A questionnaire to collect unintended effects of transcranial magnetic stimulation: A consensus based approach.

Transcranial magnetic stimulation (TMS) has been widely used in both clinical and research practice. However, TMS might induce unintended sensations and undesired effects as well as serious adverse effects. To date, no shared forms are available to report such unintended effects. This study aimed at developing a questionnaire enabling reporting of TMS unintended effects. A Delphi procedure was applied which allowed consensus among TMS experts. A steering committee nominated a number of experts to be involved in the Delphi procedure. Three rounds were conducted before reaching a consensus. Afterwards, the questionnaire was publicized on the International Federation of Clinical Neurophysiology website to collect further suggestions by the wider scientific community. A last Delphi round was then conducted to obtain consensus on the suggestions collected during the publicization and integrate them in the questionnaire. The procedure resulted in a questionnaire, that is the TMSens_Q, applicable in clinical and research settings. Routine use of the structured TMS questionnaire and standard reporting of unintended TMS effects will help to monitor the safety of TMS, particularly when applying new protocols. It will also improve the quality of data collection as well as the interpretation of experimental findings.

Street dust from a heavily-populated and industrialized city: Evaluation of spatial distribution, origins, pollution, ecological risks and human health repercussions.

Emissions from vehicles include particles from tire and brake wearing that can settle down and join industrial discharges into street dust. Metals present in street dust may create ecological and health threats and their analysis is of great environmental relevance. The city of Monterrey, Mexico is an industrial pillar of the country and shows an increasing fleet during the last years, which has yielded higher traffic and emissions. This study analyzes 44 street dust samples taken across the city for total element concentrations by using X-ray fluorescence. Associations and indicators are calculated to define possible origins, levels of pollution, natural or anthropogenic sources, and ecological and human health risks. High concentrations of As, Ba, Cu, Fe, Mo, Ni, Pb, Ti, and Zn were found. Main sources of metals were defined as: tire wearing for Zn and Fe; brake wearing for Ba, Cu, Fe, Pb and Zr; additional industrial sources for Mo, Ni, Pb, and Ti; and other natural sources for As. Ecological risk was found to be moderate across the city and risk due to Pb concentrations was established for children.

Biomarkers of resistance to radiation therapy: a prospective study in cervical carcinoma.

BACKGROUND: Clinical parameters and proteins have recently been suggested as possible causes of radiotherapy (RT) resistance in cervical carcinoma (CC). The objective of the present study was to validate prognostic biomarkers of radiation resistance. METHODS: The present prospective study included patients undergoing RT with curative intent for histologically proven locally advanced squamous cell CC. Tissues and blood samples were systematically collected before RT initiation. Immuno-histochemistry was performed (IGF-IR α and ß, GAPDH, HIF-1 alpha, Survivin, GLUT1, CAIX, hTERT and HKII). Response to radiation was assessed through tumour response 3 months after RT completion, through overall survival (OS) and through progression-free survival (PFS). RESULTS: One hundred forty nine patients with a mean age of 46 years were included, with FIGO IIB (n = 53) and FIGO IIIB (n = 96) CCs. 61 patients were treated with exclusive RT + brachytherapy and 88 underwent chemo-radiotherapy + brachytherapy. Our findings suggest an association between hemoglobin level (Hb) (>11 g/dL) and 3 months complete response (p = 0.02). Hb level < 11 g/dL was associated with decreased PFS (p = 0.05) and OS (p = 0.08). Overexpression of IGF-1R ß was correlated with a decreased OS (p = 0.007). Overexpression of GLUT1 was marginally correlated with reduced OS (p = 0.05). PFS and OS were significantly improved in patients undergoing chemoradiation versus exclusive radiotherapy (PFS: p = 0.04; OS: p = 0.01). CONCLUSIONS: IGF-1R ß overexpression and Hb level (≤11 g/dl) were associated with poor prognosis, and thus appear to be possible interesting biomarkers of radiation resistance. Our results corroborate previous pre-clinical studies suggesting IGF-1R and hypoxia to be part of the biological pathways leading to radio-resistance.

HPV-16 variants' impact on uterine cervical cancer response to radiotherapy: A descriptive pilot study.

PURPOSE: Although the large impact of Human papilloma virus (HPV) in cervical cancer is established, its place as a therapeutic target is new and according to the growing literature, could be promising. In the present study, radiosensitivity's difference based on HPV-16 variants is assessed. PATIENTS AND METHODS: Variants of Human papilloma virus were identified before the exclusive radiotherapy in patients with cervical cancer. Data were prospectively collected. Fifty-nine patients were screened. RESULTS: Among the 59 screened patients, 34 (57.6%) were identified to be HPV-16 (+), with 13 European and two non-European variants. Of the 34 patients, 15 experienced exclusive radiotherapy. Among them, eight had complete response (seven with European and one with non-European variants), four with European variant had partial response, three with European variant had tumour persistence and one with non-European variant progressed at 3 months. CONCLUSION: No radiosensitivity difference was established, probably because of the limited population. Non-European variant aggressiveness might be suggested in accordance with the literature, as it was associated with the only tumour progression. Exclusive radiotherapy provides a unique and "pure" model of radioresistance in cervical cancer and could be the missing link between in vitro studies and state of the art chemoradiotherapy studies that probably feature too many parameters to identify radioresistance causes. The present study was a first step, with the future prospects of building a larger cohort study in order to better understand HPV-induced radioresistance and then to be able to propose new made-to-measure treatments.

Avoiding a second amniocentesis to corroborate prenatal diagnosis by using refrigerated samples.

OBJECTIVE: This study is aimed to probe the usefulness of refrigerated aliquots of amniotic fluid to be used for fluorescence in situ hybridization (FISH) in order to perform an accurate prenatal diagnosis avoiding the risk related to an additional amniocentesis procedure and the psychological stress to the pregnant woman and her family. METHODS: Non-cultured amniotic fluid (AF) samples were analyzed by FISH. Such samples were divided into two groups. The first one included fresh collected AF (FCAF, N = 30). The second one included refrigerated samples of AF (RSAF, N = 12) to corroborate uncertain chromosome aberration identification obtained by conventional methods. Sample refrigeration did not exceed 18 days. RESULTS: No differences were found between groups. In the RSAF group, three cases of chromosomal mosaicismo and seven cases of pseudomosaicism were corroborated. No alteration adjudicated to aberrant chromosomal line presence was found in born children according to genetic specialists' criteria. In the two remaining cases, applied procedure allowed elucidating fetal sex in one case and the origin of a marker chromosome in the other. CONCLUSIONS: Amniocytes obtained from RAFS are a useful biological material to be assayed by FISH, achieving an accurate prenatal diagnosis and avoiding an additional amniocentesis.

Working memory performance of early MS patients correlates inversely with modularity increases in resting state functional connectivity networks.

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating and neurodegenerative disorder of the central nervous system characterized by multifocal white matter brain lesions leading to alterations in connectivity at the subcortical and cortical level. Graph theory, in combination with neuroimaging techniques, has been recently developed into a powerful tool to assess the large-scale structure of brain functional connectivity. Considering the structural damage present in the brain of MS patients, we hypothesized that the topological properties of resting-state functional networks of early MS patients would be re-arranged in order to limit the impact of disease expression. A standardized dual task (Paced Auditory Serial Addition Task simultaneously performed with a paper and pencil task) was administered to study the interactions between behavioral performance and functional network re-organization. We studied a group of 16 early MS patients (35.3±8.3 years, 11 females) and 20 healthy controls (29.9±7.0 years, 10 females) and found that brain resting-state networks of the MS patients displayed increased network modularity, i.e. diminished functional integration between separate functional modules. Modularity correlated negatively with dual task performance in the MS patients. Our results shed light on how localized anatomical connectivity damage can globally impact brain functional connectivity and how these alterations can impair behavioral performance. Finally, given the early stage of the MS patients included in this study, network modularity could be considered a promising biomarker for detection of earliest-stage brain network reorganization, and possibly of disease progression.

A method for obtaining Schwann cell cultures from adult rabbit nerve based on "in vitro" pre-degeneration and neuregulin treatment.

Schwann cells (SCs) are basic elements for cell therapy and tissue engineering in the central and peripheral nervous system. Therefore, the development of a reliable method to obtain SC cultures is required. For possible therapeutic applications the cultures need to produce a sufficiently large number of SCs with a high level of purity in a relatively short period of time. To increase SC yield and purity we pre-degenerated pieces of 1-2 mm of adult rabbit sciatic nerves by incubating them for seven days in Dulbecco's Modified Eagle's Medium supplemented with 10% fetal bovine serum, penicillin/streptomycin and NRG1-ß1. Following pre-degeneration the nerve pieces were dissociated and then cultured for 6 or 15 days in the same culture medium. After 6 days of culture we obtained around 9.5x10³ cells/mg with approximately 94% SCs (S-100 positive) purity. After 15 days of culture the yield was about 80x10³ cells/mg and the purity was approximately 75%. Pre-degeneration and subsequent culture of small pieces of adult nerve with NRG1-ß1 supplemented medium increased the number of SCs and restricted the overgrowth of fibroblast-like cells.

Cost-effectiveness analysis of the early conversion of tacrolimus to mammalian target of rapamycin inhibitors in patients with renal transplantation.

BACKGROUND: Renal replacement therapies which consist of renal transplantation and dialysis are the only treatment options for patients with terminal renal failure. These therapies have changed the outcome from being fatal to being a chronic disease. Kidney transplantation involves the use of immunosuppressive agents to prevent rejection. Currently, several immunosuppressive agents have shown efficacy, safety, and different costs. OBJECTIVE: The aim was to evaluate the cost-effectiveness of early conversion from tacrolimus to mammalian target of rapamycin inhibitors sirolimus or everolimus versus continuous treatment with tacrolimus among renal transplantat patients in Colombia. METHODS: We performed systematic literature review to extract data for clinical effectiveness and safety of tacrolimus replacement schemes for immunosuppressive therapy in renal transplantation in adults. A Markov model in TreeAge was developed, simulating the patient's natural history with renal transplantation. The perspective of the Colombian Health System was used, including only direct costs. The cost-effectiveness ratio and incremental cost-effectiveness ratio were estimated. Deterministic and probabilistic sensitivity analyses were performed. A 5% discount rate was applied in costs and health results. RESULTS: Results for the replacement of tacrolimus to sirolimus are provided. The cost per year of additional life gained for sirolimus was Col$2,441,171.43; the cost for avoided loss was Col$4,014,152.84. The acceptability curve shows that a strategy with sirolimus is the most cost-effective one. CONCLUSIONS: This study suggested that the sirolimus strategy is cost-effective in Colombia for patients with renal transplantation using as threshold less than three times the gross domestic product (GDP) per capita of Colombia per life of years gained.

Absence of relevant effects of 5 mT static magnetic field on morphology, orientation and growth of a rat Schwann cell line in culture.

The aim of this study is to observe possible changes in the morphology, orientation or cell growth of an in vitro cultured Schwann cell line by 24 h exposure to 5 mT static magnetic fields. The magnetic field generator basically consists of a pair of circular coils in a Helmholtz arrangement and enables temperature to be controlled (37+/-0.1 degrees C). We did not find any statistically significant differences in the cell growth rate between control and exposed cells, nor did we observe any differences in cell morphology or orientation.