Parentification, distress, and relationship with parents as factors shaping the relationship between adult siblings and their brother/sister with disabilities.

According to parentification theory, when the siblings of a brother/sister with disabilities assume parent-like duties, this role reversal is known as sibling-focused parentification. It has a significant impact on these siblings' distress and the quality of their family relationships; 605 Italian adult siblings (19-26 years) of people with disabilities completed the online survey. Measures of siblings' parentification, distress, quality of family relationships, social support, and perceived benefits of parentification were used. The hypothesized model aims to test, on the target sample, the distress and the quality of the relationship with parents as mediators on the interplay between the siblings' parentification and their sibling relationship. Additionally, social support and perceived benefits of parentification as protective factors were considered. Results showed that the distress and the low quality of the relationship with parents negatively affected the interplay between the siblings' parentification and the relationship with their own brother/sister with disabilities. Social support and the perceived benefits of parentification decreased the siblings' distress levels; the perceived benefits of parentification served as a protective factor for the quality of the relationship with parents. Current findings extend the knowledge regarding the risk and protective factors of the siblings' mental health when disability occurs in the family. Additionally, they inform family-based intervention programs, which should involve the whole family system for reducing distress and improving the wellbeing of siblings without disabilities.

The Carers' Needs Assessment for Dementia (CNA-D): a validation study in the Italian population.

BACKGROUND: Dementia has devastating consequences for families with important physical, psychological, social, and financial effects. Evaluation of caregiver's needs may be an important step to reduce the burden of family caregivers of dementia patients. An Austrian scale, the Carers' Needs Assessment for Dementia, is now available for measuring the caregiver's needs. The aim of our study was to evaluate the psychometric properties of the Italian version of the CNA-D (iCNA-D). METHODS: A sample of 214 voluntary caregivers of dementia patients was recruited at the Department of Neuroscience, University of Turin (Italy). All participants were administered the iCNA-D. Validity and reliability of the instrument were evaluated using Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Symptom Checklist-90 (SCL-90), and the Italian version of Zarit Burden Interview (I-ZBI). RESULTS: The most common unmet need reported for the iCNA-D was "counseling and emotional support" (31.5%). This item demonstrates adequate reliability with moderate internal consistency for all "summary scores" of iCNA-D (α ≥ 0.75) and split-half correlation of more than 0.80 for two of them. We also found positive correlations in two out of three "summary scores" of iCNA-D and in the overall outcomes of BDI, BAI, SCL-90, and I-ZBI. CONCLUSIONS: The iCNA-D could be a valid and reliable tool for a comprehensive assessment of needs and possible social supports proposed to relatives who take care of patients with dementia. Better understanding of family caregivers' needs could improve planning of local services and reduce caregivers' perception of distress and burden.

Metacognitive impairment in patients with episodic and chronic migraine.

Migraine is one of the most common medical disorder in the world. Metacognition is the ability to monitor one's own cognitive functioning and consequently direct one's behavior. In adult migraine patients, the neuropsychological profile has been poorly investigated, and metacognitive functions have never been assessed. The aim of the present study was therefore to evaluate executive metacognitive abilities in patients with episodic and chronic migraine. Sixty-four migraine patients (male/female = 18/46; mean age = 45.65 ± 11.61 years): 27 patients with episodic migraine without aura (male/female = 9/18; mean age ± SD = 45.11 ± 12.18 years) and 37 patients with chronic migraine and medication-overuse headache (male/female = 9/28; mean age ± SD = 46.05 ± 11.32 years) were selected for the study. Twenty-nine controls (male/female = 12/17; mean age ± SD = 42.86 ± 14.78 years) were also enrolled in the research. Metacognitive and executive skills were assessed using the metacognitive version of Wisconsin Card Sorting Test. Migraine patients exhibited a lower performance in metacognitive tasks in respect to controls in term of worse outcomes in accuracy score (p = 0.012), global monitoring (p = 0.015), monetary gains (p = 0.022), and control sensitivity (p = 0.027). A reduction in accuracy score (p = 0.001), free-choice improvement (p = 0.002), global monitoring (p = 0.003), monetary gains (p = 0.009), and control sensitivity (p < 0.001) was also found in patients with chronic migraine and medication-overuse headache in respect to patients with episodic migraine. Our study supports the hypothesis that migraine patients show metacognitive dysfunctions that become worse with the chronicization of the disease and the increase of medication use.

High Risk of Suicide in Behavioral Variant Frontotemporal Dementia.

AIM: The purpose of the study was to determine the prevalence of suicidal ideation and attempts in patients with behavioral variant frontotemporal dementia (bvFTD), evaluating possible risk factors for suicidality. METHODS: Risk of suicide was assessed using the Scale for Suicide Ideation (SSI) in 35 patients with bvFTD and 25 controls. RESULTS: According to SSI, 40% of patients with bvFTD had suicidal ideation in comparison to 8% of controls ( P = .009). Four patients with bvFTD have attempted suicide versus none control ( P = .006). Patients with bvFTD with suicide risk showed higher levels of anxiety, depression, stress, and hopelessness than patients without suicide risk ( P < .001). Patients who attempted suicide were younger and had a longer disease duration than those with only suicide ideation. Intriguingly, 40% of patients with parkinsonism presented high level of suicide ideation. CONCLUSIONS: Our findings show that patients with bvFTD have a high risk of suicide. Additional studies in larger populations are needed to confirm our results.

Investigating the role of adipokines in chronic migraine.

Background and aims Adiponectin, leptin, and resistin are adipocyte-derived secretory factors involved in endothelial function, weight, inflammation, and insulin resistance. Recent studies suggested a role for adipokines in episodic migraine as mediators of inflammatory processes. The aim of this study was to investigate plasma concentrations of adiponectin, leptin, and resistin in patients with chronic migraine. Materials and methods Twenty-seven chronic migraineurs (20 females, 7 males; mean age 49.0 ± 9.0 yrs) and 37 healthy controls (23 females, 14 males; mean age 49.8 ± 15.0 yrs) were selected for the study. Fasting plasmatic levels of total adiponectin, leptin, and resistin were measured using ELISA kits during a pain-free period. Fasting glucose, insulin, total and HDL-cholesterol, triglycerides, and ESR were also determined. Results Serum levels of adiponectin and resistin were significantly increased in chronic migraineurs in comparison with controls ( p = 0.001 and p = 0.032, respectively). After correction for BMI, sex and age, leptin levels were significantly increased in chronic migraineurs ( p = 0.007). A positive correlation between leptin concentrations and both indices of insulin resistance and markers of inflammation was found. Discussion Our data suggest that adiponectin and resistin are altered in non-obese chronic migraineurs. Further studies are needed to elucidate the neurobiological mechanisms underlying adipokine dysfunction in migraine.

Is HCRTR2 a genetic risk factor for Alzheimer's disease?

BACKGROUNDS/AIMS: Alzheimer's disease (AD) is one of the main types of dementia affecting about 50-55% of all demented patients. Sleep disturbances in AD patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble the core symptoms of narcolepsy, a sleep disorder caused by a general loss of the neurotransmitter hypocretin. The aim of our study was to investigate whether genetic variants in the hypocretin (HCRT) and in the hypocretin receptors 1 and 2 (HCRTR1, HCRTR2) genes could modify the occurrence and the clinical features of AD and to examine if these possible variants influence the role of the protein in sleep regulation. METHODS: Using a case-control strategy, we genotyped 388 AD patients and 272 controls for 10 SNPs in the HCRT, HCRTR1 and HCRTR2 genes. In order to evaluate which residues belong to the HCRTR2 binding site, we built a molecular model. RESULTS: The genotypic and allelic frequencies of the rs2653349 polymorphism were different (χ(2) = 5.77, p = 0.016; χ(2) = 6.728, p = 0.035) between AD patients and controls. The carriage of the G allele was associated with an increased AD risk (OR 2.53; 95% CI 1.10-5.80). No significant differences were found in the distribution of either genotypic or allelic frequencies between cases and controls in the HCRTR1 polymorphisms rs2271933, rs10914456 and rs4949449 and in the HCRTR2 polymorphism rs3122156. CONCLUSION: Our data support the hypothesis that the HCRTR2 gene is likely to be a risk factor for AD. The increased risk inferred is quite small, but in the context of a multi-factorial disease, the presence of this polymorphism may significantly contribute to influencing the susceptibility for AD by interacting with other unknown genetic or environmental factors in sleep regulation.

Genes and primary headaches: discovering new potential therapeutic targets.

Genetic studies have clearly shown that primary headaches (migraine, tension-type headache and cluster headache) are multifactorial disorders characterized by a complex interaction between different genes and environmental factors. Genetic association studies have highlighted a potential role in the etiopathogenesis of these disorders for several genes related to vascular, neuronal and neuroendocrine functions. A potential role as a therapeutic target is now emerging for some of these genes. The main purpose of this review is to describe new advances in our knowledge regarding the role of MTHFR, KCNK18, TRPV1, TRPV3 and HCRTR genes in primary headache disorders. Involvement of these genes in primary headaches, as well as their potential role in the therapy of these disorders, will be discussed.

Apolipoprotein E polymorphisms in frontotemporal lobar degeneration: a meta-analysis.

OBJECTIVE: Case-control studies have not been consistent in showing association between apolipoprotein E (APOE) polymorphisms and frontotemporal lobar degeneration (FTLD), producing contradictory findings. The study objective was to define and quantify further the disease risk associated with the carriage of different APOE alleles to determine whether APOE gene polymorphism is a risk factor for FTLD. METHODS: A systematic review of all case-control studies investigating the association between the APOE gene and FTLD up to December 2011 was conducted. Case-control studies using clinical or pathological criteria for FTLD and reporting APOE allelic or genotypic data were included. Pooled odds ratios (ORs) were estimated using a random effects model, and 95% confidence intervals (CIs) were calculated. RESULTS: Twenty-eight case-control studies met the inclusion criteria. Carriage of the ε2 allele had no effect on disease risk. On the contrary, carriage of the ε4 allele was associated with a significantly increased disease risk (ε4 carriers vs non-ε4 carriers: OR, 1.94; 95% CI, 1.43-2.64; ε4 vs ε3 allele: OR, 1.83; 95% CI, 1.34-2.52). Furthermore, a gene-dosage effect for the ε4 allele was found. There was no evidence of publication bias, but heterogeneity between the studies was high. CONCLUSIONS: Our study provides evidence for an association between the APOE ε4 allele and frontotemporal lobar degeneration.

Genetic variants in the NOTCH4 gene influence the clinical features of migraine.

BACKGROUND: Recent studies suggested an important role for vascular factors in migraine etiopathogenesis. Notch4 belongs to a family of transmembrane receptors that play an important role in vascular development and maintenance. The aim of this study was to test the hypothesis that polymorphisms of the NOTCH4 gene would modify the occurrence and the clinical features of migraine. FINDINGS: Using a case-control strategy, we genotyped 239 migraine patients and 264 controls for three different non-synonymous polymorphisms (T320A, G835V, R1346P) of the NOTCH4 gene and for the (CTG) n-encoding polyleucine polymorphism in exon 1. Although the analyzed polymorphisms resulted not associated with migraine, the clinical characteristics of our patients were significantly influenced by the different NOTCH4 genotypes. Longer duration of disease and severity of neurovegetative symptoms during headache attacks were associated with the R1346P and G835V polymorphisms, respectively. In female patients, worsening of migraine symptoms at menarche was significantly correlated with T320A polymorphism. CONCLUSIONS: Our study shows that genetic variations within the NOTCH4 gene significantly modify the clinical characteristics of migraine and may have a role in disease pathogenesis.

Direct patterning of silver particles on porous silicon by inkjet printing of a silver salt via in-situ reduction.

We have developed a method for obtaining a direct pattern of silver nanoparticles (NPs) on porous silicon (p-Si) by means of inkjet printing (IjP) of a silver salt. Silver NPs were obtained by p-Si mediated in-situ reduction of Ag+ cations using solutions based on AgNO3 which were directly printed on p-Si according to specific geometries and process parameters. The main difference with respect to existing literature is that normally, inkjet printing is applied to silver (metal) NP suspensions, while in our experiment the NPs are formed after jetting the solution on the reactive substrate. We performed both optical and scanning electron microscopes on the NPs traces, correlating the morphology features with the IjP parameters, giving an insight on the synthesis kinetics. The patterned NPs show good performances as SERS substrates.

Association between major mood disorders and the hypocretin receptor 1 gene.

BACKGROUND: Recent studies suggested a role for hypocretins in the neurobiology of Major Mood Disorders (MMD). The purpose of this study was to investigate hypocretin involvement in MMD evaluating whether particular alleles or genotypes of the hypocretin pathway genes (HCRT, HCRTR1 and HCRTR2) would modify the occurrence and clinical features of the disease. METHODS: We selected for the study 229 MMD patients and 259 healthy age-, sex- and ethnicity-matched controls. Cases and controls were genotyped for several single-nucleotide polymorphisms (SNPs) of the HCRT, HCRTR1, and HCRTR2 genes. RESULTS: We found that allelic and genotypic frequencies of the rs2271933 G>A polymorphism (Ile408Val) in the HCRTR1 gene were significantly different between cases and controls (p=0.003 and p=0.0004, respectively). The carriage of the A allele was associated with a significantly increased disease risk (OR:1.60, 95% C.I. 1.22-2.10). In addition, we found a significant association between HCRTR1 haplotypes and the disease (permutation p<0.0001). In the analysis of subgroups we confirmed the association only in patients with unipolar depression. LIMITATIONS: Our sample was relatively small and included only cases and controls recruited from Northern Italy. Analysis of the disease subgroups warrants reexamination with more subjects. Finally, the effects of the rs2271933 G>A polymorphism on the hypocretin-1 receptor function are unknown. CONCLUSIONS: Our study suggests that the HCRTR1 gene or a linked locus may modulate the risk for Major Mood Disorders and supports recent studies suggesting an involvement of hypocretin neurotransmitter system in affective disorders.

Cluster headache is associated with the alcohol dehydrogenase 4 (ADH4) gene.

BACKGROUND/OBJECTIVES: Alcohol is a well-known trigger factor for cluster headache attacks during the active phases of the disease. The alcohol dehydrogenase (ADH) pathway, which converts alcohol to the toxic substance acetaldehyde, is responsible for most of the alcohol breakdown in the liver. Humans have 7 ADH genes, tightly clustered on chromosome 4q21-q25, that encode different ADH isoforms. The ADH4 gene encodes the class II ADH4 pi subunit, which contributes, in addition to alcohol, to the metabolization of a wide variety of substrates, including retinol, other aliphatic alcohols, hydroxysteroids, and biogenic amines. The purpose of this study was to investigate the association of genetic variants within the ADH4 gene with cluster headache susceptibility and phenotype. METHODS: A total of 110 consecutive unrelated cluster headache patients and 203 age- and sex-matched healthy controls of Caucasian origin were involved in the study. Patients and controls were genotyped for 2 bi-allelic single nucleotide polymorphisms (SNPs) of the ADH4 gene: SNP1 - rs1800759 and SNP2 - rs1126671. Allele, genotype, and haplotype frequencies of the examined polymorphisms were compared between cases and controls. RESULTS: Genotype frequencies of the rs1126671 polymorphism resulted significantly different between cluster headache patients and controls (chi(2) = 10.269, P = .006). The carriage of the AA genotype, in comparison with remaining genotypes, was associated with a significantly increased disease risk (OR = 2.33, 95% CI: 1.25-4.37). Haplotype analysis confirmed the association between the ADH4 gene and the disease. No association between different clinical characteristics of cluster headache and the examined polymorphisms was found. CONCLUSION: Our data suggest that cluster headache is associated with the ADH4 gene or a linked locus. Additional studies are warranted to elucidate the role of this gene in the etiopathogenesis of the disease.

The usefulness of preoperative dual-phase 99mTc MIBI-scintigraphy and IO-PTH assay in the treatment of secondary and tertiary hyperparathyroidism.

BACKGROUND: Persistent secondary or tertiary hyperparathyroidism (HPT) results from failure to remove enough hyperfunctioning parathyroid tissue. Ectopically situated parathyroid glands and supernumerary glands make failure more likely. Recurrent HPT after subtotal Ptx is usually due to regrowth of the remaining parathyroid tissue. Recurrence may also develop from a hyperplastic supernumerary gland or rarely from parathyromatosis. Recurrent HPT after total Ptx with autotransplantation is usually due to overgrowth of the autograft or for the previously mentioned reasons. METHODS: Since 1995, 464 patients with SHPT or THPT were treated surgically; intraoperative parathormone (PTH) was measured in 277 patients. Sixty-eight patients also had a preoperative MIBI scan. We compared the preoperative MIBI scan results with intraoperative findings, parathyroid gland weight and histology. We questioned whether MIBI uptake corresponded to parathyroid gland size and weight. We also correlated the number of Ki67 nuclear positive cells with MIBI uptake. For SHPT in group I with 145 patients, neither intraoperative PTH (IO-PTH) assay nor MIBI scanning was done. In group II with 163 patients IO-PTH was used and in group III with 48 patients both IO-PTH and MIBI scanning was used. For THPT in group I with 42 patients, neither IO-PTH assay nor MIBI scanning was done. In group II with 46 patients IO-PTH was used and in group III with 20 patients both IO-PTH and MIBI scanning was used. RESULTS: Parathyroid weight correlated directly with MIBI uptake. No correlation, however, occurred between MIBI uptake and parathyroid histology or between Ki67 staining and MIBI scanning. For SHPT in group I the persistence rate was 6.2% and recurrence rate 11%; in group II the persistence rate was 4.9% and recurrence rate 4.9%; in group III the persistence rate was 2%, and recurrence 4.2% (P < 0.05 between group I and III for persistence and recurrence). We obtained similar results in THPT, but recurrence was 0 in groups II and III, also when only 3 glands were removed, probably due to asymmetric hyperplasia commonly seen in this particular population (P < 0.05 regarding recurrence between group I and II-III, no difference between group II and III). CONCLUSION: In conclusion our findings support that the surgeon experience is a very important factor for good results in patients with SHPT and THPT. Preoperative MIBI scanning and IO-PTH are helpful but not essential except in reoperations.

Hypocretins and primary headaches: neurobiology and clinical implications.

Hypocretins (or orexins) are two neuropeptides synthesized by neurons located exclusively in the hypothalamus. Hypocretin-containing neurons have widespread projections throughout the CNS; with particularly dense excitatory projections to monoaminergic and serotonergic brainstem centers. The hypocretin system influences a wide range of physiological processes in mammals, such as feeding, arousal, rewards and drug addiction. Recently, a number of studies in experimental animals showed that hypocretins are involved in pain modulation within the CNS, and suggested the presence of a link between these peptides and nociceptive phenomena observed in primary headaches. The aim of this review is to describe and discuss recent studies in humans suggesting a role for the hypocretin neuronal system in cluster headache and chronic migraine.

Characterization of human hair melanin and its degradation products by means of magnetic resonance techniques.

Melanin granules (MGs) have been extracted from human Chinese black hairs by either acid hydrolysis (CH-type MGs) or enzymatic digestion (CP-type MGs), and their chemical structure investigated at the solid state by means of (13)C cross polarization magic angle spinning (CPMAS NMR) and EPR spectroscopy. Both types of MGs contain a large amount of protein that is tightly bound to the true melanin polymer, with CP-type MGs having a larger protein content than CH-type ones. Moreover, MGs may also contain variable amounts of lipid-like material. A high amount of paramagnetic metals is detected by EPR in CP-type MGs, in particular Fe(III). Iron can be bound in two chemical forms: as isolated high spin Fe(III) ions with rhombic symmetry and as small oxy-hydroxy Fe(III) aggregates. Iron is poorly available to chelators. CH-type MGs contain much fewer metals. CP-type MGs have then been subjected to partial bleaching by hydrogen peroxide in ammonia, yielding a residual solid, called residual oxidized melanin (ROM) and a soluble but still pigmented fraction called melanin free acid (MFA). MFA can be isolated by precipitation at acidic pH. The (13)C-CPMAS NMR and EPR spectra of these derivatives indicated that ROM has a structure very similar to that of parent MGs, whereas MFA shows a decrease of the protein content with respect to the melanin and a decreased amount of bound iron. Thus, the oxidative degradation of CP-type MGs is a process not involving the bulk of MGs, but rather it proceeds from the solvent-exposed outer parts to the interior.

Association between the G1246A polymorphism of the hypocretin receptor 2 gene and cluster headache: a meta-analysis.

The objective of this study was to investigate the association between polymorphisms of the hypocretin receptor 2 gene (HCRTR2) and the risk of cluster headache (CH). The study is a meta-analysis of published case-control studies investigating the association between polymorphisms of the HCRTR2 gene and CH. Pooled odds ratios (OR) were estimated using both random (RE) and fixed effects (FE) models. Three studies, performed in five different European countries, with 593 cases and 599 controls, were included in the study. Allele G of the G1246A HCRTR2 polymorphism was significantly associated with CH (FE OR 1.58, CI 95% 1.27-1.95; RE OR 1.55 (1.14-2.12)). Carriers of the GG genotype showed a higher disease risk compared to the remaining genotypes (FE OR 1.75, CI 95% 1.37-2.25; RE OR 1.69, CI 95% 1.11-2.58). Our data confirm that the G1246A polymorphism of the HCRTR2 gene may modulate the genetic risk for CH.

EPR study of the surface basicity of calcium oxide. 3. Surface reactivity and nonstoichiometry.

High surface area polycrystalline calcium oxide forms ozonide O3- ions upon O2 adsorption and NO3(2-) anions under low pressures of NO. Both radical anions, detected by electron paramagnetic resonance (EPR), are not observed in the case of the homologous magnesium oxide. This behavior reveals the presence, in CaO, of anomalies with respect to the ideal composition of an ionic oxide which are identified in terms of two main types of defects. The first type consists of positive holes dispersed in the bulk and originated by the unavoidable presence of Na+ ions in the composition of the solid. The decomposition of the surface ozonide shows the formation of a transient surface stabilized O- (the chemical notation of a positive hole associated to an oxide ion) which is for the first time reported at the surface of CaO. The second type of defect consists of surface peroxide groups (present at particular surface sites where they are formed by pairing of two distinct O-) which react with nitric oxide (NO) yielding NO3(2-) radical anions. The presence of peroxide is not related to the presence of impurities but, rather, to a certain propensity of the solid to form such ions at the surface along the dehydration process.

Association between migraine and HLA-DRB1 gene polymorphisms.

We examined the distribution of HLA-DRB1 alleles in a cohort of 255 Italian migraine patients and in a control group of 325 healthy subjects. The frequency of DRB1*12 allele was found to be significantly reduced (p=0.02) in patients with migraine while the DRB1*16 allele was significantly increased (p=0.04) in comparison with controls. When the patients were divided into disease subgroups (migraine with and without aura), HLA-DRB1**16 allele was significantly increased (p<0.05) only in migraine without aura patients. We conclude that, in Italian patients, migraine is associated with different alleles of the HLA-DRB1 locus. Our data suggest the presence of a genetic susceptibility factor for migraine within the HLA region.