Insomnia symptoms and their correlates among the elderly in geriatric homes in Alexandria,Egypt

The prevalence of sleep complaints increases steadily with age. Studies investigating insomnia among elderly people living in geriatric homes, especially among Egyptians, are scarce. This study aimed to determine the prevalence of insomnia symptoms among the elderly living in geriatric homes in Alexandria and their correlates. A cross-sectional survey of a representative sample of elderly population of geriatric homes in Alexandria was implemented. A total of 177 persons aged 60 years or older participated. Difficulty initiating sleep was reported by 65% of the participants. Approximately half of them had difficulty maintaining their sleep (50.8%) or had non-restful sleep (51.4%). Short sleep was reported by 43.5% of the participants, while early morning awakening was reported by 28.2%. Advanced age (≥75 years) was significantly associated with increased risk for early morning awakening, non-restful sleep and short sleep. Women had approximately a fourfold risk of non-restful sleep as opposed to men. Short stay in geriatric homes (<1 year) was associated with 2.5-fold increased risk of non-restful sleep. Unmarried status was strongly and positively related to difficulty to maintain sleep and non-restful sleep. Depressive status was significantly associated with an increased risk of difficulty to maintain sleep and decreased risk of early morning awakening. Conclusively, the present study showed that insomnia symptoms are highly prevalent among the elderly living in geriatric homes. It also revealed that although age, gender, and other socio-demographic factors are correlated with insomnia symptoms, other factors are highly important. Health care providers should take these factors in consideration when dealing with elderly patients who complain of insomnia.     

Development and Evaluation of an Affordable Real-Time Qualitative Assay for Determining HIV-1 Virological Failure in Plasma and Dried Blood Spots

Virological failure (VF) has been identified as the earliest, most predictive determinant of HIV-1 antiretroviral treatment (ART) failure. Due to the high cost and complexity of virological monitoring, VF assays are rarely performed in resource-limited settings (RLS). Rather, ART failure is determined by clinical monitoring and to a large extent immunological monitoring. This paper describes the development and evaluation of a low-cost, dried blood spot (DBS)-compatible qualitative assay to determine VF, in accordance with current WHO guideline recommendations for therapy switching in RLS. The assay described here is an internally controlled qualitative real-time PCR targeting the conserved long terminal repeat domain of HIV-1. This assay was applied to HIV-1 subtypes A to H and further evaluated on HIV-1 clinical plasma samples from South Africa (n = 191) and Tanzania (n = 42). Field evaluation was performed in Uganda using local clinical plasma samples (n = 176). Furthermore, assay performance was evaluated for DBS. This assay is able to identify VF for all major HIV-1 group M subtypes with equal specificity and has a lower detection limit of 1.00E+03 copies/ml for plasma samples and 5.00E+03 copies/ml for DBS. Comparative testing yielded accurate VF determination for therapy switching in 89% to 96% of samples compared to gold standards. The assay is robust and flexible, allowing for “open platform” applications and producing results comparable to those of commercial assays. Assay design enables application in laboratories that can accommodate real-time PCR equipment, allowing decentralization of testing to some extent. Compatibility with DBS extends access of sampling and thus access to this test to remote settings.     

A longitudinal perspective of hormone replacement therapies (HRTs) on neuromotor capabilities in males with 47,XXY (Klinefelter syndrome)

PurposeThe purpose of this study was to delineate the effects of variable hormone replacement therapies on neuromotor function in a large cohort of males with 47,XXY from birth to adulthood.MethodsA total of 270 participants aged 16 days to 17 years 11 months prenatally diagnosed with 47,XXY were assessed by their pediatric endocrinologist and were administered hormone replacement therapies accordingly. Infants and school-aged children with 47,XXY were administered neuromotor assessments during routine neurodevelopmental evaluations. For statistical analysis, participants were segregated on the basis of treatment status. Two-tailed t tests, 1-way analysis of variance, and post hoc analysis determined significant group differences on each assessment.ResultsIn infants, the early hormonal treatment (EHT) group performed significantly better than the untreated group on fine motor and motor composite domains. In school-aged children, we observed significantly improved scores on fine motor control, coordination, agility, and strength domains among males treated with EHT (or any combination thereof) compared with those who did not receive early treatment.ConclusionThe highest treated combination group was associated with the highest neuromotor function, although the EHT group also often performed better than the other groups. This suggests EHT may be essential in promoting long-term optimal neuromotor outcome in males with an additional X.     

Staining of human sperm with fluorochrome-labeled inhibitor of caspases to detect activated caspases: correlation with apoptosis and sperm parameters

BACKGROUND: Detection of apoptosis in sperm samples may help evaluate sperm quality. Recently, it has been suggested that in some ejaculated sperm populations, apoptosis is caspase dependent. The aim of this study was to investigate the presence of activated caspases and examine possible correlations with apoptosis and sperm parameters in semen samples prepared for IVF. METHODS: To detect activated caspases, neat semen from infertile patients and sperm prepared by PureSperm gradient were stained with the fluorescein isothyocyanate-Val-Ala-Asp-fluoromethylketone (FITC-VAD-fmk) and analysed by flow cytometry. Cell death was determined by DNA fragmentation (TUNEL) and mitochondrial membrane potential. Sperm parameters were studied by conventional microscopy. RESULTS: FITC-VAD-fmk stained sperm cells in situ and the subcellular labeling pattern was compatible with the known localization of caspases. A significant correlation was found between the frequency of FITC-VAD-fmk stained cells and cell death markers. In both prepared sperm and neat semen a negative correlation was found between the percentage of FITC-VAD-fmk positive cells and standard parameters (concentration/motility). FITC-VAD-fmk positive cells negatively correlated with high fertilization rates after IVF. CONCLUSIONS: Labelling of sperm cells with the activated caspases-reacting fluorochrome provides a sensitive assay for detection of sperm apoptosis. This cytometric assay can be helpful to test sperm before IVF.     

Mechanisms of azole resistance in petite mutants of Candida glabrata

We previously showed that resistant colonies of Candida glabrata inside the azole inhibition zones had respiratory deficiency due to mutations in mitochondrial DNA. Here, we analyzed the mechanisms of azole resistance in petite mutants of C. glabrata obtained by exposure to fluconazole or induced by ethidium bromide. The respiratory deficiency of these mutants was confirmed by oxygraphy and flow cytometric analysis with rhodamine 123, and its mitochondrial origin was demonstrated by transmission electron microscopy and restriction endonuclease analysis of the mitochondrial DNA. Flow cytometry with rhodamine 6G suggested an increased drug efflux in mutant cells, which was further supported by Northern blot analysis of the expression of the C. glabrata CDR1 (CgCDR1) and CgCDR2 genes, encoding efflux pumps. Conversely, the expression of CgERG11, which encodes the azole target, was not affected by petite mutations, and no differences were seen in the sequence of this gene between parent isolates and mutants. Moreover, sterol analysis showed similar overall amount of sterols in parent and mutant cells, but quantitative modifications were observed in the mutants, with almost undetectable biosynthesis intermediates. Further analysis performed after separation of free sterols from steryl esters revealed a defect in sterol esterification in mutant cells, with free ergosterol representing 92% of the overall sterol content. Thus, resistance or decreased susceptibility to azoles in petite mutants of C. glabrata is associated with increased expression of CgCDR1 and, to a lesser extent, of CgCDR2. In addition, the marked increase in free ergosterol content would explain their increased susceptibility to polyenes.     

New insights on IgA vasculitis with underlying solid tumor: a nationwide French study of 30 patients

Clinical Rheumatology - IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the...     

IL-34 is a Treg-specific cytokine and mediates transplant tolerance

Cytokines and metabolic pathway–controlling enzymes regulate immune responses and have potential as powerful tools to mediate immune tolerance. Blockade of the interaction between CD40 and CD40L induces long-term cardiac allograft survival in rats through a CD8⁺CD45RC^lo Treg potentiation. Here, we have shown that the cytokine IL-34, the immunoregulatory properties of which have not been previously studied in transplantation or T cell biology, is expressed by rodent CD8⁺CD45RC^lo Tregs and human FOXP3⁺CD45RC^loCD8⁺ and CD4⁺ Tregs. IL-34 was involved in the suppressive function of both CD8⁺ and CD4⁺ Tregs and markedly inhibited alloreactive immune responses. Additionally, in a rat cardiac allograft model, IL-34 potently induced transplant tolerance that was associated with a total inhibition of alloantibody production. Treatment of rats with IL-34 promoted allograft tolerance that was mediated by induction of CD8⁺ and CD4⁺ Tregs. Moreover, these Tregs were capable of serial tolerance induction through modulation of macrophages that migrate early to the graft. Finally, we demonstrated that human macrophages cultured in the presence of IL-34 greatly expanded CD8⁺ and CD4⁺ FOXP3⁺ Tregs, with a superior suppressive potential of antidonor immune responses compared with non–IL-34–expanded Tregs. In conclusion, we reveal that IL-34 serves as a suppressive Treg–specific cytokine and as a tolerogenic cytokine that efficiently inhibits alloreactive immune responses and mediates transplant tolerance.     

Maternal and personal cigarette smoking synergize to increase airflow limitation in adults

Susceptibility of the lungs to cigarette smoke is poorly understood. It is not known whether maternal smoking increases chronic obstructive pulmonary disease (COPD) risk. In 1998 we reported an inverse association between maternal smoking (prerecorded) and FEV(1) in adults. Because FEV(1) and FVC are strongly correlated, it is unclear whether the association in question reflects a link with lung volume, airflow limitation, or both. We extended our original analysis to investigate whether maternal and personal smoking synergize to increase airflow limitation. We estimated residual FEV(1) to express FEV(1) variation that was not associated with FVC. Maternal smoking was inversely associated with FVC and FEV(1) irrespective of personal smoking. It was inversely associated with FEV(1)/FVC, forced midexpiratory flow rates (FEF(25-75) [mean forced expiratory flow during the middle half of the FVC], FEF(25-75)/FVC), and residual FEV(1) in current smokers but not in never or former smokers (heterogeneity p = 0.016, 0.024, 0.021, and 0.016, respectively). We tested the clinical relevance of findings in ever smokers without asthma: 10 cigarettes/day maternal smoking increased prevalent COPD by 1.7 (95% confidence interval: 1.2-2.5) after adjustment for covariates. Maternal smoking impairs lung volume irrespective of personal smoking and appears to synergize with personal smoking to increase airflow limitation and COPD.