A Social-Ecological View of Barriers and Facilitators for HIV Treatment Adherence: Interviews with Puerto Rican HIV Patients

PURPOSE: To identify perceived barriers and facilitators for HAART adherence among people living with HIV/AIDS in Southern Puerto Rico using a Social Ecological framework. PATIENTS AND METHODS: Individual in-depths interviews were conducted with 12 HIV patients with a history of HAART non-adherence. Interviews were audio-taped and transcribed. Content analysis was performed for each transcribed interview by three independent coders using a codebook. Using Atlas TI, super-codes and families were generated to facilitate the categorization tree as well as grounded analyses and density estimates. RESULTS: Most participants reported a monthly income of $500 or less (n = 7), a high school education level (n = 7), being unemployed (n = 9) and being recipients of government health insurance (n = 11). Three out of six women reported living alone with their children and most men informed living with their parents or other relatives (n = 4). For the grounded analyses, the top four sub-categories linked to high number of quotations were mental health barriers (G = 32) followed by treatment regimen (G = 28), health system (G = 24) and interpersonal relations (G = 16). The top four sub-categories linked to high number of codes are treatment regimen (D = 4), health status perception (D = 3), interpersonal relations (D = 3) and health system (D = 3). CONCLUSION: The results of this study suggest the interconnection of HIV treatment adherence barriers at various system levels. Future studies on HIV treatment barriers should explore these interactions and investigate the possible synergistic effect on non-adherent behavior

Mortality attributable to extreme temperatures in Spain: A comparative analysis by city

BACKGROUND: The Low Temperature Days (LTD) have attracted far less attention than that of High Temperature Days (HTD), though its impact on mortality is at least comparable. This lower degree of attention may perhaps be due to the fact that its influence on mortality is less pronounced and longer-term, and that there are other concomitant infectious winters factors. In a climate-change scenario, the studies undertaken to date report differing results. The aim of this study was to analyse mortality attributable to both thermal extremes in Spain's 52 provinces across the period 2000-2009, and estimate the related economic cost to show the benefit or "profitability" of implementing prevention plans against LTD. METHODS: Previous studies enabled us: to obtain the maximum daily temperature above which HTD occurred and the minimum daily temperature below which LTD occurred in the 52 provincial capitals analysed across the same study period; and to calculate the relative and attributable risks (%) associated with daily mortality in each capital. These measures of association were then used to make different calculations to obtain the daily mean mortality attributable to both thermal extremes. To this end, we obtained a summary of the number of degrees whereby the temperature exceeded (excess °C) or fell short (deficit °C) of the threshold temperature for each capital, and calculated the respective number of extreme temperatures days. The economic estimates rated the prevention plans as being 68% effective. RESULTS: Over the period considered, the number of HTD (4373) was higher than the number of LTD (3006) for Spain as a whole. Notwithstanding this, in every provincial capital the mean daily mortality attributable to heat was lower (3deaths/day) than that attributable to cold (3.48deaths/day). In terms of the economic impact of the activation of prevention plans against LTD, these could be assumed to avoid 2.37 deaths on each LTD, which translated as a saving of €0.29M. Similarly, in the case of heat, 2.04 deaths could be assumed to be avoided each day on which the prevention plan against HTD was activated, amounting to a saving of €0.25M. While the economic cost of cold-related mortality across the ten-year period 2000-2009 was €871.7M, that attributable to heat could be put at €1093.2M. CONCLUSION: The effect of extreme temperatures on daily mortality was similar across the study period for Spain overall. The lower number of days with LTD meant, however, that daily cold-related mortality was higher than daily heat-related mortality, thereby making prevention plans against LTD more "profitable" prevention plans against HTD in terms of avoidable mortality.This study was supported by grants FIS ENPY 1001/13 & SEPY 1037/14 from Spain's Health Research Fund.S

Preferences, use of and satisfaction with mental health services among a sample of Puerto Rican cancer patients

OBJECTIVE: The purpose of this study was to describe the preferences, the use, satisfaction of mental health services (MHS) among a sample of Puerto Rican patients with cancer undergoing oncology treatment. METHODS: A convenience sample of 120 patients diagnosed with cancer was recruited. Self-report questionnaires assessed socio-demographic and background questions, and the Mental Health Service Preference, Utilization and Satisfaction Questionnaire (MHSPUS). The Socio-demographic and Background Questionnaire inquired about participants\u27 demographic and socioeconomic characteristics, and included questions such as history of psychiatric diagnosis and spiritual practices. Univariate and Chi square analyses were used for descriptive purposes. Logistic regressions were used to explore associations between sociodemographic factors and MHS preferences and use. RESULTS: The majority of the sample were females (53.8%), 61 and older (53.8%), and married or living with partner (57.1%), and reported an income equal to or less than $12,000 per year (44.4%), which places them under the US federal poverty line. Most of the participants (66.7%) reported being receptive to seeking services. Findings showed a significant association between living situation and past (p \u3c .05) and lifetime use (p \u3c .05) of MHS and past use of MHS. Participants living alone were more like to have used MHS in the past and during their lifetime. Adjusted logistic regression analyses revealed that living with someone was a protective factor for not using MHS in their lifetime (OR = 0.28; C1 = 0.08-0.95). Participants preferred to receive MHS at the oncology clinic, preferably on the date of their oncology appointments and during morning hours. CONCLUSION: Findings support the integration of mental health services within the oncology practice setting

Brief Report: Hispanic Patients\u27 Trajectory of Cancer Symptom Burden, Depression, Anxiety, and Quality of Life

Background: Anxiety and depression symptoms are known to increase cancer symptom burden, yet little is known about the longitudinal integrations of these among Hispanic/Latinx patients. The goal of this study was to explore the trajectory and longitudinal interactions among anxiety and depression, cancer symptom burden, and health-related quality of life in Hispanic/Latinx cancer patients undergoing chemotherapy. METHODS: Baseline behavioral assessments were performed before starting chemotherapy. Follow-up behavioral assessments were performed at 3, 6, and 9 months after starting chemotherapy. Descriptive statistics, chi-square tests, Fisher\u27s exact tests, and Mann-Whitney tests explored associations among outcome variables. Adjusted multilevel mixed-effects linear regression models were also used to evaluate the association between HADS scores, follow-up visits, FACT-G scale, MDASI scale, and sociodemographic variables. RESULTS: Increased cancer symptom burden was significantly related to changes in anxiety symptoms\u27 scores (adjusted beta^ = 0.11 [95% CI: 0.02, 0.19]. Increased quality of life was significantly associated with decreased depression and anxiety symptoms (adjusted beta^ = -0.33; 95% CI: -0.47, -0.18, and 0.38 adjusted beta^= -0.38; 95% CI: -0.55, -0.20, respectively). CONCLUSIONS: Findings highlight the need to conduct periodic mental health screenings among cancer patients initiating cancer treatment

Formate overflow drives toxic folate trapping in MTHFD1 inhibited cancer cells

Cancer cells fuel their increased need for nucleotide supply by upregulating one-carbon (1C) metabolism, including the enzymes methylenetetrahydrofolate dehydrogenase-cyclohydrolase 1 and 2 (MTHFD1 and MTHFD2). TH9619 is a potent inhibitor of dehydrogenase and cyclohydrolase activities in both MTHFD1 and MTHFD2, and selectively kills cancer cells. Here, we reveal that, in cells, TH9619 targets nuclear MTHFD2 but does not inhibit mitochondrial MTHFD2. Hence, overflow of formate from mitochondria continues in the presence of TH9619. TH9619 inhibits the activity of MTHFD1 occurring downstream of mitochondrial formate release, leading to the accumulation of 10-formyl-tetrahydrofolate, which we term a 'folate trap'. This results in thymidylate depletion and death of MTHFD2-expressing cancer cells. This previously uncharacterized folate trapping mechanism is exacerbated by physiological hypoxanthine levels that block the de novo purine synthesis pathway, and additionally prevent 10-formyl-tetrahydrofolate consumption for purine synthesis. The folate trapping mechanism described here for TH9619 differs from other MTHFD1/2 inhibitors and antifolates. Thus, our findings uncover an approach to attack cancer and reveal a regulatory mechanism in 1C metabolism.In this study, Green, Marttila, Kiweler et al. characterize one-carbon metabolism rewiring in response to a dual MTHFD1 and MTHFD2 inhibitor. This work provides insight into one-carbon fluxes, and reveals a previously uncharacterized vulnerability in cancer cells created by folate trapping

Family Firms and Firm Performance: Evidence from Japan

Corrigendum: Nature Structural and Molecular Biology 16 (12), 1331 (2009) doi:10.1038/nsmb1209-1331bInternational audienceThioredoxins (Trxs) are oxidoreductase enzymes, present in all organisms, that catalyze the reduction of disulfide bonds in proteins. By applying a calibrated force to a substrate disulfide, the chemical mechanisms of Trx catalysis can be examined in detail at the single-molecule level. Here we use single-molecule force-clamp spectroscopy to explore the chemical evolution of Trx catalysis by probing the chemistry of eight different Trx enzymes. All Trxs show a characteristic Michaelis-Menten mechanism that is detected when the disulfide bond is stretched at low forces, but at high forces, two different chemical behaviors distinguish bacterial-origin from eukaryotic-origin Trxs. Eukaryotic-origin Trxs reduce disulfide bonds through a single-electron transfer reaction (SET), whereas bacterial-origin Trxs show both nucleophilic substitution (SN2) and SET reactions. A computational analysis of Trx structures identifies the evolution of the binding groove as an important factor controlling the chemistry of Trx catalysis

Evaluación frecuente, mentorías y rendimiento académico en el programa mentor de Aeronáuticos

El Programa Mentor de Aeronáuticos se inicia en 2004con una doble vertiente de actuación. Por un lado, Tutores y Mentores facilitan el proceso de integración de los Alumnos de Nuevo Ingreso en la vida universitaria; por otro, el estudio de las dificultades académicas de los Alumnos Tutelados conduce a Cambios Metodológicas en el Aula que ayudan a activar las relaciones profesor-alumno y a mejorar el rendimiento del esfuerzo de todos, profesores y alumnos. Se describen éstas experiencias, así como los resultados obtenidos en los últimos cuatro año

Genome-Wide Identification of Transcription Start Sites, Promoters and Transcription Factor Binding Sites in E. coli

Despite almost 40 years of molecular genetics research in Escherichia coli a major fraction of its Transcription Start Sites (TSSs) are still unknown, limiting therefore our understanding of the regulatory circuits that control gene expression in this model organism. RegulonDB (http://regulondb.ccg.unam.mx/) is aimed at integrating the genetic regulatory network of E. coli K12 as an entirely bioinformatic project up till now. In this work, we extended its aims by generating experimental data at a genome scale on TSSs, promoters and regulatory regions. We implemented a modified 5′ RACE protocol and an unbiased High Throughput Pyrosequencing Strategy (HTPS) that allowed us to map more than 1700 TSSs with high precision. From this collection, about 230 corresponded to previously reported TSSs, which helped us to benchmark both our methodologies and the accuracy of the previous mapping experiments. The other ca 1500 TSSs mapped belong to about 1000 different genes, many of them with no assigned function. We identified promoter sequences and type of σ factors that control the expression of about 80% of these genes. As expected, the housekeeping σ70 was the most common type of promoter, followed by σ38. The majority of the putative TSSs were located between 20 to 40 nucleotides from the translational start site. Putative regulatory binding sites for transcription factors were detected upstream of many TSSs. For a few transcripts, riboswitches and small RNAs were found. Several genes also had additional TSSs within the coding region. Unexpectedly, the HTPS experiments revealed extensive antisense transcription, probably for regulatory functions. The new information in RegulonDB, now with more than 2400 experimentally determined TSSs, strengthens the accuracy of promoter prediction, operon structure, and regulatory networks and provides valuable new information that will facilitate the understanding from a global perspective the complex and intricate regulatory network that operates in E. coli