Temporal trends and spatial clusters of high risk for maternal death due to COVID-19 pre and during COVID-19 vaccination in Brazil: a national population-based ecological study.

OBJECTIVE: This study comprehensively analyzed the temporal and spatial dynamics of COVID-19 cases and deaths within the obstetric population in Brazil, comparing the periods before and during mass COVID-19 vaccination. We explored the trends and geographical patterns of COVID-19 cases and maternal deaths over time. We also examined their correlation with the SARS-CoV-2 variant circulating and the social determinants of health. STUDY DESIGN: This is a nationwide population-based ecological study. METHODS: We obtained data on COVID-19 cases, deaths, socioeconomic status, and vulnerability information for Brazil's 5570 municipalities for both the pre-COVID-19 vaccination and COVID-19 vaccination periods. A Bayesian model was used to mitigate indicator fluctuations. The spatial correlation of maternal cases and fatalities with socioeconomic and vulnerability indicators was assessed using bivariate Moran. RESULTS: From March 2020 to June 2023, a total of 23,823 cases and 1991 maternal fatalities were recorded among pregnant and postpartum women. The temporal trends in maternal incidence and mortality rates fluctuated over the study period, largely influenced by widespread COVID-19 vaccination and the dominant SARS-CoV-2 variant. There was a significant reduction in maternal mortality due to COVID-19 following the introduction of vaccination. The geographical distribution of COVID-19 cases and maternal deaths exhibited marked heterogeneity in both periods, with distinct spatial clusters predominantly observed in the North, Northeast, and Central West regions. Municipalities with the highest Human Development Index reported the highest incidence rates, while those with the highest levels of social vulnerability exhibited elevated mortality and fatality rates. CONCLUSION: Despite the circulation of highly transmissible variants of concern, maternal mortality due to COVID-19 was significantly reduced following the mass vaccination. There was a heterogeneous distribution of cases and fatalities in both periods (before and during mass vaccination). Smaller municipalities and those grappling with social vulnerability issues experienced the highest rates of maternal mortality and fatalities.

Frequency and characterization of the accessory heads of the biceps brachii: A multicentric cadaveric study.

PURPOSE: The biceps brachii muscle (BBM) is a large and thick muscle on the ventral portion of the upper arm. The scientific literature reports the existence of extra heads. OBJECTIVE: The present work investigated the frequency of occurrence of BBM accessory head(s) in four different Anatomy Laboratories at universities in Northeast Brazil. MATERIAL AND METHODS: Once the upper limbs with an anatomical variation of the BBM heads were identified, the accessory head was evaluated for morphometric characterization (the length, width, and thickness). RESULTS: The sample consisted of 249 upper limbs and the outcomes were 26 members with BBM accessory heads (10.44% of the total sample). Among the 26 members studied was found a single accessory head in 22 (84.62%), two accessory heads in 3 (11.54%), and three accessory heads in 1 (3.85%). BBMs with one, two, and three accessory heads were found, with different origins. The average length, width, and thickness of these accessory heads were 169.39mm, 10.25mm, and 3.39mm, respectively. CONCLUSION: The frequency of BBM accessory heads in a population of northeastern Brazil in this cadaveric study was 10.44%.

An efficient removal approach for degradation of metformin from aqueous solutions with sulfate radicals.

Metformin consumption for diabetes treatment is increasing, leading to its presence in wastewater treatment plants where conventional methods cannot remove it. Therefore, this work aims to analyze the performance of advanced oxidation processes using sulfate radicals in the degradation of metformin from water. Experiments were performed in a photoreactor provided with a low-pressure Hg lamp, using K2S2O8 as oxidant and varying the initial metformin concentration (CA0), oxidant concentration (Cox), temperature (T), and pH in a response surface experimental design. The degradation percentages ranged from 26.1 to 87.3%, while the mineralization percentages varied between 15.1 and 64%. Analysis of variance (ANOVA) showed that the output variables were more significantly affected by CA0, Cox, and T. Besides, a reduction of CA0 and an increase of Cox up to 5000 µM maximizes the metformin degradation since the generation of radicals and their interaction with metformin molecules are favored. For the greatest degradation percentage, the first order apparent rate constant achieved was 0.084 min-1. Furthermore, while in acidic pH, temperature benefits metformin degradation, an opposite behavior is obtained in a basic medium because of recombination and inhibition reactions. Moreover, three degradation pathways were suggested based on the six products detected by HPLC-MS: N-cyanoguanidine m/z = 85; N,N-dimethylurea m/z = 89; N,N-dimethyl-cyanamide m/z = 71 N,N-dimethyl-formamide m/z = 74; glicolonitrilo m/z = 58; and guanidine m/z = 60. Finally, it was shown that in general the toxicity of the degradation byproducts was lower than the toxicity of metformin toward Chlamydomonas reinhardtii.

Excess mortality associated with COVID-19 in Brazil: 2020-2021.

OBJECTIVE: To evaluate excess mortality in Brazil from January 2020 to April 2021, according to the primary causes of death registered in the Brazilian Mortality Information System (MIS). METHODS: Cross-sectional study with data extracted from the MIS. Excess deaths were examined by the primary cause of death according to 11 grouped causes. Autoregressive models used mortality data from 2015 to 2019 to predict expected deaths from January 2020 to April 2021. Excess deaths were calculated as the difference between the observed and the expected number of deaths. RESULTS: Total excess deaths of 370 055 were observed in the studied period, corresponding to a ratio of observed to expected of 1.14 in 2020 and 1.40 in 2021. Excess deaths were seen in three groups: symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified; other diseases of the respiratory system and coronavirus infection, unspecified site. CONCLUSIONS: The excess mortality in Brazil in these 16 months was 1.20 times greater than the previous year. The increase in not elsewhere classified causes and causes of death associated to COVID-19 indicate caution about the negative balance for some causes. Furthermore, the inequalities of mortality reporting systems in low- and middle-income countries in relation to underestimation of mortality still need to be addressed.

Polycystic ovary syndrome: clinical and laboratory variables related to new phenotypes using machine-learning models.

PURPOSE: Polycystic Ovary Syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. Machine learning (ML) is the area of artificial intelligence with a focus on predictive computing algorithms. We aimed to define the most relevant clinical and laboratory variables related to PCOS diagnosis, and to stratify patients into different phenotypic groups (clusters) using ML algorithms. METHODS: Variables from a database comparing 72 patients with PCOS and 73 healthy women were included. The BorutaShap method, followed by the Random Forest algorithm, was applied to prediction and clustering of PCOS. RESULTS: Among the 58 variables investigated, the algorithm selected in decreasing order of importance: lipid accumulation product (LAP); abdominal circumference; thrombin activatable fibrinolysis inhibitor (TAFI) levels; body mass index (BMI); C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-c), follicle-stimulating hormone (FSH) and insulin levels; HOMA-IR value; age; prolactin, 17-OH progesterone and triglycerides levels; and family history of diabetes mellitus in first-degree relative as the variables associated to PCOS diagnosis. The combined use of these variables by the algorithm showed an accuracy of 86% and area under the ROC curve of 97%. Next, PCOS patients were gathered into two clusters in the first, the patients had higher BMI, abdominal circumference, LAP and HOMA-IR index, as well as CRP and insulin levels compared to the other cluster. CONCLUSION: The developed algorithm could be applied to select more important clinical and biochemical variables related to PCOS and to classify into phenotypically different clusters. These results could guide more personalized and effective approaches to the treatment of PCOS.

Evaluation of hydrogen peroxide efficacy against AZD1222 chimpanzee adenovirus strain in the recombinant COVID-19 vaccine for application in cleaning validation in a pharmaceutical manufacturing industry.

This study aimed to evaluate the performance of hydrogen peroxide vapour (HPV) to inactivate the chimpanzee adenovirus AZD1222 vaccine strain used in the production of recombinant COVID-19 vaccine for application in cleaning validation in pharmaceutical industries production areas. Two matrixes were tested: formulated recombinant COVID-19 vaccine (FCV) and active pharmaceutical ingredient (API). The samples were dried on stainless steel and exposed to HPV in an isolator. One biological indicator with population >106 Geobacillus stearothermophilus spores was used to validate the HPV decontamination cycle as standard. HPV exposure resulted in complete virus inactivation in FVC (≥5·03 log10 ) and API (≥6·40 log10 ), showing HPV efficacy for reducing chimpanzee adenovirus AZD1222 vaccine strain. However, the optimum concentration and contact time will vary depending on the type of application. Future decontamination studies scaling up the process to the recombinant COVID-19 vaccine manufacturing areas are necessary to evaluate if the HPV will have the same or better virucidal effectivity in each specific production area. In conclusion, HPV showed efficacy for reducing AZD1222 chimpanzee adenovirus strain and can be a good choice for pharmaceutical industries facilities disinfection during recombinant COVID-19 vaccine production.

Efficacy of hydrogen peroxide wipes for decontamination of AZD1222 adenovirus COVID-19 vaccine strain on pharmaceutical industry materials.

This study aimed to evaluate the performance of accelerated hydrogen peroxide® wipes (HPW) for decontamination of the chimpanzee adenovirus AZD1222 vaccine strain used in the production of recombinant COVID-19 vaccine in a pharmaceutical industry. Two matrices were tested on stainless-steel (SS) and low-density-polyethylene (LDP) surfaces: formulated recombinant COVID-19 vaccine (FCV) and active pharmaceutical ingredient (API). The samples were spiked, dried and the initial inoculum, possible residue effect (RE) and titre reduction after disinfection with HPW were determined. No RE was observed. The disinfection procedure with HPW resulted in complete decontamination the of AZD1222 adenovirus strain in FCV (≥7·46 and ≥7·49 log10 infectious unit [IFU] ml-1 for SS and LDP carriers respectively) and API (≥8·79 and ≥8·78 log10 IFU ml-1 for SS and LDP carriers respectively). In conclusion, virucidal activity of HPW was satisfactory against the AZD1222 adenovirus strain and can be a good option for disinfection processes of SS and LPD surfaces in pharmaceutical industry facilities during recombinant COVID-19 vaccine production. This procedure is simple and can be also applied on safety unit cabins and sampling bags made of LDP as well.

Rich but random: parasite communities of snouted treefrog, Scinax fuscovarius (Anura: Hylidae), in Bodoquena Mountains, western Brazil.

Hosts represent discrete habitats that contain finite parasite communities, and individual hosts can be used as replicates in parasitism studies, such as investigations of the processes that mediate the formation of parasite communities. However, within a single host population, there may be singularities among individuals that affect parasite contact rates. Accordingly, the goals of the present study were to document the parasites associated with the small treefrog Scinax fuscovarius, to verify possible variation and co-occurrences in parasite infracommunities, and to assess the effects of host characteristics (size and sex) on infracommunity structure. Treefrog specimens (n = 75) were collected from the Bodoquena Mountains in Mato Grosso do Sul, Brazil. After collection, the specimens were transported to the laboratory, and examined for parasitic. The parasites found were removed, fixed, and identified. Patterns in parasite infracommunity organization were analyzed using the checkerboard score index, which was calculated using a presence-absence matrix. The matrix was randomized under the null hypothesis that the infracommunities independently represent the component community. Forty-two (56%) of the individuals harbored at least one parasite, and a total of 500 metazoan parasites were recovered, with a particularly rich composite community of 18 taxa, including 13 nematodes, two trematodes, one cestode, one oligochaete, and one mite larvae. The parasite species were randomly distributed among the infracommunities, with no evidence of co-occurrence, segregation, or aggregation. However, both body size and sex influenced infection, with larger hosts harboring more parasites and parasites were more abundant in male specimens and more species rich in female specimens. These results suggest that the parasite infracommunities of S. fuscovarius are shaped by both random factors and individual host characteristics.

Effects of in vitro exposure of sheep ovarian tissue to zearalenone and matairesinol on preantral follicles.

The aim of this study was to evaluate the effect of 1 µmol/l zearalenone (ZEN) and 1 µmol/l matairesinol (MAT), alone or in combination, on the morphology of in vitro-cultured ovarian preantral follicles. Ovaries from four adult sheep were collected at a local slaughterhouse and fragmented, and the ovarian pieces were submitted to in vitro culture for 3 days in the presence or absence of the test compounds. The morphology of primordial and primary follicles was impaired by ZEN. The plant lignan MAT alone did not maintain the morphology of the ovarian follicles; its combination with ZEN counteracted the negative effects observed when follicles were cultured in the presence of the mycotoxin alone. However, MAT was not able to promote the in vitro development of the ovarian follicles.

Breast cancer: the real road of the Brazilian northeast.

Objective: To characterize the clinical and sociodemographic aspects of breast cancer patients undergoing cancer treatment in the State of Maranhão, in a public reference hospital. Methods: Descriptive, correlational and analytical cross-sectional study, conducted between January 2019 and February 2020, at the Tarquínio Lopes Filho State Cancer Hospital. The study population consisted of all women, in first consultation, with breast cancer undergoing chemotherapy, in agreement with the study and with no brain metastasis evidenced. Statistical analysis was performed using SPSS v. 19 software, considering a significance level of 5%. Results: Eighty adult women were part of the study, whose average age was 52.54. Most of the women were born in São Luís, white, housewives, sedentary, married, former smokers, and Catholic. They had technical/specialized training. In the clinical results, the histological type of infiltrative ductal carcinoma predominated, as well as stage III, mastectomy and the doxorubicin-cyclophosphamide-taxol chemotherapy regimen. Conclusion: The knowledge of each regional profile assists health professionals regarding the characterization of a target population and the design of targeted preventive and self-care strategies by managers.

SAFETY AND EFFICACY OF THYMIC PEPTIDES IN THE TREATMENT OF HOSPITALIZED COVID-19 PATIENTS IN HONDURAS.

Coronavirus disease 2019 (Covid-19) active cases continue to demand the development of safe and effective treatments. This is the first clinical trial to evaluate the safety and efficacy of oral thymic peptides. ; We conducted a nonrandomized phase 2 trial with a historic control group to evaluate the safety and efficacy of a daily 250-mg oral dose of thymic peptides in the treatment of hospitalized Covid-19 patients. Comparisons based on standard care from registry data were performed after propensity score matching. The primary outcomes were survival, time to recovery, and number of participants with treatment-related adverse events or side effects by day 20. ; A total of 44 patients were analyzed in this study: 22 in the thymic peptide group and 22 in the standard care group. There were no deaths in the intervention group compared to 24% mortality in standard care by day 20 (log-rank P=0.02). Kaplan-Meier analysis showed a significantly shorter time to recovery by day 20 in the thymic peptide group than in the standard care group (median, 6 days vs. 12 days; hazard ratio for recovery, 2.75 [95% confidence interval, 1.34 to 5.62]; log-rank P=0.002). No side effects or adverse events were reported. ; In patients hospitalized with Covid-19, the use of thymic peptides resulted in no side effects, adverse events, or deaths by day 20. Compared with the registry data, a significantly shorter time to recovery and mortality reduction were measured.

Two novel pathogenic variants in MED13L: one familial and one isolated case.

BACKGROUND: Genetic variants involving the MED13L gene can lead to an autosomal dominant syndrome characterised by intellectual disability/developmental delay and facial dysmorphism. METHODS: We investigated two cases (one familial and one isolated) of intellectual disability with speech delay and dysmorphic facial features by whole-exome sequencing analyses. Further, we performed a literature review about clinical and molecular aspects of MED13L gene and syndrome. RESULTS: Two MED13L variants have been identified [MED13L(NM_015335.5):c.4417C>T and MED13L(NM_015335.5):c.2318delC] and were classified as pathogenic according to the ACMG (American College of Medical Genetics and Genomics) guidelines. One of the variants was present in sibs. CONCLUSIONS: The two pathogenic variants identified have not been previously reported. Importantly, this is the first report of a familial case of MED13L nonsense mutation. Although the parents of the affected children were no longer available for analysis, their apparently normal phenotypes were surmised from familial verbal descriptions corresponding to normal mental behaviour and phenotype. In this situation, the familial component of mutation transmission might be caused by gonadal mosaicism of a MED13L mutation in a gonad from either the father or the mother. The case reports and the literature review presented in this manuscript can be useful for genetic counselling.

Association between screen time and accelerometer-measured 24-h movement behaviors in a sample of Brazilian adolescents.

OBJECTIVES: Different screen time activities may be related to sleep, physical activity, and sedentary behavior. The objective was to examine the association between self-reported screen time activities and accelerometer-measured 24-h movement behaviors. STUDY DESIGN: This was a cross-sectional study. METHODS: Adolescents' (n = 718, 50.4% girls, 16 years) sleep duration, sedentary behavior, light-intensity physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) were estimated with wrist-worn accelerometry. Time spent on screen time activities related to studying, working, watching videos, playing video games, and using social media was self-reported. Multilevel linear regressions were used to test the association between screen time with sleep, sedentary behavior, and physical activity. RESULTS: Boys and girls slept 6.4 and 6.7 h per night, spent 10.4 and 10.1 h/d in sedentary behavior, spent 4.0 and 4.4 h/d in LPA, and spent 34.7 and 29.2 min/d in MVPA, respectively. Studying was inversely related to LPA and MVPA. Working was inversely related to sleep and positively related to LPA. Watching videos was associated with lower LPA and MVPA. For boys, videogames were associated with increased sedentary behavior and lower LPA and MVPA. For girls, studying and/or using social media were associated with lower LPA and MVPA. CONCLUSIONS: Indicators of screen time were associated with different accelerometer-measured 24-h movement behaviors in this sample of Brazilian adolescents.

Evaluation of the salivary function of patients in treatment with radiotherapy for head and neck cancer submitted to photobiomodulation.

BACKGROUND: Head and neck radiotherapy is typically associated with toxicities that can have profound effects on the patient's quality of life. Xerostomia, which may or may not be related to hypofunction of the salivary gland, leading to negative consequences, mainly in quality of life, leaving patients more susceptible to the development of oral mucositis, dental caries, oral infection and difficulties in speech is one of the most common side effects of such treatment. The aim of the present study was to evaluate salivary function of patients in treatment with radiotherapy for head and neck cancer submitted to photobiomodulation. MATERIAL AND METHODS: A cross-sectional study with a quantitative approach was carried out in the Dentistry Department of the Hospital de Câncer de Pernambuco between February and September 2019. RESULTS: The study sample comprised 23 patients of both genders, treated with radiotherapy for cancer in the head and neck region. The patients were submitted to photobiomodulation with infrared laser, as intraoral applications in order to prevent mucositis and extraoral applications to stimulate salivary glands. The applications were undertaken three times a week on alternate days throughout the radiotherapy period. The following parameters were used: Intraoral 15mW, 12J / cm2, 10s / point, 2.4 J / point, and extraoral 30mW, 7.5J / cm2, 10s / point, 0.3J / point, both with a wavelength of 830nm and area of 0.028cm². Subjective and objective symptoms were evaluated by measuring the unstimulated salivary flow (USF) using the spitting technique before, during and after radiotherapy treatment. For statistical analysis, a significance level of 5% was adopted. Most patients were male (70%) with 60 years of age on average. At the beginning of treatment, 22 patients had USF > 0.2 ml / min (grade 1), at the end of which 15 patients remained unchanged and only 3 patients progressed to grade 3. As for the subjective classification, most (52%) remained in grade 1 (absence of disability) throughout the treatment. CONCLUSION: Based upon the results of this study it was possible to conclude that the use of photobiomodulation did not significantly interfere with the xerostomia complaint of patients in treatment with radiotherapy, however, it does seem to prevent patients from reaching higher degrees of xerostomia taking into account salivary flow measures.

Pathogenicity of Aphelenchoides Pseudogoodeyi on the Ornamental Plants Asplenium Nidus and Lilium Speciosum in Brazil.

Aphelenchoides pseudogoodeyi has recently been reported in association with seeds of forage grasses and rice in Brazil and senescent strawberry plants, in the United States. This nematode is likely a mycophagous species; however, so far, its pathogenicity potential to plants is unclear. This study aimed to verify the pathogenicity of A. pseudogoodeyi to two species of ornamental plants. The experiments were conducted by inoculating A. pseudogoodeyi onto Bird's-Nest Fern (Asplenium nidus) and Oriental Lily (Lilium speciosum) leaves, using two inoculation methods (with and without injury). After 40 days of inoculation (DAI) in Bird's-Nest Fern and 5, 10, 20 and 40 DAI in Oriental Lily, the pathogenicity and the host efficiency were evaluated by symptoms observation and by severity, final nematode population and reproductive factor (RF), respectively. Additionally, a histopathological study was performed by inoculating A. pseudogoodeyi onto Bird's-Nest Fern for observing anatomical alterations. A. pseudogoodeyi was able to cause local necrotic lesions on both Bird's-Nest Fern and Oriental Lily leaves. However, the presence of injury was essential to enable A. pseudogoodeyi to penetrate and cause those symptoms in both plant species. Also, the total population of A. pseudogoodeyi decreased drastically over time and RF was <1, which characterized these species as poor-host or resistant plants. A. pseudogoodeyi penetrated into the foliar tissue and induced a total destruction of the mesophyll and collapse of the cells, with the formation of large intercellular spaces. It is concluded that A. pseudogoodeyi is an opportunistic pathogen as injury was required to induce symptoms in Bird's-Nest Fern and Oriental Lily.

A pig slurry feast/famine feeding regime strategy to improve mesophilic anaerobic digestion efficiency and digestate hygienisation.

The increasing concentration of livestock farms results in large amounts of waste production and the need for their management. The study of anaerobic digestion (AD) technology, under mesophilic conditions, applied to pig slurry is of the upmost importance for biogas recovery and sanitised digestate, contributing to a circular economy. The assessment of the effects of a feast/famine regime on biogas and biomethane (bio-CH4) yield with different feeding frequencies was performed. The evaluation was made in regards to three scenarios: the first is based on daily feeding (FR1); in the second, the feeding occurs once every two days (FR2); and in the third, the feeding happens once every three days (FR3). The results demonstrate that the biogas and methane yield increased by 34% and 37% between FR1 and FR3. The stability inside the reactor was maintained since specific loading energetic rate values did not exceed the recommended limit (0.4 d-1). It was also possible to conclude that the AD technology was efficient to sanitise the pig slurry, with the count of Escherichia coli going from 1 × 105 colony-forming units (CFU) g-1 to less than 100 CFU g-1, meeting the legal requirements for agricultural valorisation. The total anaerobic mesophile plate counts were significantly (p < 0.1) reduced from feeding to digestate, and the plate counts of Clostridia were significantly (p < 0.05) increased, reflecting the changes in the composition of the microbiota. The increasing yield in bio-CH4 in accordance with Clostridium counts suggests this genus as a positive microbiological key indicator of the AD performance.

Activation of Prejunctional P2x2/3 Heterotrimers by ATP Enhances the Cholinergic Tone in Obstructed Human Urinary Bladders.

The objective of this study was to investigate the role of ATP in cholinergic neurotransmission in the urinary bladder of control men and of patients obstructed as a result of benign prostatic hyperplasia (BPH). Human detrusor samples were collected from 41 patients who submitted to transvesical prostatectomy resulting from BPH and 26 male organ donors. The release of [3H]acetylcholine ([3H]ACh) was evoked by electrical field stimulation (10 Hz, 200 pulses) in urothelium-denuded detrusor strips. Myographic recordings were performed to test detrusor strip sensitivity to ACh and ATP. Nerve-evoked [3H]ACh release was 1.5-fold higher in detrusor strips from BPH patients compared with controls. This difference was abolished after desensitization of ionotropic P2X1-3 receptors with an ATP analog, α,ß-methylene ATP (30 µM, applied for 15 minutes). TNP-ATP (10 nM, a preferential P2X2/3 antagonist) and A317491 (100 nM, a selective P2X3 antagonist) were about equipotent in decreasing nerve-evoked [3H]ACh release in control detrusor strips, but the selective P2X1 receptor antagonist NF023 (3 µM) was devoid of effect. The inhibitory effect of TNP-ATP (10 nM) increased from 27% ± 9% to 43% ± 6% in detrusor strips of BPH patients, but the effect of A317491 (100 nM) [3H]ACh release unaltered (20% ± 2% vs. 24% ± 4%). The amplitude of ACh (0.1-100 µM)-induced myographic recordings decreased, whereas sensitivity to ATP (0.01-3 mM) increased in detrusor strips from BPH patients. Besides the well characterized P2X1 receptor-mediated contractile activity of ATP in pathologic human bladders, we show here for the first time that cholinergic hyperactivity in the detrusor of BPH patients is facilitated by activation of ATP-sensitive P2X2/3 heterotrimers. SIGNIFICANCE STATEMENT: Bladder outlet obstruction often leads to detrusor overactivity and reduced bladder compliance in parallel to atropine-resistant increased purinergic tone. Our data show that P2X1 purinoceptors are overexpressed in the detrusor of patients with benign prostatic hyperplasia. Besides the P2X1 receptor-mediated detrusor contractions, ATP favors nerve-evoked acetylcholine release via the activation of prejunctional P2X2/3 excitatory receptors in these patients Thus, our hypothesis is that manipulation of the purinergic tone may be therapeutically useful to counteract cholinergic overstimulation in obstructed patients.

Anti-inflammatory and immune properties of the peltatoside, isolated from the leaves of Annona crassiflora Mart., in a new experimental model zebrafish.

Establishing new animal models for the study of inflammation is very important in the process of discovering new drugs, since the inflammatory event is the basis of many pathological processes. Whereas rodent models have been the primary focus of inflammation research, we defend the zebrafish (Danio rerio) test as a feasible alternative for preclinical studies. Moreover, despite all the technological development already achieved by humanity, nature can still be considered a relevant source of new medicines. In this context, the aim of this work was to evaluate the anti-inflammatory effect of a substance isolated from the medicinal plant Annona crassilfora Mart, the peltatoside, in an inflammatory model of zebrafish. It was determined: (i) total leukocyte count in the coelomate exudate; (ii) N-acetyl-ß-d-glucuronidase (NAG); (iii) myeloperoxidase (MPO); (iv) and the histology of liver, intestine and mesentery. Peltotoside (25, 50 and 100 µg) and dexamethasone (25 µg) were administered intracelomatically (i.c.) 30 min before carrageenan (i.c.). Pretreatment with peltatoside at three doses significantly inhibited leukocyte recruitment in the coelomic cavity, and inhibited NAG and MPO activity against the action of Cg, in a similar manner as dexamethasone. However, some microlesions in the evaluated organs were detected. The dose of 25 µg showed an anti-inflammatory effect with lower undesirable effects in the tissues. Our results suggest that the zebrafish test was satisfactory in performing our analyzes and that the peltotoside has a modulatory action in reducing leukocyte migration.

Transport of blood particles: Chaotic advection even in a healthy scenario.

We study the advection of blood particles in the carotid bifurcation, a site that is prone to plaque development. Previously, it has been shown that chaotic advection can take place in blood flows with diseases. Here, we show that even in a healthy scenario, chaotic advection can take place. To understand how the particle dynamics is affected by the emergence and growth of a plaque, we study the carotid bifurcation in three cases: a healthy bifurcation, a bifurcation with a mild stenosis, and the another with a severe stenosis. The result is non-intuitive: there is less chaos for the mild stenosis case even when compared to the healthy, non-stenosed, bifurcation. This happens because the partial obstruction of the mild stenosis generates a symmetry in the flow that does not exist for the healthy condition. For the severe stenosis, there is more irregular motion and more particle trapping as expected.

Antinociception induced by artemisinin nanocapsule in a model of postoperative pain via spinal TLR4 inhibition.

Artemisinin (ART) was initially described for the control of inflammation and pain. However, the mechanisms involved with its antinociceptive effect are still poorly understood. Thus, this present study aimed to investigate the effect of ART in both free and nanocapsulated form on postoperative pain, as well as the participation of the spinal Toll-like receptor 4 (TLR4) in this process. Postoperative pain was induced using the skin/muscle incision retraction (SMIR) model in male Swiss mice. After 3 and 28 days of SMIR, the animals received an intrathecal injection of free or nanocapsulated ART, and the nociceptive threshold was evaluated by von Frey filament test. To evaluate the involvement of the microglia, astrocytes, and TLR4, minocycline (a microglia inhibitor), fluorocitrate (an astrocyte inhibitor), and Lipopolysaccharide Rhodobacter sphaeroides (LPS-RS), a TLR4 antagonist, were intrathecally injected on the third day of SMIR. The levels of spinal TLR4 protein and proinflammatory cytokines tumor necrosis factor-alpha (TNF-α), and interleukin-1-beta (IL-1ß) were quantified by western blot and enzyme-linked immunosorbent assay, respectively. The results showed that free ART reduced postoperative pain (P < 0.001, F5,30 = 7.49, 16.66% for 1000 ng dose; and P < 0.01, F5,30 = 7.49, 14.58% for 500 ng dose) on the 3rd day of SMIR; while the ART nanocapsule had this effect on both the third (P < 0.001; F5,30 = 4.94; 43.75, 39.58 and 72.91% for the 250, 500 and 1000 ng doses, respectively) and 28th (P < 0.05; F5,30 = 7.71; 29.16 and 33.33% for the 500 and 1000 ng doses, respectively) day. The ART nanocapsule had a more potent and longer antinociceptive effect than free ART or morphine. Postoperative pain was also reduced by minocycline and LPS-RS. The ART nanocapsule also reduced the increased levels of TLR4, TNF-α, and IL-1ß induced by SMIR. These data suggest that the ART nanocapsule has a potent analgesic effect on postoperative pain at the spinal level, and this response involves the inhibition of TLR4 and the proinflammatory cytokines TNF-α and IL-1ß.