A randomized controlled trial of targeted prefrontal cortex modulation with tDCS in patients with alcohol dependence.

Preliminary small studies have shown that transcranial direct current stimulation (tDCS) reduces craving in alcoholic subjects. It is unclear whether tDCS also leads to changes in clinically meaningful outcomes for alcohol dependence in a properly powered phase II randomized clinical trial. We aimed to investigate whether repetitive tDCS changes the risk of alcohol use relapse in severe alcoholics from outpatient services. Thirty-five subjects were randomized to receive active bilateral [left cathodal/right anodal over the dorsolateral prefrontal cortex (dlPFC)] repetitive (five consecutive days) tDCS (2 mA, 35 cm2, two times daily stimulation for 13 min with a 20-min interval) or sham-tDCS. There were two dropouts before treatment. From 33 alcoholic subjects, 17 (mean age 45.5±8.9 s.d., 16 males) were randomized to sham and 16 (44±7.8 s.d., 16 males) to real tDCS treatment. By the end of the six months of follow-up, two subjects treated with sham (11.8%) and eight treated with real tDCS (50%) were still alcohol-abstinent [p=0.02, Long-rank (Mantel-Cox) Test, HR=0.35 (95% CI, 0.14-0.85)]. No differences with regard to changes on scores of craving, frontal function, global mental status, depressive or anxiety symptoms were observed between groups. However, subjects from the tDCS group improved with regard to their overall perception of quality of life (p=0.02), and increased their scores in the environment domain (p=0.04) after treatment. Bilateral tDCS over dlPFC reduces relapse probability in severe alcoholic subjects and results in improved perception of quality of life.

Unruptured Brain Arteriovenous Malformations: A Systematic Review and Meta-Analysis of Mortality and Morbidity in Aruba-Eligible Studies.

BACKGROUND: Treating unruptured brain arteriovenous malformations (bAVMs) represent significant challenges, with numerous uncertainties still in debate. The ARUBA trial induced further investigation into optimal management strategies for these lesions. Here, we present a systematic-review and meta-analysis focusing on ARUBA-eligible studies, aiming to correlate patient data with outcomes and discuss key aspects of these studies. METHODS: Following PRISMA guidelines, we conducted a systematic-review. Variables analyzed included bAVM Spetzler-Martin (SM) grade, treatment modalities, and outcomes such as mortality and neurological deficits. We compared studies with a minimum of 50% cases classified as SM 1-2 lesions and those with less than 50% in this category. Similarly, a comparison between studies with at least 50% microsurgery-cases and those with less than 50% was performed. We examined correlations between mortality incidence, SM distribution, and treatment modalities. RESULTS: Our analysis included 16 studies with 2.417 patients. The frequency of bAVMs SM-grade 1-2 ranged from 44% to 76%, SM-grade 3 from 19% to 48%, and SM 4-5 from 5 to 23%. Notably, studies with more than 50% cases presenting lesions SM-grade 1-2 presented significantly lower mortality rates than those with less than 50% cases of SM 1-2 lesions (P < 0.001). No significant difference in mortality rates or neurological deficits was identified between studies with more than 50% of microsurgery-cases and those with less than 50%. CONCLUSIONS: The analysis revealed that studies with a higher proportion of bAVMs presenting SM 1-2 lesions were associated with lower mortality rates. Mortality did not show a significant association with treatment modalities.

Quantitative analysis of external carotid artery bypass donor vessels by recipient and approach.

INTRODUCTION: Utilization an in-situ pedicle of the external carotid artery (ECA) as an arterial donor can allow for the successful augmentation or replacement of flow to a large vascular territory. We propose a mathematical model for quantitatively analyzing and grading the suitability of donor and recipient bypass vessels based on a set of anatomical and surgical variables in order to predict which pair has the greatest possibility for success. Using this method, we analyze all of the potential donor-recipient pairs for each ECA donor vessel-including the superficial temporal (STA), middle meningeal (MMA), and occipital (OA) arteries. METHODS: The ECA pedicles were dissected in frontotemporal, middle fossa, subtemporal, retrosigmoid, far lateral, suboccipital, supracerebellar, and occipital transtentorial approaches. For each approach, every potential donor-recipient pair was identified, and donor length and diameter were measured as well as depth of field, angle of exposure, ease of proximal control, maneuverability, and length and diameter of the recipient segment. Anastomotic pair scores were determined by adding the weighted donor and recipient. RESULTS: The best overall anastomotic pairs were OA-vertebral artery (V3, 17.1) and STA-insular (M2, 16.3) and STA-sylvian (M3, 15.9) segments of the middle cerebral artery. Other strong anastomotic combinations were OA- telovelotonsillar (15) and OA- tonsilomedullary (14.9) segments of the posterior inferior cerebellar artery, and MMA-lateral pontomesencephalic segment of the superior cerebellar artery (14.2). CONCLUSIONS: This novel model for anastamotic pair scoring can serve as a useful clinical tool for selecting the optimal donor, recipient, and approach combination that can help facilitate a successful bypass.

Captopril inhibits Matrix Metalloproteinase-2 and extends survival as a temozolomide adjuvant in an intracranial gliosarcoma model.

BACKGROUND: Captopril is a well-characterized, FDA-approved drug that has demonstrated promise as a repurposed oncology therapeutic. Captopril's known anti-cancer effects include inhibition of Matrix Metalloproteinase-2 (MMP-2), an endopeptidase which selectively breaks down the extracellular matrix to promote cell migration. MMP-2 is a known therapeutic target in gliomas, tumors with significant clinical need. Using an aggressive gliosarcoma model, we assessed captopril's effects on MMP-2 expression in vitro and in vivo as well as its efficacy as an adjuvant in combination therapy regimens in vivo. METHODS: Following captopril treatment, MMP-2 protein expression and migratory capabilities of 9 L gliosarcoma cells were assessed in vitro via western blots and scratch wound assays, respectively. Rats were intracranially implanted with 9 L gliosarcoma tumors, and survival was assessed in the following groups: control; captopril (30 mg/kg/day); temozolomide (TMZ) (50 mg/kg/day), and captopril+TMZ. In vivo experiments were accompanied by immunohistochemistry for MMP-2 from brain tissue. RESULTS: In vitro, captopril decreased MMP-2 protein expression and reduced migratory capacity in 9 L gliosarcoma cells. In a gliosarcoma animal model, captopril decreased MMP-2 protein expression and extended survival as a TMZ adjuvant relative to untreated controls, captopril monotherapy, and TMZ monotherapy groups (27.5 versus 14 (p < 0.001), 16 (p < 0.001), and 23 (p = 0.018) days, respectively). CONCLUSIONS: Captopril decreases gliosarcoma cell migration, which may be mediated by reduction in MMP-2 protein expression. Captopril provided a survival advantage as a TMZ adjuvant in a rat intracranial gliosarcoma model. Captopril may represent a promising potential adjuvant to TMZ therapy in gliosarcoma as a modulator of the MMP-2 pathway.

Fractional anisotropy in degenerative cervical stenosis surgery prognostic: a systematic review / Anisotropia fracionada no prognóstico de cirurgia de estenose cervical degenerativa: revisão sistemática / Anisotropía fraccional en el pronóstico de cirugía de la estenosis cervical degenerativa: revisión sistemática

ABSTRACT: Cervical spondylotic myelopathy (CSM) is a common disease with an increased anticipated burden to health systems worldwide. Methods to predict outcomes in these patients are needed so physicians can provide more effective care. Fractional anisotropy (FA) analysis is a promising technique used to quantify how preserved the diffusion is in neural pathways. A systematic review and meta-analysis were performed using the PRISMA guidelines. Full articles available online were searched for correlation coefficients between FA values and mJOA scores. Average FA values, preoperative mJOA, and postoperative mJOA scores were gathered to perform a correlation analysis. A total of 5 articles presented correlations between FA and mJOA change and were included in the correlation meta-analysis. Correlation coefficients varied from -0.42 and 0.55. The number of patients in each study varied from 15 to 95. The Random effects model resulted in a non-significant correlation coefficient of 0.1315 (95% CI: -0.2575 to 0.4839; p= 0.5124). Spearman's correlation analysis was significant for preoperative vs postoperative mJOA (r = 0.79, p = 0.02), while preoperative FA did not correlate significantly with preoperative or postoperative mJOA. At this point, the data available in the literature is insufficient to determine a real correlation between FA and mJOA scores. More studies are necessary for a better understanding of this matter. Level of Evidence III; Study Review.

RESUMO: A mielopatia espondilótica cervical (CSM, pelas suas siglas em inglês) é uma doença comum com elevados gastos para os sistemas de saúde em todo o mundo. Métodos para prever resultados nesses pacientes são necessários para que a atenção médica seja mais eficaz. A análise de anisotropia fracionada (FA) é uma técnica promissora usada para quantificar a preservação da difusão nas vias neurais. Uma revisão sistemática e meta-análise foi realizada usando as diretrizes PRISMA. Artigos completos disponíveis online foram avaliados em busca de coeficientes de correlação entre valores de FA e escores de mJOA. Valores médios de FA, escores de mJOA pré-operatórios e pós-operatórios foram coletados para realizar uma análise de correlação. Um total de 5 artigos apresentaram correlações entre alteração de FA e mJOA e foram incluídos na meta-análise de correlação. Os coeficientes de correlação variaram entre -0,42 e 0,55. O número de pacientes em cada estudo variou de 15 a 95. O modelo de efeitos aleatórios resultou em um coeficiente de correlação não significativo de 0,1315 (95% CI: -0,2575 a 0,4839; p= 0,5124). A análise de correlação de Spearman foi significativa para mJOA pré-operatório vs. pós-operatório (r = 0,79, p = 0,02), enquanto a FA pré-operatório não apresentou correlação significativa com o mJOA pré-operatório ou pós-operatório. Os dados disponíveis na literatura neste momento são insuficientes para determinar uma correlação real entre os escores FA e mJOA. Mais estudos são necessários para uma melhor compreensão deste assunto. Nível de Evidência III; Revisão de Estudos.

RESUMEN: La mielopatía cervical espondilótica (CSM, por sus siglas en inglés) es una enfermedad común con una mayor carga anticipada para los sistemas de salud en todo el mundo. Se necesitan métodos para predecir los resultados en estos pacientes para que los médicos puedan brindar una atención más eficaz. El análisis de anisotropía fraccional (FA) es una técnica prometedora que se utiliza para cuantificar cuán preservada está la difusión en las vías neurales. Se realizó una revisión sistemática y un metanálisis utilizando las pautas PRISMA. Se buscaron artículos completos disponibles en línea para encontrar coeficientes de correlación entre los valores de FA y las puntuaciones de mJOA. Se recopilaron los valores promedio de FA, mJOA preoperatorios y mJOA postoperatorios para realizar un análisis de correlación. Un total de 5 artículos presentaron correlaciones entre el cambio de FA y mJOA y se incluyeron en el metanálisis de correlación. Los coeficientes de correlación variaron entre -0,42 y 0,55. El número de pacientes en cada estudio varió de 15 a 95. El modelo de efectos aleatorios resultó en un coeficiente de correlación no significativo de 0,1315 (IC 95%: -0,2575 a 0,4839; p= 0,5124). El análisis de correlación de Spearman fue significativo para la mJOA preoperatoria frente a la posoperatoria (r = 0,79, p = 0,02), mientras que la FA preoperatoria no presentó una correlación significativa con la mJOA preoperatoria o posoperatoria. Los datos disponibles en la literatura en este momento son insuficientes para determinar una correlación real entre las puntuaciones de FA y mJOA. Son necesarios más estudios para una mejor comprensión de este asunto. Nivel de Evidencia III; Revisión de Estudios.

Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas.

Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are characterized by their propensity to invade surrounding brain parenchyma, making curative resection difficult. These tumors typically recur within two centimeters of the resection cavity even after gross total removal. As a result, there has been an emphasis on developing therapeutics aimed at achieving local disease control. In this review, we will summarize the current developments in the delivery of local therapeutics, namely direct injection, convection-enhanced delivery and implantation of drug-loaded polymers, as well as the application of these therapeutics in future methods including microchip drug delivery and local gene therapy.

Craniossinostoses não sindrômicas: uma análise retrospectiva / Non-syndromic craniosynostosis: a retrospective analysis

Introdução: Craniossinostoses são definidas como fusões prematuras de uma ou mais suturas cranianas. Podem ser classificadas de acordo com as suturas envolvidas, malformações correlacionadas e alterações genéticas, podendo ser sindrômicas ou não. Sua incidência estimada em 1:2.000-2.500 nascidos vivos, sendo apenas 8% sindrômicas. Existem múltiplas opções cirúrgicas para a correção destas malformações, e o encaminhamento precoce para centros especializados no tratamento destes doentes é necessário para uma melhor indicação terapêutica. O diagnóstico é pautado no exame físico e tomografia computadorizada. O tratamento cirúrgico traz melhoras significativas estéticas e no convívio social dos pacientes. O objetivo é analisar os dados, retrospectivamente, dos pacientes submetidos à cirurgia para correção de craniossinostoses, no HC da UNESP-Botucatu. Métodos: Análise retrospectiva dos prontuários de pacientes submetidos à correção cirúrgica de craniossinostoses entre 2012 e 2017. Resultados: A prevalência de escafocefalia e trigonocefalia foi igual (38,5%), idade média de abordagem de 24 meses, o tempo cirúrgico médio foi de 3h48min, sendo menor nas escafocefalias, 2h50min. Todos os pacientes receberam transfusão de sangue no perioperatório com média percentual em relação ao volume sanguíneo pré-operatório de 24,9% e fizeram pós-operatório em UTI pediátrica. Não houve óbitos ou complicações, e os resultados tidos como bom pela equipe e familiares. Conclusão: O tratamento cirúrgico aberto das craniossinostoses não sindrômicas é um procedimento seguro. As equipes de cirurgia plástica conseguem alcançar resultados equiparáveis aos descritos na literatura, com baixas taxas de complicações, bom resultado estético, quando executado de maneira adequada, e com abordagem multidisciplinar.

Introduction: Craniosynostoses are defined as premature fusions of one or more cranial sutures. They can be classified according to the sutures involved, correlated malformations and genetic alterations, and maybe syndromic or not. Its incidence is estimated at 1: 2,000-2,500 live births, with only 8% being syndromic. There are multiple surgical options for the correction of these malformations, and early referral to specialized centers for the treatment of these patients is necessary for a better therapeutic indication. The diagnosis is based on physical examination and computed tomography. The surgical treatment brings significant aesthetic and social improvements to patients. The objective is to analyze retrospectively patient data who underwent surgery to correct craniosynostosis at HC of UNESP-Botucatu. Methods: Retrospective analysis of the medical records of patients who underwent surgical correction of craniosynostosis between 2012 and 2017. Results: The prevalence of scaphocephaly and trigonocephaly was the same (38.5%). The mean age of the approach was 24 months; the mean surgical time was 3h48min, lower in scaphocephaly, 2h50min. All patients received blood transfusions in the perioperative period, with a mean percentage of 24.9% in relation to the preoperative blood volume. They underwent postoperative in a pediatric ICU. There were no deaths or complications, and the results were considered good by the team and family. Conclusion: Open surgical treatment of non-syndromic craniosynostosis is a safe procedure. Plastic surgery teams can achieve results comparable to those described in the literature, with low complication rates, good aesthetic results when performed correctly and with a multidisciplinary approach.

Could formaldehyde induce mutagenic and cytotoxic effects in buccal epithelial cells during anatomy classes?

BACKGROUND: Due to increased formaldehyde exposure, carcinogenic to humans, several researches have been studying the potential toxicity and the safe levels for human beings. The aim of this study was to investigate mutagenicity and cytotoxicity in buccal epithelial exfoliated cells (BEC) of students subjected to formaldehyde (FA) during anatomy classes. MATERIAL AND METHODS: BEC were collected periodically from 17 volunteers of undergraduate programs, who had participated in practical anatomy classes, before and after FA exposure. Cells were stained according to Feulgen method and then micronucleus test was applied. A total of 1,500 cells were assessed per individual in this study for the micronucleus frequency and other parameters of cytotoxicity. RESULTS: There was statistically significant increase in number of micronucleated BEC after FA exposure (after 1 month p=.034 and after 3.5 months p=.017). However, FA exposure caused no significant increase in other nuclear alterations closely related to cytotoxicity (p≥.05). CONCLUSIONS: FA induced mutagenicity during anatomy classes. Cell death increased, but it was not statistically significant. Efforts have to be made to improve air quality and reduce exposures during anatomy classes

Nuclear alterations in nasal mucosa epithelial cells of students exposed to formaldehyde / Alteraciones en los núcleos de las células epiteliales de la mucosa nasal de los estudiantes expuestos a formaldehído

INTRODUCTION: Formaldehyde is a compound with a wide range and is commonly used in anatomy and pathology laboratories. At room temperature is quickly volatilized to a pungent and suffocating gas and its inhalation has been correlated to nuclear alterations in different tissues. We aimed to investigate whether exposure to this compound was correlated with the appearance of cytotoxic and genotoxic features in the nasal epithelial cells of students enrolled in a human anatomy course. MATERIAL AND METHODS: This prospective study collected periodically nasal cells from mucosa of 17 volunteers from two different undergraduate programs with different workloads of practical lessons in an anatomy laboratory, 30 and 90 hours per semester. Cells were staining according to Feulgen method and nuclear morphology was analyzed to detect possible damage. Dunn's post hoc test was used in the statistical analysis. Pearson's correlation was performed for gender, age and questionnaire responses. RESULTS: Epithelial cells showed indicators of cytotoxicity and mutagenicity. Students with a more extensive workload in anatomy laboratory displayed a more severe profile with an increase in karyorrhexis (p 0.05). CONCLUSION: Individuals exposed for short periods of time to formaldehyde are subject to the toxic action of this gas. Karyorrhexis was the most frequently observed cytotoxic feature and micronucleus showed an increase between the first time point. The patterns observed between the student's groups suggest a negative effect due to exposure time

INTRODUCCIÓN: El formaldehído es un compuesto con una amplia variedad y se utiliza comúnmente en los laboratorios de anatomía y patología. En la temperatura ambiente se volatiliza rápidamente en un gas acre sofocante. Su inhalación se ha correlacionado con la aparición de alteraciones nucleares en diferentes tejidos. El objetivo fue investigar si la exposición a este compuesto podría estar relacionado con la aparición de aspectos citotóxicos y genotóxicos en las células epiteliales nasales de los estudiantes del curso de anatomía humana. MATERIAL Y MÉTODOS: En este estudio las células nasales proclives se recogieron periódicamente de la mucosa de los 17 voluntarios de las carreras universitarias con diferentes cargas de clases prácticas en el laboratorio de anatomía, 30 y 90 horas semestrales. Las células fueron teñidas por el método de Feulgen y la morfología nuclear fue evaluada para la detección de posibles daños. Prueba post hoc de Dunn fue utilizada para el análisis estadístico. Correlación de Pearson fue realizada con los datos de sexo, edad y las respuestas del cuestionario. RESULTADOS: Las células epiteliales mostraron indicadores de citotoxicidad, mutagenicidad. Los estudiantes con una carga de trabajo más extensa en el laboratorio de anatomía mostraron perfil más grave con el aumento de cariorrexis (p 0,05). CONCLUSIÓN: Individuos expuestos durante cortos períodos de tiempo a formaldehído están sujetos a la acción tóxica de gas. Cariorrexis fue la característica citotóxica observada con mayor frecuencia y micronúcleos mostraron un aumento entre el primer punto de tiempo. Los diferentes patrones de daños observados entre los grupos de estudiantes sugieren que el efecto negativo de gas puede está relacionado con el tiempo de exposición