Effectiveness of psychological support in patients undergoing primary total hip or knee arthroplasty: a controlled cohort study.

BACKGROUND: We hypothesised that psychological support would have a significant improvement on the mental and physical recovery of patients undergoing primary total hip or knee arthroplasty. MATERIALS AND METHODS: 200 patients were consecutively alternately assigned (1:1) to receive routine care (control group) or, in addition, psychological support from a professional psychologist (experimental group). The psychological support was provided at the pre-operative visit, during the hospitalisation period and at the rehabilitation centre. RESULTS: Upon discharge, based on the 'Hospital Anxiety and Depression Scale, a state of anxiety was observed in 12.8 % and 78.9 % of the patients in the experimental and in the control group, respectively (p < 0.0001). A state of depression was observed in 12.8 % and 73.7 % of the patients in the experimental and in the control group, respectively (p < 0.0001). With regard to the 'Physical Component Scale' of the SF-36 questionnaire, a similar temporal trend of values was observed in the two study groups, significantly increasing over time in both groups, taking into consideration both the joint population and the two hip and knee populations separately (p < 0.0001). With regard to the 'Mental Component Scale' of the SF-36 questionnaire, in both the joint population and the two hip and knee populations separately, an exact opposite temporal trend was observed in the experimental group compared to the control group (p < 0.0001), with generally higher scores in the experimental group (p < 0.0001). In patients with hip arthroplasty, the average time to reach the physiotherapy objective (i.e., the patient ability to walk 50 metres independently and to climb 10 steps) was 6.7 ± 1.8 days (range 4-12) in the experimental group and 7.9 ± 2.2 days (range 0-13) in the control group (p = 0.0015). CONCLUSIONS: In summary, there was a lower incidence of anxiety and depression and better mental well-being in the group of patients who received the psychological support. Within the hip arthroplasty group, the patients who received the psychological support reached the physiotherapy objective 1.2 days earlier than the patients in the control group (p = 0.0015). LEVEL OF EVIDENCE: Level 3, Non-randomized prospective controlled cohort.

Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes.

Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients and their parents that were not detected in 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, were found in the ADHD cohort relative to controls, the inherited rare CNV-associated gene set was significantly enriched for genes reported as candidates in studies of autism, schizophrenia and Tourette syndrome, including A2BP1, AUTS2, CNTNAP2 and IMMP2L. The ADHD CNV gene set was also significantly enriched for genes known to be important for psychological and neurological functions, including learning, behavior, synaptic transmission and central nervous system development. Four independent deletions were located within the protein tyrosine phosphatase gene, PTPRD, recently implicated as a candidate gene for restless legs syndrome, which frequently presents with ADHD. A deletion within the glutamate receptor gene, GRM5, was found in an affected parent and all three affected offspring whose ADHD phenotypes closely resembled those of the GRM5 null mouse. Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD.

Relevance of CD38 expression on CD8 T cells to evaluate antiretroviral therapy response in HIV-1-infected youths.

Surrogate markers for monitoring immuno-virological discordant responders, in addition to plasma viral load and CD4 cells, are still lacking. We assessed the diagnostic utility of CD38 expression on CD8 T cell assay, alone or in association with lymphocyte proliferation to mycotic antigens, in evaluating antiretroviral response. 28 vertically HIV-infected youths, 21 HAART- and seven 2 nucleotide reverse transcriptase inhibitors-treated, were enrolled in a retrospective study. Responders (57.1%) and non-responders (42.9%) to stable antiretroviral therapy for a minimum of 6 months, on the basis of viral load and CD4 T cells, comprehensively evaluated by CD38 expression on CD8 T lymphocytes [measured as CD38 antibody bound per CD8 T cell (CD38 ABC) and %CD38+ of total CD8 T cells (%CD38/CD8)] and lymphocyte proliferation to P. jiroveci, C. albicans, C. neoformans, A. fumigatus at a single time point after treatment, were selected. CD38 expression > or =2401 CD38 ABC and > or =85% CD38/CD8 cut-off points, accurately discriminates responders versus non-responders, both measures resulting in 75.0% (CI 42.8-94.5) sensitivity (identification of non-responder) and 93.8% (CI 69.8-99.8) specificity (identification of responder), when considered as single assays. The association '> or =2401 CD38 ABC or > or =85% CD38/CD8' improved sensitivity to 83.3% (CI 51.6-97.9), while the association '<2401 CD38ABC (or <85% CD38/CD8) and lymphoproliferative response positive to > or =2 tested organisms' improved specificity to 100% (CI 79.4-100). In conclusions, CD38 expression and mycotic antigen-specific T-cell proliferation may be used as additional parameters to existing criteria to evaluate antiretroviral response in immuno-virological discordant patients.

Hirschsprung disease, associated syndromes and genetics: a review.

Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.

DRD3 Ser9Gly variant is not associated with essential tremor in a series of Italian patients.

BACKGROUND: Essential tremor (ET) is the most common movement disorder worldwide. Three susceptibility loci on chromosomes 3q13, 2p24.1, and 6p23 have been reported, but no causative genes were found. The Ser9Gly variant of dopamine D3 receptor (DRD3) receptor was found associated to ET in a French and US population. METHODS: A case-control study to evaluate the association between the Ser9Gly variant and ET was performed in a cohort of 116 Italian patients with familial ET and in 158 normal controls. RESULTS: No significant difference in allele and genotype frequencies was found between the two groups. CONCLUSIONS: These results do not support an association between DRD3 Ser9Gly and susceptibility to ET in Italian patients.

Haplotypes of the human RET proto-oncogene associated with Hirschsprung disease in the Italian population derive from a single ancestral combination of alleles.

The RET proto-oncogene is the major gene involved in the complex genetics of Hirschsprung disease (HSCR), or aganglionic megacolon, showing causative loss-of-function mutations in 15-30% of the sporadic cases. Several RET polymorphisms and haplotypes have been described in association with the disease, suggesting a role for this gene in HSCR predisposition, also in the absence of mutations in the coding region. Finally, the presence of a functional variant in intron 1 has repeatedly been proposed to explain such findings. Here we report a case-control study conducted on 97 Italian HSCR sporadic patients and 85 population matched controls, using 13 RET polymorphisms distributed throughout the gene, from the basal promoter to the 3'UTR. Linkage disequilibrium and haplotype analyses have shown increased recombination between the 5' and 3' portions of the gene and an over-representation, in the cases studied, of two haplotypes sharing a common allelic combination that extends from the promoter up to intron 5. We propose that these two disease-associated haplotypes derive from a single founding locus, extending up to intron 19 and successively rearranged in correspondence with a high recombination rate region located between the proximal and distal portions of the gene. Our results suggests the possibility that a common HSCR predisposing variant, in linkage disequilibrium with such haplotypes, is located further downstream than the previously suggested interval encompassing intron 1.

CDKN2A and CDK4 mutation analysis in Italian melanoma-prone families: functional characterization of a novel CDKN2A germ line mutation.

Physical interaction between CDKN2A/p16 and CDK4 proteins regulates the cell cycle progression through the G1 phase and dysfunction of these proteins by gene mutation is implicated in genetic predisposition to melanoma. We analysed 15 Italian melanoma families for germ line mutations in the coding region of the CDKN2A gene and exon 2 of the CDK4 gene. One novel disease-associated mutation (P48T), 3 known pathological mutations (R24P, G101W and N71S) and 2 common polymorphisms (A148T and Nt500 G>C) were identified in the CDKN2A gene. In a family harbouring the R24P mutation, an intronic variant (IVS1, +37 G>C) of uncertain significance was detected in a non-carrier melanoma case. The overall incidence of CDKN2A mutations was 33.3%, but this percentage was higher in families with 3 or more melanoma cases (50%) than in those with only 2 affected relatives (25%). Noteworthy, functional analysis established that the novel mutated protein, while being impaired in cell growth and inhibition assays, retains some in vitro binding to CDK4/6. No variant in the p16-binding region of CDK4 was identified in our families. Our results, obtained in a heterogeneous group of families, support the view that inactivating mutations of CDKN2A contribute to melanoma susceptibility more than activating mutations of CDK4 and that other genetic factors must be responsible for melanoma clustering in a high proportion of families. In addition, they indicate the need for a combination of functional assays to determine the pathogenetic nature of new CDKN2A mutations.