Pediatric anesthesiology in Brazil, Chile, and Mexico.

BACKGROUND: Latin America comprises an extensive and diverse territory composed of 33 countries in the Caribbean, Central, and South America where Romance languages-languages derived from Latin are predominantly spoken. Economic disparities exist, with inequitable access to pediatric surgical care. The Latin American Surgical Outcomes Study in Pediatrics (LASOS-Peds), a multi-national collaboration, will determine safety of pediatric anesthesia and perioperative care. OBJECTIVE: Below, we provide a descriptive initiative to share how pediatric anesthesia in Brazil, Chile, and Mexico operate. Theses descriptions do not represent all of Latin America. DESCRIPTIONS AND CONCLUSIONS: Brazil an upper middle-income country, population 203 million, has a public system insufficiently resourced and a private system, resulting in inequitable safety and accessibility. Surgical complications constitute the third leading cause of mortality. Anesthesiology residency is 3 years, with required rotations in pediatric anesthesia; five hospitals offer pediatric anesthesia fellowships. Anesthesiology is a physician-only practice. A Pediatric Anesthesia Committee within the Brazilian Society of Anesthesiology offers education through seasonal courses and workshops including pediatric advanced life support. Chile is a high-income country, population 19.5 million, the majority cared for in the public system, the remainder in university, private, or military systems. Government efforts have gradually corrected the long-standing anesthesiology shortage: twenty 3-year residency programs prepare graduates for routine pediatric cases. The Chilean Society of Anesthesiology runs a 1-month program for general anesthesiologists to enhance pediatric anesthesia skills. Pediatric anesthesia fellowship training occurs in Europe, USA, and Australia, or in two 2-year Chilean university programs. Public health policies have increased the medical and surgical pediatric specialists and general anesthesiologists, but not pediatric anesthesiologists, which creates safety concerns for neonates, infants, and medically complex. Chile needs more pediatric anesthesia fellowship programs. Mexico, an upper middle-income country, with a population of about 126 million, has a five-sector healthcare system: public, social security for union workers, state for public employees, armed forces for the military, and a private "self-pay." There are inequities in safety and accessibility for children. Pediatric Anesthesiology fellowship is 2 years, after 3 years residency. A shortage of pediatric anesthesiologists limits accessibility and safety for surgical care, driven by added training at low salary and hospital under appreciation. The Mexican Society of Pediatric Anesthesiology conducts refresher courses, workshops, and case conferences. Insufficient resources and culture limits research.

The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice.

The endocannabinoid system (ECS) regulates energy metabolism, has been implicated in the pathogenesis of metabolic diseases and exerts its actions mainly through the type 1 cannabinoid receptor (CB1). Likewise, autophagy is involved in several cellular processes. It is required for the normal development of muscle mass and metabolism, and its deregulation is associated with diseases. It is known that the CB1 regulates signaling pathways that control autophagy, however, it is currently unknown whether the ECS could regulate autophagy in the skeletal muscle of obese mice. This study aimed to investigate the role of the CB1 in regulating autophagy in skeletal muscle. We found concomitant deregulation in the ECS and autophagy markers in high-fat diet-induced obesity. In obese CB1-KO mice, the autophagy-associated protein LC3 II does not accumulate when mTOR and AMPK phosphorylation levels do not change. Acute inhibition of the CB1 with JD-5037 decreased LC3 II protein accumulation and autophagic flux. Our results suggest that the CB1 regulates autophagy in the tibialis anterior skeletal muscle in both lean and obese mice.

Validation of Embedded State Estimator Modules for Decentralized Monitoring of Power Distribution Systems Using IoT Components.

Recent theoretical studies demonstrate the advantages of using decentralized architectures over traditional centralized architectures for real-time Power Distribution Systems (PDSs) operation. These advantages include the reduction of the amount of data to be transmitted and processed when performing state estimation in PDSs. The main contribution of this paper is to provide lab validation of the advantages and feasibility of decentralized monitoring of PDSs. Therefore, this paper presents an advanced trial emulating realistic conditions and hardware setup. More specifically, the paper proposes: (i) The laboratory development and implementation of an Advanced Measurement Infrastructure (AMI) prototype to enable the simulation of a smart grid. To emulate the information traffic between smart meters and distribution operation centers, communication modules, that enable the use of wireless networks for sending messages in real-time, are used, bridging concepts from both IoT and Edge Computing. (ii) The laboratory development and implementation of a decentralized architecture based on Embedded State Estimator Modules (ESEMs) are carried out. ESEMs manage information from smart meters at lower voltage networks, performing real-time state estimation in PDSs. Simulations performed on a real PDS with 208 buses (considering both medium and low voltage buses) have met the aims of this paper. The results show that by using ESEMs in a decentralized architecture, both the data transit through the communication network, as well as the computational requirements involved in monitoring PDSs in real-time, are reduced considerably without any loss of accuracy.

New Insights into the Interaction of Class II Dihydroorotate Dehydrogenases with Ubiquinone in Lipid Bilayers as a Function of Lipid Composition.

The fourth enzymatic reaction in the de novo pyrimidine biosynthesis, the oxidation of dihydroorotate to orotate, is catalyzed by dihydroorotate dehydrogenase (DHODH). Enzymes belonging to the DHODH Class II are membrane-bound proteins that use ubiquinones as their electron acceptors. We have designed this study to understand the interaction of an N-terminally truncated human DHODH (HsΔ29DHODH) and the DHODH from Escherichia coli (EcDHODH) with ubiquinone (Q10) in supported lipid membranes using neutron reflectometry (NR). NR has allowed us to determine in situ, under solution conditions, how the enzymes bind to lipid membranes and to unambiguously resolve the location of Q10. Q10 is exclusively located at the center of all of the lipid bilayers investigated, and upon binding, both of the DHODHs penetrate into the hydrophobic region of the outer lipid leaflet towards the Q10. We therefore show that the interaction between the soluble enzymes and the membrane-embedded Q10 is mediated by enzyme penetration. We can also show that EcDHODH binds more efficiently to the surface of simple bilayers consisting of 1-palmitoyl, 2-oleoyl phosphatidylcholine, and tetraoleoyl cardiolipin than HsΔ29DHODH, but does not penetrate into the lipids to the same degree. Our results also highlight the importance of Q10, as well as lipid composition, on enzyme binding.

Comparative pharmacokinetics and pharmacokinetic/pharmacodynamic analysis by nonlinear mixed-effects modeling of cefquinome in nonpregnant, pregnant, and lactating goats after intravenous and intramuscular administration.

Cefquinome is a fourth-generation cephalosporin that is used empirically in goats. Different physiologic factors like pregnancy or lactation could determine the pharmacokinetic behavior of drugs in the organism. The objectives of this study are to (a) compare the pharmacokinetics of cefquinome after intravenous and intramuscular administration in adult nonpregnant (n = 6), pregnant (n = 6), and lactating goats (n = 6), at a dose of 2 mg/kg, with rich sampling by nonlinear mixed-effects modeling, (b) conduct a pharmacokinetic/pharmacodynamic analysis to evaluate the efficacy of the recommended posology in goats with different physiological states, and (c) determine the optimal posology that achieve a PTA value ≥ 90%, taking into account a T > MIC ≥ 60% of a MIC value ≤ 0.25 µg/ml, in the different subpopulations of goats for both routes. Gestation significantly increased Ka and V1, while reduced F0, Cl, and Q. On the other hand, lactation significantly increased V1 and reduced Tk0. Cefquinome concentrations achieved in placental cotyledon, amniotic fluid, and fetal serum indicate a minimal penetration across the placental barrier. Moreover, milk penetration of cefquinome was minimal. The total body clearance of cefquinome for goats was 0.29 L kg-1  hr-1 , that is apparently higher than the reported for cows (0.13 L kg-1  hr-1 ) and pigs (0.16 L kg-1  hr-1 ). So, the optimal dose regimen for cefquinome after intravenous and intramuscular administration required higher dose and frequency of administration compared with recommendations for cows or pigs. Therefore, 2 mg kg-1  8 hr-1 and 5 mg kg-1  12 hr-1 could be used for IV and IM routes, respectively, for the treatment of respiratory infections caused by P. multocida and M. haemolytica, but only 5 mg kg-1  12 hr-1 by both routes should be recommended for Escherichia coli infections.

Influence of general anaesthesia on the intravenous acetaminophen pharmacokinetics in Beagle dogs.

OBJECTIVE: To determine if general anaesthesia influences the intravenous (IV) pharmacokinetics (PK) of acetaminophen in dogs. STUDY DESIGN: Prospective, crossover, randomized experimental study. ANIMALS: A group of nine healthy Beagle dogs. METHODS: Acetaminophen PK were determined in conscious and anaesthetized dogs on two separate occasions. Blood samples were collected before, and at 5, 10, 15, 30, 45, 60 and 90 minutes and 2, 3, 4, 6, 8, 12 and 24 hours after 20 mg kg-1 IV acetaminophen administration. Haematocrit, total proteins, albumin, alanine aminotransferase, aspartate aminotransferase, urea and creatinine were determined at baseline and 24 hours after acetaminophen. The anaesthetized group underwent general anaesthesia (90 minutes) for dental cleaning. After the administration of dexmedetomidine (3 µg kg-1) intramuscularly, anaesthesia was induced with propofol (2-3 mg kg-1) IV, followed by acetaminophen administration. Anaesthesia was maintained with isoflurane in 50% oxygen (Fe'Iso 1.3-1.5%). Dogs were mechanically ventilated. Plasma concentrations were analysed with high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling. A Wilcoxon test was used to compare PK data between groups, and clinical laboratory values between groups, and before versus 24 hours after acetaminophen administration. Data are presented as median and range (p < 0.05). RESULTS: A two-compartmental model best described time-concentration profiles of acetaminophen. No significant differences were found for volume of distribution values 1.41 (0.94-3.65) and 1.72 (0.89-2.60) L kg-1, clearance values 1.52 (0.71-2.30) and 1.60 (0.91-1.78) L kg-1 hour-1 or terminal elimination half-life values 2.45 (1.45-8.71) and 3.57 (1.96-6.35) hours between conscious and anaesthetized dogs, respectively. Clinical laboratory variables were within normal range. No adverse effects were recorded. CONCLUSIONS AND CLINICAL RELEVANCE: IV acetaminophen PK in healthy Beagle dogs were unaffected by general anaesthesia under the study conditions. Further studies are necessary to evaluate the PK in different clinical contexts.

Suitable climatic habitat changes for Mexican conifers along altitudinal gradients under climatic change scenarios.

The high biodiversity of the Mexican montane forests is concentrated on the Trans-Mexican Volcanic Belt, where several Protected Natural Areas exist. Our study examines the projected changes in suitable climatic habitat for five conifer species that dominate these forests. The species are distributed sequentially in overlapping altitudinal bands: Pinus hartwegii at the upper timberline, followed by Abies religiosa, the overwintering host of the Monarch butterfly at the Monarch Butterfly Biosphere Reserve, P. pseudostrobus, the most important in economic terms, and P. devoniana and P. oocarpa, which are important for resin production and occupy low altitudes where montane conifers merge with tropical dry forests. We fit a bioclimatic model to presence-absence observations for each species using the Random Forests classification tree with ground plot data. The models are driven by normal climatic variables from 1961 to 1990, which represents the reference period for climate-induced vegetation changes. Climate data from an ensemble of 17 general circulation models were run through the classification tree to project current distributions under climates described by the RCP 6.0 watts/m2 scenario for the decades centered on years 2030, 2060 and 2090. The results suggest that, by 2060, the climate niche of each species will occur at elevations that are between 300 to 500 m higher than at present. By 2060, habitat loss could amount to 46-77%, mostly affecting the lower limits of distribution. The two species at the highest elevation, P. hartwegii and A. religiosa, would suffer the greatest losses while, at the lower elevations, P. oocarpa would gain the most niche space. Our results suggest that conifers will require human assistance to migrate altitudinally upward in order to recouple populations with the climates to which they are adapted. Traditional in situ conservation measures are likely to be equivalent to inaction and will therefore be incapable of maintaining current forest compositions.

Automatic Irrigation Scheduling on a Hedgerow Olive Orchard Using an Algorithm of Water Balance Readjusted with Soil Moisture Sensors.

Recent technological advances have made possible automated irrigation scheduling using decision-support tools. These tools help farmers to make better decisions in the management of their irrigation system, thus increasing yields while preserving water resources. The aim of this study is to evaluate in a commercial plot an automated irrigation system combined with remote-sensing techniques and soil mapping that allows the establishment of regulated deficit irrigation (RDI) strategies. The study was carried out over 3 years (2015-2017) in a commercial hedgerow olive orchard of the variety 'Arbequina' located in Alvarado (Extremadura, Spain). An apparent electrical conductivity (ECa) map and a normalized difference vegetation index (NDVI) map were generated to characterize the spatial variability of the plot and classify the zones in homogeneous areas. Then, reference points were selected to monitor the different irrigation sectors. In 2015, the plot was irrigated according to the farmer's technical criteria throughout the plot. In 2016 and 2017, two different areas of the plot were irrigated applying an RDI strategy, one under expert supervision and the other automatically. The results show that in a heterogeneous plot the use of new technologies can be useful to establish the ideal location for an automatic irrigation system. Furthermore, automatic irrigation scheduling made it possible to establish an RDI strategy recommended by an expert, resulting in the homogenization of production throughout the plot without the need for human intervention.

Comparative pharmacokinetics and a clinical laboratory evaluation of intravenous acetaminophen in Beagle and Galgo Español dogs.

OBJECTIVE: To assess the pharmacokinetics (PK) and conduct a clinical laboratory evaluation of acetaminophen in Beagle and Galgo Español (GE) dogs. STUDY DESIGN: Prospective randomized experimental trial. ANIMALS: A total of 20 healthy dogs - 10 Beagles and 10 GE (six males and four females in both groups). METHODS: Acetaminophen (10 and 20 mg kg-1) was administered intravenously (IV) to the dogs on two different occasions. Plasma concentrations were analysed by high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling with ADAPT 5 software. Simulations after multiple IV doses were investigated. Clinical laboratory values such as red blood cell (RBC) count, haemoglobin (Hb), haematocrit (Ht), white blood cell (WBC) count, platelet count, total proteins, alanine aminotransferase (ALT), aspartate aminotransferase, urea and creatinine were measured before and 24 hours after acetaminophen administration in combination with clinical examination to assess side effects resulting from the drug. RESULTS: A two-compartmental model best described time-concentration profiles of acetaminophen. PK parameters were different as a result of a breed effect. For doses of 10 and 20 mg kg-1, respectively, clearance values were 1.70 (1.15-2.27) and 1.62 (1.06-2.86) L kg-1 hour-1 for Beagles and 1.18 (0.70-1.39) and 1.08 (0.67-1.35) L kg-1 hour-1 for GE; elimination half-life values were 2.64 (0.52-4.46) and 2.86 (0.87-4.63) hours for Beagles and 3.49 (1.89-7.80) and 4.57 (2.08-8.90) hours for GE. Significant differences were also found between GE and Beagles in the RBC count, Ht, Hb, WBC count and serum ALT before drug administration, and these differences were maintained 24 hours later, independent of the dosage used. For each breed, no side effects resulting from IV acetaminophen administration were observed at doses of either 10 or 20 mg kg-1. CONCLUSIONS AND CLINICAL RELEVANCE: IV PK of acetaminophen was different between Beagles and GE dogs. Side effects were not detected. Further studies are necessary to evaluate the PK in a clinical context.

Valor pronóstico de la troponina I posintervencionismo coronario percutáneo electivo.

INTRODUCCIÓN: El significado de la elevación de la troponina I (Tn-I) después de una intervención coronaria percutánea (ICP) es tema de debate. OBJETIVO: Determinar el pronóstico cardiovascular a un año asociado con el incremento de Tn-I posterior a ICP electiva exitosa. MÉTODO: Estudio observacional, retrospectivo y longitudinal. Se incluyeron pacientes sometidos a ICP electiva exitosa. Se dividieron en dos grupos: con y sin elevación de Tn-I, para comparar la ocurrencia de eventos cardiacos adversos mayores (ECAM) a un año; la Tn-I pos-ICP se correlacionó con características demográficas y angiográficas. RESULTADOS: Se detectó elevación de Tn-I en 32 pacientes (35.2 %). La elevación fue más frecuente en pacientes con enfermedad coronaria multivascular, más compleja y con complicaciones peri-ICP. Los ECAM a un año fueron mayores en el grupo de Tn-I elevada (25 versus 3.4 %, p = 0.002). Los predictores independientes de ECAM fueron elevación cinco veces de Tn-I al valor normal (RM = 7.5, IC 95 % = 1.25-45, p = 0.027) y las complicaciones peri-ICP (RM = 7.5, IC 95 % = 1.25-45, p = 0.027). CONCLUSIÓN: En pacientes con enfermedad coronaria estable, la elevación de Tn-I posterior a ICP electiva se asoció con eventos cardiacos adversos a un año, complicaciones peri-ICP y enfermedad coronaria más extensa y compleja. INTRODUCTION: The significance of troponin I (Tn-I) elevation after percutaneous coronary intervention (PCI) is the subject of debate. OBJECTIVE: To determine cardiovascular prognosis associated with Tn-I elevation one year after successful elective PCI. METHODS: Observational, retrospective, longitudinal study. Patients who underwent successful elective PCI were included and divided in two groups: with and without Tn-I elevation, in order to compare the occurrence of major adverse cardiac events (MACE) at 1 year; post-PCI Tn-I was correlated with demographic and angiographic characteristics. RESULTS: Tn-I elevation was detected in 32 patients (35.2%). Elevation was more common in patients with multivascular and more complex coronary artery disease, and with peri-PCI complications. MACE incidence at one year was higher in the elevated Tn-I group (25% vs. 3.4%; p = 0.002). Independent predictors of MACE were Tn-I 5-fold elevation from normal value (OR: 7.5; 95% CI: 1.25-45; p = 0.027) and peri-PCI complications (OR: 7.5; 95% CI: 1.25-45; p = 0.027). CONCLUSIONS: In patients with stable coronary artery disease, Tn-I elevation after successful elective PCI is associated with adverse cardiac events at 1 year, more extensive and complex coronary artery disease and peri-PCI complications.

Effects of Two Training Modalities on Body Fat and Insulin Resistance in Postmenopausal Women.

Henríquez, S, Monsalves-Alvarez, M, Jimenez, T, Barrera, G, Hirsch, S, de la Maza, MP, Leiva, L, Rodriguez, JM, Silva, C, and Bunout, D. Effects of two training modalities on body fat and insulin resistance in postmenopausal women. J Strength Cond Res 31(11): 2955-2964, 2017-Our objective was to compare the effects of a low-load circuit resistance training protocol and usual aerobic training in postmenopausal women. Postmenopausal women with at least 1 feature of the metabolic syndrome were randomly allocated to a low-load circuit resistance training protocol or traditional aerobic training in a braked cycle ergometer. The intervention consisted in supervised sessions lasting 40 minutes, 3 times per week, during 6 months. At baseline and at the end of the intervention, fasting serum lipid levels, serum interleukin 6, C-reactive protein, 8 isoprostanes, and insulin resistance (assessed through QUICKI and HOMA-IR) were measured. Body fat was measured by double-beam X-ray absorptiometry and by computed tomography densitometric quantification at lumbar 3 vertebral level. Twenty-one women aged 58 (54-59) years were allocated to aerobic training and 21 women aged 55 (52-61) years were allocated to the low-load circuit resistance training protocol. Eighteen and 16 women in each group completed the 6 months training period. Women in both groups experienced significant reductions in blood pressure, total body, subcutaneous, and intraabdominal body fat. Reductions in total cholesterol and triacylglycerol levels were also observed. No changes in insulin resistance indexes, 8 isoprostanes, C-reactive protein, or interleukin 6 were observed in either group. No significant differences between treatment groups were observed in any of the measured parameters. We conclude that low-load circuit resistance training and aerobic training resulted in the same reductions in body fat and serum lipid levels.

Associations between socioeconomic status, aging and functionality among older women.

To assess if there is an association between socioeconomic status and quality of life, functional status and markers of aging, we studied 86 women aged 73 ± 7 years, who answered the WHO Qol Bref quality of life survey. Mini mental state examination, timed up and go test, 12 minutes' walk, hand grip and quadriceps strength, dual X-ray absorptiometry (DEXA), carotid intima-media thickness and telomere length in peripheral leukocytes were measured. Successful aging was defined as a walking speed, handgrip strength, appendicular lean body mass, timed up and go and minimental values above cutoff points for disability. Participants with successful aging had a higher quality of life score and were more likely to live in rich municipalities. There was a positive correlation between telomere length, right handgrip strength and total fat free mass. Therefore, there is an association between socioeconomic status, successful aging and quality of life.

Osteometric sorting of skeletal elements from a sample of modern Colombians: a pilot study.

The Colombian armed conflict has been catalogued not only as the longest civil war in the western hemisphere, but also as having one of the highest indexes of missing persons. Among the several challenges faced by forensic practitioners in Colombia, the commingling of human remains has been recognised as one of the most difficult to approach. The method of osteometric sorting described by Byrd and Adams and Byrd (2008) has proven relevant as a powerful tool to aid in the reassociation process of skeletal structures. The aim of this research was to evaluate the three osteometric sorting models developed by Byrd (2008) (paired elements, articulating bone portions and other bone portions) in a sample of modern Colombian individuals. A set of 39 linear measurements was recorded from a sample of 100 individuals (47 females and 53 males aged between 20 and 74 and 18 and 77 years, respectively), which was used to create a reference sample database. A different subset of eight individuals (five females aged between 23 and 48 years, and three males aged between 27 and 43 years) was employed to randomly create six small-scale commingled assemblages for the purposes of testing the osteometric sorting models. Results demonstrate that this method has significant potential for use in the Colombian forensic context.

Pharmacokinetics (PK), pharmacodynamics (PD), and PK-PD integration of ceftiofur after a single intravenous, subcutaneous and subcutaneous-LA administration in lactating goats.

BACKGROUND: Bacterial pneumonia in goats is usually caused by Mannheimia haemolytica and Pasteurella multocida. Another important infection disease in lactating goats is intramammary infection producing mastitis, usually associated with coagulase-negative Staphylococcus spp. However, treatment of bacterial pneumonia in goats not affected by mastitis problems should be restricted to antimicrobials with scant penetration to milk in order to avoid long withdrawal times. Ceftiofur is a third-generation cephalosporin antimicrobial with activity against various gram-positive and gram-negative, aerobic and anaerobic bacteria encountered by domestic animals. The objectives of the present study were to establish the serum concentration-time profile for ceftiofur in lactating goats after intravenous, subcutaneous and a SC-long-acting ceftiofur formulation; to determine ceftiofur penetration into milk; to determine in vitro and ex vivo activity of ceftiofur establishing MIC, MBC, MPC and time-kill profiles against field strains of M. haemolytica and finally to calculate the main surrogate markers of efficacy. RESULTS: The pharmacokinetics studies revealed an optimal PK properties for the SC-LA formulation tested. Ceftiofur was well absorbed following SC and SC-LA administration, with absolute bioavailabilities (F) of 85.16 and 84.43 %, respectively. After ceftiofur analysis from milk samples, no concentrations were found at any sampling time. The MIC, MBC and MPC data of ceftiofur against five M. haemolytica strains isolated from goats affected by pneumonia were tested showing excelent sensitivity of ceftiofur against this pathogen. For PK-PD analysis, ratios were calculated suggesting a high level of bacterial kill against the five strains of M. haemolytica tested. CONCLUSIONS: The systemic ceftiofur exposure achieved in lactating goats following IV, SC and especially with the SC-LA administration is consistent with the predicted PK-PD ratios needed for a positive therapeutic outcome for M. haemolytica. Subcutaneous administration of the long-acting formulation showed safety and tolerance for all the animals used. Ceftiofur concentrations exceeded the MIC and MBC for up to 72 h and MPC for up 32 h in serum. Thus, this drug could be effective in treating infectious diseases of goats caused by M. haemolytica at a dose of 6 mg/kg with the SC-LA formulation.

Preferences of caregivers and patients regarding opioid analgesic use in terminal care.

CONTEXT: Patients and caregivers participate in decision-taking, and their views should be considered in the preparation of Clinical Practice Guidelines (CPGs). We involved them in the development of a CPG on the safe use of major opioids. OBJECTIVE: To identify the values and preferences of patients and caregivers on the use of opioids and the desired outcomes, to investigate motives for the acceptance/rejection of opioid therapy, and to evaluate their beliefs and information about these drugs. METHODS: A qualitative study was conducted using semi-structured interviews in an Andalusian population of terminal patients and caregivers (N = 42). Study variables included the role, diagnosis, and adherence to treatment. Content and validity analyses were performed. RESULTS: Less than one-third of participants recognized the term opioid. Among these, false beliefs were held related to the addictive nature of these drugs, their exclusive use in terminal cases and at the end of life, and their association with premature death. The information received was very general: it was known that they are "useful for pain," and some were informed about the administration route, composition, and habituation. Participation in decision making was usually limited to reporting symptoms to the physician. CONCLUSION: These patients and caregivers demonstrated a preference for pain alleviation by opioid treatment and gave negative assessments on adverse digestive effects that can cause this treatment to be abandoned. They expressed interest in receiving more information and in participating in therapeutic decision making, and they reported erroneous beliefs and a lack of information about the effects of these drugs.

Persistent Barriers of the Gluten-Free Basic Food Basket: Availability, Cost, and Nutritional Composition Assessment.

Gluten-related disorders are treated with a gluten-free diet. The "basic food basket" (BFB) consists of a list of basic foods consumed by low-income groups in society, including those lowest-cost versions within each food category. To evaluate the cost, availability, and nutritional quality of the BFB and gluten-free BFB (GF-BFB), foods were photographed, registering their cost, availability, and nutritional characteristics, in high quality and mid-range supermarkets, wholesalers, health shops, and corner shops, matching each regular BFB product with a gluten-free equivalent. Of the 1177 potential products, the selection of lowest-cost foods yielded 55 and 47 products (BFB and GF-BFB, respectively). Breads/cereals and drinks showed the highest differences (279% and 146%, respectively) while meats and sausages showed the lowest ones (18.6%). The GF-BFB cost represents 30.1% of the minimum wage, which covers the cost of 5.2 and 3.3 of the BFB and GF-BFB per month, respectively. Availability ranged between 22.7 and 42.4%. Lower availability was associated with poorer nutritional quality in the GF-BFB, which provides 5% less energy, 26% more fat, and 25% less protein than the BFB. Only 47% of gluten-free products declared their "gluten-free" condition. The results strongly suggest that the GF-BFB must be redesigned to be both gluten-free and nutritionally adequate.

Metabolomic and Lipidomic Tools for Tracing Fish Escapes from Aquaculture Facilities.

During adverse atmospheric events, enormous damage can occur at marine aquaculture facilities, as was the case during Storm Gloria in the southeastern Spanish Mediterranean in January 2020, with massive fish escapes. Fishes that escape were caught by professional fishermen. The objective of this study was to identify biomarkers in fish that enable differentiation among wild fish, escaped farm-raised fish, and farm-raised fish kept in aquaculture facilities until their slaughter. We focused on gilthead sea bream (Sparus aurata). We used nuclear magnetic resonance to search for possible biomarkers. We found that wild gilthead sea bream showed higher levels of taurine and trimethylamine-N-oxide (TMAO) in their muscle and higher levels of ω-3 fatty acids, whereas farm-escaped and farmed gilthead sea bream raised until slaughter exhibit higher levels of ω-6 fatty acids. From choline, carnitine, creatinine, betaine, or lecithin, trimethylamine (TMA) is synthesized in the intestine by the action of bacterial microflora. In the liver, TMA is oxidized to TMAO and transported to muscle cells. The identified biomarkers will improve the traceability of gilthead sea bream by distinguishing wild specimens from those raised in aquaculture.

Dose regimen optimization of cephalothin for surgical prophylaxis against Staphylococcus aureus and coagulase negative staphylococci in dogs by pharmacokinetic/pharmacodynamic modeling.

First generation cephalosporins such cephalothin of cefazolin are indicated for antimicrobial prophylaxis for clean and clean contaminated surgical procedures because its antimicrobial spectrum, relative low toxicity and cost. Anesthesia and surgery could alter the pharmacokinetic behavior of different drugs administered perioperative by many mechanisms that affect distribution, metabolism or excretion processes. Intravenous administration of the antimicrobial within 30 and 60 min before incision is recommended in order to reach therapeutic serum and tissue concentrations and redosing is recommended if the duration of the procedure exceeds two half-life of the antimicrobial. To the author's knowledge there are no pharmacokinetic studies of cephalothin in dogs under anesthesia/surgery conditions. The aim of this study was (1) to evaluate the pharmacokinetics of cephalothin in anesthetized dogs undergoing ovariohysterectomy by a nonlinear mixed-effects model and to determine the effect of anesthesia/surgery and other individual covariates on its pharmacokinetic behavior; (2) to determine the MIC and conduct a pharmacodynamic modeling of time kill curves assay of cephalothin against isolates of Staphylococcus spp. isolated from the skin of dogs; (3) to conduct a PK/PD analysis by integration of the obtained nonlinear mixed-effects models in order to evaluate the antimicrobial effect of changing concentrations on simulated bacterial count; and (4) to determine the PK/PD endpoints and PK/PDco values in order to predict the optimal dose regimen of cephalothin for antimicrobial prophylaxis in dogs. Anesthesia/surgery significantly reduced cephalothin clearance by 18.78%. Based on the results of this study, a cephalothin dose regimen of 25 mg/kg q6h by intravenous administration showed to be effective against Staphylococcus spp. isolates with MIC values ≤2 µg/mL and could be recommended for antimicrobial prophylaxis for clean surgery in healthy dogs.

A Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection.

In the context of continuous emergence of SARS-CoV-2 variants of concern (VOCs), one strategy to prevent the severe outcomes of COVID-19 is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies of a RBD vaccine derived from the Gamma SARS-CoV-2 variant adjuvanted with Alum. The Gamma-adapted RBD vaccine is more immunogenic than the Ancestral RBD vaccine in terms of inducing broader neutralizing antibodies. The Gamma RBD presents more immunogenic B-cell restricted epitopes and induces a higher proportion of specific-B cells and plasmablasts than the Ancestral RBD version. The Gamma-adapted vaccine induces antigen specific T cell immune responses and confers protection against Ancestral and Omicron BA.5 SARS-CoV-2 challenge in mice. Moreover, the Gamma RBD vaccine induces higher and broader neutralizing antibody activity than homologous booster vaccination in mice previously primed with different SARS-CoV-2 vaccine platforms. Our study indicates that the adjuvanted Gamma RBD vaccine is highly immunogenic and a broad-spectrum vaccine candidate.

Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN. METHODS: This study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment. DISCUSSION: This study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05521737 Registered on 30 August 2022. International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b].