Deep brain stimulation of dorsal and ventral borders of the subthalamic nucleus in patients with parkinson's disease: a systematic review / Estimulação cerebral profunda das bordas dorsal e ventral do núcleo subtalâmico em pacientes com doença de parkinson: uma revisão sistemática

Parkinson's disease patients experience motor signs and non-motor symptoms caused by the disease. Deep brain stimulation of the Subthalamic Nucleus (STN) itself or its ventral or dorsal borders is one of the treatment options indicated to treat the refractory symptoms of this disease. However, it is still unknown which edge, when stimulated, generates more beneficial effects for these patients, which is the objective of this systematic review. To answer this question, electronic and manual searches were conducted in five databases and gray literature to identify studies that answered the question in this review. The selection of studies, data extraction, and analysis of the risk of bias of the included studies were performed. In total, seven studies were included in this systematic review. Most studies presented a minimal risk of bias, and their main methodological limitation was related to the sample inclusion criteria. Stimulation of the dorsal or ventral borders of the STN resulted in improved motor signs of Parkinson's disease, with some of the studies tending towards the choice of dorsal border stimulation for better motor effects, while the improvement in non-motor symptoms and inhibitory control was due to stimulation of the ventral border. The findings of this systematic review suggest that the improvement in the motor signs of Parkinson's disease can be brought about by stimulating the dorsal or ventral borders of the subthalamic nucleus, whereas non-motor symptoms such as anxiety improve with stimulation of the ventral border.

Pacientes com doença de Parkinson frequentemente experimentam sinais motores e sintomas não motores ocasionados pela doença. A estimulação cerebral profunda do Núcleo Subtalâmico (NST) ou de suas bordas ventral ou dorsal é uma das opções de tratamento indicada para tratar sintomas refratários dessa doença. No entanto, ainda não se sabe qual a borda que, ao ser estimulada, gera mais efeitos benéficos a esses pacientes, sendo esse o objetivo dessa revisão sistemática. Para responder essa questão foram realizadas buscas eletrônicas e manuais em cinco bancos de dados e na literatura cinzenta para identificar estudos que abordassem essa temática. Foram executados a seleção dos estudos, extração de dados e análise do risco de viés dos estudos incluídos. No total, sete artigos foram selecionados para comporem o estudo. A maioria dos estudos apresentou baixo risco de viés, sendo que a principal limitação metodológica deles se relacionou com os critérios de inclusão da amostra. A estimulação da borda dorsal ou ventral do NST resultou na melhora dos sinais motores da doença de Parkinson, com alguns dos estudos inclusos com tendência para a escolha da estimulação da borda dorsal para melhores efeitos motores, enquanto a melhora dos sintomas não motores e do controle inibitório foi devido à estimulação da borda ventral. Os achados sugerem que a melhora dos sinais motores da doença de Parkinson pode ser ocasionada ao estimular a borda dorsal ou ventral do Núcleo subtalâmico, enquanto os sintomas não motores, como a ansiedade, melhoram com a estimulação da borda ventral.

Mechanism by which exercise improves inhibitory control and drug craving in methamphetamine abstinent patients / 中国组织工程研究

BACKGROUND:Inhibitory control and drug craving are the core elements of evaluating drug withdrawal in methamphetamine addicts,which has attracted much attention in academic circles.As we all know,in order to achieve complete abstinence from drug addiction,the key is to restore the damaged inhibition and control function of drug addicts and effectively reduce the craving for drugs. OBJECTIVE:To systematically analyze the relationship between exercise and methamphetamine abstinence inhibitory control and drug craving,to find out an effective exercise intervention scheme that can promote methamphetamine abstinence,and to further explore the internal mechanism of exercise,in order to provide theoretical support and applied reference for the future use of exercise in drug withdrawal. METHODS:CNKI,WanFang,VIP,Web of Science,and PubMed databases were searched for relevant literature using the keywords of"exercise,physical activity,methamphetamine,inhibitory function,craving,addiction"in Chinese and"sport*,exercise,methamphetamine,drug craving,executive function,addiction"in English.According to the inclusion and exclusion criteria,86 documents were finally included for review. RESULTS AND CONCLUSION:In terms of inhibitory control in methamphetamine abstinent individuals,either acute and long-term moderate-intensity aerobic exercise or acute high-intensity interval training can significantly improve the inhibitory control capacity of methamphetamine abstinent individuals.For long-term aerobic exercise,aerobic group exercise or full-body comprehensive exercise is more effective.If the exercise format is power cycling,it is recommended to increase the frequency of exercise intervention.In terms of the drug craving intensity in methamphetamine abstinent individuals,acute moderate-intensity aerobic exercise and resistance training,as well as long-term moderate-intensity,high-intensity,or progressive load aerobic and resistance training,can effectively reduce the drug craving in methamphetamine abstinent individuals.Exercise exerts intrinsic regulatory effects on methamphetamine-mediated addiction.Exercise can influence the expression of tyrosine hydroxylase in the brain's ventral tegmental area,thereby stimulating the expression of dopamine receptor coupling proteins and promoting dopamine synthesis in the brain's reward regions,thereby compensating for dopamine depletion caused by methamphetamine addiction.Furthermore,exercise can also regulate protein kinase A inhibitors,affecting the protein kinase A signaling pathway mediated by dopamine D1 receptors,by inhibiting protein kinase A,thus affecting cAMP response element-binding protein and regulating methamphetamine addiction.Additionally,exercise can also,at the genetic level,affect the expression of the c-fos gene in the brain's nucleus accumbens region,activate a subset of glutamatergic neurons in this area,generate a rewarding effect,and thus improve methamphetamine addiction.Although current research has confirmed the relationship between exercise and methamphetamine addiction and has clarified the brain mechanisms underlying the effects of exercise,whether there are other brain regulatory pathways for the effects of exercise remains to be explored through more scientifically rigorous animal or human experiments,starting from the cellular or molecular level.

Reward effect of flubromazolam and its underlying neural circuit mechanism / 中国药科大学学报

@#Abstract: Flubromazolam (Flub) is a novel psychoactive substance of benzodiazepines and the mechanism underlying its addiction still remains elusive. This study investigated the reward effect of Flub using conditioned place preference (CPP) mouse model. The neuronal activity was evaluated by c-Fos expression, and the neural circuit was tracked by virus tracing. This study also investigated the regulatory effect of neural circuits on Flub-induced reward effects through chemogenetic approach. The results showed that, at the dose of 3 mg/kg, Flub significantly increased CPP score and c-Fos expression in dopaminergic (DA) neurons of ventral tegmental area (VTA). Inhibition of VTA dopaminergic neuron activity dramatically decreased Flub-induced CPP score. Virus tracing verified GABAergic neuronal projection of medial rostrum tegmental nucleus (RMTg) to VTA dopaminergic neurons. Activation of RMTgGABA→VTADA circuit or blockade of benzodiazepine receptors (BZR) in RMTg significantly decreased Flub-induced CPP score. These results indicate that Flub produced reward effect via BZR-mediated RMTgGABA→VTADA circuit.

Food Addiction and Its Neural Circuitry Regulation Mechanism / 生物化学与生物物理进展

Food addiction refers to the individual dependence on certain specific foods (high-calorie foods) to the extent that it becomes difficult to control and manifests a series of addictive-like behavioral changes. Food addiction is an important factor in the development of human obesity and is also a core factor that most people cannot maintain weight loss or adhere to restrictive diets to maintain a healthy weight. A deeper understanding of food addiction and its neurobiological mechanisms will provide accurate targets for intervening in food addiction to improve obesity. Food addiction is characterized by compulsive, chronic and repetitive nature. The Yale Food Addiction Scale (YFAS), a scale specifically designed to assess food addiction, was developed in 2009 by modeling all the DSM-IV for substance dependence to be applicable to eating behavior. In 2016, Gearhardt developed the Yale Food Addiction Scale 2.0, which contains 35 survey questions, to align the YFAS scale with the diagnostic criteria for addictive disorders in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. One of the most valid and used animal models for food addiction is the mouse food self-administration model. The mouse food self-administration model was modified according to the rat cocaine addiction model, and the food addiction status of the animals was evaluated based on three behaviors: persistence of feeding response, feeding motivation, and compulsive feeding. Studies have shown that the neural circuits of the lateral hypothalamus-ventral tegmental area-nucleus accumbens and ventral tegmental area-prelimbic-nucleus accumbens are key neurobiological mechanisms that regulate food addiction. Dopaminergic neurons in the ventral tegmental area project to the nucleus accumbens (NAc) to facilitate food reinforcement, food reward, and food addiction. The corticotropin-releasing factor (CRF) secreted by the hypothalamus may mediate chronic stress-induced VTA-nucleus accumbens reward system dysfunction and promote food addiction in mice. Meanwhile, the nucleus accumbens receives glutamatergic projections from the prelimbic cortex, an integral part of the reward system. Specific inhibition of the PL-NAc neural circuit develops a food addiction-susceptible phenotype in mice. Furthermore, dopaminergic projections from the ventral tegmental area to the prelimbic cortex specifically inhibited the PL-NAc neural circuit to promote a food-addicted phenotype in mice. Additionally, neurotensin-positive neurons in the lateral septum (LSNts) project to the tuberal nucleus (TU) via GABA signaling to suppress hedonic feeding.

Umbilical and epigastric hernia repair: a systematic review / Tratamento das hérnias umbilicais e epigástricas: uma revisão sistemática

ABSTRACT BACKGROUND: Umbilical and epigastric hernias are among the most common hernias of the abdominal wall; however, there is a lack of standardization for their treatment. AIMS: To clarify the controversies regarding therapeutic possibilities, indications, and surgical techniques for umbilical and epigastric hernia repair. METHODS: A systematic review and qualitative analysis of randomized clinical trials published in the last 20 years, involving adults (aged 18 years and over) with umbilical and/or epigastric hernias, was performed by systematically searching the PubMed/Medline, Cochrane, SciELO, and LILACS databases. The risk of bias in individual studies was assessed using the Cochrane Risk of Bias Tool. RESULTS: Initially, 492 studies were selected and, subsequently, 15 randomized controlled clinical trials were chosen that met the inclusion criteria and underwent full reading and qualitative analysis, considering possible bias. CONCLUSIONS: This review concluded that it is evident the superiority of the use of meshes in the repair of epigastric/primary umbilical hernias with a defect larger than 1 cm, even in certain emergency situations. However, suture repair is a good option for patients with a defect smaller than 1 cm. In the laparoscopic approach, recent evidence points towards possible superiority in fixation with fibrin sealant, and fascial defect closure is recommended. In addition, due to a scarcity of randomized controlled trials with low risk of bias, further studies are needed on types, positioning and fixation techniques, as well as the real role of video-assisted laparoscopic surgery in the correction of hernias, especially umbilical.

RESUMO RACIONAL: As hérnias umbilicais e epigástricas estão entre as hérnias mais comuns da parede abdominal, porém falta padronização em relação ao seu tratamento. OBJETIVOS: Esclarecer as controvérsias acerca das possibilidades terapêuticas, indicações e técnicas cirúrgicas relacionadas ao tratamento das hérnias umbilicais e epigástricas. MÉTODOS: Foi realizada revisão sistemática e análise qualitativa dos estudos publicados nos últimos 20 anos, envolvendo indivíduos maiores de 18 anos com hérnias umbilicais e/ou epigástricas, por meio de busca nas bases de dados PubMed/Medline, Cochrane, LILACS e SciELO, sendo selecionados estudos do tipo ensaios clínicos randomizados controlados para análise. Foi determinado o risco de viés de cada estudo individualmente de acordo com a ferramenta Cochrane Risk of Bias Tool. RESULTADOS: Foram inicialmente selecionados 492 estudos e, posteriormente, escolhidos 15 ensaios clínicos randomizados controlados que preencheram os critérios de inclusão e foram submetidos à leitura integral e análise qualitativa, considerando os possíveis viés. CONCLUSÕES: Esta revisão concluiu que é evidente a superioridade do uso de telas no tratamento das hérnias epigástricas/umbilicais primárias com defeito superior a 1 cm, mesmo em certas situações de emergência. No entanto, o reparo com sutura pode ser uma opção em pacientes com defeito menor que 1 cm. Na abordagem laparoscópica, evidências recentes apontam para possível superioridade na fixação com selantes de fibrina e o fechamento do defeito fascial é recomendado. Ademais, devido à escassez de ensaios clínicos randomizados controlados com baixo risco de viés, foi identificada a necessidade de desenvolver mais estudos sobre os tipos, técnicas de posicionamento e fixação das telas, assim como sobre qual o real papel da cirurgia videolaparoscópica na correção das hérnias, especialmente as umbilicais.

Intra-abdominal pressure monitoring during lázaro da silva's procedure for ventral hernia repair: a cross-sectional study / Monitoramento da pressão intra-abdominal durante procedimento de lázaro da silva para correção de hérnia ventral: estudo transversal

ABSTRACT BACKGROUND: Maintaining normal intra-abdominal pressure (IAP) levels must be one major outcome of any ventral hernia repair, avoiding hypertension or abdominal compartment syndrome. AIMS: To evaluate IAP during ventral hernia repair using Lázaro da Silva's procedure. METHODS: IAP measurements using intravesical pressure were performed during four crucial intraoperative moments. Twenty-eight patients submitted to incisional herniorrhaphy were analyzed. RESULTS: The IAP increased by 0.5 mmHg during the procedure, regardless of the type of prior laparotomy, sex, age, obesity, or hernia width. CONCLUSIONS: Despite the IAP increase observed, Lázaro da Silva's procedure did not result in intra-abdominal hypertension or abdominal compartment syndrome.

RESUMO RACIONAL: A manutenção dos níveis normais de pressão intra-abdominal (PIA) deve ser um dos principais resultados de qualquer correção de hérnia ventral, evitando hipertensão ou síndrome do compartimento abdominal. OBJETIVOS: Avaliar a PIA durante a correção de hérnia ventral pela técnica de Lázaro da Silva. MÉTODOS: As medidas da PIA por meio de pressão intravesical foram realizadas durante quatro momentos cruciais do intraoperatório. Foram analisados 28 pacientes submetidos à herniorrafia incisional. RESULTADOS: A PIA aumentou 0,5 mmHg durante o procedimento, independentemente do tipo de laparotomia prévia, sexo, idade, obesidade ou extensão da hérnia. CONCLUSÕES: Apesar do aumento da PIA observado, o procedimento de Lázaro da Silva não resultou em hipertensão intra-abdominal ou síndrome do compartimento abdominal.

Prone position in intubated patients with acute respiratory failure due to COVID-19 in an ICU in the state of São Paulo / Postura prona em pacientes intubados com insuficiência respiratória aguda por COVID-19 em uma UTI do estado de São Paulo

Abstract Introduction The severity of acute respiratory distress syndrome (ARDS) caused by COVID-19 can vary and be influenced by comorbidities. The position is a treatment strategy for critically ill patients; however, it is unclear what the physiological response is and which patients benefit. Objective To determine whether the prone position (PP) and the length of stay in the intensive care unit (ICU) are associated with the time of orotracheal intubation (OTI) and with the death rate in patients on mechanical ventilation with moderate to severe ARDS. Methods An observational, longitudinal, retrospective study was carried out in a tertiary public hospital in the city of São Paulo. Data were collected from the medical records of all patients diagnosed with COVID-19, with a positive PCR, admitted to the ICU and intubated, from April 2020 to July 2021. Pearson's chi-square and Fischer's exact tests were used to compare sample data, and distributions in the two groups were compared using the Mann-Whitney test. Results There was no statistically significant difference for ICU length of stay, OTI time and death rate between patients who were prone versus non-prone [13 (4.0 - 23.0) vs. 13.5 (7.2 - 17.0), p = 0.453; 12 (3.0 - 13.0) vs. 10 (6.0 -15.5), p = 0.772; 71 vs. 68%, p = 0.817, respectively]. Conclusion This study did not demonstrate an association between PP and days of OTI, days of hospitalization and mortality in patients with severe hypoxemia.

Resumo Introdução A gravidade da síndrome do desconforto respiratório agudo (SDRA) ocasionada pela COVID-19 pode variar e ser influenciada por comorbidades presentes. A postura prona é estratégia de tratamento para pacientes graves, no entanto, não está claro qual é a resposta fisiológica e quais pacientes se beneficiam. Objetivo Verificar se existe associação da postura prona (PP) com o tempo de internação em unidade de terapia intensiva (UTI), tempo de intubação orotraqueal (IOT) e taxa de óbito em pacientes em ventilação mecânica com SDRA de moderada a grave. Métodos Trata-se de um estudo observacional, longitudinal e retrospectivo, realizado em hospital público terciário no município de São Paulo. Foram coletados dados dos prontuários de todos os pacientes com diagnóstico de COVID-19, com PCR positivo, internados na UTI e intubados, no período de abril de 2020 a julho de 2021. Os testes qui-quadrado de Pearson e exato de Fischer foram utilizados para comparar dados da amostra, e as distribuições nos dois grupos foram comparadas por meio do teste de Mann-Whitney. Resultados Não houve diferença estatisticamente significante para o tempo de internação na UTI, tempo de IOT e taxa de óbito entre os pacientes que foram pronados versus os não pronados [13 (4,0 - 23,0) vs. 13 (7,2 - 17,0), p = 0,453; 12 (3,0 - 13,0) vs. 10 (6,0 - 15,5), p = 0,772; 71% vs. 68%, p = 0,817, respectivamente]. Conclusão Este estudo não demonstrou associação da PP com os dias de IOT, dias de internação na UTI e mortalidade em pacientes com hipoxemia grave.

Central line-associated bloodstream infections in patients with COVID-19 / Infecciones de la circulación sanguínea relacionadas con catéter venoso central en pacientes con COVID-19 / Infecção primária de corrente sanguínea relacionada a cateter venoso central em pacientes com COVID-19

Objective: to investigate the association between central line-associated bloodstream infections and clinical and care variables of intensive care unit patients with COVID-19 hospitalized at a reference public health institution. Method: a case-control study. Results: the study sample consisted of 70 patients diagnosed with central line-associated bloodstream infections (case group) and 70 non-infected patients (control group). Most patients were male, with mean age of 57.93±13.93 years old and provided with a double lumen catheter. Median time of central line-associated bloodstream infections onset was 11 (8-18) days. Longer time on mechanical ventilation ( P =0.014; OR: 1.79; 95% CI: 0.91-3.51) and prone position ( P =0.017; OR: 2.41; 95% CI: 1.22-4.81) were associated with central line-associated bloodstream infections onset. Conclusion: longer time on invasive mechanical ventilation and prone position contributed to central line-associated bloodstream infections onset in COVID-19 patients.

Objetivo: investigar la asociación entre infecciones de la circulación sanguínea relacionadas con catéter venoso central y variables clínicas y asistenciales de pacientes con COVID-19 ingresados en la unidad de cuidados intensivos de una institución pública de salud de referencia. Método: un estudio caso-control. Resultados: la muestra del estudio estuvo compuesta por 70 pacientes con diagnóstico de infección de la circulación sanguínea relacionada con catéter venoso central (grupo caso) y 70 pacientes no infectados (grupo control). La mayoría de los pacientes eran del sexo masculino, con edad media de 57,93±13,93 años y provistos de catéter de doble luz. El tiempo medio de aparición de las infecciones del torrente sanguíneo asociadas a catéter venoso central fue de 11 (8-18) días. Un mayor tiempo en ventilación mecánica ( P =0,014; RP: 1,79; IC 95%: 0,91-3,51) y en posición de decúbito prono ( P =0,017; RP: 2,41; IC del 95 %: 1,22-4,81) se asociaron con la aparición de infecciones de la circulación sanguínea relacionadas con catéter venoso central. Conclusión: un tiempo más prolongado con ventilación mecánica invasiva y posición de decúbito prono contribuyeron a la aparición de infecciones de la circulación sanguínea relacionadas con catéter venoso central en pacientes con COVID-19.

Objetivo: investigar a associação entre infecção primária de corrente sanguínea relacionada a cateter venoso central e variáveis clínicas e assistenciais de pacientes com COVID-19 internados na unidade de terapia intensiva de uma instituição pública de saúde de referência. Método: estudo caso-controle. Resultados: o estudo foi composto por 70 pacientes com diagnóstico de infecção primária de corrente sanguínea relacionada a cateter venoso central (grupo caso) e 70 pacientes sem infecção (grupo controle). Pacientes predominantemente do sexo masculino, média de idade de 57,93±13,93 anos e portadores de cateter de duplo lúmen. A mediana de tempo de ocorrência das infecções primárias de corrente sanguínea relacionadas a cateter venoso central foi de 11 (8-18) dias. Maior tempo em ventilação mecânica ( P =0,014; RP: 1,79; IC 95%: 0,91-3,51) e posição prona ( P =0,017; RP: 2,41; IC 95%: 1,22-4,81) foram associados à ocorrência de infecções primárias de corrente sanguínea relacionadas a cateter venoso central. Conclusão: maior tempo em ventilação mecânica invasiva e posição prona contribuíram para a ocorrência de infecções primárias de corrente sanguínea relacionadas a cateter venoso central em pacientes com COVID-19.

Experiencia del tratamiento de la hernia incisional en un hospital de tercer nivel en Colombia / Experience of the treatment of incisional hernia in a third level hospital in Colombia

Introducción. El manejo de las hernias se ha instaurado como un problema quirúrgico común, estimándose su aumento en los próximos años. El objetivo del presente trabajo fue describir el curso clínico, los aspectos del tratamiento quirúrgico y factores asociados a la presencia de complicaciones en pacientes intervenidos por hernia incisional. Métodos. Estudio descriptivo en el que se analizaron las características de una cohorte de pacientes llevados a corrección quirúrgica de hernia incisional en el Hospital Universitario Hernando Moncaleano Perdomo, un centro de alta complejidad en Neiva, Colombia, entre 2012 y 2019. Los datos fueron recolectados en programa Microsoft Excel® y analizados en SPSSTM, versión 21. Resultados. Se realizaron 133 correcciones de hernias incisionales, 69,9 % en mujeres y la mayoría ubicadas en la línea media (84,2 %). La edad media de los pacientes al momento de la intervención fue de 52 años ±14,6. Las comorbilidades más frecuentes fueron obesidad, hipertensión y diabetes. La causa más frecuente de la hernia fue traumática (61,7 %). La frecuencia de complicaciones fue superior al 50 %, en su mayoría menores; se encontró asociación con obesidad para la presencia de seroma. La mortalidad fue del 2,3 %. Conclusión.La hernia incisional es un problema de salud pública. Consideramos que la obesidad y el uso de malla pueden ser factores de riesgo asociados con la presentación de complicaciones postoperatorias, así como el aumento de los gastos relacionados con días de hospitalización

Introduction. Hernias management has become a common surgical problem, with an estimated increase in the coming years. The objective of this study was to describe the clinical course, aspects of surgical treatment and factors associated with the presence of complications in patients operated on for incisional hernia. Methods. Descriptive study, in which the characteristics of a cohort of patients taken to surgical correction of incisional hernia at the Hospital Universitario Hernando Moncaleano Perdomo, a high complexity medical center located in Neiva, Colombia, between 2012 and 2019 were analyzed, whose data were collected in Microsoft Excel® software and analyzed in SPSSTM, version 21. Results. One-hundred-thirty-three incisional hernia corrections were performed. The mean age at the intervention was 52 years ±14.6. The most frequent comorbidities were weight disorders, hypertension and diabetes. Only one laparoscopy was performed, the first etiology of the hernia was traumatic (61.7%) and midline (84.2%). The frequency of complications was greater than 50%, mostly minors. An association with obesity was found for the presence of seroma. Mortality was 2.3%. Conclusion. Incisional hernia is a public health problem. We consider that obesity and the use of mesh are a risk factor associated with the presentation of postoperative complications as well as the increase in costs related to days of hospitalization

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study

Introduction: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. Methods: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. Results: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. Conclusion: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

Effects of cloperastine, a non-narcotic antitussive, on the expression of GIRK channels in the brain of methamphetamine-induced hyperactive mice

Objectives: Centrally-acting antitussives with inhibitory effects on G protein-coupled inwardly rectifying potassium (GIRK) channels have been shown to also inhibit methamphetamine-induced hyperactivity in mice. In this study, we examined if cloperastine, which is the most potent inhibitor of the GIRK channels among antitussives, is sensitive to the expression levels of GIRK channels in the brain of methamphetaminetreated mice. Materials and Methods: The brain tissues have been removed and the total RNA has been extracted from tissues. The mRNA levels were evaluated using semiquantitative reverse transcription-polymerase chain reaction. Results: The concentration levels of the mRNA of GIRK channels within the ventral midbrain of methamphetamine-treated mice increased as compared with that in control and cloperastine reduced an upregulation in GIRK2, one of the subunits of the GIRK channels, by the injection of methamphetamine. Conclusion: These findings suggest that cloperastine might ameliorate hyperactivity by inhibiting the GIRK channels in the brain.

Resting-state functional connectivity alterations of ventral tegmental area in adult male smokers: a functional magnetic resonance imaging study / 中华行为医学与脑科学杂志

Objective:To investigate the alterations of resting-state functional connectivity (RSFC) in ventral tegmental area (VTA) and substantia nigra (SN) among male smokers, and its correlation with clinical characteristics of smoking.Methods:The resting-state functional magnetic resonance data of 131 subjects recruited from January 2014 to December 2018 were analyzed retrospectively, including 76 smokers (smoking group) and 55 non-smokers (control group). VTA/SN was selected as regions of interest (ROI), and then calculated RSFC between VTA/SN and the whole brain.Based on SPM12 software, independent sample t-test was conducted to compare the differences in RSFC between smoking group and control group.Based on SPSS 22.0 software, Pearson correlation analysis was used to investigate the relationships between the RSFC of brain regions with significant differences and Fagerstr?m test for nicotine dependence (FTND) score, pack-year of smokers. Results:Compared with control group, the results showed decreased RSFC between VTA and the brain regions related default mode network (DMN)(including posterior cingulate cortex, right anterior cuneiform lobe, bilateral superior temporal gyrus, right middle temporal gyrus and right inferior parietal lobule), and regions of limbic system(including right marginal lobe and right angular gyrus), right calcarine (MNI: x, y, z=24, -55, -14) and left insula(MNI: x, y, z=-35, -11, 9) in smoking group(GRF corrected, voxel level P<0.005, cluster level P<0.05). Taking SN as the seed, there was no significant difference between smoking group and control group ( P>0.05). RSFC of VTA-left superior temporal gyrus was positively correlated with pack-year( r=0.243, P=0.034) and FTND ( r=0.282, P=0.014). VTA-left insula RSFC was positively correlated with FTND ( r=0.316, P=0.006). Conclusion:The RSFC in the mesolimbic system and the VTA-DMN circuit exist abnormal changes in smokers.To some extent, it may explain the reward deficits and dysfunction of emotion regulation in smokers, which may provide clues for further understanding the mechanism of tobacco addiction.

Roles of HMGB1 in spread of pain sensitization of trigeminal neuropathic pain / 中国药理学与毒理学杂志

OBJECTIVE Trigeminal pain is mostly uni-lateral orofacial,but pain sensitization often spreads to contralateral orofacial or distal body regions.Widespread trigeminal pain has more severe intensity,longer dura-tion,and wider distribution,accompanied by more serious comorbid emotional syndrome.Unfortunately,the first-line analgesics for neuropathic pain has limited effect on widespread pain along with unavoidable side effects.In-depth understanding of the pathogenesis of wide-spread trigeminal pain is urgently needed.METHODS Trigeminal pain was induced by partial transection of the infraorbital nerve(p-IONX)and evaluated by measur-ing nociceptive thresholds to mechanical or heat stimula-tion.Neuronal activity was evaluated by single-unit and patch clamp recordings.HMGB1 expression was mea-sured by immunohistochemistry.Antagonism of HMGB1 was achieved by injecting anti-HMGB1 monoclonal anti-body(mAb)intracerebrally or intraperitoneally.RESULTS P-IONX model induced not only orofacial algesia but also somatic algesia in hind paw.Spontaneous firing frequency of glutamatergic neurons in the ventral posteromedial tha-lamic nucleus(VPMGlu)as well as the amplitude and fre-quency of sEPSCs significantly increased after p-IONX.Moreover,calcium signal recording showed that VPMGlu became to be activated by the noxious mechanical stimu-lation given on the hind paw,suggesting that VPMGlu recruited somatic afferents after p-IONX.We further explored the upstream brain regions of VPMGlu by virus retrograde tracing.We found the afferents from the grac-ile nucleus/cuneate nucleus(Gr/Cu),which are involved in the conduction of somatic sensation,markedly increased.And chemogenetical inhibiting Gr/Cu-VPM circuit alleviated the widespread neuropathic pain.In addition,the expression of HMGB1 in the VPM was sig-nificantly increased after p-IONX.Local administration of anti-HMGB1 mAb in the VPM relieved widespread neuro-pathic pain in mice receiving p-IONX.CONCLUSION These results demonstrate that the remodeling of affer-ent neurons in VPM underlie the spreading of wide-spread trigeminal neuropathic pain.Highly expressed HMGB1 in VPM plays an important role in these patho-logical changes after nerve injury and systemic adminis-tration of anti-HMGB1 mAb concurrently relieves wide-spread pain.

Recent advance in anxiety related neural circuits regulating by ventral tegmental area / 中华神经医学杂志

As a common emotional and psychogenic disorder, anxiety disorder seriously threats the human physical and mental health. Ventral tegmental area (VTA) is the canter of the mesocortical limbic circuit, with extensive bidirectional connections to forebrain areas, and plays important role in regulating reward, motivation, cognition, and disgust. Besides, VTA is involved in anxiety regulation by forming functional connections with multiple brain regions and connecting external stimulus information and feedback output behaviours. This article briefly summarizes the different cell subsets of VTA and its involvement in anxiety-related neural circuits.

An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice / 神经科学通报·英文版

Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex-midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.

Research progress on the involvement of dopaminergic neurons in the ventral tegmental area in the regula-tion of anxiety-like behavior / 中国神经精神疾病杂志

Anxiety disorders,dopaminergic neurons and ventral tegmental area(VTA)are related closely.VTA dopaminergic neurons play an important role in the regulation of anxiety.Numerous research results in animals indicated that the VTA dopaminergic neurons,involving in multiple neural pathways,respectively regulate anxiety-like behavior in physiological or pathological condition.Dopamine,the main neurotransmitters in VTA regulates anxiety through dopamine D1 and D2 receptors.In addition,the VTA glutamate,GABA and acetylcholine also play directly or indirectly roles in regulating anxiety.The clinical imaging research showed that the integrity of dopaminergic VTA structural of anxiety disorder group is lower than healthy control.Current researches of VTA dopamine neurons involving in the regulation of anxiety-like behavior is developing at a high speed and deserving further exploration,which will further elucidate the pathogenesis and provide new ideas for prevention and treatment of anxiety disorders.

Clinical effectiveness and its mechanisms of deep brain stimulation in treatment-resistant depressive disor-ders / 中国神经精神疾病杂志

Deep brain electrical stimulation is one of the emerging therapeutic approaches for treatment-resistant depressive disorders.This article outlines a variety of potential targets for deep brain electrical stimulation in the treatment of treatment-resistant depressive disorders and summarizes the results of relevant clinical studies.These targets include the subgenual cingulate gyrus,nucleus accumbens,ventral capsule and ventral striatum area,medial forebrain bundle,and lateral habenula,among other regions.Based on these studies,the article integrates relevant basic research and further discusses the possible mechanisms through which deep brain stimulation may exert therapeutic effects,including synaptic plasticity,neurophysiology,neural circuits,and neurotransmitters.The article also assesses and prospects the further application potential of deep brain electrical stimulation.The authors believe that the multi-target stimulation combining existing clinical research results and neurobiological mechanisms could be a crucial development direction to enhance the treatment of treatment-resistant depressive disorders using deep brain electrical stimulation.

Lesão por pressão em pacientes críticos acometidos pela COVID-19: protocolo de prona / Pressure ulcer in critical patients affected by COVID19: prone position protocol / Úlcera por presión en pacientes críticos afectados por COVID-19: protocolo de decúbito prona

Objetivo: avaliar a incidência de lesão por pressão, por localização, o risco de desenvolvimento pela escala de Braden e o uso de protetores, em pacientes críticos em protocolo de prona com Covid-19, em um hospital em Belo Horizonte. Método: trata-se de um estudo observacional, quantitativo, descritivo e prospectivo. Os dados foram coletados através de prontuário eletrônico, no sistema MV, e no sistema AGEIS Nutrition, durante o período entre 12 de abril de 2021 e 13 de agosto de 2021. Resultados: no total de 251 prontuários analisados de pacientes adultos, evidenciou-se 42,2% apresentaram lesão por pressão, sendo a localização mais frequente em zigomático com 50,9%. A maioria dos pacientes utilizaram espuma multicamadas (92%) e 51,4% de pacientes apresentaram risco elevado de lesão. Conclusão: a incidência de lesão por pressão foi de 42,2%. A presença de comorbidades e o risco elevado na escala de Braden podem ter contribuído para a considerável porcentagem.

Objective: to evaluate the incidence of pressure injury, by location, the risk of development by the Braden scale and the use of protectors, in critical patients in a prone protocol with Covid-19, in a hospital in Belo Horizonte. Method: this is an observational, quantitative, descriptive and prospective study. Data were collected through electronic medical records, in the MV system, and in the AGEIS Nutrition system, during the period between April 12 and August 13, 2021. Results: in the total of 251 analyzed medical records of adult patients, it was evidenced 42.2% had pressure injuries, the most frequent location being zygomatic with 50.9%. Most patients used multilayer foam (92%) and 51.4% of patients were at high risk of injury. Conclusion: the incidence of pressure injuries was 42.2%. The presence of comorbidities and the high risk on the Braden scale may have contributed to the considerable percentage.

Objetivo: evaluar la incidencia de lesión por presión, por localización, el riesgo de desarrollo por la escala de Braden y el uso de protectores, en pacientes críticos en protocolo prono con Covid-19, en un hospital de Belo Horizonte. Método: se trata de un estudio observacional, cuantitativo, descriptivo y prospectivo. Los datos fueron recolectados a través de historias clínicas electrónicas, en el sistema MV y en el sistema AGEIS Nutrición, durante el período comprendido entre el 12 de abril de 2021 y el 13 de agosto de 2021. Resultados: en un total de 251 historias clínicas analizadas de pacientes adultos, se evidenció que el 42,2% presentaba lesiones por presión, siendo la localización más frecuente la cigomática con un 50,9%. La mayoría de los pacientes usaban espuma multicapa (92 %) y el 51,4 % de los pacientes tenían un alto riesgo de lesión. Conclusión: la incidencia de lesiones por presión fue del 42,2%. La presencia de comorbilidades y el alto riesgo en la escala de Braden pueden haber contribuido al considerable porcentaje.

Algoritmos para prevenir lesão por pressão em paciente com COVID-19 em prona / Algoritmos para prevenir la úlcera por presión en pacientes con COVID-19 en prona / Algorithms to prevent pressure injury in COVID-19 patients in prone position

Resumo Objetivo Elaborar e validar o conteúdo de dois algoritmos para orientar profissionais da linha de frente na prevenção e no tratamento da lesão por pressão em paciente com COVID-19 em posição prona. Métodos Estudo realizado entre setembro e novembro de 2021. Para a construção dos algoritmos, realizou-se revisão da literatura junto às bases de dados MEDLINE®, SciELO e Lilacs. Foram pesquisados artigos publicados entre 2011 e 2021. A validação dos algoritmos foi feita por 59 profissionais da saúde (enfermeiros, fisioterapeutas e médicos), que trabalhavam na linha de frente da COVID-19, utilizando-se a técnica Delphi. Para a análise de dados, foi adotado o Índice de Validade de Conteúdo e o coeficiente alfa de Cronbach. Resultados No primeiro ciclo de avaliação, os itens dos algoritmos foram considerados pelos juízes como "parcialmente adequados a totalmente adequados", e o Índice de Validade de Conteúdo variou entre 0,87 e 0,92. O coeficiente alfa de Cronbach variou entre 0,95 e 0,96, indicando excelente consistência interna do questionário de avaliação utilizado pelos juízes. Após implementados os ajustes sugeridos pelos juízes, os algoritmos foram reenviados para o segundo ciclo de avaliação, no qual todos os itens foram julgados como "adequado" e "totalmente adequado", resultando em um Índice de Validade do Conteúdo de 1,0. Conclusão Os algoritmos para orientar profissionais da saúde na prevenção e no tratamento da lesão por pressão em pacientes com COVID-19 em posição prona foram avaliados por enfermeiros, fisioterapeutas e médicos que estavam na linha de frente de combate à COVID-19, que chegaram a um consenso quanto ao conteúdo no segundo ciclo de avaliação.

Resumen Objetivo Elaborar y validar el contenido de dos algoritmos para orientar profesionales de la línea de frente sobre la prevención y tratamiento de la úlcera por presión en pacientes con COVID-19 en posición prona. Métodos Estudio realizado entre septiembre y noviembre de 2021. Para la elaboración de los algoritmos, se realizó revisión de la literatura en las bases de datos MEDLINE®, SciELO y Lilacs. Se buscaron artículos publicados entre 2011 y 2021. La validación de los algoritmos fue realizada por 59 profesionales de la salud (enfermeros, fisioterapeutas y médicos), que trabajaban en la línea de frente del COVID-19, utilizando el método Delphi. Para el análisis de datos se adoptó el Índice de Validez de Contenido y el coeficiente alfa de Cronbach. Resultados En el primer ciclo de evaluación, los ítems de los algoritmos fueron considerados por los jueces como "parcialmente adecuados a totalmente adecuados", y el Índice de Validez de Contenido varió entre 0,87 y 0,92. El coeficiente alfa de Cronbach varió entre 0,95 y 0,96, lo que indica una excelente consistencia interna del cuestionario de evaluación utilizado por los jueces. Después de implementar las mejoras sugeridas por los jueces, se reenviaron los algoritmos para el segundo ciclo de evaluación, en el cual todos los ítems fueron calificados como "adecuado" y "totalmente adecuado", con un resultado del Índice de Validez de Contenido de 1,0. Conclusión Los algoritmos para orientar profesionales de la salud sobre la prevención y el tratamiento de la úlcera por presión en pacientes con COVID-19 en posición prona fueron evaluados por enfermeros, fisioterapeutas y médicos que estaban en la línea de frente de combate al COVID-19 y llegaron a un consenso respecto al contenido en el segundo ciclo de evaluación.

Abstract Objective To develop and validate the content of two algorithms to guide frontline professionals in the prevention and treatment of pressure injuries in COVID-19 patients in prone position. Methods Study conducted between September and November 2021. A literature review was performed in MEDLINE®, SciELO and Lilacs databases to build the algorithms. Articles published between 2011 and 2021 were searched. The validation of algorithms was performed by 59 health professionals (nurses, physical therapists and physicians) who worked on the frontline of COVID-19. The Delphi technique was used, and Content Validity Index and Cronbach's alpha coefficient were adopted for data analysis. Results In the first evaluation cycle, the items of algorithms were considered as "partially adequate to totally adequate" by the judges, and the Content Validity Index ranged between 0.87 and 0.92. Cronbach's alpha coefficient ranged between 0.95 and 0.96, indicating excellent internal consistency of the evaluation questionnaire used by the judges. After implementing the adjustments suggested by judges, the algorithms were sent to a second evaluation cycle, in which all items were judged as "adequate" and "totally adequate", resulting in a Content Validity Index of 1.0. Conclusion Algorithms to guide healthcare professionals in the prevention and treatment of pressure injury in COVID-19 patients in prone position were evaluated by nurses, physical therapists and physicians working on the frontline of COVID-19. They achieved consensus on content in the second evaluation cycle.

Endoscopic Mini-or Less-Open Sublay Operation (E/MILOS) in ventral hernia repair: a minimally invasive alternative technique / Endoscopic Mini or Less Open Sublay Repair (E/MILOS) na correção das hérnias ventrais: uma alternativa técnica minimamente invasiva

ABSTRACT The ideal ventral hernia surgical repair is still in discussion1. The defect closure with a mesh-based repair is the base of surgical repair, in open or minimally invasive techniques2. The open methods lead to a higher surgical site infections incidence, meanwhile, the laparoscopic IPOM (intraperitoneal onlay mesh) increases the risk of intestinal lesions, adhesions, and bowel obstruction, in addition to requiring double mesh and fixation products which increase its costs and could worsen the post-operative pain3-5. The eTEP (extended/enhanced view totally intraperitoneal) technique has also arisen as a good option for this hernia repair. To avoid the disadvantages found in classic open and laparoscopic techniques, the MILOS (Endoscopically Assisted Mini or Less Open Sublay Repair) concept, created by W. Reinpold et al. in 2009, 3 years after eTEP conceptualization, allows the usage of bigger meshes through a small skin incision and laparoscopic retro-rectus space dissection, as the 2016 modification, avoiding an intraperitoneal mesh placement6,7. This new technique has been called E-MILOS (Endoscopic Mini or Less Open Sublay Repair)8. The aim of this paper is to report the E-MILOS techniques primary experience Brazil, in Santa Casa de Misericórdia de São Paulo.

RESUMO O tratamento cirúrgico ideal para correção das hérnias ventrais ainda é motivo de grande discussão1. O fechamento do defeito associado a utilização de telas para reforço da parede abdominal são passos fundamentais da terapia cirúrgica, podendo ser realizados tanto pela via aberta quanto pelas técnicas minimamente invasivas2. A via aberta apresenta maiores taxas de infecção de sítio cirúrgico, enquanto o reparo laparoscópico IPOM (intraperitoneal onlay mesh) acarreta um risco aumentado de lesões intestinais, aderências e obstruções intestinais, além de requerer uso de telas de dupla face e dispositivos de fixação que encarecem o procedimento e não raro aumentam a dor no pós-operatório3-5. A técnica eTEP (extended/enhanced view totally extraperitoneal), tem ganhado importância, mostrando-se uma boa opção para a correção das hérnias ventrais também2. A fim de se evitar as desvantagens das técnicas abertas e laparoscópicas "clássicas" o conceito MILOS (Endoscopically Assisted Mini or Less Open Sublay Repair), desenvolvido por W. Reinpold et al. em 2009, 3 anos antes do advento do eTEP, possibilita ao cirurgião o uso de telas de grandes dimensões no plano retromuscular através de uma pequena incisão na pele e dissecção laparoscópica deste espaço, conforme modificação realizada em 2016, evitando a colocação de uma tela no espaço intraperitoneal6-7. Esta nova técnica passou a se chamar EMILOS (Endoscopic Mini or Less Open Sublay Repair)8 Este artigo tem como objetivo relatar nossa experiência inicial no emprego da técnica E-MILOS no Brasil, na Santa Casa de Misericórdia de São Paulo.