In silico analyses of acetylcholinesterase (AChE) and its genetic variants in interaction with the anti-Alzheimer drug Rivastigmine.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Despite causing great social and economic impact, there is currently no cure for AD. The most effective therapy to manage AD symptoms is based on acetylcholinesterase inhibitors (AChEi), from which rivastigmine presented numerous benefits. However, mutations in AChE, which affect approximately 5% of the population, can modify protein structure and function, changing the individual response to Alzheimer's treatment. In this study, we performed computer simulations of AChE wild type and variants R34Q, P135A, V333E, and H353N, identified by one or more genome-wide association studies, to evaluate their effects on protein structure and interaction with rivastigmine. The functional effects of AChE variants were predicted using eight machine learning algorithms, while the evolutionary conservation of AChE residues was analyzed using the ConSurf server. Autodock4.2.6 was used to predict the binding modes for the hAChE-rivastigmine complex, which is still unknown. Molecular dynamics (MD) simulations were performed in triplicates for the AChE wild type and mutants using the GROMACS packages. Among the analyzed variants, P135A was classified as deleterious by all the functional prediction algorithms, in addition to occurring at highly conserved positions, which may have harmful consequences on protein function. The molecular docking results suggested that rivastigmine interacts with hAChE at the upper active-site gorge, which was further confirmed by MD simulations. Our MD findings also suggested that the complex hAChE-rivastigmine remains stable over time. The essential dynamics revealed flexibility alterations at the active-site gorge upon mutations P135A, V333E, and H353N, which may lead to strong and nonintuitive consequences to hAChE binding. Nonetheless, similar binding affinities were registered in the MMPBSA analysis for the hAChE wild type and variants when complexed to rivastigmine. Finally, our findings indicated that the rivastigmine binding to hAChE is an energetically favorable process mainly driven by negatively charged amino acids.

Microcirculation assessment of dexmedetomidine constant rate infusion during anesthesia of dogs with sepsis from pyometra: a randomized clinical study.

OBJECTIVE: To compare dexmedetomidine and fentanyl constant rate infusions in anesthetic protocols for septic dogs with pyometra, using microcirculatory, hemodynamic and metabolic variables. STUDY DESIGN: Randomized clinical study. ANIMALS: A total of 33 dogs with pyometra with two or more systemic inflammatory response syndrome variables undergoing ovariohysterectomy. METHODS: Dogs were randomized into two groups: group DG, dexmedetomidine (3 µg kg-1 hour-1; 17 dogs) and group FG, fentanyl (5 µg kg-1 hour-1; 16 dogs) infused during isoflurane anesthesia and mechanical ventilation. Microcirculation flow index (MFI), total vessel density and De Backer score were assessed using orthogonal polarization spectral imaging at the sublingual site. Heart rate, invasive blood pressure, temperature, arterial blood gas analysis and lactate concentration were obtained at various time points. Variables were recorded at baseline (BL), immediately before (T0), 30 (T30) and 60 (T60) minutes after infusion, and 60 minutes after surgery. Data were analyzed using the Shapiro-Wilk test. To compare variables between groups, the unpaired Student t test was used. Comparison between evaluation time points was performed with two-way anova for repeated measures. Where statistical significance was detected, the Bonferroni post hoc test was used. RESULTS: MFI was significantly higher in group FG at T30. Mean arterial pressure at T30 was higher in group DG (89 ± 15 mmHg) than in group FG (72 ± 13 mmHg). Lactate concentrations were not significantly different between groups at each time point. Both groups had similar clinical outcomes (mortality, extubation time and occurrence of hypotension and bradyarrhythmias). CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine (3 µg kg-1 hour-1) without a loading dose can be included in the maintenance of anesthesia in dogs with pyometra and sepsis without compromising microcirculation and hemodynamic values when compared with fentanyl (5 µg kg-1 hour-1).

Cyclooxygenases 1 and 2 inhibition and analgesic efficacy of dipyrone at different doses or meloxicam in cats after ovariohysterectomy.

OBJECTIVE: To evaluate the cyclooxygenases (COX) inhibition, adverse effects and analgesic efficacy of dipyrone or meloxicam in cats undergoing elective ovariohysterectomy. STUDY DESIGN: Prospective, blinded, randomized, clinical study. ANIMALS: A total of 30 healthy young cats. METHODS: The cats were randomly assigned to three postoperative groups: D25 (dipyrone 25 mg kg-1 every 24 hours), D12.5 (dipyrone 12.5 mg kg-1 every 12 hours) and M (meloxicam 0.1 mg kg-1 every 24 hours). In the first 24 hours, the drugs were administered intravenously (IV), and then orally for 6 (dipyrone) or 3 days (meloxicam). Prostanoids thromboxane B2 and prostaglandin E2 concentrations served as indicators of COX activity and, with physiological variables and pain and sedation scores, were measured for 24 hours after first analgesic administration. Rescue analgesia (tramadol, 2 mg kg-1 IV) was provided if Glasgow feline composite measure pain scale (CMPS-Feline) ≥5. Laboratory tests included symmetric dimethylarginine and adverse effects were evaluated regularly up to 7 and 10 days after surgery, respectively. Parametric and nonparametric data were analyzed with two-way anova and Kruskal-Wallis tests, respectively (p < 0.05). RESULTS: In the first half hour after analgesic administration, COX-1 activity was close to zero and remained significantly lower than before drug administration for 24 hours in all groups. The inhibition of COX-2 activity was significant for 30 minutes in all groups and up to 4 hours in group M. No alterations in laboratory tests or significant adverse effects were observed. Pain scores and need for rescue analgesia did not differ statistically among groups. CONCLUSIONS: Dipyrone at both doses and meloxicam provided a nonselective inhibition of COX-1 and -2 activities and effective analgesia without causing significant adverse effects or laboratory tests alterations. CLINICAL RELEVANCE: Dipyrone at both doses provides equally effective analgesia without causing adverse effects in cats undergoing ovariohysterectomy.

Trehalose synthesis inhibitor: A molecular in silico drug design.

Infectious diseases are serious public health problems, affecting a large portion of the world's population. A molecule that plays a key role in pathogenic organisms is trehalose and recently has been an interest in the metabolism of this molecule for drug development. The trehalose-6-phosphate synthase (TPS1) is an enzyme responsible for the biosynthesis of trehalose-6-phosphate (T6P) in the TPS1/TPS2 pathway, which results in the formation of trehalose. Studies carried out by our group demonstrated the inhibitory capacity of T6P in the TPS1 enzyme from Saccharomyces cerevisiae, preventing the synthesis of trehalose. By in silico techniques, we compiled sequences and experimentally determined structures of TPS1. Sequence alignments and molecular modeling were performed. The generated structures were submitted in validation of algorithms, aligned structurally and analyzed evolutionarily. Molecular docking methodology was applied to analyze the interaction between T6P and TPS1 and ADMET properties of T6P were analyzed. The results demonstrated the models created presented sequence and structural similarities with experimentally determined structures. With the molecular docking, a cavity in the protein surface was identified and the molecule T6P was interacting with the residues TYR-40, ALA-41, MET-42, and PHE-372, indicating the possible uncompetitive inhibition mechanism provided by this ligand, which can be useful in directing the molecular design of inhibitors. In ADMET analyses, T6P had acceptable risk values compared with other compounds from World Drug Index. Therefore, these results may present a promising strategy to explore to develop a broad-spectrum antibiotic of this specific target with selectivity, potency, and reduced side effects, leading to a new way to treat infectious diseases like tuberculosis and candidiasis.

Comparison of pulse pressure variation versus echocardiography-derived stroke volume variation for prediction of fluid responsiveness in mechanically ventilated anesthetized dogs.

OBJECTIVE: To evaluate the ability and accuracy of aortic flow velocity-time integral variation (ΔVTI) and peak aortic velocity variation (ΔVpeak) compared with pulse pressure variation (PPV) to predict fluid responsiveness in mechanically ventilated dogs. STUDY DESIGN: Prospective clinical study. ANIMALS: A group of 50 mechanically ventilated dogs with spontaneous hypotension during orthopedic or oncologic surgery. METHODS: Investigations were performed in the surgery room. When mean arterial pressure (MAP) decreased to <65 mmHg, measurements were performed before and after a fluid challenge (lactated Ringer's solution 5 mL kg-1 over 15 minutes). Responders were defined as a change in stroke volume (SV; transesophageal Doppler) ≥15%. Data were analyzed using paired/unpaired t test or Mann-Whitney/Wilcoxon test when appropriate and receiver operating characteristics (ROC) curves; a p value <0.05 was considered statistically significant. RESULTS: After the fluid challenge, 35 (70%) of 50 dogs were responders with significant increases in SV and decreases in PPV; 15 dogs were nonresponders. ΔVTI and ΔVpeak correlated with a 15% increase in SV. The optimum cut-off value for PPV was 15.6% (sensitivity, 88%; specificity, 100%), for ΔVTI was 10.65% (sensitivity, 65%; specificity, 100%) and for ΔVpeak was 10.15% (sensitivity, 80%; specificity, 100%). The area under the ROC curve for PPV was (0.93 ± 0.08) and for ΔVpeak was (0.89 ± 0.09), before fluid challenge. The gray zone area spread from 6.15% to 15.6% for PPV (18 dogs), 2.45% to 10.65% for ΔVTI (22 dogs) and 0.6% to 10.15% for ΔVpeak (25 dogs). CONCLUSIONS: When using mechanical ventilation, ΔVTI and ΔVpeak predicted fluid responsiveness with the same ability as PPV, based on the area under the ROC curve analysis. However, PPV showed great accuracy demonstrated by a narrower gray zone that included fewer individuals. CLINICAL RELEVANCE: ΔVTI and ΔVpeak can be used as indices of fluid responsiveness in anesthetized dogs.

Complete genome sequencing of sixteen Francisella noatunensis subsp. orientalis isolates: A genomic approach for molecular characterization and spread dynamics of this clonal population.

Francisella noatunensis subsp. orientalis (FNO) is an important emerging pathogen associated with disease outbreaks in farm-raised Nile tilapia. FNO genetic diversity using PCR-based typing, no intra-species discrimination was achieved among isolates/strains from different countries, thus demonstrating a clonal behaviour pattern. In this study, we aimed to evaluate the population structure of FNO isolates by comparing whole-genome sequencing data. The analysis of recombination showed that Brazilian isolates group formed a clonal population; whereas other lineages are also supported by this analysis for isolates from foreign countries. The whole-genome multilocus sequence typing (wgMLST) analysis showed varying numbers of dissimilar alleles, suggesting that the Brazilian clonal population are in expansion. Each Brazilian isolate could be identified as a single node by high-resolution gene-by-gene approach, presenting slight genetic differences associated to mutational events. The common ancestry node suggests a single entry into the country before 2012, and the rapid dissemination of this infectious agent may be linked to market sales of infected fingerlings.

Postoperative pain and short-term complications after two elective sterilization techniques: ovariohysterectomy or ovariectomy in cats.

BACKGROUND: Surgical sterilization of cats is one of the most commonly performed procedures in veterinary practice and it can be accomplished by two different techniques: ovariohysterectomy (OVH) or ovariectomy (OVE). Although there is an apparent preference for OVH in United States and Canada, OVE seems to be the standard of care in many European countries due to its advantages, such as a smaller surgical incision and potentially less complications associated with surgical manipulation of the uterus. The aim of this randomized, blind, prospective study was to compare postoperative pain and short-term complications in cats undergoing ovariohysterectomy or ovariectomy. METHODS: Twenty female cats were randomly assigned into two groups (OVH, n = 10 and OVE, n = 10). Pain was assessed prior to surgery (baseline) and 1, 2, 4, 8 12 and 24 h after the procedure using pain and sedation scales, physiologic parameters and blood glucose levels. Short-term complications were evaluated in the early postoperative period and reassessed at day 7 and day 10. RESULTS: Changes in cardiovascular parameters were not clinically relevant, however cats in OVH group had higher heart rates at T1 h compared with baseline (p = 0.0184). Blood glucose levels in OVH group were also higher at T1 h compared with baseline (p = 0.0135) and with OVE group (p = 0.0218). Surgical time was higher in OVH group (p = 0.0115). Even though no significant differences in pain scores were observed between groups or time points, cats in OVH group had greater need for rescue analgesia compared with OVE (2/10 and 0/10, respectively). Complications were not observed in any cat during surgery, at days 7 and 10 postoperatively or at discharge. CONCLUSIONS: Both surgical techniques promoted similar intensity of postoperative pain in cats and there were no short-term complications throughout the study's evaluation period. Therefore, both techniques may be indicated for surgical sterilization of cats, according to the surgeon's preference and expertise. Cats that underwent ovariectomy did not require rescue analgesia and surgical time was shorter in that group.

Influence of early progesterone removal on follicular development, expression of estrus, and pregnancy rates in presynchronized postpartum beef cows.

The objective of this study was to evaluate the impact of early progesterone removal on pregnancy rates to fixed-time artificial insemination (FTAI) in presynchronized beef cows. Postpartum beef cows (n = 882) were randomly assigned to 1 of 2 treatments: 1) 7&7 Synch: cows received a controlled internal drug release insert (CIDR) and a 25-mg injection of prostaglandin F2α on day 0, 100 µg of GnRH on day 7, a second injection of prostaglandin F2α (PG2) at CIDR removal on day 14, and a second injection of GnRH at FTAI 60-66 h after PG2 (day 17); 2) 7&6 Synch: cows received the same treatment as 7&7 Synch; however, CIDR removal occurred in conjunction with PG2 on day 13, while FTAI remained at 60-66 h after CIDR removal (day 16). Ovarian ultrasonography was performed to determine follicle diameter at PG2 and FTAI in a subset of cows (n = 40). Cows exposed to the 7&7 Synch tended to have larger follicle diameter at PG2 compared with 7&6 Synch cows (P = 0.09); however, there were no differences in follicle diameter at FTAI. No differences were determined between treatments for the expression of estrus (7&7 Synch: 61.6 ± 5.30; 7&6 Synch: 54.1 ± 5.45; P = 0.31) or pregnancy rates to FTAI (7&7 Synch: 60.8 ± 3.83; 7&6 Synch: 57.0 ± 3.84; P = 0.42). In conclusion, early removal of progesterone did not impact pregnancy rates in presynchronized beef cows.

The Synthetic Peptide LyeTx I mn∆K, Derived from Lycosa erythrognatha Spider Toxin, Is Active against Methicillin-Resistant Staphylococcus aureus (MRSA) In Vitro and In Vivo.

The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrates remarkable efficacy against planktonic cells (MIC 8-16 µM) and biofilms (>30% of inhibition) of MRSA, and outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight the versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, this study showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wounds in mice. Together, the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.

Chalcone Derivatives as Antibacterial Agents: An Updated Overview.

BACKGROUND: The indiscriminate use of antibiotics brings an alarming reality: in 2050, bacterial resistance could be the main cause of death in the world, resulting in the death of 10 million people, according to the World Health Organization (WHO). In this sense, to combat bacterial resistance, several natural substances, including chalcones, have been described in relation to antibacterial, representing a potential tool for the discovery of new antibacterial drugs. OBJECTIVE: The objective of this study is to perform a bibliographic survey and discuss the main contributions in the literature about the antibacterial potential of chalcones in the last 5 years. METHOD: A search was carried out in the main repositories, for which the publications of the last 5 years were investigated and discussed. Unprecedented in this review, in addition to the bibliographic survey, molecular docking studies were carried out to exemplify the applicability of using one of the molecular targets for the design of new entities with antibacterial activity. RESULTS: In the last 5 years, antibacterial activities were reported for several types of chalcones, for which activities were observed for both gram-positive and gram-negative bacteria with high potency, including MIC values in the nanomolar range. Molecular docking simulations demonstrated important intermolecular interactions between chalcones and residues from the enzymatic cavity of the enzyme DNA gyrase, one of the validated molecular targets in the development of new antibacterial agents. CONCLUSION: The data presented demonstrate the potential of using chalcones in drug development programs with antibacterial properties, which may be useful to combat resistance, a worldwide public health problem.

Morphological Characteristics of Proximal Ulna Fractures: A Proposal for a New Classification and Agreement for Validation.

Historically, proximal ulna fractures have been simplistically diagnosed and treated as simple olecranon fractures, leading to an unacceptable number of complications. Our hypothesis was that the recognition of lateral, intermediate, and medial stabilizers of the proximal ulna and ulnohumeral and proximal radioulnar joints would facilitate decision-making, including the choice of approach and type of fixation. The primary aim was to propose a new classification for complex fractures of the proximal ulna based on morphological characteristics seen on three-dimensional computed tomography (3D CT). The secondary aim was to validate the proposed classification regarding its intra- and inter-rater agreement. Three raters with different levels of experience analyzed 39 cases of complex fractures of the proximal ulna using radiographs and 3D CT scans. We presented the proposed classification (divided into four types with subtypes) to the raters. In this classification, the medial column of the ulna involves the sublime tubercle and is where the anterior medial collateral ligament is inserted, the lateral column contains the supinator crest and is where the lateral ulnar collateral ligament is inserted, and the intermediate column involves the coronoid process of the ulna, olecranon, and anterior capsule of the elbow. Intra- and inter-rater agreement was analyzed for two different rounds, and the results were evaluated according to Fleiss kappa, Cohen kappa, and Kendall coefficient. Intra- and inter-rater agreement values were very good (0.82 and 0.77, respectively). Good intra- and inter-rater agreement attested to the stability of the proposed classification among the raters, regardless of the level of experience of each one. The new classification proved to be easy to understand and had very good intra- and inter-rater agreement, regardless of the level of experience of each rater.

First case report of feline sporotrichosis caused by Sporothrix brasiliensis in the state of Ceará - Brazil.

Feline sporotrichosis is a zoonotic mycosis caused by fungi belonging to the Sporothrix schenckii complex. In the state of Ceará, there are no reports of isolation of this fungus in cats. This study presents the first report of feline sporotrichosis caused by the species Sporothrix brasiliensis in the state of Ceará - Brazil. The diagnosis was made through cytopathological examination, mycological culture and PCR. The findings were compatible with feline sporotrichosis caused by Sporothrix brasiliensis.

Comparison of Hemodynamic Effects of Dobutamine and Ephedrine Infusions in Isoflurane-Anesthetized Horses.

The objective of this study was to compare the hemodynamic effects of dobutamine and ephedrine during the management of anesthesia-related hypotension in healthy horses. Thirteen horses underwent general anesthesia with isoflurane and were randomly divided into two different groups, one of which received a dobutamine constant rate infusion (CRI) (1 µg/kg bwt/min) and the other received an ephedrine CRI (20 µg/kg bwt/min) when hypotension (<60 mmHg) was identified, following up to 15 min after the blood pressure reached 70 mmHg. All horses were equipped with a pulmonary artery catheter and a peripheral artery catheter, and multiparameter monitoring commenced as soon as they were under mechanical ventilation. Hemodynamic parameters were recorded, while tissue perfusion markers (peripheral oxygen saturation, arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial plasma bicarbonate concentration, arterial oxygen saturation, mixed venous oxygen saturation, mixed venous oxygen content, arterial oxygen content, arteriovenous oxygen difference, oxygen delivery index, oxygen consumption index, and oxygen extraction ratio), serum lactate concentration, and troponin I concentrations were analyzed before the start of infusions (T0), when the blood pressure reached 70 mmHg (T1), and 15 min after T1 (T2). The time to restore the arterial pressure was similar in both groups (p > 0.05); however, the heart rate was higher in the ephedrine group (p = 0.0098), and sinus bradyarrhythmia occurred in the dobutamine group. Furthermore, both experimental protocols increased cardiac output (p = 0.0012), cardiac index (p = 0.0013), systemic vascular resistance (p = 0.008), systemic vascular resistance index (p < 0.001), and ameliorated perfusion markers. In the dobutamine group, the pulmonary artery wedge pressure (p < 0.001) and systolic index (p = 0.003) were elevated, while the arteriovenous oxygen difference was reduced in the ephedrine group (p = 0.02). Troponin I was used as a myocardial injury indicator, and did not differ between moments or between groups (p > 0.05). We concluded that both drugs were effective and safe to treat anesthetic hypotension under the conditions of this study.

Intraoperative Protective Mechanical Ventilation in Dogs: A Randomized Clinical Trial.

Objective: To evaluate gas exchange, respiratory mechanics, and hemodynamic impact of mechanical ventilation with low tidal volume (VT) in dogs with the use of positive end-expiratory pressure (PEEP) or preceded by alveolar recruitment maneuver (ARM). Study Design: Prospective randomized clinical trial. Animals: Twenty-one healthy client-owned mesocephalic healthy dogs, 1-7 years old, weighing 10-20 kg, and body condition scores 4-6/9 admitted for periodontal treatment. Methods: Isoflurane-anesthetized dogs in dorsal recumbency were ventilated until 1 h with a volume-controlled ventilation mode using 8 mL kg-1 of VT. The dogs were distributed in 2 groups: in the ARM group, PEEP starts in 0 cmH2O, increasing gradually 5 cmH2O every 3 min, until reach 15 cmH2O and decreasing in the same steps until 5 cmH2O, maintaining this value until the end; and PEEP group, in which the pressure 5 cmH2O was instituted from the beginning of anesthesia and maintained the same level up to the end of the anesthesia. Cardiopulmonary, metabolic, oxygenation parameters, and respiratory mechanics were recorded after the anesthesia induction (baseline-BL), 15, 45, and 75 min after BL and during the recovery. Results: The ARM increased the static compliance (Cst) (15 min after baseline) when compared with baseline moment (24.9 ± 5.8 mL cmH20-1 vs. 20.7 ± 5.4 mL cmH20-1-p = 0.0364), oxygenation index (PaO2/FIO2) (505.6 ± 59.2 mmHg vs. 461.2 ± 41.0 mmHg-p = 0.0453) and reduced the shunt fraction (3.4 ± 2.4% vs. 5.5 ± 1.6%-p = 0.062). In the PEEP group, no statistical differences were observed concerning the variables evaluated. At the beginning of the evaluation, the driving pressure (DP) before ARM was significantly greater than all other evaluation time points (6.9 ± 1.8 cmH20). Conclusions and Clinical Relevance: The use of 8 mL kg-1 of VT and 5 cmH20 PEEP without ARM maintain adequate oxygenation and mechanical ventilation in dental surgeries for up to 1 h. The use of ARM slightly improved compliance and oxygenation during the maneuver.

Corrigendum: Intraoperative protective mechanical ventilation in dogs: A randomized clinical trial.

[This corrects the article DOI: 10.3389/fvets.2022.842613.].

Bacterial Co-Infection in Patients with COVID-19 Hospitalized (ICU and Not ICU): Review and Meta-Analysis.

The prevalence of patients hospitalized in ICUs with COVID-19 and co-infected by pathogenic bacteria is relevant in this study, considering the integrality of treatment. This systematic review assesses the prevalence of co-infection in patients admitted to ICUs with SARS-CoV-2 infection, using the PRISMA guidelines. We examined the results of the PubMed, Embase, and SciELO databases, searching for published English literature from December 2019 to December 2021. A total of 542 rec ords were identified, but only 38 were eligible and, and of these only 10 were included. The tabulated studies represented a sample group of 1394 co-infected patients. In total, 35%/138 of the patients were co-infected with Enterobacter spp., 27% (17/63) were co-infected with methicillin-sensitive Staphylococ cus aureus, 21% (84/404) were co-infected with Klebsiella spp., 16% (47/678) of patients were co-infected with coagulase-negative Staphylococcus, 13% (10/80) co-infected with Escherichia coli (ESBL), and 3% (30/1030) of patients were co-infected with Pseudomonas aeruginosa. The most common co-infections were related to blood flow; although in the urinary and respiratory tracts of patients Streptococcus pneumoniae was found in 57% (12/21) of patients, coagulase negative Staphylococcus in 44% (7/16) of patients, and Escherichia coli was found in 37% (11/29) of patients. The present research demonstrated that co-infections caused by bacteria in patients with COVID-19 are a concern.

Multisystem inflammatory syndrome (MIS-C): a systematic review and meta-analysis of clinical characteristics, treatment, and outcomes.

OBJECTIVE: The clinical cases of patients with multisystem inflammatory syndrome (MIS-C) were analyzed via a systematic review and meta-analysis of the clinical findings, treatments, and possible outcomes of articles retrieved via database searches. SOURCES: The authors searched the PubMed, Scielo, Web of Science, Science Direct, EMBASA, EBSCO, and Scopus databases for articles containing the keywords "multisystem inflammatory syndrome in children" or "MIS-C" or "PIMS-TS" or "SIMP" and "COVID-19" or "SARS-CoV-2" published between December 1st, 2019 and July 10th, 2021. Patient characteristics, tissue and organ comorbidities, the incidence of symptoms after COVID-19 infection, treatment, and patient evolution in the articles found were evaluated. The data were abstracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Newcastle-Ottawa Scale (NOS). FINDINGS: In total, 98 articles (2275 patients) were selected for demographics, clinical treatment, and outcomes of patients diagnosed with MIS-C. The average age of children with MIS-C, 56.8% of whom were male, was of nine years. Fever (100%), gastrointestinal (GI) (82%), and abdominal pain (68%) were the decisive symptoms for the diagnosis of MIS-C. Shock and/or hypotension were common in patients with MIS-C. Cardiac symptoms (66%) predominated over respiratory (39%) and neurological (28%) symptoms. MIS-C treatment followed the common guidelines for treating children with septic shock and Kawasaki disease (KD) and proved to be effective. CONCLUSIONS: This meta-analysis highlights the main clinical symptoms used for the diagnosis of MIS-C, the differences between MIS-C and KD, and the severity of the inflammatory process and urgency for hospital care.

Efficacy and Complications of Subcutaneous versus Conventional Cardioverter Defibrillators: A Systematic Review and Meta-analysis.

BACKGROUND/OBJECTIVES: Implantable cardioverter defibrillators are used to prevent sudden cardiac death. The subcutaneous implantable cardioverter-defibrillator was newly developed to overcome the limitations of the conventional implantable cardioverter defibrillator-transvenous device. The subcutaneous implantable cardioverter defibrillator is indicated for young patients with heart disease, congenital heart defects, and poor venous access, who have an indication for implantable cardioverter defibrillator without the need for anti-bradycardic stimulation. We aimed to compare the efficacy and complications of subcutaneous with transvenous implantable cardioverter- defibrillator devices. METHODOLOGY: A systematic review was conducted using different databases. The inclusion criteria were observational and clinical randomized trials with no language limits and no publication date limit that compared subcutaneous with transvenous implantable cardioverter-defibrillators. The selected patients were aged > 18 years with complex ventricular arrhythmia. RESULTS: Five studies involving 2111 patients who underwent implantable cardioverter defibrillator implantation were included. The most frequent complication in the subcutaneous device group was infection, followed by hematoma formation and electrode migration. For the transvenous device, the most frequent complications were electrode migration and infection. Regarding efficacy, the total rates of appropriate shocks were 9.04% and 20.47% in the subcutaneous and transvenous device groups, respectively, whereas inappropriate shocks to the subcutaneous and transvenous device groups were 11,3% and 10,7%, respectively. CONCLUSION: When compared to the transvenous device, the subcutaneous device had lower complication rates owing to lead migration and less inappropriate shocks due to supraventricular tachycardia; nevertheless, infection rates and improper shocks due to T wave oversensing were comparable for both devices CRD42021251569.

The optimal PEEP after alveolar recruitment maneuver assessed by electrical impedance tomography in healthy horses.

Background: Electrical impedance tomography (EIT) has been an essential tool for assessing pulmonary ventilation in several situations, such as the alveolar recruitment maneuver (ARM) in PEEP titration to maintain the lungs open after atelectasis reversion. In the same way as in humans and dogs, in horses, this tool has been widely used to assess pulmonary aeration undergoing anesthesia, mechanical ventilation, recruitment maneuver, standing horses, or specific procedures. Objectives: The present study aimed to evaluate the distribution of regional ventilation during ARM based on lung monitoring assessment by EIT, with a focus on better recruitment associated with less or no overdistention. Methods: Fourteen horses of 306 ± 21 kg undergoing isoflurane anesthesia in dorsal recumbency were used. The animals were mechanically ventilated with a tidal volume of 14 ml kg-1 and a respiratory rate of 7-9. An alveolar recruitment maneuver was instituted, increasing the PEEP by five cmH2O every 5 min until 32 cmH2O and decreasing it by five cmH2O every 5 min to 7 cmH2O. At each step of PEEP, arterial blood samples were collected for blood gas analysis, EIT images, hemodynamic, and respiratory mechanics. Results: Associated with the CoV-DV increase, there was a significant decrease in the DSS during the ARM and a significant increase in the NSS when PEEP was applied above 12 cmH2O compared to baseline. The ComplROI showed a significant increase in the dependent area and a significant decrease in the non-dependent area during ARM, and both were compared to their baseline values. The driving pressure decreased significantly during the ARM, and Cst, PaO2, and PaO2/FiO2 ratio increased significantly. The VD/VT decreased significantly at DEPEEP17 and DEPEEP12. There was an HR increase at INPEEP27, INPEEP 32, and DEPEEP17 (p < 0.0001; p < 0.0001; and p < 0.05, respectively), those values being above the normal reference range for the species. The SAP, MAP, DAP, CI, and DO2I significantly decreased INPEEP32 (p < 0.05). Conclusion: The ARM by PEEP titration applied in the present study showed better ventilation distribution associated with better aeration in the dependent lung areas, with minimal overdistention between PEEP 17 and 12 cmH2O decreasing step. Those changes were also followed by improvements in static and regional compliance associated with increased oxygenation and pulmonary ventilation. ARM promoted a transitory decrease in arterial blood pressure and depression in CI with a concomitant drop in oxygen delivery, which should be best investigated before its routine use in clinical cases.