Somatodendritic orientation determines tDCS-induced neuromodulation of Purkinje cell activity in awake mice.

Transcranial direct-current stimulation (tDCS) of the cerebellum is a promising non-invasive neuromodulatory technique being proposed for the treatment of neurological and neuropsychiatric disorders. However, there is a lack of knowledge about how externally applied currents affect neuronal spiking activity in cerebellar circuits in vivo. In this study, we observe that tDCS induces a heterogeneous polarity-dependent modulation of the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex. Using a combination of juxtacellular labeling and high-density Neuropixels recordings, we demonstrate that the apparently heterogeneous effects of tDCS on PC activity can be explained by taking into account the somatodendritic orientation relative to the electric field. Our findings emphasize the importance of considering neuronal orientation and morphological aspects to increase the predictive power of tDCS computational models, enhance the reliability of current stimulation protocols and optimize desired effects in basic and clinical human applications.

Altered Cerebellar Response to Somatosensory Stimuli in the Cntnap2 Mouse Model of Autism.

Atypical sensory processing is currently included within the diagnostic criteria of autism. The cerebellum is known to integrate sensory inputs of different modalities through its connectivity to the cerebral cortex. Interestingly, cerebellar malformations are among the most replicated features found in postmortem brain of individuals with autism. We studied sensory processing in the cerebellum in a mouse model of autism, knock-out (KO) for the Cntnap2 gene. Cntnap2 is widely expressed in Purkinje cells (PCs) and has been recently reported to regulate their morphology. Further, individuals with CNTNAP2 mutations display cerebellar malformations and CNTNAP2 antibodies are associated with a mild form of cerebellar ataxia. Previous studies in the Cntnap2 mouse model show an altered cerebellar sensory learning. However, a physiological analysis of cerebellar function has not been performed yet. We studied sensory evoked potentials in cerebellar Crus I/II region on electrical stimulation of the whisker pad in alert mice and found striking differences between wild-type and Cntnap2 KO mice. In addition, single-cell recordings identified alterations in both sensory-evoked and spontaneous firing patterns of PCs. These changes were accompanied by altered intrinsic properties and morphologic features of these neurons. Together, these results indicate that the Cntnap2 mouse model could provide novel insight into the pathophysiological mechanisms of autism core sensory deficits.

Impact of chronic transcranial random noise stimulation (tRNS) on GABAergic and glutamatergic activity markers in the prefrontal cortex of juvenile mice.

Transcranial random noise stimulation (tRNS), a non-invasive neuromodulatory technique capable of altering cortical activity, has been proposed to improve the signal-to-noise ratio at the neuronal level and the sensitivity of the neurons following an inverted U-function. The aim of this study was to examine the effects of tRNS on vGLUT1 and GAD 65-67 and its safety in terms of pathological changes. For that, juvenile mice were randomly distributed in three different groups: "tRNS 1×" receiving tRNS at the density current used in humans (0.3A/m2, 20min), "tRNS 100×" receiving tRNS at two orders of magnitude higher (30.0A/m2, 20min) and "sham" (0.3A/m2, 15s). Nine tRNS sessions during 5 weeks were administered to the prefrontal cortex of awake animals. No detectable tissue macroscopic lesions were observed after tRNS sessions. Post-stimulation immunohistochemical analysis of GAD 65-67 and vGLUT1 immunoreactivity showed reduced GAD 65-67 immunoreactivity levels in the region directly beneath the electrode for tRNS 1× group with no significant effects in the tRNS 100× nor sham group. The observed results suggest an excitatory effect associated with a decrease in GABA levels in absence of major histopathological alterations providing a novel mechanistic explanation for tRNS effects.

Immediate and after effects of transcranial direct-current stimulation in the mouse primary somatosensory cortex.

Transcranial direct-current stimulation (tDCS) is a non-invasive brain stimulation technique consisting in the application of weak electric currents on the scalp. Although previous studies have demonstrated the clinical value of tDCS for modulating sensory, motor, and cognitive functions, there are still huge gaps in the knowledge of the underlying physiological mechanisms. To define the immediate impact as well as the after effects of tDCS on sensory processing, we first performed electrophysiological recordings in primary somatosensory cortex (S1) of alert mice during and after administration of S1-tDCS, and followed up with immunohistochemical analysis of the stimulated brain regions. During the application of cathodal and anodal transcranial currents we observed polarity-specific bidirectional changes in the N1 component of the sensory-evoked potentials (SEPs) and associated gamma oscillations. On the other hand, 20 min of cathodal stimulation produced significant after-effects including a decreased SEP amplitude for up to 30 min, a power reduction in the 20-80 Hz range and a decrease in gamma event related synchronization (ERS). In contrast, no significant changes in SEP amplitude or power analysis were observed after anodal stimulation except for a significant increase in gamma ERS after tDCS cessation. The polarity-specific differences of these after effects were corroborated by immunohistochemical analysis, which revealed an unbalance of GAD 65-67 immunoreactivity between the stimulated versus non-stimulated S1 region only after cathodal tDCS. These results highlight the differences between immediate and after effects of tDCS, as well as the asymmetric after effects induced by anodal and cathodal stimulation.

Surgical errors and the relationships of disease, risks, and adverse events.

BACKGROUND: Relationships between surgical errors and adverse events have not been fully explored and were examined in this study. MATERIALS AND METHODS: This retrospective cohort study reviewed records of deceased surgical patients over 12 months. Bivariate associations between predictors and errors were examined. RESULTS: 84 deaths occurred following 5,209 operations. Errors in care (63%) compared to those without had significantly more adverse events, (98% vs 80% respectively, p = 0.004). Significant association occurred between error and emergency status, p = 0.016); length of stay >10 days, p = 0.011; adverse events, p = 0.005). Regression results indicated number of adverse events (OR = 1.27, 95% CI (1.08-1.49), p = 0.003) and length of stay (OR = 1.05, 95% CI (1.01-1.09), p = 0.008) were associated with surgical errors. CONCLUSIONS: Examining postoperative adverse events in error cases identified opportunities for improvement. Reducing medical errors requires measuring medical errors.

Robotic compared with laparoscopic cholecystectomy: A propensity matched analysis.

BACKGROUND: As robotic surgery becomes more ubiquitous, determining clinical benefit is necessary to justify the cost and time investment required to become proficient. We hypothesized that robotic cholecystectomy would be associated with improved clinical outcomes but also increased cost as compared with standard laparoscopic cholecystectomy. MATERIALS AND METHODS: All patients undergoing robotic or laparoscopic cholecystectomy at a single academic hospital between 2007 and 2017 were identified using an institutional clinical data repository. Patients were stratified by operative approach (robotic versus laparoscopic) for comparison and propensity score matched 1:10 based on relevant comorbidities and demographics. Categorical variables were analyzed by the χ2 test and continuous variables using the Mann-Whitney U test. RESULTS: A total of 3,255 patients underwent cholecystectomy during the study period. We observed no differences in demographics or body mass index, but greater rates of diabetes mellitus, hypertension, and gastroesophageal reflux disease were present in the laparoscopic group. After matching (n = 106 robotic, n = 1,060 laparoscopic), there were no differences in preoperative comorbidities. Patients who underwent robotic cholecystectomy had lesser durations of stay (robotic: 0.1 ± 0.7 versus laparoscopic: 0.8 ± 1.9, P < .0001) and lesser 90-day readmission rates (robotic: 0% [0], laparoscopic: 4.1% [43], P = 0.035); however, both operative and hospital costs were greater compared with laparoscopic cholecystectomy. CONCLUSION: Robotic cholecystectomy is associated with lesser duration of stay and lesser readmission rate within 90 days of the index operation, but also greater operative duration and hospital cost compared with laparoscopic cholecystectomy. Hospitals and surgeons need to consider the improved clinical outcomes but also the monetary and time investment required before pursuing robotic cholecystectomy.

Exploring new transcranial electrical stimulation strategies to modulate brain function in animal models.

Transcranial electrical stimulation (tES) refers to a group of non-invasive brain stimulation techniques to induce changes in the excitability of cortical neurons in humans. In recent years, studies in animal models have been shown to be essential for disentangling the neuromodulatory effects of tES, defining safety limits, and exploring potential therapeutic applications in neurological and neuropsychiatric disorders. Testing in animal models is valuable for the development of new unconventional protocols intended to improve tES administration and optimize the desired effects by increasing its focality and enabling deep-brain stimulation. Successful and controlled application of tES in humans relies on the knowledge acquired from studies meticulously performed in animal models.

Using animal models to improve the design and application of transcranial electrical stimulation in humans.

PURPOSE OF REVIEW: Transcranial electrical stimulation (tES) is a non-invasive stimulation technique used for modulating brain function in humans. To help tES reach its full therapeutic potential, it is necessary to address a number of critical gaps in our knowledge. Here, we review studies that have taken advantage of animal models to provide invaluable insight about the basic science behind tES. RECENT FINDINGS: Animal studies are playing a key role in elucidating the mechanisms implicated in tES, defining safety limits, validating computational models, inspiring new stimulation protocols, enhancing brain function and exploring new therapeutic applications. SUMMARY: Animal models provide a wealth of information that can facilitate the successful utilization of tES for clinical interventions in human subjects. To this end, tES experiments in animals should be carefully designed to maximize opportunities for applying discoveries to the treatment of human disease.

Inguinal hernia repair: is there a benefit to using the robot?

BACKGROUND: The number of robotic surgical procedures performed yearly is constantly rising, due to improved dexterity and visualization capabilities compared with conventional methods. We hypothesized that outcomes after robotic-assisted inguinal hernia repair would not be significantly different from outcomes after laparoscopic or open repair. METHODS: All patients undergoing inguinal hernia repair between 2012 and 2016 were identified using institutional American College of Surgeons National Surgical Quality Improvement Program data. Demographics; preoperative, intraoperative, and postoperative characteristics; and outcomes were evaluated based on method of repair (Robot, Lap, or Open). Categorical variables were analyzed by Chi-square test and continuous variables using Mann-Whitney U. RESULTS: A total of 510 patients were identified who underwent unilateral inguinal hernia repair (Robot: 13.8% [n = 69], Lap: 48.1% [n = 241], Open: 38.1% [n = 191]). There were no demographic differences between groups other than age (Robot: 52 [39-62], Lap: 57 [45-67], and Open: 56 [48-67] years, p = 0.03). Operative duration was also different (Robot: 105 [76-146] vs. Lap: 81 [61-103] vs. Open: 71 [56-88] min, p < 0.001). There were no operative mortalities and all patients except one were discharged home the same day. Postoperative occurrences (adverse events, readmissions, and death) were similar between groups (Robot: 2.9% [2], Lap: 3.3% [8], Open: 5.2% [10], p = 0.53). Although rare, there was a significant difference in rate of postoperative skin and soft tissue infection (Robot: 2.9% [2] vs. Lap: 0% [0] vs. Open: 0.5% [1], p = 0.02). Cost was significantly different between groups (Robot: $7162 [$5942-8375] vs. Lap: $4527 [$2310-6003] vs. Open: $4264 [$3277-5143], p < 0.001). CONCLUSIONS: Outcomes after robotic-assisted inguinal hernia repair were similar to outcomes after laparoscopic or open repair. Longer operative duration during robotic repair may contribute to higher rates of skin and soft tissue infection. Higher cost should be considered, along with surgeon comfort level and patient preference when deciding whether inguinal hernia repair is approached robotically.

Sex- and diagnosis-dependent differences in mortality and admission cytokine levels among patients admitted for intensive care.

OBJECTIVES: To investigate the role of sex on cytokine expression and mortality in critically ill patients. DESIGN: A cohort of patients admitted to were enrolled and followed over a 5-year period. SETTING: Two university-affiliated hospital surgical and trauma ICUs. PATIENTS: Patients 18 years old and older admitted for at least 48 hours to the surgical or trauma ICU. INTERVENTIONS: Observation only. MEASUREMENTS AND MAIN RESULTS: Major outcomes included admission cytokine levels, prevalence of ICU-acquired infection, and mortality during hospitalization conditioned on trauma status and sex. The final cohort included 2,291 patients (1,407 trauma and 884 nontrauma). The prevalence of ICU-acquired infection was similar for men (46.5%) and women (44.5%). All-cause in-hospital mortality was 12.7% for trauma male patient and 9.1% for trauma female patient (p = 0.065) and 22.9% for nontrauma male patients and 20.6% for nontrauma female patients (p = 0.40). Among trauma patients, logistic regression analysis identified female sex as protective for all-cause mortality (odds ratio, 0.57). Among trauma patients, men had significantly higher admission serum levels of interleukin-2, interleukin-12, interferon-γ, and tumor necrosis factor-α, and among nontrauma patients, men had higher admission levels of interleukin-8 and tumor necrosis factor-α. CONCLUSIONS: The relationship between sex and outcomes in critically ill patients is complex and depends on underlying illness. Women appear to be better adapted to survive traumatic events, while sex may be less important in other forms of critical illness. The mechanisms accounting for this gender dimorphism may, in part, involve differential cytokine responses to injury, with men expressing a more robust proinflammatory profile.

Differences in morbidity and mortality with percutaneous versus open surgical drainage of postoperative intra-abdominal infections: a review of 686 cases.

Intra-abdominal infections following surgical procedures result from organ-space surgical site infections, visceral perforations, or anastomotic leaks. We hypothesized that open surgical drainage is associated with increased patient morbidity and mortality compared with percutaneous drainage. A single-institution, prospectively collected database over a 13-year period revealed 2776 intra-abdominal infections, 686 of which required an intervention after the index operation. Percutaneous procedures (simple aspiration or catheter placement) were compared with all other open procedures by univariate and multivariate analyses. Analysis revealed 327 infections in 240 patients undergoing open surgical drainage and 359 infections in 260 patients receiving percutaneous drainage. Those undergoing open drainage had significantly higher Acute Physiology Score (APS) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores and were more likely to be immunosuppressed, require intensive care unit treatment, and have longer hospital stays. Mortality was higher in the open group: 14.6 versus 4.2 per cent (P = 0.0001). Variables independently associated with death by multivariate analysis were APACHE II, dialysis, intensive care unit (ICU) care, age, immunosuppression, and drainage method. Open intervention for postsurgical intra-abdominal infections is associated with increased mortality compared with percutaneous drainage even after controlling for severity of illness by multivariate analysis. Although some patients are not candidates for percutaneous drainage, it should be considered the preferential treatment in eligible patients.

Common complications in the surgical intensive care unit.

Surgical and trauma intensive care units provide the facilities, resources, and personnel needed to care for patients who have been severely injured, present with acute surgical emergencies, require prolonged and complex elective surgical procedures, or have severe underlying medical conditions. Correcting the immediately evident physiologic derangement is only the first step in the care of these patients, because in many cases their prognosis and ultimate outcome will depend on whether additional insults accrued during their intensive care unit and hospital stay will prevent them from a full recovery. The nature, number, and complexity of the interventions used to provide advanced support requires a unique attention to the concept of patient safety, particularly when the population involved is that most vulnerable to injury and with the least amount of physiologic reserve to recover from it. The medical community, the public, and even regulatory agencies have focused on specific preventable complications that are common in surgical and injured patients, such as medical errors, healthcare-associated infections, and venous thromboembolism. Enough scientific knowledge has been obtained through well-conducted clinical trials to generate detailed evidence-based guidelines for the prevention and management of some of these pathologies, but still there are outstanding questions in terms of the applicability of the recommendations to the critically ill. In addition to clinical and technical expertise, performance improvement and quality monitoring activities provide direction for system solutions required to properly address many complications that are not provider specific.

Does preoperative ejection fraction predict operative mortality with left ventricular restoration?

BACKGROUND: Ischemic cardiomyopathy and aneurysmal disease have been treated surgically with coronary artery bypass grafting in the past. The Dor technique for left ventricular restoration has demonstrated improved outcomes in patients with ischemic, akinetic ventricles. Our hypothesis was that even marked reduction in preoperative cardiac function (ejection fraction < .25) would not correlate with worse outcomes since the ventricle would be reshaped to improve function. METHODS: A retrospective analysis was performed on all patients who had undergone ventricular restoration with the Dor procedure from January 1996 through September 2005. Patients with a preoperative ejection fraction (EF) < .25 and those with a EF > or = .25 were compared. All Society of Thoracic Surgeons database characteristics, mortality, length of stay (LOS), and need for intraaortic balloon pump (IABP) were analyzed. RESULTS: The study included 89 patients (69 men, 20 women), 28 of whom had preoperative EFs < .25 (mean, .183 +/- .035; range, .08 to .25) and 61 had an EF > or = .25 (mean, .334 +/- .074; mean, .25 to .45). Overall operative mortality was 3.4% (3/89), with no statistically significant difference between the two groups (3.6% versus 3.3%). LOS was 7.4 +/- 3.6 days versus 8.9 +/- 15.6 days (p = NS), and need for IABP was 39.2% versus 8.1% (p < 0.05). Overall 5-year survival was 82%. Five-year survival in the EF < .25 cohort was 69.6% versus 88.3% in the EF > or = .25 cohort (p = 0.066). CONCLUSIONS: Ventricular restoration with the Dor technique is a safe procedure. Marked reduction in ejection fraction is not a contraindication to left ventricular restoration; however, increased usage of IABP should be anticipated.

Interaction of haemodynamic and metabolic pathways in the genesis of diabetic nephropathy.

Clinical diabetic nephropathy is characterized by an earlier functional phase in which hyperglycaemia is accompanied by an increased glomerular filtration rate and microalbuminuria; the persistence of this high-flow and high-pressure state, added to a poor control of hyperglycaemia, fosters renal damage and proteinuria, accompanied by a decline in glomerular filtration rate and progression to end-stage renal disease. In this review, we present glucose transporter 1 (GLUT-1) as a novel link that connects the glomerular hyperfiltration (hypertension) state and the complex cascade of events that leads to nephropathy. The interplay between angiotensin II and nitric oxide, and its interactions with reactive oxygen species, are also discussed, in an attempt to provide an integrated view of the pathophysiology of diabetic nephropathy.

Comparación del efecto de la amisulprida y la viloxacina en el tratamiento de la distimia / Comparison of the amisulpride and viloxazine effect in the dysthymia treatment

El presente trabajo se propone evaluar la eficacia terapéutica de la amisulprida, comparándola con la viloxacina en un grupo de pacientes diagnosticados como distímicos de acuerdo con los criterios de clasificación del DSM-III-R. Se trata de un estudio controlado doble ciego con asignación aleatoria, de una serie de 80 pacientes evaluados en un examen incial y a lo largo de 4 semanas de tratamiento. Entre los instumentos empleados para la evaluación figuran la escala de depresión de Hamilton, la del retardo psicomotor de Widlocher y la de síntomas negativos de Andreasen. Se evalúa tanto la eficacia como la seguridad de los medicamentos. Se presentan un análisis de los resultados que sugiere una mejor respuesta terapéutica en el grupo de la amisulprida

Comparación del efecto de la amisulprida y la viloxacina en el tratamiento de la distimia / Comparison of the amisulpride and viloxazine effect in the dysthymia treatment

El presente trabajo se propone evaluar la eficacia terapéutica de la amisulprida, comparándola con la viloxacina en un grupo de pacientes diagnosticados como distímicos de acuerdo con los criterios de clasificación del DSM-III-R. Se trata de un estudio controlado doble ciego con asignación aleatoria, de una serie de 80 pacientes evaluados en un examen incial y a lo largo de 4 semanas de tratamiento. Entre los instumentos empleados para la evaluación figuran la escala de depresión de Hamilton, la del retardo psicomotor de Widlocher y la de síntomas negativos de Andreasen. Se evalúa tanto la eficacia como la seguridad de los medicamentos. Se presentan un análisis de los resultados que sugiere una mejor respuesta terapéutica en el grupo de la amisulprida (AU)