The family physician and the psychologist in the office together: a response to fragmentation

It is well known that motives for consulting the family physician, though expressed as physical symptoms, often derive from problems needing a holistic, psychosocial approach. Progressive differentiation between medicine and psychology makes co-operation through referral to the psychologist by the physician quite problematic, in terms of both which patients are referred and the modalities of referral. Acceptance of psychological referral may, in any case, be difficult, due to the social stigma that still surrounds mental distress.The authors report a possible solution in an experiment implemented by the postgraduate Health Psychology School of the Rome University 'Sapienza', entailing joint, direct co-operation between a family physician and a psychologist through the psychologist's presence in the doctor's office during consultations. This allowed direct access to a psychologist in the absence of any filter and without the need for a formal request on the patient's part and a biopsychosocial approach to distress. In a small number of cases, more formal consultation with the psychologist was proposed. Cases were always discussed between the two professionals. To date, the experiment has involved nine psychologists and seven physicians over a period of nine years. It appears to be entirely feasible, though requiring a period of adaptation between the two professionals. Patients have welcomed the presence of the psychologist and, as expected, take a broader approach in reporting their distress.An illustrative case is presented, in which finding the meaning of a symptom avoided unnecessary and costly investigations, and facilitated the patient in taking a new direction in his life.     

The Atlantic salmon Z-DNA binding protein kinase phosphorylates translation initiation factor 2 alpha and constitutes a unique orthologue to the mammalian dsRNA-activated protein kinase R

The translation initiation factor 2 alpha (eIF2alpha)-kinase, dsRNA-activated protein kinase (PKR), constitutes one of the major antiviral proteins activated by viral infection of vertebrates. PKR is activated by viral double-stranded RNA and subsequently phosphorylates the alpha-subunit of translation initiation factor eIF2. This results in overall down regulation of protein synthesis in the cell and inhibition of viral replication. Fish appear to have a PKR-like protein that has Z-DNA binding domains instead of dsRNA binding domains in the regulatory domain, and has thus been termed Z-DNA binding protein kinase (PKZ). We present the cloning of the Atlantic salmon PKZ cDNA and show its upregulation by interferon in Atlantic salmon TO cells and poly inosinic poly cytodylic acid in head kidney. We also demonstrate that recombinant Atlantic salmon PKZ, expressed in Escherichia coli, phosphorylates eIF2alphain vitro. This is the first demonstration that PKZ is able to phosphorylate eIF2alpha. PKZ activity, as measured by phosphorylation of eIF2alpha, was increased after addition of Z-DNA, but not by dsRNA. In addition, we show that wild-type Atlantic salmon PKZ, but not the kinase defective variant K217R, has a direct inhibitory effect on protein synthesis after transient expression in Chinook salmon embryo cells. Overall, the results support a role for PKZ, like PKR, in host defense against virus infection.     

Yeast as a model of human mitochondrial tRNA base substitutions: investigation of the molecular basis of respiratory defects

We investigate the relationships between acylation defects and structure alterations due to base substitutions in yeast mitochondrial (mt) tRNA(UUR)(Leu). The studied substitutions are equivalent to the A3243G and T3250C human pathogenetic tRNA mutations. Our data show that both mutations can produce tRNA(UUR)(Leu) acylation defects, although to a different extent. For mutant A14G (equivalent to MELAS A3243G base substitution), the presence of the tRNA and its defective aminoacylation could be observed only in the nuclear context of W303, a strain where the protein synthesis defects caused by tRNA base substitutions are far less severe than in previously studied strains. For mutant T20C (equivalent to the MM/CPEO human T3250C mutation), the acylation defect was less severe, and a thermosensitive acylation could be detected also in the MCC123 strain. The correlation between the severity of the in vivo phenotypes of yeast tRNA mutants and those obtained in in vitro studies of human tRNA mutants supports the view that yeast is a suitable model to study the cellular and molecular effects of tRNA mutations involved in human pathologies. Furthermore, the yeast model offers the possibility of modulating the severity of yeast respiratory phenotypes by studying the tRNA mutants in different nuclear contexts. The nucleotides at positions 14 and 20 are both highly conserved in yeast and human mt tRNAs; however, the different effect of their mutations can be explained by structure analyses and quantum mechanics calculations that can shed light on the molecular mechanisms responsible for the experimentally determined defects of the mutants.     

The Clinical Breast Care Project: an important resource in investigating environmental and genetic contributions to breast cancer in African American women

Age at diagnosis, pathological characteristics, and tumor behavior differ between African American (AAW) and Caucasian women (CW) with breast cancer, with AAW having more aggressive tumors and higher mortality rates. Although both societal and molecular contributions to these disparities have been suggested, the African American population has traditionally been under-represented in research and clinical protocols, limiting the power of epidemiologic and molecular studies to provide better understanding of disease pathogenesis in this minority population. The Clinical Breast Care Project (CBCP) has developed a large tissue and blood repository from patients undergoing treatment for breast cancer, with previous history of breast cancer, counseled in the Risk Reduction Clinic, screened by routine mammography, or undergoing elective reductive mammoplasty. Recruitment of AAW into the CBCP was successful; 25% of the 2,454 female patients were African American, including 35% disease-free, 3% high-risk, 40% benign, 8% preinvasive and 14% with invasive breast disease. More than 500 data fields regarding lifestyle choices, socioeconomic status, health history and geography were collected from all participants, and all consenting individuals provided blood specimens for genomic and proteomic studies. Tissues were collected from all patients undergoing surgical procedures using protocols that preserve the macromolecules for downstream research applications. In addition, patients were followed after diagnosis, with >85% of patients providing ongoing and updated demographic and clinical information. Thus, recruitment efforts in the CBCP have resulted in collection of well-annotated information and research-quality specimens from a large number of AAW. This unique resource will allow for the identification of biological and environmental factors associated with the identification of genetic and non-genetic factors associated with the occurrence, detection, prognosis, or survival of breast cancer in AAW. The opinion and assertions contained herein are the private views of the authors and are not to be construed as official or as representing the views of the Department of the Army or the Department of Defense.     

Survival of Infants Born to HIV-Positive Mothers,by Feeding Modality,in Rakai,Uganda

Background

Data comparing survival of formula-fed to breast-fed infants in programmatic settings are limited. We compared mortality and HIV-free of breast and formula-fed infants born to HIV-positive mothers in a program in rural, Rakai District Uganda.

Methodology/Principal Findings

One hundred eighty two infants born to HIV-positive mothers were followed at one, six and twelve months postpartum. Mothers were given infant-feeding counseling and allowed to make informed choices as to whether to formula-feed or breast-feed. Eligible mothers and infants received antiretroviral therapy (ART) if indicated. Mothers and their newborns received prophylaxis for prevention of mother-to-child HIV transmission (pMTCT) if they were not receiving ART. Infant HIV infection was detected by PCR (Roche Amplicor 1.5) during the follow-up visits. Kaplan Meier time-to-event methods were used to compare mortality and HIV-free survival. The adjusted hazard ratio (Adjusted HR) of infant HIV-free survival was estimated by Cox regression. Seventy-five infants (41%) were formula-fed while 107 (59%) were breast-fed. Exclusive breast-feeding was practiced by only 25% of breast-feeding women at one month postpartum. The cumulative 12-month probability of infant mortality was 18% (95% CI = 11%–29%) among the formula-fed compared to 3% (95% CI = 1%–9%) among the breast-fed infants (unadjusted hazard ratio (HR)  = 6.1(95% CI = 1.7–21.4, P-value<0.01). There were no statistically significant differentials in HIV-free survival by feeding choice (86% in the formula-fed compared to 96% in breast-fed group (Adjusted RH = 2.8[95%CI = 0.67–11.7, P-value = 0.16]

Conclusions/Significance

Formula-feeding was associated with a higher risk of infant mortality than breastfeeding in this rural population. Our findings suggest that formula-feeding should be discouraged in similar African settings.     

Functional characterization of integrin alpha6beta4 adhesion interactions using soluble integrin constructs reveals the involvement of different functional domains in the beta4 subunit

Integrin alpha6beta4-mediated adhesion interactions play key roles in keratinocyte and epithelial tumor cell biology. In order to evaluate how alpha6beta4 adhesion interactions contribute to these important cellular processes, the authors generated soluble versions of the integrin by recombinant expression of the subunit ectodomains fused to a human immunoglobulin G (IgG) Fc constant domain. Coexpression of the appropriate subunits enabled dimerization, secretion and purification of stable Fc-containing alpha6beta4 heterodimers. The soluble proteins exhibited the same metal ion and ligand dependency in their binding characteristics as intact alpha6beta4. Using these reagents in combination with anti-beta4 antibodies, the authors identified two distinct functional epitopes on the beta4 subunit. They demonstrated the involvement of one epitope in adhesion interactions and the other in regulating adhesion-independent growth in alpha6beta4-expressing tumor cell lines. The availability of these soluble integrin reagents and the data provided herein help to further delineate the structure-function relationships regulating alpha6beta4 signaling biology.