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Abstract Diabetes mellitus (DM) prevalence is rising worldwide. Current therapies comprising subcutaneous insulin injections can cause adverse effects such as lipodystrophy, local reactions like redness and swelling, fluid retention, and allergic reactions. Nanoparticle carriers for oral insulin are groundbreaking compared to existing methods because they are non-invasive treatments, showing operational convenience, controlled release profile, and ability to simulate the physiological delivery route into the bloodstream. These systems improve patient adherence and have demonstrated the potential to lower blood glucose levels in DM. We present a systematic review and meta-analysis aimed at compiling relevant data to pave the way for developing innovative nano- and microparticles for the oral delivery of insulin. Our analysis of 85 articles revealed that the diminution of glucose levels is not proportional to the administered insulin dosage, which ranged from 1 to 120 International Units (IU). The meta-analysis data indicated that 25 IU of encapsulated porcine insulin did not produce a statistically significant outcome (p = 0.93). In contrast, a dosage of 30 IU was efficacious in eliciting an optimal hypoglycemic effect compared to excipient controls. Parameters such as a high degree of encapsulation (~ 90%), particle size (200–400 nm), and polydispersity index (0.086–0.3) are all associated with lower blood glucose levels. These parameters were also significant in the linear regression analysis. Among the excipients employed, chitosan emerged as a prevalent excipient in formulations due to its biocompatible and biodegradable properties and its ability to establish stable polymeric matrices. Even though oral insulin administration is a promising therapeutic method, it cannot guarantee preclinical safety and therapeutic efficacy yet in regulating glucose levels in diabetic conditions. Graphical Abstract

Acute kidney injury (AKI) is a highly prevalent and a critical complication of cardiac surgery (CS). Serum lactate (sLac) levels have consistently shown an association with morbimortality after CS. We performed a cross-sectional study including 264 adult patients that had a cardiac surgery between January and December 2020. Logistic regression analysis was performed to determine factors associated with AKI development. We measured the postoperative levels of sLac for all participants immediately after CS (T0) and at 4 h (T4) after the surgical intervention. A linear regression model was used to identify the factors influencing both sLac metrics. We identified four risk predictors of AKI; one was preoperative (atrial fibrillation), one intraoperative (cardiopulmonary bypass time), and two were postoperative (length of hospital stay and postoperative sLac). T0 and T4 sLac levels were higher among CS-AKI patients than in Non-CS-AKI patients. Postoperative sLac levels were significant independent predictors of CSA-AKI, and sLac levels are influenced by length of hospital stay, the number of transfused packed red blood cells, and the use of furosemide in CS-AKI patients. These findings may facilitate the earlier identification of patients susceptible to AKI after CS.

We describe a new species of leaflitter frog of the genus Noblella from southern Ecuador, province of Zamora Chinchipe. The new species is diagnosed from all its congeners by having one or two tubercles on the upper eyelids; distal phalanges strongly T-shaped; phalangeal formula on hands 2-2-3-3; phalangeal formula on feet 2-2-3-4-3; heel with a small subconical tubercle; disc on all toes with papillae; dorsum brown or brown with gray, with V-shaped inverted or scattered irregular darker marks. We include a detailed description of its osteology and a study of its phylogenetic relationships. Finally, we evaluate its conservation status and discuss the threats that are currently impacting at the type locality.

Background Buprenorphine (BPN) is a widely used analgesic in the pediatric population, although there are few studies on the pharmacokinetics and pharmacodynamics of this drug. Objective The objective was to characterize the pharmacokinetics of BPN after intravenous administration and analyze the effect of age, gender, weight, height, body mass index (BMI), and drug-drug interactions as covariates. Methods Ninety-nine children (2-10 years), who underwent orthopedic surgery under regional, general, or combined anesthesia were included. Patients evaluated according to the American Society of Anesthesiologists Physical Status Classification, who received intravenous BPN 2 μg/kg were enrolled. Blood was collected from 1-240 min. Drug plasma concentrations were determined by LC-MS/MS. Population pharmacokinetic parameters were obtained with Monolix 2021R1 software. Pearson’s correlation and/or ANOVA were used for statistical analysis. Results Age was associated with changes in clearance and central compartment volume and the female gender was associated with lower intercompartmental clearance, while BMI modified clearance, central and peripheral compartment volume. Concomitant administration of BPN with fentanyl and dexamethasone produced decreases in clearance. Conclusions The covariates of sex, age, and BMI are directly related to the increase or decrease in BPN pharmacokinetic parameters.

Delayed wound healing increases the wound’s vulnerability to possible infections, which may have lethal outcomes. The treatments available can be effective, but the urgency is not fully encompassed. The drug repositioning strategy proposes effective alternatives for enhancing medical therapies for chronic diseases. Likewise, applying wound dressings as biodegradable membranes is extremely attractive due to their ease of application, therapeutic effectiveness, and feasibility in industrial manufacturing. This article aims to demonstrate the pleiotropic effects during insulin repositioning in wound closure by employing a biopolymeric membrane-type formulation with insulin. We prepared biopolymeric membranes with sodium alginate cross-linked with calcium chloride, supported in a mixture of xanthan gum and guar gum, and plasticized with glycerol and sorbitol. Human insulin was combined with poloxamer 188 as a protein stabilizing agent. Our investigation encompassed physicochemical and mechanical characterization, antioxidant and biological activity through antibacterial tests, cell viability assessments, and scratch assays as an in vitro and in vivo wound model. We demonstrated that our biopolymeric insulin membranes exhibited adequate manipulation and suitable mechanical resistance, transparency, high swelling capability (1100%), and 30% antioxidant activity. Furthermore, they exhibited antibacterial activity (growth inhibition of S. aureus at 85% and P. aeruginosa at 75%, respectively), and insulin promoted wound closure in vitro with a 5.5-fold increase and 72% closure at 24 h. Also, insulin promoted in vivo wound closure with a 3.2-fold increase and 92% closure at 10 days compared with the groups without insulin, and this is the first report that demonstrates this therapeutic effect with two administrations of 0.7 IU. In conclusion, we developed a multifunctional insulin-loaded biopolymeric membrane in this study, with the main activity derived from insulin’s role in wound closure and antioxidant activity, augmented by the antimicrobial effect attributed to the polymer poloxamer 188. The synergistic combination of excipients enhances its usefulness and highlights our innovation as a promising material in wound healing materials.

Background and aimsUnconjugated bilirubin (UCB) is a byproduct of the heme group that indicates irregularities in the metabolism of several important biological molecules, such as hemoglobin. UCB is processed by hepatic UGT1A1, which catalyzes its conjugation to the metabolites bilirubin diglucuronide (BDG) and bilirubin monoglucuronide (BMG). The serum concentrations of BDG and BMG may indicate liver injury or dysfunction. The aim of this study was to standardize and validate a method for the identification and simultaneous quantification of BMG, BDG and UCB by LC‒MS/MS.MethodsLiquid‒liquid extraction allows the separation of UCB, BMG and BDG from the serum of healthy subjects or patients with liver injury. Detection and quantification were performed using an LC‒MS/MS method. Compound separation was achieved with a BEH-C18 column at 40°C. The mobile phase was prepared with 5 mM ammonium acetate (pH 6) and acetonitrile, and a flow gradient was applied.ResultsThis is the first study to directly quantify BMG and UCB levels in human serum; no postcalculations or correction factors are needed. However, BDG quantification requires calculations and a correction factor. We identified the molecular species with ionic transitions m/z1+ 585.4 > 299.2 for UCB, 761.3 > 475.3 for BMG, 937.3 > 299.5 for BDG and mesobilirubin 589.4 > 301.3 (IS).ConclusionThe procedures used in this study allowed the simultaneous identification and quantification of the molecular species of bilirubin, BDG, BMG and UCB. Analysis of the serum levels in patients with hyperbilirubinemia revealed that patients with acute-on-chronic liver failure had elevated levels of these species.

The COVID-19 pandemic has resulted in millions of fatalities worldwide. The case of pediatric cancer patients stands out since, despite being considered a population at risk, few studies have been carried out concerning symptom detection or the description of the mechanisms capable of modifying the course of the COVID-19 disease, such as the interaction and response between the virus and the treatment given to cancer patients. By synthesizing existing studies, this paper aims to expose the treatment challenges for pediatric patients with COVID-19 in an oncology context. Additionally, this updated review includes studies that utilized the antiviral agents Remdesivir and PaxlovidTM in pediatric cancer patients. There is no specific treatment designed exclusively for pediatric cancer patients dealing with COVID-19, and it is advisable to avoid self-medication to prevent potential side effects. Managing COVID-19 in pediatric cancer patients is indeed a substantial challenge. New strategies, such as chemotherapy application rooms, have been implemented for children with cancer who were positive for COVID-19 but asymptomatic since the risk of disease progression is greater than the risk of complications from SARS-CoV-2.

Plain English summary Insulin regulates the synthesis of carbohydrates, lipids and proteins differently between males, and females. One of its primary functions is maintaining adequate blood glucose levels favoring glucose entry in muscle and adipose tissue after food consumption. Insulin resistance (IR) is a condition in which the response of organs to insulin is impaired. IR is frequently associated with metabolic dysfunction such as inflammation, obesity, or type 2 diabetes. However, physiological IR develops in healthy individuals during periods of rapid growth, pregnancy, or aging by mechanisms not fully understood. We studied the postnatal development, specifically around weaning at postnatal day 20 (p20) of Wistar rats. In previous works, we identified insulin resistance during this period in male rats. This work aimed to characterize IR at p20, determine its underlying mechanisms, and identify whether sexual dimorphism in physiological IR occurs during this stage. We found that p20 rats of both sexes have elevated blood glucose and insulin levels, low systemic insulin sensitivity, and glucose intolerance. We identified differences in insulin-regulated protein activation (S6K1, IRS1, Akt, and GLUT4) between sexes in different tissues and adipose tissue depots. Studying these mechanisms and their differences between males and females is essential to understanding insulin actions and their relationship with the possible development of metabolic diseases in both sexes.

La crisis sanitaria del Covid-19 desencadenó en Guatemala la automedicación con fármacos de venta libre por público en general. La Organización Mundial de la Salud sugiere los ensayos clínicos para establecer los riesgos de los medicamentos usados durante la pandemia. El objetivo del estudio es evaluar los efectos tóxicos de tres fármacos de venta libre (ivermectina, azitromicina y acetaminofén) sobre la salud de un modelo animal estandarizado (ratones Mus musculus CD1). Se realizó un ensayo de toxicidad a dosis repetidas durante 28 días por vía oral en 21 ratones, divididos en tres grupos: control, dosis y sobredosis. Se estimaron valores hematológicos, bioquímicos e histopatológicos para evaluar el estado de salud de los grupos experimentales. Se encontraron alteraciones significativas en el peso (P < 0.001), en el hematocrito (P < 0.001), la hemoglobina (P < 0.001), los glóbulos blancos (P < 0.001), los linfocitos (P < 0.05), los glóbulos rojos (P < 0.001), el nitrógeno de urea en sangre (P < 0.05), la urea (P < 0.05) y en la proteína total (P = 0.06). Las lesiones macroscópicas congruentes fueron hígado friable (n=2) y bordes pálidos del hígado (n=4) aunadas a lesiones microscópicas de degeneración hidrópica el hígado (n=11), descamación epitelial en intestino (n=8), hialinización en riñón (n=7) y tumefacción turbia en hígado (n=5). Las sobredosis repetidas de ivermectina, azitromicina y acetaminofén redujeron la salud de los individuos experimentales. Se discuten las implicaciones en la salud derivadas de la automedicación repetida con estos fármacos.

Midazolam (MDZ) is a short-acting benzodiazepine that is widely used to induce and maintain general anesthesia during diagnostic and therapeutic procedures in pediatric patients due to its sedative properties. The aim of this study was to perform a systematic review without a meta-analysis to identify scientific articles and clinical assays concerning MDZ-induced sedation for a pediatric surgery approach. One hundred and twenty-eight results were obtained. After critical reading, 37 articles were eliminated, yielding 91 publications. Additional items were identified, and the final review was performed with a total of 106 publications.In conclusion, to use MDZ accurately, individual patient characteristics, the base disease state, comorbidities, the treatment burden and other drugs with possible pharmacological interactions or adverse reactions must be considered to avoid direct alterations in the pharmacokinetics and pharmacodynamics of MDZ to obtain the desired effects and avoid overdosing in the pediatric population.

Lactoferrin (LF) is a glycoprotein that binds to iron ions (Fe2+) and other metallic ions, such as Mg2+, Zn2+, and Cu2+, and has antibacterial and immunomodulatory properties. The antibacterial properties of LF are due to its ability to sequester iron. The immunomodulatory capability of LF promotes homeostasis in the enteric environment, acting directly on the beneficial microbiota. LF can modulate antigen-presenting cell (APC) biology, including migration and cell activation. Nonetheless, some gut microbiota strains produce toxic metabolites, and APCs are responsible for initiating the process that inhibits the inflammatory response against them. Thus, eliminating harmful strains lowers the risk of inducing chronic inflammation, and consequently, metabolic disease, which can progress to type 2 diabetes mellitus (T2DM). LF and retinoic acid (RA) exhibit immunomodulatory properties such as decreasing cytokine production, thus modifying the inflammatory response. Their activities have been observed both in vitro and in vivo. The combined, simultaneous effect of these molecules has not been studied; however, the synergistic effect of LF and RA may be employed for enhancing the secretion of humoral factors, such as IgA. We speculate that the combination of LF and RA could be a potential prophylactic alternative for the treatment of metabolic dysregulations such as T2DM. The present review focuses on the importance of a healthy diet for a balanced gut and describes how probiotics and prebiotics with immunomodulatory activity as well as inductors of differentiation and cell proliferation could be acquired directly from the diet or indirectly through the oral administration of formulations aimed to maintain gut health or restore a eubiotic state in an intestinal environment that has been dysregulated by external factors such as stress and a high-fat diet.

We describe a new species of microhylid frog of the genus Synapturanus from the lower Putumayo basin in Loreto, Perú. Specimens inhabited the soils of stunted pole forests growing on peat. The new species is distinguished from other species of Synapturanus through morphology, genetics, and acoustic characteristics. This species differs from most nominal congeners by having a head flat in lateral view (vs convex in the rest of species), a characteristic only shared by S. rabus and S. salseri. The new species can be distinguished from S. rabus and S. salseri by a combination of morphological characters and by having an advertisement call with a note length of 0.05–0.06 seconds (vs 0.03 seconds in S. rabus) and a dominant frequency ranging from 1.73 to 1.81 kHz (vs 1.10–1.47 kHz in S. salseri). Principal component analyses of 12 morphological characters and three acoustic variables further support differences between the new species and its described and undescribed congeners.

Epilepsy is a chronic neurological disease characterized by the presence of spontaneous seizures, with a higher incidence in the pediatric population. Anti-seizure medication (ASM) may produce adverse drug reactions (ADRs) with an elevated frequency and a high severity. Thus, the objective of the present study was to analyze, through intensive pharmacovigilance over 112 months, the ADRs produced by valproic acid (VPA), oxcarbazepine (OXC), phenytoin (PHT), and levetiracetam (LEV), among others, administered to monotherapy or polytherapy for Mexican hospitalized pediatric epilepsy patients. A total of 1034 patients were interviewed; 315 met the inclusion criteria, 211 patients presented ADRs, and 104 did not. A total of 548 ASM-ADRs were identified, and VPA, LEV, and PHT were the main culprit drugs. The most frequent ADRs were drowsiness, irritability, and thrombocytopenia, and the main systems affected were hematologic, nervous, and dermatologic. LEV and OXC caused more nonsevere ADRs, and PHT caused more severe ADRs. The risk analysis showed an association between belonging to the younger groups and polytherapy with ADR presence and between polytherapy and malnutrition with severe ADRs. In addition, most of the severe ADRs were preventable, and most of the nonsevere ADRs were nonpreventable.

Midazolam (MDZ) is used for sedation in surgical procedures; its clinical effect is related to its receptor affinity and the dose administered. Therefore, a pharmacokinetic–pharmacodynamic (PK-PD) population model of MDZ in pediatric patients undergoing minor surgery is proposed. A descriptive, observational, prospective, and longitudinal, study that included patients of both sexes, aged 2–17 years, ASA I/II, who received MDZ in IV doses (0.05 mg/kg) before surgery. Three blood samples were randomly taken between 5–120 min; both sedation by the Bispectral Index Scale (BIS) and its adverse effects were recorded. The PK-PD relationship was determined using a nonlinear mixed-effects, bicompartmental first-order elimination model using Monolix Suite™. Concentrations and the BIS were fitted to the sigmoid Emax PK-PD population and sigmoid Emax PK/PD indirect binding models, obtaining drug concentrations at the effect site (biophase). The relationship of concentrations and BIS showed a clockwise hysteresis loop, probably indicating time-dependent protein binding. Of note, at half the dose used in pediatric patients, adequate sedation without adverse effects was demonstrated. Further PK-PD studies are needed to optimize dosing schedules and avoid overdosing or possible adverse effects.

This work was aimed at the characterization of residual generated biomass from pruned tree species present in the Andean areas of Ecuador as a source of energy, both in plantations and in urban areas, as a response to the change in the energy matrix proposed by the Ecuadorian government. From the proximate analysis (volatiles, ashes, and fixed carbon content), elemental analysis (C, H, N, S, O, and Cl), structural analysis (cellulose, lignin, and hemicellulose content), and higher heating value, the studied species were pine (Pinus radiata), cypress (Cupressus macrocarpa), eucalyptus (Eucalyptus globulus), poplar (Populus sp.), arupo (Chionanthus pubescens), alder (Alnus Acuminata), caper spurge (Euphorbia laurifolia), and lime (Sambucus nigra L.) trees. We evaluated the influence of the presence of leaves in the biomass. From this characterization, we developed a method based on obtaining the main components for the identification of the biomass’s species. If the origin of the biomass was unknown, this method enabled us to identify the species, with all its characteristics. If the origin of the biomass was unknown, this innovative method enabled the identification of the species from the lignocellulosic biomass, with all of its characteristics. Finally, we developed regression models that relate the higher heating value to the elemental, proximate, and structural composition.

Phytochemicals (Pch) present in fruits, vegetables and other foods, are known to inhibit or induce drug metabolism and transport. An exhaustive search was performed in five databases covering from 2000 to 2021. Twenty-one compounds from plants were found to modulate CYP3A and/or P-gp activities and modified the pharmacokinetics and the therapeutic effect of 27 different drugs. Flavonols, flavanones, flavones, stilbenes, diferuloylmethanes, tannins, protoalkaloids, flavans, hyperforin and terpenes, reduce plasma concentration of cyclosporine, simvastatin, celiprolol, midazolam, saquinavir, buspirone, everolimus, nadolol, tamoxifen, alprazolam, verapamil, quazepam, digoxin, fexofenadine, theophylline, indinavir, clopidogrel. Anthocyanins, flavonols, flavones, flavanones, flavonoid glycosides, stilbenes, diferuloylmethanes, catechin, hyperforin, alkaloids, terpenes, tannins and protoalkaloids increase of plasma concentration of buspirone, losartan, diltiazem, felodipine, midazolam, cyclosporine, triazolam, verapamil, carbamazepine, diltiazem, aripiprazole, tamoxifen, doxorubicin, paclitaxel, nicardipine. Interactions between Pchs and drugs affect the gene expression and enzymatic activity of CYP3A and P-gp transporter, which has an impact on their bioavailability; such that co-administration of drugs with food, beverages and food supplements can cause a subtherapeutic effect or overdose. Therefore, it is important for the clinician to consider these interactions to obtain a better therapeutic effect.

This article shows the effect that biogases obtained from crop residuals from the Andean region have on the performance of a whole medium-sized electrical-generating gas turbine. This technology could be used to supply electricity in energy-depressed areas where biogas is the only accessible resource. The gas turbine worked with higher efficiencies when the obtained biogases were used compared to natural gas. The biofuel that presented the highest efficiencies was the one obtained from wheat residuals alone. Despite this fact, this biofuel would be the most prone to create aerodynamic problems in the stages of the gas turbine. In this work, it was found that the addition of guinea pig manure to different crop residuals created biofuels less prone to create aerodynamic problems in the compression and expansion stages. In particular, the studied biofuel that had the most similar aerodynamic behavior to the design natural gas case was the one obtained from guinea pig manure and quinoa residuals. On the other hand, this biogas presented the lowest efficiencies of the studied biofuels. Despite this fact, this biofuel showed higher efficiencies than the natural gas case. In the gas turbine combustion chamber, all the studied biofuels operated at lower temperatures than the ones with natural gas, even in the high-power range. This would be an important feature for the running of the combustion chamber and the high-pressure turbine superalloys.

This study investigated whether the coadministration of vitamin E (VitE) diminishes the harmful effects provoked by plasticizer bisphenol S (BPS) in the serum metabolites related to hepatic and renal metabolism, as well as the endocrine pancreatic function in diabetic male Wistar rats. Rats were divided into five groups (n = 5–6); the first group was healthy rats (Ctrl group). The other four groups were diabetic rats induced with 45 mg/kg bw of streptozotocin: Ctrl-D (diabetic control); VitE-D (100 mg/kg bw/d of VitE); BPS-D (100 mg/kg bw/d of BPS); The animals from the VitE + BPS-D group were administered 100 mg/kg bw/d of VitE + 100 mg/kg bw/d of BPS. All compounds were administered orally for 30 days. Body weight, biochemical assays, urinalysis, glucose tolerance test, pancreas histopathology, proximate chemical analysis in feces, and the activity of antioxidants in rat serum were assessed. The coadministration of VitE + BPS produced weight losses, increases in 14 serum analytes, and degeneration in the pancreas. Therefore, the VitE + BPS coadministration did not have a protective effect versus the harmful impact of BPS or the diabetic metabolic state; on the contrary, it partially aggravated the damage produced by the BPS. VitE is likely to have an additive effect on the toxicity of BPS.

We describe a new species of marsupial frog, genus Gastrotheca, using morphological characters and molecular data as lines of evidence. The new species was discovered in the páramo and the ecotone between páramo and humid montane forest of Cordillera de Colán, at elevations between 3136 and 3179 m a.s.l., in northeastern Peru. The new species is distinguished from all its congeners by the combination of the following characters: coarsely granular skin on dorsum, a green dorsal coloration without pattern, finger I shorter than finger II, turquoise iris, and a venter without blotches, flecks or dots. Furthermore, we include a detailed osteological description of the new Gastrotheca species based on Micro-CT scanning. Based on our phylogenetic analyses, the new species belongs to the Gastrotheca marsupiata species group, is sister to G. oresbios and closely related to G. psychrophila, G. spectabilis, G. stictopleura and one undescribed species. Additionally, we test for the presence of the fungal pathogen Batrachochytrium dendrobatidis (Bd). No Bd infection was detected for G. gemma sp. nov. specimens but Bd prevalence was detected among syntopic frogs.

The tropical Andes are known to be the richest and most diverse place on earth. This mountainous region covers almost one third of the Peruvian territory, and its herpetofauna remains poorly known. The lizard genus Stenocercus Duméril & Bibron, 1837 contains 69 species and most of them occur in the tropical Andes, although some exist as high as 4000 m a.s.l. The examination of newly collected material from the Andes of northern Peru in the Department of Amazonas reveals four new species of Stenocercus which we describe below. Of these four new species, three inhabit the ecoregion of Peruvian Yungas at elevations of 1460 to 2370 m a.s.l., and one the Marañón dry forest ecoregion at elevations of 1340 to 1470 m a.s.l. Additionally, we provide new data about coloration, natural history and distribution of the poorly known S. aculeatus O’Shaughnessy, 1879; and discuss the identity of some populations of S. prionotus Cadle, 2001 and S. scapularis Boulenger, 1901.

A healing material must have desirable characteristics such as maintaining a physiological environment, protective barrier-forming abilities, exudate absorption, easy handling, and non-toxicity. Laponite is a synthetic clay with properties such as swelling, physical crosslinking, rheological stability, and drug entrapment, making it an interesting alternative for developing new dressings. This study evaluated its performance in lecithin/gelatin composites (LGL) as well as with the addition of maltodextrin/sodium ascorbate mixture (LGL MAS). These materials were applied as nanoparticles, dispersed, and prepared by using the gelatin desolvation method—eventually being turned into films via the solvent-casting method. Both types of composites were also studied as dispersions and films. Dynamic Light Scattering (DLS) and rheological techniques were used to characterize the dispersions, while the films’ mechanical properties and drug release were determined. Laponite in an amount of 8.8 mg developed the optimal composites, reducing the particulate size and avoiding the agglomeration by its physical crosslinker and amphoteric properties. On the films, it enhanced the swelling and provided stability below 50 °C. Moreover, the study of drug release in maltodextrin and sodium ascorbate from LGL MAS was fitted to first-order and Korsmeyer–Peppas models, respectively. The aforementioned systems represent an interesting, innovative, and promising alternative in the field of healing materials.

Whether age and sex influence the depth of sedation and the pharmacokinetics of midazolam is currently unknown. The influence of age and sex was investigated in 117 children (2 to 17 years) who required intravenous sedation for minor surgery (0.05 mg/kg). Plasma concentrations and sedation effects were simultaneously measured. The measured concentrations were analyzed using a two-compartment model with first-order elimination. Among the age ranges, significant differences were found (p < 0.05) between the volume of distribution (Vd) of the first compartment (V1) and that of the second (V2). With respect to sex, differences in V2 were found between age groups. At the administered dose, in patients younger than 6 years, a profound sedative effect (40–60 BIS) was observed for up to 120 min, while in older children, the effect lasted only half as long. The differences found in the Vd and bispectral index (BIS) in patients younger than 6 years compared to older patients may be due to immature CYP3A activity and body fat content; furthermore, the Vd varies with age due to changes in body composition and protein binding. Patients younger than 6 years require intravenous (IV) doses

Bacterial biofilms are a major cause of harm related to medical infections and biofouling. Thus, 80% of total infections are caused by biofilm-forming microorganisms. Consequently, knowledge of biofilm formation stages is crucial to develop effective treatments to prevent their formation in medical implants, tools, and devices. For this purpose, quartz crystal microbalance (QCM) sensors are becoming a good alternative to analytical methods for the real-time monitoring of bacterial growth in liquid media culture. In a previous paper, the authors described an affordable multi-channel measurement instrument based on QCM sensors. However, in order to validate its correct operation, complementary experimental measurements based on bacterial biofilm growth were performed. In this work, the experimental measurements that allow the identification of the different biofilm formation stages are described. The results obtained are discussed.

Metformin pharmacokinetics in a liquid extemporaneous formulation from commercial tablets was determined in paediatric patients. A randomized, transversal clinical trial was conducted in 34 children and adolescents between 7 and 17 years of age. 17 children were randomized to take metformin in the liquid formulation and, after a 1-week wash period, a 500 mg metformin tablet was administered to them. Blood samples were obtained in Whatman 903® cards at 0, 1, 2, 4, 8, 12 and 24 hours. Extraction was made by direct precipitation with acetonitrile (ACN) and methanol, detection by UPLC and tandem mass spectrometry. The method was accurate, precise, selective and linear from 50 to 1000 ng/mL (r = .9982). Comparative pharmacokinetics, tablet vs formulation, were as follows: C max 1503.2 ng/mL vs 1521.4, T max 1.5 h vs 2.3, and half-life 8.2 vs 7.5 h. The liquid formulation of metformin showed similar pharmacokinetics to the tablet, and the ratios (90% CI) of geometric mean for metformin were 100.63% (89.13–113.6), 98.08% (88.04–109.2), and 97.52% (84.9–112.01), for C max , AUC 0-t , and AUC 0-∞, respectively. Pharmacokinetics was determined using WinNonlin Pro 3.1 software. The liquid formulation of metformin showed similar pharmacokinetics to the tablet, allowing a more precise dose adjustment and ease of administration.

La actividad económica resultado de la elaboración de quesos artesanales, es de gran importancia para la economía local, no existe un estudio de este tipo que permita a los productores conocer a detalle los costos de manufactura del queso artesanal, actualmente los productores sólo tienen aproximaciones y sus precios de venta los determinan de acuerdo al comportamiento del mercado, sin tener certeza acerca del margen de utilidad. Por ello, se realizó este trabajo que consistió en determinar la estructura de costos en cada tipo de queso artesanal, que se elabora en la Quesería “El Bejucal”. Esta empresa es una de las más emblemáticas debido a su tradición y prestigio, ubicada en el municipio de Balancán, Tabasco, y cuya marca está protegida ante el Instituto Mexicano de la Propiedad Industrial (IMPI). Se realizaron cálculos basados en la clasificación de costos directos, indirectos y gastos de administración y ventas. Se encontró que el queso de poro es el producto que más alto costo de producción tiene, respecto a los demas productos, debido principalmente al elevado costo del material de empaque. Sin embargo, el ingreso por la comercialización del queso de poro corresponde al 70% y el restante a los otros quesos; el queso de poro es de pasta friable,blanda y prensada; ligeramente madurado, elaborado a partir de leche bronca, se comercializa en piezas de aproximadamente 300 g.

Introduction The CYP450 complex participates in the metabolism of ifosfamide, an antineoplastic drug used to treat solid tumors. genes contain several single nucleotide polymorphisms (SNPs) that confer different activity towards the enzyme. The aim of our study was to analyze gene frequencies of allelic variants and their association with ifosfamide blood levels and patient prognosis. Material and methods 148 DNA samples from children were analyzed. Genotyping was performed by real-time PCR with TaqMan probes and ifosfamide levels were determined in dried blood drop by UPLCMS/MS. Results Ifosfamide levels increased according to the genotype, and patients with the variant rs1799853 in CYP2C9 genotype CC had lower levels of ifosfamide (median = 1.8 µmol/l, Q25 0.9–Q75 4.6) compared with patients with genotype TT + CT (median = 2.8 µmol/l, Q25 1.9–Q75 5.1), p < 0.001. In the case of the rs2740574 variant in the CYP3A4 gene, patients with normal genotype (TT) presented median = 1.4 µmol/l, (Q25 0.7–Q75 2.7), while patients with the CC + TC genotype had higher levels of ifosfamide (median = 2.0 µmol/l, Q25 1.0–Q75 4.3), p = 0.024. In addition, patients with CC + CT genotype of this variant had a higher risk of non-response to treatment compared to patients with TT genotype (RR = 1.3, 95% CI: 1.07–1.59, p = 0.03). Conclusions Polymorphisms in CYP2C9 and CYP3A4 genes are associated with high levels of ifosfamide. In addition, the polymorphism rs2740574 in CYP3A4 was associated with a worse therapeutic response.

Midazolam is a drug that is metabolized by cytochrome P450 (CYP450) enzymes, particularly CYP3A4 and CYP3A5. The present study aimed to determine the sex and age influence on association of CYP450 polymorphism with midazolam levels in critically ill children. Seventy-two DNA samples were genotyped by real-time PCR. Children ≤ five years of age who carry the rs776746 (T) allele in CYP3A5 gene were associated with lower plasma midazolam levels. The concentration median in patients was 0.0 ng/mL, while in patients with the normal (C) allele, it was 438.17 ng/mL (Q25 135.75–Q75 580.24), p = 0.005. The midazolam plasmatic concentration in female patients with the minor (T) allele was 0.0 ng/mL (Q250.00–Q75204.3), while in patients with the normal (C) allele median it was 459.0 ng/mL (Q25296.9–Q75789.7), p = 0.002. Analysis of the dominant model for the rs2740574 variant in CYP3A4 revealed a median of 0.38 L/kg (Q250.02–Q751.5) for the volume of distribution parameter in female patients with the normal T allele, while female patients with the minor C allele showed a median of 18.1 L/kg (Q257.5–Q7528.7) p = 0.02. Our results suggest an altered midazolam metabolism due to the presence the allelic rs2740574 variants of CYP3A4 and rs776746 of CYP3A5, and also the strong influence of age and sex.

Objetivo. Determinar la casuística de enfermedades neurológicas, así como la edad, raza y los sitios neuroanatómicos afectados. Materiales y métodos. Se realizó un estudio retrospectivo de los expedientes clínicos de los pacientes caninos atendidos en el Hospital Veterinario de la Facultad de Medicina Veterinaria y Zootecnia de la Universidad de San Carlos de Guatemala en el año 2017. Los datos fueron clasificados según la regla nemotécnica VITAMIN D. Se incluyeron las variables sexo, raza, edad y localización neuroanatómica de lesiones. Los datos fueron resumidos utilizando estadística descriptiva por medio de tablas de distribución de frecuencias. Resultados. De los 1,127 registros de casos la prevalencia de enfermedades neurológicas fue de 8.43%. La frecuencia fue mayor en machos que en hembras (53.68% vs 46.32%). El grupo etario más afectado oscila entre los cero y los siete años. Respecto a razas, se observó una mayor frecuencia en caninos sin raza definida (25.53%) seguido de los perros French Poodle (20.21%). Las patologías encontradas fueron: vascular (1.05%), inflamatoria/ infecciosa (25.26%), traumática (13.68%), metabólica (8.42%), idiopática (6.32%), neoplásica (1.05%) y degenerativa (44.21%). La neurolocalización más frecuente fue a nivel de SNC (86.32%). Conclusiones. Según los hallazgos de este estudio se determinó que las enfermedades de carácter degenerativo representaron la mayor parte de la casuística neurológica. La mayor frecuencia de casos se presentó en pacientes caninos jóvenes, machos de razas mixtas. El sitio neuroanatómico más frecuente de localización de lesiones fue en medula espinal a nivel toracolumbar.

Ernesto Guevara is a well-known character. Before he participated in various revolutions throughout Latin America, he dedicated his early life and daily work to medicine, his profession, some of which he performed in Hospital General de México.

El presente artículo plantea el lenguaje inclusivo como un horizonte múltiple y flexible, a partir del cual se abordan las representaciones de lo foráneo, la discapacidad y el sexismo. Bajo esta premisa, se vale de una serie de ejemplos discursivos y dos manifestaciones literarias para arribar a una perspectiva en que la comunicación gana en claridad, pertinencia, justicia y empatía.

The effect of temperature variations recorded in eight meteorological stations in Yaqui Valley, Sonora, Mexico, on the tillering capacity and grain yield of wheat variety CIRNO C2008 in the growing cycles December 2016-May 2017 and December 2017-May 2018 was studied. In one of the sites, the crop canopy temperature was increased by +2°C with a T-FACE system (warming) based on the temperature recorded in the nearest meteorological station. With the two experimental variants, the abscisic (ABA) and gibberellic (GA) acid hormones were determined during tillering (initial tillering: 30 d after emergence and final tillering: 45 d after emergence) to explain their contribution to the tillering capacity response. A temperature variability of 1°C was observed in the cycle December 2017- May 2018, as compared to the previous cycle and between the evaluated sites. As a result of the temperature increase effect, the tiller number was significantly reduced. The experimental warming caused a highly significant decrease in the ABA content and an increase in the GA. The temperature variation found in Yaqui Valley had a negative and significant correlation with the grain yield in both experiment crop cycles, which demonstrated that global warming is reducing the tillering capacity and grain yield of wheat in Yaqui Valley.

The methacrylic acid–ethyl acrylate copolymer nanoparticles were prepared using the solvent displacement method. The independent variables were the drug/polymer ratio, surfactant concentration, Polioxyl 40 hydrogenated castor oil, the added water volume, time, and stirring speed, while size, PDI, zeta potential, and encapsulation efficiency were the response variables analyzed. A design of screening experiments was carried out to subsequently perform the optimization of the nanoparticle preparation process. The optimal formulation was characterized through the dependent variables size, PDI, zeta potential, encapsulation efficiency and drug release profiles. In vivo tests were performed in Wistar rats previously induced with diabetes by administration of streptozotocin. Once hyperglycemia was determined in rats, a suspension of nanoparticles loaded with glibenclamide was administered to them while the other group was administered with tablets of glibenclamide. The optimal nanoparticle formulation obtained a size of 18.98 +/− 9.14 nm with a PDI of 0.37085 +/− 0.014 and a zeta potential of −13.7125 +/− 1.82 mV; the encapsulation efficiency was of 44.5%. The in vivo model demonstrated a significant effect (p < 0.05) between the group administered with nanoparticles loaded with glibenclamide and the group administered with tablets compared to the group of untreated individuals.

In this work a protocol for the extraction of DNA from the meat of different animals (beef, pork, and horse) was established. The protocol utilized TE lysis buffer with varying concentrations of phenol and chloroform as a base reagent. Reactions were carried out for verying time periods and under differing temperatures. All samples analyzed were obtained from commercial grade meat sourced from the local region. 12 samples were used for methodological optimization with 30 repetitions per sample. Once optimized, purity results for the three species were 1.7 with a concentration (determined spectrophotometrically at 260 nm) of 100 μl/ml of DNA. The protocol was tested using 465 different meat samples from different animal species. All meat used was fresh and processed. Results showed a purity of 1.35 ± 0.076 and a DNA concentration of 70 ± 0.31 μl for a time duration of 1.5 hours. These results were tested by polymerase chain reaction (PCR) as reported by several authors. The extracts were tested using different PCR reactions using specific primers for horses. Results suggest that there was 39 positive samples. The proposed methodology provides an efficient way to detect DNA concentration and purity, suitable for amplification with PCR.

In this article, we analyze the relationship between the economic growth rate and a rule of law indicator in Mexican states during the period 2006–2013. Specifically, we employ information regarding the time it takes to solve commercial disputes in local courts, which we use as a proxy variable to measure the efficiency of the justice system. In principle, we expect that the shorter the time it takes to resolve commercial disputes, the higher the growth rates will be in the states where the firms are located. Long, drawn-out court disputes are costly for firms, which in turn may translate into lower growth rates due to the negative impact of these costs on their levels of investment. The results suggest that a 100-day decrease in the time it takes to resolve a commercial dispute is associated with an increase of 0.6 per cent in the average GDP per capita growth rate in Mexican states.

Purpose: The objective of this study was to determine whether a comorbidity index could be used to predict mortality in pediatric patients with chemotherapy-treated solid tumors.Methods: Pediatric patients who underwent chemotherapy treatment for solid tumors were included, and demographic, clinical, and comorbidity data were obtained from patient electronic records.Results: A total of 196 pediatric patients with embryonic solid tumors were included. Metastatic tumors were the most frequently observed (n = 103, 52.6%). The most common comorbidities encountered for the Charlson comorbidity index (CCI) were cellulitis (n = 24, 12.2%) and acute renal failure (n = 15, 7.7%). For the Pediatric Comorbidity Index (PCI), the most frequent comorbidities were pneumonia and sepsis, with n = 64 (32.7%) for each. We evaluated established the prognostic values for both indexes using Kaplan-Meier curves, finding that the CCI and PCI could predict mortality with p < 0.0001.Conclusion: Using the PCI, we observed 100% survival in patients without comorbidities, 70% survival in patients with a low degree of comorbidity, and 20% survival in patients with a high degree of comorbidity. Greater discrimination of probability of survival could be achieved using degrees of comorbidity on the PCI than using degrees of comorbidity on the CCI. The application of the PCI for assessing the hospitalized pediatric population may be of importance for improving clinical evaluation.