Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial.

Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown. Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023. Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models. Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group. Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin. Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.

Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19.

BACKGROUND: Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. METHODS: We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. RESULTS: A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. CONCLUSIONS: Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).

A hybrid linear discriminant analysis and genetic algorithm to create a linear model of aging when performing motor tasks through inertial sensors positioned on the hand and forearm.

BACKGROUND: During the aging process, cognitive functions and performance of the muscular and neural system show signs of decline, thus making the elderly more susceptible to disease and death. These alterations, which occur with advanced age, affect functional performance in both the lower and upper members, and consequently human motor functions. Objective measurements are important tools to help understand and characterize the dysfunctions and limitations that occur due to neuromuscular changes related to advancing age. Therefore, the objective of this study is to attest to the difference between groups of young and old individuals through manual movements and whether the combination of features can produce a linear correlation concerning the different age groups. METHODS: This study counted on 99 participants, these were divided into 8 groups, which were grouped by age. The data collection was performed using inertial sensors (positioned on the back of the hand and on the back of the forearm). Firstly, the participants were divided into groups of young and elderly to verify if the groups could be distinguished through the features alone. Following this, the features were combined using the linear discriminant analysis (LDA), which gave rise to a singular feature called the LDA-value that aided in verifying the correlation between the different age ranges and the LDA-value. RESULTS: The results demonstrated that 125 features are able to distinguish the difference between the groups of young and elderly individuals. The use of the LDA-value allows for the obtaining of a linear model of the changes that occur with aging in the performance of tasks in line with advancing age, the correlation obtained, using Pearson's coefficient, was 0.86. CONCLUSION: When we compare only the young and elderly groups, the results indicate that there is a difference in the way tasks are performed between young and elderly individuals. When the 8 groups were analyzed, the linear correlation obtained was strong, with the LDA-value being effective in obtaining a linear correlation of the eight groups, demonstrating that although the features alone do not demonstrate gradual changes as a function of age, their combination established these changes.

Prevalence of distinct types of hardware failures related to deep brain stimulation.

Deep brain stimulation (DBS) is an effective treatment of several types of neurological conditions, including Parkinson's disease, essential tremor, dystonia, and epilepsy. Despite technological progress in the past 10 years, the number of studies reporting side effects of DBS has increased, mainly due to hardware failures. This review investigated studies published between 2017 and 2021 to identify the prevalence of distinct types of hardware failures related to DBS. In total, fifteen studies were selected for the estimate of the prevalence of five distinct types of hardware failures: high impedance, fracture or failure of the lead or other parts of the implant, skin erosion and infection, lead malposition or migration, and implantable pulse generator (IPG) malfunction. The quality evaluation of the studies suggests a need to report results including populations from distinct regions of the world so that results can be generalized. The objective analysis of the prevalence of hardware failures showed that skin erosion and infection presented the highest prevalence in relation to other hardware failures. Despite the sophistication of the surgical technique of DBS over time, there is a considerable complication rate, about 7 per 100 individuals ([Formula: see text], in which CI is the confidence interval). Future research can also include correlation analysis with the aim of understanding the correlation between distinct hardware failures and variables such as gender, type of disorder, and age.

Maize Inbred Mp708 is Highly Susceptible to Western Corn Rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae), in Field and Greenhouse Assays.

The western corn rootworm (WCR), Diabrotica vifgirera virgifera LeConte, (Coleoptera: Chrysomelidae) causes significant economic damage in corn production each year. Resistance to insecticides and transgenic corn with Bacillus thuringiensis (Bt), Berliner toxins have been reported throughout the United States Corn Belt. Corn breeding programs for natural resistance against WCR larvae could potentially assist in rootworm management. Root damage and root regrowth of eight corn lines were evaluated in field assays at three different locations. Results indicated the inbred 'Mp708' had the greatest root damage and was significantly greater than damage for the susceptible control, B37×H84. In greenhouse assays, we evaluated four of these lines plus a hybrid expressing the mCry3A Bt toxin for damage. The results indicated that Mp708 had significantly higher root damage when compared to 'CRW3(S1)C6' and 'MIR604'. Despite previous work suggesting otherwise, we conclude that Mp708 is highly susceptible to the WCR larvae based on root damage in field and greenhouse plant assays.

Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial.

BACKGROUND: The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19. METHODS: We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278. FINDINGS: 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94-1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups. INTERPRETATION: In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19. FUNDING: COALITION COVID-19 Brazil and EMS.

Host resistance to Bacillus thuringiensis is linked to altered bacterial community within a specialist insect herbivore.

Evolution of resistance to transgenic crops producing toxins from Bacillus thuringiensis (Bt) threatens the sustainability of the technology. Examination of resistance mechanisms has largely focused on characterization of mutations in proteins serving as Bt toxin binding sites. However, insect microbial communities have the potential to provide host resistance to pesticides in a myriad of ways. Previous findings suggest the killing mechanism of Bt relies on enteric bacteria becoming pathogenic in the disrupted gut environment of the insect following Bt intoxication. Thus, here we hypothesized that resistance to Bt would alter the microbiome composition of the insect. Previous studies have manipulated the microbiome of susceptible insects and monitored their response to Bt. In our study, we characterized the associated bacterial communities of Bt-resistant and -susceptible western corn rootworms, a widespread pest of maize in the United States. We found resistant insects harbor a bacterial community that is less rich and distinct from susceptible insects. After feeding on Bt-expressing maize, susceptible insects exhibited dysbiosis of the associated bacterial community, whereas the community within resistant insects remained relatively unchanged. These results suggest resistance to Bt produces alterations in the microbiome of the western corn rootworm that may contribute to resistance. We further demonstrated that by itself, feeding on Bt toxin-expressing seedlings caused a shift in the microbiota. This work provides a broader picture of the effect stressors have on microbiome composition, and the potential heritable changes induced as a result of intense selection.

Discrimination between healthy and patients with Parkinson's disease from hand resting activity using inertial measurement unit.

BACKGROUND: Parkinson's disease (PD) is a neurological disease that affects the motor system. The associated motor symptoms are muscle rigidity or stiffness, bradykinesia, tremors, and gait disturbances. The correct diagnosis, especially in the initial stages, is fundamental to the life quality of the individual with PD. However, the methods used for diagnosis of PD are still based on subjective criteria. As a result, the objective of this study is the proposal of a method for the discrimination of individuals with PD (in the initial stages of the disease) from healthy groups, based on the inertial sensor recordings. METHODS: A total of 27 participants were selected, 15 individuals previously diagnosed with PD and 12 healthy individuals. The data collection was performed using inertial sensors (positioned on the back of the hand and on the back of the forearm). Different numbers of features were used to compare the values of sensitivity, specificity, precision, and accuracy of the classifiers. For group classification, 4 classifiers were used and compared, those being [Random Forest (RF), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), and Naive Bayes (NB)]. RESULTS: When all individuals with PD were analyzed, the best performance for sensitivity and accuracy (0.875 and 0.800, respectively) was found in the SVM classifier, fed with 20% and 10% of the features, respectively, while the best performance for specificity and precision (0.933 and 0.917, respectively) was associated with the RF classifier fed with 20% of all the features. When only individuals with PD and score 1 on the Hoehn and Yahr scale (HY) were analyzed, the best performances for sensitivity, precision and accuracy (0.933, 0.778 and 0.848, respectively) were from the SVM classifier, fed with 40% of all features, and the best result for precision (0.800) was connected to the NB classifier, fed with 20% of all features. CONCLUSION: Through an analysis of all individuals in this study with PD, the best classifier for the detection of PD (sensitivity) was the SVM fed with 20% of the features and the best classifier for ruling out PD (specificity) was the RF classifier fed with 20% of the features. When analyzing individuals with PD and score HY = 1, the SVM classifier was superior across the sensitivity, precision, and accuracy, and the NB classifier was superior in the specificity. The obtained result indicates that objective methods can be applied to help in the evaluation of PD.

Emergence and Infestation Level of Hypothenemus hampei (Coleoptera: Curculionidae) on Coffee Berries on the Plant or on the Ground During the Post-harvest Period in Brazil.

The coffee berry borer (CBB), Hypothenemus hampei Ferrari (Coleoptera: Curculionidae), is the most important coffee pest in most of the coffee growing countries. CBB females leave old dry berries after harvest and search for dry noninfested berries on the plant or on the ground to lay eggs or to use as refuge until new berries are available on the coffee trees in the following season. The CBB infestation level and emergence from berries on the ground or on the plants were evaluated in two fields post-harvest in the Spring in Brazil over two seasons. Twenty infested or noninfested berries in separate cages (250 ml plastic cups) were placed on the plants or on the ground under the tree canopy, in each field. The number of infested berries and CBB females that emerged from the infested berries were recorded weekly. CBB emergence was higher from berries on the ground than those on the coffee trees in both seasons, whereas CBB infestation was higher on coffee berries on the plants than those on the ground in season I. Insolation (hours of sunlight) and temperature were the main covariates that affected emergence and infestation by this insect. The results are discussed for monitoring CBB during the time of dispersal with implications on integrated management of this pest.

Identification of arthropathy and myopathy of the temporomandibular syndrome by biomechanical facial features.

BACKGROUND: Temporomandibular disorders (TMDs) are pathological conditions affecting the temporomandibular joint and/or masticatory muscles. The current diagnosis of TMDs is complex and multi-factorial, including questionnaires, medical testing and the use of diagnostic methods, such as computed tomography and magnetic resonance imaging. The evaluation, like the mandibular range of motion, needs the experience of the professional in the field and as such, there is a probability of human error when diagnosing TMD. The aim of this study is therefore to develop a method with infrared cameras, using the maximum range of motion of the jaw and four types of classifiers to help professionals to classify the pathologies of the temporomandibular joint (TMJ) and related muscles in a quantitative way, thus helping to diagnose and follow up on TMD. METHODS: Forty individuals were evaluated and diagnosed using the diagnostic criteria for temporomandibular disorders (DC/TMD) scale, and divided into three groups: 20 healthy individuals (control group CG), 10 individuals with myopathies (MG), 10 individuals with arthropathies (AG). A quantitative assessment was carried out by motion capture. The TMJ movement was captured with camera tracking markers mounted on the face and jaw of each individual. Data was exported and analyzed using a custom-made software. The data was used to identify and place each participant into one of three classes using the K-nearest neighbor (KNN), Random Forest, Naïve Bayes and Support Vector Machine algorithms. RESULTS: Significant precision and accuracy (over 90%) was reached by KNN when classifying the three groups. The other methods tested presented lower values of sensitivity and specificity. CONCLUSION: The quantitative TMD classification method proposed herein has significant precision and accuracy over the DC/TMD standards. However, this should not be used as a standalone tool but as an auxiliary method for diagnostic TMDs.

Which Multicenter Randomized Controlled Trials in Critical Care Medicine Have Shown Reduced Mortality? A Systematic Review.

OBJECTIVES: To determine which multicenter randomized controlled trials in critically ill patients have shown that the study intervention was associated with a statistically significant reduction in mortality. Our analysis provides an update to a report published 10 years ago. DATA SOURCES: MEDLINE database and PubMed interface from inception until April 30, 2019. STUDY SELECTION: All adult multicenter randomized controlled trials that evaluated the effects of any intervention or monitoring system in critically ill patients and reported mortality as a primary or secondary outcome were included. DATA EXTRACTION: Numbers of centers and patients, type of intervention, reported mortality outcome, and rate and level of significance were extracted into predefined tables. Included randomized controlled trials were classified as reporting reduced, increased, or no effect of the intervention on mortality. Methodologic quality of trials was evaluated using the updated Consolidated Standards of Reporting Trials statement. DATA SYNTHESIS: A total of 212 trials met the inclusion criteria: 27 (13%) reported a significant reduction in mortality, 16 (7%) an increase in mortality, and 170 (80%) no difference in mortality (one study was reported in 2 groups). Of the 27 trials reporting reduced mortality, six had assessed interventions likely to decrease ventilator-induced lung injury, including low tidal volume, prone position, and neuromuscular blockers, demonstrating the negative effects of mechanical ventilation strategies or improved process of care rather than positive effects of new therapies. Seven of the 27 trials reported beneficial effects of noninvasive ventilation. Results from some positive randomized controlled trials, for example, studies of recombinant activated protein C, talactoferrin, interleukin-1 receptor antagonist in sepsis, and muscle relaxants in severe acute respiratory distress syndrome were not replicated in subsequent randomized controlled trials. Other interventions, for example, gastric tonometry, have been abandoned. CONCLUSIONS: A systematic literature search provided no conclusive evidence of any pharmacologic intervention that has consistently reduced mortality in critically ill patients. Strategies associated with improved or noninvasive mechanical ventilation were associated with reduced mortality.

Quality Improvement Initiatives in Sepsis in an Emerging Country: Does the Institution's Main Source of Income Influence the Results? An Analysis of 21,103 Patients.

OBJECTIVE: We aimed to assess the results of a quality improvement initiative in sepsis in an emerging setting and to analyze it according to the institutions' main source of income (public or private). DESIGN: Retrospective analysis of the Latin American Sepsis Institute database from 2005 to 2014. SETTINGS: Brazilian public and private institutions. PATIENTS: Patients with sepsis admitted in the participant institutions. INTERVENTIONS: The quality improvement initiative was based on a multifaceted intervention. The institutions were instructed to collect data on 6-hour bundle compliance and outcomes in patients with sepsis in all hospital settings. Outcomes and compliance was measured for eight periods of 6 months each, starting at the time of the enrollment in the intervention. The primary outcomes were hospital mortality and compliance with 6-hour bundle. MEASUREMENTS AND MAIN RESULTS: We included 21,103 patients; 9,032 from public institutions and 12,071 from private institutions. Comparing the first period with the eigth period, compliance with the 6-hour bundle increased from 13.5% to 58.2% in the private institutions (p < 0.0001) and from 7.4% to 15.7% in the public institutions (p < 0.0001). Mortality rates significantly decreased throughout the program in private institutions, from 47.6% to 27.2% in the eighth period (adjusted odds ratio, 0.45; 95% CI, 0.32-0.64). However, in the public hospitals, mortality diminished significantly only in the first two periods. CONCLUSION: This quality improvement initiative in sepsis in an emerging country was associated with a reduction in mortality and with improved compliance with quality indicators. However, this reduction was sustained only in private institutions.

Time course of blood lactate levels, inflammation, and mitochondrial function in experimental sepsis.

BACKGROUND: A decrease in blood lactate levels (Lac) >10% during the first hours of resuscitation in sepsis is associated with better outcomes, but the mechanisms are unclear. Our objective was to investigate the relationship between the time course of Lac, inflammatory response, and mitochondrial respiration during experimental sepsis. METHODS: Original data from two previously published studies were reanalyzed. In cohort 1, pigs were randomized to be resuscitated for 48 h starting at 6, 12, and 24 h, respectively, after fecal peritonitis induction (n = 8 each). Animals were categorized according to the decrease in Lac during the first 6 h of resuscitation (early if ≥10% [Lac ≥10%] or late if <10% or increased [Lac <10%]), and systemic hemodynamics, inflammatory parameters, and mitochondrial function were compared between groups. In a second group of animals with fecal peritonitis and 24 h of resuscitation (n = 16, cohort 2), abdominal regional Lac exchange was measured, and animals were categorized according to the decrease in Lac as in cohort 1. RESULTS: Overall mortality was 20% (4 of 20) in the Lac ≥10% group and 60% (12 of 20) in the Lac <10% group (p = 0.022). In cohort 1, systemic hemodynamics were similar in the Lac ≥10% (n = 13) and Lac <10% (n = 11) groups. Plasma interleukin-6 levels increased during unresuscitated sepsis and decreased during resusciation in both groups, but they were lower at study end in the Lac ≥10% group (p = 0.047). Complexes I and II maximal (state 3) and resting (state 4) isolated brain mitochondrial respiration at study end was higher in the Lac ≥10% group than in the Lac <10% group, whereas hepatic, myocardial, and skeletal muscle mitochondrial respiration was similar in both groups. In cohort 2, mesenteric, total hepatic, and renal blood flow at study end was higher in the Lac ≥10% group (n = 7) than in the Lac <10% group (n = 9), despite similar cardiac output. Hepatic lactate influx and uptake in the Lac ≥10% group were approximately 1.5 and 3 times higher, respectively, than in the Lac <10% group (p = 0.066 for both). CONCLUSIONS: A decrease in Lac >10% during early resuscitation (6 h) after abdominal sepsis is associated with lower levels of plasma interleukin-6 and improved brain but not hepatic or muscle mitochondrial respiration. Blood flow redistribution to abdominal organs in animals with early decrease in Lac concentrations increases the potential to both deliver and extract Lac.

Esmolol Administration to Control Tachycardia in an Ovine Model of Peritonitis.

BACKGROUND: Excessive adrenergic signaling may be harmful in sepsis. Using ß-blockers to reduce sympathetic overactivity may modulate sepsis-induced cardiovascular, metabolic, immunologic, and coagulation alterations. Using a randomized ovine fecal peritonitis model, we investigated whether administration of a short-acting ß-blocker, esmolol, could control tachycardia without deleterious effects on hemodynamics, renal perfusion, cerebral perfusion, cerebral metabolism, or outcome. METHODS: After induction of fecal peritonitis, 14 anesthetized, mechanically ventilated, and hemodynamically monitored adult female sheep were randomly assigned to receive a continuous intravenous infusion of esmolol to control heart rate between 80 and 100 bpm (n = 7) or a saline infusion (control group, n = 7). Esmolol was discontinued when the mean arterial pressure decreased below 60 mm Hg. Fluid resuscitation was titrated to maintain pulmonary artery occlusion pressure at baseline values. Left renal blood flow and cerebral cortex perfusion and metabolism were monitored in addition to standard hemodynamic variables. RESULTS: Esmolol was infused for 11 (9-14) hours; the target heart rate (80-100 bpm) was achieved between 3 and 8 hours after feces injection. In the first 5 hours after the start of the infusion, the decrease in heart rate was compensated by an increase in stroke volume index; later, stroke volume index was not statistically significantly different in the 2 groups, so that the cardiac work index was lower in the esmolol than in the control group. Hypotension (mean arterial pressure <60 mm Hg) occurred earlier (10 [8-12] vs 14 [11-20] hours; P= .01) in the esmolol group than in the control animals. Renal blood flow decreased earlier in the esmolol group, but there were no differences in urine output, cerebral cortex perfusion, metabolism, or survival between the groups. CONCLUSIONS: In this ovine model of abdominal sepsis, early control of tachycardia by esmolol was associated with a transient increase in stroke volume, followed by earlier hypotension. There were no significant effects of esmolol on cerebral perfusion, metabolism, urine output, or survival.

Feature visualization and classification for the discrimination between individuals with Parkinson's disease under levodopa and DBS treatments.

BACKGROUND: Over the years, a number of distinct treatments have been adopted for the management of the motor symptoms of Parkinson's disease (PD), including pharmacologic therapies and deep brain stimulation (DBS). Efficacy is most often evaluated by subjective assessments, which are prone to error and dependent on the experience of the examiner. Our goal was to identify an objective means of assessing response to therapy. METHODS: In this study, we employed objective analyses in order to visualize and identify differences between three groups: healthy control (N = 10), subjects with PD treated with DBS (N = 12), and subjects with PD treated with levodopa (N = 16). Subjects were assessed during execution of three dynamic tasks (finger taps, finger to nose, supination and pronation) and a static task (extended arm with no active movement). Measurements were acquired with two pairs of inertial and electromyographic sensors. Feature extraction was applied to estimate the relevant information from the data after which the high-dimensional feature space was reduced to a two-dimensional space using the nonlinear Sammon's map. Non-parametric analysis of variance was employed for the verification of relevant statistical differences among the groups (p < 0.05). In addition, K-fold cross-validation for discriminant analysis based on Gaussian Finite Mixture Modeling was employed for data classification. RESULTS: The results showed visual and statistical differences for all groups and conditions (i.e., static and dynamic tasks). The employed methods were successful for the discrimination of the groups. Classification accuracy was 81 ± 6% (mean ± standard deviation) and 71 ± 8%, for training and test groups respectively. CONCLUSIONS: This research showed the discrimination between healthy and diseased groups conditions. The methods were also able to discriminate individuals with PD treated with DBS and levodopa. These methods enable objective characterization and visualization of features extracted from inertial and electromyographic sensors for different groups.

Do different anesthesia regimes affect hippocampal apoptosis and neurologic deficits in a rodent cardiac arrest model?

BACKGROUND: Different anesthesia regimes are commonly used in experimental models of cardiac arrest, but the effects of various anesthetics on clinical outcome parameters are unknown. We conducted a study in which we subjected rats to cardiac arrest under medetomidine/ketamine or sevoflurane/fentanyl anesthesia. METHODS: Asystolic cardiac arrest for 8 minutes was induced in 73 rats with a mixture of potassium chloride and esmolol. Daily behavioral and neurological examination included the open field test (OFT), the tape removal test (TRT) and a neurodeficit score (NDS). Animals were randomized for sacrifice on day 2 or day 5 and brains were harvested for histology in the hippocampus cornus ammonis segment CA1. The inflammatory markers IL-6, TNF-α, MCP-1 and MIP-1α were assessed in cerebrospinal fluid (CSF). Proportions of survival were tested with the Fisher's exact test, repeated measurements were assessed with the Friedman's test; the baseline values were tested using Mann-Whitney U test and the difference of results of repeated measures were compared. RESULTS: In 31 animals that survived beyond 24 hours neither OFT, TRT nor NDS differed between the groups; histology was similar on day 2. On day 5, significantly more apoptosis in the CA1 segment of the hippocampus was found in the sevoflurane/fentanyl group. MCP-1 was higher on day 5 in the sevoflurane/fentanyl group (p = 0.04). All other cyto- and chemokines were below detection threshold. CONCLUSION: In our cardiac arrest model neurological function was not influenced by different anesthetic regimes; in contrast, anesthesia with sevoflurane/fentanyl results in increased CSF inflammation and histologic damage at day 5 post cardiac arrest.

Hyperbaric oxygen therapy for choroidal neovascularization: a pilot study.

INTRODUCTION: Choroidal neovascularization (CNV) is one of the leading causes of blindness worldwide and affects patients with wet age-related macular degeneration (AMD). Its natural course may lead to impaired central vision and macular fibrosis. Even VEGF blockade, currently the best available treatments for CNV, may fail to improve vision. Hyperbaric oxygen (HBO2) therapy may be an alternative or ancillary treatment for CNV. METHODS: AMD patients with active CNV underwent 10 daily sessions of HBO2 at 2 atmospheres absolute (atm abs) for 120 minutes each session. After the end of the sessions, patients with clinical or tomographical signs of CNV activity underwent standard anti-VEGF treatment. RESULTS: Seven patients (average age 73) underwent 10 daily 120-minute sessions of HBO2 at 2 atm abs. After the sessions, five patients underwent intravitreal injection of bevacizumab. Average follow-up was 150 days. Average CNV area at baseline was 14.42 mm2; average CNV greatest linear diameter at baseline was 4.56 mm. Statistical analysis of variance (ANOVA) was performed for central retinal thickness and volume mean percentage changes post-treatment. At the end of follow up, five patients showed anatomical improvement, one patient maintained anatomical aspect and one patient showed anatomical worsening. CONCLUSION: HBO2 may be a safe and tolerable treatment option for patients with active CNV, potentially delaying its progression, as monotherapy or in combination with intravitreal bevacizumab.

Interference of angiotensin II and enalapril with hepatic blood flow regulation.

Acute reduction of portal vein blood flow (Qpv) increases hepatic arterial perfusion (Qha) [the hepatic arterial buffer response (HABR)]. Angiotensin II (AT-II) reduces Qpv, but its effect on HABR is not known. We explored interactions of AT-II and enalapril with hepatic blood flow regulation. Twenty healthy anesthetized pigs were randomized to receive AT-II (n = 8) from 5 to 61 ng/kg per min, enalapril (n = 8) from 3 to 24 µg/kg per h, or saline (n = 4). HABR was assessed by occluding portal vein and expressed as 1) ratio between changes in Qha and Qpv, 2) hepatic arterial conductance (Cha). AT-II infusion increased mean arterial blood pressure from 74 (66-77) mmHg to 116 (109-130) mmHg (median, IQR; P < 0.0001) and decreased cardiac output, Qpv, and renal artery flow (-24%, -28% and -45%, respectively). The fraction of cardiac output of Qha, carotid, and femoral flows increased. With enalapril, blood pressure decreased, whereas cardiac output was maintained with flow redistribution favoring hepatic and renal arteries. In AT-II group, dQha/dQpv increased from 0.06 (0.03, 0.17) to 0.24 (0.13, 0.31) (P = 0.002), but Cha during acute portal vein occlusion decreased from 4.3 (1.6, 6.6) to 2.9 (1.2, 3.7) ml/mmHg (P = 0.003). Both variables remained unchanged in the enalapril group and in controls. AT-II infusion reduces portal flow in parallel with cardiac output and induces a dose-dependent redistribution of flow, favoring brain, hepatic artery, and peripheral tissues at the expense of renal perfusion. During HABR, AT-II decreases Cha but increases Qha compensation, likely as result of increased hepatic arterial perfusion pressure. Enalapril had no effect on HABR.

Angiotensin II in septic shock: effects on tissue perfusion, organ function, and mitochondrial respiration in a porcine model of fecal peritonitis.

OBJECTIVES: To compare effects of norepinephrine and angiotensin II in experimental sepsis on hemodynamics, organ function, and mitochondrial respiration. DESIGN: Randomized, controlled, study. SETTING: University experimental laboratory. SUBJECTS: Twenty-eight anesthetized, mechanically ventilated pigs. INTERVENTIONS: Sixteen pigs were randomized to receive after 12 hours of fecal peritonitis fluid resuscitation and either norepinephrine (group NE; n = 8) or angiotensin II (group AT-II; n = 8) for 48 hours. A separate group (n = 8), treated with enalapril for 1 week before peritonitis and until study end, received fluids and norepinephrine (group E). The blood pressure dose-response to angiotensin II was evaluated in additional four nonseptic pigs. MEASUREMENTS AND MAIN RESULTS: Blood pressure target (75-85 mm Hg) was reached in both NE and AT-II, and cardiac output increased similarly (NE: from 64 mL/kg/min [60-79 mL/kg/min] to 139 mL/kg/min [126-157 mL/kg/min]; AT-II from 79 mL/kg/min [65-86 mL/kg/min] to 145 mL/kg/min [126-147 mL/kg/min]; median, interquartile range). Renal plasma flow, prevalence of acute kidney injury, inflammation and coagulation patterns, and mitochondrial respiration did not differ between NE and AT-II. In group E, blood pressure targets were not achieved (mean arterial pressure at study end: NE: 81 mm Hg [76-85 mm Hg]; AT-II: 80 mm Hg [77-84 mm Hg]; E: 53 mm Hg [49-66 mm Hg], p = 0.002, compared to NE), whereas skeletal muscle adenosine triphosphate concentrations were increased. During resuscitation one animal died in groups AT-II and E. CONCLUSIONS: Angiotensin II reversed sepsis-induced hypotension with systemic and regional hemodynamic effects similar to those of norepinephrine. Inhibition of angiotensin-converting enzyme before sepsis worsened the hypotension but enhanced skeletal muscle adenosine triphosphate. Modifying the renin-angiotensin system in sepsis should be further evaluated.

On the Effect of Vibrotactile Stimulation in Essential Tremor.

(1) Background: Vibrotactile stimulation has been studied for tremor, but there is little evidence for Essential Tremor (ET). (2) Methods: This research employed a dataset from a previous study, with data collected from 18 individuals subjected to four vibratory stimuli. To characterise tremor changes before, during, and after stimuli, time and frequency domain features were estimated from the signals. Correlation and regression analyses verified the relationship between features and clinical tremor scores. (3) Results: Individuals responded differently to vibrotactile stimulation. The 250 Hz stimulus was the only one that reduced tremor amplitude after stimulation. Compared to the baseline, the 250 Hz and random frequency stimulation reduced tremor peak power. The clinical scores and amplitude-based features were highly correlated, yielding accurate regression models (mean squared error of 0.09). (4) Conclusions: The stimulation frequency of 250 Hz has the greatest potential to reduce tremors in ET. The accurate regression model and high correlation between estimated features and clinical scales suggest that prediction models can automatically evaluate and control stimulus-induced tremor. A limitation of this research is the relatively reduced sample size.