RESUMEN
Maintenance of a minimal telomere length is essential to prevent cellular senescence. When critically short telomeres arise in the absence of telomerase, they can be repaired by homology-directed repair (HDR) to prevent premature senescence onset. It is unclear why specifically the shortest telomeres are targeted for HDR. We demonstrate that the non-coding RNA TERRA accumulates as HDR-promoting RNA-DNA hybrids (R-loops) preferentially at very short telomeres. The increased level of TERRA and R-loops, exclusively at short telomeres, is due to a local defect in RNA degradation by the Rat1 and RNase H2 nucleases, respectively. Consequently, the coordination of TERRA degradation with telomere replication is altered at shortened telomeres. R-loop persistence at short telomeres contributes to activation of the DNA damage response (DDR) and promotes recruitment of the Rad51 recombinase. Thus, the telomere length-dependent regulation of TERRA and TERRA R-loops is a critical determinant of the rate of replicative senescence.
Asunto(s)
Ciclo Celular , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/metabolismo , Telómero/metabolismo , Senescencia Celular , Daño del ADN , Exorribonucleasas/metabolismo , Hibridación de Ácido Nucleico , Reparación del ADN por Recombinación , Proteínas Represoras/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Telómero/química , Proteínas de Unión a Telómeros/metabolismoRESUMEN
In cells lacking telomerase, telomeres gradually shorten during each cell division to reach a critically short length, permanently activate the DNA damage checkpoint, and trigger replicative senescence. The increase in genome instability that occurs as a consequence may contribute to the early steps of tumorigenesis. However, because of the low frequency of mutations and the heterogeneity of telomere-induced senescence, the timing and mechanisms of genome instability increase remain elusive. Here, to capture early mutation events during replicative senescence, we used a combined microfluidic-based approach and live-cell imaging in yeast. We analyzed DNA damage checkpoint activation in consecutive cell divisions of individual cell lineages in telomerase-negative yeast cells and observed that prolonged checkpoint arrests occurred frequently in telomerase-negative lineages. Cells relied on the adaptation to the DNA damage pathway to bypass the prolonged checkpoint arrests, allowing further cell divisions despite the presence of unrepaired DNA damage. We demonstrate that the adaptation pathway is a major contributor to the genome instability induced during replicative senescence. Therefore, adaptation plays a critical role in shaping the dynamics of genome instability during replicative senescence.
Asunto(s)
Adaptación Fisiológica/genética , Puntos de Control del Ciclo Celular/genética , Daño del ADN/genética , Inestabilidad Genómica/genética , Saccharomyces cerevisiae/genética , Reparación del ADN , Genoma Fúngico/genética , Técnicas Analíticas Microfluídicas , Mutación , Imagen Óptica , Saccharomyces cerevisiae/enzimología , Telomerasa/genéticaRESUMEN
BACKGROUND: Prenatal exposure to Zika virus has potential teratogenic effects, with a wide spectrum of clinical presentation referred to as congenital Zika syndrome. Data on survival among children with congenital Zika syndrome are limited. METHODS: In this population-based cohort study, we used linked, routinely collected data in Brazil, from January 2015 through December 2018, to estimate mortality among live-born children with congenital Zika syndrome as compared with those without the syndrome. Kaplan-Meier curves and survival models were assessed with adjustment for confounding and with stratification according to gestational age, birth weight, and status of being small for gestational age. RESULTS: A total of 11,481,215 live-born children were followed to 36 months of age. The mortality rate was 52.6 deaths (95% confidence interval [CI], 47.6 to 58.0) per 1000 person-years among live-born children with congenital Zika syndrome, as compared with 5.6 deaths (95% CI, 5.6 to 5.7) per 1000 person-years among those without the syndrome. The mortality rate ratio among live-born children with congenital Zika syndrome, as compared with those without the syndrome, was 11.3 (95% CI, 10.2 to 12.4). Among infants born before 32 weeks of gestation or with a birth weight of less than 1500 g, the risks of death were similar regardless of congenital Zika syndrome status. Among infants born at term, those with congenital Zika syndrome were 14.3 times (95% CI, 12.4 to 16.4) as likely to die as those without the syndrome (mortality rate, 38.4 vs. 2.7 deaths per 1000 person-years). Among infants with a birth weight of 2500 g or greater, those with congenital Zika syndrome were 12.9 times (95% CI, 10.9 to 15.3) as likely to die as those without the syndrome (mortality rate, 32.6 vs. 2.5 deaths per 1000 person-years). The burden of congenital anomalies, diseases of the nervous system, and infectious diseases as recorded causes of deaths was higher among live-born children with congenital Zika syndrome than among those without the syndrome. CONCLUSIONS: The risk of death was higher among live-born children with congenital Zika syndrome than among those without the syndrome and persisted throughout the first 3 years of life. (Funded by the Ministry of Health of Brazil and others.).
Asunto(s)
Mortalidad Infantil , Infección por el Virus Zika/congénito , Infección por el Virus Zika/mortalidad , Peso al Nacer , Brasil/epidemiología , Preescolar , Estudios de Cohortes , Femenino , Edad Gestacional , Humanos , Lactante , MasculinoRESUMEN
The microsporidian genus Nosema is primarily known to infect insects of economic importance stimulating high research interest, while other hosts remain understudied. Nosema granulosis is one of the formally described Nosema species infecting amphipod crustaceans, being known to infect only two host species. Our first aim was to characterize Nosema spp. infections in different amphipod species from various European localities using the small subunit ribosomal DNA (SSU) marker. Second, we aimed to assess the phylogenetic diversity, host specificity and to explore the evolutionary history that may explain the diversity of gammarid-infecting Nosema lineages by performing a phylogenetic reconstruction based on RNA polymerase II subunit B1 (RPB1) gene sequences. For the host species Gammarus balcanicus, we also analyzed whether parasites were in excess in females to test for sex ratio distortion in relation with Nosema infection. We identified Nosema spp. in 316 individuals from nine amphipod species being widespread in Europe. The RPB1-based phylogenetic reconstruction using newly reported sequences and available data from other invertebrates identified 39 haplogroups being associated with amphipods. These haplogroups clustered into five clades (A-E) that did not form a single amphipod-infecting monophyletic group. Closely related sister clades C and D correspond to Nosema granulosis. Clades A, B and E might represent unknown Nosema species infecting amphipods. Host specificity seemed to be variable with some clades being restricted to single hosts, and some that could be found in several host species. We show that Nosema parasite richness in gammarid hosts is much higher than expected, illustrating the advantage of the use of RPB1 marker over SSU. Finally, we found no hint of sex ratio distortion in Nosema clade A infecting G. balcanicus. This study shows that Nosema spp. are abundant, widespread and diverse in European gammarids. Thus, Nosema is as diverse in aquatic as in terrestrial hosts.
Asunto(s)
Anfípodos , Nosema , Humanos , Femenino , Animales , Nosema/genética , Anfípodos/genética , Filogenia , Agua DulceRESUMEN
Complex incubation strategies have evolved to solve the trade-off between parent survival and care for their eggs with often brief departures (recesses) that maximize egg survival, and infrequent extended recesses maximizing adult condition. Here we examined incubation behaviour of sanderlings (Calidris alba), a species that exhibits both biparental and uniparental incubation behaviour. During 11 breeding seasons in Greenland, we have quantified incubation variability with thermologgers placed in nests. We estimated the impact of environmental conditions and individual characteristics on the occurrence and the duration of recesses. We found that extended recesses are a unique feature of uniparentals, and their frequency and duration increased in colder temperatures. The relationship was mediated by body condition, with individuals in poor condition performing longer extended recesses in colder temperatures. This suggests that extended recesses may represent a shift towards self-maintenance at the expense of the egg care, allowing birds to continue incubating under unfavourable conditions. Our study illustrates how extended recesses may be a key breeding strategy to overcome high energetic costs associated with incubation. Quantifying such behavioural flexibility paves the way for tracking future behavioural responses of individuals in the face of changing environments.
Asunto(s)
Charadriiformes , Humanos , Animales , Temperatura , Aves/fisiología , Frío , CruzamientoRESUMEN
This study aimed to identify evidence from animal studies examining genetic variants underlying maxillomandibular discrepancies resulting in a skeletal Class III (SCIII) malocclusion phenotype. Following the Manual for Evidence Synthesis of the JBI and the PRISMA extension for scoping reviews, a participant, concept, context question was formulated and systematic searches were executed in the PubMed, Scopus, WOS, Scielo, Open Gray, and Mednar databases. Of the 779 identified studies, 13 met the selection criteria and were included in the data extraction. The SCIII malocclusion phenotype was described as mandibular prognathism in the Danio rerio, Dicentrarchus labrax, and Equus africanus asinus models; and as maxillary deficiency in the Felis silvestris catus, Canis familiaris, Salmo trutta, and Mus musculus models. The identified genetic variants highlight the significance of BMP and TGF-ß signaling. Their regulatory pathways and genetic interactions link them to cellular bone regulation events, particularly ossification regulation of postnatal cranial synchondroses. In conclusion, twenty genetic variants associated with the skeletal SCIII malocclusion phenotype were identified in animal models. Their interactions and regulatory pathways corroborate the role of these variants in bone growth, differentiation events, and ossification regulation of postnatal cranial synchondroses.
Asunto(s)
Maloclusión de Angle Clase III , Animales , Gatos , Perros , Humanos , Ratones , Maloclusión de Angle Clase III/genética , Mandíbula , Modelos Animales , FenotipoRESUMEN
Skeletal Class III (SCIII) is among the most challenging craniofacial dysmorphologies to treat. There is, however, a knowledge gap regarding which syndromes share this clinical phenotype. The aims of this study were to: (i) identify the syndromes affected by the SCIII phenotype; (ii) clarify the involvement of maxillary and/or mandibular structures; (iii) explore shared genetic/molecular mechanisms. A two-step strategy was designed: [Step#1] OMIM, MHDD, HPO, GeneReviews and MedGen databases were explored; [Step#2]: Syndromic conditions indexed in [Step#1] were explored in Medline, Pubmed, Scopus, Cochrane Library, WOS and OpenGrey. Eligibility criteria were defined. Individual studies were assessed for risk of bias using the New Ottawa Scale. For quantitative analysis, a meta-analysis was conducted. This scoping review is a hypothesis-generating research. Twenty-two studies met the eligibility criteria. Eight syndromes affected by the SCIII were targeted: Apert syndrome, Crouzon syndrome, achondroplasia, X-linked hypohidrotic ectodermal dysplasia (XLED), tricho-dento-osseous syndrome, cleidocranial dysplasia, Klinefelter and Down syndromes. Despite heterogeneity between studies [p < 0.05], overall effects showed that midface components were affected in Apert and Down Syndromes, lower face in Klinefelter Syndrome and midface and lower face components in XLED. Our review provides new evidence on the craniofacial characteristics of genetically confirmed syndromes exhibiting the SCIII phenotype. Four major regulatory pathways might have a modulatory effect on this phenotype. IMPACT: What does this review add to the existing literature? To date, there is no literature exploring which particular syndromes exhibit mandibular prognathism as a common trait. Through this research, it was possibly to identify the particular syndromes that share the skeletal Class III phenotype (mandibular prognathism) as a common trait highlighting the common genetic and molecular pathways between different syndromes acknowledging their impact in craniofacial development.
Asunto(s)
Anomalías Craneofaciales , Genotipo , Fenotipo , Humanos , Anomalías Craneofaciales/genética , Anomalías Craneofaciales/terapia , Maloclusión de Angle Clase III/genética , SíndromeRESUMEN
The objective of this study is to evaluate the association between the consumption of ultra-processed foods (UPF) and the mental health of pregnant women from the South of Brazil. This is a cross-sectional study carried out in Criciúma, Brazil, through face-to-face interviews, from April to December 2022. Pregnant women aged 18 or older who underwent prenatal care in the forty-eight basic health care units of the municipality and who were in their third trimester of pregnancy were included. High consumption of UPF was considered as six or more items or subgroups of UPF consumed on the day before the interview, using the Nova-UPF screener. The mental health variables were depressive symptoms, stress, sadness and anxiety. Crude and adjusted analyses were conducted using the Fisher's exact test and the Poisson regression with robust variance. In total, 428 pregnant women were studied; most of them were aged between 20 and 25 years and were white. Pregnant women who presented high consumption of UPF were 1·42-fold (95 % CI 1·06, 1·92) more likely to experience anxiety and presented a prevalence 56 % (95 % CI 1·18, 2·07) higher of stress when compared with those who did not present high consumption of UPF. The prevalence of depressive symptoms and feelings of sadness was 1·31-fold (95 % CI 1·08, 1·60) and 3·41-fold (95 % CI 1·77, 6·58) higher among those with high consumption of UPF, respectively. The results suggest that diet quality is associated with the mental health of pregnant women. Promoting joint actions focused on food and nutritional education, and mental health, for pregnant women, is necessary.
RESUMEN
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.
RESUMEN
BACKGROUND: Interplay between physical and mental health (MH) is widely recognised amongst patients with Musculoskeletal and co-existing MH conditions. Evidence suggests that psychological interventions improve outcomes and satisfaction in patients with physical conditions, however current healthcare models continue to separate physical and mental health care, as health services are fragmented. If the delivery of MH support could be facilitated by Allied Health Professionals (AHPs), such as physiotherapists and occupational therapists (OTs), this could be an effective, low-cost way to achieve routine integration. This study aimed to explore the experiences of UK physiotherapists and OTs working with patients with MSK and co-existing MH conditions and to understand views on improving MSK services. METHODS: This was an exploratory-descriptive qualitative study using semi-structured interviews. Participants were recruited via social media and professional organisations using convenience sampling. Participants included registered UK physiotherapists or OTs within MSK settings who managed patients with MH conditions. Inductive thematic analysis was used, where single and double-level coding, single counting and inclusion of divergent cases were conducted to enhance methodological rigour. RESULTS: Three overarching themes were identified. Overarching theme one referred to openness to provide MH support, with scope of practice and lack of confidence as themes. Overarching theme two described challenges, incorporating mental health stigma, the clinical environment, and limited experience. The overarching theme referring to training, identified the need for further training and strategies to implement as themes. CONCLUSION: Many challenges to achieving optimal integration of physical and mental health care exist within MSK services. These challenges go beyond the need for additional training and knowledge acquisition and include departmental readiness such as funding, diary management, and supervision by senior colleagues/or psychologists. These need consideration in parallel to match the evolving needs of the MSK population.
Asunto(s)
Trastornos Mentales , Salud Mental , Humanos , Técnicos Medios en Salud , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , Trastornos Mentales/psicología , Investigación Cualitativa , Reino Unido/epidemiologíaRESUMEN
Mushrooms are a source of primary and secondary metabolites. Little is known about the most suitable conditions for production of mushrooms by submerged fermentation. This article reports antioxidant and cytotoxic assays, in addition to quantitatively evaluating the content of proteases with fibrinolytic action in the crude extracts of two species of edible mushrooms produced in different formulations, as well as evaluating the recovery of these enzymes by aqueous two-phase systems (ATPS). The mushrooms Pleurotus ostreatus and Pleurotus eryngii, at concentration of 100 µg/mL, displayed inhibition of DPPH and ABTS radicals below 50%. In the cytotoxicity test, the cells human fibroblast cell lines (MRC-5) showed cell viability greater than 80%. Concerning fibrinolytic activity, P. eryngii presented 226.47 ± 7.26 U/mL, therefore being more efficient than P. ostreatus (71.5 ± 0.56 U/mL). In the recovery of the P. eryngii extract by ATPS, the fibrinolytic protease was partitioned in the salt phase (30.25 U/mL). The molecular mass of the proteases was between 75 and 100 kDa. These results prove the low cytotoxicity of the extracts produced and that fermentation in supplemented malt broth favored the excretion of fibrinolytic proteases compared to the other evaluated media.
Asunto(s)
Agaricales , Antineoplásicos , Pleurotus , Humanos , Antioxidantes/química , Pleurotus/química , Péptido Hidrolasas/metabolismo , Agaricales/química , Endopeptidasas/metabolismo , Antineoplásicos/metabolismoRESUMEN
BACKGROUND: For adolescents who have criminal convictions, achieving a positive progress including desistance from offending may depend on a sense of well-being. Factors associated with growth in well-being are not widely researched, but there is some work that suggests that qualities in other internal states as well as in the environment may foster well-being. AIMS: To examine the well-being of young male incarcerated offenders, and its relationship with frequency of contacts with the family, perceptions of socio-educational environment, feelings about the future and self-efficacy. METHODS: Participants were recruited from three secure education institutions in the Federal District of Brasília, Brazil, under the management of the Secretariat of Justice. They were invited to complete anonymous self-report questionnaires, which included the Psychological Well-Being Scale, the Perception of the Socio-Educational Environment Scale, the Feelings about the Future Scale and the Multidimensional Scale of Perceived Self-Efficacy, and to provide limited sociodemographic data. RESULTS: 195 young male offenders participated and their mean age was 16.8 years (SD = 1.58, range 14-20). There was a positive correlation between well-being and perceptions of the socio-educational environment, positive feelings about the future and self-efficacy self-ratings. Multiple linear regression analyses confirmed that the frequency of family contacts, positive perceptions of the socio-educational environment, positive feelings about the future, and self-efficacy in leisure and social activities independently contributed to the well-being of young offenders. CONCLUSION: Although well-being has been associated with desistance from committing crimes, the factors that may predispose to well-being have been researched less and never before examined among inmates in Brazil. While longitudinal work is needed to be certain of the direction of the relationship, the fact that the results are broadly consistent with a similar study carried out on the other side of the world is encouraging in terms of indicating ways forward in rehabilitation. It is necessary to develop interventions that support family relationships and promote personal relationships and personal development, not only of useful skills but also of personal confidence in those skills.
Asunto(s)
Adolescente Institucionalizado , Criminales , Prisioneros , Adolescente , Humanos , Masculino , Prisioneros/psicología , Criminales/psicología , Encuestas y Cuestionarios , Instituciones AcadémicasRESUMEN
The correct diagnosis is fundamental for the appropriate treatment to be employed in a particular pathology. The best treatment is not the one that solves only local problems, fragmenting the patient, and therefore, it is necessary to integrate the entire systemic condition of the individual before initiating any local treatment. This context inevitably requires dentistry to participate in a multidisciplinary approach, where the role of the dentist is expanded in concepts that encompass ethics, human dignity, and professional valorization. This article describes a clinical case of a patient with mucopolysaccharidosis type I, whose treatment of cystic lesions present in the mandible was exclusively performed through marsupialisation. The objective of this study is to demonstrate, within the complexity of this rare syndrome, the difficulties of diagnosis and the need for evaluation of the patient beyond the limits of the oral cavity, as well as to report two cases of large dentigerous cysts, surgically treated conservatively through marsupialisation, without the need for re-approach for enucleation and without recurrences over a 20-year period.
Asunto(s)
Quiste Dentígero , Mucopolisacaridosis I , Humanos , Quiste Dentígero/cirugía , Quiste Dentígero/diagnóstico , Mucopolisacaridosis I/complicaciones , Mucopolisacaridosis I/diagnóstico , Mucopolisacaridosis I/terapia , Masculino , Enfermedades Mandibulares/cirugía , Enfermedades Mandibulares/diagnóstico , FemeninoRESUMEN
BACKGROUND: Children with congenital Zika syndrome (CZS) have severe damage to the peripheral and central nervous system (CNS), greatly increasing the risk of death. However, there is no information on the sequence of the underlying, intermediate, immediate, and contributing causes of deaths among these children. The aims of this study are describe the sequence of events leading to death of children with CZS up to 36 months of age and their probability of dying from a given cause, 2015 to 2018. METHODS AND FINDINGS: In a population-based study, we linked administrative data on live births, deaths, and cases of children with CZS from the SINASC (Live Birth Information System), the SIM (Mortality Information System), and the RESP (Public Health Event Records), respectively. Confirmed and probable cases of CZS were those that met the criteria established by the Brazilian Ministry of Health. The information on causes of death was collected from death certificates (DCs) using the World Health Organization (WHO) DC template. We estimated proportional mortality (PM%) among children with CZS and among children with non-Zika CNS congenital anomalies (CA) by 36 months of age and proportional mortality ratio by cause (PMRc). A total of 403 children with confirmed and probable CZS who died up to 36 months of age were included in the study; 81.9% were younger than 12 months of age. Multiple congenital malformations not classified elsewhere, and septicemia unspecified, with 18 (PM = 4.5%) and 17 (PM = 4.2%) deaths, respectively, were the most attested underlying causes of death. Unspecified septicemia (29 deaths and PM = 11.2%) and newborn respiratory failure (40 deaths and PM = 12.1%) were, respectively, the predominant intermediate and immediate causes of death. Fetuses and newborns affected by the mother's infectious and parasitic diseases, unspecified cerebral palsy, and unspecified severe protein-caloric malnutrition were the underlying causes with the greatest probability of death in children with CZS (PMRc from 10.0 to 17.0) when compared to the group born with non-Zika CNS anomalies. Among the intermediate and immediate causes of death, pneumonitis due to food or vomiting and unspecified seizures (PMRc = 9.5, each) and unspecified bronchopneumonia (PMRc = 5.0) were notable. As contributing causes, fetus and newborn affected by the mother's infectious and parasitic diseases (PMRc = 7.3), unspecified cerebral palsy, and newborn seizures (PMRc = 4.5, each) were more likely to lead to death in children with CZS than in the comparison group. The main limitations of this study were the use of a secondary database without additional clinical information and potential misclassification of cases and controls. CONCLUSION: The sequence of causes and circumstances involved in the deaths of the children with CZS highlights the greater vulnerability of these children to infectious and respiratory conditions compared to children with abnormalities of the CNS not related to Zika.
Asunto(s)
Parálisis Cerebral , Malformaciones del Sistema Nervioso , Complicaciones Infecciosas del Embarazo , Sepsis , Infección por el Virus Zika , Virus Zika , Embarazo , Femenino , Recién Nacido , Niño , Humanos , Brasil , Causas de Muerte , ConvulsionesRESUMEN
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.
Asunto(s)
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.
Asunto(s)
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
BACKGROUND: Fetal loss is one of the most serious adverse outcomes of pregnancy. Since the onset of the COVID-19 pandemic, Brazil has recorded an unprecedented number of hospitalizations of pregnant women due to acute respiratory distress (ARD), thereby, we aimed to assess the risk of fetal deaths associated to ARD during pregnancy in Bahia state, Brazil, in the context of the COVID-19 pandemic. METHODS: This is an observational population-based retrospective cohort study, developed with women at or after 20 weeks of pregnancy, residents in Bahia, Brazil. Women who had acute respiratory distress (ARD) in pregnancy during the COVID-19 pandemic (Jan 2020 to Jun 2021) were considered 'exposed'. Women who did not have ARD in pregnancy, and whose pregnancy occurred before the onset of the COVID-19 pandemic (Jan 2019 to Dec 2019) were considered 'non-exposed'. The main outcome was fetal death. We linked administrative data (under mandatory registration) on live births, fetal deaths, and acute respiratory syndrome, using a probabilistic linkage method, and analyzed them with multivariable logistic regression models. RESULTS: 200,979 pregnant women participated in this study, 765 exposed and 200,214 unexposed. We found four times higher chance of fetal death in women with ARD during pregnancy, of all etiologies (adjusted odds ratio [aOR] 4.06 confidence interval [CI] 95% 2.66; 6.21), and due to SARS-CoV-2 (aOR 4.45 CI 95% 2.41; 8.20). The risk of fetal death increased more when ARD in pregnancy was accompanied by vaginal delivery (aOR 7.06 CI 95% 4.21; 11.83), or admission to Intensive Care Unit (aOR 8.79 CI 95% 4.96; 15.58), or use of invasive mechanical ventilation (aOR 21.22 CI 95% 9.93; 45.36). CONCLUSION: Our findings can contribute to expanding the understanding of health professionals and managers about the harmful effects of SARS-CoV-2 on maternal-fetal health and alerts the need to prioritize pregnant women in preventive actions against SARS-CoV-2 and other respiratory viruses. It also suggests that pregnant women, infected with SARS-CoV-2, need to be monitored to prevent complications of ARD, including a careful assessment of the risks and benefits of early delivery to prevent fetal death.
Asunto(s)
COVID-19 , Complicaciones Infecciosas del Embarazo , Síndrome de Dificultad Respiratoria , Femenino , Embarazo , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Brasil/epidemiología , Estudios Retrospectivos , Estudios de Cohortes , Pandemias , Complicaciones Infecciosas del Embarazo/epidemiología , Muerte Fetal/etiología , Nacimiento Vivo , Resultado del Embarazo/epidemiologíaRESUMEN
Arbovirus can cause diseases with a broad spectrum from mild to severe and long-lasting symptoms, affecting humans worldwide and therefore considered a public health problem with global and diverse socio-economic impacts. Understanding how they spread within and across different regions is necessary to devise strategies to control and prevent new outbreaks. Complex network approaches have widespread use to get important insights on several phenomena, as the spread of these viruses within a given region. This work uses the motif-synchronization methodology to build time varying complex networks based on data of registered infections caused by Zika, chikungunya, and dengue virus from 2014 to 2020, in 417 cities of the state of Bahia, Brazil. The resulting network sets capture new information on the spread of the diseases that are related to the time delay in the synchronization of the time series among different municipalities. Thus the work adds new and important network-based insights to previous results based on dengue dataset in the period 2001-2016. The most frequent synchronization delay time between time series in different cities, which control the insertion of edges in the networks, ranges 7 to 14 days, a period that is compatible with the time of the individual-mosquito-individual transmission cycle of these diseases. As the used data covers the initial periods of the first Zika and chikungunya outbreaks, our analyses reveal an increasing monotonic dependence between distance among cities and the time delay for synchronization between the corresponding time series. The same behavior was not observed for dengue, first reported in the region back in 1986, either in the previously 2001-2016 based results or in the current work. These results show that, as the number of outbreaks accumulates, different strategies must be adopted to combat the dissemination of arbovirus infections.
RESUMEN
Phaeurus antarcticus is a member of the Desmarestiaceae family endemic to the Antarctic Peninsula. Reports addressing its chemical composition and biological activities are scarce. Herein, bioactive non-polar compounds of P.â antarcticus against pathogenic bacteria, Leishmania amazonensis and Neospora caninum parasites were targeted through GC-MS Molecular Networking and multivariate analysis (OPLS-DA). The effects on horseradish peroxidase (HRP) were also evaluated. P.â antarcticus exhibited selective bacteriostatic and bactericidal activities against Staphylococcus aureus with MIC and MBC values from 6.25-100â µg mL-1 . Fractions HX-FC and HX-FD were the most active against L.â amazonensis with EC50 ranging from 18.5-62.3â µg mL-1 . Additionally, fractions HX-FC and HX-FD showed potent inhibition of N. caninum at EC50 values of 2.8 and 6.3â µg mL-1 , respectively. All fractions inhibited HRP activity, indicating possible interactions with Heme proteins. It was possible to annotate compounds from tree mains clusters, containing terpenoids, steroids, fatty acids, and alcohols by correlating the spectral data of the GC-MS analysis with Molecular Networking and the OPLS-DA results.
Asunto(s)
Antiinfecciosos , Algas Marinas , Extractos Vegetales/química , Cromatografía de Gases y Espectrometría de Masas/métodos , Regiones Antárticas , Antiinfecciosos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Pruebas de Sensibilidad MicrobianaRESUMEN
Recycling nutrients helps to reduce the environmental impact of agriculture and contributes to alleviating the effects of global climate change. A recent trend in sugarcane cultivation is the application of concentrated vinasse (CV) combined with fertilizers into an organo-mineral formulation to improve logistics, reduce costs and foster the circular economy. However, the implications of the application of such organo-mineral formulation in sugarcane fields are unclear. In this study, we evaluated the effects of the organo-mineral formulation containing granular urea (UR), and a nitrification inhibitor (NI) on crop yields, NH3 volatilization, and N2O emissions. Field experiments were conducted during two fertilization seasons, dry and wet, and the treatments were: control; UR; UR + NI; CV; CV + UR; and CV + UR + NI. CV was applied at 7 m3 ha-1. The treatments (except control and CV) were balanced to receive the same amount of N and K. Compared with UR, the organo-mineral formulation of CV + UR decreased NH3 volatilization losses from 7% to 4% in the dry season and from 3.5% to 0.5% in the wet season. Conversely, compared with UR, N2O emissions increased significantly (p ≤ 0.05) in CV + UR in the wet season from 1% to 2% of applied N. In the dry season, no differences were observed. The addition of NI was effective in mitigating N2O emissions in both seasons. Emission reductions ranged from 43 to 48% in the dry season and from 71 to 84%, in the wet season. Fertilization with UR or the organo-mineral formulation influenced sugarcane yield only in the dry season, with the highest yield in CV + UR. NI did not affect crop yield. In general, emission intensities (kg CO2eq Mg-1 of stalk) were highest in CV + UR. We conclude that the organo-mineral formulation reduced NH3 losses and increased N2O emissions compared with regular solid fertilizer and that NI was effective for mitigating N2O emissions.