Medical Library

PATHs approach to product introduction in developing countries.

Health interventions developed for wealthy nations are difficult to introduce in developing countries due to a lack of sufficient technological, financial, political, or infrastructural resources. Increasingly, however, product developers are creating new technologies that meet the needs of low-resource settings. Experience has shown that many activities must be undertaken to prepare health systems to accept and embrace new, improved, or under-utilized health technologies. This article describes three health technologies-a diagnostic test for vitamin A deficiency, new cervical cancer vaccines, and the vaccine vial monitor-that PATH, a global health organization, has helped advance for developing-country markets. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.

Harner-Jay C, Sherris J.

PATH, Technology Solutions, Program Officer, 1455 NW Leary Way, Seattle, Washington 98107.

Treatment barriers for low-income, urban African Americans with undiagnosed posttraumatic stress disorder.

African Americans in low-income, urban communities are at high risk for exposure to traumatic events as well as for symptoms of posttraumatic stress disorder (PTSD). Approximately 22% of 220 participants recruited from urban hospital medical clinics met survey criteria for PTSD. Among the common traumas were having relatives/friends murdered (47%), being attacked with weapons (64% of men), and being sexually attacked (36% of women). Although desiring mental health services, only 13.3% of those with PTSD had prior trauma-focused treatment. Barriers to treatment included limited transportation and finances, family disapproval, and unfamiliarity with accessing treatment, among others. These data highlight the need for an awareness of the high prevalence of trauma and PTSD in this population.

Davis RG, Ressler KJ, Schwartz AC, Stephens KJ, Bradley RG.

Departments of Psychiatry and Behavioral Sciences, Emory University, and Grady Memorial Hospital, Atlanta, GA.

Virtual reality exposure therapy using a virtual Iraq: Case report.

Posttraumatic stress disorder (PTSD) has been estimated to affect up to 18% of returning Operation Iraqi Freedom (OIF) veterans. Soldiers need to maintain constant vigilance to deal with unpredictable threats, and an unprecedented number of soldiers are surviving serious wounds. These risk factors are significant for development of PTSD; therefore, early and efficient intervention options must be identified and presented in a form acceptable to military personnel. This case report presents the results of treatment utilizing virtual reality exposure (VRE) therapy (virtual Iraq) to treat an OIF veteran with PTSD. Following brief VRE treatment, the veteran demonstrated improvement in PTSD symptoms as indicated by clinically and statistically significant changes in scores on the Clinician Administered PTSD Scale (CAPS; Blake et al., 1990) and the PTSD Symptom Scale Self-Report (PSS-SR; Foa, Riggs, Dancu, & Rothbaum, 1993). These results indicate preliminary promise for this treatment.

Gerardi M, Rothbaum BO, Ressler K, Heekin M, Rizzo A.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA.

Meta-analysis of alexithymia in posttraumatic stress disorder.

The authors present a meta-analysis investigating the prevalence of alexithymia in 12 studies encompassing 1,095 individuals with posttraumatic stress disorder (PTSD). A large effect size was found associating PTSD with alexithymia. Effect sizes were higher in studies of male combat PTSD samples in comparison with studies of other PTSD samples. Clinical and research directions are discussed.

Frewen PA, Dozois DJ, Neufeld RW, Lanius RA.

Department of Psychology, The University of Western Ontario, Ontario, Canada.

Geminin is overexpressed in human pancreatic cancer and downregulated by the bioflavanoid apigenin in pancreatic cancer cell lines.

Pancreatic adeniocarcinoma is among the deadliest of human cancers. Apigenin, an antitumor flavonoid, inhibits pancreatic cancer cell proliferation in vitro. Geminin is a recently identified novel protein that plays a critical role in preventing abnormal DNA replication by binding to and inhibiting the essential replication factor Cdt1. Microarray analysis identified geminin to be downregulated in pancreatic cancer cells treated with apigenin. Therefore, we investigated the effects of apigenin on geminin expression and other proteins involved in replication (Cdc6, Cdt1, and MCM7) in pancreatic cancer cell lines CD18 and S2013. Real time RT-PCR and western blotting analysis showed that geminin expression is downregulated by apigenin at both mRNA and protein levels. Furthermore, treatment of cells with proteosome inhibitor MG132 reversed the downregulation of geminin by apigenin, supporting our hypothesis that the degradation pathway is another mechanism by which apigenin affects geminin expression. Apigenin treatment also resulted in downregulation of Cdc6 at both mRNA and protein levels. However, Cdt1 and MCM7 expression was not affected in apigenin-treated cells. The effect of apigenin treatment on geminin promoter activity was measured by transient transfection of Hela cells with a reporter gene, demonstrating that apigenin inhibited geminin promoter activity. Geminin expression was also evaluated in human pancreatic tissue (n = 15) by immunohistochemistry and showed that geminin is overexpressed in human pancreatic cancer compared to normal adjacent pancreatic tissue. In conclusion, our studies demonstrated that geminin is overexpressed in human pancreatic cancer and downregulated by apigenin which may contribute to the antitumor effect of this natural flavonoid. (c) 2008 Wiley-Liss, Inc.

Salabat MR, Melstrom LG, Strouch MJ, Ding XZ, Milam BM, Ujiki MB, Chen C, Pelling JC, Rao S, Grippo PJ, McGarry TJ, Bentrem DJ.

Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

FBXL21 association with schizophrenia in irish family and case-control samples.

FBXL21 gene encodes an F-box containing protein functioning in the SCF ubiquitin ligase complex. The role of the F-box protein is to recruit proteins designated for degradation to the ligase complex so they would be ubiquitinated. Using both family and case-control samples, we found consistent associations in and around FBXL21 gene. In the family sample (Irish study of high density schizophrenia families, ISHDSF, 1,350 subjects from 273 families), a minimal PDT P-value of 0.0011 was observed at rs31555. In the case-control sample (Irish case-control study of schizophrenia, ICCSS, 814 cases and 625 controls), significant associations were observed at two markers (rs1859427 P = 0.0197, and rs6861170 P = 0.0197). In haplotype analyses, haplotype 1-1 (C-T) of rs1859427-rs6861170 was overtransmitted in the ISHDSF (P = 0.0437) and was overrepresented in the ICCSS (P = 0.0177). For both samples, the associated alleles and haplotypes were identical. These data suggested that FBXL21 may be associated with schizophrenia in the Irish samples. (c) 2008 Wiley-Liss, Inc.

Chen X, Wang X, Sun C, Chen Q, O\’Neill FA, Walsh D, Fanous A, Kendler KS.

Department of Psychiatry and Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, Virginia.

Genetic association between alpha-synuclein and idiopathic parkinson\’s disease.

Point mutations and copy number variations in SNCA, the gene encoding alpha-synuclein, cause familial Parkinson\’s disease (PD). A dinucleotide polymorphism (REP1) in the SNCA promoter may be a risk factor for common forms of PD. We studied 1,802 PD patients and 2,129 controls from the NeuroGenetics Research Consortium, using uniform, standardized protocols for diagnosis, subject recruitment, data collection, genotyping, and data analysis. Three common REP1 alleles (257, 259, and 261 bp, with control frequencies of 0.28, 0.65, and 0.06) and several rare alleles (combined frequency <0.01) were detected. We confirmed association of REP1 with PD risk [odds ratio (OR) = 0.86, P = 0.006 for 257-carriers; OR = 1.25, P = 0.022 for 261-carriers]. Using a normalization procedure, we showed that the 257 and 261 alleles are both independently associated with PD risk (for 257, P = 0.002 in overall data, 0.003 in non-familial PD, 0.001 in early-onset PD; for 261, P = 0.056 in overall data, 0.024 in non-familial PD, 0.052 in early-onset PD). The 257-associated risk was consistent with a dominant model [hazard ratio (HR) = 0.99, P = 0.91 for 257/257 vs. 257/X where X denotes all other common alleles; HR = 1.16, P = 0.004 for X/X vs. 257/X]. The 261-associated risk was consistent with a recessive model (HR = 1.89, P = 0.026 for 261/261 vs. 261/X; HR = 0.95, P = 0.42 for X/X vs. 261/X). Genotype-specific mean onset ages (+/-SD) ranged from 54.8 +/- 12.1 for 261/261 to 59.4 +/- 11.5 for 257/257, displaying a trend of decreasing onset age with increasing allele size (P = 0.055). Genetic variation in SNCA and its regulatory regions play an important role in both familial and sporadic PD. (c) 2008 Wiley-Liss, Inc.

Kay DM, Factor SA, Samii A, Higgins DS, Griffith A, Roberts JW, Leis BC, Nutt JG, Montimurro JS, Keefe RG, Atkins AJ, Yearout D, Zabetian CP, Payami H.

Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York.

Juvenile and adult immature and in vitro matured ovine oocytes evaluated in relation to membrane electrical properties, calcium stores, IP3 sensitivity and apoptosis occurrence in cumulus cells.

The analysis of differences between juvenile and adult oocytes may provide useful information on the acquisition of meiotic and developmental competence of the female gamete. In oocytes collected from either ewes or 40-day-old lambs, we evaluated membrane electrical proprieties, such as resting potential, conductance, activation ion currents, L-type Ca(2+) currents as well as calcium stores and IP3 sensitivity; in addition, the incidence of apoptosis in cumulus cells in these two age categories was compared. The analysis was carried out in oocytes both prior to and after in vitro maturation. Significant differences were found in all the examined parameters in relation to maturational stages whereas minor differences were recorded in relation to age of the donor. IP3 sensitivity strongly increased after in vitro maturation following a dose-dependent pattern from 1 to 500 micromol/L with a significant interaction (P < 0.01) between dose and maturational stage. The incidence of apoptosis in cumulus cells strongly increased after in vitro maturation and was greater in adult than in juvenile cumulus cells (39.2 +/- 5.8% vs. 21.9 +/- 3.5%; P < 0.01). In conclusion, all the examined parameters were greatly affected by the maturational stage, whereas minor differences were due to age-related oocyte quality, that is, at plasma membrane levels to conductance, activation current peaks and calcium currents, at cytosol level to calcium stores and IP3 sensitivity, and to incidence of apoptosis in cumulus cells. These parameters were compared with previous data in bovine to analyze oocyte quality in juvenile and adult individuals or between species. Mol. Reprod. Dev. (c) 2008 Wiley-Liss, Inc.

Boni R, Cocchia N, Silvestre F, Tortora G, Lorizio R, Tosti E.

Dept Scienze delle Produzioni Animali, Università della Basilicata, Potenza, Italy.

Anorexia nervosa and parental bonding: the contribution of parent-grandparent relationships to eating disorder psychopathology.

The present study adopted an intergenerational approach in examining the association between parental bonding and anorexia nervosa. Forty-three anorexic participants and 33 nonclinical comparison participants completed eating disorder questionnaires and the Parental Bonding Instrument (PBI). The participant\’s parents also completed the PBI. The anorexic participants perceived both parents as less caring and fathers as more controlling than nonclinical participants. Among anorexic participants, mother control and father care were associated with symptom severity. Intergenerational effects were present. Among anorexic participants, maternal grandmother care was associated with eating disorder psychopathology. The present findings suggest that parental characteristics of grandparents might play a role in the development of eating disorders in granddaughters. (c) 2008 Wiley Periodicals, Inc. J Clin Psychol 64: 1-14, 2008.

Canetti L, Kanyas K, Lerer B, Latzer Y, Bachar E.

Hadassah University Hospital, Israel.

Entering exile: Trauma, mental health, and coping among Tibetan refugees arriving in Dharamsala, India.

Each year thousands of Tibetans escape Chinese-controlled Tibet. The authors present findings on the experiences, coping strategies, and psychological distress (depression, anxiety, somatization, and posttraumatic stress disorder) of 769 Tibetan refugees arriving in Dharamsala, India (2003-2004). Distress increased significantly with greater trauma exposure. However, despite a high prevalence of potentially traumatizing events, levels of psychological distress were extremely low. Coping activity (primarily religious) and subjective appraisals of trauma severity appeared to mediate the psychological effects of trauma exposure. The potential impact of other variables, including culturally determined attitudes about trauma and timing of assessment, are discussed.

Sachs E, Rosenfeld B, Lhewa D, Rasmussen A, Keller A.

Department of Psychology, Fordham University, Bronx, NY.