Human cortical responses during one-bit delayed-response tasks: an fMRI study

Neuroimaging study of cognition across aging requires simple tasks ensuring: (i) high rate of correct performances in neurophysiological settings; and (ii) significant modulation of cortical activity. As a preliminary step, the present functional magnetic resonance imaging (fMRI) study tested the hypothesis that very simple delayed-response tasks fit these requirements in normal young adults. The short-term memory (STM) variant included a sequence of cue stimulus (two vertical bars), delay period (blank screen for only 5s), go stimulus, and motor response compatible with the taller vertical bar. Noteworthy, the retention (only one bit) could be based on visuo-spatial, phonological, and somatomotor coding. In the control variant (no STM, NSTM), the cue stimulus was present during the delay period. Results showed high rate of correct performances in both tasks (about 95%). Compared to the NSTM task (delay period), the STM task enhanced cortical responses in bilateral dorsolateral prefrontal (Brodmann area 8-9 (BA 8-9)), lateral premotor (BA 6L), medial premotor (BA 6M), inferior parietal (BA 40), and superior parietal (BA 7) areas. In the STM task, cortical responses were stronger in right than left BA 8-9 and BA 6L. These results indicate that, in normal young adults, a simple STM variant of delayed-response tasks (one bit to be retained) is correctly performed and enhances bilateral fronto-parietal responses. Therefore, it may be used for future cognitive neuroimaging studies on aging.     

Night-time and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients

BACKGROUND: In newly diagnosed apnoeic patients without a history of hypertension, clinical hypertension is underdiagnosed in at least 40% of the cases. An increase in diastolic blood pressure is the most frequent pattern encountered. OBJECTIVE: To assess clinic and 24-h blood pressure, baroreflex sensitivity and left ventricular mass for identifying the prevalence, the type and the consequences of hypertension in newly diagnosed apnoeic patients. PATIENTS AND METHODS: Fifty-nine unselected patients (age = 48 +/- 12 years, body mass index = 28.1 +/- 4.5 kg/m2) referred to a university hospital sleep laboratory for symptoms suggesting obstructive sleep apnoea were included. Diagnosis of apnoea was accepted when respiratory disturbance index was > or = 15/h of sleep. Blood pressure was considered as normal by their general practitioner and all of them were free of any medication for hypertension. Echocardiography, 24-hour ambulatory blood pressure monitoring and assessment of the baroreflex sensitivity were performed. RESULTS: Forty-two percent of the apnoeic patients demonstrated a clinical hypertension, 34 subjects (58%) had a daytime hypertension, and 45 patients (76%) had a night-time hypertension, using 24-h monitoring. All the daytime hypertensives also had night-time hypertension. Forty-seven of the 59 patients (80%) were hypertensive either in the clinic or using 24-h recording. Diastolic and systolo-diastolic hypertension were the prominent types of hypertension observed both by clinic or ambulatory measurements. Respiratory disturbance index was significantly higher in apnoeic patients suffering isolated diastolic hypertension than in the normotensives (50.9 +/- 26.5/h versus 36.0 +/- 12.3/h, respectively; P = 0.02). The prevalence rate of left ventricular hypertrophy was high (between 15 and 20%) and occurred independently of associated hypertension. Baroreflex sensitivity was altered whatever the type of hypertension and decreased with the severity of obstructive sleep apnoea. CONCLUSION: Hypertension is hugely underdiagnosed in apnoeic patients unknown to be hypertensive. Use of 24-h blood pressure monitoring allowed the diagnosis of twice as much hypertension than did clinical measurement. Even at the beginning of their history of hypertension, apnoeic patients exhibited chronic adaptations of their cardiovascular system, as shown by early changes in baroreflex sensitivity and an increased prevalence of left ventricular hypertrophy.     

Analysis of recurrences in 322 Tis, T1, or T2 glottic carcinomas treated by carbon dioxide laser

An endoscopic approach to early glottic carcinoma is considered a sound treatment for both previously untreated lesions and selected recurrent lesions. Between January 1988 and December 2000, we treated 322 patients by CO2 laser at a single institution; 37 had Tis, 191 T1a, 55 T1b, and 39 T2 lesions (mean follow-up, 77 months; range, 6 to 180 months). Kaplan-Meier curves showed a 5-year overall survival rate of 88%, a determinate survival rate of 99%, a disease-free survival rate of 81%, a rate of ultimate local control with laser alone of 91%, and a laryngeal preservation rate of 97%. Univariate and multivariate analysis showed that the only factor that statistically affected endoscopic control was lateral extension of the tumor with involvement of the bottom of the ventricle (hazard risk ratio, 4.0; 95% confidence interval, 1.71 to 9.35). The 58 recurrences were classified according to their location compared with the site of the primary tumor as follows: 14 in the same area (group A), 27 in adjacent subsites with superficial spreading or multifocal distribution (group B), and 17 in adjacent sites by submucosal diffusion to the visceral spaces, cartilaginous framework, or extralaryngeal tissues (group C). For each group, we analyzed the rate of patients who underwent salvage by endoscopic or open neck procedures and the rate of laryngeal preservation. Recurrences in groups A and B were endoscopically treated in 86% and 74% of cases, respectively. By contrast, in group C no patient was endoscopically cured, and there was a low laryngeal preservation rate (47%). The pathways of spread in recurrent carcinoma are therefore the single most important factor in predicting its endoscopic curability.     

Combination of ion beam stabilisation, plasma etching and plasma deposition for the development of tissue engineering micropatterned supports

The performance of biomedical assays at both molecular and cellular level depends greatly on the ability to design new polymer surfaces. Patterns can be created by using materials with contrasted surface properties. In this work we describe in detail the preparation of micropatterned surfaces to be used as tissue engineering supports. Poly(ethylene glycol) (PEG) was used as the 'anti-fouling' polymer in opposition to functional regions covered by acrylic acid (AAc). Since spin-casted PEG films are unstable, ion beam stabilization (IBS) treatment was applied in order to render it insoluble. On the other hand, AAc films were deposited by low-power plasma chemical vapour deposition. Chemical properties of both polymers were monitored by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy while topographic features were followed by atomic force microscopy. Finally, a micropattern was produced by using a mask, which isolated the IBS-PEG from the AAc-deposited regions. Endothelial cells cultured on the surface were observed to follow the micropatterns. In fact, for a certain surface density it was observed that the cells present tensile or compressive stresses when forced to remain in the anti-fouling or the functionalised regions, respectively.     

Effect of oral vitamin D2 yearly bolus on hip fracture risk in elderly women: a community primary prevention study

BACKGROUND AND AIMS: Vitamin D deficiency is a well-known risk for hip fracture, and vitamin D insufficiency is so frequent in the elderly that population-wide preventive intervention would be useful. The objective of the study was to evaluate the efficacy of vitamin D bolus on hip fracture incidence in elderly women. METHODS: All women aged > 65 years registered at Health District 20 of the Regione Veneto, Italy, were eligible for this quasi-experimental, prospective community intervention study. A vial containing 400,000 IU vitamin D2 (Ostelin 800, Teofarma, Italy) was offered for oral administration to all women in the winters of 2000-2001 and 2001-2002. The only exclusion criteria for treatment were age and gender, and the control group included women who did not participate in the Health District initiative. Analysis of hip fracture incidence was carried out for 4 years, from 1999 to 2002. Patients with incident hip fracture were identified as soon as they were admitted to one of the 3 hospitals of the health district and interviewed regarding their participation in the vitamin D preventive intervention program. In 120 of the women (age range 68-90 years), serum concentrations of 25-OH vitamin D were measured from October to June, both before and 1 and 4 months after vitamin D administration. RESULTS: 23,325 and 24,747 women received the vitamin D bolus during winters 2000-2001 and 2001-2002 respectively, i.e. 45-47% of eligible women. The proportion of women who accepted the bolus declined with advancing age, from 50-55% in women aged 60-70 years to 22-26% in those aged > 90 years. The two-year intervention on the community decreased the incidence of fracture by 10% (p = 0.050) in comparison with the previous two years. The age-adjusted risk reduction (RR) of hip fracture during 2001 and 2002 in women who had received vitamin D, with respect to women who had not, decreased by 17% (p = 0.056) and 25% (p = 0.005) respectively. The RR was considerably greater and statistically significant over both 2001 and 2002 in the cohort aged > 75 years. 25-OH vitamin D concentrations, in the subset of women in whom it was measured, rose significantly (p < 0.0001) by 9 ng/ml over 4 months after administration. CONCLUSION: Despite several obvious limitations due to its nature, this study sufficiently documents that yearly vitamin D bolus supplements, given as primary prevention to elderly Caucasian women, may decrease the incidence of hip fracture. For its probable safety and excellent feasibility and cost-effectiveness, this primary intervention has a great potential for generalisability.     

Neurophysiological investigations in restless legs syndrome and other disorders of movement during sleep

Besides polysomnographic techniques, other neurophysiological methods have been utilized in order to understand the pathophysiology of restless legs and periodic limb movement syndromes. By using electromyography with nerve conduction velocity (EMG-CV) and somatosensory evoked potentials (SEPs) it has been possible to determine how frequently each muscle was involved in periodic limb movements, how frequently EMG activity started in a given muscle and the time delay and pattern of activation between the first and the other activated muscles. The etiology of symptoms does not involve structural lesions since brainstem and spinal pathways are intact. Recent evidence from paired transcranial magnetic stimulation suggests that the pathophysiological key in sleep motor disorders is a modified global excitability of corticospinal pathways. The next neurophysiological goal will be to localize the unresolved anatomical level of sleep disorder movement generators and to describe their mechanism.     

Comparison of response to fluvoxamine in nondemented elderly compared to younger patients affected by major depression

Although it is well established that the diagnosis and treatment of depression in the elderly are major health care problems, the relative efficacy of antidepressant treatment in the elderly compared with younger adults has not been definitively established. In this study, we analyzed antidepressant response in 528 nondemented consecutive inpatients affected by a major depressive episode. The sample was divided based on a cut-off of 60 years (< or = 60 n = 354; mean age 46.6 +/- 10.4 years; > 60 n = 174; mean age 66.1 +/- 4.2 years); all the patients were treated with fluvoxamine for at least 6 weeks and they were assessed weekly by using the Hamilton Rating Scale for Depression. Fluvoxamine proved to be effective in our elderly sample, even if antidepressant response was lower in the elderly compared with that of younger subjects (chi2 = 6.27, P = 0.01). Moreover, when compared with younger subjects, the older ones showed significantly slower reduction of depressive symptoms (P = 0.0006). This difference between the 2 age groups was evident since the 2nd week of treatment, and it appeared to be independent of other clinical variables.     

Translating data from animal models into methods for preventing human autoimmune diabetes mellitus: caveat emptor and primum non nocere

Type 1 diabetes in humans is a serious autoimmune disorder of children that is still poorly understood, unpreventable, and irreversible. Study of its animal models, notably the NOD mouse and BB rat, has generated a wealth of information concerning genetics and immunopathogenesis, but that information has still not altered the way in which we treat children with diabetes. In this review we attempt to identify the most promising avenues of continuing research in these models and the most important issues that must be faced by the designers of human therapies based on the animal dataset.     

Intravenous intermittent neridronate in the treatment of postmenopausal osteoporosis

Bisphosphonates have been used with success in the treatment of osteoporosis, but oral therapy often lacks compliance. Here we report the results of clinical trial with aminobisphosphonate neridronate administered intravenously (i.v.). The study included 78 postmenopausal women with spine bone mineral density (BMD) at least -2.5 SD below peak. Patients were randomized to receive for 2 years either 50 mg i.v. neridronate bimonthly and 500 mg calcium plus 400 U vitamin D supplements daily (n=39) or calcium-vitamin D supplements alone (control group, n=39). Treatment was continued over 2 years with an additional 1 year follow-up of calcium-vitamin D supplements alone. Neridronate was well tolerated with the appearance of typical clinical signs of an acute phase reaction in only 3 of the patients after the first infusion. In the control group no significant changes in BMD or bone markers were observed. In the neridronate group BMD rose progressively at the spine rose up to 7.4% +/- 6.1% (SD) and at the femoral neck up to 5.8% +/- 8.2% (SD) at the end of the second year. In the succeeding follow-up these gains were maintained at both skeletal sites. Serum bone alkaline phosphatase (bone ALP) and serum type I collagen C-telopeptide (s-CTX) significantly decreased within 2 months. The bone ALP values reached a -35% plateau after 6 months, while s-CTX attained the lowest mean value (-47%) only by the end of the treatment with neridronate. Both bone markers returned almost to baseline values 1 year after treatment discontinuation. Treatment of postmenopausal osteoporosis with 50 mg i.v. neridronate bimonthly results in clinically relevant increases in BMD, among the largest so far observed with any other bisphosphonate.