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Medulloblastoma is a malignant childhood brain tumor arising from the developing cerebellum. In Sonic Hedgehog (SHH) subgroup medulloblastoma, aberrant activation of SHH signaling causes increased proliferation of granule neuron progenitors (GNPs), and predisposes these cells to tumorigenesis. A second, cooperating genetic hit is often required to push these hyperplastic cells to malignancy and confer mutation-specific characteristics associated with oncogenic signaling. Somatic loss-of-function mutations of the transcriptional corepressor BCOR are recurrent and enriched in SHH medulloblastoma. To investigate BCOR as a putative tumor suppressor, we used a genetically engineered mouse model to delete exons 9/10 of Bcor (BcorΔE9-10 ) in GNPs during development. This mutation leads to reduced expression of C-terminally truncated BCOR (BCORΔE9-10). While BcorΔE9-10 alone did not promote tumorigenesis or affect GNP differentiation, BcorΔE9-10 combined with loss of the SHH receptor gene Ptch1 resulted in fully penetrant medulloblastomas. In Ptch1+/- ;BcorΔE9-10 tumors, the growth factor gene Igf2 was aberrantly up-regulated, and ectopic Igf2 overexpression was sufficient to drive tumorigenesis in Ptch1+/- GNPs. BCOR directly regulates Igf2, likely through the PRC1.1 complex; the repressive histone mark H2AK119Ub is decreased at the Igf2 promoter in Ptch1+/- ;BcorΔE9-10 tumors. Overall, our data suggests that BCOR-PRC1.1 disruption leads to Igf2 overexpression, which transforms preneoplastic cells to malignant tumors.
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Neoplasias Cerebelosas/genética , Regulación Neoplásica de la Expresión Génica/genética , Proteínas Hedgehog/metabolismo , Meduloblastoma/genética , Proteínas del Grupo Polycomb/metabolismo , Proteínas Represoras/genética , Animales , Carcinogénesis/genética , Modelos Animales de Enfermedad , Proteínas Hedgehog/genética , Humanos , Ratones , Mutación , Receptor Patched-1/genética , Proteínas del Grupo Polycomb/genética , Proteínas Represoras/metabolismo , Eliminación de SecuenciaRESUMEN
BACKGROUND: The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19). METHODS: In this international, double-blind, placebo-controlled trial, we randomly assigned health care workers to receive the BCG-Denmark vaccine or saline placebo and followed them for 12 months. Symptomatic Covid-19 and severe Covid-19, the primary outcomes, were assessed at 6 months; the primary analyses involved the modified intention-to-treat population, which was restricted to participants with a negative test for severe acute respiratory syndrome coronavirus 2 at baseline. RESULTS: A total of 3988 participants underwent randomization; recruitment ceased before the planned sample size was reached owing to the availability of Covid-19 vaccines. The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1703 in the BCG group and 1683 in the placebo group. The estimated risk of symptomatic Covid-19 by 6 months was 14.7% in the BCG group and 12.3% in the placebo group (risk difference, 2.4 percentage points; 95% confidence interval [CI], -0.7 to 5.5; P = 0.13). The risk of severe Covid-19 by 6 months was 7.6% in the BCG group and 6.5% in the placebo group (risk difference, 1.1 percentage points; 95% CI, -1.2 to 3.5; P = 0.34); the majority of participants who met the trial definition of severe Covid-19 were not hospitalized but were unable to work for at least 3 consecutive days. In supplementary and sensitivity analyses that used less conservative censoring rules, the risk differences were similar but the confidence intervals were narrower. There were five hospitalizations due to Covid-19 in each group (including one death in the placebo group). The hazard ratio for any Covid-19 episode in the BCG group as compared with the placebo group was 1.23 (95% CI, 0.96 to 1.59). No safety concerns were identified. CONCLUSIONS: Vaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo. (Funded by the Bill and Melinda Gates Foundation and others; BRACE ClinicalTrials.gov number, NCT04327206.).
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Adyuvantes Inmunológicos , Vacuna BCG , COVID-19 , Personal de Salud , Humanos , Vacuna BCG/uso terapéutico , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/uso terapéutico , Método Doble Ciego , SARS-CoV-2 , Adyuvantes Inmunológicos/uso terapéuticoRESUMEN
Familial Dysautonomia (FD) is an autosomal recessive disorder caused by a splice site mutation in the gene ELP1, which disproportionally affects neurons. While classically characterized by deficits in sensory and autonomic neurons, neuronal defects in the central nervous system have also been described. Although ELP1 expression remains high in the normal developing and adult cerebellum, its role in cerebellar development is unknown. To explore the role of Elp1 in the cerebellum, we knocked out Elp1 in cerebellar granule cell progenitors (GCPs) and examined the outcome on animal behavior and cellular composition. We found that GCP-specific conditional knockout of Elp1 (Elp1cKO) resulted in ataxia by 8 weeks of age. Cellular characterization showed that the animals had smaller cerebella with fewer granule cells. This defect was already apparent as early as 7 days after birth, when Elp1cKO animals also had fewer mitotic GCPs and shorter Purkinje dendrites. Through molecular characterization, we found that loss of Elp1 was associated with an increase in apoptotic cell death and cell stress pathways in GCPs. Our study demonstrates the importance of ELP1 in the developing cerebellum, and suggests that loss of Elp1 in the GC lineage may also play a role in the progressive ataxia phenotypes of FD patients.
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Cerebelo , Disautonomía Familiar , Ratones Noqueados , Fenotipo , Animales , Disautonomía Familiar/genética , Disautonomía Familiar/patología , Cerebelo/metabolismo , Cerebelo/patología , Ratones , Modelos Animales de Enfermedad , Ataxia/genética , Ataxia/patología , Ataxia/metabolismo , Células-Madre Neurales/metabolismo , Apoptosis/fisiología , Péptidos y Proteínas de Señalización IntracelularRESUMEN
Despite success in achieving viral suppression during pregnancy in people living with HIV (PLWH), postpartum adherence remains a challenge. We aimed to describe rates of adherence at a Prevention of Mother-to-Child HIV Transmission (PMTCT) Center before and during the COVID-19 pandemic. This study was conducted from a cohort of PLWH who received prenatal care and were virally suppressed near delivery. We tracked combined antiretroviral therapy (cART) pickups for 12 months and HIV viral load (VL) from 2 to 12 months after delivery. We defined flexible adherence as a monthly pickup of cART and strict adherence as also having VL < 200 copies/mL and at least one maternal HIV VL between two and twelve months postpartum. Pre-pandemic was defined as delivery from March 2017-February 2019 and pandemic as March 2020-February 2022. During the study, 1119 PLWH were followed, and 965 (86%) were suppressed near delivery. There were 511 pre-pandemic and 290 pandemic participants. Adherence rates were 66/511 (13%) and 38/290 (13%), respectively. During the pandemic, more participants conceived using cART and were undetectable at the start of prenatal care; nevertheless, postpartum adherence was no better than pre-pandemic underscoring the need to improve strategies for adherence specific to this subset of PLWH in the postpartum period.
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BACKGROUND: An inherent difference exists between male and female bodies, the historical under-representation of females in clinical trials widened this gap in existing healthcare data. The fairness of clinical decision-support tools is at risk when developed based on biased data. This paper aims to quantitatively assess the gender bias in risk prediction models. We aim to generalize our findings by performing this investigation on multiple use cases at different hospitals. METHODS: First, we conduct a thorough analysis of the source data to find gender-based disparities. Secondly, we assess the model performance on different gender groups at different hospitals and on different use cases. Performance evaluation is quantified using the area under the receiver-operating characteristic curve (AUROC). Lastly, we investigate the clinical implications of these biases by analyzing the underdiagnosis and overdiagnosis rate, and the decision curve analysis (DCA). We also investigate the influence of model calibration on mitigating gender-related disparities in decision-making processes. RESULTS: Our data analysis reveals notable variations in incidence rates, AUROC, and over-diagnosis rates across different genders, hospitals and clinical use cases. However, it is also observed the underdiagnosis rate is consistently higher in the female population. In general, the female population exhibits lower incidence rates and the models perform worse when applied to this group. Furthermore, the decision curve analysis demonstrates there is no statistically significant difference between the model's clinical utility across gender groups within the interested range of thresholds. CONCLUSION: The presence of gender bias within risk prediction models varies across different clinical use cases and healthcare institutions. Although inherent difference is observed between male and female populations at the data source level, this variance does not affect the parity of clinical utility. In conclusion, the evaluations conducted in this study highlight the significance of continuous monitoring of gender-based disparities in various perspectives for clinical risk prediction models.
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To determine the diaphragm thickness, thickening fraction, and excursion and thickness of the quadriceps femoris muscle in full-term newborns and to evaluate the intra- and interrater reliability of these measurements. This was a prospective, observational clinical study including full-term newborns born within the first 48 h after birth. Serial measurements of the thickness, thickening fraction, and mobility of the diaphragm muscles and the thickness of the quadriceps muscle were obtained using ultrasound images. A total of 69 newborns with a mean gestational age of 39 weeks were included. The following measurements were obtained and are expressed as the mean (standard deviation): inspiratory diaphragm thickness, 0.19 cm (0.04); expiratory diaphragm thickness, 0.16 cm (0.04); diaphragm thickness fraction, 16.70 cm (10.27); diaphragmatic excursion, 0.68 cm (0.22); and quadriceps thickness, 0.99 cm (0.14). Intrarater reliability was assessed using intraclass correlation coefficients (ICCs). Excellent intrarater agreement was observed for the two groups of operators (ICC > 0.86, p < 0.001) for all measurements except for the diaphragm thickening fraction, which showed good agreement for both operator groups (ICC = 0.70, p < 0.001). Regarding interrater reliability, moderate agreement between the raters was observed in the means of all measures (ICC > 0.49, p < 0.001), except for the diaphragm thickening fraction, which showed poor agreement. Conclusion: Good intrarater and moderate interrater reliability were achieved in ultrasound evaluations of the thickness and mobility of the diaphragm and quadriceps femoris muscles in full-term newborns, demonstrating the feasibility of this technique for clinical use. This pioneering study offers reference values for these muscles in a single study, allowing comparisons between different clinical conditions. What is Known: ⢠Ultrasound is a highly reliable tool for muscle assessment that can be used to assess muscular atrophy in critically ill patients. ⢠Muscle atrophy worsens the patient's condition and has been associated with worse outcomes. What is New: ⢠To our knowledge, this is the first study to jointly evaluate the diaphragm and quadriceps muscle thickness and evaluate the reliability of all measurements. ⢠Our study presents reference values for both muscles, enabling comparisons between different clinical conditions.
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Diafragma , Músculo Cuádriceps , Ultrasonografía , Humanos , Recién Nacido , Diafragma/diagnóstico por imagen , Músculo Cuádriceps/diagnóstico por imagen , Músculo Cuádriceps/anatomía & histología , Ultrasonografía/métodos , Estudios Prospectivos , Reproducibilidad de los Resultados , Masculino , Femenino , Valores de Referencia , Variaciones Dependientes del Observador , Edad GestacionalRESUMEN
Amoebiasis is a disease caused by Entamoeba histolytica, affecting the large intestine of humans and occasionally leading to extra-intestinal lesions. Entamoeba dispar is another amoeba species considered commensal, although it has been identified in patients presenting with dysenteric and nondysenteric colitis, as well as amoebic liver abscess. Amoebic virulence factors are essential for the invasion and development of lesions. There is evidence showing that the association of enterobacteria with trophozoites contributes to increased gene expression of amoebic virulence factors. Enteropathogenic Escherichia coli is an important bacterium causing diarrhea, with high incidence rates in the world population, allowing it to interact with Entamoeba sp. in the same host. In this context, this study aims to evaluate the influence of enteropathogenic Escherichia coli on ACFN and ADO Entamoeba dispar strains by quantifying the gene expression of virulence factors, including galactose/N-acetyl-D-galactosamine-binding lectin, cysteine proteinase 2, and amoebapores A and C. Additionally, the study assesses the progression and morphological aspect of amoebic liver abscess and the profile of inflammatory cells. Our results demonstrated that the interaction between EPEC and ACFN Entamoeba dispar strains was able to increase the gene expression of virulence factors, as well as the lesion area and the activity of the inflammatory infiltrate. However, the association with the ADO strain did not influence the gene expression of virulence factors. Together, our findings indicate that the interaction between EPEC, ACFN, and ADO Entamoeba dispar strains resulted in differences in vitro and in vivo gene expression of Gal/GalNAc-binding lectin and CP2, in enzymatic activities of MPO, NAG, and EPO, and consequently, in the ability to cause lesions.
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Entamoeba , Escherichia coli Enteropatógena , Factores de Virulencia , Escherichia coli Enteropatógena/patogenicidad , Escherichia coli Enteropatógena/genética , Entamoeba/patogenicidad , Entamoeba/genética , Entamoeba/fisiología , Factores de Virulencia/genética , Virulencia , Animales , Ratones , Absceso Hepático Amebiano/parasitología , Entamebiasis/parasitología , Humanos , Expresión GénicaRESUMEN
Marine mollusk production is increasing worldwide, and this trend is being evidenced in South American countries, where several species of bivalves are produced, exploited, and traded. This activity brings benefits either for the ecosystem, as it is a less impactful and polluting than other aquaculture practices, and to coastal human communities, as it provides food and income. However, emergence of outbreaks by pathogens is a major concern and can put an entire developing sector at risk. Perkinsosis is a disease caused by Perkinsus spp. protozoans that affect mollusks worldwide. In this review we provide information on Perkinsus spp. among bivalves from South America. Infections by these parasites were only reported to date among coastal Atlantic bivalves of Argentina, Uruguay, and Brazil. The vast majority of cases and studies are reported from Brazil. We comprehensively review those results here. Finally, we suggest some considerations for future investigations that may expand our knowledge of these parasites.
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Alveolados , Animales , América del Sur/epidemiología , Bivalvos/parasitologíaRESUMEN
Understanding and classifying brain states as a function of sleep quality and age has important implications for developing lifestyle-based interventions involving sleep hygiene. Current studies use an algorithm that captures non-linear features of brain complexity to differentiate awake electroencephalography (EEG) states, as a function of age and sleep quality. Fifty-eight participants were assessed using the Pittsburgh Sleep Quality Inventory (PSQI) and awake resting state EEG. Groups were formed based on age and sleep quality (younger adults n = 24, mean age = 24.7 years, SD = 3.43, good sleepers n = 11; older adults n = 34, mean age = 72.87; SD = 4.18, good sleepers n = 9). Ten non-linear features were extracted from multiband EEG analysis to feed several classifiers followed by a leave-one-out cross-validation. Brain state complexity accurately predicted (i) age in good sleepers, with 75% mean accuracy (across all channels) for lower frequencies (alpha, theta, and delta) and 95% accuracy at specific channels (temporal, parietal); and (ii) sleep quality in older groups with moderate accuracy (70 and 72%) across sub-bands with some regions showing greater differences. It also differentiated younger good sleepers from older poor sleepers with 85% mean accuracy across all sub-bands, and 92% at specific channels. Lower accuracy levels (<50%) were achieved in predicting sleep quality in younger adults. The algorithm discriminated older vs. younger groups excellently and could be used to explore intragroup differences in older adults to predict sleep intervention efficiency depending on their brain complexity.
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Envejecimiento , Encéfalo , Electroencefalografía , Calidad del Sueño , Humanos , Electroencefalografía/métodos , Anciano , Masculino , Adulto , Femenino , Envejecimiento/fisiología , Encéfalo/fisiología , Algoritmos , Adulto Joven , Sueño/fisiologíaRESUMEN
Recently, the diarylpentanoid BP-M345 (5) has been identified as a potent in vitro growth inhibitor of cancer cells, with a GI50 value between 0.17 and 0.45 µM, showing low toxicity in non-tumor cells. BP-M345 (5) promotes mitotic arrest by interfering with mitotic spindle assembly, leading to apoptotic cell death. Following on from our previous work, we designed and synthesized a library of BP-M345 (5) analogs and evaluated the cell growth inhibitory activity of three human cancer cell lines within this library in order to perform structure-activity relationship (SAR) studies and to obtain compounds with improved antimitotic effects. Four compounds (7, 9, 13, and 16) were active, and the growth inhibition effects of compounds 7, 13, and 16 were associated with a pronounced arrest in mitosis. These compounds exhibited a similar or even higher mitotic index than BP-M345 (5), with compound 13 displaying the highest antimitotic activity, associated with the interference with mitotic spindle dynamics, inducing spindle collapse and, consequently, prolonged mitotic arrest, culminating in massive cancer cell death by apoptosis.
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Antimitóticos , Antineoplásicos , Neoplasias , Humanos , Antimitóticos/farmacología , Mitosis , Proliferación Celular , Ciclo Celular , Huso Acromático/metabolismo , Neoplasias/metabolismo , Apoptosis , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/metabolismoRESUMEN
Cancer is a complex disease characterized by several alterations, which confer, to the cells, the capacity to proliferate uncontrollably and to resist cellular death. Multiresistance to conventional chemotherapy drugs is often the cause of treatment failure; thus, the search for natural products or their derivatives with therapeutic action is essential. Chiral derivatives of xanthones (CDXs) have shown potential inhibitory activity against the growth of some human tumor cell lines. This work reports the screening of a library of CDXs, through viability assays, in different cancer cell lines: A375-C5, MCF-7, NCI-H460, and HCT-15. CDXs' effect was analyzed based on several parameters of cancer cells, and it was also verified if these compounds were substrates of glycoprotein-P (Pgp), one of the main mechanisms of resistance in cancer therapy. Pgp expression was evaluated in all cell lines, but no expression was observed, except for HCT-15. Also, when a humanized yeast expressing the human gene MDR1 was used, no conclusions could be drawn about CDXs as Pgp substrates. The selected CDXs did not induce significant differences in the metabolic parameters analyzed. These results show that some CDXs present promising antitumor activity, but other mechanisms should be triggered by these compounds.
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Aminoácidos , Xantonas , Humanos , Xantonas/farmacología , Xantonas/química , Línea Celular Tumoral , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genéticaRESUMEN
The female prostate, also known as Skene's gland, is present in both humans and rodents. Prenatal exposure to ethinylestradiol (EE2), a synthetic estrogen found in oral contraceptives, induces pormotes neoplasic prostate lesions in gerbils (Meriones unguiculatus). Conversely, pequi oil (Pe), extracted from the Brazilian Cerrado fruit, has antioxidant, anti-inflammatory, and anticancer properties, mitigates risks associated with chronic diseases related to lifestyle and aging. This study evaluates the impact of prenatal exposure to Pe (300 mg/kg) on senile gerbil offspring's male and female prostates under normal conditions and EE2 exposure (15 µg/kg/day). Histological and morphometric analyses revealed that Pe reduced male body weight and prostate epithelial height, along with a thinner muscle layer. In females, EE2 exposure reduced prostatic weight, while Pe exposure lowered epithelial height and the relative stromal compartment volume, increasing the muscle layer. Pequi oil holds potential in mitigating alterations induced by exposure to the endocrine disruptor EE2.
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Etinilestradiol , Gerbillinae , Efectos Tardíos de la Exposición Prenatal , Próstata , Animales , Masculino , Femenino , Próstata/efectos de los fármacos , Próstata/patología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Etinilestradiol/toxicidad , Embarazo , Aceites de Plantas , Envejecimiento/efectos de los fármacos , Disruptores Endocrinos/toxicidad , EricalesRESUMEN
Construction and demolition waste (CDW) worldwide generation accounts 10 billion tonnes yearly. The major fraction is landfilled requiring innovative recycling methods to reduce the associated environmental impacts and to increase its circularity. Our study demonstrated the feasibility of using different CDW fines to develop recycled cements and optimized the content of CDW recycled cements with well-graded crushed stone (WGCS) for use as pavement base layer. We scaled up the study obtaining CDW cement and aggregates from a local recycling plant, as well as pilot pavement sections designed, constructed and field deflections measured. As results, the CDW cement pastes exhibited accumulated heat values of up to 111 J g-1 and achieved a compressive strength of approximately 16 MPa. The unconfined compressive strength and resilient modulus (RM) achieved using CDW cement and WGCS were 2-3 and >3000 MPa, respectively. The sections constructed using CDW cement exhibited intermediate behaviour compared to those obtained using reference materials (6% Portland cement-WGCS and a conventional granular base made using WGCS). The deflection decreased over time owing to the pozzolanic reaction.
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A third vaccine dose against COVID-19 is already a reality in some countries around the world. In this study, we aimed to evaluate the effectiveness of the Brazilian immunization policy for COVID-19, which involves a booster shot. Participants (n = 210) provided serum samples, which were subjected to enzyme-linked immunosorbent assay (ELISA). Immunological profiles were defined as individuals with or without previous SARS-CoV-2 infection who received at least one vaccine dose in the immunization regimens of AstraZeneca, CoronaVac, or CoronaVac plus a booster shot with Pfizer. In addition, nonvaccinated/infected individuals were also included. As main results, we observed that the numbers of infected individuals were significantly reduced among those who were vaccinated, even with one dose. This result indicates that vaccines are highly protective against COVID-19. However, we observed a significant tendency of serum level decreases of specific antibodies over the time after the second dose. In contrast, the booster shot with the Pfizer vaccine after a CoronaVac immunization regimen showed a significant increase in the specific SARS-CoV-2 IgG serum levels. Moreover, we found that vaccination induced a significantly higher humoral immunological status than only the natural infection with SARS-CoV-2. Collectively, results presented here indicate that vaccines are necessary to induce a robust immunological status, which is maintained, restored, or even improved by booster shots. IMPORTANCE COVID-19 continues to spread around the world despite significant progress in vaccine distribution and population immunity. The dynamics of the antiviral antibody response postvaccination is critical to evaluate vaccine effectiveness across different vaccine platforms and over time. In this study, we evaluate the serum levels of antiviral antibodies in patients from Brazil that received either the CoronaVac or the AstraZeneca vaccine. We found that antibody levels wane over time, vaccines induce protective immunity, and humoral immunity is enhanced with a third vaccine dose. This study reveals that the COVID-19 humoral immunological status induced by vaccines significantly benefits from a booster shot.
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Vacunas contra la COVID-19 , COVID-19 , Anticuerpos Antivirales/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/normas , Humanos , SARS-CoV-2/inmunologíaRESUMEN
OBJECTIVES: We assessed real-world weight change and pregnancy outcomes among pregnant women living with HIV who used integrase strand transferase inhibitor (INSTI)-based combined antiretroviral therapy (cART). METHODS: In a retrospective cohort study from 2014 to 2021 for prevention of perinatal HIV infection, we evaluated changes in weight from the first prenatal visit to near delivery for two groups. The categories of change were: low (< 0.18 kg/week), normal (0.18-0.59 kg/week), and high (> 0.59 kg/week). The backbones were lamivudine + tenofovir disoproxil or lamivudine + zidovudine. The comparison groups were women with body mass index (BMI) < 25 kg/m2 versus BMI ≥ 25 kg/m2 and INSTI-naïve versus INSTI-experienced. Continuous variables were analysed with a Kruskal-Wallis test and count or categorical data with χ2 tests. RESULTS: We enrolled 198 pregnant women. At study entry, 74 had BMI < 25 kg/m2 and 124 had BMI ≥ 25 kg/m2 . Excess gestational weight gain was more frequent among women who were INSTI-naïve among both BMI groups (< 25 and ≥ 25). However, the proportion of participants per weight change category was only significantly different between INSTI-naïve women with baseline BMI < 25 kg/m2 and INSTI-experienced women with BMI < 25 kg/m2 . In particular, INSTI-naïve women with BMI < 25 kg/m2 had significantly higher rates of excess gestational weight gain (31.6%) compared with participants with BMI < 25 kg/m2 who conceived while on INSTIs (11.8%, p = 0.004). Rates of unfavourable pregnancy outcomes were low and did not differ significantly between groups. CONCLUSIONS: INSTI-naïve participants with BMI < 25 kg/m2 gained more weight during pregnancy than participants with BMI ≥ 25 kg/m2 who conceived while using INSTIs. Rates of adverse pregnancy outcomes did not differ between the groups.
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Fármacos Anti-VIH , Ganancia de Peso Gestacional , Infecciones por VIH , Inhibidores de Integrasa VIH , Integrasa de VIH , Humanos , Femenino , Embarazo , Masculino , Infecciones por VIH/tratamiento farmacológico , Lamivudine/uso terapéutico , Mujeres Embarazadas , Estudios Retrospectivos , Fármacos Anti-VIH/uso terapéutico , Aumento de Peso , Inhibidores de Integrasa VIH/uso terapéutico , Resultado del EmbarazoRESUMEN
OBJECTIVES: To update nucleoside reverse transcriptase inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI) resistance rates and describe the frequency of HIV subtypes in a cohort of pregnant people living with HIV (PPLH) at a national Prevention of Mother-To-Child HIV Transmission (PMTCT) centre. METHODS: We evaluated genotypic resistance among PPLH during prenatal care who were antiretroviral therapy-naïve or experienced. We determined mutations by the Surveillance of Drug Resistance Mutations (SDRM) dataset and also focused on studying participants with intermediate or high resistance defined through the Stanford score. RESULTS: From 2018 to 2021, 1170 PPLH received prenatal care at the centre and 550 were genotyped. Among the 295 SDRMs, with respect to NRTI resistance mutations, there were 27/295 (9.2%) M184V/I, 14/295 (4.7%) T215Y/C/D/E/F/V/I/S and 12/295 (4.1%) M41L. For NNRTI, there were 75/295 (25.4%) K103N, 18/295 (6.1%) M230L and 14/295 (4.7%) G190A/E/S mutations. For PI, the most frequent mutations were 13/295 (4.4%) V82A/S/F/T, 12/295 (4.1%) M46I/L and 10/295 (3.4%) D30N. Based on the Stanford score, 36/224 (16%) naïve participants had one or more antiretroviral resistance mutations, 81% of whom had NNRTI resistance. In the treatment-experience group, 108/326 (33%) had one or more mutations, 91% of whom had NNRTI resistance. The most frequent HIV subtype was B (82.5%). CONCLUSIONS: Our findings suggest that continuous surveys of HIV genotype appear to be important tools to map the distribution and evolution of HIV subtypes and resistance to provide information to support treatment policies. Furthermore, concerns about the use of rilpivirine-containing regimens underscore the importance of resistance surveillance.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Humanos , Femenino , Embarazo , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Inhibidores de la Transcriptasa Inversa/farmacología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , VIH-1/genética , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Antirretrovirales/uso terapéutico , Mutación , Genotipo , Farmacorresistencia Viral/genéticaRESUMEN
Nowadays, there is an emergent interest in new trend-driven biomolecules to improve health and wellbeing, which has become an interesting and promising field, considering their high value and biological potential. Astaxanthin is one of these promising biomolecules, with impressive high market growth, especially in the pharmaceutical and food industries. This biomolecule, obtained from natural sources (i.e., microalgae), has been reported in the literature to have several beneficial health effects due to its biological properties. These benefits seem to be mainly associated with Astaxanthin's high antioxidant and anti-inflammatory properties, which may act on several brain issues, thus attenuating symptoms. In this sense, several studies have demonstrated the impact of astaxanthin on a wide range of diseases, namely on brain disorders (such as Alzheimer's disease, Parkinson, depression, brain stroke and autism). Therefore, this review highlights its application in mental health and illness. Furthermore, a S.W.O.T. analysis was performed to display an approach from the market/commercial perspective. However, to bring the molecule to the market, there is still a need for more studies to increase deep knowledge regarding the real impact and mechanisms in the human brain.HIGHLIGHTSAstaxanthin has been mainly extracted from the algae Haematococcus pluvialisAstaxanthin, bioactive molecule with high antioxidant and anti-inflammatory propertiesAstaxanthin has an important protective effect on brain disordersAstaxanthin is highly marketable, mainly for food and pharmaceutical industries.
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The present study compared bacterial and fungal diversity of kefir beverages produced using milk (MK) or sugared water (WK) as propagation matrices and grains from the cities of Curitiba (CU) or Salvador (SA), Brazil, by sequencing the complete set of RNA transcripts produced in four products. In Brazil, milk and sugared water are used as matrices to propagate kefir grains. In all beverages, the bacterial community was composed of Lactobacillaceae and Acetobacteraceae. Saccharomycetaceae was the yeast family more abundant in WK, and Dipodascaceae and Pichiaceae in MK. Regarding KEGG mapping of functional orthologs, the four kefir samples shared 70% of KO entries of yeast genes but only 36% of bacterial genes. Concerning main metabolic processes, the relative abundance of transcripts associated with metabolism (energy metabolism) and environmental information processing (membrane transport) had the highest water/milk kefir ratio observed in Firmicutes. In contrast, transcripts associated with genetic information processing (protein translation, folding, sorting, and degradation) oppositely had the lowest water/milk ratios. Concluding, milk and water kefir have quite different communities of microorganisms. Still, the main mapped functional processes are similar, with only quantitative variation in membrane transport and energy acquisition in the water kefir and protein synthesis and turnover in the milk kefir.
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Soil conditioner is class of products used to enhance physics, physicochemical or soil biological activities, being able to recover disturbed or nutritional unbalanced soils. The formulation of a soil conditioner composed by bauxite residue (BR), and organic oil palm wastes, as raw materials, was recently proposed as an innovative strategy for the Brazilian acid soils amendment. Here we show the results of soil conditioner amended soil leaching tests and agronomical performance. The soil conditioners were formulated by BR mixed with decomposed POC (palm oil compost) and non-decomposed POMW (palm oil mill waste) oil palm wastes, in the proportion of 25% BR + 75% POC (T1) and 50% BR + 50% POMW (T2), in addition to the treatment with 100% POMW without BR (T3) and limestone at a dose calculated to raise soil pH to 6.0 (T4). Except for T4, all conditioners were applied to the soil at doses of 40, 80, and 120 t ha-1 for leaching tests. The experimental plots were composed of polyvinyl chloride columns, filled with 5 kg of soil, with bottles adapted with hoses at the bottom to facilitate drainage of the leachate. After leaching tests, the respective columns were used as pots for the cultivation of Brachiaria grass, stage with addition of a control composed by undisturbed soil (T5). The pH of the leachates had changes, but the use of BR associated with POMW was similar to the use of limestone. Of the 65 chemical elements evaluated, only nine were identified in the leachate, being most of them considered as plant nutrients. As for soil pH, limestone was slightly higher (6.6) than treatments that had BR (5.5). Brachiaria grass cultivated in the soil amended with conditioners showed similar results of limestone treated soil for the parameters of plant development and showed fertility improvement.
Asunto(s)
Contaminantes del Suelo , Suelo , Suelo/química , Óxido de Aluminio , Aceite de Palma , Agricultura/métodos , Poaceae , Contaminantes del Suelo/análisis , Carbonato de CalcioRESUMEN
Alzheimer's disease (AD) is an illness that affects people aged 65 or older and affects around 6.5 million in the United States. Resveratrol is a chemical obtained from natural products and it exhibits biological activity based on inhibiting the formation, depolymerization of the amyloid, and decreasing neuroinflammation. Due to the insolubility of this compound; its incorporation in surfactant-based systems was proposed to design an intranasal formulation. A range of systems has been produced by mixing oleic acid, CETETH-20 and water. Polarised light microscopy (PLM), small angle x-ray scattering (SAXS) and transmission electron microscopy (TEM) confirm the initial liquid formulation (F) presented as microemulsion (ME). After dilution, the gelled systems were characterized as hexagonal mesophase and they showed feasibility proprieties. Pharmacological assays performed after intranasal administration showed the ability to improve learning and memory in animals, as well as remission of neuroinflammation via inhibition of interleukin.