Multiple brownish macules on child's cheeks.

n/

Digital Dermoscopy Monitoring: Is it Time to Define a Quality Standard?

n/

Thrombin regulates the ability of Schwann cells to support neuritogenesis and to maintain the integrity of the nodes of Ranvier

Schwann cells (SC) are characterized by a remarkable plasticity that enables them to promptly respond to nerve injury promoting axonal regeneration. In peripheral nerves after damage SC convert to a repair-promoting phenotype activating a sequence of supportive functions that drive myelin clearance, prevent neuronal death, and help axon growth and guidance. Regeneration of peripheral nerves after damage correlates inversely with thrombin levels. Thrombin is not only the key regulator of the coagulation cascade but also a protease with hormone-like activities that affects various cells of the central and peripheral nervous system mainly through the protease-activated receptor 1 (PAR1). Aim of the present study was to investigate if and how thrombin could affect the axon supportive functions of SC. In particular, our results show that the activation of PAR1 in rat SC cultures with low levels of thrombin or PAR1 agonist peptides induces the release of molecules, which favor neuronal survival and neurite elongation. Conversely, the stimulation of SC with high levels of thrombin or PAR1 agonist peptides drives an opposite effect inducing SC to release factors that inhibit the extension of neurites. Moreover, high levels of thrombin administered to sciatic nerve ex vivo explants induce a dramatic change in SC morphology causing disappearance of the Cajal bands, enlargement of the Schmidt-Lanterman incisures and calcium-mediated demyelination of the paranodes. Our results indicate thrombin as a novel modulator of SC plasticity potentially able to favor or inhibit SC pro-regenerative properties according to its level at the site of lesion

Acute generalized exanthematous pustulosis following paracetamol ingestion in a child

N/

Very early onset of ATTRE89Q amyloidosis in a homozygous patient

Case Presentarion: Hereditary transthyretin amyloidosis is a progressive, fatal disease that generally involves the peripheral nervous system, the autonomic nervous system, and the heart. It is autosomal dominant with different penetrance depending on the mutation and the genetic background. Many other missense mutations of the TTR gene may cause the disease. Being an overall rare disease is very rare to observe the condition of homozygosity. In particular, cases of homozygosity have been described in patients with ATTRV30M and ATTRV122I amyloidosis. In the former, the phenotype does not seem to be aggravated, having an age of onset and disease course that does not appear to differ from those of heterozygotes, while in the latter, the onset appears to be earlier. Conclusion: We report the first case of ATTRE89Q amyloidosis in a patient that was homozygous for the E89Q mutation in the TTR gene. The clinical phenotype resulted in the earlier disease onset reported in this form of amyloidosis, suggesting that the homozygous condition may be prognostically negative

Calcipotriol/betamethasone dipropionate ointment compared with tacrolimus ointment for the treatment of erosive pustular dermatosis of the scalp: A split-lesion comparison

N/

effect of quenching and tempering process on a medium c steel with low chromium and molybenum addition for forged components

In this paper the effect of quenching and tempering (Q&amp;T) thermal treatment on mechanical properties of a C-Mn steel with 0.22% Cr for forged components is studied. Due to the lack od any micro-alloying elements (such as vanadium or niobium) such steel can just reach mechanical target allowed by its intrinsic hardenability. Aim of this work is to evaluate the mechanical properties dependence as a function of different quenching and tempering treatments. Results show that, after Q&amp;T, steel can reach a yield strength of 330 MPa combined with a -20°C fracture appearance transition temperature (50% FATT) measured with a Charpy-V impact test making this steel suitable for low temperature application.</p

Charcot-Marie-Tooth Type 2B: A New Phenotype Associated with a Novel RAB7A Mutation and Inhibited EGFR Degradation

The rare autosomal dominant Charcot-Marie-Tooth type 2B (CMT2B) is associated with mutations in the RAB7A gene, involved in the late endocytic pathway. CMT2B is characterized by predominant sensory loss, ulceromutilating features, with lesser-to-absent motor deficits. We characterized clinically and genetically a family harboring a novel pathogenic RAB7A variant and performed structural and functional analysis of the mutant protein. A 39-year-old woman presented with early-onset walking diculties, progressive distal muscle wasting and weakness in lower limbs and only mild sensory signs. Electrophysiology demonstrated an axonal sensorimotor neuropathy. Nerve biopsy showed a chronic axonal neuropathy with moderate loss of all caliber myelinated fibers. Next-generation sequencing (NGS) technology revealed in the proband and in her similarly affected father the novel c.377A&gt;G (p.K126R) heterozygous variant predicted to be deleterious. The mutation affects the biochemical properties of RAB7 GTPase, causes altered interaction with peripherin, and inhibition of neurite outgrowth, as for previously reported CMT2B mutants. However, it also shows differences, particularly in the epidermal growth factor receptor degradation process. Altogether, our findings indicate that this RAB7A variant is pathogenic and widens the phenotypic spectrum of CMT2B to include predominantly motor CMT2. Alteration of the receptor degradation process might explain the different clinical presentations in this family

Psychosocial burden and professional and social support in patients with hereditary transthyretin amyloidosis (ATTRv) and their relatives in Italy

Hereditary transthyretin amyloidosis (hATTR), alias ATTR variant (ATTRv) is a severe and disabling disease causing sensory and motor neuropathy, autonomic dysfunction, and cardiomyopathy. The progressive decline of patient's functional autonomy negatively affects the patient's quality of life and requires increasing involvement of relatives in the patient's daily life. Family caregiving may become particularly demanding when the patient is no longer able to move independently. This study is focused on the psychosocial aspects of ATTRv from the patient and relative perspectives. In particular, it explored: the practical and psychological burdens experienced by symptomatic patients with ATTRv and their key relatives and the professional and social network support they may rely on; whether burden varied in relation to patients' and relatives' socio-demographic variables, patients' clinical variables, and perceived professional and social network support; and, any difference in burden and support between patients and their matched relatives

Anxiety and depression in Charcot-Marie-Tooth disease: data from the Italian CMT national registry

Background There is little information about neuropsychiatric comorbidities in Charcot-Marie-Tooth disease (CMT). We assessed frequency of anxiety, depression, and general distress in CMT.Methods We administered online the Hospital Anxiety-Depression Scale (HADS) to CMT patients of the Italian registry and controls. HADS-A and HADS-D scores &gt;= 11 defined the presence of anxiety/depression and HADS total score (HADS-T) &gt;= 22 of general distress. We analysed correlation with disease severity and clinical characteristics, use of anxiolytics/antidepressants and analgesic/anti-inflammatory drugs.Results We collected data from 252 CMT patients (137 females) and 56 controls. CMT patient scores for anxiety (mean +/- standard deviation, 6.7 +/- 4.8), depression (4.5 +/- 4.0), and general distress (11.5 +/- 8.1) did not differ from controls and the Italian population. However, compared to controls, the percentages of subjects with depression (10% vs 2%) and general distress (14% vs 4%) were significantly higher in CMT patients. We found no association between HADS scores and disease duration or CMT type. Patients with general distress showed more severe disease and higher rate of positive sensory symptoms. Depressed patients also had more severe disease. Nineteen percent of CMT patients took antidepressants/anxiolytics (12% daily) and 70% analgesic/anti-inflammatory drugs. Patients with anxiety, depression, and distress reported higher consumption of anxiolytics/antidepressants. About 50% of patients with depression and/or general distress did not receive any specific pharmacological treatment.Conclusions An appreciable proportion of CMT patients shows general distress and depression. Both correlated with disease severity and consumption of antidepressants/anxiolytics, suggesting that the disease itself is contributing to general distress and depression