Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-Analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = \uc3\ua2 '0.24 to \uc3\ua2 '0.73; P < 1.49 \uc3\u97 10 \uc3\ua2 '4), and lower thickness in the precentral gyri bilaterally (d = \uc3\ua2 '0.34 to \uc3\ua2 '0.52; P < 4.31 \uc3\u97 10 \uc3\ua2 '6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = \uc3\ua2 '1.73 to \uc3\ua2 '1.91, P < 1.4 \uc3\u97 10 \uc3\ua2 '19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = \uc3\ua2 '0.36 to \uc3\ua2 '0.52; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = \uc3\ua2 '0.29 to \uc3\ua2 '0.54; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = \uc3\ua2 '0.27 to \uc3\ua2 '0.51; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < \uc3\ua2 '0.0018; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): study protocol for a randomized controlled trial

BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). METHODS/DESIGN: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH2O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure 6430 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. DISCUSSION: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration metho

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Nutrient addition does not enhance leaf decomposition in a Southeastern Brazilian stream (Espinha\ue7o mountain range)

A decomposition experiment using eucalyptus leaves was carried out in a Southeastern Brazilian mountain stream located at the transition between the Cerrado and the Atlantic Forest to test whether nutrient addition increases microbial and invertebrate colonisation and accelerates breakdown rates. The results show that none of the tested variables was significantly affected by nutrient addition, despite the average increase in ATP concentrations and invertebrate colonisation observed in the fertilised leaf bags. This could mean that breakdown in the stream was already at its maximum due to the relatively high water temperature and nutrient content, or that the breakdown rate of eucalyptus leaves was too fast to allow the detection of any effects of nutrient addition. Breakdown rates of eucalyptus leaves were much faster than the values reported in literature for most species in Brazilian Cerrado streams, suggesting that the replacement of the natural vegetation by eucalyptus may affect nutrient dynamics in the region

Pectin hydrolysis in cashew apple juice by Aspergillus aculeatus URM4953 polygalacturonase covalently-immobilized on calcium alginate beads: A kinetic and thermodynamic study

The kinetics and thermodynamics of pectin hydrolysis in cashew apple juice by polygalacturonase (PG) from Aspergillus aculeatus URM4953 covalently-immobilized on calcium alginate beads were investigated. Immobilized-PG activity in cashew apple juice was the highest at 20\u202f\ub0C, showing a maximum hydrolysis rate of 58.2\u202fmg/mL\ub7min, a catalytic constant of 166.2\u202fs-1 and an affinity constant of 113.0\u202fmg/mL. Since the enzyme exhibited an allosteric behavior, the hydrolysis rate was modeled, with excellent accuracy, by the Hill Equation as function of pectin concentration. The Hill coefficient increased from 3 to 5 with increasing temperature from 20 to 50\u202f\ub0C, evidencing a positive cooperativity mechanism. The reaction activation energy and the standard enthalpy variation of enzyme unfolding were 80.3 and 16.6\u202fkJ/mol, respectively. Consistently with the kinetic results, PG-catalyzed pectin hydrolysis proceeded with maximum spontaneity at 20\u202f\ub0C, showing activation Gibbs free energy, enthalpy and entropy of 59.3\u202fkJ/mol, 77.9\u202fkJ/mol and 63.4\u202fJ/mol\ub7K, respectively. Immobilized PG was successful in the hydrolysis of cashew apple juice pectin, requiring a low temperature to act optimally

Laser treatment of leg ulcers: selected concepts

An overview on different laser devices, available for the treatment of the different phases of wound healing: debridement, wound repair and scars correction

Kinetic and thermodynamic characterization of a novel Aspergillus aculeatus URM4953 polygalacturonase. Comparison of free and calcium alginate-immobilized enzyme

Polygalacturonase (EC 3.2.1.15) (PG) from Aspergillus aculeatus URM4953 was covalently immobilized on calcium alginate beads using glutaraldehyde as a cross-linking agent. The immobilization conditions were optimized by a central composite design. Only the time influenced significantly PG immobilization, whose highest yield (95%) was obtained using 2% glutaraldehyde after 45 min. PG, characterized in terms of kinetic and thermodynamic parameters, displayed the same pH profile in free and immobilized forms, with two optimum pH values under acidic (4.0) and neutral (7.0) conditions. Although lowering the PG optimum temperature from 50 to 40 \ub0C, the immobilization did not influence the enzyme stability in the range 30\u201340 \ub0C, preserving more than 90% of its initial activity after 60 min. The kinetic parameters of immobilized PG revealed higher affinity for pectin than free PG, which nonetheless was slightly more efficient in pectin degradation. The thermodynamic parameters of immobilized PG thermoinactivation suggested a predominating mechanism of reversible unfolding, which was responsible for lower sensitivity to heating than free PG and allowed four successive cycles of immobilized enzyme utilization with only 33% of activity loss. Immobilized PG showed satisfactory performance and features as well as great potential for future industrial applications

Embryonic and larval development of Brycon amazonicus (SPIX &amp; AGASSIZ, 1829)

Abstract The objective of this study was to describe the embryonic and larval development of Brycon amazonicus, featuring the main events up to 50 hours after fertilization (AF). The material was provided by the Aquaculture Training, Technology and Production Center, Presidente Figueiredo (AM). The characterization was based on stereomicroscopic examination of the morphology of eggs, embryos and larvae and comparison with the literature. Matrinxã eggs are free, transparent, and spherical, with a perivitelline space of 0.56 ± 0.3 mm. The successive divisions give rise to cells with 64 blastomeres during the first hour AF. The gastrula stage, beginning 02 h 40 min AF, was characterized by progressive regression cells and the formation of the embryonic axis, leading to differentiation of the head and tail 05 h 30 min AF. From 06 to 09 h AF the somites, notochord, otic and optic vesicles and otoliths were observed, in addition to heart rate and the release of the tail. The larvae hatched at 10 h 30 min AF (29.9 °C), with a total length of 3.56 ± 0.46 mm. Between 19 and 30 h AF, we observed 1) pigmentation and gut formation, 2) branchial arches, 3) pectoral fins, 4) a mouth opening and 5) teeth. Cannibalism was initiated earlier (34 h AF) which was associated with rapid yolk absorption (more than 90% until 50 h AF), signaling the need for an exogenous nutritional source. The environmental conditions (especially temperature) influenced the time course of some events throughout the embryonic and larval development, suggesting the need for further studies on this subject