Neutrophil-Lymphocyte Ratio as a Predictor of the Risk of Death in Severe Cases of COVID-19.

BACKGROUND: Identifying clinical characteristics and risk factors, comorbid conditions, and complications arising from SARS-CoV-2 infection is important to predict the progression to more severe forms of the disease among hospitalized individuals to enable timely intervention and to prevent fatal outcomes. The aim of the study is to assess the possible role of the neutrophil/lymphocyte ratio (NLR) as a biomarker of the risk of death in patients with comorbidities hospitalized with COVID-19 in a tertiary hospital in southern Brazil. METHODS: This is a prospective cohort study on patients with SARS-CoV-2 infection admitted to a hospital in the metropolitan region of Porto Alegre from September 2020 to March 2022. RESULTS: The sample consisted of 185 patients with associated comorbidities, namely, hypertension, diabetes mellitus, obesity, cardiovascular, pulmonary, and renal diseases, hospitalized with COVID-19. Of these, 78 died and 107 were discharged alive. The mean age was 66.5 years for the group that died and 60.1 years for the group discharged. Statistical analysis revealed that a difference greater than or equal to 1.55 in the NLR, from hospitalization to the 5th day, was associated with a relative risk of death greater than 2. CONCLUSIONS: Measuring a simple inflammatory marker such as NLR may improve the risk stratification of comorbid patients with COVID-19 and can be considered a useful biomarker.

Abdominal perfusion in canine patients with pyometra and sepsis evaluated by Doppler and contrast-enhanced ultrasound.

BACKGROUND: Sepsis is a condition characterized by organic dysfunction, leading to hemodynamic instability and high morbidity and mortality rates in humans and animals. Early identification of perfusion changes and appropriate management of sepsis are crucial for improving patient prognosis. Currently, the Systemic Inflammatory Response Syndrome (SIRS) and Sequential Organ Failure Assessment (SOFA) scores are widely studied for sepsis identification and evaluation of organ dysfunction. However, these scores do not assess gastrointestinal involvement, which is common in this condition. Contrast-enhanced ultrasound (CEUS) and Doppler have been considered promising diagnostic techniques for detecting changes in vascularization and microcirculation in a non-invasive and safe manner, particularly in the gastrointestinal system. This study aimed to evaluate duodenal perfusion using CEUS, as well as abdominal aortic and cranial mesenteric artery blood flow using Doppler ultrasound, and systolic arterial pressure (SAP) in 17 bitches with pyometra and in 10 healthy animals. RESULTS: The variables were compared between the pyometra and control groups, as well between patients with and without sepsis determined by the SOFA or SIRS scores. Pyometra was found to cause a reduction in abdominal aortic blood flow volume, aortic peak systolic velocity, and resistivity index as evaluated by Doppler ultrasound. Patients with sepsis according to the SOFA criteria only presented lower SAP. In contrast, sepsis animals identified by the SIRS score exhibited lower SAP, aortic peak systolic velocity, aortic blood flow volume, and aortic resistivity index and additionally, higher peak intensity of contrast in the duodenal wall. CONCLUSIONS: Pyometra causes a reduction in abdominal aortic blood flow, which is more pronounced in animals with sepsis identified by the SIRS criteria. These animals also exhibited a decrease in systolic blood pressure and an increase in duodenal perfusion, as evident by CEUS. However, these changes were not observed in patients with sepsis identified by the SOFA criteria. The alterations in intestinal perfusion observed in animals with sepsis indicate the presence of inflammation or dysfunction. In this regard, CEUS proves to be a valuable technique for detecting subtle changes in tissue hemodynamics that may not be apparent in conventional exams.

A new ROV storage device for deep-sea sampling.

Sampling deep-sea biota is a significant challenge because of the logistics required, in terms of vessels and equipment, to obtain minimally preserved specimens. Traditional methods (trawls, nets, and dredges) cause physical damage, stress, and even contamination during the process of removal from the seabed and their displacement through the water column to the surface. Preserving conditions similar to those found in situ is particularly important when the sampling strives to maintain living organisms and for analyses where contamination or degradation by stress or damage may interfere with the results. Therefore, for the sampling and storage of this biota with less interference, a polypropylene box was designed based on the model of Kellogg et al. (2009) incorporating adaptations to be used by a Remotely Operated Vehicle (ROV). This new device has been successfully used in eight oceanographic campaigns, adequately performing for sediment and biota sampling, including coral reef forming or framework species (Scleractinia), octocorals, associated fauna, and rhodoliths, at depths between 50 and 900 m.

The Use of Proteins, Lipids, and Carbohydrates in the Management of Wounds.

Despite the fact that skin has a stronger potential to regenerate than other tissues, wounds have become a serious healthcare issue. Much effort has been focused on developing efficient therapeutical approaches, especially biological ones. This paper presents a comprehensive review on the wound healing process, the classification of wounds, and the particular characteristics of each phase of the repair process. We also highlight characteristics of the normal process and those involved in impaired wound healing, specifically in the case of infected wounds. The treatments discussed here include proteins, lipids, and carbohydrates. Proteins are important actors mediating interactions between cells and between them and the extracellular matrix, which are essential interactions for the healing process. Different strategies involving biopolymers, blends, nanotools, and immobilizing systems have been studied against infected wounds. Lipids of animal, mineral, and mainly vegetable origin have been used in the development of topical biocompatible formulations, since their healing, antimicrobial, and anti-inflammatory properties are interesting for wound healing. Vegetable oils, polymeric films, lipid nanoparticles, and lipid-based drug delivery systems have been reported as promising approaches in managing skin wounds. Carbohydrate-based formulations as blends, hydrogels, and nanocomposites, have also been reported as promising healing, antimicrobial, and modulatory agents for wound management.

Impact of allogeneic stem cell transplantation in childhood and adolescence on quality of adulthood life: A case-control study.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with late complications that can impair the quality of life (QoL) of patients for years after transplant. The purpose of the present study was to determine the difference in the QoL of adults that underwent allo-HSCT in childhood and adolescence compared with not transplanted adults. METHODS: In this prospective case-control cross-sectional study, we included patients aged ≥18 years that received an allo-HSCT during childhood or adolescence and subsequently survived at least 2 years after transplantation. The control group consisted of blood donors matched for age and sex. QoL assessment was performed using the Short Form-36 (SF-36) Health Survey, Portuguese version 2. RESULTS: Thirty-four transplanted patients and controls were included. 58.8% were male, and the median age at transplant was 13.5 years (range, 4-17 years). The median follow-up was 11.5 years (range, 2.0-23.0 years). The most common late effect was skeletally followed by endocrine complications. Patients with these late complications had the worst QOL in the following dimensions: physical functioning, role physical, bodily pain, general health, and mental health. When compared to the control group, patients had a lower score in two dimensions: physical functioning and role physical. CONCLUSIONS: Although skeletal and endocrine complications of transplant patients in childhood have an impact on physical functioning, most parameters of QoL of these patients in adulthood are similar to healthy individuals of the same age and gender. Early detection and long-term monitoring of late complications can prevent impairment of the QoL.

Variation in nest building, aggression, learning, and steroid hormone levels in Betta splendens.

Individuals within a population present behavioral responses that vary according to intrinsic and extrinsic factors such as ontogenetic phase, nutritional status, reproductive stage, and previous experiences. These differences can be explained by endogenous changes, such as hormone release, that can modulate reproductive behaviors, stress response, and cognitive processes. In order to investigate the relationship between behavior and hormonal levels in the fighting fish Betta splendens, the present study characterized nest building, aggressive behavior, learning of a task, and levels of cortisol and 11-ketotestosterone (11-KT) in 86 male Fighting fish. At the beginning of the experiment (days 1-4), fish were characterized as nest builders, intermediate builders, or non-builders. They were then sequentially tested for aggression (days 7-8), learning performance (days 11-21), and circulating hormone levels (day 23). Nest builders showed the lowest hormonal levels at the end of the experiment and low aggressiveness; Intermediate builders presented low cortisol, but high KT levels and best learned the task; Non-builders were the most aggressive animals with higher cortisol levels (at day 23). Our data suggest that in B. splendens, aggressive behavior and learning performance are related to the relative investment in reproduction and variation in circulating levels of corticosteroids and androgens.

Molecular characterization of canine filarioids in a previously non-endemic area of Rio de Janeiro State, Brazil.

Dirofilaria immitis is the causative agent of canine heartworm disease, a severe health problem in dogs, especially in coastal areas of tropical and subtropical regions of the world. We employed molecular methods to investigate the occurrence of canine infection by filarioids in five municipalities of Baixada Fluminense (Magé, Duque de Caxias, Guapimirim, Nova Iguaçu, and São João de Meriti), a non-endemic area of Rio de Janeiro State, Southeast Brazil. A total of 110 canine blood samples collected from 2017 to 2018 and positive for microfilariae at the modified Knott's test were screened by cPCR targeting DNA fragments of the 12S rDNA gene for filarial nematodes. Seventy-seven samples (70%) tested positive at the molecular analysis. Of these, 72 were identified as D. immitis and 5 (4.5%) as Acanthocheilonema reconditum. Dirofilaria repens was not detected in the studied municipalities of Baixada Fluminense. This is the first record of D. immitis and A. reconditum in the Baixada Fluminense region, Rio de Janeiro State, Brazil. The prevalence of D. immitis cases in the five municipalities suggests the establishment and maintenance of its enzootic cycle in the studied region, which indicate vulnerability to the occurrence of epidemic cycles and, possibly, human cases.

Effect of experimental stress and cortisol release induced by ACTH administration on expression of key genes related to milk synthesis and apoptosis during mammary involution of Saanen goats.

This research paper addresses the hypothesis that stress, induced by ACTH administration and cortisol release increases somatic cell count (SCC) in mammary secretion, and improves the effectiveness of dry off in goats. We report indicators of milk synthesis and mammary gland involution during dry off. Thirty Saanen goats were subjected to abrupt dry off and treatments: (1) ACTH administration (ACTH) or (2) placebo (Control) on days 1, 3, 6, 9, 12, 15, 30, and 60 of dry off. The expression of target genes in mammary tissue that are related to milk synthesis and cell survival such as insulin-like growth factor 1 receptor (IGF1R), phosphatidylinositol-3-kinase (PIK3CA), protein kinase B (AKT1) and mechanistic target of rapamycin (MTOR), casein (CSN2), lactalbumin (LALBA) and lactoferrin (LF) were evaluated, and plasma cortisol concentration, SCC, leucocyte count, and microbiological analyses in milk and mammary secretions were assessed. ACTH significantly downregulated the expression of IGF1R and upregulated the expression of PIK3CA in mammary tissue, increased lactoferrin concentration and SCC, and changed immune cell levels in mammary secretions compared to Control. Furthermore, ACTH administration increased the percentage of dry goats compared to the Control (73 vs. 46%, respectively). We conclude that the effect of stress via ACTH administration and cortisol release accelerated mammary involution during the early dry-off period.

Population-based approaches for monitoring the nurturing care environment for early childhood development: A scoping review.

Selecting indicators to monitor nurturing care (NC) environments that support decision-making and guide the implementation of integrated early childhood development (ECD) programmes has become a priority globally. Several population-based approaches have been attempted to create a set of indicators or a composite index methodology to measure the NC environment using existing secondary data. However, they have not been systematized. Our scoping review aimed to analyse the population-based approaches for monitoring the domains of the NC (e.g. good health, adequate nutrition, responsive caregiving, security and safety, and opportunities for early learning). ECD experts, peer-reviewed, and grey literature were systematically searched with no year or language restrictions. Data extraction used a standard predefined protocol. Thirty-two population-based approaches were identified. Most approaches were composed of a set of indicators (53.1%, n = 17) versus composite indexes (46.9%, n = 15) and had the country as their unit of analysis (68.8%, n = 22). Twenty-seven approaches were applied in middle-income countries (84.4%) and thirteen in low-income countries (40.6%). Four approaches were guided by the NC framework (12.5%), and 56.3% (n = 18) did not include any indicator representing responsive caregiving. NC indicators (n = 867) were sorted into 100 groups of indicators. Twenty of the 32 approaches had some kind of methodological validation (62.5%). We identified six methodological challenges to build a population-based approach. Standardized methods for selecting and validating indicators, and coordinated efforts to share findings/data with stakeholders should be prioritized. Given the great variability in methods and indicators used to measure NC environments, valid approaches should be flexible to work well across different contexts.

Potentiating activity of Norfloxacin by synthetic chalcones against NorA overproducing Staphylococcus aureus.

Staphylococcus aureus is responsible for a series of infections occurring in both human and animal hosts. S. aureus SA1199B is a strain resistant to hydrophilic fluoroquinolone due to overproduction of the NorA efflux pump that has been used as a microbial model to evaluate if a compound act as efflux pump inhibitor. Finding substances from natural or synthetic origin able to reverse resistance mechanisms like those of efflux pumps is a challenge. The use of Chalcones and their derivatives is of great chemical and pharmacological interest, as they present a simple structure and several pharmacological activities. This study aims to evaluate the antibacterial potential of 4 synthetic chalcones, as well as to evaluate their action in the modulation of Norfloxacin resistance against the strain SA1199B strain. Microdilution assays were performed for evaluation of the antimicrobial activity. For evaluation of the modulating effect on resistance to Norfloxacin or EtBr, MIC values of these compounds were determined in the absence or presence of subinhibitory concentrations used of each chalcone. MICs values of both Norfloxacin and EtBr were significantly reduced in the presence of all tested chalcones, indicating that inhibition of the active efflux of these compounds by NorA could be a possible mechanism of action of the chalcones. These results show that the compounds studied have a high potential as a NorA inhibitor, with the best modulating effect verified for the compound 3. Pharmacokinetic and toxicity predictive studies indicated a high intestinal absorption and good volume of distribution for chalcones by oral administration, activity in the central nervous system and ease to be transported between biological membranes. Emphasizing that analogs 1 and 4 were easily metabolized by CYP3A4 enzyme, constituting a pharmacological active ingredient without toxic risk due to metabolic activation. These chalcones combined with Norfloxacin could be a promise technological strategy to be applied in the treatment of infections caused by S. aureus overproducing NorA.

Inflammatory effect of Bothropstoxin-I from Bothrops jararacussu venom mediated by NLRP3 inflammasome involves ATP and P2X7 receptor.

Muscle tissue damage is one of the local effects described in bothropic envenomations. Bothropstoxin-I (BthTX-I), from Bothrops jararacussu venom, is a K49-phospholipase A2 (PLA2) that induces a massive muscle tissue injury, and, consequently, local inflammatory reaction. The NLRP3 inflammasome is a sensor that triggers inflammation by activating caspase 1 and releasing interleukin (IL)-1ß and/or inducing pyroptotic cell death in response to tissue damage. We, therefore, aimed to address activation of NLRP3 inflammasome by BthTX-I-associated injury and the mechanism involved in this process. Intramuscular injection of BthTX-I results in infiltration of neutrophils and macrophages in gastrocnemius muscle, which is reduced in NLRP3- and Caspase-1-deficient mice. The in vitro IL-1ß production induced by BthTX-I in peritoneal macrophages (PMs) requires caspase 1/11, ASC and NLRP3 and is dependent on adenosine 5'-triphosphate (ATP)-induced K+ efflux and P2X7 receptor (P2X7R). BthTX-I induces a dramatic release of ATP from C2C12 myotubes, therefore representing the major mechanism for P2X7R-dependent inflammasome activation in macrophages. A similar result was obtained when human monocyte-derived macrophages (HMDMs) were treated with BthTX-I. These findings demonstrated the inflammatory effect of BthTX-I on muscle tissue, pointing out a role for the ATP released by damaged cells for the NLRP3 activation on macrophages, contributing to the understanding of the microenvironment of the tissue damage of the Bothrops envenomation.

Indexes to assess feeding practices of children under 2 years old: a systematic review.

OBJECTIVE: To systematically review studies that used indexes to assess feeding practices of children under 2 years. DESIGN: Seven databases were searched with no limit on language or publication date. SETTING: The reviewed studies included thirteen Asian, ten Latin American, four European, four North American, three Oceanian and three African. PARTICIPANTS: Children under 2 years. RESULTS: We analysed thirty-six studies: twenty-two presenting original indexes and fourteen using adapted indexes. Among the original indexes, thirteen assess breast-feeding, fourteen food consumption, ten food groups, and ten other feeding practices. Original indexes were mainly adapted to fit the data available in the study, to update for current nutritional recommendations or to add components not present in the original indexes. Seven studies evaluated the associations between the indexes and nutrient intake or nutritional status. The main limitations cited by the authors were: flaws in the definition of the index components, criteria for cut-off points and weighting of the evaluated index components. CONCLUSIONS: The assessment of feeding practices for young children and its comparison across countries remains a challenge, especially due to the lack of consensus on the construction of indexes and regional differences in dietary recommendations and practices. Lack of validation for some indexes also makes it difficult to choose the most appropriate index for a given objective. Adapting existing indexes is a viable option. We point out relevant recommendations that may contribute to future research. Validation and longitudinal studies in diverse populations are favourable to qualify the assessment of feeding practices in this group.

Synthesis and biological evaluation of thiazolidinedione derivatives with high ligand efficiency to P. aeruginosa PhzS.

The thiazolidinone ring is found in compounds that have widespan biology activity and there is mechanism-based evidence that compounds bearing this moiety inhibit P. aeruginosa PhzS (PaPzhS), a key enzyme in the biosynthesis of the virulence factor named pyocyanin. Ten novel thiazolidinone derivatives were synthesised and screened against PaPhzS, using two orthogonal assays. The biological results provided by these and 28 other compounds, whose synthesis had been described, suggest that the dihydroquinazoline ring, found in the previous hit (A- Kd = 18 µM and LE = 0.20), is not required for PaPzhS inhibition, but unsubstituted nitrogen at the thiazolidinone ring is. The molecular simplification approach, pursued in this work, afforded an optimised lead compound (13- 5-(2,4-dimethoxyphenyl)thiazolidine-2,4-dione) with 10-fold improvement in affinity (Kd= 1.68 µM) and more than 100% increase in LE (0.45), which follows the same inhibition mode as the original hit compound (competitive to NADH).Executive summaryPhzS is a key enzyme in the pyocyanin biosynthesis pathway in P. aeruginosa.Orthogonal assays (TSA and FITC) show that fragment-like thiazolidinedione derivatives bind to PaPhzS with one-digit micromolar affinity.Fragment-like thiazolidinedione derivatives bind to the cofactor (NADH) binding site in PaPhzS.The molecular simplification optimised the ligand efficiency and affinity of the lead compound.

HCC Detection on Surveillance US: Comparing Focused Liver Protocol Using US LI-RADS Technical Guidelines to a General Complete Abdominal US Protocol.

OBJECTIVE: Focused US examinations of the liver in the routine hepatocellular carcinoma (HCC) screening reduce the time spent on evaluating other structures deemed irrelevant to the clinical setting. It is still unknown, however, if such a strategy may additionally improve the frequency of nodules detection. We aimed to assess the impact of an HCC surveillance program in high-risk patients by means of targeted liver US following LI-RADS technical guidelines in comparison to a complete upper abdominal scan. METHODS: In this IRB-approved, single-center, prospective study, patients at high-risk for HCC enrolled from 06/2016 to 09/2019 were randomly assigned to 1 of the 2 institutional protocols: Group A (targeted liver US) or Group B (complete upper abdominal scan). Twenty examiners with similar experience in abdominal US were randomly assigned to perform the examinations exclusively in 1 of the groups (10 in each group). Frequency of hepatic nodules between groups was compared by using Fisher's exact test. RESULTS: Four hundred and sixty-five patients were enrolled, with no significant differences in both groups regarding sex, age, etiology of liver disease, MELD scores, and alpha-fetoprotein levels. A significantly higher frequency of nodules detection was found in Group A (230 patients; 23 nodules detected; 10% of the sample) in comparison to Group B (235 patients; 3 nodules; 1.3% of the sample) (p <.001). Five patients in Group A and 1 in Group B were positive for HCC after full diagnostic work-up. CONCLUSION: Adopting an HCC screening program based on targeted liver US improved the detection of hepatic nodules among high-risk individuals.

Long-term heat stress at final gestation: physiological and heat shock responses of Saanen goats.

The long exposure to heat negatively changes performance and productivity of animals, particularly when heat stress is associated with gestation. Indeed, little is known about the negative effects of long-term heat stress on the final gestation of dairy goats. In this context, the physiological and cellular responses of Saanen goats submitted to heat stress (37°C from 10:00 to 16:00 h) were investigated from day 60th pre-partum to day 60th post-partum. At final gestation, 46 pregnant Saanen goats were randomly assigned to the treatments: control (CT; thermal neutral conditions) and heat stress (HS; climatic chamber). After partum, all experimental goats were maintained in thermal neutral conditions. The rectal, dorsal, mammary temperatures and respiratory frequency, cortisol release, milk yield, milk quality, and the genes HSP60, HSP70, HSP90, Glucocorticoid receptor and ACTHR. Goats subjected to HS showed significantly (P < 0.05) higher rectal, dorsal, and mammary temperatures and significantly mobilized the increase of respiratory frequency to lose heat as compared to CT goats. The HS challenge significantly increased cortisol release from day 15th pre-partum to day 15th post-partum. CT goats produced more milk than HS from weeks 4 to 10 of lactation (P <0.001), with no difference in milk quality. However, on day 15th post-partum, there was a significant effect of HS treatment on the expression of HSP70 and ACTHR genes as compared to CT treatment, confirming the long-term effect of HS on Saanen goats. In conclusion, the physiological parameters studied increased pre-partum in the hottest hour, and cortisol peaked on day 15 pre-partum for heat-stressed goats. Although on the 15th day post-partum, all goats were in thermal comfort, and the physiological parameters were within the normal range, the concentration of cortisol continued to be significantly higher for goats submitted to thermal stress. Indeed, milk yield was greater for goats subjected to pre-partum thermal comfort. Furthermore, the expression of HSP70 and ACTHR genes on peripheral blood mononuclear cells are interesting biomarkers for studying the long-term effect of heat stress on Saanen goats.

Scope of Preparation of Oval and Long-Oval Root Canals: A Review of the Literature.

Successful endodontic treatment depends on cleaning and disinfecting the root canals, in order to provide conditions for three-dimensional filling, which should prevent root canal reinfection. However, anatomical complexities pose a challenge during endodontic treatment. The present study was a literature review carried out in the following databases: PubMed, SciELO, and MEDLINE, which were searched for articles published from 2017 to 2021. Micro-CT studies published in English, which analysed the capacity for preparation of oval and long-oval root canals, were included. The following keywords were used: "oval-shaped canals," "long-oval-shaped canals," "endodontics," and "micro-CT." The aim of this study was to carry out a literature review of micro-CT studies on the scope of the capacity for preparation performed in oval and long-oval root canals with rotary and reciprocating instruments.

Identification and validation of mutation points associated with waxy phenotype in cassava.

BACKGROUND: The granule-bound starch synthase I (GBSSI) enzyme is responsible for the synthesis of amylose, and therefore, its absence results in individuals with a waxy starch phenotype in various amylaceous crops. The validation of mutation points previously associated with the waxy starch phenotype in cassava, as well as the identification of alternative mutant alleles in the GBSSI gene, can allow the development of molecular-assisted selection to introgress the waxy starch mutation into cassava breeding populations. RESULTS: A waxy cassava allele has been identified previously, associated with several SNPs. A particular SNP (intron 11) was used to develop SNAP markers for screening heterozygote types in cassava germplasm. Although the molecular segregation corresponds to the expected segregation at 3:1 ratio (dominant gene for the presence of amylose), the homozygotes containing the SNP associated with the waxy mutation did not show waxy phenotypes. To identify more markers, we sequenced the GBSS gene from 89 genotypes, including some that were segregated from a cross with a line carrying the known waxy allele. As a result, 17 mutations in the GBSSI gene were identified, in which only the deletion in exon 6 (MeWxEx6-del-C) was correlated with the waxy phenotype. The evaluation of mutation points by discriminant analysis of principal component analysis (DAPC) also did not completely discriminate the waxy individuals. Therefore, we developed Kompetitive Allele Specific PCR (KASP) markers that allowed discrimination between WX and wx alleles. The results demonstrated the non-existence of heterozygous individuals of the MeWxEx6-del-C deletion in the analyzed germplasm. Therefore, the deletion MeWxEx6-del-C should not be used for assisted selection in genetic backgrounds different from the original source of waxy starch. Also, the alternative SNPs identified in this study were not associated with the waxy phenotype when compared to a panel of accessions with high genetic diversity. CONCLUSION: Although the GBSSI gene can exhibit several mutations in cassava, only the deletion in exon 6 (MeWxEx6-del-C) was correlated with the waxy phenotype in the original AM206-5 source.

Hematopoietic cell transplantation in pediatric patients with acute leukemias or myelodysplastic syndrome using unrelated adult or umbilical cord blood donors in Brazil.

The choice of alternative donors for HCT for patients without an HLA-matched related donor depends on several factors. We compared major HCT outcomes in 212 consecutive children transplanted at 11 centers in Brazil for acute leukemia or MDS from an HLA-matched unrelated donor (MUD, n = 95), mismatched unrelated donor (MMUD, n = 47) or unrelated umbilical cord blood (UCB, n = 70). Most had ALL (61%), bone marrow (57%) as the graft source and 95% received a MAC regimen. The 3-year OS probability were 57, 55, and 37% after HCT from MUD, MMUD, and UCB, respectively (HR 1.68, 95%CI 1.07-2.63; P = .02). In comparison with MUD, OS was similar after transplantation of a ≥ 6/8 HLA-matched or a high cell dose (>5 × 107 TNC/kg) CB unit (HR 1.41, 95%CI 0.88-2.27; P = .15). NRM was higher for UCB (HR 3.90, 95%CI 1.43-10.7; P = .01) but not for MMUD (HR 1.03, 95%CI 0.53-2.00; P > .20). Advanced disease (HR 2.05, 95%CI 1.26-3.33; P < .001) and UCB with high probability of being < 6/8 HLA-matched (HR 5.34, 95%CI 2.0-13.9; P < .001) were associated with higher mortality. Relapse and acute GVHD were similar among groups, while PGF was higher among UCB transplants (P = .002) and chronic GVHD among MMUD group (HR 2.88, 95% CI 1.05-7.88; P = .04). Our results suggest that in Brazil HCT outcomes performed with MMUD and MUD donors were comparable, while with UCB units < 6/8 HLA-matched were associated with higher NRM for children with acute leukemia or MDS.

Impact of moderate-severe persistent allergic rhinitis on thoraco-abdominal kinematics and respiratory muscle function.

Objective: To assess thoraco-abdominal kinematics, respiratory muscle strength and electromyographic activity of the diaphragm (EAdi) in moderate-severe allergic rhinitis (AR) patients. Methods: A cross-sectional study involving 40 individuals (20 in the AR group) and 20 in the control group [CG]) was conducted. Ventilatory pattern and chest wall volume distribution (optoelectronic plethysmography), respiratory muscle strength (manovacuometry and sniff nasal inspiratory pressure [SNIP]), and EAdi were assessed in both groups. Results: The AR patients had impaired thoraco-abdominal kinematics (reduced total chest wall volume) (p = 0.004), lower values of total respiratory cycle time (p = 0.014) and expiratory time (p = 0.006). They also presented an increase of percentage contribution of the abdominal rib cage (p = 0.475) and respiratory rate (p = 0.019). A positive correlation among pulmonary rib cage tidal volume and MIP (r = 0.544; p < 0.001), SNIP (r = 0.615; p < 0.001), and MEP (r = 0.604; p < 0.001) was observed. After adjusting for age, BMI and gender through multivariate analysis, the individuals with AR presented lower values ​​of MIP (ß = -24.341; p < 0.001), MEP (ß = -0.277; p < 0.001), SNIP (ß = -34.687; p < 0.001) and RMS (ß = -0.041; p = 0.017). Conclusions: The individuals with moderate-severe persistent AR had worse respiratory muscle strength, diaphragm activation and chest wall volume distribution with a higher abdominal contribution to tidal volume than the control group. These findings reinforce the notion that the upper and lower airways work in an integrated and synergistic manner.

Antileishmanial activity evaluation of thiazolidine-2,4-dione against Leishmania infantum and Leishmania braziliensis.

Leishmaniasis is responsible for approximately 65,000 annual deaths. Despite the mortality data, drugs available for the treatment of patients are insufficient and have moderate therapeutic efficacy in addition to serious adverse effects, which makes the development of new drugs urgent. To achieve this goal, the integration of kinetic and DSF assays against parasitic validated targets, along with phenotypic assays, can help the identification and optimization of bioactive compounds. Pteridine reductase 1 (PTR1), a validated target in Leishmania sp., is responsible for the reduction of folate and biopterin to tetrahydrofolate and tetrahydrobiopterin, respectively, both of which are essential for cell growth. In addition to the in vitro evaluation of 16 thiazolidine-2,4-dione derivatives against Leishmania major PTR1 (LmPTR1), using the differential scanning fluorimetry (ThermoFluor®), phenotypic assays were employed to evaluate the compound effect over Leishmania braziliensis (MHOM/BR/75/M2903) and Leishmania infantum (MHOM/BR/74/PP75) promastigotes viability. The ThermoFluor® results show that thiazolidine-2,4-dione derivatives have micromolar affinity to the target and equivalent activity on Leishmania cells. 2b is the most potent compound against L. infantum (EC50 = 23.45 ± 4.54 µM), whereas 2a is the most potent against L. braziliensis (EC50 = 44.16 ± 5.77 µM). This result suggests that lipophilic substituents on either-meta and/or-para positions of the benzylidene ring increase the potency against L. infantum. On the other hand, compound 2c (CE50 = 49.22 ± 7.71 µM) presented the highest selectivity index.