Estimating fuzzy measures of deprivation at local level in Tuscany.

In this paper we estimate monetary and non-monetary poverty measures at two sub-regional levels in the region of Tuscany (Italy) using data from the ad-hoc Survey on Vulnerability and Poverty held by Regional Institute from Economic Planning of Tuscany (IRPET). We estimate the percentage of households living in poverty conditions and three supplementary fuzzy measures of poverty regarding deprivation in basic needs and lifestyle, children deprivation, and financial insecurity. The key feature of the survey is that it was carried out after the COVID-19 pandemic, therefore, some of the items collected focus on the subjective perception of poverty eighteen months after the beginning of the pandemic. We assess the quality of these estimates either with initial direct estimates along with their sampling variance, and with a secondary small area estimation when the formers are not sufficiently accurate.

Family ties and child obesity in Italy.

This paper examines the impact of overweight family members on weight outcomes of Italian children aged 6-14 years. We use an original dataset matching the 2012 cross sections of the Italian Multipurpose Household Survey and the Household Budget Survey. Since the identification of within-family peer effects is known to be challenging, we implement our analysis on a partially identified model using inferential procedures recently introduced in the literature and based on standard Bayesian computation methods. We find evidence of a strong, positive effect of both overweight peer children in the family and of overweight adults on children weight outcomes. The impact of overweight peer children in the household is larger than the impact of adults. In particular, the estimated confidence sets associated to the peer children variable is positive with upper bound around one or larger, while the confidence sets for the parameter associated to obese adults often include zero and have upper bound that rarely is larger than one.

Multiple beneficial effects of melanocortin MC4 receptor agonists in experimental neurodegenerative disorders: Therapeutic perspectives.

Melanocortin peptides induce neuroprotection in acute and chronic experimental neurodegenerative conditions. Melanocortins likewise counteract systemic responses to brain injuries. Furthermore, they promote neurogenesis by activating critical signaling pathways. Melanocortin-induced long-lasting improvement in synaptic activity and neurological performance, including learning and memory, sensory-motor orientation and coordinated limb use, has been consistently observed in experimental models of acute and chronic neurodegeneration. Evidence indicates that the neuroprotective and neurogenic effects of melanocortins, as well as the protection against systemic responses to a brain injury, are mediated by brain melanocortin 4 (MC4) receptors, through an involvement of the vagus nerve. Here we discuss the targets and mechanisms underlying the multiple beneficial effects recently observed in animal models of neurodegeneration. We comment on the potential clinical usefulness of melanocortin MC4 receptor agonists as neuroprotective and neuroregenerative agents in ischemic stroke, subarachnoid hemorrhage, traumatic brain injury, spinal cord injury, and Alzheimer's disease.

NDP-α-MSH attenuates heart and liver responses to myocardial reperfusion via the vagus nerve and JAK/ERK/STAT signaling.

Melanocortin peptides afford cardioprotection during myocardial ischemia/reperfusion via janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal transducers/activators of transcription (STAT) pathways. Here we investigated whether melanocortin-induced modulation of the JAK/ERK/STAT signaling occurs via the cholinergic anti-inflammatory pathway, focusing our study on cardiac and hepatic responses to prolonged myocardial ischemia/reperfusion. Ischemia was produced in rats by ligature of the left anterior descending coronary artery for 30min; effects of ischemia/reperfusion were evaluated using Western blot of heart and liver proteins. Intravenous treatment, during coronary artery occlusion, with the melanocortin analog (Nle(4), D-Phe(7))α-melanocyte-stimulating hormone (NDP-α-MSH) induced a left ventricle up-regulation of the cardioprotective transcription factors pJAK2, pERK1/2 and pTyr-STAT3 (JAK-dependent), and a reduction in the levels of the inflammatory mediators tumor necrosis factor-α (TNF-α) and pJNK (a transcription factor also involved in apoptosis), as assessed at the end of the 2-h reperfusion period. Further, these beneficial effects of NDP-α-MSH were associated with heart over-expression of the pro-survival proteins heme oxygenase-1 (HO-1) and Bcl-XL, and decrease of ventricular arrhythmias and infarct size. In the liver NDP-α-MSH induced a decrease in the pJAK2 and pTyr-STAT3 levels, and strongly reduced pERK1/2 expression. In the liver of ischemic rats NDP-α-MSH also blunted pJNK activity and TNF-α expression, and up-regulated Bcl-XL. Bilateral cervical vagotomy prevented all effects of NDP-α-MSH, both in the heart and liver. These results indicate that melanocortins inhibit heart and liver damage triggered by prolonged myocardial ischemia/reperfusion likely, as main mechanism, via the vagus nerve-mediated modulation of the JAK/STAT/ERK signaling pathways.

NDP-α-MSH induces intense neurogenesis and cognitive recovery in Alzheimer transgenic mice through activation of melanocortin MC4 receptors.

Melanocortins exert neuroprotection in a variety of experimental neurodegenerative disorders, including Alzheimer's disease (AD). Further, in previous research we showed that these endogenous peptides stimulate neurogenesis in an acute neurodegenerative disorder such as ischemic stroke. In the present research, we investigated the potential neurogenic effect of melanocortins in AD using APPSwe transgenic mice (Tg2576). To this purpose, 24week-old animals were prepared for 5-bromo-2'-deoxyuridine (BrdU) labeling of proliferating cells on days 1-11 of the study. Treatment of Tg2576 mice with nanomolar doses of the melanocortin analog [Nle(4),D-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH), administered once daily from day 1 to 50, improved brain histology and cognitive functions relative to saline-treated Tg2576 animals. No signs of toxicity were observed. Immunohistochemical examination of the hippocampus at the end of the study (day 50) showed that NDP-α-MSH-treated Tg2576 mice had a greater number of BrdU immunoreactive cells colocalized with NeuN (an indicator of mature neurons) and Zif268 (an indicator of functionally integrated neurons) in the dentate gyrus, relative to saline-treated Tg2576 animals; no newly formed astrocytes were found. Animal pretreatment with the selective melanocortin MC4 receptor antagonist HS024 before each NDP-α-MSH administration prevented all the beneficial effects of the peptide. The present data indicate that MC4 receptor stimulation by a melanocortin prevents cognitive decline in experimental AD, this effect being associated not only with neuroprotection but also with an intense neurogenesis. MC4 receptor agonists could be innovative and safe candidates to counteract AD progression in humans.

Protective effects of the melanocortin analog NDP-α-MSH in rats undergoing cardiac arrest.

We previously reported that melanocortins afford cardioprotection in conditions of experimental myocardial ischemia/reperfusion, with involvement of the janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal transducers and activators of transcription (STAT) signalings. We investigated the influence of the melanocortin analog [Nle(4), D-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH) on short-term detrimental responses to cardiac arrest (CA) induced in rats by intravenous (i.v.) administration of potassium chloride, followed by cardiopulmonary resuscitation (CPR) plus epinephrine treatment. In CA/CPR rats i.v. treated with epinephrine (0.1 mg/kg) and returned to spontaneous circulation (48%) we recorded low values of mean arterial pressure (MAP) and heart rate (HR), alteration of hemogasanalysis parameters, left ventricle low expression of the cardioprotective transcription factors pJAK2 and pTyr-STAT3 (JAK-dependent), increased oxidative stress, up-regulation of the inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and down-regulation of the anti-inflammatory cytokine IL-10, as assessed at 1h and 3h after CPR. On the other hand, i.v. treatment during CPR with epinephrine plus NDP-α-MSH (340 µg/kg) almost completely restored the basal conditions of MAP and HR, reversed metabolic acidosis, induced left ventricle up-regulation of pJAK2, pTyr-STAT3 and IL-10, attenuated oxidative stress, down-regulated TNF-α and IL-6 levels, and improved survival rate by 81%. CA/CPR plus epinephrine alone or in combination with NDP-α-MSH did not affect left ventricle pSer-STAT3 (ERK1/2-dependent) and pERK1/2 levels. These results indicate that melanocortins improve return to spontaneous circulation, reverse metabolic acidosis, and inhibit heart oxidative stress and inflammatory cascade triggered by CA/CPR, likely via activation of the JAK/STAT signaling pathway.

Melanocortins protect against brain damage and counteract cognitive decline in a transgenic mouse model of moderate Alzheimer׳s disease.

We previously reported that melanocortins induce neuroprotection in experimental acute and chronic neurodegenerative conditions, including Alzheimer׳s disease (AD) of mild severity. Here we investigated whether melanocortins afford neuroprotection and counteract cognitive decline in AD with a medium level of severity by using 24 week-old (at the start of the study) APPSwe transgenic mice (Tg2576). Saline-treated (days 1-50) control Tg2576 mice showed an impairment in spatial learning and memory, associated (at day 50, end of the study) with hippocampus at low levels of the synaptic activity-dependent gene Zif268, relevant brain changes such as cerebral cortex/hippocampus increased level of ß-amyloid (Aß) deposit, and neuronal loss, in comparison with wild-type animals. Treatment of Tg2576 mice (once daily at days 1-50) with a nanomolar dose of the melanocortin analog [Nle4,D-Phe7]α-melanocyte-stimulating hormone (NDP-α-MSH) reduced cerebral cortex/hippocampus level of Aß deposit, decreased neuronal loss, increased hippocampus Zif268 expression and improved cognitive functions, relative to saline-treated Tg2576 mice. Pharmacological blockade of melanocortin MC4 receptors with the MC4 receptor antagonist HS024 prevented all favorable effects of NDP-α-MSH. Our data indicate that MC4 receptor-stimulating melanocortins are able to counteract cognitive decline in experimental AD of medium severity through induction of neuroprotection and improvement of synaptic transmission. After further studies, these agents could gain a role as disease modifying therapeutics for AD.

Melanocortins protect against progression of Alzheimer's disease in triple-transgenic mice by targeting multiple pathophysiological pathways.

Besides specific triggering causes, Alzheimer's disease (AD) involves pathophysiological pathways that are common to acute and chronic neurodegenerative disorders. Melanocortins induce neuroprotection in experimental acute neurodegenerative conditions, and low melanocortin levels have been found in occasional studies performed in AD-type dementia patients. Here we investigated the possible neuroprotective role of melanocortins in a chronic neurodegenerative disorder, AD, by using 12-week-old (at the start of the study) triple-transgenic (3xTg-AD) mice harboring human transgenes APPSwe, PS1M146V, and tauP301L. Treatment of 3xTg-AD mice, once daily until the end of the study (30 weeks of age), with the melanocortin analog [Nle(4),D-Phe(7)]-α-melanocyte-stimulating hormone (NDP-α-MSH) reduced cerebral cortex/hippocampus phosphorylation/level of all AD-related biomarkers investigated (mediators of amyloid/tau cascade, oxidative/nitrosative stress, inflammation, apoptosis), decreased neuronal loss, induced over-expression of the synaptic activity-dependent gene Zif268, and improved cognitive functions, relative to saline-treated 3xTg-AD mice. Pharmacological blockade of melanocortin MC4 receptors prevented all neuroprotective effects of NDP-α-MSH. Our study identifies, for the first time, a class of drugs, MC4 receptor-stimulating melanocortins, that are able to counteract the progression of experimental AD by targeting pathophysiological mechanisms up- and down-stream of ß-amyloid and tau. These data could have important clinical implications.

Modulation of the JAK/ERK/STAT signaling in melanocortin-induced inhibition of local and systemic responses to myocardial ischemia/reperfusion.

The janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal transducers and activators of transcription (STAT) pathways have been shown to play a cardioprotective role. We previously gave evidence that melanocortins afford cardioprotection in conditions of myocardial ischemia/reperfusion. Here we aimed to investigate the influence of melanocortins on the JAK/ERK/STAT signaling in cardiac and systemic responses to prolonged myocardial ischemia/reperfusion. Ischemia was produced in rats by ligature of the left anterior descending coronary artery for 30 min. At the end of the 2-h reperfusion, western blot analysis of the cardioprotective transcription factors pJAK2, pERK1/2, pTyr-STAT3 and pSer-STAT3, the inflammatory mediator tumor necrosis factor-α (TNF-α), the pro-apoptotic factors BAX and c-jun N-terminal kinases (pJNK), the anti-apoptotic protein Bcl-XL, as well as of the cardioprotective enzyme heme oxygenase-1 (HO-1), was performed in the left ventricle and spleen. Intravenous treatment, during coronary artery occlusion, with the melanocortin analogs [Nle(4), D-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH) and adrenocorticotropic hormone 1-24 [ACTH-(1-24)], induced a left ventricle up-regulation of pJAK2, pERK1/2 and pTyr-STAT3 (JAK-dependent), and a reduction in pJNK and TNF-α levels; these effects of NDP-α-MSH and ACTH-(1-24) were associated with over-expression of the pro-survival proteins HO-1 and Bcl-XL, and marked decrease of the myocardial infarct size. Melanocortin treatment did not affect left ventricle pSer-STAT3 (ERK1/2-dependent) and BAX levels. In the spleen, NDP-α-MSH and ACTH-(1-24) induced similar effects on the expression of the above transcription factors/proteins, except for pERK1/2 (down-regulated) and HO-1 (unaffected). Blockade of JAK and ERK pathways with AG490 and U0126, respectively, abrogated the myocardial infarct size reduction by NDP-α-MSH. These results indicate that melanocortins inhibit local and systemic inflammatory and apoptotic cascades triggered by prolonged myocardial ischemia/reperfusion, with consequent reduction in myocardium infarct size, seemingly via activation of the JAK/STAT signaling and with modulation of an ERK (STAT unrelated) signaling pathway.

Up-regulation of the canonical Wnt-3A and Sonic hedgehog signaling underlies melanocortin-induced neurogenesis after cerebral ischemia.

In experimental cerebral ischemia, melanocortin MC4 receptor agonists induce neuroprotection and neurogenesis with subsequent long-lasting functional recovery. Here we investigated the molecular mechanisms underlying melanocortin-induced neurogenesis. Gerbils were subjected to transient global cerebral ischemia, then they were treated every 12 h, and until sacrifice, with 5-bromo-2'-deoxyuridine (BrdU; to label proliferating cells), and the melanocortin analog [Nle(4),d-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH) or saline. NDP-α-MSH increased hippocampus dentate gyrus (DG) expression of Wnt-3A, ß-catenin, Sonic hedgehog (Shh), Zif268, interleukin-10 (IL-10) and doublecortin (DCX), as detected at days 3, 6 and 10 after the ischemic insult. Further, an elevated number of BrdU immunoreactive cells was found at days 3 and 10, and an improved histological picture with reduced neuronal loss at day 10, associated with learning and memory recovery. Pharmacological blockade of the Wnt-3A/ß-catenin and Shh pathways, as well as of melanocortin MC4 receptors, prevented all effects of NDP-α-MSH. These data indicate that, in experimental brain ischemia, treatment with melanocortins acting at MC4 receptors induces neural stem/progenitor cell proliferation in the DG by promptly and effectively triggering the canonical Wnt-3A/ß-catenin and Shh signaling pathways. Activation of these pathways is associated with up-regulation of the repair factor Zif268 and the neurogenesis facilitating factor IL-10, and it seems to address mainly toward a neuronal fate, as indicated by the increase in DCX positive cells.

Adolescent idiopathic scoliosis and eating disorders: is there a relation? Results of a cross-sectional study.

UNLABELLED: A recent study suggests a correlation between idiopathic scoliosis in adolescence and eating disorders. However, this does not correspond with our clinical experience in the same population. The aim of this study was to verify the correlation between scoliosis and eating disorders in adolescence. A cross-sectional study was designed including 187 consecutive adolescent girls with a diagnosis of idiopathic scoliosis (mean Cobb angle 26°, range 11-73°, age 15.2±2.5; 24% juveniles, 76% adolescent type) and 93 schoolgirls as controls (age 14.9±1.0). All of the participants answered the Italian validated questionnaire EAT-26 about eating habits in order to identify any eating disorders. Body mass index (BMI) was calculated for all participants and compared to reference data. STATISTICAL ANALYSIS: chi-square test, Student's t-test, Pearson's correlation coefficient. Only 3 (1.6%; 95% CI -0.2-3.4%) participants in the scoliosis group showed EAT-26 scores suggestive for eating disorders versus 7 (7.5%; 95% CI 2.2-12.9%) in the school population (p<0.05). The BMI was slightly lower (p<0.05) for scoliosis patients (19±0.2) than for school girls (21±0.3). EAT-26 is recognized among the most valid questionnaires for eating disorders and has been widely applied in various countries. By applying this questionnaire, a lower incidence of eating disorders in female scoliosis patients was found than in the general population (using both our own controls and Italian reference values). This contrasts with some expert opinions and a recent study performed in Italy. The low BMI already reported in the literature as being typical of scoliosis participants is confirmed by our data.

Clinical pharmacology of topiramate in migraine prevention.

INTRODUCTION: Migraine is a widespread disorder. Migraine patients experience worse health-related quality of life than the general population. The availability of effective and tolerable treatments for this disorder is an important medical need. This narrative review focuses on the clinical pharmacology of topiramate, an antiepileptic drug that was approved for the prophylaxis of migraine where it should act as a neuromodulator. AREAS COVERED: A PubMed database search (from 2000 to 24 January 2011) and a review of the human studies published on topiramate and migraine was conducted. EXPERT OPINION: Topiramate is an important option for the prophylaxis of migraine and is of proven efficacy and tolerability. It has also been studied in chronic migraine with encouraging results, even in patients with medication overuse. However, in migraine prevention its efficacy is comparable to the other first-line drugs and there are no published trials with a superiority design which can establish topiramate's role in the available therapeutic armamentarium.

Why pharmacokinetic differences among oral triptans have little clinical importance: a comment.

Triptans, selective 5-HT1B/1D receptor agonists, are specific drugs for the acute treatment of migraine that have the same mechanism of action. Here, it is discussed why the differences among kinetic parameters of oral triptans have proved not to be very important in clinical practice. There are three main reasons: (1) the differences among the kinetic parameters of oral triptans are smaller than what appears from their average values; (2) there is a large inter-subject, gender-dependent, and intra-subject (outside/during the attack) variability of kinetic parameters related to the rate and extent of absorption, i.e., those which are considered as critical for the response; (3) no dose-concentration-response curves have been defined and it is, therefore, impossible both to compare the kinetics of triptans, and to verify the objective importance of kinetic differences; (4) the importance of kinetic differences is outweighed by non-kinetic factors of variability of response to triptans. If no oral formulations are found that can allow more predictable pharmacokinetics, the same problems will probably also arise with new classes of drugs for the acute treatment of migraine.

Remote cerebellar haematoma after lumbar disc surgery. Case report.

Remote cerebellar haematoma (RCH) from the operative site is one of the most serious, although extremely rare, complications of spinal surgery. Dural opening is common to every reported case of a spinal procedure complicated by cerebellar hemorrhage, supporting the hypothesis that CSF loss is central to the pathogenesis of this condition. We report our experience with the case of cerebellar haematoma after lumbar disc surgery and the literature is reviewed.

Development and validation of the ABC pain scale for healthy full-term babies.

AIM: We developed and validated a pain scale (ABC scale) for term babies based on acoustic features of crying. METHODS: The scale consisted of three different cry parameters: (a) pitch of the first cry; (b) rhythmicity of the crying bout; (c) constancy of crying intensity. These parameters were previously found to distinguish between medium and high levels of pain measured by spectral analysis of crying. We validated the scale using healthy term babies undergoing routine heel prick. Concurrent validity was assessed comparing pain values obtained with our scale with those obtained with another pain scale; this relationship was also used to assess the sensitivity of the scale. To assess specificity we compared the ABC scores during a painful event (heel prick) with two non-painful events (preliminary phase of prick in the same group of babies, and heel prick with analgesia in another group). RESULTS: Specificity: (a) analgesic/non-analgesic comparison, p < 0.0001; (b) pain/sham comparison, p < 0.0001). Sensitivity: a high correlation between scores of the ABC scale and the Douleur Aigue du Nouveau-Né scale indicates good sensitivity. Concurrent validity: Spearman rho = 0.91. Internal consistency: Cronbach's alpha = 0.76. Inter-rater reliability: Cohen's kappa for multiple raters = 0.83. Intra-rater reliability: Cohen's kappa = 0.85. Practicality: All nurses who used it scored the scale as "good". CONCLUSION: The ABC scale proved to be simple and reliable for assessing pain in healthy, non-intubated term newborns.

The in vitro elution characteristics of vancomycin combined with imipenem-cilastatin in acrylic bone-cements: a pharmacokinetic study.

The aim of this in vitro study was to compare the elution characteristics of vancomycin alone and in combination with imipenem-cilastatin from 3 acrylic bone-cements (CMW1 [DePuy International, Blackpool, UK], Palacos R [Schering-Plough, Wehrheim, Germany], and Simplex P [Howmedica International, London, UK]). Six groups of 3 antibiotic-loaded cement disks were prepared, incorporating 2 g of vancomycin (3 groups) and 2 g of vancomycin plus 2 g of imipenem-cilastatin (3 groups). The disks were placed in saline baths for 5 weeks, with the baths being sampled periodically and the elution rates calculated. The total amount of vancomycin released by the cements treated with vancomycin alone was 7.98 mg for CMW1, 7.74 mg for Palacos R, and 6.76 mg for Simplex P; with the addition of imipenem-cilastatin, the total amount of vancomycin released by the 3 cements increased by 30.58%, 50.52%, and 50.15%. CMW1 had better elution characteristics than the other cements when treated with vancomycin alone; the elution of Palacos R and Simplex P was better than that of CMW1 when vancomycin was combined with imipenem-cilastatin.