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Background and purpose Anterior temporal lobectomy ( ATL) within the language-dominant hemisphere can impair naming. This prospective study examined the pre-operative to post-operative course of different language components, clarifying which changes are relevant within the short-term and long-term outcome of language. Methods Patients with drug-resistant temporal lobe epilepsy ( TLE) were evaluated using the Token, Boston Naming and Word Fluency tests assessing sentence comprehension and word-finding on visual, semantic or phonemic cues. Results A total of 106 patients were evaluated before and 6 months, 1 and 2 years after ATL; 60 patients were also evaluated after 5 years and 38 controls were assessed at baseline. Seizure outcome was comparable between the left and right TLE patients. Before surgery, naming and word fluency were impaired in the left and right TLE patients, whereas sentence comprehension was normal. After left or right ATL, word fluency progressively improved, naming showed early worsening and late improvement after left ATL and progressive improvement after right ATL, and sentence comprehension did not change. At the 5-year follow-up, naming improvement was clinically significant in 31% and 71% of the left and right TLE patients, respectively. Pre-operative naming, ATL laterality, schooling, and post-operative seizure frequency and number of antiepileptic drugs predicted post-operative naming. Pre-operative word fluency and schooling predicted post-operative word fluency. Conclusions Left or right TLE can impair word-finding but not sentence comprehension. After ATL, word-finding may improve for a long time, depending on TLE laterality, seizure control and mental reserve. These findings may clarify prognosis prior to treatment. [ABSTRACT FROM AUTHOR]

Background: Several classes of drugs are effective in prevention and treatment of migraine, although they may differ among each other in their mode of action and in indications. One such class is represented by antiepileptics. Lacosamide is an approved antiepileptic drug that also shows antinociceptive activity in animal models, including analgesic efficacy in central and trigeminal pain. Calcitonin gene-related peptide (CGRP) is considered the main neuro-mediator of trigeminal signalling, playing an essential role in headache, migraine in particular. Here, we investigated the effects of lacosamide on CGRP signalling in both in vitro and ex vivo/vitro models in the rat.Methods: We assessed: (1) CGRP released from brainstem explants at baseline or after pharmacological challenges; and (2) CGRP levels in brain areas after in vivo treatments with test drugs.Results: We found that: (1) lacosamide inhibits CGRP release from brainstem explants under basal conditions as well as after stimulation by 56 mM KCl, 10 μM veratridine or 1 μM capsaicin; and (2) the i.p. administration of nitroglycerine produces an increase in CGRP levels in the brainstem and trigeminal ganglia, which is inhibited by a pre-treatment with lacosamide.Conclusions: These findings provide preliminary evidence suggesting that lacosamide is able to control pain transmission under conditions affecting the trigeminal system, such as migraine. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated that the obesity-related hyposomatropism is usually reversible after a consistent weight loss induced by diet and/or bariatric surgery. Recently, a single bout of respiratory muscle endurance training (RMET) by means of a specific commercially available device (Spiro Tiger ® ) has been reported to induce a marked GH response in obese adults, its GH-releasing effect being significantly lower in obese adolescents. The GH response disappeared in both obese adults and adolescents when RMET was repeated at 2-h intervals inbetween. The aim of the present study was to evaluate GH responses to repeated bouts of RMET administered before and after a 3-week in-hospital multidisciplinary body weight reduction program (entailing energy-restricted diet, 90 min/daily aerobic physical activity, psychological counseling, and nutritional education) combined with a progressively increasing RMET (15 daily sessions, 5 sessions per week) in 7 obese male adolescents [age: 12-17 years; body mass index (BMI): 38.5 ± 3.1 kg/m 2 ; percent fat mass (FM): 37.0 ± 2.0 %]. Blood samplings for GH determinations were collected during the 1 st and 15 th sessions, which were composed of 2 consecutive bouts of RMET (of identical intensity and duration) at 2-h interval in-between. At the beginning of the study, baseline GH levels significantly increased after the first bout of RMET in all subjects (p < 0.05). The administration of the second bout of RMET resulted in a significantly lower (p < 0.05) GH increase in comparison with the first one. Three weeks of the integrated intervention significantly reduced both body weight (from 115.3 ± 9.2 kg to 111.5 ± 8.7 kg, p < 0.05) and FM (from 43.1 ± 5.7 kg to 41.9 ± 5.3 kg, p < 0.05), these combined effects being, however, not sufficient to influence GH responsiveness to the 2 repeated bouts of RMET (GH peaks to the first bout: 4.8 ± 1.6 ng/ml vs. 4.8 ± 1.6 ng/ml; GH peaks to the second bout: 0.9 ± 0.2 ng/ml vs. 1.1 ± 0.1 ng/ ml, before and after 3 weeks of the treatment, respectively, p = NS). In conclusion, a 3-week incremental RMET combined with a body weight reduction intervention does not seem useful to positively influence the reduced GH responsiveness to 2 repeated RMET bouts in obese adolescents. More intensive and/or long-term RMET protocols, associated with energy-restricted diets, determining more consistent changes in body composition, are likely needed to restore the impaired GH-IGF-1 function of obese adolescents. [ABSTRACT FROM AUTHOR]

Repeated bouts of GH-releasing stimuli (both pharmacological and physiological, such as aerobic exercise) at 2-h intervals are associated with a blunting of somatotropic responsiveness in normal adults, while a persistent GH responsiveness to consecutive stimuli is reported to occur in children and adolescents. Recently, a single bout of respiratory muscle endurance training (RMET) by means of a specifi c commercially available device (Spiro Tiger ® ) has been shown to induce relevant GH responses in both normal-weighted and obese adult subjects. The aim of the present study was to evaluate GH responses to repeated bouts of RMET in obese adolescents and adults. Seven obese male adolescents (age: 15.7 ± 0.4 years; body mass index, BMI: 38.0 ± 3.3 kg/m ² ) and 10 obese adults (age: 22.2 ± 1.4 years; BMI: 39.9 ± 1.0 kg/m 2 ) underwent an incremental progressive RMET protocol of 11 daily sessions. Blood samplings for GH determinations were collected during the 12 th session, which was composed of 2 consecutive bouts of RMET (of identical intensity and duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) at a 2-h interval in-between. Baseline GH levels significantly increased after the first bout of RMET in all subjects, higher GH peaks being found in obese adults than in obese adolescents (peaks: 14.3 ± 2.1 ng/ml vs. 4.8 ± 1.6 ng/ml, respectively, p < 0.05). The administration of the second bout of RMET resulted in signifi cantly lower (p < 0.05) GH increases in both obese adolescents and obese adults (peaks: 0.9 ± 0.2 ng/ml and 1.6 ± 0.2 ng/ml, respectively) in comparison with the first one. In conclusion, exercise protocols based on repeated bouts of RMET do not seem a valid strategy to persistently stimulate GH-IGF-1 release in obese adolescents, since GH responses to a single bout are actually modest in comparison with those of obese adults and completely abolished after repeated bouts at 2 h interval in-between. [ABSTRACT FROM AUTHOR]

It is well established that obese patients are hypo-responsive to classical GH-releasing stimuli, including aerobic exercise. Recently, we have demonstrated that whole body vibration was able to markedly stimulate GH secretion in obese patients, thus suggesting that this refractoriness is not absolute but dependent on the GH-releasing stimulus. Furthermore, we have shown the ability of a respiratory muscle endurance training (RMET) to stimulate GH and cortisol secretion in healthy subjects. The objective of this study was to evaluate the effects of RMET on GH and cortisol responses in severely obese patients. Eight severely obese patients (4 M/4 F, mean age ± SEM: 22.8 ± 1.6 years, body mass index, BMI: 39.9 ± 1.1 kg/m 2 ) underwent an incremental progressive RMET protocol of 11 daily sessions, obtained through the use of a specifically designed respiratory device (Spiro Tiger ® ). The 12th session of RMET (15 min duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/ min, 5 min at 34 acts/min, 4 min at 36 acts/min) was associated with blood samplings for determination of GH, cortisol, and lactate (LA) levels. An age- and sex-matched normal-weighted control group (n = 7, 4 M/3 F, age: 26.1 ± 3.1 years, BMI: 22.4 ± 0.6 kg/m 2 ) was also recruited. In both normal-weighted subjects and obese patients, GH secretion significantly increased after a 15-min RMET session. Although serum GH levels at 30 min were higher in normal-weighted subjects than in obese patients, there was no statistically significant difference in either GH peaks or net GH areas under the curve between the 2 groups. RMET significantly increased serum cortisol levels in normal-weighted subjects, but was associated to a progressive cortisol decline in obese patients. RMET stimulated LA production, with no significant differences in normalweighted subjects and in obese patients. A 15-min RMET session was capable to induce a GH response in severely obese patients, which was comparable to that recorded in normalweighted subjects. A progressive decline in serum cortisollevels occurred in obese patients after RMET, while an opposite pattern (i. e., a significant cortisol increase) was found in normalweighted subjects. Optimization of long-term RMET protocols could represent a valid strategy to (physiologically) stimulate GH/IGF-I system in those GH hyposecretory states such as obesity. [ABSTRACT FROM AUTHOR]

Background: Genetic polymorphisms of APO-E, homocysteine, and the IL-1 gene cluster (IL-1A, IL-1B, receptor antagonist IL-1RN) are associated with sporadic Alzheimer's disease and may involve interdependent pathways of neuronal toxicity.Objective: To determine whether these polymorphisms and the genetic determinants of homocysteine (methylenetetrahydrofolate reductase, MTHFR; methionine synthase, MTR; transcobalamin, TC) are associated with an increased risk of severe dementia in Alzheimer's disease.Methods: 152 patients with Alzheimer's disease and 136 controls were studied. The association of occurrence and dementia severity (Reisberg score <6 and >or=6) of Alzheimer's disease with APO-E, IL-1A, IL-1B, IL-1RN, MTHFR677 C-->T and 1298A-->C, MTR 2756 A-->G, and TC 776 C-->G polymorphisms was evaluated by multivariate logistic regression analysis after adjustment for age, sex, and age of onset of Alzheimer's disease.Results: IL-1A TT and IL-1B CT/TT associated genotypes were at risk of Alzheimer's disease (odds ratio 4.80 (95% confidence interval, 1.32 to 17.40), p = 0.017); the MTR 2756 AA genotype was at risk of severe dementia (OR 2.97 (1.23 to 7.21), p = 0.016); IL-1 RN*2 was protective (OR 0.28, (0.11 to 0.69), p = 0.006). Allele epsilon4 of the APO-E and IL-1B CC genotypes increased the risk of severe Alzheimer's disease associated with the MTR 2756 AA genotype by 3.3-fold and 1.5-fold, respectively.Conclusions: Distinct determinants of the IL-1 gene cluster are related to the generation and progression of Alzheimer's disease. MTR only influences progression of the disease, which may be enhanced by carriage of allele epsilon4 of APO-E. [ABSTRACT FROM AUTHOR]

Abstract: A reliable quantification of human DNA is necessary in the process of routine forensic human identification. When DNA is degraded, contaminated or associated with inhibitors, is important to accurately estimate the concentration of extracted DNA prior to perform an analysis based on nuclear markers amplified. In this work, a new approaches to DNA quantification employees the use of a real-time fluorescence probe system. The real-time PCR assay is highly sensitive, specific, rapid, cost-effective and flexible assay for analysis of forensic casework samples, can perform with DNA of poor quality and detect specifically amplifiable DNA rather than total DNA for STR analysis. [Copyright &y& Elsevier]

Abstract: The human sex test in forensic multiplexes is based on the amelogenin gene on both the X and Y chromosomes commonly used in sex genotyping. In this work sex determination across the quantification of nuclear DNA was achieved by real-time PCR of a segment of the X–Y homologous amelogenin (AMG) gene that allowed the simultaneous estimation of a Y- and an X-specific fragment. The AMG real-time PCR design has been used to quantify a set of forensic casework samples. [Copyright &y& Elsevier]

Abstract: Atherosclerosis and osteoporosis appear to be epidemiologically correlated. Most (but not all) animal and clinical studies suggest that osteoprotegerin (OPG) may represent a possible molecular link between bone loss and vascular calcification. The aim of this study was to investigate the association of OPG with bone mineral density (BMD) and vascular plaques, in order to contribute to a better understanding of the link between atherosclerosis and osteoporosis. The study population consisted of 100 consecutive postmenopausal women referred for routine osteoporosis screening. BMD was evaluated by dual-energy X-ray absorptiometry. Presence of carotid or femoral plaques was examined by ultrasonography. OPG was measured by enzyme immunoassay. Seventy-two subjects had low bone mass and were categorized as osteopenic (32) or osteoporotic (40). Fifty-two subjects had one or more atherosclerotic plaques at carotid or femoral level. Both lumbar spine and femoral BMD were associated with the number of plaques (r =−0.5370; p <0.0001, and r =−0.4423; p =0.0012, respectively), however only spine BMD remained significantly associated with the number of plaques after adjustment. OPG serum values showed a significant association with age (r 2 =0.057; p =0.042). The association between OPG and the number of plaques was significant only in patients with concomitant involvement of carotid and femoral districts (r 2 =0.758; p <0.0001). [ABSTRACT FROM AUTHOR]

In this work we have developed and characterized primary cultures of neonatal rat trigeminal ganglia neurones; calcitonin-gene-related-peptide (CGRP) released from cells was taken as a marker of neuronal function. A significant and consistent increase in CGRP secretion was elicited by non-specific (56 mm KCl or veratridine) or specific (capsaicin) depolarizing stimuli. This paradigm was subsequently used to investigate the effects of nociceptin, an opioid-like peptide involved in central and peripheral control of nociception. We found that the nociceptin analogue nociceptin (1–13)NH2 (NOC) did not affect baseline CGRP release, but it reduced in a concentration-dependent manner CGRP release induced by all tested stimuli. NOC-induced reduction was statistically significant from 0.01 nm onward and achieved maximal effects at 10 nm. Such effects of NOC were seemingly mediated by the activation of specific ORL1 receptors, as a well-known nociceptin antagonist, N(Phe1)nociceptin (1–13)NH2, was able to completely revert NOC inhibition of capsaicin-stimulated CGRP release. [ABSTRACT FROM AUTHOR]