RESUMO
BACKGROUND: Cervical cerclage, cervical pessary, and vaginal progesterone have each been shown to reduce preterm birth (PTB) in high-risk women, but to our knowledge, there has been no randomised comparison of the 3 interventions. The SuPPoRT "Stitch, Pessary, or Progesterone Randomised Trial" was designed to compare the rate of PTB <37 weeks between each intervention in women who develop a short cervix in pregnancy. METHODS AND FINDINGS: SuPPoRT was a multicentre, open label 3-arm randomised controlled trial designed to demonstrate equivalence (equivalence margin 20%) conducted from 1 July 2015 to 1 July 2021 in 19 obstetric units in the United Kingdom. Asymptomatic women with singleton pregnancies with transvaginal ultrasound cervical lengths measuring <25 mm between 14+0 and 23+6 weeks' gestation were eligible for randomisation (1:1:1) to receive either vaginal cervical cerclage (n = 128), cervical pessary (n = 126), or vaginal progesterone (n = 132). Minimisation variables were gestation at recruitment, body mass index (BMI), and risk factor for PTB. The primary outcome was PTB <37 weeks' gestation. Secondary outcomes included PTB <34 weeks', <30 weeks', and adverse perinatal outcome. Analysis was by intention to treat. A total of 386 pregnant women between 14+0 and 23+6 weeks' gestation with a cervical length <25 mm were randomised to one of the 3 interventions. Of these women, 67% were of white ethnicity, 18% black ethnicity, and 7.5% Asian ethnicity. Mean BMI was 25.6. Over 85% of women had prior risk factors for PTB; 39.1% had experienced a spontaneous PTB or midtrimester loss (>14 weeks gestation); and 45.8% had prior cervical surgery. Data from 381 women were available for outcome analysis. Using binary regression, randomised therapies (cerclage versus pessary versus vaginal progesterone) were found to have similar effects on the primary outcome PTB <37 weeks (39/127 versus 38/122 versus 32/132, p = 0.4, cerclage versus pessary risk difference (RD) -0.7% [-12.1 to 10.7], cerclage versus progesterone RD 6.2% [-5.0 to 17.0], and progesterone versus pessary RD -6.9% [-17.9 to 4.1]). Similarly, no difference was seen for PTB <34 and 30 weeks, nor adverse perinatal outcome. There were some differences in the mild side effect profile between interventions (vaginal discharge and bleeding) and women randomised to progesterone reported more severe abdominal pain. A small proportion of women did not receive the intervention as per protocol; however, per-protocol and as-treated analyses showed similar results. The main study limitation was that the trial was underpowered for neonatal outcomes and was stopped early due to the COVID-19 pandemic. CONCLUSIONS: In this study, we found that for women who develop a short cervix, cerclage, pessary, and vaginal progesterone were equally efficacious at preventing PTB, as judged with a 20% equivalence margin. Commencing with any of the therapies would be reasonable clinical management. These results can be used as a counselling tool for clinicians when managing women with a short cervix. TRIAL REGISTRATION: EU Clinical Trials register. EudraCT Number: 2015-000456-15, clinicaltrialsregister.eu., ISRCTN Registry: ISRCTN13364447, isrctn.com.
Assuntos
Cerclagem Cervical , Colo do Útero , Pessários , Nascimento Prematuro , Progesterona , Humanos , Feminino , Nascimento Prematuro/prevenção & controle , Progesterona/administração & dosagem , Progesterona/uso terapêutico , Gravidez , Cerclagem Cervical/métodos , Adulto , Administração Intravaginal , Colo do Útero/diagnóstico por imagem , Resultado do Tratamento , Medida do Comprimento CervicalRESUMO
BACKGROUND: Fetal growth restriction (FGR) corresponds to the fetus's inability to achieve an adequate weight gain based on genetic potential and gestational age. It is an important cause of morbidity and mortality. SUMMARY: In this review, we address the challenges of diagnosis and classification of FGR. We review how chronic fetal hypoxia impacts brain development. We describe recent advances on placental and fetal brain imaging using magnetic resonance imaging and how they offer new noninvasive means to study growth restriction in humans. We go on to review the impact of FGR on brain integrity in the neonatal period, later childhood, and adulthood and review available therapies. KEY MESSAGES: FGR consequences are not limited to the perinatal period. We hypothesize that impaired brain reserve, as defined by structure and size, may predict some concerning epidemiological data of impaired cognitive outcomes and dementia with aging in this group of patients.
RESUMO
Relative uteroplacental insufficiency of labor (RUPI-L) is a clinical condition that refers to alterations in the fetal oxygen "demand-supply" equation caused by the onset of regular uterine activity. The term RUPI-L indicates a condition of "relative" uteroplacental insufficiency which is relative to a specific stressful circumstance, such as the onset of regular uterine activity. RUPI-L may be more prevalent in fetuses in which the ratio between the fetal oxygen supply and demand is already slightly reduced, such as in cases of subclinical placental insufficiency, post-term pregnancies, gestational diabetes, and other similar conditions. Prior to the onset of regular uterine activity, fetuses with a RUPI-L may present with normal features on the cardiotocography. However, with the onset of uterine contractions, these fetuses start to manifest abnormal fetal heart rate patterns which reflect the attempt to maintain adequate perfusion to essential central organs during episodes of transient reduction in oxygenation. If labor is allowed to continue without an appropriate intervention, progressively more frequent, and stronger uterine contractions may result in a rapid deterioration of the fetal oxygenation leading to hypoxia and acidosis. In this Commentary, we introduce the term relative uteroplacental insufficiency of labor and highlight the pathophysiology, as well as the common features observed in the fetal heart rate tracing and clinical implications.
RESUMO
INTRODUCTION: It is a shortcoming of traditional cardiotocography (CTG) classification table formats that CTG traces are frequently classified differently by different users, resulting in poor interobserver agreements. A fast-and-frugal tree (FFTree) flow chart may help provide better concordance because it is straightforward and has clearly structured binary questions with understandable "yes" or "no" responses. The initial triage to determine whether a fetus is suitable for labor when utilizing fetal ECG ST analysis (STAN) is very important, since a fetus with restricted capacity to respond to hypoxic stress may not generate STAN events and therefore may become falsely negative. This study aimed to compare physiology-focused FFTree CTG interpretation with FIGO classification for assessing the suitability for STAN monitoring. MATERIAL AND METHODS: A retrospective study of 36 CTG traces with a high proportion of adverse outcomes (17/36) selected from a European multicenter study database. Eight experienced European obstetricians evaluated the initial 40 minutes of the CTG recordings and judged whether STAN was a suitable fetal surveillance method and whether intervention was indicated. The experts rated the CTGs using the FFTree and FIGO classifications at least 6 weeks apart. Interobserver agreements were calculated using proportions of agreement and Fleiss' kappa (κ). RESULTS: The proportions of agreement for "not suitable for STAN" were for FIGO 47% (95% confidence interval [CI] 42%-52%) and for FFTree 60% (95% CI 56-64), ie a significant difference; the corresponding figures for "yes, suitable" were 74% (95% CI 71-77) and 70% (95% CI 67-74). For "intervention needed" the figures were 52% (95% CI 47-56) vs 58% (95% CI 54-62) and for "expectant management" 74% (95% CI 71-77) vs 72% (95% CI 69-75). Fleiss' κ agreement on "suitability for STAN" was 0.50 (95% CI 0.44-0.56) for the FIGO classification and 0.57 (95% CI 0.51-0.63) for the FFTree classification; the corresponding figures for "intervention or expectancy" were 0.53 (95% CI 0.47-0.59) and 0.57 (95% CI 0.51-0.63). CONCLUSIONS: The proportion of agreement among expert obstetricians using the FFTree physiological approach was significantly higher compared with the traditional FIGO classification system in rejecting cases not suitable for STAN monitoring. That might be of importance to avoid false negative STAN recordings. Other agreement figures were similar. It remains to be shown whether the FFTree simplicity will benefit less experienced users and how it will work in real-world clinical scenarios.
Assuntos
Eletrocardiografia , Monitorização Fetal , Triagem , Feminino , Humanos , Gravidez , Cardiotocografia/métodos , Eletrocardiografia/métodos , Monitorização Fetal/métodos , Feto , Frequência Cardíaca Fetal/fisiologia , Variações Dependentes do Observador , Estudos RetrospectivosRESUMO
BACKGROUND: The consumption of high-caloric diets strongly contributes to the development of non-communicable diseases (NCDs), including cardiovascular disease, the leading cause of mortality worldwide. Exercise (along with diet intervention) is one of the primary non-pharmacological approaches to promote a healthier lifestyle and counteract the rampant prevalence of NCDs. The present study evaluated the effects of exercise cessation after a short period training on the cardiac metabolic and mitochondrial function of female rats. METHODS: Seven-week-old female Sprague-Dawley rats were fed a control or a high-fat, high-sugar (HFHS) diet and, after 7 weeks, the animals were kept on a sedentary lifestyle or submitted to endurance exercise for 3 weeks (6 days per week, 20-60 min/day). The cardiac samples were analysed 8 weeks after exercise cessation. RESULTS: The consumption of the HFHS diet triggered impaired glucose tolerance, whereas the HFHS diet and physical exercise resulted in different responses in plasma adiponectin and leptin levels. Cardiac mitochondrial respiration efficiency was decreased by the HFHS diet consumption, which led to reduced ATP and increased NAD(P)H mitochondrial levels, which remained prevented by exercise 8 weeks after cessation. Exercise training-induced cardiac adaptations in redox balance, namely increased relative expression of Nrf2 and downstream antioxidant enzymes persist after an eight-week exercise cessation period. CONCLUSIONS: Endurance exercise modulated cardiac redox balance and mitochondrial efficiency in female rats fed a HFHS diet. These findings suggest that exercise may elicit cardiac adaptations crucial for its role as a non-pharmacological intervention for individuals at risk of developing NCDs.
RESUMO
Maternal obesity (MO) is rising worldwide, affecting half of all gestations, constituting a possible risk-factor for some pregnancy-associated liver diseases (PALD) and hepatic diseases. PALD occur in approximately 3% of pregnancies and are characterized by maternal hepatic oxidative stress (OS) and mitochondrial dysfunction. Maternal hepatic disease increases maternal and fetal morbidity and mortality. Understanding the role of MO on liver function and pathophysiology could be crucial for better understanding the altered pathways leading to PALD and liver disease, possibly paving the way to prevention and adequate management of disease. We investigated specific hepatic metabolic alterations in mitochondria and oxidative stress during MO at late-gestation. Maternal hepatic tissue was collected at 90% gestation in Control and MO ewes (fed 150% of recommended nutrition starting 60 days before conception). Maternal hepatic redox state, mitochondrial respiratory chain (MRC), and OS markers were investigated. MO decreased MRC complex-II activity and its subunits SDHA and SDHB protein expression, increased complex-I and complex-IV activities despite reduced complex-IV subunit mtCO1 protein expression, and increased ATP synthase ATP5A subunit. Hepatic MO-metabolic remodeling was characterized by decreased adenine nucleotide translocator 1 and 2 (ANT-1/2) and voltage-dependent anion channel (VDAC) protein expression and protein kinase A (PKA) activity (P<0.01), and augmented NAD+/NADH ratio due to reduced NADH levels (P<0.01). MO showed an altered redox state with increased OS, increased lipid peroxidation (P<0.01), decreased GSH/GSSG ratio (P=0.005), increased superoxide dismutase (P=0.03) and decreased catalase (P=0.03) antioxidant enzymatic activities, lower catalase, glutathione peroxidase (GPX)-4 and glutathione reductase protein expression (P<0.05), and increased GPX-1 abundance (P=0.03). MO-related hepatic changes were more evident in the right lobe, corroborated by the integrative data analysis. Hepatic tissue from obese pregnant ewes showed alterations in the redox state, consistent with OS and MRC and metabolism remodeling. These are hallmarks of PALD and hepatic disease, supporting MO as a risk-factor and highlighting OS and mitochondrial dysfunction as mechanisms responsible for liver disease predisposition.
Assuntos
Hepatopatias , NAD , Humanos , Feminino , Gravidez , Animais , Ovinos , Catalase/metabolismo , NAD/metabolismo , Fígado/metabolismo , Estresse Oxidativo , Obesidade/metabolismo , Antioxidantes/metabolismo , Hepatopatias/metabolismo , Superóxido Dismutase/metabolismo , Glutationa/metabolismoRESUMO
The onset of regular, strong, and progressive uterine contractions may result in both mechanical (compression of the fetal head and/or umbilical cord) and hypoxic (repetitive and sustained compression of the umbilical cord or reduction in uteroplacental oxygenation) stresses to a human fetus. Most fetuses are able to mount effective compensatory responses to avoid hypoxic-ischemic encephalopathy and perinatal death secondary to the onset of anaerobic metabolism within the myocardium, culminating in myocardial lactic acidosis. In addition, the presence of fetal hemoglobin, which has a higher affinity for oxygen even at low partial pressures of oxygen than the adult hemoglobin, especially increased amounts of fetal hemoglobin (ie, 180-220 g/L in fetuses vs 110-140 g/L in adults), helps the fetus to withstand hypoxic stresses during labor. Different national and international guidelines are currently being used for intrapartum fetal heart rate interpretation. These traditional classification systems for fetal heart rate interpretation during labor are based on grouping certain features of fetal heart rate (ie, baseline fetal heart rate, baseline variability, accelerations, and decelerations) into different categories (eg, category I, II, and III tracings, "normal, suspicious, and pathologic" or "normal, intermediary, and abnormal"). These guidelines differ from each other because of the features included within different categories and because of their arbitrary time limits stipulated for each feature to warrant an obstetrical intervention. This approach fails to individualize care because the "ranges of normality" for stipulated parameters apply to the population of human fetuses and not to the individual fetus in question. Moreover, different fetuses have different reserves and compensatory responses and different intrauterine environments (presence of meconium staining of amniotic fluid, intrauterine inflammation, and the nature of uterine activity). Pathophysiological interpretation of fetal heart rate tracing is based on the application of the knowledge of fetal responses to intrapartum mechanical and/or hypoxic stress in clinical practice. Both experimental animal studies and observational human studies suggest that, just like adults undertaking a treadmill exercise, human fetuses show predictable compensatory responses to a progressively evolving intrapartum hypoxic stress. These responses include the onset of decelerations to reduce myocardial workload and preserve aerobic metabolism, loss of accelerations to abolish nonessential somatic body movements, and catecholamine-mediated increases in the baseline fetal heart rate and effective redistribution and centralization to protect the fetal central organs (ie, the heart, brain, and adrenal glands), which are essential for intrauterine survival. Moreover, it is essential to incorporate the clinical context (progress of labor, fetal size and reserves, presence of meconium staining of amniotic fluid and intrauterine inflammation, and fetal anemia) and understand the features suggestive of fetal compromise in nonhypoxic pathways (eg, chorioamnionitis and fetomaternal hemorrhage). It is important to appreciate that the timely recognition of the speed of onset of intrapartum hypoxia (ie, acute, subacute, and gradually evolving) and preexisting uteroplacental insufficiency (ie, chronic hypoxia) on fetal heart rate tracing is crucial to improve perinatal outcomes.
Assuntos
Cardiotocografia , Doenças do Recém-Nascido , Adulto , Animais , Feminino , Humanos , Gravidez , Hemoglobina Fetal , Frequência Cardíaca Fetal/fisiologia , Hipóxia , Inflamação , OxigênioRESUMO
BACKGROUND: Although human-animal interactions (HAI) have been associated with health benefits, they have not been extensively studied among cancer patients nor which factors may influence HAI during cancer survivorship. Therefore, this study aims to describe pet ownership in a breast cancer cohort within 5 years post-diagnosis and to identify associated factors. METHODS: Four hundred sixty-six patients from the NEON-BC cohort were evaluated. Four groups of pet ownership over the 5 years were defined: 'never had', 'stopped having', 'started having' and 'always had'. Multinomial logistic regression was used to quantify the association between the patient characteristics and the groups defined (reference: 'never had'). RESULTS: 51.7% of patients had pets at diagnosis, which increased to 58.4% at 5 years; dogs and cats were the most common. Women presenting depressive symptoms and poor quality of life were more likely to stop having pets. Older and unpartnered women were less likely to start having pets. Those retired, living outside Porto, having diabetes or having owned animals during adulthood were more likely to start having pets. Women with higher education and unpartnered were less likely to always have pets. Those living in larger households, with other adults or having animals throughout life, were more likely to always have pets. Obese women had lower odds of stopping having dogs/cats. Women submitted to neoadjuvant chemotherapy and longer chemotherapy treatments were more likely to stop having dogs/cats. CONCLUSIONS: Pet ownership changed over the 5 years and is influenced by sociodemographic, clinical and treatment characteristics, patient-reported outcomes and past pet ownership, reflecting the importance of HAI during cancer survivorship.
Assuntos
Neoplasias da Mama , Doenças do Gato , Doenças do Cão , Humanos , Adulto , Animais , Cães , Gatos , Feminino , Animais de Estimação , Neônio , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Propriedade , Qualidade de VidaRESUMO
PURPOSE: To find the cut-off values in the Myelopathy Disability Index (MDI) that will allow us to classify the severity of Degenerative Cervical Myelopathy (DCM) into mild, moderate and severe. METHODS: Cross-sectional study with prospective data collection, with a total of 64 patients diagnosed with Degenerative Cervical Myelopathy (DCM). Anthropometric, diagnostic, neurological, functional and quality of life variables were collected. A Receiver Operating Curve (ROC) was performed. The cut-off points were validated by comparing the functional status of patients in the 3 groups and their Nurick scores. RESULTS: Sixty-four patients (23 women) with a mean age of 61.97 (SD 11.57) participated in this study. The majority of patients were Nurick I (28.13%) and Nurick II (32.81%). The medium MDI was 7.36 (SD 6.66) and the mJOA was 14.08 (SD 2.57). The mild-moderate cut-off value was between 4 and 5, with an Area Under the Curve (AUC) of 0.805, sensitivity of 0.853 and specificity of 0.6. For moderate-severe, the cut-off value obtained was between 7 and 8, with an AUC of 0.862, sensitivity of 0.857 and specificity of 0.684. Patients with greater severity had significantly lower functionality, with a P-value of 0.004 in the 30 Metre Walking Test and 0.005 in the Nine-Hole Peg Test. Established severity groups were also significantly related to the different categories of the Nurick score (P-value = 0.000). CONCLUSION: MDI values between 0 and 4 correspond to mild DCM, between 5 and 7 would be moderate DCM and from 8 to 30 indicate severe DCM.
Assuntos
Doenças da Medula Óssea , Doenças da Medula Espinal , Humanos , Feminino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Transversais , Estudos Prospectivos , Vértebras Cervicais , Doenças da Medula Espinal/diagnóstico , Resultado do TratamentoRESUMO
PURPOSE: Pan Lumbar Arthodesis (PLA) are often required for Adult Spinal Deformity (ASD) correction, reducing significantly the compensatory capacity in case of postoperative sagittal malalignment. Few papers have investigated outcomes and complications in this vulnerable subset of patients. The objective of this study was to assess revision surgery rate for PLA in ASD, its risk factors and impact on clinical outcomes. METHODS: Retrospective multicenter review of prospective ASD data from 7 hospitals covering Europe and Asia. ASD patients included in two prospective databases having a posterior instrumentation spanning the whole lumbar region with more than 2-years of follow-up were reviewed. Demographic, surgical, radiographic parameters and Health-Related Quality of Life (HRQoL) scores were analyzed. Univariate and multivariate regression models analyzed risk factors for revision surgery as well as surgical outcomes. Patients with Early versus Late and PJK versus Non-PJK mechanical complications were also compared. RESULTS: Out of 1359 ASD patients included in the database 589 (43%) had a PLA and 357 reached 2-years mark. They were analyzed and compared to non-PLA patients. Average age was 67 and 82% were females. 100 Patients (28.1%) needed 114 revision surgeries (75.4% for mechanical failures). Revised patients were more likely to have a nerve system disorder, higher BMI and worst immediate postoperative alignment (as measured by GAP Parameters). These risk factors were also associated with earlier mechanical complications and PJK. Deformity and HRQoL parameters were comparable at baseline. Non-revised patients had significantly better clinical outcomes at 2-years (SRS 22 scores, ODI, Back pain). Multivariate analysis could identify nerve system disorder (OR 4.8; CI 1.8-12.6; p = 0.001), postoperative sagittal alignment (GAP Score) and high BMI (OR 1.07; CI 1.01-1.13; p = 0.004) as independent risk factors for revisions. CONCLUSIONS: Revision surgery due to mechanical failures is relatively common after PLA leading to worse clinical outcomes. Prevention strategies should focus on individualized restoration of sagittal alignment and better weight control to decrease stress on these rigid constructs in non-compliant spines. Nerve system disorders independently increase revision risk in PLA. LEVEL OF EVIDENCE II: Prognosis.
Assuntos
Qualidade de Vida , Fusão Vertebral , Coluna Vertebral , Adulto , Idoso , Feminino , Humanos , Masculino , Dor nas Costas/etiologia , Seguimentos , Reoperação , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Resultado do Tratamento , Coluna Vertebral/anormalidadesRESUMO
The mechanisms of toxicity of engineered nanomaterials (ENMs) to the early life stages of freshwater fish, and the relative hazard compared to dissolved metals, is only partially understood. In the present study, zebrafish embryos were exposed to lethal concentrations of copper sulphate (CuSO4) or copper oxide (CuO) ENMs (primary size â¼15 nm), and then the sub-lethal effects investigated at the LC10 concentrations over 96 h. The 96 h-LC50 (mean ± 95% CI) for CuSO4 was 303 ± 14 µg Cu L-1 compared to 53 ± 9.9 mg L-1 of the whole material for CuO ENMs; with the ENMs being orders of magnitude less toxic than the metal salt. The EC50 for hatching success was 76 ± 11 µg Cu L-1 and 0.34 ± 0.78 mg L-1 for CuSO4 and CuO ENMs respectively. Failure to hatch was associated with bubbles and foam-looking perivitelline fluid (CuSO4), or particulate material smothering the chorion (CuO ENMs). In the sub-lethal exposures, about 42% of the total Cu as CuSO4 was internalised, as measured by Cu accumulation in the de-chorionated embryos, but for the ENMs exposures, nearly all (94%) of the total Cu was associated with chorion; indicating the chorion as an effective barrier to protect the embryo from the ENMs in the short term. Both forms of Cu exposure caused sodium (Na+) and calcium (Ca2+), but not magnesium (Mg2+), depletion from the embryos; and CuSO4 caused some inhibition of the sodium pump (Na+/K+-ATPase) activity. Both forms of Cu exposure caused some loss of total glutathione (tGSH) in the embryos, but without induction of superoxide dismutase (SOD) activity. In conclusion, CuSO4 was much more toxic than CuO ENMs to early life stage zebrafish, but there are subtle differences in the exposure and toxic mechanisms for each substance.
Assuntos
Nanoestruturas , Poluentes Químicos da Água , Animais , Cobre/toxicidade , Cobre/análise , Sulfato de Cobre/toxicidade , Peixe-Zebra , Nanoestruturas/toxicidade , Óxidos , Poluentes Químicos da Água/toxicidadeRESUMO
Intra-uterine growth restriction (IUGR) is a common cause of fetal/neonatal morbidity and mortality and is associated with increased offspring predisposition for cardiovascular disease (CVD) development. Mitochondria are essential organelles in maintaining cardiac function, and thus, fetal cardiac mitochondria could be responsive to the IUGR environment. In this study, we investigated whether in utero fetal cardiac mitochondrial programming can be detectable in an early stage of IUGR pregnancy. Using a well-established nonhuman IUGR primate model, we induced IUGR by reducing by 30% the maternal diet (MNR), both in males (MNR-M) and in female (MNR-F) fetuses. Fetal cardiac left ventricle (LV) tissue and blood were collected at 90 days of gestation (0.5 gestation, 0.5 G). Blood biochemical parameters were determined and heart LV mitochondrial biology assessed. MNR fetus biochemical blood parameters confirm an early fetal response to MNR. In addition, we show that in utero cardiac mitochondrial MNR adaptations are already detectable at this early stage, in a sex-divergent way. MNR induced alterations in the cardiac gene expression of oxidative phosphorylation (OXPHOS) subunits (mostly for complex-I, III, and ATP synthase), along with increased protein content for complex-I, -III, and -IV subunits only for MNR-M in comparison with male controls, highlight the fetal cardiac sex-divergent response to MNR. At this fetal stage, no major alterations were detected in mitochondrial DNA copy number nor markers for oxidative stress. This study shows that in 90-day nonhuman primate fetuses, a 30% decrease in maternal nutrition generated early in utero adaptations in fetal blood biochemical parameters and sex-specific alterations in cardiac left ventricle gene and protein expression profiles, affecting predominantly OXPHOS subunits. Since the OXPHOS system is determinant for energy production in mitochondria, our findings suggest that these early IUGR-induced mitochondrial adaptations play a role in offspring's mitochondrial dysfunction and can increase predisposition to CVD in a sex-specific way.
Assuntos
Doenças Cardiovasculares , Desenvolvimento Fetal , Gravidez , Humanos , Animais , Masculino , Feminino , Feto/metabolismo , Retardo do Crescimento Fetal/metabolismo , Primatas , Nutrientes , Doenças Cardiovasculares/metabolismoRESUMO
The distal arteriovenous fistula (AVF) has less complications and better patency than the proximal fistula, when it works properly. The complications of outflow of the fistula are complex, and it is necessary to analyze all solutions to solve the problem. We introduce a novel approach to solve outflow problems of a radio-cephalic AVF by straightening of the forearm cephalic vein with drainage into the median basilic vein.
Assuntos
Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Humanos , Antebraço/irrigação sanguínea , Antebraço/cirurgia , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Grau de Desobstrução Vascular , Diálise Renal , Veias/diagnóstico por imagem , Veias/cirurgia , Drenagem , Resultado do TratamentoRESUMO
PURPOSE: The cognitive performance of patients with breast cancer (BCa) may be affected by cancer and its treatments. The Montreal Cognitive Assessment (MoCA) is a widely used cognitive impairment screening tool, but practice effects must be considered for longitudinal assessments. Since learning effects could be overcome through the alternate use of two versions of the MoCA, we aimed to explore their interchangeability by comparing their overall, and domain- and task-specific, scores among patients with BCa. METHODS: BCa patients from the NEON-BC cohort were evaluated with the MoCA, version 7.1, after diagnosis and after 1 year. At the 3-year follow-up (n = 422), the 7.1 and 7.3 versions were applied at the beginning and at the end (approximately 1 h later) of this evaluation, respectively. Agreements between versions, regarding total, sub-domain, and task scores, were assessed using Bland-Altman plots and intraclass correlation coefficients (ICC). RESULTS: The mean total scores were not statistically different between versions and the ICC was 0.890. The Bland-Altman limits of agreement were - 3.70 to 3.88. For women with midrange scores, total scores were significantly higher in version 7.1. There were significant differences in the percentage of correct answers in 7 out of 12 tasks, being the highest for the copy of a geometric figure (more than twofold higher with version 7.3). In version 7.1, the language and memory domains presented higher scores and lower visuospatial ability. CONCLUSION: Despite similar overall scores being obtained with the two versions of the MoCA, there were item-specific differences that may compromise their interchangeable use.
Assuntos
Neoplasias da Mama , Disfunção Cognitiva , Neoplasias da Mama/diagnóstico , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Feminino , Humanos , Testes de Estado Mental e Demência , Testes Neuropsicológicos , Psicometria , Reprodutibilidade dos TestesRESUMO
PURPOSE: Anterior approaches are gaining popularity for adult spinal deformity (ASD) surgeries especially with the introduction of hyperlordotic cages and improvement in MIS techniques. Combined Approaches provide powerful segmental sagittal correction potential and increase the surface area available for fusion in ASD surgery, both of which would improve overall. This is the first study directly comparing surgical outcomes between combined anterior-posterior approaches and all-posterior approach in a matched ASD population. METHODS: This is a retrospective matched control cohort analysis with substitution using a multicenter prospectively collected ASD data of patients with > 2 year FU. Matching criteria include: age, American Society of Anesthesiologists Score, Lumbar Cobb angle, sagittal deformity (Global tilt) and ODI. RESULTS: In total, 1024 ASD patients were available for analysis. 29 Combined Approaches patients met inclusion criteria, and only 22 could be matched (1:2 ratio). Preoperative non-matched demographical, clinical, surgical and radiological parameters were comparable between both groups. Combined approaches had longer surgeries (548 mns vs 283) with more blood loss (2850 ml vs 1471) and needed longer ICU stays (74 h vs 27). Despite added morbidity, they had comparable complication rates but with significantly less readmissions (9.1% vs 38.1%) and reoperations (18.2% vs 43.2%) at 2 years. Combined Approaches achieved more individualised and harmonious deformity correction initially. At the 2 years control, Combined Approaches patients reported better outcomes as measured by COMI and SRS scores. This trend was maintained at 3 years. CONCLUSION: Despite an increased initial surgical invasiveness, combined approaches seem to achieve more harmonious correction with superior sagittal deformity control; they need fewer revisions and have improved long-term functional outcomes when compared to all-posterior approaches for ASD deformity correction.
Assuntos
Lordose , Escoliose , Fusão Vertebral , Adulto , Humanos , Lordose/cirurgia , Reoperação , Estudos Retrospectivos , Escoliose/cirurgia , Fusão Vertebral/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Surgeons often rely on their intuition, experience and published data for surgical decision making and informed consent. Literature provides average values that do not allow for individualized assessments. Accurate validated machine learning (ML) risk calculators for adult spinal deformity (ASD) patients, based on 10 year multicentric prospective data, are currently available. The objective of this study is to assess surgeon ASD risk perception and compare it to validated risk calculator estimates. METHODS: Nine ASD complete (demographics, HRQL, radiology, surgical plan) preoperative cases were distributed online to 100 surgeons from 22 countries. Surgeons were asked to determine the risk of major complications and reoperations at 72 h, 90 d and 2 years postop, using a 0-100% risk scale. The same preoperative parameters circulated to surgeons were used to obtain ML risk calculator estimates. Concordance between surgeons' responses was analyzed using intraclass correlation coefficients (ICC) (poor < 0.5/excellent > 0.85). Distance between surgeons' and risk calculator predictions was assessed using the mean index of agreement (MIA) (poor < 0.5/excellent > 0.85). RESULTS: Thirty-nine surgeons (74.4% with > 10 years' experience), from 12 countries answered the survey. Surgeons' risk perception concordance was very low and heterogeneous. ICC ranged from 0.104 (reintervention risk at 72 h) to 0.316 (reintervention risk at 2 years). Distance between calculator and surgeon prediction was very large. MIA ranged from 0.122 to 0.416. Surgeons tended to overestimate the risk of major complications and reintervention in the first 72 h and underestimated the same risks at 2 years postop. CONCLUSIONS: This study shows that expert surgeon ASD risk perception is heterogeneous and highly discordant. Available validated ML ASD risk calculators can enable surgeons to provide more accurate and objective prognosis to adjust patient expectations, in real time, at the point of care.
Assuntos
Cirurgiões , Adulto , Aconselhamento , Tomada de Decisões , Humanos , Percepção , Estudos Prospectivos , Medição de RiscoRESUMO
Plants must adapt to cope with adverse environmental conditions that affect their growth and development. To overcome these constraints, they can alter their developmental patterns by modulating cellular processes and activating stress-responsive signals. Alongside the activation of the antioxidant (AOX) system, a high number of genes are expressed, and proteins must be distributed to the correct locations within the cell. The endomembrane system and associated vesicles thus play an important role. Several pathways have been associated with adverse environmental conditions, which is the case for the exocyst-positive organelle-EXPO. The present work, using Arabidopsis mutants with T-DNA insertions in the gene EXO70, essential for EXPO vesicles formation, was designed to characterise the anatomical (morphology and root length), biochemical (quantification of stress markers and antioxidant system components), and molecular responses (gene expression) to abiotic stresses (saline, drought, oxidative, and metal-induced toxicity). The results obtained showed that mutant plants behave differently from the wild type (WT) plants. Therefore, in the exo70 mutant, morphological changes were more noticeable in plants under stress, and the non-enzymatic component of the antioxidant system was activated, with no alterations to the enzymatic component. Furthermore, other defence strategies, such as autophagy, did not show important changes. These results confirmed the EXPO as an important structure for tolerance/adaptation to stress.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Antioxidantes/metabolismo , Citoplasma/metabolismo , Estresse Fisiológico/genética , Homeostase/genética , Plantas Geneticamente Modificadas/metabolismo , Secas , Regulação da Expressão Gênica de PlantasRESUMO
Xylanases can boost pulp bleachability in Elemental Chlorine Free (ECF) processes, but their industrial implementation for producing bleached kraft pulps is not straightforward. It requires enzymes to be active and stable at the extreme conditions of alkalinity and high temperature typical of this industrial process; most commercial enzymes are unable to withstand these conditions. In this work, a novel highly thermo and alkaline-tolerant xylanase from Pseudothermotoga thermarum was overproduced in E. coli and tested as a bleaching booster of hardwood kraft pulps to save chlorine dioxide (ClO2) during ECF bleaching. The extremozyme-stage (EXZ) was carried out at 90 °C and pH 10.5 and optimised at lab scale on an industrial oxygen-delignified eucalyptus pulp, enabling us to save 15% ClO2 to reach the mill brightness, and with no detrimental effect on paper properties. Then, the EXZ-assisted bleaching sequence was validated at pilot scale under industrial conditions, achieving 25% ClO2 savings and reducing the generation of organochlorinated compounds (AOX) by 18%, while maintaining pulp quality and papermaking properties. Technology reproducibility was confirmed with another industrial kraft pulp from a mix of hardwoods. The new enzymatic technology constitutes a realistic step towards environmentally friendly production of kraft pulps through industrial integration of biotechnology.
Assuntos
Eucalyptus , Extremófilos , Escherichia coli , Reprodutibilidade dos Testes , Eucalyptus/química , Cloro , PapelRESUMO
BACKGROUND AND OBJECTIVES: Available information about infection after spine instrumentation (IASI) and its management are scarce. We aimed to analyse DAIR (debridement, antibiotics and implant retention) prognosis and evaluate effectiveness of short antibiotic courses on early forms. METHODS: Multicentre retrospective study of patients with IASI managed surgically (January 2010-December 2016). Risk factors for failure were analysed by multivariate Cox regression and differences between short and long antibiotic treatment were evaluated with a propensity score-matched analysis. RESULTS: Of the 411 IASI cases, 300 (73%) presented in the first month after surgery, 48 in the second month, 22 in the third and 41 thereafter. Infections within the first 2 months (early cases) occurred mainly to older patients, with local inflammatory signs and predominance of Enterobacteriaceae, unlike those in the later periods. When managed with DAIR, prognosis of early cases was better than later ones (failure rate 10.4% versus 26.1%, respectively; P = 0.02). Risk factors for DAIR failure in early cases were female sex, Charlson Score, large fusions (>6 levels) and polymicrobial infections (adjusted HRs of 2.4, 1.3, 2.6 and 2.26, respectively). Propensity score matching proved shorter courses of antibiotics (4-6 weeks) as effective as longer courses (failure rates 11.4% and 10.5%, respectively; P = 0.870). CONCLUSIONS: IASIs within the first 2 months could be managed effectively with DAIR and shorter antibiotic courses. Clinicians should be cautious when faced with patients with comorbidities, large fusions and/or polymicrobial infections.
Assuntos
Infecções Relacionadas à Prótese , Antibacterianos/uso terapêutico , Desbridamento , Feminino , Humanos , Infecções Relacionadas à Prótese/tratamento farmacológico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Embryonic and foetal development are critical periods of development in which several environmental cues determine health and disease in adulthood. Maternal conditions and an unfavourable intrauterine environment impact foetal development and may programme the offspring for increased predisposition to metabolic diseases and other chronic pathologic conditions throughout adult life. Previously, non-communicable chronic diseases were only associated with genetics and lifestyle. Now the origins of non-communicable chronic diseases are associated with early-life adaptations that produce long-term dysfunction. Early-life environment sets the long-term health and disease risk and can span through multiple generations. Recent research in developmental programming aims at identifying the molecular mechanisms responsible for developmental programming outcomes that impact cellular physiology and trigger adulthood disease. The identification of new therapeutic targets can improve offspring's health management and prevent or overcome adverse consequences of foetal programming. This review summarizes recent biomedical discoveries in the Developmental Origins of Health and Disease (DOHaD) hypothesis and highlight possible developmental programming mechanisms, including prenatal structural defects, metabolic (mitochondrial dysfunction, oxidative stress, protein modification), epigenetic and glucocorticoid signalling-related mechanisms suggesting molecular clues for the causes and consequences of programming of increased susceptibility of offspring to metabolic disease after birth. Identifying mechanisms involved in DOHaD can contribute to early interventions in pregnancy or early childhood, to re-set the metabolic homeostasis and break the chain of subsequent events that could lead to the development of disease.