Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Spatial neglect and perseveration in visuomotor exploration

OBJECTIVE: Right-brain-damaged patients with left spatial neglect make perseveration errors in target cancellation tasks. A recent study (Ronchi, Posteraro, Fortis, Bricolo, & Vallar, 2009) showed that perseveration occurred more frequently in star than in letter cancellation, possibly due to different stimulus disposition. In this study we investigated the role of the spatial organization of targets (scattered vs. arranged) of the star and letter cancellation tasks in eliciting omission and perseveration errors; the role of impairments of divided attentional resources; and the lesion correlates of perseveration. METHOD: Thirty-three right-brain-damaged patients (27 with neglect, and six without neglect; 17 showing perseveration, 16 of them with spatial neglect) were given two versions of the star and letter cancellation tasks (with stimuli scattered or in rows), and a dual task. RESULTS: A scattered target disposition increased omission and perseveration errors. Target type modulated differently omission and perseveration, with the former being more elicited by verbal targets, and the latter occurring more frequently in the star cancellation task, with scattered stimuli. Perseveration behavior was unrelated to deficits of divided attention, as assessed by the dual task. Lesion analysis indicated damage to the right insula as a neural correlate of perseveration. CONCLUSIONS: A display including nonverbal (star) and scattered targets brings about more perseveration errors. Target type and organization modulate in a different fashion omission and perseveration, suggesting the involvement of independent pathological mechanisms, which, however, do not implicate deficits of divided attention. The role of insular damage in motor perseveration in spatial neglect is discussed

Left neglect dyslexia: Perseveration and reading error types

Right-brain-damaged patients may show a reading disorder termed neglect dyslexia. Patients with left neglect dyslexia omit letters on the left-hand-side (the beginning, when reading left-to-right) part of the letter string, substitute them with other letters, and add letters to the left of the string. The aim of this study was to investigate the pattern of association, if any, between error types in patients with left neglect dyslexia and recurrent perseveration (a productive visuo-motor deficit characterized by addition of marks) in target cancellation. Specifically, we aimed at assessing whether different productive symptoms (relative to the reading and the visuo-motor domains) could be associated in patients with left spatial neglect. Fifty-four right-brain-damaged patients took part in the study: 50 out of the 54 patients showed left spatial neglect, with 27 of them also exhibiting left neglect dyslexia. Neglect dyslexic patients who showed perseveration produced mainly substitution neglect errors in reading. Conversely, omissions were the prevailing reading error pattern in neglect dyslexic patients without perseveration. Addition reading errors were much infrequent. Different functional pathological mechanisms may underlie omission and substitution reading errors committed by right-brain-damaged patients with left neglect dyslexia. One such mechanism, involving the defective stopping of inappropriate responses, may contribute to both recurrent perseveration in target cancellation, and substitution errors in reading. Productive pathological phenomena, together with deficits of spatial attention to events taking place on the left-hand-side of space, shape the manifestations of neglect dyslexia, and, more generally, of spatial neglect. (C) 2016 Elsevier Ltd. All rights reserved

(Un)awareness of unilateral spatial neglect: A quantitative evaluation of performance in visuo-spatial tasks

Right-brain-damaged patients with unilateral spatial neglect are usually unaware (anosognosic) about their spatial deficits. However, in the scientific literature there is a lack of systematic and quantitative evaluation of this kind of unawareness, despite the negative impact of anosognosia on rehabilitation programs. This study investigated anosognosia for neglect-related impairments at different clinical tasks, by means of a quantitative assessment. Patients were tested in two different conditions (before and after execution of each task), in order to evaluate changes in the level of awareness of neglect-related behaviours triggered by task execution. Twenty-nine right-brain-damaged patients (17 with left spatial neglect) and 27 neurologically unimpaired controls entered the study. Anosognosia for spatial deficits is not pervasive, with different tasks evoking different degrees of awareness about neglect symptoms. Indeed, patients showed a largely preserved awareness about their performance in complex visuo-motor spatial and reading tasks; conversely, they were impaired in evaluating their spatial difficulties in line bisection and drawing from memory, showing over-estimation of their performance. The selectivity of the patients' unawareness of specific manifestations of spatial neglect is further supported by their preserved awareness of performance at a linguistic task, and by the absence of anosognosia for hemiplegia. This evidence indicates that discrete processes are involved in the aware monitoring of cognitive and motor performance, which can be selectively compromised by brain damage. Awareness of spatial difficulties is supported by a number of distinct components, and influenced by the specific skills required to perform a given task. (C) 2014 Elsevier Ltd. All rights reserved

A home-based prism adaptation training for neglect patients

Spatial neglect is a debilitating disorder frequently observed after damage to the right cerebral hemisphere. Previous investigations have revealed that prism adaptation (PA) therapy can lead to improvements in neglect-related symptoms. In the typical PA protocol patients repeatedly point toward a visual target while wearing prism goggles. A few years ago, a novel PA procedure, involving a variety of more "ecological" visuo-motor activities during adaptation, less repetitive than a sequence of pointings, was introduced by our research group, and shown to be able to improve neglect-related symptoms to the same extent as the standard pointing task. The ecological procedure was easy to administer and pleasant for the patients. In all previous studies, patients were treated by specialized personnel during hospitalization. In the current study, we investigated the effectiveness of the ecological PA method when performed in a home-based setting, with the help of caregivers and family members. Seven right-brain-damaged patients with chronic left spatial neglect underwent a two-week ecological PA treatment, extended, for two extra weeks, in 6 patients, who were available for this additional rehabilitation session. As a control treatment, patients performed the same activities while wearing neutral goggles, before the PA procedure. Two weeks of ecological PA training proved to be able to significantly improve performance in neuropsychological tests (BIT, Cancellation tasks), a neurological scale (NIH), and functional abilities (CBS), when compared to both the baseline and the neutral control treatment, with improvements being maintained over 6 months. The ecological home-based PA training is effective in alleviating signs of spatial neglect. Importantly, this training is affordable, pleasant, and feasible to be performed in the comfort of the patient's home. Easily extendable to larger patient populations and prolonged periods, this method has a real potential to benefit the quality of life of brain-damaged patients with left spatial neglect

Peritoneal carcinomatosis from advanced ovarian cancer:To treat or not to treat ethical issues suggested by a case study

This article provides a brief description of an Epithelial Ovarian Cancer (EOC) case (stage \u2163) treated with the association of complete CytoReductive Surgery and Hypertermic IntraPEritoneal Chemotherapy (HIPEC). The use of HIPEC in EOC makes theoretic sense in view of the high rates of recurrence following standard treatment, but there are no randomized clinical trial to date and HIPEC for these patients still represents a radical treatment where the choice of no treatment may be acceptable since definitive cure is unlikely. We reviewed the entire decision making process considering the risk/benefit of the procedure in term of mortality/morbidity, the quality of life and the psychological profile of the patient 1 year after surgery. The platform World Health Organization- International Classification of Functioning, Disability and Health that permits evaluation of the person in relation to the psycho-social context is presented. A person-centred approach and assessment of health-related quality-of-life and disability in EOC survivors are of central importance for decision making

Inhibition of vaginal transmission of HIV-1 in hu-SCID mice by the non-nucleoside reverse transcriptase inhibitor TMC120 in a gel formulation

OBJECTIVE: The development of drugs that can be used as topical microbicides is currently recognized as a priority area of research. DESIGN: A preclinical evaluation of the potential effectiveness of TMC120, a non-nucleoside reverse transcriptase inhibitor (NNRTI), as a topical microbicide to prevent vaginal HIV-1 transmission in a humanized severe combined immunodeficient (hu-SCID) mouse model. METHODS: Reconstituted mice received an intravaginal application of a TMC120-containing gel 20 min prior to a non-invasive vaginal challenge with cell-associated HIV. The possible cytotoxic effect of TMC120-containing-gel on lymphocytes was assessed and their in vivo migration was followed using fluorescently labelled human lymphocytes. Systemic infection was monitored by p24 antigen detection in culture supernatant from cocultured intraperitoneal cells using antigen capture enzyme-linked immunosorbent assay test and by the presence of integrated proviral HIV-1 DNA in DNA extracted from spleen cells. In vivo migration of labelled lymphocytes was examined by analysis of cells isolated from regional lymph nodes. RESULTS: In this model, systemic infection was successfully inhibited by the presence of TMC120-containing gel at vaginal level. The in vivo migration of human lymphocytes from the vagina to regional lymph nodes, following the deposition of TMC120-containing gel, excluded the possibility that inhibition of systemic infection was a result of NNRTI toxicity. CONCLUSIONS: Vaginal transmission of HIV was successfully prevented by the application of a gel formulation containing TMC120. This is the first evidence of the in vivo effectiveness of a microbicide preparation containing an NNRTI against cell-associated HIV.status: publishe

The CC genotype of transforming growth factor-β1 increases the risk of late-onset Alzheimer's disease and is associated with AD-related depression

Transforming growth factor-β1 (TGF-β1) is a neurotrophic factor that exerts neuroprotective effects against β-amyloid-induced neurodegeneration. Recently, a specific impairment of the TGF-β1 signaling pathway has been demonstrated in Alzheimer's disease (AD) brain. TGF-β1 is also involved in the pathogenesis of depressive disorders, which may occur in 30-40% of AD patients. The TGF-β1 gene contains single nucleotide polymorphisms (SNPs) at codon +. 10 (T/C) and +. 25 (G/C), which are known to influence the level of expression of TGF-β1.We investigated TGF-β1 +10 (T/C) and +25 (G/C) SNPs and allele frequencies in 131 sporadic AD patients and in 135 healthy age- and sex-matched controls. Genotypes of the TGF-β1 SNPs at codon +10 (T/C) and +25 (G/C) did not differ between AD patients and controls, whereas the allele frequencies of codon +10 polymorphism showed a significant difference (P=0.0306). We also found a different distribution of the +10 (C/C) phenotype (continuity-corrected χ 2 test with one degree of freedom=4.460, P=0.0347) between late onset AD (LOAD) patients and controls (P=0.0126), but not between early onset AD (EOAD) patients and controls. In addition, the presence of the C/C genotype increased the risk of LOAD regardless of the status of apolipoprotein E4 (odds ratio [OR]=2.34; 95% CI=1.19-4.59). Compared to patients bearing the T/T and C/T polymorphisms, LOAD TGF-β1 C/C carriers also showed >5-fold risk to develop depressive symptoms independently of a history of depression (OR=5.50; 95% CI=1.33-22.69). An association was also found between the TGF-β1 C/C genotype and the severity of depressive symptoms (HAM-D 17≥14) (P<0.05). These results suggest that the CC genotype of the TGF-β1 gene increases the risk to develop LOAD and is also associated with depressive symptoms in AD. © 2011 Elsevier B.V. and ECNP