AI-Guided Design of MALDI Matrices: Exploring the Electron Transfer Chemical Space for Mass Spectrometric Analysis of Low-Molecular-Weight Compounds.

The development of matrices for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI MS) has traditionally relied on experimental efforts. Here, we propose a Goal-Directed artificial intelligence generative model, fueled by computational chemistry calculated data, to construct a chemical space optimized for Electron Transfer (ET) processes in MALDI analysis. We utilized a group of 30 reported ET matrices, subjected to structural enumeration and molecular properties prediction using semiempirical and ab initio calculations, to establish a comprehensive database comprising diverse structural and property data. Subsequently, employing a protocol of structural enumeration with 68 canonical SMILES of Bemis-Murcko (BM) fragments, we expanded the structural complexity of the initial library. This process generated 82753 compounds organized into 10 scaffold levels, with a p50 index from the Cyclic System Retrieval (CSR) curve of scaffolds of 50%. From the resulting enumerated library, a diverse subset of structures was selected by using the Jarvis-Patrick clustering method. These structures, along with their associated properties measured from quantum mechanics and experimental data, were used to train a Machine Learning (ML) model to predict ionization energy (Ei) values. Subsequently, a Scoring Neural Network (SNN), coupled with our Goal-Directed generative model using a Recurrent Neural Network (RNN) with Deep Learning (DL) architectures, was trained. The generative model was guided using a prior network within a Reinforcement/Transfer Learning environment. The final AI-generative model learned that structures with high unsaturation, H/C ratios under 1, and molecular weights between 100 and 300 u are favorable for ET MALDI matrices, as well as those with few aromatic rings and zero aliphatic rings. Other molecular features were also favored. The resulting AI-generated library exhibits Ei values over 8.0 eV, akin to those of reported "good" ET MALDI matrices, indicating successful design with high synthesis accessibility scores. In conclusion, our generative model provided valuable insights into the molecular features ideal for ET MALDI compounds while generating a wide range of structurally diverse molecules within a similar molecular property space. The next critical step in this process is to synthesize a selection of these generated compounds for the experimental validation and further characterization.

Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li2CO3) in an In Vitro Cervical Cancer Model.

Lithium, a natural element, has been employed as a mental stabilizer in psychiatric treatments; however, some reports indicate it has an anticancer effect, prompting the consideration of repurposing lithium for cancer treatment. The potential anticancer use of lithium may depend on its form (salt type) and the type of cancer cells targeted. Little is known about the effects of Li2CO3 or LiCl on cancer cells, so we focused on exploring their effects on proliferation, apoptosis, migration, and cell cycle as part of the hallmarks of cancer. Firstly, we established the IC50 values on HeLa, SiHa, and HaCaT cells with LiCl and Li2CO3 and determined by crystal violet that cell proliferation was time-dependent in the three cell lines (IC50 values for LiCl were 23.43 mM for SiHa, 23.14 mM for HeLa, and 15.10 mM for HaCaT cells, while the IC50 values for Li2CO3 were 20.57 mM for SiHa, 11.52 mM for HeLa, and 10.52 mM for HaCaT cells.) Our findings indicate that Li2CO3 and LiCl induce DNA fragmentation and caspase-independent apoptosis, as shown by TUNEL, Western Blot, and Annexin V/IP assay by flow cytometry. Also, cell cycle analysis showed that LiCl and Li2CO3 arrested the cervical cancer cells at the G1 phase. Moreover, lithium salts displayed an anti-migratory effect on the three cell lines observed by the wound-healing assay. All these findings imply the viable anticancer effect of lithium salts by targeting several of the hallmarks of cancer.

Comparative profiling of Chlorella vulgaris cells, extracts, and intact chloroplasts using electron transfer matrix-assisted laser desorption/ionization mass spectrometry (ET-MALDI-MS).

The intricate composition of microalgal pigments plays a crucial role in various biological processes, from photosynthesis to biomarker identification. Traditional pigment analysis methods involve complex extraction techniques, posing challenges in maintaining analyte integrity. In this study, we employ Electron Transfer Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (ET-MALDI-MS) to compare the pigmentary profiles of Chlorella vulgaris intact cells, chloroplasts, and solvent extracts. We aim to obtain comprehensive extracts rich in polar and non-polar compounds using ultrasound-assisted and supercritical fluid extraction methods. Additionally, intact chloroplasts are isolated using a lysis buffer and sucrose density gradient centrifugation. Our ET-MALDI-MS analysis reveals distinct compositional differences, highlighting the impact of extraction protocols on microalgal pigment identification. We observe prominent signals corresponding to radical cations of key pigments, including chlorophylls and carotenoids, which are crucial for C. vulgaris identification. Furthermore, ET-MALDI-MS facilitates the identification of specific lipids within chloroplast membranes and other organelles. This study underscores the rapid and precise nature of ET-MALDI-MS in microalgal biomarker analysis, providing valuable insights into phytoplankton dynamics, trophic levels, and environmental processes. C. vulgaris emerges as a promising model for studying pigment composition and membrane lipid diversity, enhancing our understanding of microalgal ecosystems.

Antitumoral and Antimetastatic Activity by Mixed Chelate Copper(II) Compounds (Casiopeínas®) on Triple-Negative Breast Cancer, In Vitro and In Vivo Models.

Triple-negative breast cancer (TNBC), accounting for 15-20% of all breast cancers, has one of the poorest prognoses and survival rates. Metastasis, a critical process in cancer progression, causes most cancer-related deaths, underscoring the need for alternative therapeutic approaches. This study explores the anti-migratory, anti-invasive, anti-tumoral, and antimetastatic effects of copper coordination compounds Casiopeína IIIia (CasIIIia) and Casiopeína IIgly (CasIIgly) on MDA-MB-231 and 4T1 breast carcinoma cell lines in vitro and in vivo. These emerging anticancer agents, mixed chelate copper(II) compounds, induce apoptosis by generating reactive oxygen species (ROS) and causing DNA damage. Whole-transcriptome analysis via gene expression arrays indicated that subtoxic concentrations of CasIIIia upregulate genes involved in metal response mechanisms. Casiopeínas® reduced TNBC cell viability dose-dependently and more efficiently than Cisplatin. At subtoxic concentrations (IC20), they inhibited random and chemotactic migration of MDA-MB-231 and 4T1 cells by 50-60%, similar to Cisplatin, as confirmed by transcriptome analysis. In vivo, CasIIIia and Cisplatin significantly reduced tumor growth, volume, and weight in a syngeneic breast cancer model with 4T1 cells. Furthermore, both compounds significantly decreased metastatic foci in treated mice compared to controls. Thus, CasIIIia and CasIIgly are promising chemotherapeutic candidates against TNBC.

Caracterización clínico-epidemiológica y agentes etiológicos de las infecciones respiratorias agudas graves en adultos en Paraguay

Introducción: La Vigilancia Centinela de las Infecciones Respiratorias Agudas Graves (IRAG) incluye el monitoreo y caracterización de casos hospitalizados. Objetivo: Describir las características clínico-epidemiológicas y agentes etiológicos de los adultos con IRAG en un hospital centinela en Paraguay. Metodología: Estudio observacional, descriptivo, de corte transversal, con recolección de datos retrospectivos de los pacientes adultos con IRAG hospitalizados en el Hospital Nacional de Itauguá entre junio de 2022 a agosto de 2023. La información se tomó de la base de datos del Sistema Nacional de Vigilancia Epidemiológica. Resultados: Se analizaron los datos de 1598 pacientes con IRAG, 820 varones (51,3%), 875 (54,8%) con 60 o más años, 1054 (66,0%) del departamento Central. El 79.2% (n=1265) de los pacientes presentaba algún factor de riesgo de gravedad o comorbilidad, 764 (47,8%) con hipertensión arterial. El 38.5% (n=632) fue admitido a UCI y la mortalidad fue de 34,7% (n=554). En el 13,8% (n=353) se confirmó SARSCoV-2, rhinovirus (1,7%), influenza A (1,5%), influenza B (0,6%), parainfluenza 3 (0,6%), VSR (0,2%), bocavirus (0,4%) e influenza AH1N1 (0,6%). Hubo significativamente mayor frecuencia de fallecidos en los de 60 años y más (40,7%), con algún factor de riesgo de gravedad (35,5% vs 25,9%) y en los confirmados con COVID-19 (38,2% vs 30,5%). Discusión: SARSCoV-2 sigue siendo el agente etiológico principal de las IRAG. El conocimiento de la epidemiología y los agentes virales es crucial para desarrollar estrategias de prevención y terapéuticas efectivas.

Introduction: Sentinel Surveillance of Severe Acute Respiratory Infections (SARI) includes the monitoring and characterization of hospitalized cases. Objective: To describe the clinical-epidemiological characteristics and etiological agents of adults with SARI in a sentinel hospital in Paraguay. Methodology: Observational, descriptive, cross-sectional study, with retrospective data collection, of adult patients with SARI hospitalized at the National Hospital of Itauguá between June 2022 and August 2023. The information was taken from the database of the National System of Epidemiological surveillance. Results: The data of 1598 patients with SARI were analyzed, 820 men (51.3%), 875 (54.8%) aged 60 or older, 1054 (66.0%) from the Central department. 79.2% (n=1265) of patients had some risk factor or comorbidity, 764 with hypertension (47.8%). 38.5% (n=632) were admitted to the ICU and mortality was 34.7% (n=554). SARSCoV-2 was confirmed in 13.8% (n=353), rhinovirus (1.7%), influenza A (1.5%), influenza B (0.6%), parainfluenza 3 (0.6%), RSV (0.2%), bocavirus (0.4%) and Influenza AH1N1 (0.6%). There was a significantly higher frequency of deaths in those aged 60 years and over (40.7%), with some risk factor (35.5% vs 25.9%), and in those confirmed with covid-19 (38.2% % vs 30.5%). Discussion: SARSCoV-2 continues to be the main etiological agent of SARI in a sentinel hospital in Paraguay. Continued knowledge of the epidemiology and viral agents involved is crucial to developing effective prevention and treatment strategies.

The Oxidative Potential of Airborne Particulate Matter Research Trends, Challenges, and Future Perspectives-Insights from a Bibliometric Analysis and Scoping Review.

This study is a comprehensive analysis of the oxidative potential (OP) of particulate matter (PM) and its environmental and health impacts. The researchers conducted a bibliometric analysis and scoping review, screening 569 articles and selecting 368 for further analysis. The study found that OP is an emerging field of study, with a notable increase in the number of publications in the 2010s compared to the early 2000s. The research is primarily published in eight journals and is concentrated in a few academic and university-based institutions. The study identified key research hotspots for OP-PM, emphasizing the importance of capacity building, interdisciplinary collaboration, understanding emission sources and atmospheric processes, and the impacts of PM and its OP. The study highlighted the need to consider the effects of climate change on OP-PM and the regulatory framework for PM research. The findings of this study will contribute to a better understanding of PM and its consequences, including human exposure and its effects. It will also inform strategies for managing air quality and protecting public health. Overall, this study provides valuable insights into the field of OP-PM research and highlights the need for continued research and collaboration to address the environmental and health impacts of PM.

A Survey of MPSoC Management toward Self-Awareness.

Managing Multi-Processor Systems-on-Chip (MPSoCs) is becoming increasingly complex as demands for advanced capabilities rise. This complexity is due to the involvement of more processing elements and resources, leading to a higher degree of heterogeneity throughout the system. Over time, management schemes have evolved from simple to autonomous systems with continuous control and monitoring of various parameters such as power distribution, thermal events, fault tolerance, and system security. Autonomous management integrates self-awareness into the system, making it aware of its environment, behavior, and objectives. Self-Aware Cyber-Physical Systems-on-Chip (SA-CPSoCs) have emerged as a concept to achieve highly autonomous management. Communication infrastructure is also vital to SoCs, and Software-Defined Networks-on-Chip (SDNoCs) can serve as a base structure for self-aware systems-on-chip. This paper presents a survey of the evolution of MPSoC management over the last two decades, categorizing research works according to their objectives and improvements. It also discusses the characteristics and properties of SA-CPSoCs and explains why SDNoCs are crucial for these systems.

Hormones and B-cell development in health and autoimmunity.

The development of B cells into antibody-secreting plasma cells is central to the adaptive immune system as they induce protective and specific antibody responses against invading pathogens. Various studies have shown that, during this process, hormones can play important roles in the lymphopoiesis, activation, proliferation, and differentiation of B cells, and depending on the signal given by the receptor of each hormone, they can have a positive or negative effect. In autoimmune diseases, hormonal deregulation has been reported to be related to the survival, activation and/or differentiation of autoreactive clones of B cells, thus promoting the development of autoimmunity. Clinical manifestations of autoimmune diseases have been associated with estrogens, prolactin (PRL), and growth hormone (GH) levels. However, androgens, such as testosterone and progesterone (P4), could have a protective effect. The objective of this review is to highlight the links between different hormones and the immune response mediated by B cells in the etiopathogenesis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). The data collected provide insights into the role of hormones in the cellular, molecular and/or epigenetic mechanisms that modulate the B-cell response in health and disease.

Cobertura de vacunación contra COVID-19 e influenza en personal de salud y administrativo en Paraguay

Introducción: A nivel mundial, la cobertura de vacunación contra el COVID-19, así como contra la influenza es baja tanto en la población general como en los profesionales de la salud a pesar de que la vacuna es gratuita y obligatoria en el personal sanitario. Objetivo: Describir la cobertura de vacunación contra el COVID -19, y la influenza en personal de salud y administrativo de un hospital de referencia del Ministerio de Salud Pública y Bienestar Social en el periodo 2021-2022. Metodología: Estudio observacional descriptivo de corte trasverso. Se hizo la revisión de los registros del personal sanitario y administrativo del centro vacunatorio del Hospital Nacional de Itauguá de la campaña vacunal contra el COVID-19 y de anti-influenza en el periodo 2021- 2022. Resultados: De los 3.586 funcionarios, 999 (27,9 %) eran médicos, 1494 (41,7 %) personal de enfermería, 366 (10,2 %) otra categoría de personal sanitario, y 727 (20,3 %) personal administrativo. En forma global, el 86,5 % de los funcionarios recibió por lo menos las dos dosis que constituyen el esquema primario y el 73 % la dosis de refuerzo. El 2,1 % del personal no recibió ninguna dosis de vacuna anti covid-19, la cifra fue mayor en el personal administrativo (4,8 %). La cobertura de vacunación contra la influenza fue de 20 % en el 2021 y 25 % en el 2022. Discusión: Si bien cobertura de vacunación anti-COVID-19 fue comparable a otros países, la vacunación contra la influenza fue muy baja. Es urgente implementar estrategias dirigidas a aumentar la percepción de riesgo y aceptabilidad de las vacunas obligatorias para el personal sanitario.

Introduction: Worldwide, vaccination coverage against COVID-19, as well as against influenza, is low both in the general population and in health professionals, despite the fact that the vaccine is free and mandatory for health personnel. Objective: To describe the COVID -19 and influenza vaccination coverage in health and administrative personnel of a reference hospital of the Ministry of Public Health and Social Welfare in the period 2021-2022. Methods: Cross-sectional descriptive observational study. Charts of the health and administrative personnel of the vaccination center of the Itauguá National Hospital of the COVID-19 and influenza vaccination campaign in the period 2021-2022 were reviewed. Results: Of the 3,586 personnel, 999 (27.9%) were medical personnel, 1,494 (41.7%) nursing personnel, 366 (10.2%) other category of health personnel, and 727 (20.3%) administrative personnel. Overall, 86.5% of the employees received at least the two doses that constitute the primary schedule and 73% the booster dose; 2.1% of the staff did not receive any dose of the anti COVID-19 vaccine, which was higher in the administrative staff (4.8%). Influenza vaccination coverage was 20% in 2021 and 25% in 2022. Discussion: Even though the vaccination coverage of anti-COVID-19 was comparable to other countries, vaccination anti-influenza was very low. It is urgent to implement strategies aimed at increasing the perception of risk and acceptability of mandatory vaccines for health personnel.

Determinación de tiempos quirúrgicos estándar de los procedimientos más comunes de cirugía general y su probabilidad de extensión para eficientizar la programación de cirugías / Estimation of the standard surgical times of the most common general surgery procedures and the probability of extending them to make surgery scheduling more efficient

RESUMEN Objetivo: Determinar los tiempos quirúrgicos estándar de los cuatro procedimientos más comunes en cirugía general (hernioplastia inguinal unilateral, hernioplastia inguinal bilateral, hernioplastia umbilical y colecistectomía) de un hospital de segundo nivel y calcular la probabilidad de extensión de cada uno de los procedimientos. La eficiencia es un fenómeno ampliamente estudiado en el ámbito económico, pues hace referencia a la necesidad de menor cantidad de factores para la producción de un determinado nivel de bienes y servicios, por ello, es de vital importancia incluirlo en el ámbito quirúrgico. Materiales y métodos: Estudio observacional, descriptivo y retrospectivo. Se utilizaron los registros de quirófano de un hospital de segundo nivel del año 2017 al 2019 del servicio de Cirugía General. A partir de esta información, se estandarizó el tiempo necesario para cada procedimiento mediante la media de cada uno (hernioplastia umbilical, hernioplastia inguinal unilateral o bilateral y colecistectomía). Se calculó la probabilidad de extensión de las cirugías tomando en consideración los datos obtenidos y el intervalo de confianza. Resultados: Para el procedimiento de hernioplastia inguinal unilateral se obtuvo una media de 76 min (IC 95,00 %: 72-80 min, DE 23); en hernioplastia inguinal bilateral, una media de 104,38 min (IC 95,00 %: 91-116 min, DE 41,7); en hernioplastia umbilical, una media de 59,31 min (IC 95,00 %: 54-63 min, DE 29,9), y en colecistectomía, una media de 85,735 min (IC 95,00 %: 83-88 min). La probabilidad de que se programen tres cirugías y todas estén a tiempo (límite superior del IC) es de 92,69 %, la probabilidad de que se programen tres cirugías y todas se prolonguen es de 0,0016 % (límite inferior del IC). Conclusiones: Es posible realizar la planeación de las cirugías programadas mediante el uso de tiempos quirúrgicos estandarizados. Se requiere contar con estadística actualizada de los procedimientos quirúrgicos (promedios del tiempo de realización de cada procedimiento), ya que es posible detectar y supervisar de manera más precisa la dinámica de quirófano mediante la detección de las áreas de oportunidad, de esta manera, se eficientizará el tiempo de quirófano para beneficio de los sistemas de salud y los pacientes.

ABSTRACT Objective: To determine the standard surgical times of the four most common general surgery procedures (unilateral inguinal hernioplasty, bilateral inguinal hernioplasty, umbilical hernioplasty and cholecystectomy) in a second-level hospital and to estimate the probability of extending the time of each of the procedures. Efficiency is a widely studied subject in economics. It involves the need for fewer elements in the production of a certain level of goods and services. Therefore, it is extremely important to consider it in the field of surgery. Materials and methods: An observational, descriptive and retrospective study. It used the operating room records from 2017 to 2019 of the General Surgery service in a second-level hospital. Based on this information, the time required for each procedure was standardized using the mean for each one (umbilical hernioplasty, unilateral or bilateral inguinal hernioplasty and cholecystectomy). The probability of extending surgical times was estimated based on the obtained data and confidence interval. Results: The mean for unilateral inguinal hernioplasty was 76 min (95.00 % CI: 72-80 min, SD 23), for bilateral inguinal hernioplasty 104.38 min (95.00 % CI: 91-116 min, SD 41.7), for umbilical hernioplasty 59.31 min (95.00 % CI: 54-63 min, SD 29.99) and for cholecystectomy 85.735 min (95.00 % CI: 83-88 min). The probability of scheduling three surgical interventions and completing all of them on time (upper limit of the CI) is 92.69 %, and the probability of scheduling three surgical interventions and extending the time of all of them is 0.0016 % (lower limit of the CI). Conclusions: Planning scheduled operations using standardized surgical times is feasible. Updated statistics on surgical procedures (average time for each procedure) are required since it is possible to more accurately detect and supervise operating room dynamics by identifying opportunity areas. This will make operating room time more efficient for the benefit of health care systems and patients.

In Silico Analysis of the Aromaticity of Some Carbo-Metallabenzenes and Carbo-Dimetallabenzenes (Carbo-mers Proposed from Metallabenzenes).

In the current work, we introduce a novel class of molecules termed carbo-metallabenzenes, and their aromaticity has been comprehensively analyzed. The molecules were strategically designed with the insertion of acetylene (C≡C or C2) units in some selected metallabenzenes. Furthermore, if a second metallic unit is inserted (replacing a sp2 carbon) in the carbo-metallabenzenes rings, a new family of carbo-mers is generated, and this second group has been named as carbo-dimetallabenzenes. The primary objective of this work is to ascertain, through various methodologies, whether these newly proposed molecules retain the aromatic characteristics observed in carbo-benzene. The methodologies employed for bond analysis and aromaticity exploration include the analysis of the molecular orbitals, energy decomposition analysis, electron density of delocalized bonds, magnetically induced current density, and the induced magnetic field (Bind). This study sheds light on that the insertion of the metallic centers reduces the electronic delocalization and their aromaticity is, in some cases, comparable with the electronic delocalization of the inorganic iminobora-borazine and also provides valuable insights into their electronic structure through a multifaceted analysis.

Systematic review and bioinformatics analysis of plasma and serum extracellular vesicles proteome in type 2 diabetes.

Background: Type 2 diabetes (T2D) is a complex metabolic ailment marked by a global high prevalence and significant attention in primary healthcare settings due to its elevated morbidity and mortality rates. The pathophysiological mechanisms underlying the onset and progression of this disease remain subjects of ongoing investigation. Recent evidence underscores the pivotal role of the intricate intercellular communication network, wherein cell-derived vesicles, commonly referred to as extracellular vesicles (EVs), emerge as dynamic regulators of diabetes-related complications. Given that the protein cargo carried by EVs is contingent upon the metabolic conditions of the originating cells, particular proteins may serve as informative indicators for the risk of activating or inhibiting signaling pathways crucial to the progression of T2D complications. Methods: In this study, we conducted a systematic review to analyze the published evidence on the proteome of EVs from the plasma or serum of patients with T2D, both with and without complications (PROSPERO: CRD42023431464). Results: Nine eligible articles were systematically identified from the databases, and the proteins featured in these articles underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We identified changes in the level of 426 proteins, with CST6, CD55, HBA1, S100A8, and S100A9 reported to have high levels, while FGL1 exhibited low levels. Conclusion: These proteins are implicated in pathophysiological mechanisms such as inflammation, complement, and platelet activation, suggesting their potential as risk markers for T2D development and progression. Further studies are required to explore this topic in greater detail.

An overview of air pollution research in Chile: Bibliometric analysis and scoping review, challenger and future directions.

This study provides a comprehensive overview and bibliometric analysis of air pollution research in Chile from 1980 to 2022. The analysis reveals a significant increase in scientific production, a 9.2 annual growth rate, and an H-index of 60. The research spans 33 countries and is influenced by environmental sciences, meteorology, and atmospheric sciences journals. The top ten authors account for 33.49 % of all publications, with local institutions contributing more than 35 %. The University of Chile and the Pontifical Catholic University of Chile are significant contributors. The most cited articles focus on health impacts and various pollutant sources, emphasizing air pollution as a critical public health concern. The study also emphasizes environmental science, meteorology, and atmospheric science, focusing on topics such as air pollution and health, pollutants, models, sources and chemistry, and social sciences. The findings are affirmed through rigorous discussion and review, providing a roadmap for future research, guiding decision-making processes, and expanding the knowledge frontier in the field.

Características clínicas y laboratoriales de pacientes adultos ambulatorios con Chikungunya del Hospital Nacional de Itauguá de Paraguay durante la epidemia 2022-2023

Introducción: La infección aguda por chikungunya produce una infección auto-limitada caracterizada principalmente por fiebre alta, artralgias, artritis, cefalea, mialgias y exantema pruriginoso; una minoría presenta síntomas persistentes que puede evolucionar a la cronicidad. Objetivo: describir las características clínicas y laboratoriales de pacientes adultos ambulatorios con chikungunya en un hospital de referencia durante la epidemia del 2022-2023 en Paraguay. Metodología: estudio descriptivo de corte trasversal de pacientes adultos con chikungunya que consultaron en el Hospital Nacional de Itauguá entre enero-marzo de 2023. Resultados: Se incluyeron 140 pacientes entre 19 y 79 años (edad media: 46,6±13,6), 77,9 % del sexo femenino y 89,3 % del departamento Central. El 72,9 % de los pacientes fueron confirmados por RT-PCR y el resto por la serología o nexo epidemiológico. El 48,6 % tenía alguna comorbilidad, el 65% se encontraba en la fase aguda, y el resto en la fase subaguda (35 %). Los síntomas más frecuentes fueron la poliartralgia (96,4 %); artritis (98,6 %), fiebre (95,7 %), astenia (100 %), mialgias (96,4 %), cefalea (82,9 %), exantema (95 %). Los síntomas gastrointestinales fueron menos frecuentes; náuseas (37 %), vómitos (15,7 %) y diarrea (20 %). Entre los principales hallazgos laboratoriales se encontraron la proteína C reactiva aumentada (45,7 %), leucopenia (23,6 %), eritrosedimentación aumentada (27,9 %), citólisis hepática leve (13,6 %). Todos fueron tratados con paracetamol; el 60,4 % y el 87,8 % de los pacientes en fase aguda y subaguda recibieron AINES, respectivamente. Discusión: La combinación de fiebre alta y artralgia severa fue el rasgo característico de la infección por el virus chikungunya en la epidemia en Paraguay.

Introduction: Acute infection by chikungunya produces a self-limited infection characterized mainly by high fever, arthralgia, arthritis, headache, myalgia and pruritic rash; a minority presents persistent symptoms that can evolve to chronicity. Objective: to describe the clinical and laboratory characteristics of adult ambulatory patients with chikungunya at a referral hospital during the 2022-2023 epidemic in Paraguay. Method: descriptive cross-sectional study of adult patients with chikungunya infection who consulted at the Hospital National de Itauguá between January-March 2023. Results: 140 patients between 19 and 79 years old (mean age: 46.6 ± 13.6), 77.9% female and 89.3% from the Central department, were included. 72.9% of the patients were confirmed by RT-PCR and the rest by serology or epidemiological nexus. 48.6% had some comorbidity, 65% were in the acute phase, and the rest in the subacute phase (35%). The most frequent symptoms were polyarthralgia (96.4%); arthritis (98.6%), fever (95.7%), fatigue (100%), myalgia (96.4%), headache (82.9%), rash (95%). Gastrointestinal symptoms were less frequent such as; nausea (37%), vomiting (15.7%) and diarrhea (20%). Increased C-reactive protein (45.7%), leukopenia (23.6%), increased erythrocyte sedimentation rate (27.9%), and mild hepatic cytolysis (13.6%) were among the main laboratory findings. All patients were treated with paracetamol; 60.4% and 87.8% of the patients in the acute and subacute phase, respectively, received NSAIDs. Discussion: The combination of high fever and severe arthralgia can be considered the characteristic feature of chikungunya virus infection in this epidemic.

Human Bone Marrow Mesenchymal Stem Cells Promote the M2 Phenotype in Macrophages Derived from STEMI Patients.

Acute ST-elevation myocardial infarction (STEMI) leads to myocardial injury or necrosis, and M1 macrophages play an important role in the inflammatory response. Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are capable of modulating macrophage plasticity, principally due to their immunoregulatory capacity. In the present study, we analyzed the capacity of MSCs to modulate macrophages derived from monocytes from patients with STEMI. We analyzed the circulating levels of cytokines associated with M1 and M2 macrophages in patients with STEMI, and the levels of cytokines associated with M1 macrophages were significantly higher in patients with STEMI than in controls. BM-MSCs facilitate the generation of M1 and M2 macrophages. M1 macrophages cocultured with MSCs did not have decreased M1 marker expression, but these macrophages had an increased expression of markers of the M2 macrophage phenotype (CD14, CD163 and CD206) and IL-10 and IL-1Ra signaling-induced regulatory T cells (Tregs). M2 macrophages from patients with STEMI had an increased expression of M2 phenotypic markers in coculture with BM-MSCs, as well as an increased secretion of anti-inflammatory cytokines and an increased generation of Tregs. The findings in this study indicate that BM-MSCs have the ability to modulate the M1 macrophage response, which could improve cardiac tissue damage in patients with STEMI.

The effects of female age on blood-feeding, insemination, sperm storage, and fertility in the dengue vector mosquito Aedes aegypti (Diptera: Culicidae).

Mating induces behavioral and physiological changes in female insects-collectively referred to as the female post-mating response (PMR)-that facilitate the production of progeny. PMRs are elicited by transfer of male-derived seminal components during mating, but are altered by other factors, including adult age. Increased female age is often accompanied by declines in fertility. However, mating shortly after emergence also impacts fertility in the insect model Drosophila melanogaster. Here, we determined the age post-emergence when females of the vector mosquito Aedes aegypti can be inseminated and blood-feed. We next examined fecundity, fertility, and the storage of sperm in the female reproductive tract in "young" (30-41 hours-old) and "old" (2- and 3-week-old) females, finding that blood-feeding began at 14 hours, and mating at ∼24 hours post-emergence. Although young females consumed smaller blood quantities and stored fewer sperm, they were similarly fertile to 4-day-old controls. Old females, however, suffered significant declines in fecundity by 2 weeks of age. Our results show that female Ae. aegypti start to become sexually receptive 1 day after their emergence, but can ingest blood much sooner, suggesting that mating is not a prerequisite to blood-feeding, and that females can ingest an arbovirus infected blood-meal shortly after emergence.

Moderately hypofractionated post-operative radiation therapy for breast cancer: preferences amongst radiation oncologists from countries in Latin America and the Caribbean.

Background: The safety and effectiveness of moderately hypofractionated post-operative radiation therapy for breast cancer were demonstrated by several trials. This study aimed to evaluate the current patterns of practice and prescription preference about moderately hypofractionated post-operative radiation therapy to assess possible aspects that affect the decision-making process regarding the use of fractionation in breast cancer patients in Latin America and the Caribbean (LAC). We also aimed to identify factors that can restrain the utilization of moderately hypofractionated post-operative radiation therapy for breast cancer. Materials an methods: Radiation oncologists from LAC were invited to contribute to this study. A 38-question survey was used to evaluate their opinions. Results: A total of 173 radiation oncologists from 13 countries answered the questionnaire. The majority of respondents (84.9%) preferred moderately hypofractionated post-operative radiation therapy as their first choice in cases of whole breast irradiation. Whole breast plus regional nodal irradiation, post-mastectomy (chest wall and regional nodal irradiation) without reconstruction, and post-mastectomy (chest wall and regional node irradiation) with reconstruction hypofractionated post-operative radiation therapy was preferred by 72.2% 71.1%, and 53.7% of respondents, respectively. Breast cancer stage, and flap-based breast reconstruction were the factors associated with absolute contraindications for the use of hypofractionated schedules. Conclusion: Even though moderately hypofractionated post-operative radiation therapy for breast cancer is considered a new standard to the vast majority of the patients, its unrestricted application in clinical practice across LAC still faces reluctance.