iPSC-derived retinal pigmented epithelial cells from patients with macular telangiectasia show decreased mitochondrial function.

Patient-derived induced pluripotent stem cells (iPSCs) provide a powerful tool for identifying cellular and molecular mechanisms of disease. Macular telangiectasia type 2 (MacTel) is a rare, late-onset degenerative retinal disease with an extremely heterogeneous genetic architecture, lending itself to the use of iPSCs. Whole-exome sequencing screens and pedigree analyses have identified rare causative mutations that account for less than 5% of cases.

Insulin-regulated serine and lipid metabolism drive peripheral neuropathy.

Diabetes represents a spectrum of disease in which metabolic dysfunction damages multiple organ systems including liver, kidneys and peripheral nerves. Although the onset and progression of these co-morbidities are linked with insulin resistance, hyperglycaemia and dyslipidaemia, aberrant non-essential amino acid (NEAA) metabolism also contributes to the pathogenesis of diabetes. Serine and glycine are closely related NEAAs whose levels are consistently reduced in patients with metabolic syndrome, but the mechanistic drivers and downstream consequences of this metabotype remain unclear.

Presentation, Treatment, and Natural Course of Severe Symptoms of Urinary Tract Infections Measured by a Smartphone App: Observational and Feasibility Study.

Background: Urinary tract infections (UTIs) are one of the most common conditions in women. Current information on the presentation, management, and natural course of the infection is based on paper diaries filled out and subsequently posted by patients.

Objective: The aim of this study is to explore the feasibility of a smartphone app to assess the natural course and management of UTIs.

There's a New Sheriff in Town: When Enterprise IT Takes Over Imaging IT.

The consolidation of information technology (IT) teams from individual facilities to an enterprise-wide reporting structure and the transition of IT staff from operating within a diagnostic imaging department, such as Radiology, to an enterprise IT group is common. The plan to optimize this workforce can have undesirable and unintended consequences, if not done correctly. For those organizations seeking to optimize their workforce to deliver the best possible IT services, including to areas that produce and use medical imaging, this can be an exercise of balancing specialized knowledge and centralized staffing capacity planning.

Serine biosynthesis defect due to haploinsufficiency of PHGDH causes retinal disease.

Macular telangiectasia type 2 (MacTel) is a progressive, late-onset retinal degenerative disease linked to decreased serum levels of serine that elevate circulating levels of a toxic ceramide species, deoxysphingolipids (deoxySLs); however, causal genetic variants that reduce serine levels in patients have not been identified. Here we identify rare, functional variants in the gene encoding the rate-limiting serine biosynthetic enzyme, phosphoglycerate dehydrogenase (PHGDH), as the single locus accounting for a significant fraction of MacTel. Under a dominant collapsing analysis model of a genome-wide enrichment analysis of rare variants predicted to impact protein function in 793 MacTel cases and 17,610 matched controls, the PHGDH gene achieves genome-wide significance (P = 1.

Curbing Burnout Hysteria With Self-Compassion: A Key to Physician Resilience.

Background: Never before has physician suffering received as much attention in the peer-reviewed medical literature and popular media as now. The purpose of this paper is to propose that the manner in which these concerns are being addressed is further complicating physician and medical family well-being due to the perpetuation of work ambivalence.

Methods: A search of the English literature was conducted using PubMed to identify papers addressing physician burnout and other forms of psychosocial suffering.

GPs' attitudes towards the diagnosis and treatment of male urinary tract infections: a qualitative interview study in Ireland.

Background: In general practice, males represent around 20% of the total number of urinary tract infection (UTI) consultations. The majority of UTI research focuses on the diagnosis and treatment of women with UTIs but there is little evidence on how male UTIs are treated.

Aim: To better understand GPs' attitudes towards the diagnosis and treatment of male UTIs.

Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy.

Background: Identifying mechanisms of diseases with complex inheritance patterns, such as macular telangiectasia type 2, is challenging. A link between macular telangiectasia type 2 and altered serine metabolism has been established previously.

Methods: Through exome sequence analysis of a patient with macular telangiectasia type 2 and his family members, we identified a variant in encoding a subunit of serine palmitoyltransferase (SPT).

Moving From Physician Burnout to Resilience.

We contend that work ambivalence is a key building block in fostering physician burnout and its sequalae, while engagement in meaningful work and receiving family support for that work enhances resilience. No singular approach to curbing burnout in OBGYN physicians has received empirical support. Clinical experience suggests that curbing physician burnout requires a combination of workplace redesigns, positive leadership behaviors, and resilience training that teaches practical applications from the fields of resilience, emotional intelligence, positive psychology, and relationship systems.

Comparison of Lower Extremity Recovery After Anterior Cruciate Ligament Reconstruction With Transphyseal Hamstring Versus Extraphyseal Iliotibial Band Techniques in Skeletally Immature Athletes.

Background: The influence of graft type on recovery after anterior cruciate ligament reconstruction (ACLR) has not been adequately studied in pediatric patients.

Purpose: To describe lower extremity functional recovery parameters at the 6-month mark after ACLR across 3 distinct groups of skeletally immature patients: pediatric male patients with transphyseal hamstring grafts (PM-HS), pediatric female patients with transphyseal hamstring grafts (PF-HS), and pediatric male patients with extraphyseal iliotibial band grafts (PM-ITB).

Study Design: Cohort study; Level of evidence, 3.

Fully automated, deep learning segmentation of oxygen-induced retinopathy images.

Oxygen-induced retinopathy (OIR) is a widely used model to study ischemia-driven neovascularization (NV) in the retina and to serve in proof-of-concept studies in evaluating antiangiogenic drugs for ocular, as well as nonocular, diseases. The primary parameters that are analyzed in this mouse model include the percentage of retina with vaso-obliteration (VO) and NV areas. However, quantification of these two key variables comes with a great challenge due to the requirement of human experts to read the images.

SUCCESSFUL TREATMENT OF A SOLITARY SKULL METASTASIS IN A CHILD WITH WILMS' TUMOR.

This report presents the successful treatment of a child with a solitary metastatic lesion to the calvarium following treatment for Stage III anaplastic Wilms' Tumor.

CD44 expression in endothelial colony-forming cells regulates neurovascular trophic effect.

Vascular abnormalities are a common component of eye diseases that often lead to vision loss. Vaso-obliteration is associated with inherited retinal degenerations, since photoreceptor atrophy lowers local metabolic demands and vascular support to those regions is no longer required. Given the degree of neurovascular crosstalk in the retina, it may be possible to use one cell type to rescue another cell type in the face of severe stress, such as hypoxia or genetically encoded cell-specific degenerations.

Overuse Injuries in the Pediatric Population.

Athletic overuse injuries are becoming an increasingly common entity in the active pediatric population. The prevalence of these injuries may be attributed to the combination of an underdeveloped musculoskeletal system, increased participation in competitive sport at a younger age, and increased duration and intensity of training. Many of these injuries may go unreported and/or undiagnosed, as they do not all result in time lost from sports, and are not always appreciated on imaging.

Reduction in Overt and Silent Stroke Recurrence Rate Following Cerebral Revascularization Surgery in Children with Sickle Cell Disease and Severe Cerebral Vasculopathy.

Background: Children with sickle cell disease (SCD) and moyamoya may benefit from indirect cerebral revascularization surgery in addition to chronic blood transfusion therapy for infarct prevention. We sought to compare overt and silent infarct recurrence rates in children with SCD undergoing revascularization.

Methods: This was a retrospective cohort study of all children with SCD and moyamoya treated at two children's hospitals.

Associative Learning Drives the Formation of Silent Synapses in Neuronal Ensembles of the Nucleus Accumbens.

Background: Learned associations between environmental stimuli and rewards play a critical role in addiction. Associative learning requires alterations in sparsely distributed populations of strongly activated neurons, or neuronal ensembles. Until recently, assessment of functional alterations underlying learned behavior was restricted to global neuroadaptations in a particular brain area or cell type, rendering it impossible to identify neuronal ensembles critically involved in learned behavior.

Markedly raised levels of C-reactive protein are associated with culture-proven sepsis or necrotising enterocolitis in extremely preterm neonates.

Aim: A serious inflammatory process is suspected when C-reactive protein (CRP) is very high, and we established the causes and outcomes when CRP was >100 mg/L in neonates.

Methods: We retrospectively reviewed all 277 episodes where CRP exceeded 100 mg/L between January 2007 and December 2011 at a tertiary neonatal unit.

Results: Of the 6025 neonates admitted during the study period, 258 had CRP >100 mg/L at least once.

Treatment of obesity in children and adolescents.

The prevalence of childhood and adolescent obesity continues to rise in the United States (US). Immediate health consequences are being observed, and long-term risks are mounting within the pediatric population, secondary to obesity. The hallmark of prevention and treatment of obesity in children and adolescents includes lifestyle modification (i.

Modafinil attenuates reinstatement of cocaine seeking: role for cystine-glutamate exchange and metabotropic glutamate receptors.

Modafinil may be useful for treating stimulant abuse, but the mechanisms by which it acts to do so are unknown. Indeed, a primary effect of modafinil is to inhibit dopamine transport, which typically promotes rather than inhibits motivated behavior. Therefore, we examined the role of nucleus accumbens extracellular glutamate and the group II metabotropic glutamate receptor (mGluR2/3) in modafinil effects.

Risk-prediction tool for identifying hospitalized children with a predisposition for development of venous thromboembolism: Peds-Clot clinical Decision Rule.

Background: The prevalence of VTE is increasing in tertiary pediatric hospitals. Identification of high-risk populations using uniform criteria is required to develop evidence-based VTE prevention guidelines.

Objective: To develop a VTE risk prediction rule, the Peds-Clot clinical Decision Rule (PCDR), to identify high-risk children who were at increased risk of developing VTE.

The effect of calf nutrition on the performance of dairy herd replacements.

Sixty-five Holstein-Friesian calves were randomly allocated to one of eight nutritional treatments at 4 days of age. In this factorial design study, the treatments comprised of four levels of milk replacer (MR) mixed in 6 l of water (500, 750, 1000 and 1250 g/day) × two crude protein (CP) concentrations (230 and 270 g CP/kg dry matter (DM)). MR was fed via automatic teat feeders and concentrates were offered via automated dispensers during the pre-wean period.