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Cardiovascular diseases continue to be the main cause of death in Venezuela, and hypertension is the principal risk factor. The May Measurement Month (MMM) campaign is a global initiative aimed to raising awareness of hypertension, which has been conducted in Venezuela since 2017. May Measurement Month 2021 included 46 732 participants with a mean age of 56.4 years (SD 14.4), 57.9% of whom were female. The percentage with hypertension was 60.3% (57.9% of females and 63.7% of males), 82.3% (84.8% of females and 79.2% of males) were aware, and 80.2% were taking antihypertensive medication. Of those on antihypertensive medication, 44.2% (41.2% of females and 48.2% of males) were not controlled [blood pressure (BP) ≥ 140/≥90â mmHg], with 61.3% receiving one drug, 30.0% two drugs, and 8.7% three or more drugs. 87.5% of those on treatment reported taking it regularly. Conditions associated with higher BP levels include fewer years of education, having a previous diagnosis of hypertension, and women who were hypertensive during a previous pregnancy. Physical activity and pregnancy were conditions associated with lower BP levels. A previous positive COVID-19 test was reported in 11.1%, and one or more COVID-19 vaccinations reported in 22.7% of participants. Of those on antihypertensive medication, 78.8% reported their treatment was not affected by COVID-19. Results are consistent with previous MMM campaigns and indicate that the screening campaign is feasible and useful to identify hypertension even in exceptional conditions such as the COVID-19 pandemic.
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Racialized, deficit-oriented educational practices and inadequate safe spaces for youth undermine Communities of Color. We discuss our after-school program's framework, strategies, activities, and partnerships with community stakeholders, demonstrating that a collaborative, culturally responsive, strengths-based approach to mitigate trauma and enhance health and educational opportunities is essential for empowering Chicana/o/Latina/o youth and families.
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Hispánicos o Latinos , Humanos , Adolescente , Femenino , Masculino , Niño , Instituciones Académicas , Guyana/etnologíaRESUMEN
Hemorrhagic cholecystitis is an uncommon presentation of acute cholecystitis. Due to its etiology and unspecific clinical data, it is an entity that represents a diagnostic challenge. We present a case of a 70-year-old male with diabetes type 2, hypertension, and chronic kidney disease with hemodialysis, who attended the emergency department with sudden-onset abdominal pain in the epigastrium. The patient presented no additional symptoms, a normal electrocardiogram, but due to the characteristics of the pain and elevated troponin I, emergency medicine specialists considered an acute coronary syndrome and initiated antiplatelet and anticoagulant therapy. Due to persistent abdominal pain, a decrease in hemoglobin, and the onset of arterial hypotension, a computed tomography (CT) scan was performed, which revealed perforation of the gallbladder, apparent hemorrhagic cholecystitis, and hemoperitoneum. The patient underwent emergent surgery, where CT findings were confirmed. In our case, the suspicion of hemorrhagic cholecystitis arose until the clinical case was advanced, after receiving anticoagulant and antiplatelet therapy, and it was confirmed during surgery and with histopathology. This concludes that hemorrhagic cholecystitis is a rare disease and difficult to diagnose. Therefore, studies should focus on clinical presentation and risk factors (e.g., trauma, malignancy, renal failure, cirrhosis, and anticoagulation therapy) to promote early diagnosis and avoid complications.
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Phases with spontaneous time-reversal ( T ) symmetry breaking are sought after for their anomalous physical properties, low-dissipation electronic and spin responses, and information-technology applications. Recently predicted altermagnetic phase features an unconventional and attractive combination of a strong T -symmetry breaking in the electronic structure and a zero or only weak-relativistic magnetization. In this work, we experimentally observe the anomalous Hall effect, a prominent representative of the T -symmetry breaking responses, in the absence of an external magnetic field in epitaxial thin-film Mn5Si3 with a vanishingly small net magnetic moment. By symmetry analysis and first-principles calculations we demonstrate that the unconventional d-wave altermagnetic phase is consistent with the experimental structural and magnetic characterization of the Mn5Si3 epilayers, and that the theoretical anomalous Hall conductivity generated by the phase is sizable, in agreement with experiment. An analogy with unconventional d-wave superconductivity suggests that our identification of a candidate of unconventional d-wave altermagnetism points towards a new chapter of research and applications of magnetic phases.
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Introduction: Ototoxicity is a debilitating side effect of over 150 medications with diverse mechanisms of action, many of which could be taken concurrently to treat multiple conditions. Approaches for preclinical evaluation of drug-drug interactions that might impact ototoxicity would facilitate design of safer multi-drug regimens and mitigate unsafe polypharmacy by flagging combinations that potentially cause adverse interactions for monitoring. They may also identify protective agents that antagonize ototoxic injury. Methods: To address this need, we have developed a novel workflow that we call Parallelized Evaluation of Protection and Injury for Toxicity Assessment (PEPITA), which empowers high-throughput, semi-automated quantification of ototoxicity and otoprotection in zebrafish larvae via microscopy. We used PEPITA and confocal microscopy to characterize in vivo the consequences of drug-drug interactions on ototoxic drug uptake and cellular damage of zebrafish lateral line hair cells. Results and discussion: By applying PEPITA to measure ototoxic drug interaction outcomes, we discovered antagonistic interactions between macrolide and aminoglycoside antibiotics that confer protection against aminoglycoside-induced damage to lateral line hair cells in zebrafish larvae. Co-administration of either azithromycin or erythromycin in zebrafish protected against damage from a broad panel of aminoglycosides, at least in part via inhibiting drug uptake into hair cells via a mechanism independent from hair cell mechanotransduction. Conversely, combining macrolides with aminoglycosides in bacterial inhibition assays does not show antagonism of antimicrobial efficacy. The proof-of-concept otoprotective antagonism suggests that combinatorial interventions can potentially be developed to protect against other forms of toxicity without hindering on-target drug efficacy.
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Septal Myectomy (SM) and Alcohol Septal Ablation (ASA) improve symptoms in patients with Hypertrophic Cardiomyopathy with outflow tract obstruction (oHCM). However, outcomes data in this population is predominantly from specialized centers. The National Inpatient Database was queried from 2011 to 2019 for relevant international classification of diseases (ICD)-9 and -10 diagnostic and procedural codes. We compared baseline characteristics and in-hospital outcomes of patients with oHCM who underwent SM vs ASA. A p-value < 0.001 was considered statistically significant. We identified 15,119 patients with oHCM who underwent septal reduction therapies, of whom 57.4% underwent SM, and 42.6% underwent ASA. Patients who underwent SM had higher all-cause mortality (OR: 1.8 (1.3-2.5)), post-procedure ischemic stroke (OR: 2.3 (1.7-3.2)), acute kidney injury (OR: 1.4 (1.2-1.7)), vascular complications (OR: 3.6 (2.3-5.3)), ventricular septal defect (OR: 4.4 (3.2-6.1)), cardiogenic shock (OR: 1.7 (1.3-2.3)), sepsis (OR: 3.2 (1.9-5.4)), and left bundle branch block (OR: 3.5 (3-4)), compared to ASA. Patients who underwent ASA had higher post-procedure complete heart block (OR: 1.3 (1.1-1.4)), right bundle branch block (OR: 6.3 (5-7.7)), ventricular tachycardia (OR: 2.2 (1.9-2.6)), supraventricular tachycardia (OR: 1.6 (1.4-2)), and more commonly required pacemaker insertion (OR: 1.4 (1.3-1.7)) (p < 0.001 for all) compared to SM. This nationwide analysis evidenced that patients undergoing SM had higher in-hospital mortality and periprocedural complications than ASA; however, those undergoing ASA had more post-procedure conduction abnormalities and pacemaker implantation. The implications of these findings warrant further investigation regarding patient selection strategies for these therapies.
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Cardiomiopatía Hipertrófica , Pacientes Internos , Humanos , Resultado del Tratamiento , Tabiques Cardíacos/cirugía , Etanol , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/cirugíaRESUMEN
The Cys-loop pentameric ligand-gated ion channels comprise a dynamic group of proteins that have been extensively studied for decades, yielding a wealth of findings at both the structural and functional levels. The nicotinic acetylcholine receptor (nAChR) is no exception, as it is part of this large protein family involved in proper organismal function. Our efforts have successfully produced a highly pure nAChR in detergent complex (nAChR-DC), enabling more robust studies to be conducted on it, including beginning to experiment with high-throughput crystallization. Our homogeneous product has been identified and extensively characterized with 100% identity using Nano Lc MS/MS and MALDI ToF/ToF for each nAChR subunit. Additionally, the N-linked glycans in the Torpedo californica-nAChR (Tc-nAChR) subunits have been identified. To study this, the Tc-nAChR subunits were digested with PNGase F and the released glycans were analyzed by MALDI-ToF. The MS results showed the presence of high-mannose N-glycan in all native Tc-nAChR subunits. Specifically, the oligommanose population Man8-9GlcNac2 with peaks at m/z 1742 and 1904 ([M + Na]+ ions) were observed.
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Nicotina , Receptores Nicotínicos , Animales , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Acetilcolina/metabolismo , Torpedo/metabolismo , Espectrometría de Masas en Tándem , Receptores Nicotínicos/química , Receptores Nicotínicos/metabolismoRESUMEN
This study computationally evaluates the molecular docking affinity of various perfluoroalkyl and polyfluoroalkyl substances (PFAs) towards blood proteins using a generative machine-learning algorithm, DiffDock, specialized in protein-ligand blind-docking learning and prediction. Concerns about the chemical pathways and accumulation of PFAs in the environment and eventually in the human body has been rising due to empirical findings that levels of PFAs in human blood has been rising. DiffDock may offer a fast approach in determining the fate and potential molecular pathways of PFAs in human body.
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Inteligencia Artificial , Fluorocarburos , Humanos , Simulación del Acoplamiento Molecular , Algoritmos , Proteínas SanguíneasRESUMEN
Progress in magnetoelectric materials is hindered by apparently contradictory requirements for time-reversal symmetry broken and polar ferroelectric electronic structure in common ferromagnets and antiferromagnets. Alternative routes can be provided by recent discoveries of a time-reversal symmetry breaking anomalous Hall effect (AHE) in noncollinear magnets and altermagnets, but hitherto reported bulk materials are not polar. Here, the authors report the observation of a spontaneous AHE in doped AgCrSe2 , a layered polar semiconductor with an antiferromagnetic coupling between Cr spins in adjacent layers. The anomalous Hall resistivity 3 µ Ω c m $\mu \Omega \, \textnormal {cm}$ is comparable to the largest observed in compensated magnetic systems to date, and is rapidly switched off when the angle of an applied magnetic field is rotated to ≈80° from the crystalline c-axis. The ionic gating experiments show that the anomalous Hall conductivity magnitude can be enhanced by modulating the p-type carrier density. They also present theoretical results that suggest the AHE is driven by Berry curvature due to noncollinear antiferromagnetic correlations among Cr spins, which are consistent with the previously suggested magnetic ordering in AgCrSe2 . The results open the possibility to study the interplay of magnetic and ferroelectric-like responses in this fascinating class of materials.
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Ototoxicity is a debilitating side effect of over 150 medications with diverse mechanisms of action, many of which could be taken concurrently to treat multiple conditions. Approaches for preclinical evaluation of drug interactions that might impact ototoxicity would facilitate design of safer multi-drug regimens and mitigate unsafe polypharmacy by flagging combinations that potentially cause adverse interactions for monitoring. They may also identify protective agents that antagonize ototoxic injury. To address this need, we have developed a novel workflow that we call Parallelized Evaluation of Protection and Injury for Toxicity Assessment (PEPITA), which empowers high-throughput, semi-automated quantification of ototoxicity and otoprotection in zebrafish larvae. By applying PEPITA to characterize ototoxic drug interaction outcomes, we have discovered antagonistic interactions between macrolide and aminoglycoside antibiotics that confer protection against aminoglycoside-induced damage to lateral line hair cells in zebrafish larvae. Co-administration of either azithromycin or erythromycin in zebrafish protected against damage from a broad panel of aminoglycosides, at least in part via inhibiting drug uptake into hair cells via a mechanism independent from hair cell mechanotransduction. Conversely, combining macrolides with aminoglycosides in bacterial inhibition assays does not show antagonism of antimicrobial efficacy. The proof-of-concept otoprotective antagonism suggests that combinatorial interventions can potentially be developed to protect against other forms of toxicity without hindering on-target drug efficacy.
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This report presents the case of a 25-year-old male with an infected tibial diaphyseal nonunion caused by a bone transport procedure carried out to treat an open fracture the patient had sustained 10 years before referral to our hospital. After an initial radical debridement, a bone defect was created, which was subsequently obliterated by placement of an antibiotic-impregnated cement spacer and Stimulan beads and covered by an anterolateral thigh flap. As the patient refused to wear an external fixator and his osseous biology was not amenable to a Masquelet procedure, a decision was made to apply the Capanna technique as soon as the infection healed. The second debridement resulted in a 12-cm-long bone defect that was filled with a tibial allograft and a vascularized fibular graft. At six months, the patient had regained full knee function and was able to bear his full weight, without pain or the need of support equipment. At one year, the bone had healed completely, the infection had subsided and the patient was able to resume his everyday activities. Although the Capanna technique was initially developed to reinforce reconstructions at risk of fracture or nonunion as a result of chemotherapy, its use in post-traumatic cases has been shown to be successful in a selected group of patents. Our study demonstrated that increasing the stability of a reconstruction with an allograft can accelerate the time to heal, and that using a vascularized fibular graft can enhance incorporation of the whole construct. It can be concluded that the Capanna technique is a valid treatment option for managing infected segmental bone defects in selected patients.
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In recent years, there has been a concerted drive to develop methods that are greener and more sustainable. Being an earth-abundant transition metal, cobalt offers an attractive substitute for commonly employed precious metal catalysts, though reactions engaging cobalt are still less developed. Herein, we report a method to achieve the decarboxylative allylation of nitrophenyl alkanes, nitroalkanes, and ketones employing cobalt. The reaction allows for the formation of various substituted allylated products in moderate-excellent yields with a broad scope. Additionally, the synthetic potential of the methodology is demonstrated by the transformation of products into versatile heterocyclic motifs. Mechanistic studies revealed an inâ situ activation of the Co(II)/dppBz precatalyst by the carboxylate salt to generate a Co(I)-species, which is presumed to be the active catalyst.
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Fungal infections have become a significant public health concern due to their increasing recurrence and harmful effects on plants, animals, and humans. Opportunistic pathogens (among others from the genera Candida and Aspergillus) can be present in indoor air, becoming a risk for people with suppressed immune systems. Engineered nanomaterials are novel alternatives to traditional antifungal therapy. In this work, copper(I) iodide (CuI) and a copper-doped titanium dioxide-copper(I) iodide (TiO2-Cu2+/CuI) composite nanomaterials (NMs)-were synthesized and tested as antifungal agents. The materials were synthesized using sol-gel (TiO2-Cu2+) and co-precipitation (CuI) techniques. The resulting colloids were evaluated as antifungal agents against Candida parapsilosis and Aspergillus niger strains. The NMs were characterized by XRD, HRTEM, AFM, and DLS to evaluate their physicochemical properties. The NMs present a high size dispersion and different geometrical shapes of agglomerates. The antifungal capacity of the NMs by the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) was below 15 µg/mL against Candida parapsilosis and below 600 µg/mL against Aspergillus niger for both NMs. Holotomography microscopy showed that the NMs could penetrate cell membranes causing cell death through its rupture and reactive oxygen species (ROS) production. Cytotoxicity tests showed that NMs could be safe to use at low concentrations. The synthesized nanomaterials could be potential antifungal agents for biomedical or environmental applications.
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BACKGROUND: People with cystic fibrosis (PwCF) have chronic lung disease and may be at increased risk of coronavirus disease 2019 (COVID-19)-related morbidity and mortality. This study aimed to determine seroprevalence and clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with cystic fibrosis (CF), and to assess antibody responses following SARS-CoV-2 infection or vaccination. METHODS: Children and adolescents with CF followed at Seattle Children's Hospital were enrolled between July 20, 2020 and February 28, 2021. SARS-CoV-2 serostatus was determined on enrollment at 6 and 11 months (±2 months) for nucleocapsid and spike IgG. Participants completed intake and weekly surveys inquiring about SARS-CoV-2 exposures, viral/respiratory illnesses, and symptoms. RESULTS: Of 125 PwCF enrolled, 14 (11%) had positive SARS-CoV-2 antibodies consistent with recent or past infection. Seropositive participants were more likely to identify as Hispanic (29% vs. 8%, p = 0.04) and have pulmonary exacerbations requiring oral antibiotics in the year prior (71% vs. 41%, p = 0.04). Five seropositive individuals (35.7%) were asymptomatic, while six (42.9%) reported mild symptoms, primarily cough and nasal congestion. Antispike protein IgG levels were approximately 10-fold higher in participants following vaccination compared with participants who had natural infection alone (p < 0.0001) and resembled levels previously reported in the general population. CONCLUSIONS: A majority of PwCF have mild or no symptoms of SARS-CoV-2 making it difficult to distinguish from baseline respiratory symptoms. Hispanic PwCF may be disproportionately impacted, consistent with racial and ethnic COVID-19 disparities among the general US population. Vaccination in PwCF generated antibody responses similar to those previously reported in the general population.
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COVID-19 , Fibrosis Quística , Adolescente , Humanos , Niño , COVID-19/epidemiología , Fibrosis Quística/complicaciones , Fibrosis Quística/epidemiología , SARS-CoV-2 , Estudios Seroepidemiológicos , Inmunoglobulina GRESUMEN
BACKGROUND: Raised blood pressure (BP) remains the biggest risk factor contributing to the global burden of disease and mortality, despite the COVID-19 pandemic. May Measurement Month (MMM), an annual global screening campaign aims to highlight the importance of BP measurement by evaluating global awareness, treatment and control rates among adults with hypertension. In 2021, we assessed the global burden of these rates during the COVID-19 pandemic. METHODS: Screening sites were set up in 54 countries between May and November 2021 and screenees were recruited by convenience sampling. Three sitting BPs were measured, and a questionnaire completed including demographic, lifestyle and clinical data. Hypertension was defined as a systolic BP at least 140 mmHg and/or a diastolic BP at least 90âmmHg (using the mean of the second and third readings) or taking antihypertensive medication. Multiple imputation was used to impute the average BP when readings were missing. RESULTS: Of the 642â057 screenees, 225â882 (35.2%) were classified as hypertensive, of whom 56.8% were aware, and 50.3% were on antihypertensive medication. Of those on treatment, 53.9% had controlled BP (<140/90âmmHg). Awareness, treatment and control rates were lower than those reported in MMM campaigns before the COVID-19 pandemic. Minimal changes were apparent among those testing positive for, or being vaccinated against COVID-19. Of those on antihypertensive medication, 94.7% reported no change in their treatment because of the COVID-19 pandemic. CONCLUSION: The high yield of untreated or inadequately treated hypertension in MMM 2021 confirms the need for systematic BP screening where it does not currently exist.
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COVID-19 , Hipertensión , Adulto , Humanos , Presión Sanguínea , Antihipertensivos/uso terapéutico , Pandemias , COVID-19/diagnóstico , COVID-19/epidemiología , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiologíaRESUMEN
The main objective of the present study was to find detergents that can maintain the functionality and stability of the Torpedo californica nicotinic acetylcholine receptor (Tc-nAChR). We examined the functionality, stability, and purity analysis of affinity-purified Tc-nAChR solubilized in detergents from the Cyclofos (CF) family [cyclofoscholine 4 (CF-4), cyclofoscholine 6 (CF-6), and cyclofloscholine 7 (CF-7)]. The functionality of the CF-Tc-nAChR-detergent complex (DC) was evaluated using the Two Electrode Voltage Clamp (TEVC) method. To assess stability, we used the florescence recovery after photobleaching (FRAP) in Lipidic Cubic Phase (LCP) methodology. We also performed a lipidomic analysis using Ultra-Performance Liquid Chromatography (UPLC) coupled to electrospray ionization mass spectrometry (ESI-MS/MS) to evaluate the lipid composition of the CF-Tc-nAChR-DCs. The CF-4-Tc-nAChR-DC displayed a robust macroscopic current (- 200 ± 60 nA); however, the CF-6-Tc-nAChR-DC and CF-7-Tc-nAChR-DC displayed significant reductions in the macroscopic currents. The CF-6-Tc-nAChR and CF-4-Tc-nAChR displayed higher fractional florescence recovery. Addition of cholesterol produced a mild enhancement of the mobile fraction on the CF-6-Tc-nAChR. The lipidomic analysis revealed that the CF-7-Tc-nAChR-DC displayed substantial delipidation, consistent with the lack of stability and functional response of this complex. Although the CF-6-nAChR-DC complex retained the largest amount of lipids, it showed a loss of six lipid species [SM(d16:1/18:0); PC(18:2/14:1); PC(14:0/18:1); PC(16:0/18:1); PC(20:5/20:4), and PC(20:4/20:5)] that are present in the CF-4-nAChR-DC. Overall, the CF-4-nAChR displayed robust functionality, significant stability, and the best purity among the three CF detergents; therefore, CF-4 is a suitable candidate to prepare Tc-nAChR crystals for structural studies.
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Detergentes , Receptores Nicotínicos , Animales , Espectrometría de Masas en Tándem , Torpedo , Receptores Nicotínicos/química , Lípidos/química , ElectrofisiologíaRESUMEN
We report on the synthesis and characterization of V2O5 nanoparticles grown using a sol-gel method at different calcination temperatures. We observed a surprising reduction in the optical band gap from 2.20 to 1.18 eV with increasing calcination temperature from 400 to 500 °C. Raman and X-Ray diffraction measurements indicated slight changes in the lattice parameters induced by the growth process. However, density functional theory calculations of the Rietveld-refined and pristine structures revealed that the observed optical gap reduction could not be explained by structural changes alone. By introducing oxygen vacancies to the refined structures, we could reproduce the reduction of the band gap. Our calculations also showed that the inclusion of oxygen vacancies at the vanadyl position creates a spin-polarized interband state that reduces the electronic band gap and promotes a magnetic response due to unpaired electrons. This prediction was confirmed by our magnetometry measurements, which exhibited a ferromagnetic-like behavior. Our findings suggest that oxygen vacancies play a crucial role in band gap reduction and the promotion of a ferromagnetic-like response in an otherwise paramagnetic material. This provides a promising route to engineer novel devices.
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Entre las figuras cimeras de la microbiología en Cuba, se encuentra el Dr. Juan Nicolás Dávalos y Betancourt, conocido en su época como "el sabio que sueña con las bacterias", quien fue el primer médico cubano, dedicado a tiempo completo a la práctica de esta ciencia, en específico a la bacteriología. A pesar de esto, su vida y su obra no están suficientemente difundidas, por lo que este trabajo tiene como objetivo dar a conocer su legado, en un contexto histórico, social y científico, para que se conocido y valorado por las actuales y futuras generaciones de microbiólogos cubanos. Se realizó una investigación biográfica y se adicionan testimonios gráficos. La figura del Dr. Juan Nicolás Dávalos es destacada, no solo para la microbiología, como también para la ciencia en Cuba.
Among the leading figures of microbiology in Cuba, is Dr. Juan Nicolás Dávalos y Betancourt, known in his time as "the wise man who dreams of bacteria", who was the first Cuban doctor dedicated full-time to the practice of this science, specifically bacteriology. Despite this, his life and his work are not sufficiently disseminated, so this work aims to make his legacy known, in a historical, social and scientific context, so that it is known and valued by current and future generations. of Cuban microbiologists. A biographical investigation was carried out and graphic testimonies are added. Dr. Juan Nicolás Dávalos is outstanding, not only for microbiology, but also for science in Cuba.