Genetic variation in the mouse model of Niemann Pick C1 affects female, as well as male, adiposity, and hepatic bile transporters but has indeterminate effects on caveolae.

We have previously shown that male Npc1 heterozygous mice (Npc1(+/-)), as compared to homozygous wild-type mice (Npc1(+/+)), both maintained on the "lean" BALB/cJ genetic background, become obese on a high fat but not on a low fat diet. We have now extended this result for female heterozygous mice. When fed high-fat diet, the Npc1(+/-) white adipose weight is also increased in females, therefore following the same trend as males.

Deficiency of the cytoskeletal protein SPECC1L leads to oblique facial clefting.

Genetic mutations responsible for oblique facial clefts (ObFC), a unique class of facial malformations, are largely unknown. We show that loss-of-function mutations in SPECC1L are pathogenic for this human developmental disorder and that SPECC1L is a critical organizer of vertebrate facial morphogenesis. During murine embryogenesis, Specc1l is expressed in cell populations of the developing facial primordial, which proliferate and fuse to form the face.

The relations of daily task accomplishment satisfaction with changes in affect: a multilevel study in nurses.

Focusing on a sample of nurses, this investigation examined the relationships of daily task accomplishment satisfaction (for direct and indirect care tasks) with changes in positive and negative affect from preshift to postshift. Not accomplishing tasks to one's satisfaction was conceptualized as a daily workplace stressor that should increase daily negative affect and decrease daily positive affect from preshift to postshift. Further, because of the greater centrality of direct care nursing tasks to nursing work role identities (relative to indirect care tasks), we expected that task accomplishment satisfaction (or lack thereof) for these tasks would have stronger effects on changes in affect than would task accomplishment satisfaction for indirect care tasks.

How molecular motors are arranged on a cargo is important for vesicular transport.

The spatial organization of the cell depends upon intracellular trafficking of cargos hauled along microtubules and actin filaments by the molecular motor proteins kinesin, dynein, and myosin. Although much is known about how single motors function, there is significant evidence that cargos in vivo are carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself--and motor organization on the cargo--affects transport has not been considered.

The relative importance of waterborne and dietborne arsenic exposure on survival and growth of juvenile rainbow trout.

Previous work demonstrated reduced growth of rainbow trout receiving diets containing environmentally relevant concentrations of arsenic, but did not address the relative and combined potency of waterborne and dietborne exposures. In the current study, juvenile rainbow trout were exposed for 28d to a range of arsenic concentrations in water and in a live oligochaete diet, separately and in combination. In clean water, fish fed worms previously exposed to arsenate at 4 or 8mg As/L showed pronounced reductions in growth, but fish exposed to these same water concentrations and a clean diet experienced less or no effect.

Quality of life among testicular cancer survivors: a case-control study in the United States.

Introduction: Evidence from previous studies has suggested there may be physical and mental changes in health among testicular cancer survivors. No studies have been conducted in the United States, however.

Methods: Study participants were initially enrolled in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study between 2002 and 2005.

Neurological assessments after treatment with the antimalarial β-arteether in neonatal and adult rats.

The World Health Organization currently recommends combinatorial treatment including artemisinins as first-line therapy against drug-resistant Plasmodium falciparum malaria. Although highly efficacious, artemisinin and its derivatives, including β-arteether (βAE), are associated with ototoxicity, tremors, and other autonomic and motor impairments in the clinic. Similar neurological symptoms, as well as brainstem lesions, have been observed in adult laboratory species (mice, rats, dogs, and non human primates) following acute treatment with βAE; however, few long-term, nonclinical studies have been conducted.

Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1⁻/⁻ mice.

Lung dysfunction is an important part of the pathology of the neurodegenerative disorder, Niemann-Pick C1 (NPC1). We have studied the pulmonary disease in the Npc1(NIH/NIH) mouse model. On histology, we find large numbers of alveolar foamy macrophages but no alveolar proteinosis.

WITHDRAWN. Neurological assessments after treatment with the antimalarial β-arteether in neonatal and adult rats.

The World Health Organization currently recommends combinatorial treatment including artemisinins as first-line therapy against drug-resistant Plasmodium falciparum malaria. Although highly efficacious, artemisinin and its derivatives, including β-arteether (βAE), are associated with ototoxicity, tremors, and other autonomic and motor impairments in the clinic. Similar neurological symptoms, as well as brainstem lesions, have been observed in adult laboratory species (mice, rats, dogs, and non human primates) following acute treatment with βAE; however, few long-term, nonclinical studies have been conducted.

A Case of Agonadism, Skeletal Malformations, Bicuspid Aortic Valve, and Delayed Development with a 16p13.3 Duplication Including GNG13 and SOX8 Upstream Enhancers: Are Either, Both or Neither Involved in the Phenotype?

We report a female patient with delayed growth and development, skeletal and cardiac defects, and a male XY sex chromosome complement with early failure of gonad development. SRY sequencing was normal. Array comparative genome hybridization (CGH) analysis revealed a gain in copy number in the subtelomeric region of the short arm of chromosome 16, encompassing a region of approximately 560 kb in size including GNG13 which may be involved in ovarian development.

Identification of a novel C16orf57 mutation in Athabaskan patients with Poikiloderma with Neutropenia.

Poikiloderma with Neutropenia (PN), Clericuzio-Type (OMIM #604173) is characterized by poikiloderma, chronic neutropenia, recurrent sinopulmonary infections, bronchiectasis, and nail dystrophy. First described by Clericuzio in 1991 in 14 patients of Navajo descent, it has since also been described in non-Navajo patients. C16orf57 has recently been identified as a causative gene in PN.

Emotional display rules as work unit norms: a multilevel analysis of emotional labor among nurses.

Emotional labor theory has conceptualized emotional display rules as shared norms governing the expression of emotions at work. Using a sample of registered nurses working in different units of a hospital system, we provided the first empirical evidence that display rules can be represented as shared, unit-level beliefs. Additionally, controlling for the influence of dispositional affectivity, individual-level display rule perceptions, and emotion regulation, we found that unit-level display rules are associated with individual-level job satisfaction.

Genetic contributions to the association between adult height and testicular germ cell tumors.

Background: Previously, we have shown that increasing adult height is associated with increased risk of testicular germ-cell tumor (TGCT). Recently, a number of single nucleotide polymorphisms (SNPs) have been found to be related to height. We examined whether these SNPs were associated with TGCT and whether they explained the relationship between height and TGCT.

A humanized monoclonal antibody targeting the β7 integrin selectively blocks intestinal homing of T lymphocytes.

Background And Purpose: rhuMAb Beta7 is a humanized anti-human β7 monoclonal antibody currently in phase I in inflammatory bowel disease. rhuMAb Beta7 binds the β7 subunit of the integrins α4β7 and αEβ7, blocking interaction with their ligands. These integrins play key roles in immune cell homing to and retention in mucosal sites, and are associated with chronic inflammatory diseases of the gastrointestinal tract.

Application of the tissue residue approach in ecological risk assessment.

The objective of this work is to present a critical review of the application of the tissue residue approach (TRA) in ecological risk and/or impact assessment (ERA) of chemical stressors and environmental criteria development. A secondary goal is to develop a framework for integrating the TRA into ecological assessments along with traditional, exposure concentration-based assessment approaches. Although widely recognized for its toxicological appeal, the utility of the TRA in specific applications will depend on numerous factors, such as chemical properties, exposure characteristics, assessment type, availability of tissue residue-response data, and ability to quantify chemical exposure.

Interactions of Npc1 and amyloid accumulation/deposition in the APP/PS1 mouse model of Alzheimer's.

Although Niemann-Pick C1 disease has frequently been called "juvenile Alzheimer's", the effects of introducing Npc1 mutations into a mouse model of Alzheimer's have not previously been performed. We have crossed Npc1 (+/-) mice with APP/PS1 "Alzheimer's" mice and studied Aβ42 accumulation and amyloid plaque formation. Mice heterozygous for Npc1 and positive for the APP and PS1 transgenes accumulated Aβ42 more rapidly than the APP/PS1 controls and this correlated, as expected, with the area of amyloid plaques.

A second family with dominantly inherited isolated cleft palate.

Although a number of families have been reported with apparently dominantly inherited cleft lip with or without cleft palate, there is only 1 previous report of dominantly inherited isolated cleft palate. We report a 4-generation family with dominantly inherited clefts of the soft and hard palates, affecting both sexes and showing male-to-male transmission. We believe this is only the second such family and discuss possible reasons for the rarity of such pedigrees.

Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment.

Ecological risk assessors face increasing demands to assess more chemicals, with greater speed and accuracy, and to do so using fewer resources and experimental animals. New approaches in biological and computational sciences may be able to generate mechanistic information that could help in meeting these challenges. However, to use mechanistic data to support chemical assessments, there is a need for effective translation of this information into endpoints meaningful to ecological risk-effects on survival, development, and reproduction in individual organisms and, by extension, impacts on populations.

Genes, environment, and orofacial clefting: N-acetyltransferase and folic acid.

Nonsyndromic orofacial clefting has been the subject of intense studies, both genetic and epidemiological. The findings have frequently been controversial because of lack of reproducibility. Mouse models provide the potential both for genetic and environmental uniformity.

Epidural cortical stimulation as adjunctive treatment for non-fluent aphasia: preliminary findings.

Background And Purpose: This study evaluated the safety and feasibility of targeted epidural cortical stimulation delivered concurrently with intensive speech-language therapy for treatment of chronic non-fluent aphasia.

Methods: Eight stroke survivors with non-fluent aphasia received intensive behavioural therapy for 3 h daily for 6 weeks using a combination of articulation drills, oral reading and conversational practice. Four of these participants (investigational participants) also underwent functional MRI guided surgical implantation of an epidural stimulation device which was activated only during therapy sessions.

EUS compared with endoscopy plus transabdominal US in the initial diagnostic evaluation of patients with upper abdominal pain.

Background: Primary upper endoscopy (EGD) and transabdominal US (TUS) are often performed in patients with upper abdominal pain.

Objective: Primary: Determine whether the combination of EGD and EUS was equivalent to EGD plus TUS in the diagnostic evaluation of upper abdominal pain. Secondary: Compare EUS versus TUS in detecting abdominal lesions, and compare EGD by using an oblique-viewing echoendoscope versus the standard, forward-viewing endoscope in detecting mucosal lesions.

Fertility among testicular cancer survivors: a case-control study in the U.S.

Introduction: Testicular germ cell tumors (TGCT) disproportionately affect men between the ages of 15 and 49 years, when reproduction is typical. Although TGCT treatment directly affects gonadal tissues, it remains unclear whether there are long-term effects on fertility.

Methods: To examine post-TGCT treatment fertility, study participants in a previously conducted case-control study were contacted.

Influenza and respiratory disease surveillance: the US military's global laboratory-based network.

The US Department of Defense influenza surveillance system now spans nearly 500 sites in 75 countries, including active duty US military and dependent populations as well as host-country civilian and military personnel. This system represents a major part of the US Government's contributions to the World Health Organization's Global Influenza Surveillance Network and addresses Presidential Directive NSTC-7 to expand global surveillance, training, research and response to emerging infectious disease threats. Since 2006, the system has expanded significantly in response to rising pandemic influenza concerns.

Somatic gene mutation and human disease other than cancer: an update.

Somatic mosaicism is well known in disorders where the manifestations are readily seen, e.g. the skin in neurofibromatosis I.