The assessment of the quality of life of adults with intellectual disability: The use of self-report and report of others assessment strategies

Assessment strategies that reliably and validly assess the indicators of quality of life (QOL) of individuals with intellectual disability (ID) are necessary for planning interventions and evaluating outcomes. In the present study, inter-rater reliability and concordance of the two assessment strategies report of others and self-report were evaluated in a group of 176 Italian adults with ID using the Personal Outcomes Scale, which employs the same QOL indicators in the self-report and report of others versions. Report of others resulted a reliable assessment strategy. Clients’ point of view was compared with both the estimation of their point of view and third-party-point-of-view obtained by two independent caregivers for each client. Results indicated that both self-report and report of others assessment strategies are necessary and that estimation of the client's point of view may be a valid and reliable substitute of self-report when clients are not able to answer.     

Plasminogen activator and inhibin in the human testis. An immunohistochemical investigation.

It is generally accepted that Sertoli cells are the main source of active proteins in the human testis, these proteins can act by autocrine and/or paracrine mechanism, modulating both the gametogenic and the endocrine function of the male gonad. As to the Plasminogen Activators (T-PA, U-PA) the immunocytochemical reactivity was detectable in the Sertoli cells and in some Leydig cells. A positivity in spermatocytes and early spermatides appeared to be in relation to the stage of the cycle of the seminiferous epithelium. Inhibin was studied in foetal as well in prepubertal and adult life. The positivity for alpha human and alpha porcine subunits was intense only in the interstitial cells at 12-15 weeks of foetal life. Afterwards the staining was detectable in the Sertoli cells while it decreased in the interstitial cells. In prepubertal life, only the Sertoli cells were stained. In adult life, at the light microscopic level the Sertoli and Leydig cells were positive as well as the spermatocytes. At the electron microscopic level, coated pits and vesicles containing labelled golden particles were shown in both Sertoli cells and spermatocytes, suggesting a paracrine activity of the substance.     

Objective assessment of foot strike in Parkinson's disease*

We assessed the nature of foot strike and the potential effect of acute levodopa dosing in Parkinsonian patients with mild to severe fluctuations of motor performances in comparison with healthy volunteers. Forty-eight patients were enrolled in the study and compared with 33 age and gender matched controls. Each patient was assessed by a computerized electropodographic system before levodopa dosing and 1 and 2-h after intake of a standard fasting morning dose of levodopa plus benserazide. Twelve foot strikes (six right, six left) were analysed per patient. The controls underwent three repeated examinations at 1-h intervals. Patients' motor response to acute levodopa dosing was evaluated at fixed times by a battery of motor tests. Foot strike dynamics differed between patients and controls: in particular, first ground contact of the foot was significantly shifted from heel to forefoot in patients compared to controls. The forward shift in footprint during walking was more marked on the more affected body side but was unrelated to the severity and duration of Parkinsonism and unresponsive to levodopa dosing. Tapping and walking tests were overall responsive to acute levodopa intake. The system seemed suitable to detect irregular patterns of foot strike even at the early stages of Parkinsonism, when lower limb disorder was not clinically overt, and might be useful in the search for clinical markers of Parkinsonian gait.     

Effect of laser irradiation on collagen production by fibroblasts in vitro

The effects of the low power laser irradiation (Space Mix 5 Mid Laser) on the 3H-proline incorporation in the collagenic proteins produced by two lines of normal human fibroblasts in vitro were studied. The 3H-thymidine incorporation in cultures of control and irradiated fibroblasts of the same lines was also evaluated. The obtained results show that in the experimental conditions considered, laser irradiation may have a positive effect on the production of collagen by the fibroblasts in vitro. This effect is dependent on the time of exposure, the frequency of infra-red impulses and the age of subjects from which fibroblasts were obtained. The laser irradiation in the same experimental conditions does not affect the incorporation of 3H-thymidine in the fibroblasts in vitro. Therefore, the observed increase of collagen production is not dependent on an increase of cellular population.     

Ependymomas, malignant tumors of pancreatic islets, and osteosarcomas induced in hamsters by BK virus, a human papovavirus.

BK virus (BKV), a human papovavirus, was inoculated iv into 3-week-old Syrian golden hamsters. Between 2 1/2 and 9 months after inoculation, 82% of the animals developed tumors. The induced neoplasms were ependymoma, carcinoma of the pancreatic islets, osteosarcoma, adenocarcinoma, angiosarcoma, angioma, lymphoma, and seminoma. Hypersecretion of insulin, glucagon, C-peptide, and calcitonin was detected in tumors of pancreatic islets. BKV etiology of tumors was supported by the following evidence: 1) No tumors with BKV-specific markers appeared in animals given injections of buffer, animals inoculated with BKV neutralized by anti-BKV-specific serum, or uninoculated controls; 2) BKV tumor (T) antigen was detected by immunofluorescence and complement fixation tests in tumors of animals inoculated with infectious BKV and in transplanted tumors; 3) antibodies to BKV T-antigen were detected in sera of animals bearing primary or transplanted tumors; 4) BKV could be activated by Sendai virus-mediated fusion of neoplastic cells with susceptible Vero cells; and 5) no endogenous hamster oncornaviruses were found in tumors.     

Associations between end-of-life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment

Alexi A. Wright, MD; Baohui Zhang, MS; Alaka Ray, MD; Jennifer W. Mack, MD, MPH; Elizabeth Trice, MD, PhD; Tracy Balboni, MD, MPH; Susan L. Mitchell, MD; Vicki A. Jackson, MD, MPH; Susan D. Block, MD; Paul K. Maciejewski, PhD; Holly G. Prigerson, PhD

JAMA. 2008;300(14):1665-1673.

Context  Talking about death can be difficult. Without evidence that end-of-life discussions improve patient outcomes, physicians must balance their desire to honor patient autonomy against a concern of inflicting psychological harm.

Objective  To determine whether end-of-life discussions with physicians are associated with fewer aggressive interventions.

Design, Setting, and Participants  A US multisite, prospective, longitudinal cohort study of patients with advanced cancer and their informal caregivers (n = 332dyads), September 2002-February 2008. Patients were followed up from enrollment to death, a median of 4.4 months later. Bereaved caregivers' psychiatric illness and quality of life was assessed a median of 6.5 months later.

Main Outcome Measures  Aggressive medical care (eg, ventilation, resuscitation) and hospice in the final week of life. Secondary outcomes included patients' mental health and caregivers' bereavement adjustment.

Results  One hundred twenty-three of 332 (37.0%) patients reported having end-of-life discussions before baseline. Such discussions were not associated with higher rates of major depressive disorder (8.3% vs 5.8%; adjusted odds ratio [OR], 1.33; 95% confidence interval [CI], 0.54-3.32), or more worry (mean McGill score, 6.5 vs 7.0; P = .19). After propensity-score weighted adjustment, end-of-life discussions were associated with lower rates of ventilation (1.6% vs 11.0%; adjusted OR, 0.26; 95% CI, 0.08-0.83), resuscitation (0.8% vs 6.7%; adjusted OR, 0.16; 95% CI, 0.03-0.80), ICU admission (4.1% vs 12.4%; adjusted OR, 0.35; 95% CI, 0.14-0.90), and earlier hospice enrollment (65.6% vs 44.5%; adjusted OR, 1.65;95% CI, 1.04-2.63). In adjusted analyses, more aggressive medical care was associated with worse patient quality of life (6.4 vs 4.6; F = 3.61, P = .01) and higher risk of major depressive disorder in bereaved caregivers (adjusted OR, 3.37; 95% CI, 1.12-10.13), whereas longer hospice stays were associated with better patient quality of life (mean score, 5.6 vs 6.9; F = 3.70, P = .01). Better patient quality of life was associated with better caregiver quality of life at follow-up (β = .20; P = .001).

Conclusions  End-of-life discussions are associated with less aggressive medical care near death and earlier hospice referrals. Aggressive care is associated with worse patient quality of life and worse bereavement adjustment.

     

Controlling the activation of the Bv8/prokineticin system reduces neuroinflammation and abolishes thermal and tactile hyperalgesia in neuropathic animals

Background and Purpose

Chemokines are involved in neuroinflammation and contribute to chronic pain processing. The new chemokine prokineticin 2 (PROK2) and its receptors (PKR₁ and PKR₂) have a role in inflammatory pain and immunomodulation. In the present study, we investigated the involvement of PROK2 and its receptors in neuropathic pain.

Experimental Approach

Effects of single, intrathecal, perineural and s.c. injections of the PKR antagonist PC1, or of 1 week s.c. treatment, on thermal hyperalgesia and tactile allodynia was evaluated in mice with chronic constriction of the sciatic nerve (CCI). Expression and localization of PROK2 and of its receptors at peripheral and central level was evaluated 10 days after CCI, following treatment for 1 week with saline or PC1. IL-1β and IL-10 levels, along with glia activation, were evaluated.

Key Results

Subcutaneous, intrathecal and perineural PC1 acutely abolished the CCI-induced hyperalgesia and allodynia. At 10 days after CCI, PROK2 and its receptor PKR₂ were up-regulated in nociceptors, in Schwann cells and in activated astrocytes of the spinal cord. Therapeutic treatment with PC1 (s.c., 1 week) alleviated established thermal hyperalgesia and allodynia, reduced the injury-induced overexpression of PROK2, significantly blunted nerve injury-induced microgliosis and astrocyte activation in the spinal cord and restored the physiological levels of proinflammatory and anti-inflammatory cytokines in periphery and in spinal cord.

Conclusion and Implications

The prokineticin system contributes to pain modulation via neuron–glia interaction. Sustained inhibition of the prokineticin system, at peripheral or central levels, blocked both pain symptoms and some events underlying disease progression.Table of Links

Mixture models for calibrating the BED for HIV incidence testing

A number of antibody biomarkers have been developed to distinguish between recent and established Human Immunodeficiency Virus (HIV) infection and used for HIV incidence estimation from cross‐sectional specimens. In general, a cut‐off value is specified, and estimates of the following parameters are needed: (i) the mean time interval (w) between seroconversion and reaching that cut‐off; (ii) the probability of correctly identifying individuals who became infected in the last w years (sensitivity); and (iii) the probability of correctly identifying individuals who have been infected for more than w years (specificity). We develop two statistical methods to study the distribution of a biomarker and derive a formula for estimating HIV incidence from a cross‐sectional survey. Both methods allow handling interval censored data and basically consist of using a generalized mixture model to model the growth of the biomarker as a function of time since infection. The first uses data from all followed‐up individuals and allows incidence estimation in the cohort, whereas the second only uses data from seroconverters. We illustrate our methods using repeated measures of the IgG capture BED enzyme immunoassay. Estimates of calibration parameters, that is, mean window period, mean recency period, sensitivity, and specificities obtained from both models are comparable. The formula derived for incidence estimation gives the maximum likelihood estimate of incidence which, for a given window period, depends only on sensitivity and specificity. The optimal choice of the window period is discussed. Numerical simulations suggest that data from seroconverters can provide reasonable estimates of the calibration parameters. Copyright © 2013 John Wiley & Sons, Ltd.     

Ser46 phosphorylation and prolyl-isomerase Pin1-mediated isomerization of p53 are key events in p53-dependent apoptosis induced by mutant huntingtin

Huntington disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for huntingtin protein. Several mechanisms have been proposed by which mutant huntingtin (mHtt) may trigger striatal neurodegeneration, including mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, mHtt induces DNA damage and activates a stress response. In this context, p53 plays a crucial role in mediating mHtt toxic effects. Here we have dissected the pathway of p53 activation by mHtt in human neuronal cells and in HD mice, with the aim of highlighting critical nodes that may be pharmacologically manipulated for therapeutic intervention. We demonstrate that expression of mHtt causes increased phosphorylation of p53 on Ser46, leading to its interaction with phosphorylation-dependent prolyl isomerase Pin1 and consequent dissociation from the apoptosis inhibitor iASPP, thereby inducing the expression of apoptotic target genes. Inhibition of Ser46 phosphorylation by targeting homeodomain-interacting protein kinase 2 (HIPK2), PKCδ, or ataxia telangiectasia mutated kinase, as well as inhibition of the prolyl isomerase Pin1, prevents mHtt-dependent apoptosis of neuronal cells. These results provide a rationale for the use of small-molecule inhibitors of stress-responsive protein kinases and Pin1 as a potential therapeutic strategy for HD treatment.