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 .

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.

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.

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.

Significance of pro-angiogenic estrogen metabolites in normal follicular development and follicular growth arrest in polycystic ovary syndrome.

STUDY QUESTION: Do alterations in pro- and anti-angiogenic estrogen metabolites in follicular fluid (FF) contribute to the follicular growth arrest and anovulation associated with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: FF of PCOS women with anovulation have reduced levels of pro-angiogenic estrogen metabolites (EMs) and vascular endothelial growth factor (VEGF) compared to that of fertile women with regular menstrual cycles, but exogenous gonadotropins increase the pro-angiogenic EMs and VEGF levels in PCOS women. WHAT IS KNOWN ALREADY: PCOS is characterized by the arrest of follicular development that leads to chronic anovulation. Follicular arrest is generally associated with elevated plasma levels of luteinizing hormone (LH), androgens and anti-Mullerian hormone (AMH). There is also reduced angiogenesis in the follicles of PCOS women compared to those of normal cycling women. It is known that angiogenesis is a critical factor during follicular development. We and other investigators have explored the role of EMs in ovarian angiogenesis, particularly in human corpus luteum function, showing that 4-hydroxyestrone (4-OHE1) and 16-ketoestradiol (16-kE2) have pro-angiogenic effects while 2-methoxyestradiol (2-ME2) and 2-methoxyestrone (2-ME1) have anti-angiogenic effects. Additionally, 2-hydroxyestradiol (2-OHE2), which is produced in the ovary, has proliferative and pro-angiogenic properties. We hypothesized that EMs could be involved in angiogenesis necessary for ovarian follicular development in fertile women, and that dysregulation of these factors may contribute to follicular arrest in PCOS. The relationship between EMs, VEGF and AMH in the pathophysiology of follicular arrest in PCOS has not been previously studied at a follicular level in anovulatory women without ovulation induction. STUDY DESIGN, SIZE, DURATION: This is a comparative experimental study of serum and FF collected from different sized follicles (antral ˂10 mm and dominant ˃16 mm) of women with and without ovarian stimulation. The study included women with regular menstrual cycles who were proven to be fertile (n = 20) and PCOS women with follicular arrest who were candidates for ovarian drilling (n = 17), as well as other patients requiring ovarian stimulation, i.e. control women undergoing IVF for male factor infertility (n = 12) and PCOS women undergoing IVF (n = 17). In vitro studies were carried out on granulosa-lutein cells (GCs) obtained from subsets of women undergoing IVF for male factor infertility (n = 6) and PCOS women undergoing IVF (n = 6). GCs were maintained in culture for up to 6 days. PARTICIPANTS/MATERIALS, SETTING, METHODS: Intrafollicular estradiol, estrone and EMs concentrations were determined by high performance liquid chromatography-mass spectrometry. Testosterone in serum was measured by RIA, and LH, FSH and sex hormone-binding globulin in serum were measured with IRMA kits. AMH was determined in serum and FF by enzyme linked immunosorbant assay (ELISA). VEGF levels were measured in FF and conditioned medium by ELISA. Conditioned medium were obtained from cultured GCs. The angiogenic potential was assessed by in vitro angiogenic assays. MAIN RESULTS AND THE ROLE OF CHANCE: Pro-angiogenic EMs (4-OHE1, 16-kE2 and 2-OHE2) and VEGF were lower in FF of antral follicles of PCOS women with follicular arrest compared those of fertile women with ovulatory cycles (P < 0.05). In contrast, higher concentrations of AMH were found in FF of antral follicles from PCOS women with follicular arrest compared to those of fertile women with ovulatory cycles (P < 0.05). Exogenous gonadotropins used in IVF increased pro-angiogenic EMs and VEGF production in PCOS women, reaching similar profiles compared to control women receiving gonadotropins in their IVF treatment for male factor infertility. The pro-angiogenic EM 2-OHE2 increased the angiogenic potential and VEGF levels of GCs from PCOS women compared to the basal condition (P < 0.05). These findings suggest that there is a role for pro-angiogenic EMs in the control of follicular VEGF production. LIMITATIONS, REASONS FOR CAUTION: The limitations include the possibility that in vitro analysis of GCs might not reflect the in vivo mechanisms involved in the pro-angiogenic action of 2-OHE2 since GCs obtained at the time of oocyte retrieval belong to a very early stage of the luteal phase and might not be representative of GCs during follicular growth. Therefore, our findings do not conclusively rule out the possibility that other in vivo mechanisms also account for defective angiogenesis observed in PCOS. WIDER IMPLICATIONS OF THE FINDINGS: The present study highlights the significance of EMs, angiogenic factors and AMH and their interaction in the pathophysiology of follicular development in PCOS. This study provides new insights into the role of pro-angiogenic factors in follicular arrest in PCOS. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by CONICYT/FONDECYT 1140693 and NIH grant R01HD083323. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

[Expansion of family medicine in Latin America: challenges and lines of actionExpansão da medicina familiar na América Latina: desafios e linhas de ação]. / Expansión de la medicina familiar en América Latina: desafíos y líneas de acción.

This article summarizes the current challenges of family medicine in Latin America and proposes possible lines of action to consolidate its development. In the last 40 years, the health systems of the Region of the Americas have faced reforms whose results were negative in terms of equity, and primary health care, far from being a strategy designed to reduce it, was restricted to a selective and focal policy. In this context, the technical proposals for expansion of training positions in family medicine and their insertion in medical careers have lacked consistency and a clear political direction, and thus their lack of effectiveness can be considered a symptom of these incomplete reforms. In this regard, the Ibero-American Confederation of Family Medicine made recommendations on the political commitment of governments to ensure the necessary structure and funding, consolidate the model of family medicine as a mechanism for the implementation of primary health care, the hierarchy of programs of training, the working conditions of family doctors and professional certification, among others. These technical recommendations, without a consistent and timely political action, will not be more successful than previous attempts.

Este documento tem como objetivo resumir os desafios atuais da medicina familiar na América Latina e propor possíveis linhas de ação para consolidar seu desenvolvimento. Nos últimos 40 anos, os sistemas de saúde da Região das Américas encararam reformas cujos resultados foram negativos em termos de igualdade, e a atenção primária à saúde, longe de sê-la aquela estratégia destinada a reducir-la, restringiu-se a uma política focal e seletiva. Neste contexto, as propostas técnicas de expansão das praças de formação em medicina familiar e sua inserção nas carreiras de Medicina, não dispuseram de coerência e de uma direção política clara, razão pela qual sua falta de eficácia se pode ler como um sintoma destas reformas incompletas. Neste sentido, a Confederação Ibero-americana de Medicina Familiar realizou recomendações sobre o compromisso político dos governos a fim de assegurar a estrutura e o financiamento necessários, consolidar o modelo de medicina familiar como mecanismo de instrumentação da atenção primária à saúde, a hierarquização dos programas de formação, as condições laborais dos médicos de família e a certificação profissional, entre outras. Estas recomendações técnicas, sem ação política coerente e oportuna, não serão mais exitosos que as tentativas prévias.

In-vitro study of gonadotrophin signaling pathways in human granulosa cells in relation to progesterone receptor expression.

In humans, data on gonadotrophin-activated (LH, HCG and FSH) progesterone receptor expression and signalling pathways involved in matrix metalloproteinases (MMPs) expression presumably linked to the follicle rupture, are limited. Our hypothesis is LH, HCG and FSH increase progesterone receptor expression in granulosa cells through different signalling pathways, leading to an increased expression of ADAMTS-1 and MMP3/10, which may mediate follicular rupture through the transcription factor, HIF1A. Human granulosa cells were isolated from follicular aspirates obtained from 22 healthy women participating in our IVF programme for male-factor infertility. Progesterone receptor and HIF1A expression was assessed by immunofluorescence, and PKA-PKC-PI3K- ERK1/2, ADAMTS-1 and MMP3/10 expression by Western blot in pre-ovulatory and in cultured granulosa cells. Results show that HCG, LH and FSH regulate progesterone receptor expression and activate PKA, PKC, PI3K and ERK1/2 signalling pathways in granulosa cells but progesterone receptor expression is only mediated by PKA, PKC and ERK pathways. HCG, FSH and LH regulated MMPs expression through progesterone receptors. Moreover, HCG-progesterone-receptor-dependent HIF1A expression stimulated MMP3/10 expression but not that of ADAMTS-1. These results suggest differential downstream progesterone receptor signalling, as progesterone receptor regulates MMP3/10 expression via HIF1A, which is not involved in ADAMTS-1 expression.

Manganese and lead in dust fall accumulation in elementary schools near a ferromanganese alloy plant.

Previous studies have shown elevated airborne manganese (Mn) in villages adjacent to a Mn alloy production plant in Brazil and negative associations between biomarkers of Mn and children's cognition and behavior. Since small Mn particles may be carried for long distances, we measured manganese (Mn) and lead (Pb) dust fall accumulation in 15 elementary schools, located between 1.25 and 6.48km from the plant in the municipality of Simões Filho, Bahia, Brazil. Passive samplers (polyethylene Petri dishes) were set in interior and exterior environments. After 30 days, the samplers' content was solubilized with diluted nitric acid and Mn and Pb levels were analyzed by electrothermal absorption spectrometry. The overall geometric mean and range of Mn and Pb accumulation in dust fall (loading rates) were 1582µg Mn/m(2)/30 days (37-37,967) and 43.2µg Pb/m(2)/30 days (2.9-210.4). A logarithmic decrease in interior and exterior Mn loading rates was observed with distance from the ferro-manganese alloy plant. Multiple regression analyses of log-transformed Mn loading rate within the schools showed a positive association with Mn levels in outdoor dust, a negative association with distance from the plant; as well, wind direction (downwind>upwind) and school location (urban>rural) entered significantly into the model. For the interior school environments, located within a 2-km radius from the plant, loading rate was, on average, 190 times higher than the Mn levels reported by Gulson et al., (2014) in daycare centers in Sydney, Australia, using a similar method. Pb loading rates were not associated with distance from the plant and were lower than the rates observed in the same daycare centers in Sydney. Our findings suggest that a significant portion of the children in this town in Brazil may be exposed to airborne Mn at concentrations that may affect their neurodevelopment.

Influence of experimental diabetes and insulin treatment on the enantioselective pharmacokinetics of mexiletine and its metabolites.

This study evaluates the influence of streptozotocin-induced diabetes on the kinetic disposition and metabolism of mexiletine (MEX) enantiomers in rats. Animals in the control (n = 6 for each blood collection time), diabetic (single intravenous dosage of 45 mg·(kg body mass)(-1) of streptozotocin), and insulin-treated groups (diabetic rats treated daily with 2 IU insulin) received by gavage a single dose of 10 mg·(kg body mass)(-1) racemic MEX. MEX enantiomers and the metabolites hydroxymethylmexiletine (HMM) and p-hydroxymexiletine PHM) were analyzed by LC-MS/MS. Statistical analysis was based on a serial sacrifice design, and parameter estimation was performed using a Bayesian modeling procedure. Area under the curve (AUC) for the (-)-(R) enantiomers of MEX, HMM, and PHM did not differ between the control and diabetic groups. However, AUC for (+)-(S)-MEX and (+)-(S)-HMM were lower in the diabetic than in the control group. Insulin treatment recovered glucose levels to normal and the (+)-(S)-MEX AUC and (+)-(S)-HMM AUC became similar to the AUCs observed in the nondiabetic animals.

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.

A case report of newborn with Klippel-Trenaunay syndrome from mother currently infected by COVID-19.

Background: Coronavirus disease 2019 (COVID-19) novel severe acute respiratory syndrome affected the world population with an infectious condition for which therapeutic forms are limited and vascular sequelae are major challenges. Pregnant women are physiologically immunocompromised and can be more affected by the pandemic than the general population. Extra precaution measures against COVID-19 during and after the outbreak are essential to ensure the safety of the newborn. The aim of the present study was to report the cesarean birth of a female child with Klippel-Trenaunay of a mother currently infected by COVID-19. Case Description: A newborn of a 21-year-old mother with COVID-19 in the final stage of the disease was born through a cesarean section at full term. The physical examination at birth revealed substantial edema of the left lower limb associated with port-wine stains on the limb and left torso. The ultrasound revealed venous-lymphatic malformation affecting the entire left lower limb, suprapubic region and ipsilateral abdominal region. Two evaluations for COVID-19 were performed and both were negative. Infants of mothers with active COVID-19 infection during the birth period have a low probability of being positive for the disease, but precautions should be taken. Conclusions: The association with malformations, such as the rare Klippel-Trenaunay syndrome (KTS), constitutes another challenge regarding the diagnosis and proper conduct to be taken with these children.

Modified Senning Procedure for Treatment of Transposition of the Great Arteries with Crisscross Heart.

CLINICAL DATA: A nine-month-old female infant diagnosed with transposition of the great arteries with symptoms of heart failure associated with cyanosis and difficulty in gaining weight was referred to our center with late diagnosis (at nine months of age). CHEST RADIOGRAPHY: Cardiomegaly; attenuated peripheral vascular markings.Electrocardiography: Sinus rhythm with biventricular overload and aberrantly conducted supraventricular extra systoles. ECHOCARDIOGRAPHY: Wide atrial septal defect, ventricular axis torsion with concordant atrioventricular connection and discordant ventriculoarterial connection. COMPUTED TOMOGRAPHY ANGIOGRAPHY: Concordant atrioventricular connection, right ventricle positioned superiorly and left ventricle positioned inferiorly; discordant ventriculoarterial connection with right ventricle connected to the aorta and left ventricle connected to pulmonary artery. DIAGNOSIS: Crisscross heart is a rare congenital heart defect, accounting for 0.1% of congenital heart diseases. It consists of the 90º rotation of ventricles' axis in relation to their normal position; therefore, ventricles are positioned in the superior-inferior direction rather than anterior-posterior. Most cases have associated cardiac anomalies, and in this case, it is associated with transposition of the great arteries. The complexity and rarity of its occurrence make diagnosis and surgical treatment challenging. OPERATION: Modified Senning procedure using the pericardial sac in the construction of a tunnel from pulmonary veins to the right atrium. Cardiopulmonary bypass time of 147 minutes with nine minutes of total circulatory arrest.

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.

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.

[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.

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.

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.

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.