Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States.

Importance: Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100,000 births.

Functional amyloid: widespread in Nature, diverse in purpose.

Amyloids are insoluble fibrillar protein deposits with an underlying cross-β structure initially discovered in the context of human diseases. However, it is now clear that the same fibrillar structure is used by many organisms, from bacteria to humans, in order to achieve a diverse range of biological functions. These functions include structure and protection (e.

DNA modification study of major depressive disorder: beyond locus-by-locus comparisons.

Background: Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined.

Methods: We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.

Engineering specificity changes on a RanBP2 zinc finger that binds single-stranded RNA.

The realization that gene transcription is much more pervasive than previously thought and that many diverse RNA species exist in simple as well as complex organisms has triggered efforts to develop functionalized RNA-binding proteins (RBPs) that have the ability to probe and manipulate RNA function. Previously, we showed that the RanBP2-type zinc finger (ZF) domain is a good candidate for an addressable single-stranded-RNA (ssRNA) binding domain that can recognize ssRNA in a modular and specific manner. In the present study, we successfully engineered a sequence specificity change onto this ZF scaffold by using a combinatorial approach based on phage display.

Solid-state NMR structure determination from diagonal-compensated, sparsely nonuniform-sampled 4D proton-proton restraints.

We report acquisition of diagonal-compensated protein structural restraints from four-dimensional solid-state NMR spectra on extensively deuterated and (1)H back-exchanged proteins. To achieve this, we use homonuclear (1)H-(1)H correlations with diagonal suppression and nonuniform sampling (NUS). Suppression of the diagonal allows the accurate identification of cross-peaks which are otherwise obscured by the strong autocorrelation or whose intensity is biased due to partial overlap with the diagonal.

Alteration of basilar artery rho-kinase and soluble guanylyl cyclase protein expression in a rat model of cerebral vasospasm following subarachnoid hemorrhage.

Background And Purpose: The vasoconstrictor endothelin-1 (ET-1) has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). Previous results showed that CGS 26303, an endothelin converting enzyme (ECE) inhibitor, effectively prevented and reversed arterial narrowing in animal models of SAH. In the present study, we assessed the effect of CGS 26303 on neurological deficits in SAH rats.

Characterization of pituitary tumor transforming gene in meningiomas.

Background: Pituitary tumor transforming gene (PTTG) is an oncogene and has been detected in several tumors of unrelated histological origin. However, its role in meningiomas is unknown so far. We aim to investigate PTTG expression in intracranial meningiomas, and clarify the relationship between PTTG and the histopathological types of tumors.

Differential hypermethylation of death-associated protein kinase promoter in central neurocytoma and oligodendroglioma.

Background: Central neurocytoma and oligodendroglioma are rare tumors of the central nervous system. However, diagnosis between these two types of tumors is challenging due to their many cytological and histological similarities. Death-associated protein kinase (DAPK) is a calcium/calmodulin-regulated serine/threonine protein kinase involved in many apoptosis pathways, and repressed expression of DAPK by promoter hypermethylation has been found in a variety of human cancers.

Predictors of memory and processing speed dysfunctions after traumatic brain injury.

Background: The aims of this study were to evaluate the predictive value of admission Glasgow Coma Scale (GCS) scores, duration of unconsciousness, neurosurgical intervention, and countercoup lesion on the impairment of memory and processing speed functions six months after a traumatic brain injury (TBI) based on a structural equation modeling.

Methods: Thirty TBI patients recruited from Neurosurgical Department at the Kaohsiung Medical University Hospital were administered the Wechsler Memory Scale-III (WMS-III) and the Wechsler Adult Intelligence Scale-III processing speed index to evaluate the memory and processing speed functions.

Results: The study showed that GCS scores accounted for 40% of the variance in memory/processing speed.

Autologous fat grafting alleviates burn-induced neuropathic pain in rats.

Background: The management of neuropathic pain after burn injury is a critical clinical issue. Autologous fat grafting has been shown to alleviate neuropathic pain in certain cases, but has not been shown to alleviate the pain associated with burn-induced scars. The authors assessed the effectiveness of autologous fat grafting for the management of pain in burn-induced scars.

Serial serum leukocyte apoptosis levels as predictors of outcome in acute traumatic brain injury.

Background: Apoptosis associates with secondary brain injury after traumatic brain injury (TBI). This study posits that serum leukocyte apoptosis levels in acute TBI are predictive of outcome.

Methods: Two hundred and twenty-nine blood samples from 88 patients after acute TBI were obtained on admission and on Days 4 and 7.

Surgical strategies and outcomes of spinal ependymomas of different lengths: analysis of 210 patients: clinical article.

Object: The aim of this study was to investigate the surgical strategies and outcomes for spinal ependymomas of different lengths.

Methods: The authors used data from 210 patients with spinal ependymomas (WHO Grades II and III) in this 10-year retrospective study (January 1999 to December 2008), dividing them into 3 different groups according to length (spinal ependymomas < 5 cm, 5-10 cm, and > 10 cm). All patients underwent tumor resection.

Spontaneous cyclization of polypeptides with a penultimate Asp, Asn or isoAsp at the N-terminus and implications for cleavage by aminopeptidase.

A cyclic product that forms spontaneously from peptides that contain a penultimate Asp, Asn or isoAsp residue at the N-terminus has been characterized. This 2,5-diketopiperazine derivative forms under physiological conditions and is stable, showing little degradation even following heating at 60 °C. A mechanism for its formation from Asn and Asp peptides is proposed that involves a succinimide or isoaspartate intermediate.

Magnesium lithospermate B, an active extract of Salvia miltiorrhiza, mediates sGC/cGMP/PKG translocation in experimental vasospasm.

Background: Soluble guanylyl cyclases (sGCs) and Ras homolog gene family, member A (rhoA)/Ras homolog gene family kinase(rho-kinase) plays a role in vascular smooth muscle relaxation in subarachnoid hemorrhage (SAH). It is of interest to examine the effect of MLB on rhoA/ROCK and sGC/cGMP/PKG expression.

Methods: A rodent SAH model was employed.

Coronary artery plaque volume and obesity in patients with diabetes: the factor-64 study.

Purpose: To determine the relationship between coronary plaque detected with coronary computed tomographic (CT) angiography and clinical parameters and cardiovascular risk factors in asymptomatic patients with diabetes.

Materials And Methods: All patients signed institutional review board-approved informed consent forms before enrollment. Two hundred twenty-four asymptomatic diabetic patients (121 men; mean patient age, 61.

The use of regional citrate anticoagulation continuous venovenous hemofiltration in extracorporeal membrane oxygenation.

Patients on extracorporeal membrane oxygenation (ECMO) frequently requires continuous renal replacement therapy (CRRT). Additional anticoagulation for the CRRT circuit is usually not employed, but this may increases the risk of clot embolization, which shortens oxygenator lifespan and increases patient's risk. We report our experience on the use of regional citrate anticoagulation continuous venovenous hemofiltration (RCA-CVVH) connected to an ECMO circuit, which could be useful during low heparin or heparin-free ECMO situations.

(1)H, (13)C and (15)N resonance assignments of the RodA hydrophobin from the opportunistic pathogen Aspergillus fumigatus.

Hydrophobins are fungal proteins characterised by their amphipathic properties and an idiosyncratic pattern of eight cysteine residues involved in four disulphide bridges. The soluble form of these proteins spontaneously self-assembles at hydrophobic/hydrophilic interfaces to form an amphipathic monolayer. The RodA hydrophobin of the opportunistic pathogen Aspergillus fumigatus forms an amyloid layer with a rodlet morphology that covers the surface of fungal spores.

Disk-shaped amperometric enzymatic biosensor for in vivo detection of D-serine.

At the synapse, D-serine is an endogenous co-agonist for the N-methyl-D-aspartate receptor (NMDAR). It plays an important role in synaptic transmission and plasticity and has also been linked to several pathological diseases such as schizophrenia and Huntington's. The quantification of local changes in D-serine concentration is essential to further understanding these processes.

Adenoviral-mediated glial cell line-derived neurotrophic factor gene transfer has a protective effect on sciatic nerve following constriction-induced spinal cord injury.

Neuropathic pain due to peripheral nerve injury may be associated with abnormal central nerve activity. Glial cell-line-derived neurotrophic factor (GDNF) can help attenuate neuropathic pain in different animal models of nerve injury. However, whether GDNF can ameliorate neuropathic pain in the spinal cord dorsal horn (SCDH) in constriction-induced peripheral nerve injury remains unknown.

Association of Aurora A and gamma-tubulin expression in astrocytomas and patient survival.

Objectives: The purpose was to evaluate the association of Aurora A and gamma-tubulin expression with disease characteristics and survival in patients with astrocytoma.

Methods: This is a retrospective study of patients who had surgical specimens that were pathologically diagnosed as astrocytoma. The expression level of Aurora A and gamma-tubulin in tumor tissue was evaluated by immunohistochemistry.

The relationship between BCMO1 gene variants and macular pigment optical density in persons with and without age-related macular degeneration.

Background: Recent evidence indicates that gene variants related to carotenoid metabolism play a role in the uptake of macular pigments lutein (L) and zeaxanthin (Z). Moreover, these pigments are proposed to reduce the risk for advanced age-related macular degeneration (AMD). This study provides the initial examination of the relationship between the gene variants related to carotenoid metabolism, macular pigment optical density (MPOD) and their combined expression in healthy humans and patients with AMD.

Clinical whole-exome sequencing: are we there yet?

Background: Clinical laboratories began offering whole-exome sequencing in 2011 at a cost between $4,500 and $9,000. Reported detection rates for deleterious mutations range from 25 to 50%. Based on the experience of our clinical genetics service, actual success rates may be lower than estimated rates.

Serial plasma deoxyribonucleic acid levels as predictors of outcome in acute traumatic brain injury.

Increased plasma deoxyribonucleic acid (DNA) levels may be associated with disease severity after acute traumatic brain injury (TBI). This study posits that increased plasma DNA levels in acute TBI are predictive of outcome. Both serial plasma nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) levels were examined in 88 consecutive patients with acute TBI and 66 control subjects.