Recruiting and retaining first-year college students in online health research: Implementation considerations.

Objective: Decreasing participation in intervention research among college students has implications for the external validity of behavioral intervention research. We describe recruitment and retention strategies used to promote participation in intervention research across a series of four randomized experiments. Method: We report the recruitment and retention rates by school for each experiment and qualitative feedback from students about recommendations for improving research participation. Results: There was considerable variation among schools' recruitment (4.9% to 64.7%) and retention (12% to 67.8%) rates. Student feedback suggested study timing (e.g., early in the semester), communication strategies (e.g., social media), and incentive structure (e.g., guaranteed incentives) could improve research participation. The highest survey participation rate was observed at the university which mandated students to complete the intervention (but not the survey). Conclusions: Intervention scientists must consider the population and study context to make informed decisions related to recruitment and retention strategies.

Genomic variability of Pantoea ananatis in maize white spot lesions assessed by AFLP markers.

Measures to control maize white spot (MWS) caused by Pantoea ananatis are preferentially based on resistant cultivars. A lack of knowledge on the genetic variability of pathogens could interfere with the development and utilization of controlling strategies in this pathosystem. The main goals of this study were to investigate the genetic variability of 90 P. ananatis isolates from three different eco-geographical regions of Brazil by amplified fragment length polymorphism (AFLP), and to determine the presence of a universal P. ananatis plasmid in isolates from tropical Brazil. Analysis of genetic similarity by AFLP allowed us to categorize the 90 isolates into two groups. However, no correlation between the collecting sites and genetic groupings was observed. The polymorphism percentage found in P. ananatis ranged between 24.64 and 92.46%, and genetic diversity was calculated to be 0.07-0.09. The analysis of molecular variance showed that 99.18% of genetic variability was within the populations, providing evidence that evolutionary forces were acting on these populations. All P. ananatis isolates showed the P. ananatis universal plasmid (280 or 352 kb). This is the first report on the presence of a universal P. ananatis plasmid from MWS lesions in the tropical area.

Characterization of the inaA gene and expression of ice nucleation phenotype in Pantoea ananatis isolates from Maize White Spot disease.

Maize White Spot (MWS), a foliar disease caused by Pantoea ananatis, could cause up to 60% yield loss. Some strains of P. ananatis harboring the ice nucleation gene inaA catalyze the formation of ice nuclei, causing tissue damage at temperatures slightly below freezing. Little is known about the relationship between the presence of the ina gene in this maize pathogen and its expression during the phenomenon of ice nucleus formation. Here, we attempted to verify the presence of the inaA gene and the expression of phenotype in vitro. The identity of the isolates and the presence of the inaA gene were determined by P. ananatis species-specific primers. The expression of the inaA gene was assessed in vitro by the visualization of ice-crystal formation in water at subzero temperatures. A total of ninety P. ananatis isolates from MWS lesions were characterized. The presence of the inaA gene was confirmed by gel electrophoresis of the 350-400-bp PCR products. The inaA primers did not lead to DNA fragment amplification in three isolates. The ice nucleation phenotype was expressed in 83.34% of the isolates carrying the inaA gene. Our study showed that the ice nucleation in P. ananatis isolated from MWS lesions was dependent on the presence of a functional ina gene in the genome. We also found evidence indicating that some P. ananatis strains have a mutated form of the inaA gene, producing a non-functional ice nucleation protein. This is the first report on inaA gene characterization in P. ananatis isolates from Maize White Spot.

Clinical Consensus Guidelines on the Application of Cerebrospinal Fluid Biomarkers for Alzheimer's Disease Diagnosis: Recommendations of the Irish Network for Biomarkers in Neurodegeneration.

It is accepted that a lumbar puncture (LP) and cerebrospinal fluid (CSF) biomarker analysis support the routine diagnostic work-up for the differential diagnosis of dementia due to Alzheimer's disease (AD) within certain patient cohorts1. These tests, which measure CSF protein concentrations of amyloid-ß42 (Aß42), total tau (t-tau) and phospho tau (p-tau), were recently validated, accredited and made available clinically for the first time in Ireland. A working group, comprising Irish clinical and scientific researchers, met to review a) the validation results; b) international consensus opinions, and c) research and clinical evidence as to the clinical utility of CSF biomarker analysis for AD dementia diagnosis. The outcome of this meeting was the formulation of a consensus statement paper for the benefit of health care professionals involved in the diagnosis and management of dementia to ensure appropriate use of these biomarker tests in clinical settings in Ireland.

Allogeneic hematopoietic cell transplantation for mycosis fungoides and Sezary syndrome.

We describe outcomes after allogeneic hematopoietic cell transplantation (HCT) for mycosis fungoides and Sezary syndrome (MF/SS). Outcomes of 129 subjects with MF/SS reported to the Center for the International Blood and Marrow Transplant from 2000-2009. Median time from diagnosis to transplant was 30 (4-206) months and most subjects were with multiply relapsed/ refractory disease. The majority (64%) received non-myeloablative conditioning (NST) or reduced intensity conditioning (RIC). NST/RIC recipients were older in age compared with myeloablative recipients (median age 51 vs 44 years, P=0.005) and transplanted in recent years. Non-relapse mortality (NRM) at 1 and 5 years was 19% (95% confidence interval (CI) 12-27%) and 22% (95% CI 15-31%), respectively. Risk of disease progression was 50% (95% CI 41-60%) at 1 year and 61% (95% CI 50-71%) at 5 years. PFS at 1 and 5 years was 31% (95% CI 22-40%) and 17% (95% CI 9-26%), respectively. OS at 1 and 5 years was 54% (95% CI 45-63%) and 32% (95% CI 22-44%), respectively. Allogeneic HCT in MF/SS results in 5-year survival in approximately one-third of patients and of those, half remain disease-free.

Ph+ ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: impact of tyrosine kinase inhibitor and minimal residual disease.

The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD)(neg) pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%; P=0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (P=0.058). Overall survival (OS) was similar (RIC 39% (95% confidence interval (CI) 27-52) vs 35% (95% CI 27-44); P=0.62). Patients MRD(pos) pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (HR) 1.97; P=0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared with a similar MRD population after MAC (33%; P=0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; P=0.057), but absence of pre-HCT TKI (HR 1.88; P=0.018), RIC (HR 1.891; P=0.054) and pre-HCT MRD(pos) (HR 1.6; P=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD(neg) status is preferred pre-HCT.

Efectos proinflamatorios de la contaminación atmosférica / Proinflammatory effects of air pollution in Santiago de Chile

Intermittent exposure of rats to Santiago's traffic pollution is associated to a decrease in growth after more than 100 days (range: 101-111) and to histological lung damage after 90 and particularly after 180 days. Our aim was to assess whether a 90 days exposure of rats to air from a Santiago's heavy traffic avenue, is able to induce a systemic proinflammatory reaction. Thirty-days-old Sprague-Dawley rats (n = 7) were directly exposed to air from a heavy traffic avenue (8 h, 5 days a week, from April 27 to July 29, 2009). Controls (n = 7) breathed animal room air. Rats were weighed twice a week and after completing 90 days of observation, lungs were subjected to histopathology and C reactive protein, viscosity and F2-isoprostane in plasma and microhematocrit were determined in blood samples. Exposure to PM10, PM2.5, ozone, NO2 and CO were estimated from registrations of 4 Santiago's monitoring stations. Plasmatic C reactive protein and viscosity and microhematocrit were significantly increased after 90 days of exposure as compared to controls (p < 0.05). No significant changes were observed in F2-isoprostane, nor in lung histopathology, nor in body weight curve versus time in exposed as compared to control series. Hourly mean value of PM25 in the 8 h of exposure was high: 38.9 ug/m³. It is concluded that 90 days of intermittent exposure of rats to Santiago's air pollution would promote a systemic inflammatory reaction. This response to air pollution might precede the decrease in body growth and the histological lung damage reported previously by our laboratory in the same species after intermittent Santiago's urban air pollution exposure.

La exposición intermitente de ratas centinela a la contaminación del tráfico vehicular de Santiago se ha asociado a disminución del crecimiento corporal después de cien días de exposición (rango: 101-111) y a daño histopatológico del pulmón a los 90 días y más, especialmente a los 180 días de exposición. Nuestro objetivo fue evaluar si la exposición al aire de una avenida con elevado tráfico vehicular durante 90 días era capaz de inducir en la rata una respuesta inflamatoria sistémica. Ratas Sprague-Dawley de 30 días de edad (n = 7) fueron directamente expuestas a respirar el aire de una avenida con elevado flujo vehicular (8 h, 5 días por semana, desde el 27 de abril hasta el 29 de julio de 2009). Las ratas control (n = 7) respiraron aire del bioterio. Las ratas se pesaron dos veces por semana y después de completar 90 días de observación, los pulmones se destinaron a estudio histopatológico. Se realizó microhematocrito y se determinó proteína C reactiva, viscosidad y F2-isoprostano plasmáticos en muestras de sangre. La exposición a PM10, PM2,5, ozono, NO2 y CO se calculó de los registros de cuatro estaciones de monitoreo de Santiago. Después de 90 días de exposición se observó un aumento significativo (p < 0,05) de la proteína C reactiva y de la viscosidad plasmática y también del microhematocrito, en relación a la serie control. No se observaron cambios significativos en F2-isoprostano plasmático, ni en la histopatología pulmonar, ni en la curva de peso corporal versus tiempo al comparar la serie expuesta con la serie control. El promedio horario de PM2,5 en las 8 horas de exposición fue alto: 38,9 ug/m³. Concluimos que 90 días de exposición intermitente a la contaminación aérea de Santiago en el modelo experimental promueve una reacción inflamatoria sistémica. Esta respuesta a la contaminación aérea podría preceder a la disminución del crecimiento corporal y al daño histológico pulmonar encontrado en otro de nuestros estudios en esta misma especie después...

[Efficacy of vitaprost forte in patients with prostatic adenoma].

The trial of a new bioregulatory peptide vitaprost forte (100 mg rectal suppositoria) in 30 patients with prostatic adenoma demonstrated that this drug attenuates clinical symptoms of the disease, improves quality of life, uroflowmetric parameters and reduces size of the prostate. Vitaprost forte is more effective in patients with prostatic adenoma in combination with chronic prostatitis, has antiaggregant and anticoagulant properties, stimulates synthesis of antihistamine and antiserotonine antibodies, improves microcirculation in the prostate resulting in regressioin of edema, activity of inflammation in prostatic diseases.

Cell-specific nuclear import of plasmid DNA in smooth muscle requires tissue-specific transcription factors and DNA sequences.

Two shortcomings of nonviral gene therapy are a lack of tissue-specific targeting of vectors and low levels of gene transfer. Our laboratory has begun to address these limitations by designing plasmids that enter the nucleus of specific cell types in the absence of cell division, thereby enhancing expression in a controlled manner. We have shown that a 176 bp portion of the smooth muscle gamma-actin (SMGA) promoter can mediate plasmid nuclear import specifically in smooth muscle cells (SMCs). Here, we demonstrate that the binding sites for serum response factor (SRF) and NKX3-1/3-2 within this DNA nuclear targeting sequence (DTS) are required for plasmid nuclear import. Knockdown of these factors with siRNA abrogates plasmid nuclear import, indicating that they are necessary cofactors. In addition, coinjection of recombinant SRF and Nkx3.2 with the vector in TC7 epithelial cells rescues import. Finally, we show that the SRF nuclear localization sequence (NLS) is required for vector nuclear import. We propose that SRF and NKX3-1/3-2 bind the SMGA DTS in the cytoplasm, thus coating the plasmid with NLSs that mediate translocation across the nuclear pore complex. This discovery could aid in the development of more efficient nonviral vectors for gene transfer to SMCs.

CB2 receptor-mediated migration of immune cells: it can go either way.

Though many studies have examined the role of CB2 receptors in immune cell migration, it has been difficult to form definitive conclusions about the physiopathological role of these receptors in regulating immune responses and how this might be pharmacologically targeted for therapy. Do cannabinoids promote inflammation through the recruitment of immune cells, or reduce inflammation by interfering with the action of other chemoattractants? Is therapeutic intervention with an agonist or antagonist more appropriate for the reduction of inflammation? In this review, we will summarize the progress that has been made in answering these questions and outline current hypotheses.

[The experience in postoperative administration of alpha-adrenoblockers].

The study of efficacy of alpha-blocker alfuzosine (dalphaz CP) in a dose 10 mg/day for treatment of postoperative complications after transurethral resection (TUR) of the prostate and open adenomectomy (OAE) and in quality of life (QoL) improvement enrolled 22 patients after TUR of the prostate and 18 patients after OAE. Examination of the patients was carried out before the operation 10 days and 1 month after surgery. The assessment was performed according to IPSS, QoL index, V and RU. It is shown that patients treated without the alpha-blocker had more urination defects. Administration of alpha-blocker on day 1 after surgical treatment of prostatic adenoma leads to earlier regress of urination disorders. This improves the course of the postoperative period, lowers the risk of urogenital infection and risk of acute urine retention. Therefore QoL rises significantly.

Procollagen type I gene expression and cell proliferation are increased in lipodermatosclerosis.

BACKGROUND: Lipodermatosclerosis (LDS) is characterized by a hardening and hyperpigmentation of lower leg skin as a consequence of chronic venous insufficiency. The degree of skin hardening or fibrosis associated with LDS is proposed to relate directly to skin breakdown and venous ulcer formation as well as to a subsequent delay in ulcer healing. OBJECTIVES: To determine whether elevated procollagen type I gene expression and increased cell proliferation are responsible for the fibrotic changes associated with LDS. METHODS: Skin biopsies were obtained from the legs of patients with varying degrees of chronic venous disease and were assessed for procollagen gene expression by in-situ hybridization and for cell proliferation by immunolocalization of proliferating cell nuclear antigen. RESULTS: The number of cells expressing procollagen type I mRNA (COL1A1) was significantly higher in the dermis of LDS-affected skin compared with samples from the other patient groups. In addition, there was a significant increase in the number of dermal fibroblasts undergoing proliferation in both LDS samples and skin samples prior to LDS changes compared with control samples. However, there was no significant difference in level of inflammation in biopsy samples between patient classes. CONCLUSIONS: These results suggest that enhanced cell proliferation and procollagen gene expression are both involved in LDS development. Furthermore, fibrotic changes may occur in the absence of, or subsequent to, any significant inflammatory response, indicating that additional profibrotic factors produced in the skin as a consequence of chronic venous insufficiency may play a role in LDS formation.

A phase I trial of DNA vaccination with a plasmid expressing prostate-specific antigen in patients with hormone-refractory prostate cancer.

Prostate-specific antigen (PSA) is a serine protease secreted at low levels by normal luminal epithelial cells of the prostate and in significantly higher levels by prostate cancer cells. Therefore, PSA is a potential target for various immunotherapeutical approaches against prostate cancer. DNA vaccination has been investigated as immunotherapy for infectious diseases in patients and for specific treatment of cancer in certain animal models. In animal studies, we have demonstrated that vaccination with plasmid vector pVAX/PSA results in PSA-specific cellular response and protection against tumour challenge. The purpose of the trial was to evaluate the safety, feasibility and biological efficacy of pVAX/PSA vaccine in the clinic. A phase I trial of pVAX/PSA, together with cytokine granulocyte/macrophage-colony stimulating factor (GM-CSF) (Molgramostim) and IL-2 (Aldesleukin) as vaccine adjuvants, was carried out in patients with hormone-refractory prostate cancer. To evaluate the biologically active dose, the vaccine was administered during five cycles in doses of 100, 300 and 900 microg, with three patients in each cohort. Eight patients were evaluable. A PSA-specific cellular immune response, measured by IFN-gamma production against recombinant PSA protein, and a rise in anti-PSA IgG were detected in two of three patients after vaccination in the highest dose cohort. A decrease in the slope of PSA was observed in the two patients exhibiting IFN-gamma production to PSA. No adverse effects (WHO grade >2) were observed in any dose cohort. We demonstrate that DNA vaccination with a PSA-coding plasmid vector, given with GM-CSF and IL-2 to patients with prostate cancer, is safe and in doses of 900 microg the vaccine can induce cellular and humoral immune responses against PSA protein.

Resolution of chronic idiopathic thrombocytopenia purpura following syngeneic peripheral blood progenitor transplant.

Idiopathic thrombocytopenia purpura (ITP) is an acquired disease of children and adults characterized by a low platelet count, an essentially normal bone marrow, and absence of evidence for other disease. We report the use of syngeneic peripheral blood progenitor transplantation (PBPT) in a 19-year-old male with chronic refractory ITP since the age of 5. Engraftment was successful and has resulted in resolution of his disease. We conclude that syngeneic PBPT is a potentially curative option for refractory ITP.

Inflammation as a key event in the development of neointima following vascular balloon injury.

1. The present review discusses the current evidence to implicate leucocytes as key players in the development of neointima in arteries that have been subjected to balloon angioplasty injury. 2. There is substantial clinical evidence that leucocytes are activated after angioplasty, as determined by increased plasma levels of both leucocyte granulation products and soluble leucocyte and endothelial cell adhesion molecules. 3. Experimental evidence to implicate leucocytes in neointimal formation comes from studies that demonstrate leucocyte accumulation occurs within the vascular wall soon after injury and that induction of leukopenia prevents neointimal formation. 4. The evidence implicating specific adhesion molecules and cytokines in the key events leading to neointimal formation is discussed.

Validation of a technique to measure leukocyte adhesion to arterial segments: effects of drug treatments.

Adhesion and transmigration of leukocytes into arterial walls occurs after vascular injury and may play a role in the development of atherosclerosis and restenosis. This protocol presents a simple, rapid method for quantifying leukocyte adhesion to artery segments ex vivo. The procedure involves isolating leukocytes from rabbit whole blood and labelling with the gamma-emitting isotope 51Cr. Labelled leukocytes are added to open rings of subclavian artery taken from the same rabbit. After gamma counting, percentage leukocyte adhesion can be calculated with reference to a sample containing a quantity of labelled leukocytes equivalent to that which was added to the artery. Leukocyte adhesion was increased by L-NAME, thrombin and increasing incubation time and decreased by low temperatures. In addition, leukocyte adhesion was found to be increased following a vascular stretch injury performed in vitro. This protocol offers a number of advantages: the rapidity of the leukocyte isolation and labelling; the small quantity of leukocytes required; the ability to use autologous leukocytes; the applicability to whole arteries and arteries injured in vitro or in vivo, allowing the effects of vascular injury on leukocyte adhesion to be studied.

Rapid response of severe refractory metastatic Crohn's disease to infliximab.

A case is described of a middle-aged female who developed an aggressive form of biopsy-proven metastatic Crohn's disease involving the inguinal, perineal and submammary areas. Her condition had been unresponsive to topical and systemic corticosteroids, antibiotics, immunosuppressives, and repeated surgical debridement. Administration of infliximab resulted in a rapid clinical response with subjective improvements in pain and general well-being, and an objective decline in exudate, erythema and size of the lesions. Infliximab may be a suitable therapeutic option in patients with metastatic Crohn's disease.

Uneasy promises: sexuality, health, and human rights.

Although attention to the links between health and human rights is growing globally, the full potential of a progressive human rights approach to health has not yet been explored, and it is even more faintly understood in the United States than in the rest of the world. At the same time, global claims for sexual rights, particularly for those identifying as gay, lesbian, transsexual, or bisexual, are increasingly being made as human rights claims. All of these approaches to rights advocacy risk limiting their own transformative impact unless advocates critique their own strategies. Paradoxically, using health as a way to bring attention to nonheteronormative sexualities can be both helpful and potentially dangerous, especially when coupled with human rights. Recognizing sexuality as a critical element of humanity, and establishing a fundamental human right to health, can play a role in broader social justice claims, but the tendency of both public health and human rights advocacy to "normalize" and regulate must be scrutinized and challenged.

Autotransplants for Hodgkin's disease in first relapse or second remission: a report from the autologous blood and marrow transplant registry (ABMTR).

Although patients with relapsed Hodgkin's disease have a poor prognosis with conventional therapies, high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autotransplantation) may provide long-term progression-free survival. We reviewed data from the Autologous Blood and Marrow Transplant Registry (ABMTR) to determine relapse, disease-free survival, overall survival, and prognostic factors in this group of patients. Detailed records from the ABMTR on 414 patients with Hodgkin's disease in first relapse (n = 295) or second complete remission (CR) (n = 119) receiving an autotransplant from 1989 to 1995 were reviewed. Median age was 29 (range, 7-64) years. Median time from diagnosis to relapse was 18 (range, 6-219) months; median time from relapse to transplant was 5 (range, <1-215) months. Most patients received high-dose chemotherapy without total body irradiation for conditioning (n = 370). The most frequently used high-dose regimen was cyclophosphamide, BCNU, VP-16 (CBV) (n = 240). The graft consisted of bone marrow (n = 246), blood stem cells (n = 112), or both (n = 56). Median follow-up was 46 (range, 5-96) months. One hundred-day mortality (95% confidence interval) was 7 (5-9)%. One hundred and sixty-five of 295 patients (56%) transplanted in relapse achieved CR after autotransplantation. Of these, 61 (37%) recurred. Twenty-four of 119 patients (20%) transplanted in CR recurred. The probability of disease-free survival at 3 years was 46 (40-52)% for transplants in first relapse and 64 (53-72)% for those in second remission (P < 0.001). Overall survival at 3 years was 58 (52-64)% after transplantation in first relapse and 75 (66-83)% after transplantation in second CR (P < 0.001). In multivariate analysis, Karnofsky performance score <90% at transplant, abnormal serum LDH at transplant, and chemotherapy resistance were adverse prognostic factors for outcome. Progression of Hodgkin's disease accounted for 69% of all deaths. Autotransplantation should be considered for patients with Hodgkin's disease in first relapse or second remission. Future investigations should focus on strategies designed to decrease relapse after autotransplantation, particularly in patients at high risk for relapse.