Designing and implementing the IDEAL Study: A randomized clinical trial of genotype disclosure for late-onset Alzheimer's disease in an urban Latino population.

Introduction: The (IDEAL) Study is a randomized clinical trial investigating the psychosocial, behavioral, and cognitive impacts of apolipoprotein E () genotype disclosure for late-onset Alzheimer's disease (AD) among Latinos.

Methods: We used address-based sampling to recruit English- and Spanish-speaking Latinos aged 40-64 living in northern Manhattan for a community-based Baseline Survey about their knowledge and opinions about AD. Participants eligible for the clinical trial were invited to complete an Introductory Session, including AD and genetics education and informed consent, before undergoing genotyping for .

Comparison of 3D facial photographs and clinical documentation in patients with craniofacial morphea.

Diagnosis of craniofacial morphea (CM) relies upon clinical examination of progressive craniofacial changes. We assess the utility of 3D stereophotogrammetry in documenting asymmetry of the face compared to clinical notetaking. This retrospective study of 3D images and clinical documentation included 32 patients (mean age 15.

Treatment of recurrent pediatric myelodysplastic syndrome post hematopoietic stem cell transplantation.

Treatment of recurrent myelodysplastic syndrome (MDS) after hematopoietic cell transplantation (HCT) remains challenging. We present a 4-year-old girl experiencing early MDS relapse post-HCT treated with a multimodal strategy encompassing a second HCT and innovative targeted therapies. We underscore the potential of a comprehensive treatment approach in managing recurrent pediatric MDS.

The Multistable Melanopsins of Mammals.

Melanopsin is a light-activated G protein coupled receptor that is expressed widely across phylogeny. In mammals, melanopsin is found in intrinsically photosensitive retinal ganglion cells (ipRGCs), which are especially important for "non-image" visual functions that include the regulation of circadian rhythms, sleep, and mood. Photochemical and electrophysiological experiments have provided evidence that melanopsin has at least two stable conformations and is thus multistable, unlike the monostable photopigments of the classic rod and cone photoreceptors.

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants.

Fortifying angiogenic efficacy of conditioned media using phototoxic-free blue light for wound healing.

We used a blue organic light-emitting diode (bOLED) to increase the paracrine factors secreted from human adipose-derived stem cells (hADSCs) for producing conditioned medium (CM). Our results showed that while the bOLED irradiation promotes a mild-dose reactive oxygen generation that enhances the angiogenic paracrine secretion of hADSCs, it does not induce phototoxicity. The bOLED enhances paracrine factors via a cell-signaling mechanism involving hypoxia-inducible factor 1 alpha.

Subaqueous free-standing 3D cell culture system for ultrafast cell compaction, mechano-inductive immune control, and improving therapeutic angiogenesis.

Conventional 3D cell culture methods require a comprehensive complement in labor-intensive and time-consuming processes along with in vivo circumstantial mimicking. Here, we describe a subaqueous free-standing 3D cell culture (FS) device that can induce the omnidirectional environment and generate ultrafast human adipose-derived stem cells (hADSCs) that efficiently aggregate with compaction using acoustic pressure. The cell culture conditions were optimized using the FS device and identified the underlying molecular mechanisms.

Copy Number Variation and Structural Genomic Findings in 116 Cases of Sudden Unexplained Death between 1 and 28 Months of Age.

In sudden unexplained death in pediatrics (SUDP) the cause of death is unknown despite an autopsy and investigation. The role of copy number variations (CNVs) in SUDP has not been well-studied. Chromosomal microarray (CMA) data are generated for 116 SUDP cases with age at death between 1 and 28 months.

Encoding of environmental illumination by primate melanopsin neurons.

Light regulates physiology, mood, and behavior through signals sent to the brain by intrinsically photosensitive retinal ganglion cells (ipRGCs). How primate ipRGCs sense light is unclear, as they are rare and challenging to target for electrophysiological recording. We developed a method of acute identification within the live, ex vivo retina.

Cardiac Resynchronization Therapy for Adult Patients With a Failing Systemic Right Ventricle: A Multicenter Study.

Background The objective of this international multicenter study was to investigate both early and late outcomes of cardiac resynchronization therapy (CRT) in patients with a systemic right ventricle (SRV) and to identify predictors for congestive heart failure readmissions and mortality. Methods and Results This retrospective international multicenter study included 13 centers. The study population comprised 80 adult patients with SRV (48.

Paroxysmal hyperthermia, dysautonomia and rhabdomyolysis in a patient with Lesch-Nyhan syndrome.

Lesch-Nyhan syndrome is an x-linked genetic disorder of purine metabolism that results in the overproduction of uric acid and neurologic deficits manifesting as intellectual disability, dystonia, other movement disorders and self-mutilation. We describe a 12-year-old patient with a history of Lesch-Nyhan syndrome, G6PD deficiency and central diabetes insipidus and multiple admissions for fever, acute kidney injury and transaminitis in the setting of rhabdomyolysis. The patient's temperature dysregulation and dysautonomia is likely attributable to abnormal neurotransmitter release, particularly that of dopamine, in the central nervous system.

The role of extracellular vesicles in the physiological and pathological regulation of the blood-brain barrier.

Extracellular vesicles (EVs) are a subclass of biological nanoparticles secreted by most cell types. Once secreted, EVs can travel long distances to deliver their content to target cells thereby playing a key role in cell-to-cell communication and supporting both physiological and pathological processes. In recent years, the functional versatility of EVs has come to be more widely appreciated.

Fluorescence artifact correction in the thrombin generation assay: Necessity for correction algorithms in procoagulant samples.

Introduction: The thrombin generation (TG) test is a global hemostasis assay sensitive to procoagulant conditions. However, some TG assays may underestimate elevated TG when the thrombin fluorogenic substrate is depleted or fluorescence is attenuated by the inner filter effect (IFE).

Objectives: We sought to elucidate the extent to which procoagulant conditions require correcting for fluorogenic substrate depletion and/or IFE.

Trends and variation in repeat neuroimaging for children with traumatic intracranial hemorrhage.

Objectives: We aimed to determine trends and institutional variation in repeat neuroimaging in children with traumatic intracranial hemorrhage and to identify factors associated with neuroimaging modality (subsequent magnetic resonance imaging [MRI] vs computed tomography [CT]).

Methods: We conducted a retrospective cross-sectional study of 35 hospitals in the Pediatric Health Information System database. We included children <18 years of age hospitalized from 2010-2019 with intracranial hemorrhage and who underwent a brain CT.

Racial and ethnic differences in COVID-19 vaccine hesitancy and uptake.

Background: Racial and ethnic minorities have been disproportionately impacted by COVID-19. In the initial phase of population-based vaccination in the United States (U.S.

A Rationally Designed ICAM1 Antibody Drug Conjugate for Pancreatic Cancer.

Outcomes for pancreatic cancer (PC) patients remain strikingly poor with a 5-year survival of less than 8% due to the lack of effective treatment modalities. Here, a novel precision medicine approach for PC treatment is developed, which is composed of a rationally designed tumor-targeting ICAM1 antibody-drug conjugate (ADC) with optimized chemical linker and cytotoxic payload, complemented with a magnetic resonance imaging (MRI)-based molecular imaging approach to noninvasively evaluate the efficiency of ICAM1 ADC therapy. It is shown that ICAM1 is differentially overexpressed on the surface of human PC cells with restricted expression in normal tissues, enabling ICAM1 antibody to selectively recognize and target PC tumors in vivo.

Is it Time for Reviewer 3 to Request Human Organ Chip Experiments Instead of Animal Validation Studies?

For the past century, experimental data obtained from animal studies have been required by reviewers of scientific articles and grant applications to validate the physiological relevance of in vitro results. At the same time, pharmaceutical researchers and regulatory agencies recognize that results from preclinical animal models frequently fail to predict drug responses in humans. This reviews recent advances in human organ-on-a-chip (Organ Chip) microfluidic culture technology, both with single Organ Chips and fluidically coupled human "Body-on-Chips" platforms, which demonstrate their ability to recapitulate human physiology and disease states, as well as human patient responses to clinically relevant drug pharmacokinetic exposures, with higher fidelity than other in vitro models or animal studies.

Spaced Education Through e-Learning for Ongoing Professional Development.

Background: The practice of emergency medicine has become increasingly complex. Constant advances in clinical practice, innovative technologies, patient safety and quality initiatives, and local and national policy changes continue to add to the cognitive load on providers. New and innovative professional development approaches are needed to help providers remain current despite busy and disparate clinician schedules.

Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress.

The 2020 Congress of the International Society of Thrombosis and Haemostasis (ISTH) was held virtually July 12-15, 2019, due to the coronavirus disease 2019 pandemic. The congress convenes annually to discuss clinical and basic topics in hemostasis and thrombosis. Each year, the program includes State of Art (SOA) lectures given by prominent scientists.

TAS2R20 variants confer dietary adaptation to high-quercitrin bamboo leaves in Qinling giant pandas.

Sensitivity to bitter tastes provides animals with an important means of interacting with their environment and thus, influences their dietary preferences. Genetic variants encoding functionally distinct receptor types contribute to variation in bitter taste sensitivity. Our previous study showed that two nonsynonymous sites, A52V and Q296H, in the gene are directionally selected in giant pandas from the Qinling Mountains, which are speculated to be the causative base-pair changes of Qinling pandas for the higher preference for bamboo leaves in comparison with other pandas.

Pediatric sternal fractures: A single center retrospective review.

Purpose: We sought to investigate the diagnosis, management, and outcomes of pediatric sternal fractures.

Methods: We used ICD codes to search our trauma registry and Hound Dog software to search the hospital data warehouse for all cases of radiologically confirmed sternal fracture in patients <21 years from January 1, 1997 to July 1, 2017. We extracted demographics, mechanism of injury, diagnostic modality, associated injuries, and clinical outcomes.

A comparison between placental and amniotic mesenchymal stem cells in transamniotic stem cell therapy for experimental gastroschisis.

Purpose: We compared placental and amniotic fluid-derived mesenchymal stem cells (pMSCs and afMSCs, respectively) in transamniotic stem cell therapy for experimental gastroschisis.

Methods: Gastroschisis was surgically created in 126 rat fetuses at gestational day 18 (term = 22 days), immediately followed by volume-matched intraamniotic injections of suspensions of afMSCs (n = 32), pMSCs (n = 33), or normal saline (NS) (n = 33). Untreated fetuses served as controls (n = 28).

Neurofilament as a potential biomarker for spinal muscular atrophy.

Objective: To evaluate plasma phosphorylated neurofilament heavy chain (pNF-H) as a biomarker in spinal muscular atrophy (SMA).

Methods: Levels of pNF-H were measured using the ProteinSimple platform in plasma samples from infants with SMA enrolled in ENDEAR (NCT02193074) and infants/children without neurological disease.

Results: Median pNF-H plasma level was 167.