Reviewing suicide in Native American communities: situating risk and protective factors within a transactional-ecological framework

The alarming prevalence of suicidal behaviors in Native American communities remains a major concern in the 21st-century United States. Recent reviews have demonstrated that prevention programs and intervention efforts using transactional-ecological models have effectively reduced suicidal behaviors in the American Indian and Alaska Native populations sampled. As a result, this article adopts a transactional-ecological framework for conceptualizing suicidality and identifying points of intervention. Drawing on the most current empirical reports, the epidemiology of Native American suicidal behaviors is reviewed, while situating risk and protective factors within a biopsychosocial framework. Opportunities for intervention are discussed with a focus on the interactions between individuals and their environments, and the antecedent conditions leading to zones of heightened suicide risk.     

Assessing the impact of pollution on the Japaratuba river in Brazil using the Drosophila wing spot test

The Drosophila melanogaster somatic mutation and recombination test (SMART) was used to assess the genotoxicity of surface (S) and bottom (B) water and sediment samples collected from Sites 1 and 2 on the Japaratuba River (Sergipe, Brazil), an area impacted by a petrochemical industrial complex that indirectly discharges treated effluent (produced water) into the river. The genotoxicity tests were performed in standard (ST) cross and high bioactivation (HB) cross flies and were conducted on samples taken in March (dry season) and in July (rainy season) of 2003. Mutant spot frequencies found in treatments with unprocessed water and sediment samples from the test sites were compared with the frequencies observed for similar samples taken from a clean reference site (the Jacarecica River in Sergipe, Brazil) and those of negative (ultrapure water) controls. While samples from the Japaratuba River generally produced greater responses than those from the Jacarecica River, positive responses were detected for both the test and reference site samples. All the water samples collected in March 2003 were genotoxic. In July 2003, the positive responses were restricted to water samples collected from Sites 1 B and 2 S in the ST cross. The genotoxicity of the water samples was due to mitotic recombination, and the samples produced similar genotoxic responses in ST and HB flies. The spot frequencies found in the July water samples were considerably lower than those for the March water samples, suggesting a seasonal effect. The only sediment samples that were genotoxic were from Site 1 (March and July) and from the Jacarecica River (March). The genotoxins in these samples produced both somatic mutation (limited to the Site 1 sample in HB flies) and recombination. The results of this study indicate that samples from both the Japaratuba and Jacarecica Rivers were genotoxic, with the most consistently positive responses detected with Site 1 samples, the site closest to the putative pollution source.     

Further evidence for association of GRK3 to bipolar disorder suggests a second disease mutation

OBJECTIVES: Two genome-wide linkage surveys suggest chromosome 22q12 may contain a susceptibility locus for bipolar disorder (BPD) in the immediate region of the gene G protein receptor kinase-3 (GRK3). We previously published evidence that a single nucleotide polymorphism (SNP) in the promoter region of GRK3, designated P5, was associated with BPD. This SNP, however, was too rare (allele frequency 0.007) to explain the evidence for linkage. METHODS: To identify other SNPs or haplotypes associated with illness, we have now sequenced an additional 28-kb genomic segment of GRK3 and tested an additional 35 SNPs for association with BPD in 181 Caucasian nuclear families. RESULTS: Transmission disequilibrium test analyses identified two closely related disease-associated haplotypes defined by four SNPs located upstream of the promoter region: transmission to nontransmission ratios=54:22 and 20:9, odds ratios=2.50 and 2.36, and P values=0.0009 and 0.05. The best P value remained significant after correction for multiple testing. These two haplotypes were found on an entirely different set of chromosomes from the previously identified SNP P5. They had a combined frequency of approximately 0.10 and, therefore, a much greater population attributable risk for disease than the previously identified P5 haplotype. CONCLUSIONS: These data provide evidence that at least two distinct haplotypes, and possibly two or more different underlying mutations, in GRK3 might be associated with BPD. These new findings add support for the hypothesis that a dysregulation in GRK3 expression alters signaling desensitization and thereby predisposes to the development of BPD.     

Duplication 2p and monosomy 8p in mosaicism: clinical, molecular cytogenetic and molecular markers of a unique case

We report on a female patient, with a de novo mosaicism for a structural rearrangement producing trisomy 2p21-->pter and monosomy 8p21-pter. GTG bands and fluorescence in situ hybridization (FISH) in lymphocytes identified: mos 46,XX,der(8)(8qter-->8p21::p21::2p21-->pter),9qh +[52]/ 46,XX,9qh+[82]. Fibroblasts showed the same cell lines in 15 and 12 cells respectively. DNA profiling with fourteen autosomal STR markers, did not reveal a chimerism status in our patient. She did not present the classical phenotype described for trisomy 2p and for monosomy 8p probably due to approximately 60% of the patient's cells being normal. The abnormality probably arose in a very early stage of development during the first post-fertilization divisions with a non-sister chromatid exchange event between chromosomes 2 and 8 producing three cellular clones: a normal clone, one with trisomy 2p and monosomy 8p and a third with monosomy 2p and trisomy 8p. Only the first two cell lines were found in both lymphocytes and fibroblasts of hypopigmented skin; the third may have been lost or limited to other tissues.     

New technologies applied to ultrasound diagnosis of sports injuries

Introduction  The aim of this study was to compare the ultrasound images of different soft tissue lesions from two different portable sonography devices: a conventional portable sonography device (ultrasound [US]-A, Micromaxx model; Sonosite Inc., Bothell, WA, USA), and a recently marketed compact device (US-B, Logiq e; General Electric Healthcare, Wauwatosa, WI, USA). The US-B device uses the new technologies of tissue harmonic imaging, real-time compound ultrasound, panoramic view, three-dimensional imaging, and virtual convex imaging. Methods  We compared ultrasound images of six different types of soft tissue lesions (muscle contusion, muscle strain, patellar tendinosis, calcifying patellar tendinosis, rupture of the lateral internal ligament of the knee, and deep infrapatellar synovial bursa), from six different subjects. Analysis of images was performed by the same ultrasound specialist. In accordance with the classical criteria for ultrasound studies, the following quantitative indicators and parameters of ultrasound quality were used to evaluate the images: degree of echogenicity, size of the lesion area, aspect, shape, borders, and overall visualization. Results  In muscle lesions due to contusion, not only is the edematous area better visualized with the new system, but definition of hemorrhagic area borders and their content is especially increased. In lesions of the tendons, the new system affords better definition of the borders of the hypoechogenic area of tendinous degeneration and perfect visualization of the extension of the damaged area using a panoramic study. Sonographic study of ligaments with chronic lesions permits visualization of scar areas. Finally, use of the new system with a small synovial bursa shows the content of the bursa and thickness of the walls more clearly. Conclusion  Overall, the quantitative indicators and parameters of image quality performed in this study of common sports lesions demonstrate the improvement in visualization of damaged soft tissues with the new technologies now incorporated into portable sonography devices.     

Protein tyrosine phosphatase 1B is impaired in skeletal muscle of diabetic Psammomys obesus

Protein tyrosine phosphatases (PTPases) have been suggested to modulate the insulin receptor signal transduction pathways. We studied PTPases in Psammomys obesus, an animal model of nutritionally induced insulin resistance. No changes in the protein expression level of src homology PTPase 2 (SHP-2) (muscle, liver) or leukocyte antigen receptor (LAR) (liver) were detected. In contrast, the expression level of PTPase 1B (PTP 1B) in the skeletal muscle, but not in liver, was increased by 83% in the diabetic animals, compared with a diabetes-resistant line. However, PTP 1B-specific activity (activity/protein) significantly decreased (50% to 56%) in skeletal muscle of diabetic animals, compared with both the diabetes-resistant line and diabetes-prone animals. In addition, PTP 1B activity was inversely correlated to serum glucose level (r = -.434, P < .02). These findings suggest that PTP 1B, though overexpressed, is not involved in the susceptibility to insulin resistance in Psammomys obesus and is secondarily attenuated by hyperglycemia or other factors in the diabetic milieu.     

Nutritional Status,Body Surface,and Low Lean Body Mass/Body Mass Index Are Related to Dose Reduction and Severe Gastrointestinal Toxicity Induced by Afatinib in Patients With Non‐Small Cell Lung Cancer

Background.

The main reason for dose reduction of afatinib is gastrointestinal toxicity (GT). In a phase II study, we analyzed anthropometrical, nutritional, and biochemical factors associated with GT induced by afatinib.

Materials and Methods.

Patients diagnosed with non-small cell lung cancer who progressed to prior chemotherapy received 40 mg of afatinib. Malnutrition was determined by Subjective Global Assessment, and lean body mass (LBM) was determined by computed tomography scan analysis using a pre-established Hounsfield unit threshold. Toxicity was obtained during four cycles by Common Terminology Criteria for Adverse Events.

Results.

Eighty-four patients were enrolled. Afatinib was administered as the second, third, and fourth line of treatment in 54.8%, 38.1%, and 7.12% of patients, respectively. Severe diarrhea, mucositis, and overall severe GT were present in 38.9%, 28.8%, and 57.5%, respectively. Of the patients, 50% developed dose-limiting toxicity (DLT). Patients with malnutrition have higher risk for severe GT. Patients with lower LBM and body mass index developed more DLT (71.4% vs. 18.8%).

Conclusion.

Malnutrition is associated with a higher risk of severe GT induced by afatinib. Determination of nutritional status and body composition are helpful in identifying patients at higher risk of severe GT and could allow initiating treatment with lower doses according to tolerance.

Implications for Practice:

Body composition analysis, specifically lean body mass quantification, and nutritional status assessment are significant clinical variables to take into account when assessing oncological patients. This study on patients with non-small cell lung cancer treated with afatinib showed the important impact that malnutrition and low lean body mass have on the risk for developing dose-limiting toxicity and severe gastrointestinal toxicity. Still more research needs to be done to explore dose adjustment according to lean body mass, especially in drugs that are given at fixed doses, such as afatinib. However, this study presents evidence for the clinical oncologist to have a closer follow-up with malnourished patients and even to consider a lower starting dose until therapeutic dose is achieved.     

The Lidcombe Hospital Memory (Cognitive Disorders) Clinic: Review of Clinical Experience

Objective: A retrospective review of clinical experience of the Memory (Cognitive Disorders) Clinic at Lidcombe Hospital. Method: 100 available records of patients seen consecutively in the clinic were reviewed. The following information was extracted: demographics, clinical diagnosis, investigations and results. Follow-up contact was made by phone where possible and the patients' status established in terms of mortality, domicile, dependency, use of basic community services and any significant deterioration in function. Results: 11% of patients were found not to be suffering from dementia and most of these were suffering from potentially reversible conditions, particularly depression and delirium which could be detected clinically rather than on the basis of investigations. Discussion: The clinic was felt to be useful in providing education and support to the families and others caring for those suffering from dementia, in providing a sound basis for case management of dementia sufferers, and in providing a focus for the development and dissemination of skills and knowledge among health professionals.     

Noninvasive versus invasive microbial investigation in ventilator-associated pneumonia: evaluation of outcome

Noninvasive and invasive diagnostic techniques have been shown to achieve comparable performances in the evaluation of suspected ventilator-associated pneumonia (VAP). We studied the impact of both approaches on outcome in a prospective, open, and randomized study in three intensive care units (ICUs) of a 1,000-bed tertiary care university hospital. Patients with suspected VAP were randomly assigned to noninvasive (Group 1) versus invasive (Group 2) investigation (tracheobronchial aspirates [TBAS] versus bronchoscopically retrieved protected specimen brush [PSB] and bronchoalveolar lavage [BAL]. Samples were cultured quantitatively, and BAL fluid (BALF) was examined for intracellular organisms (ICO) additionally. Initial empiric antimicrobial treatment was administered following the guidelines of the American Thoracic Society (ATS) and adjusted according to culture results (and ICO counts in Group 2). Outcome variables included length of ICU stay and mechanical ventilation as well as mortality. Overall, 76 patients (39 noninvasive, 37 invasive) were investigated. VAP was microbiologically confirmed in 23 of 39 (59%) and 23 of 37 (62%) (p = 0.78). There were no differences with regard to the frequencies of community-acquired and potentially drug-resistant microorganisms (PDRM). Antimicrobial treatment was changed in seven patients (18%) of Group 1 and 10 patients (27%) of Group 2 because of etiologic findings (including five of 17 with ICO = 2% (p = not significant [NS]). Length of ICU stay and mechanical ventilation were also not significantly different in both groups. Crude 30-d mortality was 31 of 76 (41%), and 18 of 39 (46%) in Group 1 and 14 of 37 (38%) in Group 2 (p = 0.46). Adjusted mortality was 16% versus 11% (p = 0.53), and mortality of microbiologically confirmed pneumonia 10 of 23 (44%) in both groups (p = 1.0). We conclude that the outcome of VAP was not influenced by the techniques used for microbial investigation.