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Introduction/aims The cutaneous silent period (CSP) reflects the function of A-delta sensory fibers. There are few studies on CSP in nerve entrapment syndromes. This study aims to evaluate the neurophysiological abnormalities of small-diameter sensory fibers in ulnar neuropathy at the elbow (UNE) by means of CSP. Methods We consecutively evaluated UNE patients at one electrodiagnostic laboratory. The CSP was obtained upon stimulating the fifth (D5) and third digits, recording from the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles. Results We enrolled 37 UNE patients (mean age 55.4 ± 11.2 y) and 30 controls (mean age 51.2 ± 11.1 y). The combinations of the D5-APB and D5-FDI mean onset latencies of CSP were significantly more prolonged in patients (83.7 ± 6.8 and 84.5 ± 8 ms, respectively) than in controls (78.2 ± 8.1 and 79.4 ± 7.6 ms, respectively). The D5-FDI duration of CSP was shorter in patients (52.2 ± 8.3 ms) than in controls (55.8 ± 7 ms). The mean of the onset latencies of D5-FDI and D5-APB was related to the clinical severity (P = .013 and .0025, respectively). D5-APB and D5-FDI onset latencies were more prolonged and the duration was shorter in the UNE group with absent ulnar sensory nerve action potentials (SNAPs) and axonal motor damage than in patients with preserved SNAPs and with demyelinating damage. Discussion CSP was able to demonstrate abnormalities of small-diameter myelinated sensory fibers. This damage was directly related to UNE severity and to axonal damage of motor fibers. Absence of a sensory large-diameter fiber response did not exclude preserved residual small fiber conduction.

Background Sudden unexplained death (SUD) refers to cases of sudden death where autopsy fails to identify any cardiac or extracardiac underlying cause. Guideline‐directed standard genetic testing identifies a disease‐causing mutation in less than one‐third of cases of SUD. Conversely, whole exome sequencing (WES) may provide the key to solve most cases of SUD even after several years from the subject's death. Methods We report on a case of sudden unexpected death of a 37‐year‐old male, with inconclusive autopsy conducted 14 years ago. A recent reevaluation through WES was performed on DNA extracted from left ventricular samples. A multiple step process including several “in silico” tools was applied to identify potentially pathogenic variants. Data analysis was based on a 562 gene panel, including 234 candidate genes associated with sudden cardiac death or heart diseases, with the addition of 328 genes highly expressed in the heart. WebGestalt algorithms were used for association enrichment analysis of all genes with detected putative pathogenic variants. Results WES analysis identified four potentially pathogenic variants: RYR2:c.12168G>T, TTN:c.11821C>T (rs397517804), MYBPC3:c.1255C>T (rs368770848), and ACADVL:c.848T>C (rs113994167). WebGestalt algorithms indicated that their combination holds an unfavorable arrhythmic susceptibility which conceivably caused the occurrence of the events leading to our subject's sudden death. Conclusion Associating WES technique with online prediction algorithms may allow the recognition of genetic mutations potentially responsible for otherwise unexplained deaths., We report on a case of sudden unexpected death of a 37‐year‐old male, with inconclusive autopsy conducted 14 years ago, where recent reevaluation through whole exome sequencing (WES) and WebGestalt algorithms allowed the recognition of four genetic mutations (RYR2‐K4056N, TTN‐R3941C, MYBPC3‐R419C, and ACADVL‐V283A) potentially responsible for the subject's sudden death.

Triple negative breast cancers (TNBCs) represent about 15-20% of all breast cancer cases and are characterized by a complex molecular heterogeneity. Some TNBCs exhibit clinical and pathological properties similar to BRCA-mutated tumors, without actually bearing a mutation in BRCA genes. This "BRCAness" phenotype may be explained by germline mutations in other genes involved in DNA repair. Although respond to chemotherapy with alkylating agents, they have a high risk of recurrence and progression. Some studies have shown the efficacy of neoadjuvant therapy in TNBC patients with DNA repair defects, but proper biomarkers of DNA repair deficiency are still needed. Here, we investigated if mutations in DNA repair genes may be correlated with anthracyclines/taxanes neoadjuvant therapy response. DNA from 19 TNBC patients undergoing neoadjuvant therapy were subjected to next generation sequencing of a panel of 24 genes in DNA repair and breast cancer predisposition. In this study, 5 of 19 patients (26%) carried a pathogenic mutation in BRCA1, PALB2, RAD51C and two patients carried a probable pathogenic missense variant. Moreover, VUS (Variants of Unknown Significance) in other genes, predicted to be deleterious by in silico tools, were detected in five patients. Germline mutations in DNA repair genes were found to be associated with the group of TNBC patients who responded to therapy. We conclude that a subgroup of TNBC patients have defects in DNA repair genes, other than BRCA1, and such patients respond favourably to neoadjuvant anthracyclines/taxanes therapy. © 2016 Wiley Periodicals, Inc.

Objective To identify optimal cutoff values for body, hand, and wrist measurements in order to correctly identify individuals with carpal tunnel syndrome (CTS), using receiver operating characteristic (ROC) curves. Methods We enrolled patients with CTS and control subjects at a 1:2 ratio, regardless of age and sex. The diagnosis of CTS was based on clinical findings and delayed distal conduction velocity of the median nerve. The anthropometric measurements included weight, height, waist circumference, hip circumferences, wrist depth/width, third digit length, and palm length/width. Obesity indicators and hand/wrist ratios were calculated. Area under the ROC curve (AUC), sensitivity, specificity, and likelihood ratios were calculated separately according to sex. To assess the role of multiple anthropometric measurements, we fit multivariable logistic regression models including age, wrist ratio, shape index, body mass index, and waist-to-hip ratio. Results The study group comprised 1,117 subjects (250 female patients and 474 female controls; 120 male patients and 273 male controls). In women, the accuracy of all anthropometric measures was low (AUC ≤0.64). In men, the accuracy of the hand ratio, shape index, and wrist-to-palm ratio was moderate (AUC = 0.75). The estimates from the multivariable models confirmed the well-known associations between the selected variables and the risk of CTS, but the use of multiple predictors did not dramatically improve the diagnostic performance observed for single anthropometric indexes. Conclusion In clinical practice, the cutoff values for many anthropometric measurements have limited value as tools for the diagnosis of CTS.

The neuromuscular junction has retained through evolution the capacity to regenerate after damage, but little is known on the inter‐cellular signals involved in its functional recovery from trauma, autoimmune attacks, or neurotoxins. We report here that CXCL12α, also abbreviated as stromal‐derived factor‐1 (SDF‐1), is produced specifically by perisynaptic Schwann cells following motor axon terminal degeneration induced by α‐latrotoxin. CXCL12α acts via binding to the neuronal CXCR4 receptor. A CXCL12α‐neutralizing antibody or a specific CXCR4 inhibitor strongly delays recovery from motor neuron degeneration in vivo . Recombinant CXCL12α in vivo accelerates neurotransmission rescue upon damage and very effectively stimulates the axon growth of spinal cord motor neurons in vitro . These findings indicate that the CXCL12α‐CXCR4 axis plays an important role in the regeneration of the neuromuscular junction after motor axon injury. The present results have important implications in the effort to find therapeutics and protocols to improve recovery of function after different forms of motor axon terminal damage.

BRMS1 is regarded as a metastasis suppressor gene for its ability to reduce metastatic potential of human and murine breast cancer cells as well as human melanoma cells. However, BRMS1 association to human tumor progression is not clearly understood. In the present study we analyzed BRMS1 mRNA expression in tumor progression and its potential prognostic value for breast carcinoma. BRMS1 mRNA expression level was quantified by real-time PCR in 47 tumoral, in 14 peritumoral and in 15 metastatic microdissected cellular populations from 47 breast cancer patients with 10-year follow up. We found BRMS1 expression to be higher in carcinoma cells than in matching normal epithelial cell populations in 10 out of 14 cases (p = 0.0005), while lymph-nodal carcinoma cells showed lower BRMS1 expression in 9 out of 15 cases (p = 0.001). Using both in vivo (human mammary breast carcinomas) and in vitro systems (breast cancer cell lines) we were able to demonstrate that BRMS1 overexpression was not a bias effect induced by cell proliferation rate. BRMS1 expression levels did not correlate with standard breast cancer prognostic factors but BRMS1 higher expression was associated with patient shorter disease-free and overall survival. Our findings are apparently inconsistent with the concept of BRMS1 as a metastasis suppressor gene. One possible explanation is that epithelial cells increase their BRMS1 expression as a compensatory response to tumor formation or metastasis progression, which is elevated in proportion to tumor aggressiveness, whereas those cells of the primary tumor that cannot upregulate BRMS1 escape to form metastasis.