 or more per hour. The average apnoea-hypopnoea index was about 50+/-27 (SD) per hour. Sleep apnoea resulted in arterial oxyhaemoglobin desaturation, excessive arousals, unrefreshing sleep, excessive daytime sleepiness, poor health-related quality of life, and hypertension (all P values <0.05). Weight gain since transplantation was significantly greater in recipients with obstructive sleep apnoea than those without. Thirty-three percent of patients had periodic limb movement with an index of >?15/hour and an average of 55+/-43/hour. Forty-five percent of these patients had restless legs syndrome. CONCLUSION: Thirty-six percent of cardiac transplant recipients have moderate to severe obstructive sleep apnoea. Sleep apnoea results in disrupted sleep, desaturation and impaired quality of life. Polysomnography should be routinely considered in the ongoing management of most cardiac transplant recipients. Treatment of obstructive sleep apnoea may improve quality of life and other outcomes of cardiac transplantation.