Questioning the Clinical Utility of Exome Sequencing in Developing Countries.

The availability of whole-exome sequencing has revolutionized the study of genetic disease in recent years, particularly in dermatology, where clinical phenotypes are readily recognized. As this technology becomes increasingly affordable and accessible, questions are emerging regarding the clinical and ethical responsibilities of physicians who determine variants underlying disease, especially with regard to children, for whom treatment may be warranted and clinical course improved based on a known genotype. These responsibilities are accentuated in the developing countries, which harbor most consanguineous populations and thus bear the brunt of monogenic genodermatoses.

Obstructive Acute Pancreatitis Secondary to PEG Tube Migration.

Percutaneous gastrostomy is a well-established method of providing enteral nutrition to patients incapable of oral intake, or for whom oral intake is insufficient to meet metabolic needs. In comparison to total parenteral nutrition, enteral feeding is advantageous in that it helps maintain gut mucosal integrity, which decreases the risk of bacterial translocation through the gastrointestinal tract. Complications include bleeding, aspiration, internal organ injury, perforation, periostomal leaks, tube dislodgement, and occlusion.

Impaired glucose tolerance in first-episode drug-naïve patients with schizophrenia: relationships with clinical phenotypes and cognitive deficits.

Background: Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus with impaired glucose tolerance (IGT) than normals. We examined the relationship between IGT and clinical phenotypes or cognitive deficits in first-episode, drug-naïve (FEDN) Han Chinese patients with schizophrenia.

Method: A total of 175 in-patients were compared with 31 healthy controls on anthropometric measures and fasting plasma levels of glucose, insulin and lipids.

Timing of cranial vault remodeling in nonsyndromic craniosynostosis: a single-institution 30-year experience.

OBJECTIVE Due to the changing properties of the infant skull, there is still no clear consensus on the ideal time to surgically intervene in cases of nonsyndromic craniosynostosis (NSC). This study aims to shed light on how patient age at the time of surgery may affect surgical outcomes and the subsequent need for reoperation. METHODS A retrospective cohort review was conducted for patients with NSC who underwent primary cranial vault remodeling between 1990 and 2013.

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.

[This corrects the article DOI: 10.1186/s13054-016-1208-6.].

Human adipose-derived mesenchymal stem cell spheroids improve recovery in a mouse model of elastase-induced emphysema.

Emphysema, a pathologic component of the chronic obstructive pulmonary disease, causes irreversible destruction of lung. Many researchers have reported that mesenchymal stem cells can regenerate lung tissue after emphysema. We evaluated if spheroid human adipose-derived mesenchymal stem cells (ASCs) showed greater regenerative effects than dissociated ASCs in mice with elastase-induced emphysema.

Percutaneous Sacroiliac Screw Technique.

Remembering that preoperative planning, surgical indications, and fracture reduction are paramount for this procedure, presented here is our technique for performing percutaneous sacroiliac screws, both transiliac-transsacral and sacral style. A combination of video, still pictures, and fluoroscopy images will guide the viewer through the process we routinely use highlighting specific details. Patient positioning and intraoperative fluoroscopy imaging are critical to a successful procedure.

Election 2016: Voting on Variants.

Genome sequencing studies increasingly identify variants of unknown significance in provocative genes. Kim and colleagues present a system with which to functionally annotate such variants in a high-throughput, biologically relevant series of assays. Cancer Discov; 6(7); 694-6.

A Drosophila model of Huntington disease-like 2 exhibits nuclear toxicity and distinct pathogenic mechanisms from Huntington disease.

Huntington disease-like 2 (HDL2) and Huntington disease (HD) are adult-onset neurodegenerative diseases characterized by movement disorders, psychiatric disturbances and cognitive decline. Brain tissue from HD and HDL2 patients shows degeneration of the striatum and ubiquitinated inclusions immunoreactive for polyglutamine (polyQ) antibodies. Despite these similarities, the diseases result from different genetic mutations.

Shank Modulates Postsynaptic Wnt Signaling to Regulate Synaptic Development.

Unlabelled: Prosap/Shank scaffolding proteins regulate the formation, organization, and plasticity of excitatory synapses. Mutations in SHANK family genes are implicated in autism spectrum disorder and other neuropsychiatric conditions. However, the molecular mechanisms underlying Shank function are not fully understood, and no study to date has examined the consequences of complete loss of all Shank proteins in vivo Here we characterize the single Drosophila Prosap/Shank family homolog.

Generation and Improvement of Effector Function of a Novel Broadly Reactive and Protective Monoclonal Antibody against Pneumococcal Surface Protein A of Streptococcus pneumoniae.

A proof-of-concept study evaluating the potential of Streptococcus pneumoniae Pneumococcal Surface Protein A (PspA) as a passive immunization target was conducted. We describe the generation and isolation of several broadly reactive mouse anti-PspA monoclonal antibodies (mAbs). MAb 140H1 displayed (i) 98% strain coverage, (ii) activity in complement deposition and opsonophagocytic killing (OPK) assays, which are thought to predict the in vivo efficacy of anti-pneumococcal mAbs, (iii) efficacy in mouse sepsis models both alone and in combination with standard-of-care antibiotics, and (iv) therapeutic activity in a mouse pneumonia model.

Sphingosine 1-Phosphate-Induced ICAM-1 Expression via NADPH Oxidase/ROS-Dependent NF-κB Cascade on Human Pulmonary Alveolar Epithelial Cells.

The intercellular adhesion molecule-1 (ICAM-1) expression is frequently correlated with the lung inflammation. In lung injury, sphingosine-1-phosphate (S1P, bioactive sphingolipid metabolite), participate gene regulation of adhesion molecule in inflammation progression and aggravate tissue damage. To investigate the transduction mechanisms of the S1P in pulmonary epithelium, we demonstrated that exposure of HPAEpiCs (human pulmonary alveolar epithelial cells) to S1P significantly induces ICAM-1 expression leading to increase monocyte adhesion on the surface of HPAEpiCs.

A proof-of-concept, randomized controlled trial of DAR-0100A, a dopamine-1 receptor agonist, for cognitive enhancement in schizophrenia.

Background: Evidence from preclinical and human studies indicates the presence of reduced dopamine-1 receptor (D1R) signaling in the cortex, where D1Rs predominate, in patients with schizophrenia (SCZ), which may contribute to their cognitive deficits. Furthermore, studies in nonhuman primates (NHP) have suggested that intermittent administration of low doses of D1R agonists produce long-lasting reversals in cognitive deficits. The purpose of this trial was to test whether a similar design, involving subacute intermittent administration of low doses of a full, selective agonist at D1Rs, DAR-0100A, would improve cognitive deficits in SCZ.

Effects of folylpolyglutamate synthase modulation on global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells.

Folylpolyglutamate synthase (FPGS) plays a critical role in intracellular folate homeostasis. FPGS-induced polyglutamylated folates are better substrates for several enzymes involved in the generation of S-adenosylmethionine, the primary methyl group donor, and hence FPGS modulation may affect DNA methylation. DNA methylation is an important epigenetic determinant in gene expression and aberrant DNA methylation is mechanistically linked cancer development.

Lipopolysaccharide induces ICAM-1 expression via a c-Src/NADPH oxidase/ROS-dependent NF-κB pathway in human pulmonary alveolar epithelial cells.

Upregulation of intercellular adhesion molecule-1 (ICAM-1) is frequently implicated in lung inflammation. Lipopolysaccharide (LPS) has been shown to play a key role in inflammation via adhesion molecule induction and then causes lung injury. However, the mechanisms underlying LPS-induced ICAM-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unclear.

Lateral orbitotomy for a maxillary nerve schwannoma: case report.

Authors of this report describe a Fukushima Type D(b) or Kawase Type ME2 trigeminal schwannoma involving the right maxillary division in a 59-year-old woman who presented with intermittent right-sided facial numbness and pain. This tumor was successfully resected via a right lateral orbitotomy without the need for craniotomy. This novel approach to a lesion of this type has not yet been described in the scientific literature.

Multiple Hereditary Infundibulocystic Basal Cell Carcinoma Syndrome Associated With a Germline SUFU Mutation.

Importance: Multiple hereditary infundibulocystic basal cell carcinoma syndrome (MHIBCC) is a rare genodermatosis in which numerous indolent, well-differentiated basal cell carcinomas develop primarily on the face and genitals, without other features characteristic of basal cell nevus syndrome. The cause is unknown. The purpose of the study was to identify a genetic basis for the syndrome and a mechanism by which the associated tumors develop.

Phosphorylation of Complexin by PKA Regulates Activity-Dependent Spontaneous Neurotransmitter Release and Structural Synaptic Plasticity.

Synaptic plasticity is a fundamental feature of the nervous system that allows adaptation to changing behavioral environments. Most studies of synaptic plasticity have examined the regulated trafficking of postsynaptic glutamate receptors that generates alterations in synaptic transmission. Whether and how changes in the presynaptic release machinery contribute to neuronal plasticity is less clear.

Measurement of Femoral Vein Diameter by Ultrasound to Estimate Central Venous Pressure.

Rationale: Central venous pressure (CVP) can be estimated by ultrasound of the inferior vena cava (IVC), but imaging the IVC is sometimes challenging. The femoral vein is easily imaged by ultrasound and might therefore provide an alternate target for estimating CVP.

Objectives: To assess femoral vein diameter (FVD) measured by ultrasound imaging for estimating CVP.

Encapsulating peritoneal sclerosis: surgery, sustained drug therapy and treatment of recurrence at 1 year.

A 74-year-old woman with end-stage renal disease presented with clinical symptoms of encapsulating peritoneal sclerosis 2 years after switching from peritoneal dialysis to haemodialysis. Imaging revealed a large cystic structure in her abdomen and her final diagnosis was made by exploratory laparotomy. A 10 cm×15 cm fibrous rind was excised from the peritoneum and the patient was subsequently started on tamoxifen 20 mg daily and prednisone 20 mg daily.

Racial disparities during admission to an academic psychiatric hospital in a large urban area.

Multiple studies confirm that African Americans are less likely than non-Hispanic whites to receive needed mental health services. Research has consistently shown that African Americans are under-represented in outpatient mental health treatment settings and are over-represented in inpatient psychiatric settings. Further, African Americans are more likely to receive a diagnosis of schizophrenia and are less likely receive an affective disorder diagnosis during inpatient psychiatric hospitalization compared to non-Hispanic white patients, pointing to a need for examining factors contributing to mental health disparities.

Exome sequencing of desmoplastic melanoma identifies recurrent NFKBIE promoter mutations and diverse activating mutations in the MAPK pathway.

Desmoplastic melanoma is an uncommon variant of melanoma with sarcomatous histology, distinct clinical behavior and unknown pathogenesis. We performed low-coverage genome and high-coverage exome sequencing of 20 desmoplastic melanomas, followed by targeted sequencing of 293 genes in a validation cohort of 42 cases. A high mutation burden (median of 62 mutations/Mb) ranked desmoplastic melanoma among the most highly mutated cancers.

Phylogenetic analyses of melanoma reveal complex patterns of metastatic dissemination.

Melanoma is difficult to treat once it becomes metastatic. However, the precise ancestral relationship between primary tumors and their metastases is not well understood. We performed whole-exome sequencing of primary melanomas and multiple matched metastases from eight patients to elucidate their phylogenetic relationships.

In vivo measurement of GABA transmission in healthy subjects and schizophrenia patients.

Objective: Postmortem studies in schizophrenia reveal alterations in gene products that regulate the release and extracellular persistence of GABA. However, results of in vivo studies of schizophrenia measuring total tissue GABA with magnetic resonance spectroscopy (MRS) have been inconsistent. Neither the postmortem nor the MRS studies directly address the physiological properties of GABA neurotransmission.