The value of dermoscopy of the nail plate free edge and hyponychium.

The non-invasive examination of the nail unit using a dermoscope is known as onychoscopy. This technique has become increasingly appreciated to facilitate the clinical diagnosis of nail disorders, opening up a valuable second front with a potential to avoid invasive diagnostic procedures. During a nail consultation, the nail unit should always be examined with the aid of a dermatoscope in all its components. The aim of this paper was to provide practical information about onychoscopy of the nail plate free edge and hyponychium, two components of the nail unit difficult to evaluate at naked eye and often forgotten, but of paramount importance.

Dose adjustment of biologic therapies for psoriasis in dermatological practice: a retrospective study.

INTRODUCTION: Despite the large routine use of biologic drugs in psoriasis treatment, the majority of studies do not take into consideration dose-adjustment practice in 'real-life' dermatological setting. In routine clinical practice, the disease management may include a large number of conditions requiring non-standard dosage regimens, including dose escalation, dose reduction and/or off-label treatment interruption. OBJECTIVE: The ONDA (Outcome of non-standard dosing regimen in Psoriasis and Psoriatic Arthritis) study aim was to retrospectively analyse dose-adjustment strategies among biologic therapies for psoriasis in dermatological practice during a 3-year period. RESULTS: This retrospective, observational, multicentre study was carried out in 350 patients (68% male, 32% female) affected by plaque-type psoriasis (Pso) with a coexistence of psoriatic arthritis in 164 patients (46.9%). At baseline mean PASI score was 14.9 (SD 7.2). Dose adjustment was demonstrated to be a common practice with 70/350 patients (20%) who needed a dose variation during the treatment time, in particular a dose increase in 20/70 patients (28.6%) and a dose reduction in 50/70 patients (71.4%). Dose increase was due to inefficacy on Pso parameters in 60% of cases and to inefficacy of PsA parameters in 40% of cases, while dose reduction (or temporary off-label treatment interruption) was due to prolonged remission in 54% of cases, other reason in 18% of cases, patient choice or request in 14% of cases, occurrence of concomitant event in 12% of cases. CONCLUSION: Dose adjustment is a common clinical practice, consisting of frequent dose reduction when a disease prolonged remission is obtained or dose increase to improve efficacy on Pso and PsA disease parameters.

Diet and physical exercise in psoriasis: a randomized controlled trial.

BACKGROUND: Increased body mass index and weight gain are risk factors for psoriasis, and the prevalence of obesity in patients with psoriasis is higher than in the general population. Limited data exist regarding the role of diet in psoriasis. OBJECTIVES: To assess the impact of a dietary intervention combined with physical exercise for weight loss on improving psoriasis in overweight or obese patients. METHODS: This study included 303 overweight or obese patients with moderate-to-severe chronic plaque psoriasis who did not achieve clearance after 4 weeks of continuous systemic treatment. They were randomized to receive either a 20-week quantitative and qualitative dietary plan associated with physical exercise for weight loss or simple informative counselling at baseline about the utility of weight loss for clinical control of psoriatic disease. The main outcome was any reduction of the Psoriasis Area and Severity Index (PASI) from baseline to week 20. RESULTS: Intention-to-treat analysis showed a median PASI reduction of 48% (95% confidence interval 33.3-58.3%) in the dietary intervention arm and 25.5% (95% confidence interval 18.2-33.3%) in the information-only arm (P = 0.02). Among secondary outcomes, PASI score reduction of ≥ 50% significantly differed between study arms (49.7% with dietary intervention vs. 34.2% with information only, P = 0.006). The weight-loss target (a ≥ 5% reduction from baseline) was reached by 29.8% of patients in the dietary intervention arm compared with 14.5% in the information-only arm (P = 0.001). CONCLUSIONS: A 20-week dietetic intervention associated with increased physical exercise reduced psoriasis severity in systemically treated overweight or obese patients with active psoriasis.

Small-diameter melanocytic lesions: morphological analysis by means of in vivo confocal microscopy.

BACKGROUND: Small-diameter melanocytic lesions represent a diagnostic challenge for clinicians, as they do not follow the ABCD rule for diagnosis and do not always display reliable histopathological criteria. OBJECTIVES: To analyse the confocal features of small-diameter lesions (naevi and melanomas with diameter ≤ 5 mm) to determine whether they show specific morphological criteria. METHODS: Twenty-four melanomas and 72 naevi were subjected to dermoscopic and confocal evaluation along with histopathology. Significant dermoscopic and confocal differences between melanomas and naevi were evaluated by means of the Pearson χ(2) test. Odds ratios and 95% confidence intervals were calculated for each parameter. Binary logistic regression was performed to identify the reflectance confocal microscopy (RCM) independently significant features for melanoma diagnosis. RESULTS: The seven-point checklist dermoscopic score was ≥ 3 in 22 melanomas and in 33 naevi. The combination of cells' pleomorphism and architectural disorder (i.e. nonspecific pattern or irregular junctional nests upon confocal examination) are the most striking criteria for consistent diagnosis of small melanoma. The presence of atypical cells, more than five atypical cells per mm(2) , and roundish atypical cells at the dermoepidermal junction showed the highest odds ratios. From logistic regression, the presence of at least five pagetoid cells per mm(2) , tangled lines within the epidermis, and atypical roundish cells at the dermoepidermal junction resulted in the three independent confocal parameters that characterized small melanomas. CONCLUSIONS: Small melanomas frequently reveal specific dermoscopic and confocal features. Moreover, the combination of dermoscopy and RCM can lead to a correct diagnosis of a number of naevi that share some morphological aspects with melanomas.

Teriparatide increases the maturation of circulating osteoblast precursors.

UNLABELLED: This study shows that teriparatide promotes the circulating osteoblast (OB) precursor degree of maturation in patients affected by postmenopausal osteoporosis. INTRODUCTION: Anabolic treatment with teriparatide has proven effective for the therapy of postmenopausal osteoporosis and significantly reduces the risk of non-vertebral fragility fractures. The aim of this study was to investigate the effect of teriparatide on circulating OB precursors. METHODS: We evaluated by flow cytometry and real-time PCR the expression of OBs typical markers in peripheral blood mononuclear cells during treatment with teriparatide plus calcium and vitamin D, raloxifene plus calcium and vitamin D or calcium and vitamin D alone at various time points. Serum bone alkaline phosphatase and osteocalcin (OC) were measured as markers of bone turnover. RESULTS: Our results show that circulating OB precursors are more numerous and more immature in patients affected by fragility fractures than in osteoporotic patients without fractures. We also show that teriparatide treatment increases the expression of alkaline phosphatase and of OC in OB precursors; thus, it increases their degree of maturation. CONCLUSIONS: We suggest that teriparatide acts as anabolic agents also by promoting the maturation of OB precursors.

Bone and bone marrow pro-osteoclastogenic cytokines are up-regulated in osteoporosis fragility fractures.

UNLABELLED: This study evaluates cytokines production in bone and bone marrow of patients with an osteoporotic fracture or with osteoarthritis by real time PCR, Western blot and immunohistochemistry. We demonstrate that the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in patients with osteoporotic fractures. INTRODUCTION: Fragility fractures are the resultant of low bone mass and poor bone architecture typical of osteoporosis. Cytokines involved in the control of bone cell maturation and function are produced by both bone itself and bone marrow cells, but the roles of these two sources in its control and the amounts they produce are not clear. This study compares their production in patients with an osteoporotic fracture and those with osteoarthritis. METHODS: We evaluated 52 femoral heads from women subjected to hip-joint replacement surgery for femoral neck fractures due to low-energy trauma (37), or for osteoarthritis (15). Total RNA was extracted from both bone and bone marrow, and quantitative PCR was used to identify the receptor activator of nuclear factor kB Ligand (RANKL), osteoprotegerin (OPG), macrophage colony stimulating factor (M-CSF), transforming growth factor ß (TGFß), Dickoppf-1 (DKK-1) and sclerostin (SOST) expression. Immunohistochemistry and Western blot were performed in order to quantify and localize in bone and bone marrow the cytokines. RESULTS: We found an increase of RANKL/OPG ratio, M-CSF, SOST and DKK-1 in fractured patients, whereas TGFß was increased in osteoarthritic bone. Bone marrow produced greater amounts of RANKL, M-CSF and TGFß compared to bone, whereas the production of DKK-1 and SOST was higher in bone. CONCLUSIONS: We show that bone marrow cells produced the greater amount of pro-osteoclastogenic cytokines, whereas bone cells produced higher amount of osteoblast inhibitors in patients with fragility fracture, thus the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in these patients.

Restless Legs Syndrome in NKX2-1-related chorea: An expansion of the disease spectrum.

BACKGROUND: Molecular technologies are expanding our knowledge about genetic variability underlying early-onset non-progressive choreic syndromes. Focusing on NKX2-1-related chorea, the clinical phenotype and sleep related disorders have been only partially characterized. METHODS: We propose a retrospective and longitudinal observational study in 7 patients with non-progressive chorea due to NKX2-1 mutations. In all subjects sleep and awake EEG, brain MRI with study of pituitary gland, chest X-rays, endocrinological investigations were performed. Movement disorders, pattern of sleep and related disorders were investigated using structured clinical evaluation and several validated questionnaires. RESULTS: In patients carrying NKX2-1 mutations, chorea was mainly distributed in the upper limbs and tended to improve with age. All patients presented clinical or subclinical hypothyroidism and delayed motor milestones. Three subjects had symptoms consistent with Restless Legs Syndrome (RLS) that improved with Levodopa. CONCLUSIONS: Patients with NKX2-1 gene mutations should be investigated for RLS, which, similarly to chorea, can sometimes be ameliorated by Levodopa.

A fine physical map of the CACNA1A gene region on 19p13.1-p13.2 chromosome.

The P/Q-type Ca(2+) channel alpha(1A) subunit gene (CACNA1A) was cloned on the short arm of chromosome 19 between the markers D19S221 and D19S179 and found to be responsible for Episodic Ataxia type 2, Familial Hemiplegic Migraine and Spinocerebellar Ataxia type 6. This region was physically mapped by 11 cosmid contigs spanning about 1. 4Mb, corresponding to less than 70% of the whole region. The cosmid contig used to characterize the CACNA1A gene accounted only for the coding region of the gene lacking, therefore, the promoter and possible regulation regions. The present study improves the physical map around and within the CACNA1A by giving a complete cosmid or BAC contig coverage of the D19S221-D19S179 interval. A number of new STSs, whether polymorphic or not, were characterized and physically mapped within this region. Four ESTs were also assigned to cosmids belonging to specific contigs.

Spinocerebellar ataxia type 6 and episodic ataxia type 2: differences and similarities between two allelic disorders.

Spinocerebellar ataxia type 6 (SCA6) is one of three allelic disorders caused by mutations of CACNA1A gene, coding for the pore-forming subunit of calcium channel type P/Q. SCA6 is associated with small expansions of a CAG repeat at the 3' end of the gene, while point mutations are responsible for its two allelic disorders (Episodic Ataxia type 2 and Familial Hemiplegic Migraine). Genetic, clinical, pathological and pathophysiological data of SCA6 patients are reviewed and compared to those of other SCAs with expanded CAG repeats as well as to those of its allelic channelopathies, with particular reference to Episodic Ataxia type 2. Overall SCA6 appears to share features with both types of disorders, and the question as to whether it belongs to polyglutamine disorders or to channelopathies remains unanswered at present.

Psychosocial characteristics of persons convicted of driving while intoxicated.

Psychosocial and sociodemographic characteristics were obtained on a sample of 498 Missouri DWI offenders. The information included problems associated with alcohol use, past treatment, arrest data, stressful life events, depression, and substance abuse. Descriptive results are discussed in terms of theoretical and practical implications.

Should there be a duty to report crime?

A number of studies have examined why people do or do not respond when they observe criminal activities. Traditionally, the legal system has not punished the failure to report a crime. This study sought to ascertain whether a sample of college students and public citizens thought there should be legal punishments for the failure to report crimes. Respondents (N = 301) were presented a list of illegal acts and asked to select from a list (no punishment, fine, or prison sentences) what type of punishment should be enforced for failure to report that crime. Analysis indicated that the sample thought there should be punishments for most of the crimes, with a fine as the modal response. For more serious crimes, more serious punishments were selected, and there were some sex differences. It appeared that public support for such laws might be strong.

A typology of family social environments for institutionalized juvenile delinquents: Implications for research and treatment.

A variety of studies have examined family variables in relation to juvenile delinquency. In order to measure the social environmental characteristics of families of adjudicated delinquents, a sample of 411 adolescent offenders was obtained, consisting of all youths aged 12-16 committed over a 16-month period of time. Information was obtained on the Family Environment Scale (FES), an instrument which measures perceptions of nuclear family environments. Data was also obtained on a variety of measures of personality, social, behavioral, and intellectual skills. Cluster analytic procedures on the FES data were used to develop an empirical typology of family environments. Several types were identified, and analysis of variance was utilized to determine if the other measures could describe the delinquents falling into the various types. Some clear-cut descriptors emerged, with implications for research and treatment.

Distinguishing starters from nonstarters in an employee physical activity incentive program.

Although the vast majority of Americans who are physically active are likely to extol its many physical, psychological, and social values, research indicates that approximately fifty percent of individuals who start a formal physical activity program will drop out in six months or less. The present study employed stepwise discriminant analytical techniques in an attempt to distinguish starters from nonstarters in an innovative employee physical activity incentive program. The results indicated that a combination of health beliefs and lifestyle characteristics, health locus of control expectancies, and physiological characteristics accurately discriminated 81.7% of the starters and nonstarters. It was concluded that physical activity programs need to be designed, implemented, and marketed in such a manner as to attract individuals who are sedentary, smoke, are unable to cope with home-mediated stress, have an external health locus of control expectancy, and/or have a high cardiovascular disease-risk factor profile.

DNA markers in diagnosis of adult dominant polycystic kidney disease.

We report the results of a biological and molecular study carried out on 11 Italian families, with a total of 111 individuals in which adult dominant polycystic kidney disease segregates. A restriction fragment length polymorphism analysis was performed. Two families have shown a genetic heterogeneity even if not phenotypically different from the other ones: they resulted unlinked to 16p markers. A prenatal diagnosis has been performed in a family of the linked type.

Acetazolamide-responsive episodic ataxia in an Italian family refines gene mapping on chromosome 19p13.

Episodic ataxia type 2 is an autosomal dominant disorder with attacks of vertigo and ataxia which respond to acetazolamide treatment. The gene, distinct from the KCNA1 responsible for episodic ataxia type 1, has been mapped on chromosome 19p13 in a 11-12 cM region. A large Italian kindred affected with acetazolamide-responsive episodic ataxia is reported, with onset in adulthood, a strong vestibular component during attacks and a high frequency of cerebellar vermis degeneration. The genetic analysis (i) showed strong linkage between the disease and the 19p13 microsatellite markers in a region which widely overlaps that previously reported and (ii) set a new distal boundary of the gene-containing region. Combining present and previous mapping data, the gene of episodic etaxia type 2 is most probably located in an interval approximately 1.5 Mb between markers D19S221 and D19S226.

The role of the SCA2 trinucleotide repeat expansion in 89 autosomal dominant cerebellar ataxia families. Frequency, clinical and genetic correlates.

The spinocerebellar ataxia type 2 (SCA2) is caused by a trinucleotide (CAG) expansion in the coding region of the ataxin 2 gene on chromosome 12q.89 families with autosomal dominant cerebellar ataxia (ADCA) types I, II and III, and 47 isolated cases with idiopathic late onset cerebellar ataxia (ILOCA), were analysed for this mutation. The identification of the SCA2 mutation in 31 out of 38 families with the ADCA I phenotype, but in none of those with ADCA II, ADCA III or ILOCA confirms the specificity of this mutation. A clinical comparison of the ADCA I patients with the three known mutations (SCA1, -2 or -3) highlights significant differences between the groups; SCA2 patients tended to have a longer disease duration, a higher frequency of slow saccades and depressed tendon reflexes. However, these neurological signs were also seen in an ADCA I family in which the SCA2 mutation was not identified, illustrating the importance of a direct genetic test. The SCA2 families were from different geographical and ethnic backgrounds. However, haplotype analysis failed to show evidence of a founder mutation, even in families from the same geographical origin. The range of normal alleles varied from 17 to 30 CAG repeats and from 35 to 51 repeats for the pathological alleles. Similar to the other diseases caused by unstable trinucleotide repeats, a significant inverse correlation has been found between the number of repeats and age of onset, and there is a significantly higher paternal instability of repeat length on transmission to offspring. The SCA2 mutation is the most frequent amongst ADCA I patients, accounting for 40%, compared with SCA1 and SCA3 which account for 35% and 15%, respectively.