Replication stress impairs chromosome segregation and preimplantation development in human embryos.

Human cleavage-stage embryos frequently acquire chromosomal aneuploidies during mitosis due to unknown mechanisms. Here, we show that S phase at the 1-cell stage shows replication fork stalling, low fork speed, and DNA synthesis extending into G2 phase. DNA damage foci consistent with collapsed replication forks, DSBs, and incomplete replication form in G2 in an ATR- and MRE11-dependent manner, followed by spontaneous chromosome breakage and segmental aneuploidies. Entry into mitosis with incomplete replication results in chromosome breakage, whole and segmental chromosome errors, micronucleation, chromosome fragmentation, and poor embryo quality. Sites of spontaneous chromosome breakage are concordant with sites of DNA synthesis in G2 phase, locating to gene-poor regions with long neural genes, which are transcriptionally silent at this stage of development. Thus, DNA replication stress in mammalian preimplantation embryos predisposes gene-poor regions to fragility, and in particular in the human embryo, to the formation of aneuploidies, impairing developmental potential.

Similar regional-scale survival of tropical and southern temperate birds from the New World.

The general assumption that the survival patterns of tropical and southern temperate birds are similar lacks empirical data from higher latitudes. Regional comparisons of New World species are rare, and this assumption has been based on data from African studies. Here, we estimate the survival rates of 88 tropical and southern temperate bird populations (69 species) from eight localities in South America to evaluate the hypothesis that the survival of these populations is homogeneous at the regional scale. We estimated survival based on the Cormack-Jolly-Seber model and compared values from different environments. The survival estimates ranged from 0.30 to 0.80 (0.56 ± 0.12). Apparent survival did not differ significantly between low-latitude tropical environments (03°S) and the other sites from high-latitudes (between 22° and 34°S). Despite a predicted positive trend, body size was not significantly related to survival among passerines. On the other hand, phylogenetic relationships explained more than a third of the variation in bird survival. Based on the largest available database on South American bird species, our findings support the hypothesis that bird survival is homogeneous, at the regional scale, along the southern hemisphere. In particular, we reinforce the hypothesis that climatic variation has a limited influence on bird survival in the southern hemisphere.

Efficacy and safety of tirofiban bridge as an alternative to suspension of dual antiplatelet therapy in patients undergoing surgery: a systematic review.

Use of a tirofiban bridge is an alternative to simply withdrawing dual antiplatelet therapy prior to operating on patients at high risk of stent thrombosis and bleeding. We aimed to evaluate the efficacy and safety of this protocol in patients undergoing surgery within 12 months of a percutaneous coronary intervention involving stenting. We performed a systematic review based on searches of the PubMed, Web of Science, Cochrane, Embase, Lilacs, and Scielo databases and of the references of relevant articles on the topic. Five of the 107 studies identified were included after application of eligibility criteria and analysis of methodological quality, totaling 422 patients, 227 in control groups. Notwithstanding the limitations reported, four of the five studies included indicate that the tirofiban bridge technique is effective for reducing adverse cardiac events and is safe in terms of not interfering with the risk of hemorrhagic events or bleeding. However, randomized clinical trials are needed to provide robust evidence.

Prepubertal Gynecomastia Due to Indirect Exposure to Nonformulary Bioidentical Hormonal Replacement Therapy: A Case Report.

BACKGROUND: Gynecomastia is a disorder of the endocrine system characterized by an abnormal presence of a palpable unilateral or bilateral enlargement and proliferation of glandular ductal benign breast tissue in male individuals. This case discusses the medical implications of an unregulated, indirect exposure to nonformulary, bioidentical hormone replacement therapy in male children. CASE: An 8-year-old boy presented with prepubertal gynecomastia secondary to estrogen exposure from maternal use of bioidentical hormonal replacement therapy (the Wiley protocol). We review the literature on prepubertal gynecomastia secondary to exogenous estrogen exposure, evaluation, clinical surveillance of the pubertal development, and relevant short- and long-term implications. CONCLUSION: Indirect exposure to nonformulary hormonal replacement in our case report was an etiologic factor in the development of prepubertal gynecomastia. This novel estrogen exposure source has important implications in the differential diagnosis of prepubertal gynecomastia and potential adverse effects secondary to precocious hormonal exposure.

Early REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION): Study protocol of a phase III trial.

RATIONALE: Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data are lacking to address this question. AIMS: The REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION) investigates intravenous alteplase within 4.5 h of monocular vision loss due to acute CRAO. METHODS: This study is the randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial. STUDY OUTCOMES: Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best-corrected visual acuity of the Logarithm of the Minimum Angle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy outcomes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomography/angiography, ultrasound and magnetic resonance imaging (MRI) biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha = 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm. DISCUSSION: By enrolling patients within 4.5 h of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may translate to CRAO with its similar pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.

Renal volumes measured by 3-dimensional sonography in healthy fetuses from 20 to 40 weeks.

OBJECTIVES: The purpose of this study was to establish reference values for fetal kidney volumes as a function of gestational age, estimated by 3-dimensional sonography using the Virtual Organ Computer-Aided Analysis (VOCAL) technique (GE Healthcare, Kretztechnik, Zipf, Austria). METHODS: Volumes of right and left kidneys were assessed in 213 healthy fetuses by 3-dimensional sonography using the VOCAL technique. Inclusion criteria were healthy women with singleton pregnancies, unremarkable comprehensive fetal sonographic findings, well-known gestational age established by first-trimester sonography, and gestational ages between 20 and 40 weeks. Exclusion criteria were patients lost to follow-up and birth weight abnormalities. Each patient was scanned once during pregnancy. Regression analysis was used to calculate unified formulas. RESULTS: The mathematical models calculated in the study were as follows: expected right kidney volume = exp[-1.01 + (0.12 × gestational age)]; and expected left kidney volume = exp[-0.90 + (0.12 × gestational age)]. No significant intraobserver or inter-observer variability was observed for the determined volumes. CONCLUSIONS: Reference values for right and left fetal kidney volumes throughout gestation using the rotational technique (VOCAL) are described. The use of this technique might aid in further definition of gestational age kidney volume standards to help in defining variations from the norm.

Robot-assisted extravascular stent for nutcracker syndrome: A case report.

Nutcracker syndrome (NCS) is a rare condition caused by compression of the left renal vein (LRV) between the aorta and superior mesenteric artery. Surgical treatment is reserved for patients with severe symptoms and failure of conservative treatment. A 31-year-old woman diagnosed in adolescence with NCS has had recurrent pain since age 15. For 30 days, she has had severe left flank pain and microhematuria. The patient underwent extravascular stent placement around the LRV with the Da Vinci Xi. In 30 months of follow-up, the patient has no pain and the LRV remained without compressions or thrombosis.

Chikungunya, Zika, Mayaro, and Equine Encephalitis virus detection in adult Culicinae from South Central Mato Grosso, Brazil, during the rainy season of 2018.

INTRODUCTION: Several arboviruses causing human disease have been reported in Brazil. In nature, arboviruses maintain a lifecycle involving vertebrates and vectors, which may contribute for periodical reemergence of those of public health concern in tropical regions, as Mato Grosso State (MT). In this study, we searched for arboviruses in mosquito body pools sampled during the rainy season of 2018 in 21 bird watching points of Cuiabá and Varzea Grande, South Central MT. METHODS: In total, 2873 (57%) males and 2167 (43%) females belonging to six urban and sylvatic mosquito genera allocated to 398 pools were subjected to RNA extraction and RT-PCR for arboviruses. Positive pools were subjected to virus isolation in C6/36 cells. RESULTS: A total of 102/398 pools, 66/233 (29.6%) of females, and 36/165 (21.8%) of males, mostly sampled in May (31/102), were positive for arboviruses. Chikungunya virus (CHIKV) was distributed in 19 points, Zika virus (ZIKV) was found in 14 points, Mayaro virus (MAYV) in 10 points, and East Equine encephalitis virus (EEEV) in three points. Culex quinquefasciatus pools (39/89 of females and 24/99 of males) were positive for CHIKV, ZIKV, and MAYV; Aedes (Stg) aegypti pools (11/46 of females and 12/33 of males) for CHIKV, ZIKV, MAYV, and EEEV; Aedes albopictus female pools (8/29) for CHIKV, ZIKV, and EEEV; and Psorophora albigenu (2/12) and Psorophora ferox female pools (4/16) for CHIKV. CONCLUSIONS: Arbovirus molecular detection in mosquito populations varies considerable between geographical regions and epidemics, influenced by genetic characteristics and microbiome interference on virus replication. Although infected females are responsible for the transmission to vertebrates during bloodfeeding, male infection by CHIKV, ZIKV, and MAYV resultant from vertical route could lead to interepidemic maintenance of these arboviruses in their natural reservoirs.

Distinct Imprinting Signatures and Biased Differentiation of Human Androgenetic and Parthenogenetic Embryonic Stem Cells.

Genomic imprinting is an epigenetic mechanism that results in parent-of-origin monoallelic expression of specific genes, which precludes uniparental development and underlies various diseases. Here, we explored molecular and developmental aspects of imprinting in humans by generating exclusively paternal human androgenetic embryonic stem cells (aESCs) and comparing them with exclusively maternal parthenogenetic ESCs (pESCs) and bi-parental ESCs, establishing a pluripotent cell system of distinct parental backgrounds. Analyzing the transcriptomes and methylomes of human aESCs, pESCs, and bi-parental ESCs enabled the characterization of regulatory relations at known imprinted regions and uncovered imprinted gene candidates within and outside known imprinted regions. Investigating the consequences of uniparental differentiation, we showed the known paternal-genome preference for placental contribution, revealed a similar bias toward liver differentiation, and implicated the involvement of the imprinted gene IGF2 in this process. Our results demonstrate the utility of parent-specific human ESCs for dissecting the role of imprinting in human development and disease.

Infertility and ART after transplantation.

Organ transplantation (OT) has improved the long-term survival of patients facing specific organ failure and has refocused management to a chronic condition, with emphasis on enhancing life quality, including respecting a patient's autonomy to have children. Transplant patients are often faced with subfertility, frequently a consequence of gonadotoxic medical therapy. For some patients, successful OT management, reproductive conservation measures and the use of assisted reproductive technologies (ART) may help preserve fertility. There is a growing literature on the use of ART in these patients. The main objective of ART in OT recipients is attaining a healthy pregnancy, while minimizing potential complications that would jeopardize both the maternal health status and offspring. The purpose of this article is to address the distinctive medical, ethical and psychosocial concerns surrounding the fertility management of OT recipients.

Maternal serum hormonal factors in the pathogenesis of preeclampsia.

UNLABELLED: The etiology of preeclampsia (PE) remains unknown. There are many different etiopathogenetic theories that have been proposed. One theory is based on immunologic factors that may be regulated by hormones. The primary objective of the present study was to review the main hormones that may be involved in the PE pathophysiology. The current literature has suggested the involvement of many different hormonal systems in the pathogenesis of PE such as cortisol, renin-angiotensin-aldosterone system, arginine vasopressin, epinephrine and norepinephrine, natriuretic atrial peptide, brain natriuretic peptide, and melatonin. These findings suggest the complexity of the pathophysiology of PE, which involves many different hormonal systems. In conclusion, PE is a systemic disease with all of the aforementioned hormones being involved in the mechanism of systemic arterial hypertension. This consequently plays an important role in the circadian characteristics of the maternal blood pressure in PE. TARGET AUDIENCE: Obstetricians and gynecologists, family physicians. LEARNING OBJECTIVES: After completing this CME activity, physicians should be better able to understand the pathogenesis and pathophysiologicprocess involved in this disease, improve the treatment of the disease, educate medical students and residents with a better comprehension of the pathophysiologic process of the disease, stimulate new researches to establish the regulations of these hormones all together in the pathophysiologic process of preeclampsia, and develop new methods for screening and prevention preeclampsia based on maternal serum evaluations of hormonal levels.

Perno-muñon colado. Parte II: el desafio retaurativo integral, cuando existe enfermedad uclusal severa / Cast post-and-core procedures. Part II: integrated restoration in cases of severe occlusal pathology

La parte I de este artículo mostraba el procedimiento rutinario de elaboración del perno-muñón colado. En este artículo pretendemos ilustrar secuencia¡ e iconográficamente las fases de restauración de dientes severamente destruidos mediante pernos-muñones colados en situaciones complejas. Este es el caso de los dientes que han sufrido mutilación de la corona debido a parafunciones. Las fases se resumen: 1, diagnóstico etiológico de la patología oclusal y evaluación de los dientes remanentes y tejidos de soporte; 2, restauración oclusal transitoria; 3, tratamiento de los pilares existentes (endo, perio, Ortodoncia?) y/o instalación de fijaciones oseointegradas; 4, prótesis definitivas metal/metal-cerámica. Por último, 5, fase de mantenimiento: control oclusal e higiene (AU)