Continuous Flow Synthesis of Hexyl Laurate Using Immobilized Thermomyces Lanuginosus Lipase from Residual Babassu Mesocarp.

Brazil has one of the greatest biodiversities on the planet, where various crops play a strategic role in the country's economy. Among the highly appreciated biomasses is babassu, whose oil extraction generates residual babassu mesocarp (BM), which still needs new strategies for valorization. This work aimed to use BM as a support for the immobilization of Thermomyces lanuginosus lipase (TLL) in an 8.83 mL packed-bed reactor, followed by its application as a biocatalyst for the synthesis of hexyl laurate in an integrated process. Initially, the percolation of a solution containing 5 mg of TLL at 25 °C and flows ranging from 1.767 to 0.074 mL min-1 was investigated, where at the lowest flow rate tested (residence time of 2 h), it was possible to obtain an immobilized derivative with hydrolytic activity of 504.7 U g-1 and 31.7 % of recovered activity. Subsequent studies of treatment with n-hexane, as well as the effect of temperature on the immobilization process, were able to improve the activities of the final biocatalyst BM-TLLF, achieving a final hydrolysis activity of 7023 U g-1 and esterification activity of 430 U ⋅ g-1 against 142 U g-1 and 113.5 U g-1 respectively presented by the commercial TLIM biocatalyst. Desorption studies showed that the TL IM has 18 mg of protein per gram of support, compared to 4.92 mg presented by BM-TLL. Both biocatalysts were applied to synthesize hexyl laurate, achieving 98 % conversion at 40 °C within 2 h. Notably, BM-TLLF displayed exceptional recyclability, maintaining catalytic efficiency over 12 cycles. This reflects a productivity of 180 mg of product ⋅ h-1 U-1 of the enzyme, surpassing 46 mg h-1 U-1 obtained for TLIM. These results demonstrate the efficacy of continuous flow technology in creating a competitive and integrated process offering an exciting alternative for the valorization of residual lignocellulosic biomass.

LDH-Indomethacin Nanoparticles Antitumoral Action: A Possible Coadjuvant Drug for Cancer Therapy.

Indomethacin (INDO) has a mechanism of action based on inhibiting fatty acids cyclooxygenase activity within the inflammation process. The action mechanism could be correlated with possible anticancer activity, but its high toxicity in normal tissues has made therapy difficult. By the coprecipitation method, the drug carried in a layered double hydroxides (LDH) hybrid matrix would reduce its undesired effects by promoting chemotherapeutic redirection. Therefore, different samples containing INDO intercalated in LDH were synthesized at temperatures of 50, 70, and 90 °C and synthesis times of 8, 16, 24, and 48 h, seeking the best structural organization. X-ray diffraction (XRD), vibrational Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), spectrophotometric analysis in UV-VIS, and differential thermogravimetric analysis (TGA/DTA) were used for characterization. Our results indicate that higher temperatures and longer synthesis time through coprecipitation reduce the possibility of INDO intercalation. However, it was possible to establish a time of 16 h and a temperature of 50 °C as the best conditions for intercalation. In vitro results confirmed the cell viability potential and anticancer activity in the LDH-INDO sample (16 h and 50 °C) for gastric cancer (AGP01, ACP02, and ACP03), breast cancer (MDA-MB-231 and MCF-7), melanoma (SK-MEL-19), lung fibroblast (MRC-5), and non-neoplastic gastric tissue (MN01) by MTT assay. Cell proliferation was inhibited, demonstrating higher and lower toxicity against MDA-MB-231 and SK-MEL-19. Thus, a clinical redirection of INDO is suggested as an integral and adjunctive anticancer medication in chemotherapy treatment.

Comparative analysis of uninduced and neuronally-induced human dental pulp stromal cells in a 6-OHDA model of Parkinson's disease.

BACKGROUND: In recent years, dental pulp stromal cells (DPSCs) have emerged as a promising therapeutic approach for Parkinson's disease (PD), owing to their inherent neurogenic potential and the lack of neuroprotective treatments for this condition. However, uncertainties persist regarding the efficacy of these cells in an undifferentiated state versus a neuronally-induced state. This study aims to delineate the distinct therapeutic potential of uninduced and neuronally-induced DPSCs in a rodent model of PD induced by 6-Hydroxydopamine (6-OHDA). METHODS: DPSCs were isolated from human teeth, characterized as mesenchymal stromal cells, and induced to neuronal differentiation. Neuronal markers were assessed before and after induction. DPSCs were transplanted into the substantia nigra pars compacta (SNpc) of rats 7 days following the 6-OHDA lesion. In vivo tracking of the cells, evaluation of locomotor behavior, dopaminergic neuron survival, and the expression of essential proteins within the dopaminergic system were conducted 7 days postgrafting. RESULTS: Isolated DPSCs exhibited typical characteristics of mesenchymal stromal cells and maintained a normal karyotype. DPSCs consistently expressed neuronal markers, exhibiting elevated expression of ßIII-tubulin following neuronal induction. Results from the animal model showed that both DPSC types promoted substantial recovery in dopaminergic neurons, correlating with enhanced locomotion. Additionally, neuronally-induced DPSCs prevented GFAP elevation, while altering DARPP-32 phosphorylation states. Conversely, uninduced DPSCs reduced JUN levels. Both DPSC types mitigated the elevation of glycosylated DAT. CONCLUSIONS: Our results suggested that uninduced DPSCs and neuronally-induced DPSCs exhibit potential in reducing dopaminergic neuron loss and improving locomotor behavior, but their underlying mechanisms differ.

Analysis of Factors Related to the Success of Pediatric Kidney Transplantation: A 35 Years Experience.

BACKGROUND: Despite the significant improvement results over the past 20 years, pediatric kidney transplantation remains a challenge. Chronic rejection, thrombosis, and recurrence of the primary disease are frequent causes of graft loss that have been little studied. Therefore, our objective is to analyze factors related to a better prognosis, which can be used to improve future strategies to allow higher pediatric transplant success rates. METHODS: A retrospective cohort study with patients under 15 years old submitted for kidney transplantation at the Hospital das Clínicas da UNICAMP between January 1, 1987, and January 1, 2022. Age, patient weight, time and type of dialysis, use of anticoagulation, complications, ischemia time, and donor weight were analyzed and related to graft loss. The significance level adopted for the statistical tests was 5%. RESULTS: One hundred ninety-two medical records were anaThe mean follow-up time was 11 years, and the mean graft duration was ration 8.5 years. The main causes of graft loss were chronic dysfunction, thrombosis, and acute cellular rejection. Thrombosis presented significantly with the donor's body mass index and second transplantation. There was no correlation between the analyzed variables and chronic dysfunction or acute cellular rejection. DISCUSSION: Thrombosis remains the main cause of early graft loss, followed by acute cellular rejection. Measures such as thrombophilia screening and thromboprophylaxis have been proposed to improve results. However, they are still not standardized. CONCLUSION: The main causes of graft loss were chronic dysfunction, thrombosis, and acute cellular rejection. Only the thrombosis was related to the donor's body mass index and a second transplantation.

O mercado das escolinhas de futebol em belo horizonte / The market for football schools in belo horizonte / El mercado de las escuelas de fútbol en belo horizonte

Resumo Este estudo analisa a quantidade e a distribuição territorial das escolinhas de futebol em Belo Horizonte. O objetivo é examinar quantos estabelecimentos desse tipo existem na cidade, onde estão localizados e quais critérios seus proprietários empregam para essa decisão. Para isso, utilizamos dados quantitativos e qualitativos, baseados, respectivamente, em informações sobre a localização desses estabelecimentos e dados censitários, de um lado, e entrevistas semiestruturadas realizadas com proprietários de escolinhas de futebol da cidade, de outro. Nossa interpretação geral é a de que escolinhas de futebol se distribuem aleatoriamente pela cidade em razão de circunstâncias que impõem uma lógica oportunista na tomada de decisão acerca da abertura de um estabelecimento comercial desse tipo.

Abstract The study analyzes the quantity and geographical distribution of "football schools" in Belo Horizonte. The objective is to examine how many of these establishments exist in the city, where they are located and what criteria their owners use to make this decision. For this, we used quantitative and qualitative data, based on information about the location of these establishments and census data, on the one hand, and semi-structured interviews with owners of soccer schools in the city, on the other. Our general interpretation is that football schools are distributed randomly throughout the city due to circumstances impose an opportunistic logic on decision-making.

Resumen Este estudio analiza la cantidad y la distribución territorial de las "escuelas de fútbol" en Belo Horizonte. El objetivo es examinar cuántos establecimientos de este tipo existen en la ciudad, dónde están ubicados y qué criterios utilizan sus propietarios para esta decisión. Para ello, se utilizaron datos cuantitativos y cualitativos, basados en información sobre la ubicación de estos establecimientos y datos censales, por un lado, y entrevistas semiestructuradas a propietarios de escuelas de fútbol de la ciudad, por otro. Nuestra interpretación general es que las escuelas de fútbol se distribuyen aleatoriamente por la ciudad debido a circunstancias que imponen una lógica de opotunismo en la toma de decisiones sobre la apertura de un establecimiento comercial de este tipo.

Zoonotic Parasites in Artiodactyls with Emphasis on the Feral Boar in the Atlantic Forest, State of Rio de Janeiro, Brazil.

BACKGROUND: The purpose of this study was to identify the species of artiodactyl host related to the fecal matter collected in a forest area in Rio de Janeiro state and carry out a parasitological investigation. METHODS: Artiodactyl feces were collected between 2020 and 2021. The fecal samples were examined to identify the host through macroscopic and molecular analysis. The remaining samples were subjected to a fecal parasite analysis using microscopic techniques, and feces containing cysts of the phylum Ciliophora underwent a molecular analysis. RESULTS: Of the 101 samples collected, 71.3% were found in Pavão Valley, the most anthropized area of the park. In the molecular analysis, 79 samples were identified as belonging to Sus scrofa and 2 as Mazama gouazoubira. The most frequently detected forms were cysts of the phylum Ciliophora (39.6%), followed by eggs of Ascaris spp. (11.8%) and Metastrongylus spp. (5.9%). Nucleotide sequences of Balantioides coli were characterized in 26 samples, and in 13 samples variants of type B0 and in 11 type A0 were identified. CONCLUSIONS: It should be noted that this is the first study in the Americas that has identified B. coli in free-living S. scrofa feces, citing this bioinvader as one of the reservoirs of this parasite.

Clinical, epidemiological and laboratory characteristics of cases of Covid-19-related maternal near miss and death at referral units in northeastern Brazil: a cohort study.

Objective: Covid-19 poses a major risk during pregnancy and postpartum, resulting in an increase in maternal mortality worldwide, including in Brazil; however, little research has been conducted into cases of a near miss. This study aimed to describe the frequency of COVID-19-related near miss and deaths during pregnancy or in the postpartum in referral centers in northeastern Brazil, as well as the clinical, epidemiological, and laboratory characteristics of the women who experienced a severe maternal outcome.Methods: A retrospective and prospective cohort study was performed between April 2020 and June 2021 with hospitalized pregnant and postpartum women with a diagnosis of COVID-19 confirmed by real-time polymerase chain reaction (RT-PCR). Data from five tertiary hospitals in northeastern Brazil were evaluated. Descriptive statistical analysis was performed using Epi Info, version 7.2.5.0.Results: A total of 463 patients were included. Of these, 64 (14% of the sample) had a severe maternal outcome, with 42 cases of near miss (9%) and 22 maternal deaths (5%). Patients who had a severe maternal outcome were predominantly young (median age 30 years) and 65.6% were black or brown-skinned. The women had between 6 and 16 years of schooling; 45.3% had a stable partner; 81.3% were pregnant at the time of admission to the study; and 76.6% required a Cesarean section. The great majority (82.8%) had severe acute respiratory syndrome (SARS). Other complications included hypertensive syndromes (40.6%), pneumonia (37.5%), urinary tract infections (29.7%), acute renal failure (25.0%) and postpartum hemorrhage (21.9%). Sepsis developed in 18.8% of cases, neurological dysfunction in 15.6%, and hepatic dysfunction and septic shock in 14.1% of cases each. The relative frequency of admission to an intensive care unit was 87.5%, while 67.2% of the patients required assisted mechanical ventilation, and 54.7% required noninvasive ventilation. Antibiotics were prescribed in 93.8% of cases and corticosteroids in 71.9%, while blood transfusion was required in 25.0% of cases and renal replacement therapy in 15.6%. Therapeutic anticoagulants were administered to 12.5% of the patients. Of the patients who had a severe maternal outcome, the frequency of respiratory dysfunction was 93.8%, with 50.0% developing neurological dysfunction and 37.5% cardiovascular dysfunction. Hematological dysfunction was found in 29.7%, renal dysfunction in 18.8%, and uterine dysfunction in 14.1%. Hepatic dysfunction occurred in 7.8% of the sample. The near-miss ratio for Covid-19 was 1.6/1000 live births and the maternal mortality ratio for Covid-19 was 84.8/100,000 live births, with a mortality index of 34.4% in the sample.Conclusion: This study revealed a low Covid-19-related maternal near miss (MNM) ratio of 1.6/1000 live births and a high Covid-19-related maternal mortality ratio (MMR) of 84.81/100,000 live births. The mortality index was also high. Most of the patients were admitted while pregnant, were young, married and black or brown-skinned, and none had completed university education. The majority had SARS and required admission to an intensive care unit and mechanical ventilation. Most were submitted to a Cesarean section.

Redox Metabolism in Ecophysiology and Evolution.

Aerobic organisms have developed a complex system of endogenous antioxidants to manage the reactivity of oxygen and its byproducts [...].

Erratum: Single-center developing country analysis of radium-223 therapy in prostate cancer-preliminary results.

[This corrects the article on p. 352 in vol. 11, PMID: 34754606.].

Electrophysiological damage to neuronal membrane alters ephaptic entrainment.

The brain is commonly understood as a complex network system with a particular organization and topology that can result in specific electrophysiological patterns. Among all the dynamic elements resulting from the circuits of the brain's network, ephapticity is a cellular communication mechanism that has received little attention. To understand the network's properties of ephaptic entrainment, we start investigating the ephaptic effect on a single neuron. In this study, we used numerical simulations to examine the relationship between alterations in ephaptic neuronal entrainment and impaired electrophysiological properties of the neuronal membrane, which can occur via spike field coherence (SFC). This change in frequency band amplitude is observed in some neurodegenerative diseases, such as Parkinson's or Alzheimer's. To further investigate these phenomena, we proposed a damaged model based on the impairment of both the resistance of the ion channels and the capacitance of the lipid membrane. Therefore, we simulated ephaptic entrainment with the hybrid neural model quadratic integrate-and-fire ephaptic (QIF-E), which mimics an ephaptic entrainment generated by an LFP (simulate a neuronal group). Our results indicate a link between peak entrainment (ephapticity) preference and a shift in frequency band when damage occurs mainly in ion channels. Finally, we discuss possible relationships between ephaptic entrainment and neurodegenerative diseases associated with aging factors.

The Role of Probe-Based Confocal Laser Endomicroscopy (pCLE) in the Diagnosis of Sustained Clinical Complete Response Under Watch-and-Wait Strategy After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Adenocarcinoma: a Score Validation.

BACKGROUND: Watch-and-wait strategy has been increasingly accepted for patients with clinical complete response (cCR) after multimodal treatment for locally advanced rectal adenocarcinoma. Close follow-up is essential to the early detection of local regrowth. It was previously demonstrated that probe-based confocal laser endomicroscopy (pCLE) scoring using the combination of epithelial and vascular features might improve the diagnostic accuracy of cCR. AIM: To validate the pCLE scoring system in the assessment of patients with cCR after neoadjuvant chemoradiotherapy (nCRxt) for advanced rectal adenocarcinoma. METHODS: Digital rectal examination, pelvic magnetic resonance imaging (MRI), and pCLE were performed in 43 patients with cCR, who presented either a scar (N = 33; 76.7%) or a small ulcer with no signs of tumor, and/or biopsy negative for malignancy (N = 10; 23.3%). RESULTS: Twenty-five (58.1%) patients were men, and the mean age was 58.4 years. During the follow-up, 12/43 (27.9%) patients presented local regrowth and underwent salvage surgery. There was an association between pCLE diagnostic scoring and final histological report (for patients who underwent surgical resection) or final diagnosis at the latest follow-up (p = 0.0001), while this association was not observed with MRI (p = 0.49). pCLE sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 93.5%, 80%, 88.9%, and 86%, respectively. MRI sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 48.4%, 66.7%, 78.9%, and 53.5%, respectively. CONCLUSIONS: pCLE scoring system based on epithelial and vascular features improved the diagnosis of sustained cCR and might be recommended during follow-up. pCLE might add some valuable contribution for identifying local regrowth. Trial Registration This protocol was registered at the Clinical Trials (ClinicalTrials.gov identifier NCT02284802).

Glutathione Depletion Disrupts Redox Homeostasis in an Anoxia-Tolerant Invertebrate.

The upregulation of endogenous antioxidants is a widespread phenomenon in animals that tolerate hypoxia/anoxia for extended periods. The identity of the mobilized antioxidant is often context-dependent and differs among species, tissues, and stresses. Thus, the contribution of individual antioxidants to the adaptation to oxygen deprivation remains elusive. This study investigated the role of glutathione (GSH) in the control of redox homeostasis under the stress of anoxia and reoxygenation in Helix aspersa, an animal model of anoxia tolerance. To do so, the total GSH (tGSH) pool was depleted with l-buthionine-(S, R)-sulfoximine (BSO) before exposing snails to anoxia for 6 h. Then, the concentration of GSH, glutathione disulfide (GSSG), and oxidative stress markers (TBARS and protein carbonyl) and the activity of antioxidant enzymes (catalase, glutathione peroxidase, glutathione transferase, glutathione reductase, and glucose 6-phosphate dehydrogenase) were measured in foot muscle and hepatopancreas. BSO alone induced tGSH depletion by 59-75%, but no other changes happened in other variables, except for foot GSSG. Anoxia elicited a 110-114% increase in glutathione peroxidase in the foot; no other changes occurred during anoxia. However, GSH depletion before anoxia increased the GSSG/tGSH ratio by 84-90% in both tissues, which returned to baseline levels during reoxygenation. Our findings indicate that glutathione is required to withstand the oxidative challenge induced by hypoxia and reoxygenation in land snails.

The role of solar radiation and tidal emersion on oxidative stress and glutathione synthesis in mussels exposed to air.

Preparation for oxidative stress (POS) is a widespread adaptive response to harsh environmental conditions, whose hallmark is the upregulation of antioxidants. In contrast to controlled laboratory settings, animals are exposed to multiple abiotic stressors under natural field conditions. Still, the interplay between different environmental factors in modulating redox metabolism in natural settings remains largely unexplored. Here, we aim to shed light on this topic by assessing changes in redox metabolism in the mussel Brachidontes solisianus naturally exposed to a tidal cycle. We compared the redox biochemical response of mussels under six different natural conditions in the field along two consecutive days. These conditions differ in terms of chronology, immersion/emersion, and solar radiation, but not in terms of temperature. Animals were collected after being exposed to air early morning (7:30), immersed during late morning and afternoon (8:45-15:30), and then exposed to air again late afternoon towards evening (17:45-21:25), in two days. Whole body homogenates were used to measure the activity of antioxidant (catalase, glutathione transferase and glutathione reductase) and metabolic (glucose 6-phosphate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase and pyruvate kinase) enzymes, reduced (GSH) and disulfide (GSSG) glutathione levels, and oxidative stress markers (protein carbonyl and thiobarbituric acid reactive substances). Air and water temperature remained stable between 22.5 °C and 26 °C during both days. Global solar radiation (GSR) greatly differed between days, with a cumulative GSR of 15,381 kJ/m2 for day 1 and 5,489 kJ/m2 for day 2, whose peaks were 2,240 kJ/m2/h at 14:00 on day 1 and 952 kJ/m2/h at 12:00 on day 2. Compared with animals underwater, emersion during early morning did not elicit any alteration in redox biomarkers in both days. Air exposure for 4 h in the late afternoon towards evening caused oxidative damage to proteins and lipids and elicited GSH synthesis in animals that had been previously exposed to high GSR during the day. In the following day, when GSR was much lower, exposure to air under the same conditions (duration, time, and temperature) had no effect on any redox biomarker. These findings suggest that air exposure under low-intensity solar radiation is not sufficient to trigger POS in B. solisianus in its natural habitat. Thus, natural UV radiation is possibly a key environmental factor that combined to air exposure induces the POS-response to the stressful event of tidal variation in this coastal species.

Comparison of High-Intensity Interval Training to Moderate-Intensity Continuous Training for Functioning and Quality of Life in Survivors of COVID-19 (COVIDEX): Protocol for a Randomized Controlled Trial.

OBJECTIVE: The purpose of this study was to compare high-intensity interval training (HIIT) with moderate-intensity continuous training (MICT) for feasibility, safety, adherence, and short- and long-term efficacy in improving functioning and health-related quality of life in survivors of coronavirus disease 2019 (COVID-19). METHODS: COVIDEX is a two-pronged, parallel-group, randomized controlled trial with an 8-week training intervention. The study participants will be 94 patients aged >18 years, admitted to a specialized post-COVID center. Participants will be randomized to HIIT (4 × 4 minutes of high-intensity work periods at 85% to 90% of peak heart rate) and MICT (47 minutes at 70% to 75% peak heart rate) groups for biweekly sessions for 8 weeks. The participants will undergo 2 phases of supervised training (phases 1 and 2) of 4 weeks each, in a public, specialized, post-COVID center. In phase 1, we will assess and compare the feasibility, acceptability, and short-term efficacy of HIIT and MICT intervention. In phase 2, the long-term efficacy of HIIT and MICT will be assessed and compared regarding function and health-related quality of life. To prevent any expectation bias, all study participants and assessors will be blinded to the study hypotheses. Group allocation will be masked during the analysis. All statistical analyses will be conducted following intention-to-treat principles. IMPACT: This study is the first randomized controlled trial that will compare the feasibility, safety, adherence, and efficacy of the HIIT and MICT intervention programs in this population. The findings will potentially provide important information and assist in clinical decision making on exercise to optimize the benefits of clinical health care in survivors of COVID-19.

Supramolecular Arrangement of Doxycycline with Sulfobutylether-ß-Cyclodextrin: Impact on Nanostructuration with Chitosan, Drug Degradation and Antimicrobial Potency.

Doxycycline (DX) is a well-established and broad-spectrum antimicrobial drug. However, DX has drawbacks, such as physicochemical instability in aqueous media and bacterial resistance. The inclusion of drugs in cyclodextrin complexes and their loading into nanocarriers can overcome these limitations. Thus, we studied the DX/sulfobutylether-ß-CD (SBE-ß-CD) inclusion complex for the first time and used it to reticulate chitosan. The resulting particles were evaluated by their physicochemical characteristics and antibacterial activity. DX/SBE-ß-CD complexes were characterized by nuclear magnetic resonance, infrared spectroscopy, thermal analysis, X-ray diffraction, and scanning electron microscopy (SEM), whereas DX-loaded nanoparticles were characterized by dynamic light scattering, SEM, and drug content. The partial inclusion of the DX molecule in CD happened in a 1:1 proportion and brought increased stability to solid DX upon thermal degradation. Chitosan-complex nanoparticles measured approximately 200 nm, with a narrow polydispersity and particles with sufficient drug encapsulation for microbiological studies. Both formulations preserved the antimicrobial activity of DX against Staphylococcus aureus, whereas DX/SBE-ß-CD inclusion complexes were also active against Klebsiella pneumoniae, indicating the potential use of these formulations as drug delivery systems to treat local infections.

Tube-in-tube endoscopic vacuum therapy for treatment of colorectal anastomotic leaks: A low-cost, patient-friendly, feasible and efficient technical modification of sponge-based endoscopic vacuum therapy.

BACKGROUND AND AIMS: Colorectal endoscopic vacuum therapy (CR EVT) is usually performed using sponges passed through the anus. It may be associated with patient discomfort and displacement of the aspiration tube. METHODS: With the tube-in-tube endoscopic vacuum therapy modification (CR TT-EVT), it is possible to position the aspiration tube in the pelvic cavity through the abdominal wall. In addition, it allows frequent cleaning of the fistula, eliminates the need for programmed device changes, and enables a standardized approach to such a wide variety of fistulas, leaks, and perforations. RESULTS: Here is a technical note on how to perform CR TT-EVT, while we are at the early phase of our case series we have reached 100% of technical success.