Use of Media Technologies by Native American Teens and Young Adults in the Pacific Northwest: Exploring Their Utility for Designing Culturally Appropriate Technology-Based Health Interventions

American Indian and Alaska Native (AI/AN) youth are disproportionally burdened by many common adolescent health issues, including drug and alcohol use, injury and violence, sexually transmitted infections, and teen pregnancy. Media technologies, including the Internet, cell phones, and video games, offer new avenues for reaching adolescents on a wide range of sensitive health topics. While several studies have informed the development of technology-based interventions targeting mainstream youth, no such data have been reported for AI/AN youth. To fill this gap, this study quantified media technology use among 405 AI/AN youth (13-21?years old) living in tribes and urban communities in the Pacific Northwest, and identified patterns in their health information-seeking practices and preferences. Overall, technology use was exceptionally common among survey respondents, mirroring or exceeding national rates. High rates of online health information seeking were also reported: Over 75% of AI/AN youth reported searching online for health information. These data are now being used by the Northwest Portland Area Indian Health Board and NW tribes to design culturally-appropriate, technology-based health interventions targeting AI/AN youth.     

Nonablative neonatal bone marrow transplantation rapidly reverses severe murine osteopetrosis despite low‐level engraftment and lack of selective expansion of the osteoclastic lineage

Infantile malignant osteopetrosis (IMO) is caused by lack of functional osteoclasts leading to skeletal abnormalities, blindness owing to compression of the optic nerves, bone marrow (BM) failure, and early death. In most patients, TCIRG1, a proton pump subunit essential for bone resorption, is mutated. oc/oc mice represent a model for IMO owing to a deletion in Tcirg1 and die around 4 weeks of age. To determine if hematopoietic stem cell transplantation without prior conditioning can reverse osteopetrosis, neonatal mice were transplanted intravenously with lineage‐depleted BM cells. More than 85% of oc/oc mice transplanted with 5 × 10⁶ cells survived long term with an engraftment of 3% to 5% in peripheral blood (PB). At 3 weeks, engraftment in the BM was 1% to 2%, but the cellularity had increased 60‐fold compared with untreated oc/oc mice, and RANKL and macrophage colony‐stimulating factor (M‐CSF) expression in the BM was normalized. Histopathology and micro–computed tomography revealed almost complete reversal of osteopetrosis after 4 weeks. In vitro studies showed that bone resorption by osteoclasts from transplanted oc/oc mice was 14% of transplanted controls, and immunofluorescence microscopy revealed that resorption was mainly associated with osteoclasts of donor origin. Lineage analysis of BM, PB, and spleen did not provide any evidence for selective recruitment of cells to the osteoclastic lineage. The vision also was preserved in transplanted oc/oc mice, as determined by a visual tracking drum test. In summary, nonablative neonatal transplantation leading to engraftment of only a small fraction of normal cells rapidly reverses severe osteopetrosis in the oc/oc mouse model. © 2010 American Society for Bone and Mineral Research.     

Insulin requirements in the intensive care unit in response to infection

Infectious complications in the intensive care unit (ICU) are classically identified when an elevated temperature triggers obtaining cultures. Elevated temperature, however, is a nonspecific marker of infection and may occur well into the course of the infection. The goal of this study was to evaluate whether escalating insulin demands may serve as an earlier marker for infection. A retrospective review of a prospective database from a trauma ICU over a 6-month period was done for all patients who developed infection while in the ICU. All patients in the ICU are placed at admission on an intensive insulin protocol with target blood glucose levels between 80 and 110 mg/dL. Data were collected on infection, insulin needs, blood glucose levels, temperature, white blood cell count, and antibiotic use. Twenty-four infections were identified, with 16 pneumonias, four bloodstream infections, and four urinary tract infections. Twelve of the 24 patients had increasing insulin needs in the 3 days preceding their infection diagnosis, with nine of the 12 requiring continued escalation of insulin needs from preinfection Day 3 to 2 to 1 (D3, D2, D1). In five of the 12 patients, the escalation of insulin dose preceded the elevated temperature, and in three of the 12 patients, the escalation preceded elevation of the white blood cell count above 12. For all 24 patients, the average insulin dose increased steadily, from 1.8 U/hr on D3 preinfection to 2.5 U/hr D2 and 3.1 U/hr D1. Infection does seem to be preceded by escalating insulin demands in many patients. A prospective study to evaluate the value of increased insulin demand as a marker for developing infection is warranted.     

Dalcetrapib: no off-target toxicity on blood pressure or on genes related to the renin-angiotensin-aldosterone system in rats

Background and purpose:

The association between torcetrapib and its off-target effects on blood pressure suggested a possible class-specific effect. The effects of dalcetrapib (RO4607381/JTT-705) and torcetrapib on haemodynamics and the renin-angiotensin-aldosterone system (RAAS) were therefore assessed in a rat model.

Experimental approach:

Arterial pressure (AP) and heart rate were measured by telemetry in normotensive and spontaneously hypertensive rats (SHR) receiving torcetrapib 10, 40 or 80 mg·kg⁻¹·day⁻¹; dalcetrapib 100, 300 or 500 mg⁻¹·kg·day⁻¹; or vehicle (placebo) for 5 days. Expression of RAAS genes in adrenal gland, kidney, aorta and lung from normotensive rats following 5 days'' treatment with torcetrapib 40 mg·kg⁻¹·day⁻¹, dalcetrapib 500 mg·kg⁻¹·day⁻¹ or vehicle was measured by quantitative polymerase chain reaction.

Key results:

Torcetrapib transiently increased mean AP in normotensive rats (+3.7 ± 0.1 mmHg), whereas treatment in SHR resulted in a dose-dependent and sustained increase [+6.5 ± 0.6 mmHg with 40 mg·kg⁻¹·day⁻¹ at day 1 (P < 0.05 versus placebo)], which lasted over the treatment period. No changes in AP or heart rate were observed with dalcetrapib. Torcetrapib, but not dalcetrapib, increased RAAS-related mRNAs in adrenal glands and aortas.

Conclusions and implications:

In contrast to torcetrapib, dalcetrapib did not increase blood pressure or RAAS-related gene expression in rats, suggesting that the off-target effects of torcetrapib are not a common feature of all compounds acting on cholesteryl ester transfer protein.     

聚乙二醇干扰素α-2b或α-2a与利马韦林联合治疗丙型肝炎疗效比较

背景及目的：丙型肝炎的治疗指南推荐聚乙二醇干扰素α-2b或α-2a联合利巴韦林治疗.但是,这两种方案并没有进行充分地比较,本研究通过临床观察对其疗效进行分析探讨.     

BRAF Duplications and MAPK Pathway Activation Are Frequent in Gliomas of the Optic Nerve Proper

ABSTRACT: Optic pathway gliomas represent a specific subtype of astrocytoma with unique clinicopathologic and biologic properties, but studies of tumors in the optic nerve proper have been hampered by limited tissue availability. We analyzed optic nerve gliomas of 59 patients (median age, 9 years; range, 3 months-66 years; 33 female, 26 male) using formalin-fixed paraffin-embedded material in tissue microarrays. Seven patients had the clinical diagnosis of neurofibromatosis type 1 (NF1). Fluorescence in situ hybridization studies were performed for BRAF, PTEN, CDKN2A (p16), and NF1. Immunohistochemistry was performed for glial fibrillary acidic protein, phospho-ERK, and mutant IDH1 protein. The BRAF duplication was present in 11 (73%) of 15 evaluable tumors, including 1 NF1 patient (1 of 4 tested; 25%). The single tumor lacking BRAF duplication or NF1 association had histologic features of a ganglioglioma. Conversely, heterozygous PTEN deletions were present in 2 (8%) of 25 evaluable cases, one of which was BRAF duplicated and the other was NF1 associated. CDKN2A and NF1 deletions were absent in all tumors tested. Phospho-ERK immunoreactivity was present in 55 (96%) of 57 tumors and was mostly strong and diffuse (80%). Only 1 case of 53 expressed IDH1. Thus, optic nerve gliomas demonstrated molecular alterations typical of pilocytic astrocytomas, including the universal presence of either BRAF duplication or NF1 association and common mitogen-activated protein kinase pathway activation but very rare mutant IDH1 expression.     

Immune reconstitution inflammatory syndrome of the brain: case illustrations of a challenging entity

Immune reconstitution inflammatory syndrome represents a spectrum of clinicopathologic entities encountered in human immunodeficiency virus-infected patients who have received highly active anti-retroviral therapy. The diagnosis is often challenging, treatment options are limited, and the prognosis is variable. To increase awareness and define the clinicopathologic features, we present our experience with 6 probable cases involving the brain, including 1 autopsy. Clinicopathologic review was supplemented by immunohistochemical analysis. There were 5 men and 1 woman, ranging in age from 34 to 47 (mean, 41; SD, 5.39) years. All patients experienced neurologic deterioration (focal deficits in 5/6) after highly active anti-retroviral therapy. All specimens showed a predominance of CD8+ lymphocytic inflammation. Concurrent CNS infections included human immunodeficiency virus encephalitis, progressive multifocal leukoencephalopathy, cryptococcal meningitis, and syphilis. One patient died, 1 was lost to follow-up, 2 improved, and 2 showed no substantial clinical changes. Subtle and overlapping features may preclude a definitive diagnosis. To capture all suspected cases, it is important to consider the possibility of this entity. In this study, the degree of CD8+ inflammation was more pronounced in the single fatal example, and mast cells were not identified in the infiltrates. Although nonspecific, imaging findings may offer clues to early diagnosis.     

Immunohistochemical Expression Pattern of Theragnostic Targets SSTR2 and PSMA in Endolymphatic Sac Tumors: A Single Institution Case Series

BackgroundEndolymphatic sac tumors are rare neoplasia characterized by slow growth. However, their clinical impact should not be underestimated, considering their potential for local aggressive behavior and strong association with von Hippel–Lindau syndrome. Therefore, early detection with emerging theragnostic examinations such as ⁶⁸Ga-DOTATATE-PET/CT might improve patient management and reduce morbidity.MethodsWe report the clinicopathological features of seven endolymphatic sac tumors. In this cohort, we performed immunohistochemical analysis of somatostatin receptor 2A (SSTR2A) and prostate specific membrane antigen (PSMA) protein expression patterns; two targets providing rationale for novel imaging modalities such as PSMA- or SSTR-targeted PET.ResultsThe tumor cells of all cases were negative for prostate specific membrane antigen and somatostatin receptor 2A, however immunolabeling was consistently detected in intratumoral endothelial cells of endolymphatic sac tumors for PSMA (7/7 cases, 100%), and for SSTR2A (5/7 cases, 71%).ConclusionsOur results show a high rate of PSMA and SSTR2A expression in the tumor vasculature of endolymphatic sac tumors. PSMA and SSTR2A can be targeted with appropriate radioligands for diagnostic and therapeutic purposes. This finding provides a rationale for prospective clinical studies to test this approach as a sensitive screening tool for patients with suspected endolymphatic sac tumors including an improved management of von Hippel–Lindau syndrome.