Obesity and its Relationship with Covid-19: A Review of the Main Pharmaceutical Aspects.

Important physiological changes are observed in patients with obesity, such as intestinal permeability, gastric emptying, cardiac output, and hepatic and renal function. These differences can determine variations in the pharmacokinetics of different drugs and can generate different concentrations at the site of action, which can lead to sub therapeutic or toxic concentrations. Understanding the physiological and immunological processes that lead to the clinical manifestations of COVID-19 is essential to correlate obesity as a risk factor for increasing the prevalence, severity, and lethality of the disease. Several drugs have been suggested to control COVID- 19 like Lopinavir, Ritonavir, Ribavirin, Sofosbuvir, Remdesivir, Oseltamivir, Oseltamivir phosphate, Oseltamivir carboxylate, Hydroxychloroquine, Chloroquine, Azithromycin, Teicoplanin, Tocilizumab, Anakinra, Methylprednisolone, Prednisolone, Ciclesonide and Ivermectin. Similarly, these differences between healthy people and obese people can be correlated to mechanical factors, such as insufficient doses of the vaccine for high body mass, impairing the absorption and distribution of the vaccine that will be lower than desired or can be linked to the inflammatory state in obese patients, which can influence the humoral immune response. Additionally, different aspects make the obese population more prone to persistent symptoms of the disease (long COVID), which makes understanding these mechanisms fundamental to addressing the implications of the disease. Thus, this review provides an overview of the relationship between COVID-19 and obesity, considering aspects related to pharmacokinetics, immunosuppression, immunization, and possible implications of long COVID in these individuals.

Rapid diagnostic tests for dengue would reduce hospitalizations, healthcare costs and antibiotic prescriptions in Spain: A cost-effectiveness analysis.

BACKGROUND: Current gold standard diagnostic techniques for dengue are expensive and time-consuming. Rapid diagnostic tests (RDTs) have been proposed as alternatives, although data about their potential impact in non-endemic areas is scarce. METHODS: We performed a cost-effectiveness analysis comparing the costs of dengue RDTs to the current standard of care for the management of febrile returning travelers in Spain. Effectiveness was measured in terms of potential averted hospital admissions and reduction of empirical antibiotics, based on 2015-2020 dengue admissions at Hospital Clinic Barcelona (Spain). RESULTS: Dengue RDTs were associated with 53.6% (95% CI: 33.9-72.5) reduction of hospital admissions and were estimated to save 289.08-389.31€ per traveler tested. Moreover, RDTs would have avoided the use of antibiotics in 46.4% (95% CI: 27.5-66.1) of dengue patients. DISCUSSION: Implementation of dengue RDTs for the management of febrile travelers is a cost-saving strategy that would lead to a reduction of half of dengue admissions and a reduction of inappropriate antibiotics in Spain.

Curso de investigación en Atención Primaria de la Salud: experiencia sobre módulo de búsqueda bibliográfica y gestores de citas / Research course in Primary Health Care: experience with the bibliographic search module and citation managers

La Federación Argentina de Medicina Familiar y General apoyó el desarrollo, la difusión y la implementación de una propuesta educativa sobre investigación en atención primaria. Consiste en 4 módulos independientes, destinado para miembros interesados/as, con 2 encuentros virtuales teórico-prácticos, que favorecieran el intercambio de opiniones y experiencias entre colegas. El objetivo del primer módulo fue proporcionar conocimiento, brindar pautas y ofrecer herramientas para la búsqueda bibliográfica y el uso de gestores de citas. Se realizó difusión mediante sociedades y redes sociales. Se incluyó una evaluación individual, que diera cuenta de lectura complementaria y la aplicación práctica de los contenidos. Se llevó a cabo en Junio, con 39 preinscripto/as, mayoritariamente residentes. Hubo 24 participantes efectivos (61%), asistieron 17 y 20 personas respectivamente, y 11 (46%) obtuvieron el certificado de aprobación por responder la consigna en tiempo y forma. En cuanto a los/as asistentes, hubo predominio de mujeres (79%), provenientes de Asociación Metropolitana de Medicina Familiar (25%), Asociación Cordobesa de Medicina Familiar y Comunitaria (16%), Asociación Misionera de Medicina General/Familiar y del Equipo de Salud (16%), Asociación Tucumana de Medicina Familiar, General y Comunitaria (12%), y otras minorías. Expresaron satisfacción, agradecimiento y reconocimiento por la actividad, destacando la buena predisposición de organizadores y equipo docente, la utilidad práctica de la temática, la evidente planificación, y el apoyo político-económico. Esta valiosa experiencia educativa (planteada como necesidad pendiente) resultó exitosa, ya que los/as participantes demostraron un alto nivel de interés, de asistencia de diferentes provincias, y de compromiso. Los certificados emitidos otorgan créditos educativos válidos para la recertificación (AU)

The Federación Argentina de Medicina Familiar y General supported the development, dissemination and implementation of an educational proposal on research in primary care. It consists of 4 independent modules, intended for interested members, with 2 virtual theoretical-practical meetings, which favored the exchange of opinions and experiences among colleagues. The objective of the first module was to provide knowledge, guidelines and tools for bibliographic search and the use of citation managers. Dissemination was carried out through societies and social networks. An individual evaluation was included, to account for complementary reading and the practical application of the contents. It was carried out in June, with 39 pre-registered participants, mostly residents. There were 24 effective participants (61%), 17 and 20 people attended respectively, and 11 (46%) obtained the certificate of approval for answering the instructions in due time and form. As for the attendees, there was a predominance of women (79%), coming from Asociación Metropolitana de Medicina Familiar (25%), Asociación Cordobesa de Medicina Familiar y Comunitaria (16%), Asociación Misionera de Medicina General/Familiar y del Equipo de Salud (16%), Asociación Tucumana de Medicina Familiar, General y Comunitaria (12%), and other minorities. They expressed satisfaction, gratitude, and recognition for the activity, highlighting the good predisposition of the organizers and teaching team, the practical usefulness of the subject matter, the evident planning, and the political-economic support. This valuable educational experience (raised as a pending need) was successful since the participants showed a high level of interest, attendance from different provinces, and commitment. The certificates issued grant educational credits valid for recertification (AU)

Lymphedema and Elephantiasis of the Lower Limbs: Normalization or Nearly Normalization.

Lymphedema is a clinical condition resulting from a failure in the drainage of the lymphatic system and the consequent formation of edema and is a chronic progressive condition; its development is an active dynamic process. Physiotherapy techniques are the most widely used method for such cases. However, novel concepts and treatment techniques have emerged in recent years. Godoy & Godoy have developed novel therapy concepts proposing the normalization or near normalization of all clinical stages of lymphedema, including elephantiasis.The Godoy & Godoy method has undergone continual evolution, with the improvement of established and the emergence of novel concepts making contributions to the understanding of the causes and treatment of lymphedema. These researchers developed a novel concept of manual lymphatic drainage based on linear movements, cervical lymphatic therapy, a novel concept in mechanical lymphatic drainage, and hand-crafted stockings made with grosgrain material. Therefore, the aim of the present study is to report the new concepts of treatment for lymphedema and the maintenance of such results by the Godoy & Godoy technique in all stages. The Godoy & Godoy method enables the normalization or near normalization of lymphedema in all clinical stages, including elephantiasis.

Pharmacokinetic approach in therapeutic monitoring of antineoplastic drugs and the impact on pharmacoeconomics: A systematic review.

OBJECTIVES: Therapeutic drug monitoring aims to quantify the concentration of a drug in a biological matrix. In oncology, the therapeutic arsenal is vast and therapeutic drug monitoring optimizes treatment and reduces costs. This review will analyze the financial impact of therapeutic monitoring of anticancer drugs in healthcare institutions. METHODS: Keywords were selected using Decs (MeSH). Through the Pubmed, Scopus, and Virtual Health Library (VHL) databases, 74 articles were found, of which 4 meet the inclusion criteria. Methodological quality and risk of bias were assessed according to the Research Triangle Institute Item Bank (RTI-Item Bank) scale. KEY FINDINGS: Therapeutic drug monitoring is an important tool for dose reduction or dose increase due to toxicity and lack of response, respectively. The main barriers are associated costs and lack of cost-benefit data. An alternative is to use population pharmacokinetic models, measured plasma concentration(s) and relevant patient characteristics, estimated individual pharmacokinetic parameters, and predicted drug concentrations at any point in the dosing range. CONCLUSIONS: Therapeutic drug monitoring is understood as a technology that adds costs to payers. Future studies should generate clinical evidence of population pharmacokinetics from therapeutic drug monitoring studies.

Neurogenic Background for Emotional Stress-Associated Hypertension.

PURPOSE OF REVIEW: The response to natural stressors involves both cardiac stimulation and vascular changes, primarily triggered by increases in sympathetic activity. These effects lead to immediate flow redistribution that provides metabolic support to priority target organs combined with other key physiological responses and cognitive strategies, against stressor challenges. This extremely well-orchestrated response that was developed over millions of years of evolution is presently being challenged, over a short period of time. In this short review, we discuss the neurogenic background for the origin of emotional stress-induced hypertension, focusing on sympathetic pathways from related findings in humans and animals. RECENT FINDINGS: The urban environment offers a variety of psychological stressors. Real or anticipatory, emotional stressors may increase baseline sympathetic activity. From routine day-to-day traffic stress to job-related anxiety, chronic or abnormal increases in sympathetic activity caused by emotional stressors can lead to cardiovascular events, including cardiac arrhythmias, increases in blood pressure and even sudden death. Among the various alterations proposed, chronic stress could modify neuroglial circuits or compromise antioxidant systems that may alter the responsiveness of neurons to stressful stimuli. These phenomena lead to increases in sympathetic activity, hypertension and consequent cardiovascular diseases. The link between anxiety, emotional stress, and hypertension may result from an altered neuronal firing rate in central pathways controlling sympathetic activity. The participation of neuroglial and oxidative mechanisms in altered neuronal function is primarily involved in enhanced sympathetic outflow. The significance of the insular cortex-dorsomedial hypothalamic pathway in the evolution of enhanced overall sympathetic outflow is discussed.

[Leucocyte adhesion deficiency: detection of the first cases in Paraguay]. / Deficiencia de adhesión leucocitaria: detección de los primeros casos en Paraguay.

OBJECTIVE: To implement the diagnostic technique for LAD by evaluating the expression of CD18 and CD15 in healthy patients and in a group with clinical suspicion. METHODS: Observational, descriptive, and cross-secctional study, carried out in pediatric patients attended in the Instituto de Investigaciones en Ciencias de la Salud, and patients from public hospitals with clinical suspicion of LAD were studied. The molecules CD18 and CD15 in peripheral blood leukocytes was evaluated by flow cytometry, establishing a normal range in healthy patients. The presence of LAD was established by decreased expression of CD18 or CD15. RESULTS: Sixty pediatric patients were evaluated: 20 apparently healthy and 40 with clinical suspicion of leukocyte adhesion deficiency; 12 of 20 healthy patients were male (median age: 14 years) and 27 of 40 with suspected disease were female (median age: 2 years). Persistent leukocytosis and respiratory tract (32%) infections predominated. The expression range of CD18 and CD15 in healthy patients was 95%-100%, and in patients with clinical suspicion it was 0%-100%. One patient with 0% of CD18 (LAD-1) and one patient with 0% of CD15 (LAD-2) were detecte. CONCLUSIONS: The implementation of a new diagnostic technique allowed to establish a normal range of CD18 and CD15 by flow cytometry, and it was possible to detect the first two cases of LAD in Paraguay.

OBJECTIVO: Implementar la técnica diagnóstica para deficiencia de adhesión leucocitaria mediante la evaluación de la expresión de CD18 y CD15 en pacientes sanos y con sospecha clínica de la enfermedad. MÉTODOS: Estudio observacional, descriptivo y transversal, llevado a cabo en pacientes pediátricos sanos que acudieron al Instituto de Investigaciones en Ciencias de la Salud y pacientes de hospitales públicos con sospecha clínica de deficiencia de adhesión leucocitaria. Se evaluaron las moléculas CD18 y CD15 en leucocitos periféricos por citometría de flujo, con la intención de estadarizar un rango normal en pacientes sanos. Se estableció el diagnóstico de deficiencia de adhesión lecuocitaria, según la expresión disminuida de CD18 o CD15. RESULTADOS: Se evaluaron 60 pacientes pediátricos: 20 aparentemente sanos y 40 con sospecha clínica de deficiencia de adhesión leucocitaria; 12 de 20 pacientes sanos fueron varones (mediana de edad: 14 años) y 27 de 40 con sospecha de la enfermedad fueron mujeres (mediana de edad: 2 años). Predominaron la leucocitosis persistente y las infecciones respiratorias (32%). La expresión de CD18 y CD15 en pacientes sanos fue del 95-100% y en pacientes con sospecha de deficiencia de adhesión leucocitaria de 0-100%. Se identificó una paciente con 0% de expresión de CD18 (LAD-1) y otro con 0% de CD15 (LAD-2). CONCLUSIONES: La evaluación de las moléculas CD18 y CD15 permitió detectar los primeros casos de deficiencia de adhesión leucocitaria en Paraguay, que sirve de precedente y pone a punto la técnica para el diagnóstico de la enfermedad a nivel local.

Synthesis and Physiological Remodeling of CD34 Cells in the Skin following the Reversal of Fibrosis through Intensive Treatment for Lower Limb Lymphedema: A Case Report.

A novel type of cell underwent identification between 2005 and 2008 and was denominated the "telocyte" in 2010. In 2012, transmission electron microscopy revealed the presence of telocytes in the dermis. The aim of the present study was to report important changes in immunostained CD34 cells following the treatment of lower limb lymphedema using a specific lymphatic therapy technique. A clinical trial involving the evaluation of changes in immunostained CD34 cells in the epidermis and dermis (10 randomly selected histological fields) of a patient before and after intensive treatment for clinical stage II lymphedema was conducted using the Godoy Method, which was adapted to the treatment of skin fibrosis. The evaluation involved the use of the Weibel multi-point morphometric method. Comparisons were performed using the t-test with a 95% significance level. An important increase in CD34 cells was found with redistribution occurring following treatment. The treatment of primary lymphedema of the lower limbs resulted in the clinical reversal of fibrosis and an increase in the number of immunomarked CD34 cells.

A pilot study of chemotherapy combinations in rats: Focus on mammary cancer treatment in female dogs.

The use of combined chemotherapy is an essential alternative in treating breast cancer. However, knowledge of the pharmacokinetics of drugs is necessary to obtain maximum efficiency of the protocol and reduce adverse reactions. This study suggests for the first time the effect of the association of carboplatin with ivermectin and carboplatin with cyclophosphamide. This investigation was performed with 36 healthy Wistar rats, divided into four groups: group control, carboplatin (C), carboplatin preceded by ivermectin (C + IV), and carboplatin associated with cyclophosphamide (C + CI). Plasma concentrations quantification was performed using the High-Performance Liquid Chromatographic (HPLC) equipment with an Ultraviolet (UV) detector at eight different time points. Then, the animal was euthanized and necropsied. The bioanalytical method was validated for the two matrices (dogs and rats' plasma), with full validation in female dogs and partial validation in rats, as recommended by the EMA. In both matrices, the method was linear and reproducible. Here, we show the results in female rats' plasma. When comparing the experimental rats' groups (C; C + IV, and C + CI), there is a tendency to increase the bioavailability of carboplatin when used in association, a slight increase for C + IV and more evident to the C + CI group with an AUC rise higher than 2-fold (AUC0-∞ = 2983.61 for C; 4459.06 for C + CI; 7064.68 for C + CI min·mg·mL-1). The blood count, biochemistry profile, and histopathology of the organs revealed only alterations inherent to the metabolic effects of the drugs used. The carboplatin association with ivermectin appeared safe for this pilot group. We believe the carboplatin dose can be maintained without risk to the patient. However, in the carboplatin association with cyclophosphamide, a slight reduction in carboplatin's amount is suggested, seeking to avoid increased effects due to cyclophosphamide. Thus, studies with a more significant number per group must confirm the relevance of this pilot study.

Black and non-black population: investigation of the difference in butyrylcholinesterase activity in a healthy population in Salvador, Bahia.

INTRODUCTION: Butyrylcholinesterase (BChE), an important biomarker of exposure to anticholinesterases, varies its activity according to the intensity and duration of exposure to these agents. Their normal values may vary in different populations. It is important to determine the reference values for the local population, mostly black/brown. OBJECTIVE: The objective was to investigate the baseline values of BChE activity in a sample of the Salvador city population (Bahia, Brazil), evaluating the sociodemographic characteristics. METHOD: A descriptive, quantitative study with a cross-sectional approach was carried out in 304 voluntary and healthy blood donors. BChE activity was determined using the integrated chemical system Dimension RxLMax and analyses of sociodemographic characteristics were performed. RESULTS: For the 304 participants (18 to 67 years old), BChE activity values range were 7.4 to 19.8 U/mL (male) and 6.0 to 19.6 U/mL (female), without significant inter-racial differences (p = 0.986; Mann-Whitney). The participates were predominantly black (44.7%) and brown (40.5%), with higher levels of BchE activity in males (64.8%) (p-value = 0.01) than females (35.2%). There was no relationship between alcohol use and lower BChE activity (p = 0.725, Mann-Whitney). Women using hormonal contraceptives had a median activity 9.2% lower than the non-users. CONCLUSION: Despite the high miscegenation and predominance of the black race in Salvador, contrary to what was expected, the sample did not show statistically significant intra-racial differences in BChE activity, being able to use the same reference values currently used, observing factors such as sex, use of contraceptives, and drinking alcohol.

Influence of eating with distractors on caloric intake of children and adolescents: a systematic review and meta-analysis of interventional controlled studies.

Eating habits developed during childhood can be perpetuated along life and contribute to the emergence of disorders. We aimed to investigate the influence of distractors during experimental meals on the energy intake of children and adolescents. We followed the PRISMA guidelines and the study was registered in PROSPERO (CRD42021259946). The PICOS strategy consisted of children and adolescents (P), exposed to distractors during meals (I), compared with no distraction (C) and the outcome was energy intake (Kcal) (O) evaluated in crossover and parallel randomized clinical trials (RCTs) (S). Searches were conducted in PubMed, Scopus, Web of Science, Cochrane, Proquest, Embase, and LILACs databases. We employed RoB 2 tool and NutriGrade. Databases searches returned 9,576 references. Thirteen articles were selected (five crossover and eight parallel RCTs). Volunteers aged 3 to 17 years-old. All studies evaluated TV as distractor. Most studies presented high/moderate risk of bias. Meta-analysis of parallel RCT indicated no significant difference in energy intake while eating with TV (MD = 0.05; 95% CI -0.13 - 0.23, P = 0.57), with moderate certainty level. In conclusion, under laboratory conditions, eating with distractors seems to barely alter energy intake for children and adolescents.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2055525 .

Principais manifestações clínicas oftalmológicas prevalentes em pacientes acometidos por fraturas orbitárias: revisão integrativa de literatura / The main ophthalmological clinical manifestations prevalent in patients affected by orbital fractures: an integrative literature review

RESUMO Um em cada quatro pacientes acometidos por trauma maxilofacial terão concomitantemente fraturas da órbita e lesão ocular. Por isso, uma avaliação oftalmológica minuciosa é recomendada para todos os pacientes que sofrem um trauma de face. Alguns exames oftalmológicos logo após o trauma podem ser decisivos para a preservação da acuidade visual. Sujeitos com achados de exame físico de acuidade visual deficitárias, defeito pupilar aferente e imagens radiográficas com alta profundidade da fratura da órbita estão em maior risco de perda de visão e justificam preocupação específica para avaliação de lesão ocular. O objetivo deste estudo foi reunir as manifestações clínicas oftalmológicas prevalentes em pacientes acometidos por fraturas orbitárias, com o intuito de adquirir melhor perspectiva e entendimento acerca das consequências que a patologia traz ao indivíduo, no que tange à oftalmologia e aos tratamentos mais adequados. Trata-se de estudo de revisão integrativa, utilizando as bases de dados Pubmed®/Medline®, SciELO, Biblioteca Virtual em Saúde e Lilacs, com um vocabulário controlado segundo a estratégia de busca em cada uma das bases de dados bibliográficas, por meio dos termos "ophthalmologic complications", "prevalence", "orbital fracture", em estudos publicados de 2013 a 2023. A qualidade dos artigos foi avaliada usando o Study Quality Assessment Tool from the Department of Health and Human Services. Foram encontradas 46 referências, sendo 20 no Pubmed®/Medline®, 17 na SciELO, 9 na Biblioteca Virtual em Saúde e nenhuma na Lilacs. Após excluir referências duplicadas, foram selecionadas 44 referências para avaliação de elegibilidade. Após leitura dos títulos e resumos (n=44), 36 estudos foram excluídos pelas seguintes razões: artigos que não respondiam a nossa pergunta científica (n=11) e publicação superior a 10 anos (n=25). Identificaram-se, nos oito artigos selecionados, o objetivo do estudo, a população estudada o nível de evidência. Os oito estudos tiveram como objetivo analisar traumas orbitais com alterações funcionais significativas oculares e visuais pelo prejuízo ao tecido ósseo, nervoso, vascular e até parenquimatoso cerebral na região do assoalho e paredes de cavidades orbital. Dentre as manifestações clínicas oftalmológicas mais importantes, listam-se manifestação de enoftalmia, diplopia, hifema traumático, hemorragia retiniana, amaurose, quemose, neuropatia óptica traumática e hematoma retrobulbar. Considerando os oito estudos analisados, verificou-se a presença unânime de manifestações clínicas oftalmológicas na totalidade dos pacientes acometidos, sendo predominantes a baixa acuidade visual e o hifema. No que tange aos achados de menor prevalência, ao equipará-los às manifestações clínicas oftalmológicas mais encontradas, verifica-se que possuem como fator principal o estado transitório, concluindo-se que, mesmo com toda a gravidade do quadro de fratura orbitária, sua tendência é não deixar sequelas permanentes em grande partes dos casos, ainda que não seja nítida a relação estabelecida pela ausência de sequelas permanentes, especulando-se que essa ausência se deve à identificação do quadro e à intervenção adequada em tempo hábil.

ABSTRACT One in four patients affected by maxillofacial trauma will have concomitant orbital fractures and ocular injuries; therefore, an ophthalmological evaluation is recommended for all patients who have been affected by facial trauma. Some ophthalmological exams soon after the trauma can be decisive for the preservation of visual acuity. Patients with physical examination findings of poor visual acuity, afferent pupillary defect, radiographic images with high depth of orbital fracture, are at greater risk of vision loss and specific concern for evaluation of ocular injury. The objective of this study was to gather the prevalent ophthalmologic clinical manifestations in patients affected by orbital fractures, to achieve a better perspective and understanding about the consequences that the pathology brings to the individual regarding ophthalmology and the most appropriate treatments. This is an integrative review study, using the Pubmed®/Medline®, SciELO, Virtual Health Library and Lilacs databases, with a controlled vocabulary according to the search strategy in each of the bibliographic databases, using the terms "ophthalmologic complications", "prevalence", "orbital fracture", in studies published from 2013 to 2023. The quality of the articles was assessed using the Study Quality Assessment Tool from the Department of Health and Human Services. A total of 46 references were found, 20 in Pubmed®/Medline®, 17 in SciELO, 9 in the Virtual Health Library and none in Lilacs. After excluding duplicate references, 44 references were selected for eligibility assessment. After reading the titles and abstracts (n=44), 36 studies were excluded for the following reasons: articles that did not answer our scientific question (n=11) and publication over 10 years (n=25). In the eight selected articles, the objective of the study, the population studied, and the level of evidence were identified. The eight studies aimed to analyze orbital trauma with significant ocular and visual functional changes due to damage to bone, nerve, vascular, and even brain parenchymal tissue in the region of the floor and walls of orbital cavities. Among the most important ophthalmologic clinical manifestations, there are enophthalmos, diplopia, traumatic hyphema, retinal hemorrhage, amaurosis, chemosis, traumatic optic neuropathy and retrobulbar hematoma. Considering the eight studies analyzed, there was a unanimous presence of ophthalmological clinical manifestations in all affected patients, with low visual acuity and hyphema being predominant. Regarding the findings of lower prevalence, when equating them to the most common ophthalmologic clinical manifestations, they have as main factor the transient state, which can be concluded that, even with all the severity of the orbital fracture, its tendency is not to leave permanent sequelae in most cases, although the relationship established by the absence of permanent sequelae is not clear, speculating that this absence is due to the identification of the condition and the appropriate intervention in a timely manner.

Retrospective cohort study to evaluate the continuous use of anticholesterolemics and diuretics in patients with COVID-19.

Purpose: The purpose of this study is to evaluate the interference of the continuous use of drug classes in the expression of biomarkers during the first week of hospitalization and in the prognosis of patients with COVID-19. Methods: The patients diagnosed with COVID-19 and confirmed with SARS-CoV-2 by RT-qPCR assay underwent the collection of fasting whole blood samples for further analysis. Other data also extracted for this study included age, sex, clinical symptoms, related comorbidities, smoking status, and classes of continuous use. Routine serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, C-reactive protein, N-terminal fragment of B-type natriuretic peptide, and cardiac troponin, were measured. Results: In this cross-sectional study, a total of 176 patients with COVID-19 hospitalizations were included. Among them, 155 patients were discharged (88.5%), and 21 patients died (12%). Among the drug classes evaluated, we verified that the continuous use of diuretic 4.800 (1.853-11.67) (p = 0.0007) and antihypercholesterolemic 3.188 (1.215-7.997) (p = 0.0171) drug classes presented a significant relative risk of death as an outcome when compared to the group of patients who were discharged. We evaluated biomarkers in patients who used continuous antihypercholesterolemic and diuretic drug classes in the first week of hospitalization. We observed significant positive correlations between the levels of CRP with cardiac troponin (r = 0.714), IL-6 (r = 0.600), and IL-10 (r = 0.900) in patients who used continuous anticholesterolemic and diuretic drug classes and were deceased. In these patients, we also evaluated the possible correlations between the biomarkers AST, NT-ProBNP, cardiac troponin, IL-6, IL-8, and IL-10. We observed a significantly negative correlations in AST levels with NT-ProBNP (r = -0.500), cardiac troponin (r = -1.00), IL-6 (r = -1.00), and IL-10 (r = -1.00) and a positive correlation with IL-8 (r = 0.500). We also observed significant negative correlation in the levels of NT-ProBNP with IL-10 (r = -0.800) and a positive correlation with cardiac troponin (r = 0.800). IL-6 levels exhibited positive correlations with cardiac troponin (r = 0.800) and IL-10 (r = 0.700). Conclusion: In this study, we observed that hospitalized COVID-19 patients who continued using anticholesterolemic and diuretic medications showed a higher number of correlations between biomarkers, indicating a poorer clinical prognosis. These correlations suggest an imbalanced immune response to injuries caused by SARS-CoV-2.

Hallermann-Streiff Syndrome and Lower Limb Lymphedema with Nasal Obstruction.

Background: Hallermann-Streiff syndrome (HSS) is a rare congenital abnormality involving multiple craniofacial malformations, such as micrognathia, prominent frontal and nasal bones, vision defects, and dental anomalies, which can result in obstructive sleep apnea syndrome. The aim of the present study was to report a case of nasal obstruction in an individual with Hallermann-Streiff syndrome who had never breathed through the nose during treatment for lower limb lymphedema involving cervical lymphatic therapy. Case Report. An 18-year-old female adolescent with a diagnosis of HSS was sent from the genetics service of a teaching school for the treatment of lower limb lymphedema. At around 11 years of age, the patient began to present edema in the left leg, accompanied by broadening of the face and neck. The patient reported having obstructed nostrils and breathing through the mouth her entire life. On the second day of treatment, the patient reported being able to breathe through one of the nostrils, this had never occurred before. Based on this finding, the decision was made to include linear facial lymphatic drainage using the Godoy method, which led to the complete resolution of the nasal obstruction in the first 15 minutes of treatment. Nasal obstruction in children with Hallermann-Streiff syndrome may be caused by lymphedema. Conclusion: A specific lymphatic drainage technique, such as cervical lymphatic therapy and facial linear lymphatic therapy, can resolve the obstruction and maintain the nostrils unblocked for months.

Pharmacokinetics of Carboplatin in Combination with Low-Dose Cyclophosphamide in Female Dogs with Mammary Carcinoma.

This prospective study aimed to evaluate the effect of metronomic cyclophosphamide on carboplatin's tolerability, efficacy, and pharmacokinetics in dogs with mammary carcinoma. Sixteen female dogs with mammary carcinoma were divided into groups: 300 mg/m2 intravenous (i.v.) carboplatin therapy (G1 = 8) or 300 mg/m2 i.v. carboplatin which was associated with 12.5 mg/m2 oral cyclophosphamide in a metronomic regimen (G2 = 8). The investigated animals underwent a clinical evaluation, a mastectomy, a carboplatin chemotherapy, and serial blood sampling for the pharmacokinetic analysis. The adverse events and survival rates were monitored. A non-compartmental analysis was applied to calculate the pharmacokinetic parameters of carboplatin in the 2nd and 4th chemotherapy cycles. Carboplatin PK showed high interindividual variability with a 10-fold variation in the area under the plasma concentration−time curve (AUC) in G1. The systemic plasma exposure to carboplatin was equivalent in both of the treatments considering the AUC and maximum plasma concentration (Cmax) values. Although the red blood cells (p < 0.0001), platelets (p = 0.0005), total leukocytes (p = 0.0002), and segmented neutrophils (p = 0.0007) were reduced in G2, the survival rate increased (p = 0.0044) when it was compared to G1. In conclusion, adding low daily doses of cyclophosphamide to a carboplatin therapy showed promising outcomes in female dogs with mammary tumors.

Monitor sanitario: experiencia de gestión y monitoreo de líneas de cuidado priorizadas en Córdoba / Health monitor: management and monitoring experience of prioritized lines of care in Córdoba

Para la gestión en salud, fortalecer la Atención Primaria como estrategia es un desafío. Esto implica coordinar los esfuerzos entre los distintos niveles de atención. En el caso de Argentina, la organización del sistema de salud divide las responsabilidades sobre cada nivel de atención en distintas jurisdicciones, quedando el primer nivel en la órbita de los municipios. En el caso de Córdoba, este escenario es particularmente complejo, ya que la descentralización del primer nivel de atención trajo consecuencias adversas, dificultando la integración de información sanitaria producida en los municipios. El Ministerio de Salud de la Provincia ha desarrollado una herramienta de monitoreo (el Monitor Sanitario) que construye indicadores de evaluación aprovechando los datos reportados por 754 efectores de salud públicos al programa Sumar. Estos indicadores se organizan por líneas de cuidado, y ya se encuentran en marcha los tableros que muestran los resultados para la línea de cuidado de personas gestantes y la de cuidado de personas con diabetes. La medición periódica de los desempeños por municipio de estas líneas se asocia a un pago por desempeño. Consideramos que esta experiencia permite mostrar la integración de esfuerzos para impactar en los tres componentes del sistema: en el modelo de atención (por definir priorización de cuidados y estimular la proactividad), en el modelo de financiamiento (al indicar las posibilidades de reporte al programa Sumar y al establecer un pago por resultados) y en el modelo de gestión (al orientar las gestiones locales a los resultados) (AU)

For health management, strengthening Primary Care as a strategy is a challenge. This implies coordinating efforts between the different levels of health care. In the case of Argentina, the health system assigns the responsibilities for each level of care to different jurisdictions, leaving the primary level of care in the orbit of the local governments. In the case of Córdoba, this scenario is particularly complex, considering the decentralization of the primary level of care brought adverse consequences, making it difficult to integrate health information produced in local governments.The Ministry of Health of the Province has developed a monitoring tool (the Health Monitor) that builds evaluation indicators taking advantage of the data reported by 754 public health effectors to Sumar program. These indicators are organized by lines of care, and there are two boards that already shows the results for pregnancy care and for people with diabetes. The periodic measurement of the performance of each local government in these lines is associated with a payment for performance.This experience shows how the integration of efforts impacts on the three components of the system: in the care model (by defining care prioritization and stimulating proactivity), in the financing model (by indicating the possibilities of reporting to Sumar program and establishing a payment for results) and in the management model (by directing local managements to results) (AU)

Fecal descriptor in honey: indole from a floral source as an explanation.

BACKGROUND: Animal odor, is one of the most common aroma defects described in the honey odor aroma wheel. It comprises two secondary descriptors: 'fecal' and 'cowshed'. However, the compounds responsible for these honey defects have not been fully identified. In this context, the aim of this work was to identify the compounds responsible for the aromatic defect 'fecal' in Uruguayan honeys by means of gas chromatography coupled to olfactometry (GC-O). RESULTS: Samples of honey described by beekeepers as having fecal aroma were analyzed by GC-O and gas chromatography coupled to mass spectrometry (GC-MS). Through GC-O, it was possible to establish the region of the chromatogram corresponding to the fecal descriptor, while the GC-MS analysis allowed to identify indole as the compound responsible for the fecal descriptor. The content of indole in the analyzed samples ranged between 132 and 414 µg kg-1 . The melissopalynological analysis indicated the presence of Scutia buxifolia ('quebracho' or 'coronilla') pollen in all samples studied. The volatile profile of Scutia buxifolia flowers was evaluated during the full day, enabling the identification of indole as one of its components. The detection threshold value for indole in honey was experimentally determined as 64 µg kg-1 of honey, a value lower than the concentration found in the evaluated samples. CONCLUSION: Results from the study allowed the identification of indole as the compound responsible for the 'fecal' aroma defect in Scutia buxifolia honeys. © 2022 Society of Chemical Industry.

NMDA receptors in the insular cortex modulate cardiovascular and autonomic but not neuroendocrine responses to restraint stress in rats.

The insular cortex (IC) is a brain structure involved in physiological and behavioural responses during stressful events. However, the local neurochemical mechanisms involved in control of stress responses by the IC are poorly understood. Thus, this study aimed to investigate the involvement of glutamatergic neurotransmission within the IC in cardiovascular, autonomic and neuroendocrine responses to an acute session of restraint stress. For this, the selective NMDA glutamate receptor antagonist LY235959 (1 nmol/100 nL) or the selective non-NMDA glutamate receptor antagonist NBQX (1 nmol/100 nL) were microinjected into the IC 10 min before the onset of the 60 min session of restraint stress. We observed that the antagonism of NMDA receptors within the IC enhanced the restraint-evoked increase in arterial pressure and heart rate, while blockade of non-NMDA receptors did not affect these cardiovascular responses. Spontaneous baroreflex analysis demonstrated that microinjection of LY235959 into the IC decreased baroreflex activity during restraint stress. The decrease in tail skin temperature during restraint stress was shifted to an increase in animals treated with the NMDA receptor antagonist. Nevertheless, the blockade of either NMDA or non-NMDA glutamate receptors within the IC did not affect the increase in circulating corticosterone levels during restraint stress. Overall, our findings provide evidence that IC glutamatergic neurotransmission, acting via local NMDA receptors, plays a prominent role in the control of autonomic and cardiovascular responses to restraint stress, but without affecting neuroendocrine adjustments.

Active Potential of Bacterial Cellulose-Based Wound Dressing: Analysis of Its Potential for Dermal Lesion Treatment.

The use of innate products for the fast and efficient promotion of healing process has been one of the biomedical sector's main bets for lesion treatment modernization process. The aim of this study was to develop and characterize bacterial cellulose-based (BC) wound dressings incorporated with green and red propolis extract (2 to 4%) and the active compounds p-coumaric acid and biochanin A (8 to 16 mg). The characterization of the nine developed samples (one control and eight active wound dressings) evidenced that the mechanics, physics, morphological, and barrier properties depended not only on the type of active principle incorporated onto the cellulosic matrix, but also on its concentration. Of note were the results found for transparency (28.59-110.62T600 mm-1), thickness (0.023-0.046 mm), swelling index (48.93-405.55%), water vapor permeability rate (7.86-38.11 g m2 day-1), elongation (99.13-262.39%), and antioxidant capacity (21.23-86.76 µg mL-1). The wound dressing based on BC and red propolis was the only one that presented antimicrobial activity. The permeation and retention test revealed that the wound dressing containing propolis extract presented the most corneal stratum when compared with viable skin. Overall, the developed wound dressing showed potential to be used for treatment against different types of dermal lesions, according to its determined proprieties.