An open-label, one-arm, dose-escalation study to evaluate safety and tolerability of extremely low frequency magnetic fields in acute ischemic stroke

Extremely low frequency magnetic fields (ELF-MF) could be an alternative neuroprotective approach for ischemic stroke because preclinical studies have demonstrated their effects on the mechanisms underlying ischemic damage. The purpose of this open-label, one arm, dose-escalation, exploratory study is to evaluate the safety and tolerability of ELF-MF in patients with acute ischemic stroke. Within 48 hours from the stroke onset, patients started ELF-MF treatment, daily for 5 consecutive days. Clinical follow-up lasted 12 months. Brain MRI was performed before and 1 month after the treatment. The distribution of ELF-MF in the ischemic lesion was estimated by dosimetry. Six patients were stimulated, three for 45 min/day and three for 120 min/day. None of them reported adverse events. Clinical conditions improved in all the patients. Lesion size was reduced in one patient stimulated for 45 minutes and in all the patients stimulated for 120 minutes. Magnetic field intensity within the ischemic lesion was above 1 mT, the minimum value able to trigger a biological effect in preclinical studies. Our pilot study demonstrates that ELF-MF are safe and tolerable in acute stroke patients. A prospective, randomized, placebo-controlled, double-blind study will clarify whether ELF-MFs could represent a potential therapeutic approach

An open-label, one-arm, dose-escalation study to evaluate safety and tolerability of extremely low frequency magnetic fields in acute ischemic stroke

Extremely low frequency magnetic fields (ELF-MF) could be an alternative neuroprotective approach for ischemic stroke because preclinical studies have demonstrated their effects on the mechanisms underlying ischemic damage. The purpose of this open-label, one arm, dose-escalation, exploratory study is to evaluate the safety and tolerability of ELF-MF in patients with acute ischemic stroke. Within 48 hours from the stroke onset, patients started ELF-MF treatment, daily for 5 consecutive days. Clinical follow-up lasted 12 months. Brain MRI was performed before and 1 month after the treatment. The distribution of ELF-MF in the ischemic lesion was estimated by dosimetry. Six patients were stimulated, three for 45 min/day and three for 120 min/day. None of them reported adverse events. Clinical conditions improved in all the patients. Lesion size was reduced in one patient stimulated for 45 minutes and in all the patients stimulated for 120 minutes. Magnetic field intensity within the ischemic lesion was above 1 mT, the minimum value able to trigger a biological effect in preclinical studies. Our pilot study demonstrates that ELF-MF are safe and tolerable in acute stroke patients. A prospective, randomized, placebo-controlled, double-blind study will clarify whether ELF-MFs could represent a potential therapeutic approach

Direct‐acting antivirals for HCV treatment in older patients: A systematic review and meta‐analysis

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Reduced expression of THRβ in papillary thyroid carcinomas: relationship with BRAF mutation, aggressiveness and miR expression

Purpose Down-regulation of thyroid hormone receptor beta (THRβ) gene has been described in several human malignancies, including thyroid cancer. In this study, we analyzed THRβ mRNA expression in surgical specimens from a series of human papillary thyroid carcinomas (PTCs), characterized by their genotypic and clinical–biological features. Methods Thirty-six PTCs were divided into two groups according to the 2009 American Thyroid Association risk classification (17 low, 19 intermediate), and each group was divided into subgroups based on the presence or absence of the BRAFV600E mutation (21 BRAF mutated, 15 BRAF wild type). Gene expression was analyzed using fluidic cards containing probes and primers specific for the THRβ gene, as well as for genes of thyroperoxidase (TPO), sodium/iodide symporter (NIS), thyroglobulin (Tg) and thyroid stimulating hormone receptor (TSH-R) and for some miRNAs involved in thyroid neoplasia and targeting THRβ. The mRNA levels of each tumor tissue were compared with their correspondent normal counterpart. Results THRβ transcript was down-regulated in all PTCs examined. No significant differences were found between intermediate- vs low-risk PTCs patients, and BRAF-mutated vs BRAF wild-type groups. THRβ expression was directly correlated with NIS, TPO, Tg and TSH-R, and inversely correlated to miR-21, -146a, -181a and -221 expression. Conclusions Our results demonstrate that down-regulation of THRβ is a common feature of PTCs. While it is not associated with a more aggressive phenotype of PTC, it correlates with the reduction of all the markers of differentiation and is associated with overexpression of some miRNAs supposed to play a role in thyroid tumorigenesis

Predictive Role of CD36 Expression in HER2-Positive Breast Cancer Patients Receiving Neoadjuvant Trastuzumab

CD36 expression; Breast cancer; Neoadjuvant trastuzumabExpresión CD36; Cáncer de mama; Trastuzumab neoadyuvanteExpressió CD36; Càncer de mama; Trastuzumab neoadjuvantBackground Despite huge efforts to identify biomarkers associated with long-term clinical outcomes in patients with early-stage HER2-positive breast cancer (HER2+ BC) treated with (neo)adjuvant anti-HER2 therapy, no reliable predictors have been identified so far. Fatty acid uptake, a process mediated by the transmembrane transporter CD36, has recently emerged as a potential determinant of resistance to anti-HER2 treatments in preclinical HER2+ BC models. Methods Here, we investigated the association between baseline intratumor CD36 gene expression and event-free survival in 180 patients enrolled in the phase III trial Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO), which randomly assigned stage II-III HER2+ BC patients to receive neoadjuvant lapatinib, trastuzumab, or lapatinib-trastuzumab in combination with chemotherapy. To this aim, we selected NeoALTTO trial patients for whom pretreatment whole transcriptomic data were available. The main study results were validated in an independent cohort of patients enrolled in the neoadjuvant phase II trial NeoSphere. Results In 180 NeoALTTO patients, high intratumor CD36 expression was independently associated with worse event-free survival in patients treated with trastuzumab-based therapy (hazard ratio [HR] = 1.72, 95% confidence interval [CI] = 1.20 to 2.46), but not with lapatinib-based (HR = 1.02, 95% CI = 0.68 to 1.53) or trastuzumab-lapatinib–based (HR = 1.08, 95% CI = 0.60 to 1.94) therapy. Among 331 NeoSphere patients evaluated, high CD36 expression was independently associated with worse patient disease-free survival in both the whole study cohort (HR = 1.197, 95% CI = 1.002 to 1.428) and patients receiving trastuzumab-based neoadjuvant therapy (HR = 1.282, 95% CI = 1.049 to 1.568). Conclusions High CD36 expression predicts worse clinical outcomes in early-stage HER2+ BC treated with trastuzumab-based neoadjuvant therapy.The NeoALTTO trial was sponsored by GlaxoSmithKline; the NeoSphere trial was sponsored by F. Hoffmann-La Roche. Our subanalysis of the NeoALTTO and NeoSphere trials received no funding by pharmaceutical companies

A synonymous RET substitution enhances the oncogenic effect of an in-cis missense mutation by increasing constitutive splicing efficiency

Synonymous mutations continue to be filtered out from most large-scale cancer genome studies, but several lines of evidence suggest they can play driver roles in neoplastic disease. We investigated a case of an aggressive, apparently sporadic medullary thyroid carcinoma (MTC) harboring a somatic RET p.Cys634Arg mutation (a known MTC driver). A germ-line RET substitution (p.Cys630=) had also been found but was considered clinically irrelevant because of its synonymous nature. Next generation sequencing (NGS) of the tumor tissues revealed that the RET mutations were in cis. There was no evidence of gene amplification. Expression analysis found an increase of RET transcript in p.Cys630=;p.Cys634Arg patient compared with that found in 7 MTCs harboring p.Cys634 mutations. Minigene expression assays demonstrated that the presence of the synonymous RET mutation was sufficient to explain the increased RET mRNA level. In silico analyses and RNA immunoprecipitation experiments showed that the p.Cys630 = variant created new exonic splicing enhancer motifs that enhanced SRp55 recruitment to the mutant allele, leading to more efficient maturation of its pre-mRNA and an increased abundance of mature mRNA encoding a constitutively active RET receptor. These findings document a novel mechanism by which synonymous mutations can contribute to cancer progression

Alopecia in Patients with Collagen VI-Related Myopathies: A Novel/Unrecognized Scalp Phenotype

Collagen VI-related myopathies are characterized by severe muscle involvement and skin involvement (keratosis pilaris and impaired healing with the development of abnormal scars, especially keloids). Scalp involvement and hair loss have not been reported among cutaneous changes associated with collagen VI mutations. The aim of this study is to describe the clinical, trichoscopic, and histological findings of the scalp changes in patients affected by COL VI mutations and to estimate their prevalence. Patients with Ullrich congenital muscular dystrophy were enrolled and underwent clinical and trichoscopic examinations and a scalp biopsy for histopathology. Five patients were enrolled, and all complained of hair loss and scalp itching. One patient showed yellow interfollicular scales with erythema and dilated, branched vessels, and the histological findings were suggestive of scalp psoriasis. Two patients presented with scarring alopecia patches on the vertex area, and they were histologically diagnosed with folliculitis decalvans. The last two patients presented with scaling and hair thinning, but they were both diagnosed with folliculitis and perifolliculitis. Ten more patients answered to a “scalp involvement questionnaire”, and six of them confirmed to have or have had scalp disorders and/or itching. Scalp involvement can be associated with COL VI mutations and should be investigated

Diabetes and Obesity as Independent Risk Factors for Osteoporosis: Updated Results from the ROIS/EMEROS Registry in a Population of Five Thousand Post-Menopausal Women Living in a Region Characterized by Heavy Environmental Pressure

EMEROS/ROIS Registry is a project funded by ISBEM and supported by Medicina Futura Research

The interaction between motor simulation and spatial perspective-taking in action language: a cross-cultural study

: Growing evidence has revealed the crucial role of motor simulation and spatial perspective-taking in action language. However, there is still a lack of understanding of how motor and spatial processes interact when there are multiple actors involved, and if embodied processes are consistent across different cultures. To address this gap, we examined the interaction between motor simulation and spatial perspective-taking in action-sentences comprehension, along with the consistency of embodied processes across cultures. We collected data from Italian and US English speakers using an online sentence-picture verification task. The participants completed four conditions: two congruent (i.e., the participant is the agent in the sentence and the photo; the agent is someone else interacting with the participant in both the sentence and the picture) and two incongruent (i.e., the agents of the sentence and the picture do not match). The results show that when the perspective of the picture matched that described in the sentence-processing reaction times (RTs) were faster than in the incongruent conditions. In the congruent conditions where the agent is someone else, RTs were slower compared to the condition where the participant is the agent. This has been interpreted as claiming that motor simulation and perspective-taking are independent processes interacting during sentence comprehension (e.g., motor simulation is always run in the role of the agent, but we can adopt multiple perspectives depending on the pronouns and the contextual cues). Furthermore, Bayesian analysis provided evidence that embodied processing of action language entwines a common mechanism, suggesting cross-cultural consistency of embodied processes

Prevalence of Rheumatic Heart Disease in North Madagascar: An echocardiographic screening in young and adult populations

BackgroundRheumatic Heart Disease (RHD) prevalence in Madagascar is poorly known. Echocardiographic screening detects a higher prevalence of RHD than clinical examination.AimsWe aimed to describe RHD prevalence in children and adults in North Madagascar using the most updated World Heart Federation (WHF) criteria for RHD echocardiographic diagnosis.Methods Children aged 5–19 years (Group One) and adults aged more than 20 years (Group Two) underwent a four-steps visit: clinical questionnaire, physical examination, laboratory test - oropharyngeal swab for Group One and Anti-streptolysin O (ASO) titre for Group Two - and echocardiogram using a portable machine..Results Among 859 people (522 in Group One, 337 in Group Two) RHD prevalence was 2.1 per cent. Group Two had a higher risk of having RHD than Group One (OR 4.39, CI 1.39–13.9, p=0.004), while clinical findings were more frequent in Group One (children had a higher risk of heart murmur (O.R. 3.85 C.I. 1.08–13.72; p=0.029)). RHD prevalence was 1.34 per cent in children. Those positive to oropharyngeal swab had a higher risk of RHD (OR 14.5, CI 3.04–69.44, p=0.0024); children with history of fever and sore-throat had a higher risk of positive oropharyngeal swab (OR 15.97, CI 3.14–81.19, p=0.002). RHD prevalence was 3.3 per cent in adults. None of those had history of fever and throat-pain, positive ASO titre and cardiac murmur simultaneously. ConclusionThis is the first study describing prevalence of RHD in Madagascar. Our results, although preliminary, are important to enhance prevention programs in this country