The conformational plasticity of structurally unrelated lipid transport proteins correlates with their mode of action.

Lipid transfer proteins (LTPs) are key players in cellular homeostasis and regulation, as they coordinate the exchange of lipids between different cellular organelles. Despite their importance, our mechanistic understanding of how LTPs function at the molecular level is still in its infancy, mostly due to the large number of existing LTPs and to the low degree of conservation at the sequence and structural level. In this work, we use molecular simulations to characterize a representative dataset of lipid transport domains (LTDs) of 12 LTPs that belong to 8 distinct families. We find that despite no sequence homology nor structural conservation, the conformational landscape of LTDs displays common features, characterized by the presence of at least 2 main conformations whose populations are modulated by the presence of the bound lipid. These conformational properties correlate with their mechanistic mode of action, allowing for the interpretation and design of experimental strategies to further dissect their mechanism. Our findings indicate the existence of a conserved, fold-independent mechanism of lipid transfer across LTPs of various families and offer a general framework for understanding their functional mechanism.

A comparison of RNA-Seq data preprocessing pipelines for transcriptomic predictions across independent studies.

BACKGROUND: RNA sequencing combined with machine learning techniques has provided a modern approach to the molecular classification of cancer. Class predictors, reflecting the disease class, can be constructed for known tissue types using the gene expression measurements extracted from cancer patients. One challenge of current cancer predictors is that they often have suboptimal performance estimates when integrating molecular datasets generated from different labs. Often, the quality of the data is variable, procured differently, and contains unwanted noise hampering the ability of a predictive model to extract useful information. Data preprocessing methods can be applied in attempts to reduce these systematic variations and harmonize the datasets before they are used to build a machine learning model for resolving tissue of origins. RESULTS: We aimed to investigate the impact of data preprocessing steps-focusing on normalization, batch effect correction, and data scaling-through trial and comparison. Our goal was to improve the cross-study predictions of tissue of origin for common cancers on large-scale RNA-Seq datasets derived from thousands of patients and over a dozen tumor types. The results showed that the choice of data preprocessing operations affected the performance of the associated classifier models constructed for tissue of origin predictions in cancer. CONCLUSION: By using TCGA as a training set and applying data preprocessing methods, we demonstrated that batch effect correction improved performance measured by weighted F1-score in resolving tissue of origin against an independent GTEx test dataset. On the other hand, the use of data preprocessing operations worsened classification performance when the independent test dataset was aggregated from separate studies in ICGC and GEO. Therefore, based on our findings with these publicly available large-scale RNA-Seq datasets, the application of data preprocessing techniques to a machine learning pipeline is not always appropriate.

Calcium signaling in endothelial and vascular smooth muscle cells: sex differences and the influence of estrogens and androgens.

Calcium signaling in vascular endothelial cells (ECs) and smooth muscle cells (VSMCs) is essential for the regulation of vascular tone. However, the changes to intracellular Ca2+ concentrations are often influenced by sex differences. Furthermore, a large body of evidence shows that sex hormone imbalance leads to dysregulation of Ca2+ signaling and this is a key factor in the pathogenesis of cardiovascular diseases. In this review, the effects of estrogens and androgens on vascular calcium-handling proteins are discussed, with emphasis on the associated genomic or nongenomic molecular mechanisms. The experimental models from which data were collected were also considered. The review highlights 1) in female ECs, transient receptor potential vanilloid 4 (TRPV4) and mitochondrial Ca2+ uniporter (MCU) enhance Ca2+-dependent nitric oxide (NO) generation. In males, only transient receptor potential canonical 3 (TRPC3) plays a fundamental role in this effect. 2) Female VSMCs have lower cytosolic Ca2+ levels than males due to differences in the activity and expression of stromal interaction molecule 1 (STIM1), calcium release-activated calcium modulator 1 (Orai1), calcium voltage-gated channel subunit-α1C (CaV1.2), Na+-K+-2Cl- symporter (NKCC1), and the Na+/K+-ATPase. 3) When compared with androgens, the influence of estrogens on Ca2+ homeostasis, vascular tone, and incidence of vascular disease is better documented. 4) Many studies use supraphysiological concentrations of sex hormones, which may limit the physiological relevance of outcomes. 5) Sex-dependent differences in Ca2+ signaling mean both sexes ought to be included in experimental design.

Universal Germline-Genetic Testing for Breast Cancer: Implementation in a Rural Practice and Impact on Shared Decision-Making.

BACKGROUND: Whereas the National Comprehensive Cancer Network (NCCN) criteria restrict germline-genetic testing (GGT) to a subset of breast cancer (BC) patients, the American Society of Breast Surgeons recommends universal GGT. Although the yield of pathogenic germline variants (PGV) in unselected BC patients has been studied, the practicality and utility of incorporating universal GGT into routine cancer care in community and rural settings is understudied. This study reports real-world implementation of universal GGT for patients with breast cancer and genetics-informed, treatment decision-making in a rural, community practice with limited resources. METHODS: From 2019 to 2022, all patients with breast cancer at a small, rural hospital were offered GGT, using a genetics-extender model. Statistical analyses included Fisher's exact test, t-tests, and calculation of odds ratios. Significance was set at p < 0.05. RESULTS: Of 210 patients with breast cancer who were offered GGT, 192 (91.4%) underwent testing with 104 (54.2%) in-criteria (IC) and 88 (45.8%) out-of-criteria (OOC) with NCCN guidelines. Pathogenic germline variants were identified in 25 patients (13.0%), with PGV frequencies of 15 of 104 (14.4%) in IC and ten of 88 (11.4%) in OOC patients (p = 0.495). GGT informed treatment for 129 of 185 (69.7%) patients. CONCLUSIONS: Universal GGT was successfully implemented in a rural, community practice with > 90% uptake. Treatment was enhanced or de-escalated in those with and without clinically actionable PGVs, respectively. Universal GGT for patients with breast cancer is feasible within rural populations, enabling optimization of clinical care to patients' genetic profile, and may reduce unnecessary healthcare, resource utilization.

EEG Dataset Collection for Mental Workload Predictions in Flight-Deck Environment.

High mental workload reduces human performance and the ability to correctly carry out complex tasks. In particular, aircraft pilots enduring high mental workloads are at high risk of failure, even with catastrophic outcomes. Despite progress, there is still a lack of knowledge about the interrelationship between mental workload and brain functionality, and there is still limited data on flight-deck scenarios. Although recent emerging deep-learning (DL) methods using physiological data have presented new ways to find new physiological markers to detect and assess cognitive states, they demand large amounts of properly annotated datasets to achieve good performance. We present a new dataset of electroencephalogram (EEG) recordings specifically collected for the recognition of different levels of mental workload. The data were recorded from three experiments, where participants were induced to different levels of workload through tasks of increasing cognition demand. The first involved playing the N-back test, which combines memory recall with arithmetical skills. The second was playing Heat-the-Chair, a serious game specifically designed to emphasize and monitor subjects under controlled concurrent tasks. The third was flying in an Airbus320 simulator and solving several critical situations. The design of the dataset has been validated on three different levels: (1) correlation of the theoretical difficulty of each scenario to the self-perceived difficulty and performance of subjects; (2) significant difference in EEG temporal patterns across the theoretical difficulties and (3) usefulness for the training and evaluation of AI models.

Chemical Characterization of Phoenix dactylifera L. Seeds and their Beneficial Effects on the Vascular Response in Hypertensive Rats.

Although Phoenix dactylifera dates are traditionally consumed for their health benefits, no research has been done on the vascular response in hypertensive animals. This study evaluated the vascular relaxation of hydroalcoholic extracts from seeds of three varieties of P. dactylifera; Sukkari seed (SS), Ajwa seed (AS), and Mabroom seed (MS) on L-NAME-induced hypertension and spontaneously hypertensive rats (SHR). Results showed that all extracts (10 µg/mL) caused relaxations higher than 60% in the aortic rings precontracted with 10- 6 M phenylephrine in normotensive rats, the SS extract was the most potent. Endothelial nitric oxide (NO) pathway is involved as significantly reduced vascular relaxation in denuded-endothelium rat aorta and with an inhibitor (10- 4 M L-Nω-Nitro arginine methyl ester; L-NAME) of endothelial nitric oxide synthase (eNOS). Confocal microscopy confirmed that 10 µg/mL SS extract increases NO generation as detected by DAF-FM fluorescence in intact aortic rings. Consistent with these findings, vascular relaxation in intact aortic rings at 10 µg/mL SS extract was significantly decreased in L-NAME-induced hypertensive rats (endothelial dysfunction model), but not in SHR. In both hypertensive models, the denuded endothelium blunted the vascular relaxation. In conclusion, the hydroalcoholic extract of the seed of P. dactylifera (Sukkari, Ajwa and Mabroom varieties) presents a potent endothelium-dependent vascular relaxation, via NO, in normotensive rats as well as in two different models of hypertension. This effect could be mediated by the presence of phenolic compounds identified by UHPLC-ESI-MS/MS, such as protocatechuic acid, and caftaric acid.

The effect of tyrosine supplementation on whole-body endurance performance in physically active population: A systematic review and meta-analysis including GRADE qualification.

Although tyrosine supplementation is well recognized to improve cognitive function, its impact on endurance performance is debatable and needs to be clarified further. The purpose of this systematic review and meta-analysis was to evaluate the effects of tyrosine supplementation on whole-body endurance performance in physically active population. The search strategy follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), using four databases (Cochrane Library, Web of Science, Scopus, PsycINFO, and PubMed) until 3 August 2023. The effect of tyrosine (experimental condition) was compared against placebo (control condition). The methodological quality of the included studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE Pro software) System was also used to assess the quality of evidence. A total of 10 interventions from 8 studies were included. The sub-group analysis revealed no significant differences between tyrosine and placebo conditions for time to exhaustion (SMD = 0.02; p = 0.94) and time trial performance (SMD = -0.04; p = 0.85). The level of evidence as qualified with GRADE was moderate. In conclusion, moderate-quality evidence suggests that tyrosine supplementation is ineffective on endurance performance in the physically active population, independently of the endurance task (TTE or ETT).

Unbiased MD simulations identify lipid binding sites in lipid transfer proteins.

The characterization of lipid binding to lipid transfer proteins (LTPs) is fundamental to understand their molecular mechanism. However, several structures of LTPs, and notably those proposed to act as bridges between membranes, do not provide the precise location of their endogenous lipid ligands. To address this limitation, computational approaches are a powerful alternative methodology, but they are often limited by the high flexibility of lipid substrates. Here, we develop a protocol based on unbiased coarse-grain molecular dynamics simulations in which lipids placed away from the protein can spontaneously bind to LTPs. This approach accurately determines binding pockets in LTPs and provides a working hypothesis for the lipid entry pathway. We apply this approach to characterize lipid binding to bridge LTPs of the Vps13-Atg2 family, for which the lipid localization inside the protein is currently unknown. Overall, our work paves the way to determine binding pockets and entry pathways for several LTPs in an inexpensive, fast, and accurate manner.

Optimizing the Release Pattern of Telenomus podisi for Effective Biological Control of Euschistus heros in Soybean.

An augmentative biological control program using the egg parasitoid Telenomus podisi Ashmead (Hymenoptera: Platygastridae) is a promising tool for the management of the brown stink bug, Euschistus heros (Fabricius) (Hemiptera: Pentatomidae) in soybeans. The T. podisi are released as adults or pupae within lab-reared E. heros eggs. Because of the small size of the parasitoid and potentially limited dispersal ability, determining the optimal release pattern is critical for biological control of the target pest. This study used sentinel E. heros eggs to investigate T. podisi dispersal within soybean crops during two distinct phenological stages: the beginning of flowering (Vn-R1) and the grain-filling phase (R5-R6). Data were analyzed using semi-variograms and kriging maps. The results indicate significant differences in parasitism rates between the two plant growth stages and among different matrices. The maximum dispersal range for T. podisi was calculated at 39.0 m in the Vn-R1 stage with a maximum parasitism rate of 42%, while in the R5-R6 stage, the maximum dispersal range was calculated to be 30.9 m with a maximum parasitism of 73%. Therefore, it is recommended that release points for T. podisi be spaced no further than 30 m apart. These results provide valuable insights for future research and applications in biological control strategies, including adjustment of the logistics and release technique depending upon the crop phenological stage.

A new oxime synthesized from Senecio nutans SCh. Bip (chachacoma) reduces calcium influx in the vascular contractile response in rat aorta.

Senecio nutans Sch. Bip is an endemic plant commonly employed in the Andes culture to counteract the effects of mountain sickness, and its bioactive molecules could provide new drugs for treating hypertension. The purpose was to determine whether the vascular response of the plant bioactive molecules, such as (5-acetyl-6-hydroxy-2-isopropenyl-2,3-dihydrobenzofurane; Sn-I), could be improved by a simple structural modification to synthesize oximes (Ox-Sn-I). We characterized both compounds using IR and NMR spectroscopy and Heteronuclear Multiple Quantum Coherence (HMQC). We investigated vascular relaxation mechanisms in response to Sn-I and Ox-Sn-I using rat aorta and vascular smooth muscle cells (A7r5) as experimental models. Preincubation of aortic rings with Sn-I (10-5 M) significantly (p < 0.001) decreased the contractile effect in response to phenylephrine (PE) and potassium chloride (KCl). The sensitivity (EC50) to PE significantly (p < 0.01) decreased in the presence of Sn-I (10-5 M), but not with Ox-Sn-I. Sn-I significantly (p < 0.001) reduced the PE-induced contraction under calcium-free conditions. When A7r5 cells were preincubated with Sn-I and Ox-Sn-I (10-5 M), both compounds blunted the increase in intracellular Ca2+ induced by KCl. 2,3-Dihydrobenzofurane derived from S. nutans (Sn-I) reduces the contractile response probably by blocking Ca2+ entry through voltage-gated Ca2+ channels (VGCC) in vascular smooth cells. This effect also causes relaxation in rat aorta mediated by reduction of intracellular Ca2+ concentration, rather than an increase of NO generation in endothelial vascular cells.

Phenology of five tick species in the central Great Plains.

The states of Kansas and Oklahoma, in the central Great Plains, lie at the western periphery of the geographic distributions of several tick species. As the focus of most research on ticks and tick-borne diseases has been on Lyme disease which commonly occurs in areas to the north and east, the ticks of this region have seen little research attention. Here, we report on the phenology and activity patterns shown by tick species observed at 10 sites across the two states and explore factors associated with abundance of all and life specific individuals of the dominant species. Ticks were collected in 2020-2022 using dragging, flagging and carbon-dioxide trapping techniques, designed to detect questing ticks. The dominant species was A. americanum (24098, 97%) followed by Dermacentor variabilis (370, 2%), D. albipictus (271, 1%), Ixodes scapularis (91, <1%) and A. maculatum (38, <1%). Amblyomma americanum, A. maculatum and D. variabilis were active in Spring and Summer, while D. albipictus and I. scapularis were active in Fall and Winter. Factors associated with numbers of individuals of A. americanum included day of year, habitat, and latitude. Similar associations were observed when abundance was examined by life-stage. Overall, the picture is one of broadly distributed tick species that shows seasonal limitations in the timing of their questing activity.

Chemical Composition, Antioxidant Activities, Antidepressant Effect, and Lipid Peroxidation of Peruvian Blueberry: Molecular Docking Studies on Targets Involved in Oxidative Stress and Depression.

Blueberries (Vaccinium corymbosum L.) are cultivated worldwide and are among the best dietary sources of bioactive compounds with beneficial health effects. This study aimed to investigate the components of Peruvian blueberry using high-performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS/MS), identifying 11 compounds. Furthermore, we assessed in vitro the antioxidant activity and in vivo the antidepressant effect using a rat model and protective effect on lipid peroxidation (in the serum, brain, liver, and stomach). We also conducted molecular docking simulations with proteins involved in oxidative stress and depression for the identified compounds. Antioxidant activity was assessed by measuring total phenolic and flavonoid contents, as well as using 1,1-diphenyl-2-picrylhydrazin (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS•+), and ferric-reducing antioxidant power (FRAP) assays. Peruvian blueberries demonstrated higher antioxidant activity than Vaccinium corymbosum fruits from Chile, Brazil, the United States, Turkey, Portugal, and China. The results showed that oral administration of Peruvian blueberries (10 and 20 mg/kg) for 28 days significantly (p < 0.001) increased swimming and reduced immobility in the forced swimming test (FST). Additionally, at doses of 40 and 80 mg/kg, oxidative stress was reduced in vivo (p < 0.001) by decreasing lipid peroxidation in brain, liver, stomach, and serum. Molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions were performed. In the molecular docking studies, quercitrin and 3,5-di-O-caffeoylquinic acid showed the best docking scores for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase, and xanthine oxidase; while 3,5-dicaffeoylquinic acid methyl ester and caffeoyl coumaroylquinic acid had the best docking scores for monoamine oxidase and serotonin receptor 5-HT2. In summary, our results suggest that the antidepressant and protective effects against lipid peroxidation might be related to the antioxidant activity of Peruvian Vaccinium corymbosum L.

From gut to placenta: understanding how the maternal microbiome models life-long conditions.

The microbiome -defined as the microbiota (bacteria, archaea, lower and higher eukaryotes), their genomes, and the surrounding environmental conditions- has a well-described range of physiological functions. Thus, an imbalance of the microbiota composition -dysbiosis- has been associated with pregnancy complications or adverse fetal outcomes. Although there is controversy about the existence or absence of a microbiome in the placenta and fetus during healthy pregnancy, it is known that gut microbiota can produce bioactive metabolites that can enter the maternal circulation and may be actively or passively transferred through the placenta. Furthermore, the evidence suggests that such metabolites have some effect on the fetus. Since the microbiome can influence the epigenome, and modifications of the epigenome could be responsible for fetal programming, it can be experimentally supported that the maternal microbiome and its metabolites could be involved in fetal programming. The developmental origin of health and disease (DOHaD) approach looks to understand how exposure to environmental factors during periods of high plasticity in the early stages of life (e.g., gestational period) influences the program for disease risk in the progeny. Therefore, according to the DOHaD approach, the influence of maternal microbiota in disease development must be explored. Here, we described some of the diseases of adulthood that could be related to alterations in the maternal microbiota. In summary, this review aims to highlight the influence of maternal microbiota on both fetal development and postnatal life, suggesting that dysbiosis on this microbiota could be related to adulthood morbidity.

Multiple switching between the biosimilar adalimumab PF-06410293 and reference adalimumab in patients with active rheumatoid arthritis: a phase 3, open-label, randomised, parallel-group study.

BACKGROUND: An adalimumab biosimilar with an interchangeability designation could increase access to effective treatment for more patients. We aimed to assess the interchangeability of adalimumab biosimilar PF-06410293 (adalimumab-afzb) and reference adalimumab using a multi-switch study design. METHODS: We did an open-label, randomised, parallel-group study at 61 community (n=29), hospital (n=12), and academic (n=20) sites in ten countries (Bulgaria, Bosnia and Herzegovina, Czech Republic, Lithuania, Poland, Russia, Serbia, South Africa, Ukraine, and USA). Eligible patients were aged 18-70 years and met the 2010 American College of Rheumatology-European League Against Rheumatism classification criteria for rheumatoid arthritis for at least 4 months with moderately to severely active rheumatoid arthritis, based on their physician's evaluation. Eligible patients had been receiving methotrexate for at least 12 weeks and been on a stable dose for at least 4 weeks before the first dose of study medication. All patients received subcutaneous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks) for 10 weeks before randomisation. At week 10, patients were randomly assigned (1:1) to either three switches between subcutaneous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks) and adalimumab-afzb (40 mg/0·8 mL [50 mg/mL] every 2 weeks; switching group), or continuous dosing with subcutanous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks; non-switching group) with stratification by bodyweight groups. Patients, investigators, and site personnel were not masked to treatment allocation. Primary endpoints were maximum observed serum concentration (Cmax) and area under plasma concentration-time curve (AUCτ) during weeks 30-32 in the pharmacokinetic population. Interchangeability was based on geometric mean ratios and corresponding 90% CIs within prespecified equivalence margins of 80-125% for both primary endpoints. Safety was analysed in all patients who received at least one dose of adalimumab-afzb or reference adalimumab. This trial is registered with ClinicalTrials.gov, NCT04230213. FINDINGS: Of the 569 patients assessed for eligibility between Jan 13, 2020, and June 22, 2021, 445 were enrolled, and 427 completed the first 10 weeks and were randomly assigned (213 to the switching group and 214 to the non-switching group). Participants had a median age of 56 years (IQR 46-63), 354 (83%) of 427 patients were women and 73 (17%) were men, and 422 (99%) were White. In the pharmacokinetic population (n=380), no clinically meaningful differences were observed in mean steady-state pharmacokinetic parameters between the switching and non-switching groups (geometric mean AUC 2237 µg × h/mL in the switching group and 2125 µg × h/mL in the non-switching group; Cmax 8·21 µg/mL in the switching group and 8·00 µg/mL in the non-switching group). Geometric mean ratios and 90% CIs for AUCτ (105·31, 89·16-124·39) and Cmax (102·56, 89·78-117·17) were within prespecified equivalence margins. No meaningful differences were observed in the proportion of patients who had serious adverse events (three [1%] of 213 patients in the switching group vs eight [4%] of 214 patients in the non-switching group), grade 3 or higher adverse events of special interest, discontinuations due to adverse events (eight [4%] vs nine [4%]), or immunogenic reactions in antidrug antibody-positive patients. No deaths were reported during the study. INTERPRETATION: The risk of multiple switches between reference adalimumab and adalimumab-afzb with respect to diminished efficacy (using pharmacokinetics as a surrogate) or safety is not greater than the risk of using reference adalimumab alone. FUNDING: Pfizer. VIDEO ABSTRACT.

Epidemiología y características clínicas de las mordeduras de serpientes venenosas en el norte de la Amazonía del Ecuador (2017-2021) / Epidemiology and clinical features of venomous snake bites in the Northern Amazon of Ecuador (2017-2021)

Introducción. En Ecuador, las mordeduras de serpientes venenosas son un problema de salud pública. Sin embargo, no existe información hospitalaria reciente desde la Amazonía. Objetivo. Analizar retrospectivamente las características clínico-epidemiológicas de las mordeduras de serpientes en pacientes ingresados en un hospital de la Amazonía del Ecuador. Materiales y métodos. Se llevó a cabo un estudio transversal en el hospital provincial de Nueva Loja (Sucumbíos), que colinda con Colombia, 2017-2021. La información sobre las variables demográficas, epidemiológicas y clínicas, y la condición al egreso hospitalario, se obtuvieron de la ficha epidemiológica del Ministerio de Salud Pública. Resultados. En cinco años se hospitalizaron 147 pacientes (29,4 por año), sin que se presentaran muertes. Corresponden a 26, 34, 32, 29 y 26 casos, en el 2017, 2018, 2019, 2020 y 2021, respectivamente. Según el sexo, los más afectados fueron los hombres (n=99; 67,3 %), según el grupo etario, los de 21 a 30 años (n=28; 19,0 %) y, según la raza, los de etnia mestiza (n=94; 63,9 %), estudiantes y agricultores. La mediana de edad fue de 28 años (rango: 4 a 81). Hubo mayor prevalencia en abril, junio y septiembre. Todos los accidentes fueron causados por serpientes Viperidae. Veinte (13,6 %) casos fueron leves, 90 (61,2 %), moderados, y 37 (25,2 %), graves. La mordedura fue más frecuente en los pies (45 casos). El 53,1 % recibió suero antiofídico antes de la hospitalización y en el 19,8 % de los pacientes se colocó un torniquete. La mediana de tiempo de llegada al hospital fue de 5 horas (rango: 1-192), y lo más frecuente fue entre 2 y 3 horas (41 casos). No se encontraron diferencias estadísticamente significativas según la gravedad del caso. Conclusiones. Se evidenció una gran prevalencia de mordeduras de serpientes en el norte de la región amazónica-Ecuador, con mayor incidencia en la estación lluviosa y todas causadas por Viperidae. Es importante resaltar la mortalidad nula. Las campañas informativas sobre prevención y primeros auxilios, como la desmotivación del uso de torniquetes, serían fundamentales para reducir los casos, especialmente, en los grupos vulnerables.

Introduction: In Ecuador, poisonous snakebites are a public health problem. However, there is no recent hospital information from the Amazon. Objective: To retrospectively analyse the clinical-epidemiological characteristics of snakebites in patients admitted to a hospital in the Ecuadorian Amazon. Materials and methods: This is a cross-sectional study conducted at the Nueva Loja-Sucumbíos Provincial Hospital, bordering Colombia (2017-2021). Demographic, epidemiological and clinical variables, and condition at hospital discharge, were obtained from the epidemiological file of the Ministerio de Salud Pública. Results: In 5 years, 147 patients (29.4 per year) were hospitalized with no mortality. They corresponded to 26, 34, 32, 29 and 26 cases, in 2017, 2018, 2019, 2020 and 2021, respectively. Men with 99 (67.3%), aged 21-30 years with 28, mixed race with 94 cases, students, and farmers, were the most affected. The most affected (99; 67.3%) were men, people 21 to 30 years-old (28; 19.0%), mestizos (94; 63.9%), students, and farmers. The median age was 28 (range: 4-81) years. Prevalence was higher in April, June, and September. All accidents were caused by Viperidae snakes. Twenty (13.6%) cases were mild, (61.2%) were moderate and 37 (25.2%) were severe. The feet with 45 were the most bitten. Pre-hospitalization anti-venom serum was received by 53.1% and tourniquet by 19.8% patients. Median hospital arrival time was 5 (range 1-192) hours, mostly between 2-3 hours with 41 cases. No statistically significant differences were found considering the severity. Conclusions: A high prevalence of snakebites was evidenced in the north of the Amazon in Ecuador, with a higher incidence in the rainy season and all by Viperidae species. It is important to highlight the null mortality. Information campaigns on prevention and first aid, such as discouraging the use of tourniquets, especially among vulnerable groups.

Asociación entre el Material Particulado y la Función Pulmonar durante el Ejercicio en Sujetos Físicamente Activos / Association between particulate matter and lung function during exercise in physically active subjects

Introducción: El material particulado (MP) es una mezcla de partículas potencialmente peligrosas debido a su capacidad de penetrar el sistema respiratorio. La cantidad de MP que ingresa al organismo depende de su concentración ambiental, tiempo de exposición y la ventilación pulmonar. Esta última aumenta fisiológicamente durante el ejercicio físico. Objetivo: Determinar la asociación entre el MP y la función pulmonar. Métodos: Los participantes completaron un protocolo de actividad física en condiciones ambientales con concentraciones de MP habituales durante 4 días consecutivos (24-km). La función pulmonar fue evaluada antes (día-0) y después de una exposición aguda (día-1, post 6-km) y exposición prolongada (día-4, post 24-km). Para determinar la correlación entre los niveles de MP y las variables de función pulmonar, se aplicó la prueba de correlación de Spearman. El nivel de significancia se estableció en p<0.05. Resultados: La función pulmonar, evaluada a través de las variables de espirometría de volumen espiratorio forzado al primer segundo (VEF1), su relación con la capacidad vital forzada (VEF1/CVF) y flujo espiratorio medio (FEF25-75%), se asoció inversamente con las concentraciones de MP en el día-1 (p<0.05), pero no en el día-4 (p>0.05). Conclusión: Este estudio encontró que a mayor dosis efectiva de MP inhalado, mayor es la disminución en variables de función pulmonar evaluadas con espirometría. Este efecto fue más notorio posterior a la exposición aguda que a la exposición prolongada, infiriendo una posible habituación por parte del sistema respiratorio a la inhalación permanente de material particulado.

Introduction: Particulate matter (PM) is a mixture of potentially dangerous particles due to its ability to penetrate the respiratory system. The amount of PM that enters the body depends on its environmental concentration, the exposure time and pulmonary ventilation. The latter increase physiologically during physical exercise. Objective: To determine the association between MP and lung function in physically active young adults during physical exercise. Methods: the subjects completed a physical activity protocol in environmental conditions with habitual PM concentrations for four consecutive days (24-km). Lung function was evaluated before (day-0) and after acute exposure (day-1, post-6-km) and prolonged exposure (day-4, post-24-km). To determine the correlation between MP levels and lung function variables, the Spearman correlation test was applied. The level of significance was established at p <0.05. Results: Lung function, evaluated through the spirometry variables of forced expiratory volume in the first second (FEV1), its relationship with forced vital capacity (FEV1 / FVC) and mean expiratory flow (FEF25-75%) was inversely associated with MP concentrations on day-1 (p<0.05), but not on day-4 (p>0.05). Conclusion: This study found that the higher the effective dose of inhaled PM, the greater the decrease in lung function variables evaluated with spirometry. This effect is more noticeable after acute exposure than after prolonged exposure, inferring the respiratory system's possible habituation to permanent inhalation of particulate matter.

Terapia endoscópica combinada en hemorragia diverticular de colon / Combined endoscopic therapy for colonic diverticular bleeding

La hemorragia diverticular es la causa más frecuente de hemorragia digestiva baja. La hemorragia es abrupta, indolora, abundante. La mayoría de los divertículos que sangran se localizan en el lado derecho, este sangrado se autolimita hasta en un 80% de los casos. Cuando no se autolimita su manejo puede llegar a ser complejo. El manejo de estos sangrados, pueden variar desde conservador, endoscópico, arteriografía más embolización y el quirúrgico. Entre las alternativas de manejo endoscópico, tenemos la terapia de inyección, la térmica, hemoclips, ligadura con banda. El presente caso es de un paciente con hemorragia diverticular en el que se realizó terapia endoscopica combinada, infiltración de adrenalina, aplicación indirecta de hemoclips y aplicación tópica de ácido tranexámico que es un antifibrinolítico.

Diverticular bleeding is the most common cause of lower GI bleeding. The bleeding is most often abrupt, painless and abundant. Most of the bleeding diverticula are located on the right side of the colon, this bleeding is self-limited in up to 80% of cases. When it is not, it could turn into a difficult situation to manage. The management of these bleeds can vary from conservative to an endoscopic, arteriography plus embolization and surgical. Among the endoscopic management alternatives, we have injection therapy, thermal therapy, hemoclips, band ligation. The present case is about a patient with diverticular bleeding who underwent combined endoscopic therapy, adrenaline infiltration, indirect application of hemoclips, and topical application of tranexamic acid, which is an antifibrinolytic.

Osteocondroma de patela. Reporte de caso / Patellar osteochondroma. Case report

Los osteocondromas son tumores benignos frecuentes en la niñez, usualmente localizados en la metáfisis de los huesos y se van alejando de la fisis a medida que se da el crecimiento. Los osteocondromas de patela son poco comunes, refiriéndonos a su ubicación. El objetivo es informar un raro caso de un paciente escolar quien presento este tumor en su rótula derecha.

Osteochondromas are frequent benign tumors in childhood, usually located in bone metaphysis from where they recede from the physis as growth occurs. Osteochondromas of the patella are rare as this location is unfrequent. The objective is to report a rare case of a school patient who presented this tumor in his right patella.