Latin American Consensus on the Treatment of Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery-oral cavity, Clinical oncology-oral cavity, Head and neck surgery-oropharynx, Clinical oncology-oropharynx, Head and neck surgery-larynx, Head and neck surgery-larynx/hypopharynx, Clinical oncology-larynx/hypopharynx, Clinical oncology-recurrent and metastatic head and neck cancer, Head and neck surgery-reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.

Evaluation of the Effects of Food Safety Training on the Microbiological Load Present in Equipment, Surfaces, Utensils, and Food Manipulator's Hands in Restaurants.

Training food handlers is essential to ensure food safety. However, the efficacy of training programs relying solely on theoretical information remains uncertain and often fails to induce significant changes in inadequate food practices. Training programs in good hygiene and food safety practices that integrate theoretical and practical approaches have emerged as a vital tool, enabling food handlers to apply their knowledge during work hours and clarify doubts. This study aimed to assess the impact of food safety training based on theoretical and on-the-job training on the microbiological counts of equipment, surfaces, utensils, and food handler (FH) hands. The hygiene and food safety conditions of four restaurants were analyzed through facility checklists, employee questionnaires, and microbiological analyses conducted before and after training. Eight sample collection moments were conducted at each restaurant before and after training. The pre-training results indicate that 15% and 26% of analyses for Enterobacteriaceae and total mesophilic aerobic bacteria (TMB), respectively, did not comply with hygiene safety limits. Additionally, 31% and 64% of Enterobacteriaceae and TMB values, respectively, exceeded safety limits on food handler hands. Positive cases of coagulase-positive Staphylococcus (CoPS) resulted from unprotected wounds on some FH hands. The presence of Listeria monocytogenes in drains was also identified as a concern. Following training, significant differences in results were observed. In many cases, there was a reduction of over 80% in microbial load for Enterobacteriaceae and TMB collected from equipment, surfaces, utensils, and food handler hands. The presence of L. monocytogenes in drains was also eliminated after food safety training. In conclusion, this study underscores the importance of effective training in improving food safety practices.

Experimental Determination of the Standard Enthalpy of Formation of Trimellitic Acid and Its Prediction by Supervised Learning.

The standard molar enthalpy of formation for trimellitic acid (TMAc) in the crystalline phase at 298.15 K, ΔfHm°(cr), was calculated experimentally from the enthalpy of combustion through combustion calorimetry experiments. Likewise, the standard molar enthalpy of sublimation was determined from the standard molar enthalpy of fusion and from the standard molar enthalpy of vaporization from differential scanning calorimetry and thermogravimetry, respectively. Subsequently, the standard molar enthalpies of formation in the gas-phase at 298.15 K, ΔfHm°(g), were calculated. The enthalpies of formation for TMAc, hemimellitic, and trimesic acids were predicted using multiple linear regression (MLR) with a nonreplacement evaluation technique. MLR was applied to the data set that allowed estimating these thermochemical properties with an R2 greater than 0.99. This model was used to compare the predicted and experimental results for benzene carboxylic acids.

A Protein Misfolding Shaking Amplification-based method for the spontaneous generation of hundreds of bona fide prions.

Prion diseases are a group of rapidly progressing neurodegenerative disorders caused by the misfolding of the endogenous prion protein (PrPC) into a pathogenic form (PrPSc). This process, despite being the central event underlying these disorders, remains largely unknown at a molecular level, precluding the prediction of new potential outbreaks or interspecies transmission incidents. In this work, we present a method to generate bona fide recombinant prions de novo, allowing a comprehensive analysis of protein misfolding across a wide range of prion proteins from mammalian species. We study more than 380 different prion proteins from mammals and classify them according to their spontaneous misfolding propensity and their conformational variability. This study aims to address fundamental questions in the prion research field such as defining infectivity determinants, interspecies transmission barriers or the structural influence of specific amino acids and provide invaluable information for future diagnosis and therapy applications.

Clinical Epidemiology of Extracranial Injuries in Severe Pediatric Traumatic Brain Injury in South America.

BACKGROUND: Severe traumatic brain injury (TBI) is a leading cause of pediatric mortality, with a disproportionate burden on low- and middle-income countries. The impact of concomitant extracranial injury (ECI) on these patients remains unclear. This study is the first to characterize the epidemiology and clinical course of severe pediatric TBI with extracranial injuries in any South American country. METHODS: We conducted a secondary analysis of baseline data collected prior to implementation of a clinical trial on TBI care in Argentina, Paraguay, and Chile from September 2019 to July 2020. Patients ≤18 years with CT evidence of TBI, and a Glasgow coma scale (GCS) score ≤8 were recruited. Patients were initially stratified by highest non-head abbreviated injury scale (AIS): isolated TBI (AIS=0), minor extracranial injury (MEI; AIS=1-2), and serious extracranial injury (SEI; AIS≥3). Patients were subsequently stratified by mechanism of injury. Intergroup differences were compared using ANOVA, two-tailed unpaired t-tests, and chi-square tests. RESULTS: Among the 116 children included, 33 % (n = 38) had an isolated TBI, 34 % (n = 39) had MEI, and 34 % (n = 39) had SEI. Facial (n = 53), thoracic (n = 44), and abdominal (n = 31) injuries were the most common ECIs. At discharge, there were no significant differences in median GCS, GOS, or GOS-extended between groups. Patients with SEI had a longer hospital LOS than those with isolated TBI (median 28.0 (IQR 10.6-40.1) vs 11.9 (IQR 8.7-20.7) days, p = 0.013). The most common mechanisms of injury were road traffic injuries (RTIs) (n = 50, 43 %) and falls (n = 35, 30 %). Patients with RTI-associated TBIs were more likely to be older (median 11.0 (IQR 3.0-14.0) vs 2.0 (IQR 0.8-7.0) years, p<0.001) and more likely to have an ECI (86% vs 54 %, respectively; p = 0.003). ICU and Hospital LOS for RTI patients (median 10.5 (IQR 6.1-21.1) and 24.1 (IQR 11.5-40.4) days) were longer than those of fall patients (median 6.1 (IQR 2.6-8.9) and 13.7 (IQR 7.7-24.5) days). CONCLUSIONS: Extracranial injuries are common in South American patients with severe TBI. Severe ECI is more frequently associated with RTIs and can result in a higher rate of surgical procedures and LOS. Further strategies are needed to characterize the prevention and treatment of severe pediatric TBI in the South American context.

Phalangeal microgeodic syndrome: case report of a young woman treated with pentoxifylline.

Phalangeal microgeodic syndrome (PMS) is a rare osteolytic disorder of unknown etiology that typically affects children up to 15 years old during colder months. Transient peripheral circulatory impairment probably underlines its pathogenesis. Conservative treatment with eviction of cold exposure is often successful. We report the case of a young woman presenting with joint pain in her feet, along with toe discoloration and redness, where a diagnosis of PMS was established based on magnetic resonance imaging findings and exclusion of other differential diagnostic entities. Pharmacological treatment was deemed necessary for symptomatic relief, but a trial of calcium channel blocker (CCB) was not tolerated by the patient. The patient was then started on pentoxifylline, with significant clinical improvement.

Aneurysmal Degeneration of the Brachial Artery Following Chronic Arteriovenous Fistula Ligation.

Introduction: Arteriovenous fistulas (AVF) are currently considered to be the best vascular access option for patients with end stage chronic kidney disease requiring haemodialysis. In rare cases of patients with chronic AVF, thrombosis or ligation of the access can lead to the development of brachial artery aneurysms. Despite being uncommon, reports of this phenomenon have arisen in recent decades due to an increase in the number of patients undergoing dialysis worldwide. This case presented with a brachial aneurysm that developed after AVF ligation. Case report: A 62 year old male presented to the emergency department with swelling of the medial aspect of his left arm associated with pain, inflammatory signs, and finger paraesthesia. Swelling had started two months previously but had worsened within the last week. He had history of kidney transplant 20 years ago and a chronic functioning radiocephalic fistula that had not been used since, and which had been ligated in the past year due to the development of venous aneurysms. Physical examination revealed a pulsatile mass in his left arm and absent radial and ulnar pulses, without signs of hand ischaemia. There was significant venous collateralisation of the arm and chest and numbness of the left fingers, suggesting venous and neurological compression. Computed tomography angiography showed a large left brachial artery aneurysm (108 x 87 x 180 mm). The patient underwent aneurysm sac emptying and collateral ligation followed by great saphenous vein interposition, with clinical improvement. Conclusion: The presence of a chronic AVF can lead to progressive changes in the arterial wall. Sudden ligation or thrombosis of a functioning AVF causes increased blood pressure within the artery, which may further contribute to its aneurysmal degeneration. In addition, immunosuppressive therapy following kidney transplant has been described as a synergistic risk factor leading to aneurysm formation. Despite being a rare complication, patients with a chronic AVF should be monitored closely after vascular access ligation.

Detection of NTRK gene fusions in solid tumors: recommendations from a Latin American group of oncologists and pathologists.

NTRK gene fusions have been detected in more than 25 types of tumors and their prevalence is approximately 0.3% in solid tumors. This low prevalence makes identifying patients who could benefit from TRK inhibitors a considerable challenge. Furthermore, while numerous papers on the evaluation of NTRK fusion genes are available, not all countries have guidelines that are suitable for their setting, as is the case with Latin America. Therefore, a group of oncologists and pathologists from several countries in Latin America (Argentina, Chile, Ecuador, Mexico, Peru and Uruguay) met to discuss and reach consensus on how to identify patients with NTRK gene fusions in solid tumors. To do so, they developed a practical algorithm, considering their specific situation and limitations.

n-Tuples on Scaffold Diversity Inspired by Drug Hybridisation to Enhance Drugability: Application to Cytarabine.

A mathematical concept, n-tuples are originally applied to medicinal chemistry, especially with the creation of scaffold diversity inspired by the hybridisation of different commercial drugs with cytarabine, a synthetic arabinonucleoside derived from two marine natural products, spongouridine and spongothymidine. The new methodology explores the virtual chemical-factorial combination of different commercial drugs (immunosuppressant, antibiotic, antiemetic, anti-inflammatory, and anticancer) with the anticancer drug cytarabine. Real chemical combinations were designed and synthesised for 8-duples, obtaining a small representative library of interesting organic molecules to be biologically tested as proof of concept. The synthesised library contains classical molecular properties regarding the Lipinski rules and/or beyond rules of five (bRo5) and is represented by the covalent combination of the anticancer drug cytarabine with ibuprofen, flurbiprofen, folic acid, sulfasalazine, ciprofloxacin, bortezomib, and methotrexate. The insertion of specific nomenclature could be implemented into artificial intelligence algorithms in order to enhance the efficiency of drug-hunting programs. The novel methodology has proven useful for the straightforward synthesis of most of the theoretically proposed duples and, in principle, could be extended to any other central drug.

Characterization and Evaluation of Silver Concentrations in Hydroxyapatite Powders.

The goal of this study is to evaluate the influence of the concentration of silver on the structural and antimicrobial in vitro properties of silver-doped hydroxyapatite powders obtained using the precipitation method. Different concentrations of silver were evaluated to assess the antimicrobial properties. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, scanning electron microscopy (SEM), and dispersive energy spectroscopy (EDS) were used to characterize the powders. XRD and FTIR showed that the hydroxyapatite structure is not affected by the incorporation of silver; on the other hand, EDS showed the presence of silver in the powders. Antibacterial studies showed the efficiency of hydroxyapatite powders in inhibiting bacterial growth as silver concentration increases. According to the results, silver-doped hydroxyapatite powders are suggested for use in the prevention and treatment of infections in bone and dental tissues.

Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generation.

Among transmissible spongiform encephalopathies or prion diseases affecting humans, sporadic forms such as sporadic Creutzfeldt-Jakob disease are the vast majority. Unlike genetic or acquired forms of the disease, these idiopathic forms occur seemingly due to a random event of spontaneous misfolding of the cellular PrP (PrPC) into the pathogenic isoform (PrPSc). Currently, the molecular mechanisms that trigger and drive this event, which occurs in approximately one individual per million each year, remain completely unknown. Modelling this phenomenon in experimental settings is highly challenging due to its sporadic and rare occurrence. Previous attempts to model spontaneous prion misfolding in vitro have not been fully successful, as the spontaneous formation of prions is infrequent and stochastic, hindering the systematic study of the phenomenon. In this study, we present the first method that consistently induces spontaneous misfolding of recombinant PrP into bona fide prions within hours, providing unprecedented possibilities to investigate the mechanisms underlying sporadic prionopathies. By fine-tuning the Protein Misfolding Shaking Amplification method, which was initially developed to propagate recombinant prions, we have created a methodology that consistently produces spontaneously misfolded recombinant prions in 100% of the cases. Furthermore, this method gives rise to distinct strains and reveals the critical influence of charged surfaces in this process.

Transition metal-free [2,3]-sigmatropic rearrangement in the reaction of sulfur ylides with allenoates.

An unprecedented transition metal free [2,3]-sigmatropic rearrangement involving stabilized sulfur ylides and allenoates has been thoroughly established. The scope and utility of this reaction have been extensively studied resulting in C-C bond formation under mild conditions with greater than 20 examples reported. A highlight of the work is the simple and fully operational process that does not involve the use of carbenes or the associated hazardous and sensitive reagents. The reaction can be performed at room temperature and using an open flask. Interestingly, the new C-C bond formation reaction is gram scalable, and the obtained isomers are readily separable, affording interesting building blocks that can be used in the preparation of complex molecules.

Effect of TiO2 Microparticles in Lettuce (Lactuca sativa L.) Seeds and Seedlings.

The particle size reduction technology is used in several segments, including sunscreens and new techniques and product improvement. One of the main particles used in the sunscreens formulation is titanium dioxide (TiO2). This formulation allows for better characteristics of these products. Perspectives like incorporation of the particles by other biological systems beyond humans and their effects should be observed. This work aimed to evaluate the titanium dioxide microparticles phytotoxicity on Lactuca sativa L. plants through tests of germination, growth, and weight analysis using microscopy techniques: optical microscopy (OM) and scanning electron microscopy (SEM). Some of the results showed cellular and morphological damage, mainly in the roots and 50 mg L-1 TiO2 concentration, confirmed by SEM. Additionally, anatomical damages like vascular bundle disruption and irregularity in the cortex cells were confirmed by SEM. Additionally, anatomical damages were observed on the three main organs (root, hypocotyl, and leaves) evidenced by the OM. Perspectives to confirm new hypotheses of the interaction of nanomaterials with biological systems are necessary.

Substitutional Coinage Metals as Promising Defects for Adsorption and Detection of Gases on MoS2 Monolayers: A Computational Approach.

Defective molybdenum disulfide (MoS2) monolayers (MLs) modified with coinage metal atoms (Cu, Ag and Au) embedded in sulfur vacancies are studied at a dispersion-corrected density functional level. Atmospheric constituents (H2, O2 and N2) and air pollutants (CO and NO), known as secondary greenhouse gases, are adsorbed on up to two atoms embedded into sulfur vacancies in MoS2 MLs. The adsorption energies suggest that the NO (1.44 eV) and CO (1.24 eV) are chemisorbed more strongly than O2 (1.07 eV) and N2 (0.66 eV) on the ML with a cooper atom substituting for a sulfur atom. Therefore, the adsorption of N2 and O2 does not compete with NO or CO adsorption. Besides, NO adsorbed on embedded Cu creates a new level in the band gap. In addition, it was found that the CO molecule could directly react with the pre-adsorbed O2 molecule on a Cu atom, forming the complex OOCO, via the Eley-Rideal reaction mechanism. The adsorption energies of CO, NO and O2 on Au2S2, Cu2S2 and Ag2S2 embedded into two sulfur vacancies were competitive. Charge transference occurs from the defective MoS2 ML to the adsorbed molecules, oxidizing the later ones (NO, CO and O2) since they act as acceptors. The total and projected density of states reveal that a MoS2 ML modified with copper, gold and silver dimers could be used to design electronic or magnetic devices for sensing applications in the adsorption of NO, CO and O2 molecules. Moreover, NO and O2 molecules adsorbed on MoS2-Au2s2 and MoS2-Cu2s2 introduce a transition from metallic to half-metallic behavior for applications in spintronics. These modified monolayers are expected to exhibit chemiresistive behavior, meaning their electrical resistance changes in response to the presence of NO molecules. This property makes them suitable for detecting and measuring NO concentrations. Also, modified materials with half-metal behavior could be beneficial for spintronic devices, particularly those that require spin-polarized currents.

Genetic Markers Associated with Milk Production and Thermotolerance in Holstein Dairy Cows Managed in a Heat-Stressed Environment.

Dairy production in Holstein cows in a semiarid environment is challenging due to heat stress. Under such conditions, genetic selection for heat tolerance appears to be a useful strategy. The objective was to validate molecular markers associated with milk production and thermotolerance traits in Holstein cows managed in a hot and humid environment. Lactating cows (n = 300) exposed to a heat stress environment were genotyped using a medium-density array including 53,218 SNPs. A genome-wide association study (GWAS) detected six SNPs associated with total milk yield (MY305) that surpassed multiple testing (p < 1.14 × 10-6). These SNPs were further validated in 216 Holstein cows from two independent populations that were genotyped using the TaqMan bi-allelic discrimination method and qPCR. In these cows, only the SNPs rs8193046, rs43410971, and rs382039214, within the genes TLR4, GRM8, and SMAD3, respectively, were associated (p < 0.05) with MY305, rectal temperature (RT), and respiratory rate. Interestingly, these variables improved as the number of favorable genotypes of the SNPs increased from 0 to 3. In addition, a regression analysis detected RT as a significant predictor (R2 = 0.362) for MY305 in cows with >1 favorable genotype, suggesting this close relationship was influenced by genetic markers. In conclusion, SNPs in the genes TLR4, GRM8, and SMAD3 appear to be involved in the molecular mechanism that regulates milk production in cows under heat-stressed conditions. These SNPs are proposed as thermotolerance genetic markers for a selection program to improve the milk performance of lactating Holstein cows managed in a semiarid environment.

Reproductive performance of hair ewes and rams implanted with melatonin previous to the anestrus season in northwest Mexico.

Ovine reproductive behavior depends on annual photoperiodic cycle and its impact on endogenous melatonin secretion. In this regard, exogenous melatonin administration previous to the physiological anestrus period could modify the reproductive performance of sheep in the northwest of Mexico. Two independent studies were performed to evaluate such hypothesis in hair sheep implanted with melatonin prior to the anestrus season in latitudes 24° and 25° of Mexico. Study 1 involved 15 rams assigned to one of three treatments receiving 0mg (n=5), 18mg (n=5), or 36mg (n=5) of melatonin subcutaneously. Study variables were measured monthly since implantation (d0) and included testosterone concentration, scrotal circumference, mass motility, individual motility, and sperm concentration. Study 2 included 50 ewes assigned to one of two treatments receiving 0mg (n=25) or 18mg (n=25) of melatonin subcutaneously. In ewes, progesterone concentration and the frequency of females in anestrus were measured during the implantation (-30d), as well as at the beginning (0d) and at the end (45d) of the mating period, while pregnancy rate was determined by ultrasonography 45d after. Continuous variables were analyzed using a mixed effects model considering treatment, time, and the treatment by time interaction as fixed effects. Animal nested within treatment was the random effect. Binary variables were analyzed using the chi-square test. In males, melatonin improved testosterone and sperm concentrations (P<0.05), while in females, a 28% higher pregnancy rate was observed in implanted ewes (P<0.05). Therefore, melatonin enhanced reproductive parameters in both sexes and its exogenous administration previous to the anestrus season in northwest Mexico could be more effective in rams.

Antioxidants in Traditional Mexican Medicine and Their Applications as Antitumor Treatments.

Traditional medicine in Latin America and mainly in Mexico represents an essential alternative for treating different diseases. The use of plants as medicine is the product of a rich cultural tradition of the indigenous peoples, in which a great variety of species are used for the treatment of gastrointestinal, respiratory, and mental diseases and some other sicknesses; the therapeutic efficacy that they possess is due to the properties that derive from the active ingredients of plants principally antioxidants, such as phenolic compounds, flavonoids, terpenes, and tannins. An antioxidant is a substance that, at low concentrations, delays or prevents substrate oxidation through the exchange of electrons. Different methods are used to determine the antioxidant activity and the most commonly used are described in the review. Cancer is a disease in which some cells multiply uncontrollably and spread to other parts of the body, a process known as metastasis. These cells can lead to the formation of tumors, which are lumps of tissue that can be cancerous (malignant) or noncancerous (benign). Generally, the treatment of this disease consists of surgery, radiotherapy, or chemotherapy, which have side effects that decrease the quality of life of patients, so new treatments, focusing on natural resources such as plants, can be developed. This review aims to gather scientific evidence on the antioxidant compounds present in plants used in traditional Mexican medicine, specifically as antitumor treatment in the most common cancer types worldwide (e.g., breast, liver, and colorectal cancer).