Shahkofod7045

Early change in community composition indicates that forests dominated by mesic species generally shifted toward more xeric communities, with replacing tree and shrub species exhibiting drier bioclimatic optima and distribution ranges. However, shifts toward more mesic communities also occurred and multiple pathways of forest replacement were observed for some species. Drought characteristics, species-specific environmental preferences, plant traits, and ecosystem legacies govern postdrought species turnover and subsequent ecological trajectories, with potential far-reaching implications for forest biodiversity and ecosystem services.Patients with COVID-19 are at high risk for thrombotic arterial and venous occlusions. Lung histopathology often reveals fibrin-based blockages in the small blood vessels of patients who succumb to the disease. Antiphospholipid syndrome is an acquired and potentially life-threatening thrombophilia in which patients develop pathogenic autoantibodies targeting phospholipids and phospholipid-binding proteins (aPL antibodies). Case series have recently detected aPL antibodies in patients with COVID-19. Here, we measured eight types of aPL antibodies in serum samples from 172 patients hospitalized with COVID-19. These aPL antibodies included anticardiolipin IgG, IgM, and IgA; anti-β2 glycoprotein I IgG, IgM, and IgA; and anti-phosphatidylserine/prothrombin (aPS/PT) IgG and IgM. We detected aPS/PT IgG in 24% of serum samples, anticardiolipin IgM in 23% of samples, and aPS/PT IgM in 18% of samples. Antiphospholipid autoantibodies were present in 52% of serum samples using the manufacturer's threshold and in 30% using a more stringent cutoff (≥40 ELISA-specific units). Higher titers of aPL antibodies were associated with neutrophil hyperactivity, including the release of neutrophil extracellular traps (NETs), higher platelet counts, more severe respiratory disease, and lower clinical estimated glomerular filtration rate. Similar to IgG from patients with antiphospholipid syndrome, IgG fractions isolated from patients with COVID-19 promoted NET release from neutrophils isolated from healthy individuals. Furthermore, injection of IgG purified from COVID-19 patient serum into mice accelerated venous thrombosis in two mouse models. These findings suggest that half of patients hospitalized with COVID-19 become at least transiently positive for aPL antibodies and that these autoantibodies are potentially pathogenic.Neonatal indirect hyperbilirubinemia (IHB) is caused by an imbalance in bilirubin production and elimination. Approximately 60% of term and 80% of preterm infants develop jaundice in the first week of age. This review seeks to provide the reader with a thorough understanding of the physiology of bilirubin, etiology of IHB, and management of severe IHB. Phototherapy and exchange transfusion remain the mainstays of treatment for severe IHB. Noninvasive screening tools, innovative treatments, and a better understanding of how prematurity and genetics contribute to severe IHB have improved our understanding of IHB and may help eliminate the hazards associated with severe IHB, including kernicterus spectrum disorder.Perinatal arterial ischemic stroke (PAIS) is a common cause of seizures, encephalopathy, altered mental status, and focal neurologic deficits in the neonatal period. It is the leading known cause of cerebral palsy. Other long-term risks include the development of epilepsy and impairment in cognition, language, and behavior. This article will review the known risk factors for PAIS, as well as the evaluation, management, and prognosis. Long-term neurodevelopmental surveillance is recommended, along with intensive therapies to reduce morbidity.Venovenous and venoarterial extracorporeal membrane oxygenation (ECMO) remains a crucial lifesaving therapy for critically ill neonates with severe cardiorespiratory failure. Both the roller pump as well as the centrifugal pump are safe and efficient systems, and some red blood cell breakdown and hemolysis occurs in all ECMO systems. The roller pump functions by gravity whereas the centrifugal pump promotes the flow of blood by a magnetically driven spinning rotor to generate negative pressure. Extracorporeal Life Support Organization data indicate a significant increase in intravascular hemolysis in neonatal and pediatric patients receiving ECMO when the centrifugal pump is used compared with its use in adults. Cytoskeletal Signaling inhibitor Risk factors for developing hemolysis during ECMO are small cannula size, high negative inlet pressure in the pump head, and thrombosis in the pump head and oxygenator. Excessive red blood cell breakdown and release of plasma free hemoglobin (pfHb) saturate physiologic neutralizing mechanisms such as haptoglobin and hemopexin. The increase in pro-oxidant and proinflammatory pfHb levels causes endothelial dysfunction in a dose-dependent manner. Hemolysis also increases the risk of in-hospital morbidities such as renal injury, direct hyperbilirubinemia, and thrombosis without an increase in mortality in patients receiving ECMO. Hemolysis is an unavoidable side effect of current ECMO technology and there are no approved treatments or treatment guidelines for the neonatal population. Therefore, increased vigilance, recognition of the severity of the hemolytic process, and prompt management are essential to prevent severe endothelial injury leading to proinflammatory and prothrombotic events.Neuroblastoma is the most common extracranial solid tumor diagnosed during childhood and gives rise to various heterogeneous tumors along the sympathoadrenal axis. Congenital neuroblastoma accounts for 5% of total neuroblastoma cases diagnosed annually, with the majority of cases diagnosed in the first month after birth. Interestingly, neonates demonstrate a unique disease trajectory compared with children older than 1 year of age. This article will provide information on the pathogenesis and variable clinical presentation of congenital neuroblastoma, along with the biological prognostic factors that predict long-term outcomes in affected neonates.Mothers of infants in the NICU suffer higher rates of psychological distress, anxiety, and depression compared with the general population. Often, their mental health concerns remain underidentified and undertreated, which can have deleterious effects on the offspring, both in short-term outcomes while in the NICU as well as long-term neurodevelopmental and behavioral outcomes. In this review, we present an overview of existing empirical evidence about how maternal mental health affects the health of infants, special considerations regarding the mental health needs of NICU mothers, and the findings about existing and developing interventions to address mental health concerns in this vulnerable population.Tumor-suppressor genes (TSG) are often deleted or transcriptionally suppressed in cancer. PGR codes for progesterone receptor (PR), a transcription factor whose function depends on its ligand. Although PR expression is often undetectable in cervical cancer, its relevance to the endocrine-related etiology of this prevalent gynecological disease remains unclear. In this study, we show that the deletion of one Pgr allele in cervical epithelium promoted spontaneous cervical cancer in human papilloma viral oncogene-expressing transgenic mice as efficiently as the ablation of both Pgr alleles. We also show that tumors arising in the transgenic mice with one or both Pgr alleles did not express PR or expressed at the reduced levels compared with the normal epithelium. PR status correlated with estrogen receptor α (ERα) status in the mouse model and the Cancer Genome Atlas (TCGA) dataset. TCGA data analyses revealed that PGR expression significantly decreased in cervical cancer and that the biallelic deletion of PGR was rare. Furthermore, low PGR expression was associated with poor prognosis in young patients with cervical cancer. These discoveries point to PGR as a haploinsufficient TSG in the uterine cervix. They also raise the possibility that the restoration of PGR expression may improve the survival rate. IMPLICATIONS The decreased expression of PR may increase the risk of cervical cancer in human papillomavirus-infected women. VISUAL OVERVIEW http//mcr.aacrjournals.org/content/molcanres/19/1/42/F1.large.jpg.The RAS-RAF-MEK-ERK pathway is the most well-studied of the MAPK cascades and is critical for cell proliferation, differentiation, and survival. Abnormalities in regulation resulting from mutations in components of this pathway, particularly in upstream proteins, RAS and RAF, are responsible for a significant fraction of human cancers and nearly all cutaneous melanomas. Activation of receptor tyrosine kinases by growth factors and various extracellular signals leads to the sequential activation of RAS, RAF, MEK, and finally ERK, which activates numerous transcription factors and facilitates oncogenesis in the case of aberrant pathway activation. link2 While extensive studies have worked to elucidate the activation mechanisms and structural components of upstream MAPK components, comparatively less attention has been directed toward the kinases, MEK and ERK, due to the infrequency of oncogenic-activating mutations in these kinases. However, acquired drug resistance has become a major issue in the treatment of RAS- and RAF-mutated cancers. Targeting the terminal kinases in the MAPK cascade has shown promise for overcoming many of these resistance mechanisms and improving treatment options for patients with MAPK-aberrant cancers. Here, we will describe the role of MEK and ERK in MAPK signaling and summarize the current understanding of their interaction and activation mechanisms. We will also discuss existing approaches for targeting MEK and ERK, and the benefits of alternative strategies. Areas requiring further exploration will be highlighted to guide future research endeavors and aid in the development of alternative therapeutic strategies to combat surmounting drug resistance in treating MAPK-mediated cancers. VISUAL OVERVIEW http//mcr.aacrjournals.org/content/molcanres/19/3/361/F1.large.jpg.Oil is frequently used as a solvent to inject lipophilic substances into the peritoneum of laboratory animals. Although mineral oil causes chronic peritoneal inflammation, little is known whether other oils are better suited. We show that olive, peanut, corn, or mineral oil causes xanthogranulomatous inflammation with depletion of resident peritoneal macrophages. However, there were striking differences in the severity of the inflammatory response. Peanut and mineral oil caused severe chronic inflammation with persistent neutrophil and monocyte recruitment, expansion of the vasculature, and fibrosis. Corn and olive oil provoked no or only mild signs of chronic inflammation. Mechanistically, the vegetal oils were taken up by macrophages leading to foam cell formation and induction of cell death. Olive oil triggered caspase-3 cleavage and apoptosis, which facilitate the resolution of inflammation. Peanut oil and, to a lesser degree, corn oil, triggered caspase-1 activation and macrophage pyroptosis, which impair the resolution of inflammation. As such, intraperitoneal oil administration can interfere with the outcome of subsequent experiments. As a proof of principle, intraperitoneal peanut oil injection was compared with its oral delivery in a thioglycolate-induced peritonitis model. The chronic peritoneal inflammation due to peanut oil injection impeded the proper recruitment of macrophages and the resolution of inflammation in this peritonitis model. link3 In summary, the data indicate that it is advisable to deliver lipophilic substances, like tamoxifen, by oral gavage instead of intraperitoneal injection. IMPLICATIONS This work contributes to the reproducibility of animal research by helping to understand some of the undesired effects observed in animal experiments.