Flow in fetoplacental-like microvessels in vitro enhances perfusion, barrier function, and matrix stability.

Proper placental vascularization is vital for pregnancy outcomes, but assessing it with animal models and human explants has limitations. We introduce a 3D in vitro model of human placenta terminal villi including fetal mesenchyme and vascular endothelium. By coculturing HUVEC, placental fibroblasts, and pericytes in a macrofluidic chip with a flow reservoir, we generate fully perfusable fetal microvessels.

Completeness of Race and Ethnicity Reporting in Person-Level COVID-19 Surveillance Data, 50 States, April 2020-December 2021.

Objectives: Black, Indigenous, and People of Color have borne a disproportionate incidence of COVID-19 cases in the United States. However, few studies have documented the completeness of race and ethnicity reporting in national COVID-19 surveillance data. The objective of this study was to describe the completeness of race and ethnicity ascertainment in person-level data received by the Centers for Disease Control and Prevention (CDC) through national COVID-19 case surveillance.

COVID-19 Among Non-Hispanic American Indian and Alaska Native People Residing in Urban Areas Before and After Vaccine Rollout-Selected States and Counties, United States, January 2020-October 2021.

To evaluate COVID-19 disparities among non-Hispanic American Indian/Alaska Native (AI/AN) and non-Hispanic White persons in urban areas. Using COVID-19 case surveillance data, we calculated cumulative incidence rates and risk ratios (RRs) among non-Hispanic AI/AN and non-Hispanic White persons living in select urban counties in the United States by age and sex during January 22, 2020, to October 19, 2021. We separated cases into prevaccine (January 22, 2020-April 4, 2021) and postvaccine (April 5, 2021-October 19, 2021) periods.

Concussion symptoms and temporary accommodations using a student-centered return to learn care plan.

Background: Many students return to school after concussion with symptoms but without formal support.

Objective: To examine concussion symptoms and temporary academic accommodations during school use of a four-week student-centered return to learn (RTL) care plan.

Methods: Five public high schools used the RTL care plan and contributed student-level data after student report of concussion.

Modelling the Human Placental Interface In Vitro-A Review.

Acting as the primary link between mother and fetus, the placenta is involved in regulating nutrient, oxygen, and waste exchange; thus, healthy placental development is crucial for a successful pregnancy. In line with the increasing demands of the fetus, the placenta evolves throughout pregnancy, making it a particularly difficult organ to study. Research into placental development and dysfunction poses a unique scientific challenge due to ethical constraints and the differences in morphology and function that exist between species.

Mean Arterial Pressure and Discharge Outcomes in Severe Pediatric Traumatic Brain Injury.

Background And Objective: Optimizing blood pressure is an important target for intervention following pediatric traumatic brain injury (TBI). The existing literature has examined the association between systolic blood pressure (SBP) and outcomes. Mean arterial pressure (MAP) is a better measure of organ perfusion than SBP and is used to determine cerebral perfusion pressure but has not been previously examined in relation to outcomes after pediatric TBI.

Agreement Between Arterial Carbon Dioxide Levels With End-Tidal Carbon Dioxide Levels and Associated Factors in Children Hospitalized With Traumatic Brain Injury.

Importance: Alterations in the partial pressure of carbon dioxide, arterial (Paco2) can affect cerebral perfusion after traumatic brain injury. End-tidal carbon dioxide (EtCO2) monitoring is a noninvasive tool used to estimate Paco2 values.

Objective: To examine the agreement between Paco2 and EtCO2 and associated factors in children with traumatic brain injury.

The Pediatric Guideline Adherence and Outcomes (PEGASUS) programme in severe traumatic brain injury: a single-centre hybrid implementation and effectiveness study.

Background: As far as we know, there are no tested in-hospital care programmes for paediatric traumatic brain injury. We aimed to assess implementation and effectiveness of the Pediatric Guideline Adherence and Outcomes (PEGASUS) programme in children with severe traumatic brain injury.

Methods: We did a prospective hybrid implementation and effectiveness study at the Harborview Medical Center (Seattle, WA, USA).

Huge traumatic pulmonary artery pseudoaneurysm.

Pulmonary artery pseudoaneurysm is a very rare complication of penetrating thoracic trauma. We present a case of a 27-year-old woman who developed a 6.5-cm traumatic pulmonary artery pseudoaneurysm after suffering multiple stab wounds to the chest and the abdomen.

Glenoid avulsion of the glenohumeral ligament (GAGL): a case report and review of the anatomy.

Shoulder dislocations are frequently seen in the general population and can be a cause of instability. Instability can lead to debilitating symptoms and morbidity as a result of progressive damage to the shoulder. Anterior shoulder dislocations are the most frequent type of dislocations and have been studied extensively with MRI.

Structure-guided design of a series of MCL-1 inhibitors with high affinity and selectivity.

Myeloid cell leukemia 1 (MCL-1) is a BCL-2 family protein that has been implicated in the progression and survival of multiple tumor types. Herein we report a series of MCL-1 inhibitors that emanated from a high throughput screening (HTS) hit and progressed via iterative cycles of structure-guided design. Advanced compounds from this series exhibited subnanomolar affinity for MCL-1 and excellent selectivity over other BCL-2 family proteins as well as multiple kinases and GPCRs.

Imidazo[2,1-b]thiazoles: multitargeted inhibitors of both the insulin-like growth factor receptor and members of the epidermal growth factor family of receptor tyrosine kinases.

The design and enzyme activities of a novel class of imidazo[2,1-b]thiazoles is presented.

Development of multitargeted inhibitors of both the insulin-like growth factor receptor (IGF-IR) and members of the epidermal growth factor family of receptor tyrosine kinases.

Emerging clinical and pre-clinical data indicate that both insulin-like growth factor receptor (IGF-IR) and members of the epidermal growth factor (EGF) family of receptor tyrosine kinases (RTKs) exhibit significant cross-talk in human cancers. Therefore, a small molecule that successfully inhibits the signaling of both classes of oncogenic kinases might provide an attractive agent for chemotherapeutic use. Herein, we disclose the structure activity relationships that led to the synthesis and biological characterization of 14, a novel small molecule inhibitor of both IGF-IR and members of the epidermal growth factor family of RTKs.

Discovery and optimization of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of albumin binding.

Methionine aminopeptidase-2 (MetAP2) is a novel target for cancer therapy. As part of an effort to discover orally active reversible inhibitors of MetAP2, a series of anthranilic acid sulfonamides with micromolar affinities for human MetAP2 were identified using affinity selection by mass spectrometry (ASMS) screening. These micromolar hits were rapidly improved to nanomolar leads on the basis of insights from protein crystallography; however, the compounds displayed extensive binding to human serum albumin and had limited activity in cellular assays.

Development of sulfonamide compounds as potent methionine aminopeptidase type II inhibitors with antiproliferative properties.

We have screened molecules for inhibition of MetAP2 as a novel approach toward antiangiogenesis and anticancer therapy using affinity selection/mass spectrometry (ASMS) employing MetAP2 loaded with Mn(2+) as the active site metal. After a series of anthranilic acid sulfonamides with micromolar affinities was identified, chemistry efforts were initiated. The micromolar hits were quickly improved to potent nanomolar inhibitors by chemical modifications guided by insights from X-ray crystallography.

Methionine aminopeptidase 2 inhibition is an effective treatment strategy for neuroblastoma in preclinical models.

Tumor vascularity is correlated with an aggressive disease phenotype in neuroblastoma, suggesting that angiogenesis inhibitors may be a useful addition to current therapeutic strategies. We previously showed that the antiangiogenic compound TNP-470, an irreversible methionine aminopeptidase 2 (MetAP2) inhibitor, suppressed local and disseminated human neuroblastoma growth rates in murine models but had significant associated toxicity at the effective dose. We have recently shown that a novel, reversible MetAP2 inhibitor, A-357300, significantly inhibits CHP-134-derived neuroblastoma s.

3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2.

Substituted 3-amino-2-hydroxyamides and related hydroxyamides and acylhydrazines were identified as inhibitors of human methionine aminopeptidase-2 (MetAP2). Examination of substituents through parallel synthesis and iterative structure-based design allowed the identification of potent inhibitors with good selectivity against MetAP1. Diacylhydrazine 3t (A-357300) was identified as an analogue displaying inhibition of methionine processing and cellular proliferation in human microvascular endothelial cells (HMVEC).

Tumor suppression by a rationally designed reversible inhibitor of methionine aminopeptidase-2.

Methionine aminopeptidase (MetAP)-2 has been suggested as a novel target for cancer therapy because the anticancer agent TNP-470 irreversibly inactivates the catalytic activity of this enzyme. However, the importance of MetAP2 in cell growth and tumor progression was uncertain because previous data were based on the chemically reactive TNP-470. Here we show that a rationally designed reversible MetAP2 inhibitor, A-357300, suppresses tumor growth preclinically without the toxicities observed with TNP-470.