Identification of neuronal structures and pathways corresponding to clinical functioning in galactosemia.

Classic galactosemia (OMIM# 230400) is an autosomal recessive disorder due to galactose-1-phosphate uridyltransferase deficiency. Newborn screening and prompt treatment with a galactose-free diet prevent the severe consequences of galactosemia, but clinical outcomes remain suboptimal. Five men and five women with classic galactosemia (mean age = 27.

Hospice Patient Care Goals and Medical Students' Perceptions: Evidence of a Generation Gap?

Background: The ability to perceive care goals of the dying may be an indicator of future quality patient-centered care. Research conducted on end-of-life goals indicates discrepancies between patients and physicians.

Objective: The aim of this study is to compare end-of-life care goals of hospice patients and medical student perceptions of patient care goals.

Brain structural correlates of schizotypal signs and subclinical schizophrenia nuclear symptoms in healthy individuals.

Background: Subclinical psychotic-like experiences (PLE), resembling key symptoms of psychotic disorders, are common throughout the general population and possibly associated with psychosis risk. There is evidence that such symptoms are also associated with structural brain changes.

Methods: In 672 healthy individuals, we assessed PLE and associated distress with the symptom-checklist-90R (SCL-90R) scales 'schizotypal signs' (STS) and 'schizophrenia nuclear symptoms' (SNS) and analysed associations with voxel- and surfaced-based brain structural parameters derived from structural magnetic resonance imaging at 3 T with CAT12.

Does a surgical helmet provide protection against aerosol transmitted disease?

Background and purpose - The COVID-19 pandemic caused by infection with SARS-CoV-2 has led to a global shortage of personal protective equipment (PPE). Various alternatives to ordinary PPE have been suggested to reduce transmission, which is primarily through droplets and aerosols. For many years orthopedic surgeons have been using surgical helmets as personal protection against blood-borne pathogens during arthroplasty surgery.

A healthy lifestyle and survival among women with ovarian cancer.

Ovarian cancer has a poor survival rate and, understandably, women often want to know whether there is anything they can do to improve their prognosis. Our goal was to investigate the association between a healthy lifestyle prediagnosis and postdiagnosis and survival in a cohort of Australian women with invasive epithelial ovarian cancer. We calculated a healthy lifestyle index (HLI) based on women's self-reported smoking status, height, weight, physical activity, diet and alcohol consumption before diagnosis (n = 678) and after completing primary treatment (n = 512).

Potential benefit of combination antifungal therapy in endocarditis.

endocarditis (AE) is a rare condition with a mortality rate greater than 60%. While it is generally accepted that both antifungal therapy and surgery are necessary for survival, the optimal antifungal regimen is unclear. A 62-year-old man was diagnosed with AE of a prosthetic aortic valve, complicated by cerebral emboli.

A single-cell atlas of the peripheral immune response in patients with severe COVID-19.

There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, which has infected more than three million people worldwide. Approximately 20% of patients with COVID-19 develop severe disease and 5% of patients require intensive care. Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines that may be produced by a subset of inflammatory monocytes, lymphopenia and T cell exhaustion.

A single-cell atlas of the peripheral immune response to severe COVID-19.

There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2. Here, we apply single-cell RNA sequencing (scRNA-seq) to peripheral blood mononuclear cells (PBMCs) of 7 patients hospitalized with confirmed COVID-19 and 6 healthy controls. We identify substantial reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene (ISG) signature, HLA class II downregulation, and a novel B cell-derived granulocyte population appearing in patients with acute respiratory failure requiring mechanical ventilation.

Diabetes and atherothrombosis: The circadian rhythm and role of melatonin in vascular protection.

Obesity-related euglycaemic insulin resistance clusters with cardiometabolic risk factors, contributing to the development of both type 2 diabetes and cardiovascular disease. An increased thrombotic tendency in diabetes stems from platelet hyperactivity, enhanced activity of prothrombotic coagulation factors and impaired fibrinolysis. Furthermore, a low-grade inflammatory response and increased oxidative stress accelerate the atherosclerotic process and, together with an enhanced thrombotic environment, result in premature and more severe cardiovascular disease.

Operative Results of Mitral Valve Repair and Replacement in Chronic Ischaemic Mitral Valve Regurgitation.

Background: Ischaemic mitral regurgitation (IMR) carries significant morbidity and mortality. Surgical management includes coronary artery bypass surgery alone or concomitant with mitral valve repair or replacement. There is ongoing debate regarding the appropriate approach to the mitral valve in relation to long-term outcomes.

Treated HIV Infection Alters Phenotype but Not HIV-Specific Function of Peripheral Blood Natural Killer Cells.

Natural killer (NK) cells are the predominant antiviral cells of the innate immune system, and may play an important role in acquisition and disease progression of HIV. While untreated HIV infection is associated with distinct alterations in the peripheral blood NK cell repertoire, less is known about how NK phenotype is altered in the setting of long-term viral suppression with antiretroviral therapy (ART), as well as how NK memory can impact functional responses. As such, we sought to identify changes in NK cell phenotype and function using high-dimensional mass cytometry to simultaneously analyze both surface and functional marker expression of peripheral blood NK cells in a cohort of ART-suppressed, HIV+ patients and HIV- healthy controls.

Placental MRI: Effect of maternal position and uterine contractions on placental BOLD MRI measurements.

Introduction: Before using blood-oxygen-level-dependent magnetic resonance imaging (BOLD MRI) during maternal hyperoxia as a method to detect individual placental dysfunction, it is necessary to understand spatiotemporal variations that represent normal placental function. We investigated the effect of maternal position and Braxton-Hicks contractions on estimates obtained from BOLD MRI of the placenta during maternal hyperoxia.

Methods: For 24 uncomplicated singleton pregnancies (gestational age 27-36 weeks), two separate BOLD MRI datasets were acquired, one in the supine and one in the left lateral maternal position.

Infant FreeSurfer: An automated segmentation and surface extraction pipeline for T1-weighted neuroimaging data of infants 0-2 years.

The development of automated tools for brain morphometric analysis in infants has lagged significantly behind analogous tools for adults. This gap reflects the greater challenges in this domain due to: 1) a smaller-scaled region of interest, 2) increased motion corruption, 3) regional changes in geometry due to heterochronous growth, and 4) regional variations in contrast properties corresponding to ongoing myelination and other maturation processes. Nevertheless, there is a great need for automated image-processing tools to quantify differences between infant groups and other individuals, because aberrant cortical morphologic measurements (including volume, thickness, surface area, and curvature) have been associated with neuropsychiatric, neurologic, and developmental disorders in children.

Comparison of intraoperative tranexamic acid and epsilon-aminocaproic acid in cardiopulmonary bypass patients.

Objective: To compare tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA) in patients undergoing cardiac surgery with cardiopulmonary bypass.

Methods: Over a consecutive 2-year period, 824 adult cardiac surgery patients who received TXA during an EACA shortage were compared with 778 patients who received EACA postshortage. Patient characteristics and process and outcome variables were collected through chart review and database queries.

Discovery of Highly Selective Inhibitors of Calmodulin-Dependent Kinases That Restore Insulin Sensitivity in the Diet-Induced Obesity Mouse Model.

Polymorphisms in the region of the calmodulin-dependent kinase isoform D (CaMK1D) gene are associated with increased incidence of diabetes, with the most common polymorphism resulting in increased recognition by transcription factors and increased protein expression. While reducing CaMK1D expression has a potentially beneficial effect on glucose processing in human hepatocytes, there are no known selective inhibitors of CaMK1 kinases that can be used to validate or translate these findings. Here we describe the development of a series of potent, selective, and drug-like CaMK1 inhibitors that are able to provide significant free target cover in mouse models and are therefore useful as tool compounds.

Placental Flattening via Volumetric Parameterization.

We present a volumetric mesh-based algorithm for flattening the placenta to a canonical template to enable effective visualization of local anatomy and function. Monitoring placental function promises to support pregnancy assessment and to improve care outcomes. We aim to alleviate visualization and interpretation challenges presented by the shape of the placenta when it is attached to the curved uterine wall.

Early exit from neonatal therapeutic hypothermia: A single institution experience using MRI to guide decision-making.

Background: To evaluate the feasibility of a protocol using combined magnetic resonance imaging (MRI), clinical data, and electroencephalogram (EEG) to identify neonates with mild neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH) who are eligible for "early exit".

Methods: Retrospective chart review of TH cases at a single Level III NICU over a 5-year period was used to describe the demographic, clinical, and outcome data in neonates that received early exit in contrast to 72 hour TH treatment.

Results: Two hundred and eight TH cases, including 18 early exit cases (9%) and 9 cases (4%) evaluated for early exit with MRI but continued on 72 hours of TH, were identified.

Evaluating the impact of dose reductions and delays on progression-free survival in women with ovarian cancer treated with either three-weekly or dose-dense carboplatin and paclitaxel regimens in the national prospective OPAL cohort study.

Objectives: To determine the impact of chemotherapy dose reductions and dose delays on progression-free survival (PFS) in women with ovarian cancer receiving first line chemotherapy in a real world prospective cohort study.

Methods: Patients with newly diagnosed epithelial ovarian (or peritoneal, fallopian tube) cancer enrolled in a national Australian prospective study, OPAL, who commenced three-weekly carboplatin (AUC 5 or 6) and paclitaxel 175 mg/m (CP) or carboplatin (AUC 5 or 6) and dose-dense weekly paclitaxel 80 mg/m (DD-CP) were eligible. Primary endpoint was PFS.

Female-biased gene flow between two species of Darwin's finches.

The mosaic nature of hybrid genomes is well recognized, but little is known of how they are shaped initially by patterns of breeding, selection, recombination and differential incompatibilities. On the small Galápagos island of Daphne Major, two species of Darwin's finches, Geospiza fortis and G. scandens, hybridize rarely and back-cross bidirectionally with little or no loss of fitness under conditions of plentiful food.

Extended Venous Thromboembolism Prophylaxis in Medically Ill Patients: An NATF Anticoagulation Action Initiative.

Hospitalized patients with acute medical illnesses are at risk for venous thromboembolism (VTE) during and after a hospital stay. Risk factors include physical immobilization and underlying pathophysiologic processes that activate the coagulation pathway and are still present after discharge. Strategies for optimal pharmacologic VTE thromboprophylaxis are evolving, and recommendations for VTE prophylaxis can be further refined to protect high-risk patients after hospital discharge.

An Atypical Sulcal Pattern in Children with Disorders of the Corpus Callosum and Its Relation to Behavioral Outcomes.

Hypogenesis (hCC) and dysgenesis (dCC) of the corpus callosum (CC) are characterized by its smaller size or absence. The outcomes of these patients vary considerably and are unrelated to the size of the CC abnormality. The aim of the current study was to characterize the sulcal pattern in children with hCC and dCC and to explore its relation to clinical outcome.