Impact of extended lung protection during mechanical ventilation on lung recovery in patients with COVID-19 ARDS: a phase II randomized controlled trial.

BACKGROUND: Protective ventilation seems crucial during early Acute Respiratory Distress Syndrome (ARDS), but the optimal duration of lung protection remains undefined. High driving pressures (ΔP) and excessive patient ventilatory drive may hinder lung recovery, resulting in self-inflicted lung injury. The hidden nature of the ΔP generated by patient effort complicates the situation further. Our study aimed to assess the feasibility of an extended lung protection strategy that includes a stepwise protocol to control the patient ventilatory drive, assessing its impact on lung recovery. METHODS: We conducted a single-center randomized study on patients with moderate/severe COVID-19-ARDS with low respiratory system compliance (CRS < 0.6 (mL/Kg)/cmH2O). The intervention group received a ventilation strategy guided by Electrical Impedance Tomography aimed at minimizing ΔP and patient ventilatory drive. The control group received the ARDSNet low-PEEP strategy. The primary outcome was the modified lung injury score (mLIS), a composite measure that integrated daily measurements of CRS, along with oxygen requirements, oxygenation, and X-rays up to day 28. The mLIS score was also hierarchically adjusted for survival and extubation rates. RESULTS: The study ended prematurely after three consecutive months without patient enrollment, attributed to the pandemic subsiding. The intention-to-treat analysis included 76 patients, with 37 randomized to the intervention group. The average mLIS score up to 28 days was not different between groups (P = 0.95, primary outcome). However, the intervention group showed a faster improvement in the mLIS (1.4 vs. 7.2 days to reach 63% of maximum improvement; P < 0.001), driven by oxygenation and sustained improvement of X-ray (P = 0.001). The intervention group demonstrated a sustained increase in CRS up to day 28 (P = 0.009) and also experienced a shorter time from randomization to room-air breathing (P = 0.02). Survival at 28 days and time until liberation from the ventilator were not different between groups. CONCLUSIONS: The implementation of an individualized PEEP strategy alongside extended lung protection appears viable. Promising secondary outcomes suggested a faster lung recovery, endorsing further examination of this strategy in a larger trial. Clinical trial registration This trial was registered with ClinicalTrials.gov (number NCT04497454) on August 04, 2020.

Clonal Hematopoiesis of Indeterminate Potential and Long-term Outcomes in Heart Transplantation.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) mutations, a trait of aging, has been associated with the progression of cardiovascular disease and the development of malignancy. Uncertainty prevails regarding a robust association between CHIP and heart-transplantation (HT) outcomes. OBJECTIVES: To determine the prevalence of CHIP mutations in HT and their association with long-term outcomes, including cardiac allograft vasculopathy (CAV), graft failure, malignancy, and all-cause mortality. METHODS: We conducted a mixed retrospective-prospective observational study of HT recipients with targeted sequencing for CHIP mutations (variant allele frequency [VAF] of ≥ 2%). The primary composite outcome was the first occurrence of CAV grade ≥ 2, graft failure, malignancy, cardiac retransplantation, or all-cause death. Secondary outcomes were the individual components of the composite primary outcome. Sensitivity analyses with base-case and extreme scenarios were performed. RESULTS: Among 95 HT recipients, 30 had CHIP mutations (31.6%). DNMT3A mutations were most common (44.7%), followed by PPM1D (13.2%), SF3B1 (10.5%), TET2 (7.9%), and TP53 (7.9%). The only significant independent predictor of CHIP was age at enrollment or age at transplantation. After multivariable adjustment, CHIP mutations were not associated with the primary outcome, which occurred in 44 (46.3%) patients (HR = 0.487; 95% CI:0.197-1.204; P = 0.119), nor were they associated with mlalignancy alone, or death. CONCLUSION: We demonstrated no association between CHIP mutations and post-transplant outcomes, including CAV, graft failure, malignancy, and all-cause mortality. In line with previously published data, our analysis provides additional evidence about the lack of clinical value of using CHIP mutations as a biomarker for surveillance in outcomes after HT.

Regional pulmonary perfusion, blood volume, and their relationship change in experimental early ARDS.

Regional pulmonary perfusion (Q) has been investigated using blood volume (Fb) imaging as an easier-to-measure surrogate. However, it is unclear if changing pulmonary conditions could affect their relationship. We hypothesized that vascular changes in early acute respiratory distress syndrome (ARDS) affect Q and Fb differently. Five sheep were anesthetized and received lung protective mechanical ventilation for 20 h while endotoxin was continuously infused. Using dynamic 18F-FDG and 13NN Positron Emission Tomography (PET), regional Fb and Q were analysed in 30 regions of interest (ROIs) and normalized by tissue content (Fbn and Qn, respectively). After 20 h, the lung injury showed characteristics of early ARDS, including gas exchange and lung mechanics. PET images of Fbn and Qn showed substantial differences between baseline and lung injury. Lung injury caused a significant change in the Fbn-Qn relationship compared to baseline (p < 0.001). The best models at baseline and lung injury were Fbn = 0.32 + 0.690Qn and Fbn = 1.684Qn-0.538Qn2, respectively. Endotoxine-associated early ARDS changed the relationship between Fb and Q, shifting from linear to curvilinear. Effects of endotoxin exposure on the vasoactive blood flow regulation were most likely the key factor for this change limiting the quantitative accuracy of Fb imaging as a surrogate for regional Q.

Microplastic pollution in waters of the Antarctic coastal environment of Potter Cove (25 de Mayo Island/King George Island, South Shetlands).

Plastic pollution in the Southern Ocean around Antarctica is a growing concern, but many areas in this vast region remain unexplored. This study provides the first comprehensive analysis of marine microplastic (MPs) concentrations in Potter Cove, located near the Argentinian Carlini research station on 25 de Mayo/King George Island, Antarctica. Water samples were collected at 14 sites within the cove, representing various influences from the station's activities. Two sampling methods were used: a 5 L Niskin bottle and an in-situ filtering device called Microfilter, allowing for large water volumes to be filtered. MPs were found in 100 % of the samples. Microfilter samples ranged from 0.02 to 2.14 MPs/L, with a mean concentration of 0.44 ± 0.44 MPs/L. Niskin bottle samples showed concentrations from 0.40 to 55.67 MPs/L, with a mean concentration of 19.03 ± 18.21 MPs/L. The dominant types of MPs were anthropogenic black, transparent, and pink microfibers (MFs) measuring between 0.11 and 3.6 mm (Microfilter) and 0.06 to 7.96 mm (Niskin bottle), with a median length of 0.01 mm for both methods. Transparent and black irregular microfragments (MFRs) with diameters from 0.10 to 5.08 mm and a median diameter of 0.49 mm were also prevalent. FTIR-spectroscopy revealed the presence of 14 types of polymers. Cellulose-based materials and polyethylene terephthalate were the most abundant in MFs, while polyurethanes and styrene-based copolymers dominated in MFRs. MPs were more abundant near the Carlini station. Compared to other coastal Antarctic areas, the MPs in the cove were relatively abundant and mostly smaller than 1 mm. Local activities on the island were identified as the primary source of MPs in the cove, and the cyclonic water circulation likely affects the distribution of small-sized particles. To protect the ecosystem, reducing plastic usage, improving waste management, regulating MPs debris, and enhancing wastewater practices are essential.

Influence of Fractional Inspired Oxygen Tension on Lung Perfusion Distribution, Regional Ventilation, and Lung Volume during Mechanical Ventilation of Supine Healthy Swine.

BACKGROUND: Lower fractional inspired oxygen tension (Fio2) during general anesthesia can reduce lung atelectasis. The objectives are to evaluate the effect of two Fio2 (0.4 and 1) during low positive end-expiratory pressure (PEEP) ventilation over lung perfusion distribution, volume, and regional ventilation. These variables were evaluated at two PEEP levels and unilateral lung atelectasis. METHODS: In this exploratory study, 10 healthy female piglets (32.3 ± 3.4 kg) underwent mechanical ventilation in two atelectasis models: (1) bilateral gravitational atelectasis (n = 6), induced by changes in PEEP and Fio2 in three combinations: high PEEP with low Fio2 (Fio2 = 0.4), zero PEEP (PEEP0) with low Fio2 (Fio2 = 0.4), and PEEP0 with high Fio2 (Fio2 = 1); and (2) unilateral atelectasis (n = 6), induced by left bronchial occlusion, with the left lung aerated (Fio2 = 0.21) and low aerated (Fio2 = 1; n = 5 for this step). Measurements were conducted after 10 min in each step, encompassing assessment of respiratory mechanics, oxygenation, and hemodynamics; lung ventilation and perfusion by electrical impedance tomography; and lung aeration and perfusion by computed tomography. RESULTS: During bilateral gravitational atelectasis, PEEP reduction increased atelectasis in dorsal regions, decreased respiratory compliance, and distributed lung ventilation to ventral regions with a parallel shift of perfusion to the same areas. With PEEP0, there were no differences between low and high Fio2 in respiratory compliance (23.9 ± 6.5 ml/cm H2O vs. 21.9 ± 5.0; P = 0.441), regional ventilation, and regional perfusion, despite higher lung collapse (18.6 ± 7.6% vs. 32.7 ± 14.5%; P = 0.045) with high Fio2. During unilateral lung atelectasis, the deaerated lung had a lower shunt (19.3 ± 3.6% vs. 25.3 ± 5.5%; P = 0.045) and lower computed tomography perfusion to the left lung (8.8 ± 1.8% vs. 23.8 ± 7.1%; P = 0.007). CONCLUSIONS: PEEP0 with low Fio2, compared with high Fio2, did not produce significant changes in respiratory system compliance, regional lung ventilation, and perfusion despite significantly lower lung collapse. After left bronchial occlusion, the shrinkage of the parenchyma with Fio2 = 1 enhanced hypoxic pulmonary vasoconstriction, reducing intrapulmonary shunt and perfusion of the nonventilated areas.

Intraoperative individualization of positive-end-expiratory pressure through electrical impedance tomography or esophageal pressure assessment: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review of randomized-controlled trials (RCTs) with meta-analyses aimed to compare the effects on intraoperative arterial oxygen tension to inspired oxygen fraction ratio (PaO2/FiO2), exerted by positive end-expiratory pressure (PEEP) individualized trough electrical impedance tomography (EIT) or esophageal pressure (Pes) assessment (intervention) vs. PEEP not tailored on EIT or Pes (control), in patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach. METHODS: PUBMED®, EMBASE®, and Cochrane Controlled Clinical trials register were searched for observational studies and RCTs from inception to the end of August 2022. Inclusion criteria were: RCTs comparing PEEP titrated on EIT/Pes assessment vs. PEEP not individualized on EIT/Pes and reporting intraoperative PaO2/FiO2. Two authors independently extracted data from the enrolled investigations. Data are reported as mean difference and 95% confidence interval (CI). RESULTS: Six RCTs were included for a total of 240 patients undergoing general anesthesia for surgery, of whom 117 subjects in the intervention group and 123 subjects in the control group. The intraoperative mean PaO2/FiO2 was 69.6 (95%CI 32.-106.4 ) mmHg higher in the intervention group as compared with the control group with 81.4% between-study heterogeneity (p < 0.01). However, at meta-regression, the between-study heterogeneity diminished to 44.96% when data were moderated for body mass index (estimate 3.45, 95%CI 0.78-6.11, p = 0.011). CONCLUSIONS: In patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach, PEEP personalized by EIT or Pes allowed the achievement of a better intraoperative oxygenation compared to PEEP not individualized through EIT or Pes. PROSPERO REGISTRATION NUMBER: CRD 42021218306, 30/01/2023.

Contemporary Left Ventricular Assist Device Therapy as a Bridge or Alternative to Transplantation.

Left ventricular assist devices (LVADs), which were introduced as a bridge to heart transplantation, are now an established alternative to heart transplantation (HT) for patients with advanced heart failure. These devices have undergone significant technological advancements over the years, and contemporary LVADs prolong life substantially in patients dependent on inotropic therapy or in those with severe ambulatory advanced heart failure with a median survival that exceeds 5 y, and most patients benefit from a doubling in functional capacity, even among those intended as destination therapy because of ineligibility for transplantation. Other intended goals for LVAD implantation consist of (1) bridge to remission or recovery and (2) bridge to transplant or candidacy for transplant. In the former situation, few selected patients underwent LVAD implantation, facilitating myocardial remission to recovery that allowed explantation. Among those bridged to transplantation, survival in the intended goal was excellent, with 80% success at 5 y (with a 50% rate of transplantation). In this review, we provide a brief historical background on the evolution of LVADs and discuss outcomes with contemporary pumps, immunological and infection-related impact of such devices, impact of bridging in HT, and use of devices for facilitating myocardial recovery and remission. Furthermore, we discuss implications of HT allocation policies, with a specific focus within the United States, and outline future perspectives and novel device in development.

Outcomes of untreated subclinical antibody-mediated rejection after heart transplantation.

Subclinical antibody-mediated rejection (AMR) is represented by histopathological and/or immunopathological manifestations in the absence of significant cardiac allograft dysfunction. Treatment remains uncertain as there is a lack of data on asymptomatic heart transplant (HT) recipients (HTR) with a positive cardiac biopsy. We sought to determine the impact of untreated subclinical biopsy-proven AMR, regardless of circulating donor-specific antigen (DSA) expression, when diagnosed on surveillance biopsies in the first year after HT. This retrospective case control study evaluated 260 HTR between May 2004 and February 2021. These comprised 231 controls and 29 patients with untreated subclinical AMR. The mortality event rate was higher in controls (2.63 events per 100 person-years) compared to the scAMR Group (1.71 events per 100 person-years), a difference that did not reach statistical significance (hazard ratio 0.66, CI: 0.18-2.36). The combined event rate of cardiac allograft vasculopathy (CAV), graft dysfunction, or mortality was higher in the subclinical AMR group (5.60 events per 100 person-years) than in controls (3.89 events per 100 person-years) but did not reach statistical significance (hazard ratio 1.63, CI: 0.07-40.09). Our results suggest that subclinical AMR diagnosed in the first year after HT on surveillance biopsy is not associated with decreased survival. This may sway the management of subclinical AMR towards a more conservative approach in transplant-capable institutions that currently prioritize treatment, though prospective, randomized studies of such a management strategy are required.

A strange case of pleuritic pain in the third trimester of pregnancy.

Pulmonary sequestration is an uncommon congenital malformation of the lung, generally diagnosed in childhood or adolescence, corresponding to dysplastic lung tissue not communicating with the rest of vascular or bronchial lung system but receiving an arterial blood supply from systemic arteries. Currently, surgical resection is usually indicated in order to prevent or treat related symptoms or complications, although controversy exists regarding its use in asymptomatic patients and adults. We present the case of a 32-year-old pregnant woman with acute chest pain and vomiting diagnosed with intralobar sequestration at 32+2 weeks of gestation and treated with pulmonary lobectomy after giving birth by cesarean section at 33+0 weeks of gestation.

Comparative resistome, mobilome, and microbial composition of retail chicken originated from conventional, organic, and antibiotic-free production systems.

The aim of this study was to investigate the microbial composition, and the profiles of antimicrobial resistance genes (ARGs, resistome) and mobile genetic elements (mobilome) of retail chicken carcasses originated from conventional intensive production systems (CO), certified antimicrobial-free intensive production systems (AF), and certified organic production systems with restricted antimicrobial use (OR). DNA samples were collected from 72 chicken carcasses according to a cross-sectional study design. Shot-gun metagenomics was performed by means of Illumina high throughput DNA sequencing followed by downstream bioinformatic analyses. Gammaproteobacteria was the most abundant bacterial class in all groups. Although CO, AF, and OR did not differ in terms of alpha- and beta-microbial diversity, the abundance of some taxa differed significantly across the groups, including spoilage-associated organisms such as Pseudomonas and Acinetobacter. The co-resistome comprised 29 ARGs shared by CO, AF and OR, including genes conferring resistance to beta-lactams (blaACT-8, 10, 13, 29; blaOXA-212;blaOXA-275 and ompA), aminoglycosides (aph(3')-IIIa, VI, VIa and spd), tetracyclines (tet KL (W/N/W and M), lincosamides (inu A,C) and fosfomycin (fosA). ARGs were significantly less abundant (P < 0.05) in chicken carcasses from AF and OR compared with CO. Regarding mobile genetic elements (MGEs), transposases accounted for 97.2% of the mapped genes. A higher abundance (P = 0.037) of MGEs was found in CO compared to OR. There were no significant differences in ARGs or MGEs diversity among groups according to the Simpson´s index. In summary, retail frozen chicken carcasses from AF and OR systems show similar ARGs, MGEs and microbiota profiles compared with CO, even though the abundance of ARGs and MGEs was higher in chicken carcasses from CO, probably due to a higher selective pressure.

Worsening of lung perfusion to tissue density distributions during early acute lung injury.

Lung perfusion magnitude and distribution are essential for oxygenation and, potentially, lung inflammation and protection during acute respiratory distress syndrome (ARDS). Yet, perfusion patterns and their relationship to inflammation are unknown pre-ARDS. We aimed to assess perfusion/density ratios and spatial perfusion-density distributions and associate these to lung inflammation, during early lung injury in large animals at different physiological conditions caused by different systemic inflammation and positive end-expiratory pressure (PEEP) levels. Sheep were protectively ventilated (16-24 h) and imaged for lung density, pulmonary capillary perfusion (13Nitrogen-saline), and inflammation (18F-fluorodeoxyglucose) using positron emission and computed tomography. We studied four conditions: permissive atelectasis (PEEP = 0 cmH2O); and ARDSNet low-stretch PEEP-setting strategy with supine moderate or mild endotoxemia, and prone mild endotoxemia. Perfusion/density heterogeneity increased pre-ARDS in all groups. Perfusion redistribution to density depended on ventilation strategy and endotoxemia level, producing more atelectasis in mild than moderate endotoxemia (P = 0.010) with the oxygenation-based PEEP-setting strategy. The spatial distribution of 18F-fluorodeoxyglucose uptake was related to local Q/D (P < 0.001 for Q/D group interaction). Moderate endotoxemia yielded markedly low/zero perfusion in normal-low density lung, with 13Nitrogen-saline perfusion indicating nondependent capillary obliteration. Prone animals' perfusion was remarkably homogeneously distributed with density. Lung perfusion redistributes heterogeneously to density during pre-ARDS protective ventilation in animals. This is associated with increased inflammation, nondependent capillary obliteration, and lung derecruitment susceptibility depending on endotoxemia level and ventilation strategy.NEW & NOTEWORTHY Perfusion redistribution does not follow lung density redistribution in the first 16-24 h of systemic endotoxemia and protective tidal volume mechanical ventilation. The same oxygenation-based positive end-expiratory pressure (PEEP)-setting strategy can lead at different endotoxemia levels to different perfusion redistributions, PEEP values, and lung aerations, worsening lung biomechanical conditions. During early acute lung injury, regional perfusion-to-tissue density ratio is associated with increased neutrophilic inflammation, and susceptibility to nondependent capillary occlusion and lung derecruitment, potentially marking and/or driving lung injury.

HoBi-like Pestivirus Is Highly Prevalent in Cattle Herds in the Amazon Region (Northern Brazil).

Pestiviruses are globally distributed and cause substantial economic losses to the cattle industry. In Brazil, the country with the world's largest cattle population, pestivirus infections are well described in some regions, such as in the south, where a high frequency of BVDV-2 is described and contrasts with the high prevalence of HoBi-like pestivirus (HoBiPeV) in the northeast. However, there is a lack of information about pestiviruses in the Amazon Region, in northern Brazil, with a cattle population estimated at 55.7 million head, which has a significant impact on the international livestock market. Therefore, this study investigated the seroprevalence and genetic variability of ruminant pestiviruses in 944 bovine serum samples from four states in northern Brazil: Pará (PA), Amapá (AP), Roraima (RR), and Amazonas (AM). Our results showed that 45.4% of the samples were seropositive (19.8% for BVDV-1, 14.1% for BVDV-2, and 20.9% for HoBiPeV). All samples were tested by RT-qPCR, and three were positive and classified as HoBiPeV in a phylogenetic analysis. These serological and molecular results contrast with those from other regions of the world, suggesting that the northern Brazilian states have a high prevalence of all bovine pestiviruses including HoBiPeV.

Mixed-integer quadratic programming approach for noninvasive estimation of respiratory effort profile during pressure support ventilation.

Information about respiratory mechanics such as resistance, elastance, and muscular pressure is important to mitigate ventilator-induced lung injury. Particularly during pressure support ventilation, the available options to quantify breathing effort and calculate respiratory system mechanics are often invasive or complex. We herein propose a robust and flexible estimation of respiratory effort better than current methods. We developed a method for non-invasively estimating breathing effort using only flow and pressure signals. Mixed-integer quadratic programming (MIQP) was employed, and the binary variables were the switching moments of the respiratory effort waveform. Mathematical constraints, based on ventilation physiology, were set for some variables to restrict feasible solutions. Simulated and patient data were used to verify our method, and the results were compared to an established estimation methodology. Our algorithm successfully estimated the respiratory effort, resistance, and elastance of the respiratory system, resulting in more robust performance and faster solver times than a previously proposed algorithm that used quadratic programming (QP) techniques. In a numerical simulation benchmark, the worst-case errors for resistance and elastance were 25% and 23% for QP versus <0.1% and <0.1% for MIQP, whose solver times were 4.7 s and 0.5 s, respectively. This approach can estimate several breathing effort profiles and identify the respiratory system's mechanical properties in invasively ventilated critically ill patients.

PEOPLE (NCT03447678), a first-line phase II pembrolizumab trial, in negative and low PD-L1 advanced NSCLC: clinical outcomes and association with circulating immune biomarkers.

BACKGROUND: The PEOPLE trial aimed to identify new immune biomarkers in negative and low programmed death-ligand 1 (PD-L1) (0%-49%) advanced non-small-cell lung cancer (aNSCLC) patients treated with first-line pembrolizumab. Here we report the main outcomes and the circulating immune biomarkers analysis. PATIENTS AND METHODS: The primary endpoint of this phase II trial was the identification of immune biomarkers associated with progression-free survival (PFS). Overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety were secondary endpoints. Absolute cell counts for 36 subsets belonging to innate and adaptive immunity were determined by multiparametric flow cytometry in peripheral blood at baseline and at first radiologic evaluation. An orthoblique principal components-based clustering approach and multivariable Cox regression model adjusted for clinical variables were used to analyze immune variables and their correlation with clinical endpoints. RESULTS: From May 2018 to October 2020, 65 patients were enrolled. After a median follow-up of 26.4 months, the median PFS was 2.9 months [95% confidence interval (CI) 1.8-5.6 months] and median OS was 12.1 months (95% CI 8.7-17.1 months). The ORR was 21.5%, DCR was 47.7% and median DoR was 14.5 months (95% CI 6.4-24.9 months). Drug-related grade 3-4 adverse events were 9.2%. Higher T cell and natural killer (NK) cell count at baseline and at the first radiologic evaluation were associated with improved PFS, DCR and OS. On the contrary, higher myeloid cell count at baseline or at the first radiologic evaluation was significantly associated with worse OS and DCR. CONCLUSIONS: Circulating immune biomarkers can contribute to predict outcomes in negative and low PD-L1 aNSCLC patients treated with first-line single-agent pembrolizumab.

Concise two-step chemical synthesis of molnupiravir.

A concise synthesis of molnupiravir in a one-pot two-step approach starting from uridine is described. Formally, herein, two sets of one-pot two-reaction steps introducing simplicity for purifications and using chemically available reagents are presented. In this context, molnupiravir was obtained in up to 68% overall yield and multigram-scale. In addition, HPLC analysis showed the molnupiravir purity above 99%.

Perception of poultry veterinarians on the use of antimicrobials and antimicrobial resistance in egg production.

This study aimed to describe the perception of veterinarians who work with commercial laying hens in the state of Rio Grande do Sul, Brazil, regarding the use of antibiotics and their possible impacts on animal, human, and environmental health. A descriptive epidemiological study was carried out through face-to-face or web conferencing interviews with the veterinarians that provide technical assistance at commercial laying hen operations. A standardized and structured questionnaire was developed based on the literature and expert opinion, which contained 1 opened and 40 closed questions. Conventional non-probabilistic sampling was used, based on an initial list of 15 veterinarians registered in the Poultry Production Association of Rio Grande do Sul, followed by the snowball technique. The acquisition of 26 contacts of veterinarians was accomplished, and 16 were interviewed. Through the answers obtained it was possible to verify that the interviewees' understanding regarding both the antibiotic resistance impact and the decision-making about the use of antibiotics seem to be linked to their practical experiences. Besides that, according to the veterinarians, farmers can acquire and administer the antimicrobials on their farms. Moreover, both farm storage and administration of lower doses of antibiotics than the recommended one could be contributing factors to resistant bacteria selection. Furthermore, controversially, the professionals believed that resistant bacteria can be transmitted to humans from eggs, but they said that there are no bacteria in eggs. Therefore, the veterinarians´ practices can be improved considering national and international guidelines on antimicrobial resistance to minimize the development of resistance. Finally, it is expected that the present results will contribute to a more complex discussion about antimicrobial resistance, helping to formulate public policies in the egg production industry.

Phrenic Nerve Block and Respiratory Effort in Pigs and Critically Ill Patients with Acute Lung Injury.

BACKGROUND: Strong spontaneous inspiratory efforts can be difficult to control and prohibit protective mechanical ventilation. Instead of using deep sedation and neuromuscular blockade, the authors hypothesized that perineural administration of lidocaine around the phrenic nerve would reduce tidal volume (VT) and peak transpulmonary pressure in spontaneously breathing patients with acute respiratory distress syndrome. METHODS: An established animal model of acute respiratory distress syndrome with six female pigs was used in a proof-of-concept study. The authors then evaluated this technique in nine mechanically ventilated patients under pressure support exhibiting driving pressure greater than 15 cm H2O or VT greater than 10 ml/kg of predicted body weight. Esophageal and transpulmonary pressures, electrical activity of the diaphragm, and electrical impedance tomography were measured in pigs and patients. Ultrasound imaging and a nerve stimulator were used to identify the phrenic nerve, and perineural lidocaine was administered sequentially around the left and right phrenic nerves. RESULTS: Results are presented as median [interquartile range, 25th to 75th percentiles]. In pigs, VT decreased from 7.4 ml/kg [7.2 to 8.4] to 5.9 ml/kg [5.5 to 6.6] (P < 0.001), as did peak transpulmonary pressure (25.8 cm H2O [20.2 to 27.2] to 17.7 cm H2O [13.8 to 18.8]; P < 0.001) and driving pressure (28.7 cm H2O [20.4 to 30.8] to 19.4 cm H2O [15.2 to 22.9]; P < 0.001). Ventilation in the most dependent part decreased from 29.3% [26.4 to 29.5] to 20.1% [15.3 to 20.8] (P < 0.001). In patients, VT decreased (8.2 ml/ kg [7.9 to 11.1] to 6.0 ml/ kg [5.7 to 6.7]; P < 0.001), as did driving pressure (24.7 cm H2O [20.4 to 34.5] to 18.4 cm H2O [16.8 to 20.7]; P < 0.001). Esophageal pressure, peak transpulmonary pressure, and electrical activity of the diaphragm also decreased. Dependent ventilation only slightly decreased from 11.5% [8.5 to 12.6] to 7.9% [5.3 to 8.6] (P = 0.005). Respiratory rate did not vary. Variables recovered 1 to 12.7 h [6.7 to 13.7] after phrenic nerve block. CONCLUSIONS: Phrenic nerve block is feasible, lasts around 12 h, and reduces VT and driving pressure without changing respiratory rate in patients under assisted ventilation.

Optimization of Extraction Conditions and Characterization of Volatile Organic Compounds of Eugenia klotzschiana O. Berg Fruit Pulp.

Eugenia klotzschiana O. Berg is a native species to the Cerrado biome with significant nutritional value. However, its volatile organic compounds (VOCs) chemical profile is not reported in the scientific literature. VOCs are low molecular weight chemical compounds capable of conferring aroma to fruit, constituting quality markers, and participating in the maintenance and preservation of fruit species. This work studied and determined the best conditions for extraction and analysis of VOCs from the pulp of Eugenia klotzschiana O. Berg fruit and identified and characterized its aroma. Headspace solid-phase microextraction (HS-SPME) was employed using different fiber sorbents: DVB/CAR/PDMS, PDMS/DVB, and PA. Gas chromatography and mass spectrometry (GC-MS) were employed to separate, detect, and identify VOCs. Variables of time and temperature of extraction and sample weight distinctly influenced the extraction of volatiles for each fiber. PDMS/DVB was the most efficient, followed by PA and CAR/PDMS/DVB. Thirty-eight compounds that comprise the aroma were identified among sesquiterpenes (56.4%) and monoterpenes (30.8%), such as α-fenchene, guaiol, globulol, α-muurolene, γ-himachalene, α-pinene, γ-elemene, and patchoulene.

Goal Side Selection of Penalty Shots in Soccer: A Laboratory Study and Analyses of Men's World Cup Shoot-Outs.

Penalty kicks in soccer provide a unique scenario in which to examine human choice behavior under competitive conditions. Here, we report two studies examining the tendency for soccer kickers to select the goal side with the largest area to the left or right of the goalkeeper's veridical midline, when the goalkeeper stands marginally off-center. In Study I participants viewed realistic images of a soccer goal and goalkeeper with instructions to choose the left or right side of the goalmouth to best score a goal. We systematically displaced the goalkeeper's position along the goal line; and, to simulate changes in the kicker's viewing position, we systematically displaced the lateral position of the goalmouth in each image. While, overall, participants tended to choose the left over the right goal side, this preference was modulated by the goalkeeper's position relative to the center of the goal and jointly on the lateral position of the goalmouth relative to the participants' body midline. In Study II we analyzed 100 penalty shots from men's world cup shoot-outs between the years 1982 to 2018. Again, we found a small tendency for kickers to aim the ball to the left goal side, but with barely any modulating effect of changes in the goalkeeper's position and no effect of changes in the kicker's position. In contrast to earlier claims that a goalkeeper may benefit by standing marginally to the left or right of the center of the goal to influence the direction of the kicker's shot, our findings suggest that this is probably not a good strategy in elite football competitions.