Empowering Underserved Communities in Southern Puerto Rico: A Formal Training Program in Community Health Promotion.

Community health promotion offers a potential solution to persistent healthcare challenges, with community health workers playing a pivotal role. The Community Training Institute for Health Disparities (CTIHD) implemented a problem-solving curriculum in Community Health Promotion, integrating a competency-based learning model through two courses: Introduction to Community Health Promotion and Design of an Action Plan for the Promotion of Community Health. Each course comprised ten three-hour sessions, featuring pre/post-tests, evaluations, and a cognitive debriefing. Knowledge change was assessed using pre/post-test scores among 27 community leaders from southern Puerto Rico. Cohort 1 and Cohort 2 demonstrated an overall retention rate of 62.6% and 96.7%, respectively. Although differences in knowledge gained between cohorts and courses weren't statistically significant, a trend toward increased knowledge was noted. Cohort 1 experienced a 22% knowledge increase in Course 1 and a 24% increase in Course 2. Cohort 2 demonstrated a 41% knowledge increase in Course 1 and a 25% increase in Course 2. The CTIHD's Community Health Promotion Program has made significant strides in elevating awareness and knowledge, marking a positive step toward reducing health disparities and fostering healthier, empowered communities in southern Puerto Rico.

Impacts of Chronic Obstructive Pulmonary Disease Care Pathway on Healthcare Utilization and Costs: A Matched Multiple Control Cohort Study in Saskatchewan, Canada.

OBJECTIVES: This study aimed to evaluate the real-world impacts of a chronic obstructive pulmonary disease (COPD) care pathway program on healthcare utilization and costs in Saskatchewan, Canada. METHODS: A difference-in-differences evaluation of a real-life deployment of a COPD care pathway, using patient-level administrative health data in Saskatchewan, was conducted. The intervention group (n = 759) included adults (35+ years) with spirometry-confirmed COPD diagnosis recruited into the care pathway program in Regina between April 1, 2018 and March 31, 2019. The 2 control groups comprised adults (35+ years) with COPD who lived in Saskatoon during the same period (n = 759) or Regina between April 1, 2015 and March 31, 2016 (n = 759) who did not participate in the care pathway. RESULTS: Compared with the individuals in the Saskatoon control groups, individuals in the COPD care pathway group had shorter inpatient hospital length of stay (average treatment effect on the treated [ATT] -0.46, 95% CI -0.88 to -0.04) but a higher number of general practitioner visits (ATT 1.46, 95% CI 1.14 to 1.79) and specialist physician visits (ATT 0.84, 95% CI 0.61 to 1.07). Regarding healthcare costs, individuals in the care pathway group had higher COPD-related specialist visit costs (ATT $81.70, 95% CI $59.45 to $103.96) but lower COPD-related outpatient drug dispensation costs (ATT -$4.81, 95% CI -$9.34 to -$0.27). CONCLUSIONS: The care pathway reduced inpatient hospital length of stay, but increased general practitioner and specialist physician visits for COPD-related services within the first year of implementation.

Expression of DNA Methyltransferase 3B Isoforms Is Associated with DNA Satellite 2 Hypomethylation and Clinical Prognosis in Advanced High-Grade Serous Ovarian Carcinoma.

Alterations in DNA methylation are critical for the carcinogenesis of ovarian tumors, especially ovarian carcinoma (OC). DNMT3B, a de novo DNA methyltransferase (DNMT), encodes for fifteen spliced protein products or isoforms. DNMT3B isoforms lack exons for the catalytic domain, with functional consequences on catalytic activity. Abnormal expression of DNMT3B isoforms is frequently observed in several types of cancer, such as breast, lung, kidney, gastric, liver, skin, leukemia, and sarcoma. However, the expression patterns and consequences of DNMT3B isoforms in OC are unknown. In this study, we analyzed each DNMT and DNMT3B isoforms expression by qPCR in 63 OC samples and their association with disease-free survival (DFS), overall survival (OS), and tumor progression. We included OC patients with the main histological subtypes of EOC and patients in all the disease stages and found that DNMTs were overexpressed in advanced stages (p-value < 0.05) and high-grade OC (p-value < 0.05). Remarkably, we found DNMT3B1 overexpression in advanced stages (p-value = 0.0251) and high-grade serous ovarian carcinoma (HGSOC) (p-value = 0.0313), and DNMT3B3 was overexpressed in advanced stages (p-value = 0.0098) and high-grade (p-value = 0.0004) serous ovarian carcinoma (SOC). Finally, we observed that overexpression of DNMT3B isoforms was associated with poor prognosis in OC and SOC. DNMT3B3 was also associated with FDS (p-value = 0.017) and OS (p-value = 0.038) in SOC patients. In addition, the ovarian carcinoma cell lines OVCAR3 and SKOV3 also overexpress DNMT3B3. Interestingly, exogenous overexpression of DNMT3B3 in OVCAR3 causes demethylation of satellite 2 sequences in the pericentromeric region. In summary, our results suggest that DNMT3B3 expression is altered in OC.

Real-World Cost-Consequence Analysis of an Integrated Chronic Disease Management Program in Saskatchewan, Canada.

An integrated disease management program otherwise called a clinical pathway was recently implemented in Saskatchewan, Canada for patients living with chronic obstructive pulmonary disease (COPD). This study compared the real-world costs and consequences of the COPD clinical pathway program with 2 control treatment programs. The study comprised adult COPD patients in Regina (clinical pathway group, N = 759) matched on propensity scores to 2 independent control groups of similar adults in (1) Regina (historical controls, N = 759) and (2) Saskatoon (contemporaneous controls, N = 759). The study measures included patient-level healthcare costs and acute COPD exacerbation outcomes, both tracked in population-based administrative health data over a one-year follow-up period. Analyses included Cox proportional hazards models and differences in means between groups. The bias-corrected and accelerated bootstrap method was used to calculate 95% confidence intervals (CI). The COPD pathway patients had lower risks of moderate (hazard ratio [HR] =0.57, 95% CI [0.40-0.83]) and severe (HR = 0.43, 95% CI [0.28-0.66]) exacerbations compared to the historical control group, but similar risks compared with the contemporaneous control group. The COPD pathway patients experienced fewer episodes of exacerbations compared with the historical control group (mean difference = -0.30, 95% CI [-0.40, -0.20]) and the contemporaneous control group (mean difference = -0.12, 95% CI [-0.20, -0.03]). Average annual healthcare costs in Canadian dollars were marginally higher among patients in the COPD clinical pathway (mean = $10 549, standard deviation [SD] =$18 149) than those in the contemporaneous control group ($8841, SD = $17 120), but comparable to the historical control group ($10 677, SD = $21 201). The COPD pathway provides better outcomes at about the same costs when compared to the historical controls, but only slightly better outcomes and at a marginally higher cost when compared to the contemporaneous controls.

An economic evaluation of chronic obstructive pulmonary disease clinical pathway in Saskatchewan, Canada: Data-driven techniques to identify cost-effectiveness among patient subgroups.

BACKGROUND: Saskatchewan has implemented care pathways for several common health conditions. To date, there has not been any cost-effectiveness evaluation of care pathways in the province. The objective of this study was to evaluate the real-world cost-effectiveness of a chronic obstructive pulmonary disease (COPD) care pathway program in Saskatchewan. METHODS: Using patient-level administrative health data, we identified adults (35+ years) with COPD diagnosis recruited into the care pathway program in Regina between April 1, 2018, and March 31, 2019 (N = 759). The control group comprised adults (35+ years) with COPD who lived in Saskatoon during the same period (N = 759). The control group was matched to the intervention group using propensity scores. Costs were calculated at the patient level. The outcome measure was the number of days patients remained without experiencing COPD exacerbation within 1-year follow-up. Both manual and data-driven policy learning approaches were used to assess heterogeneity in the cost-effectiveness by patient demographic and disease characteristics. Bootstrapping was used to quantify uncertainty in the results. RESULTS: In the overall sample, the estimates indicate that the COPD care pathway was not cost-effective using the willingness to pay (WTP) threshold values in the range of $1,000 and $5,000/exacerbation day averted. The manual subgroup analyses show the COPD care pathway was dominant among patients with comorbidities and among patients aged 65 years or younger at the WTP threshold of $2000/exacerbation day averted. Although similar profiles as those identified in the manual subgroup analyses were confirmed, the data-driven policy learning approach suggests more nuanced demographic and disease profiles that the care pathway would be most appropriate for. CONCLUSIONS: Both manual subgroup analysis and data-driven policy learning approach showed that the COPD care pathway consistently produced cost savings and better health outcomes among patients with comorbidities or among those relatively younger. The care pathway was not cost-effective in the entire sample.

A Qualitative Approach to Explore Perceptions, Opinions and Beliefs of Communities who Experienced Health Disparities towards Chronic Health Conditions.

The prevalence of chronic medical conditions is associated with biological, behavioral, and social factors. In Puerto Rico (PR), events such as budget cuts to essential services in recent years have contributed to deepening health disparities. This study aimed to explore community perceptions, opinions, and beliefs about chronic health conditions in the southern region of Puerto Rico. Framed by a Community-Based Participatory Research (CBPR) approach, this qualitative study developed eight focus groups (n = 59) with adults (age of 21 or older) from southern Puerto Rico, in person and remotely, during 2020 and 2021. Eight open-ended questions were used for discussions, which were recorded, transcribed, and analyzed via computer analysis. Content analysis revealed four main dimensions: knowledge, vulnerabilities, barriers, and identified resources. Relevant topics included: concerns about mental health-depression, anxiety, substance use, and suicide; individual vulnerabilities-risk behaviors, and unhealthy habits; economic factors-health access and commercialization of health. Resource identification was also explored, and participants discussed the importance of alliances between public and private sectors. These topics were addressed across all focus groups, with various recommendations. The results highlight the importance of prioritizing identified community needs, evaluating available resources, and promoting tailored-made interventions to reduce risk factors for chronic health conditions.

Mitotic and DNA Damage Response Proteins: Maintaining the Genome Stability and Working for the Common Good.

Cellular function is highly dependent on genomic stability, which is mainly ensured by two cellular mechanisms: the DNA damage response (DDR) and the Spindle Assembly Checkpoint (SAC). The former provides the repair of damaged DNA, and the latter ensures correct chromosome segregation. This review focuses on recently emerging data indicating that the SAC and the DDR proteins function together throughout the cell cycle, suggesting crosstalk between both checkpoints to maintain genome stability.

Regulation of miRNAs Expression by Mutant p53 Gain of Function in Cancer.

The p53 roles have been largely described; among them, cell proliferation and apoptosis control are some of the best studied and understood. Interestingly, the mutations on the six hotspot sites within the region that encodes the DNA-binding domain of p53 give rise to other very different variants. The particular behavior of these variants led to consider p53 mutants as separate oncogene entities; that is, they do not retain wild type functions but acquire new ones, namely Gain-of-function p53 mutants. Furthermore, recent studies have revealed how p53 mutants regulate gene expression and exert oncogenic effects by unbalancing specific microRNAs (miRNAs) levels that provoke epithelial-mesenchymal transition, chemoresistance, and cell survival, among others. In this review, we discuss recent evidence of the crosstalk between miRNAs and mutants of p53, as well as the consequent cellular processes dysregulated.

Health Sentinel: A mobile crowdsourcing platform for self-reported surveys provides early detection of COVID-19 clusters in San Luis Potosí, Mexico.

BACKGROUND: The Health Sentinel (Centinela de la Salud, CDS), a mobile crowdsourcing platform that includes the CDS app, was deployed to assess its utility as a tool for COVID-19 surveillance in San Luis Potosí, Mexico. METHODS: The CDS app allowed anonymized individual surveys of demographic features and COVID-19 risk of transmission and exacerbation factors from users of the San Luis Potosí Metropolitan Area (SLPMA). The platform's data processing pipeline computed and geolocalized the risk index of each user and enabled the analysis of the variables and their association. Point process analysis identified geographic clustering patterns of users at risk and these were compared with the patterns of COVID-19 cases confirmed by the State Health Services. RESULTS: A total of 1554 COVID-19 surveys were administered through the CDS app. Among the respondents, 50.4 % were men and 49.6 % women, with an average age of 33.5 years. Overall risk index frequencies were, in descending order: no-risk 77.8 %, low risk 10.6 %, respiratory symptoms 6.7 %, medium risk 1.4 %, high risk 2.0 %, very high risk 1.5 %. Comorbidity was the most frequent vulnerability category (32.4 %), followed by the inability to keep home lockdown (19.2 %). Statistically significant risk clusters identified at a spatial scale between 5 and 730 m coincided with those in neighborhoods containing substantial numbers of confirmed COVID-19 cases. CONCLUSIONS: The CDS platform enables the analysis of the sociodemographic features and spatial distribution of individual risk indexes of COVID-19 transmission and exacerbation. It is a useful epidemiological surveillance and early detection tool because it identifies statistically significant and consistent risk clusters in neighborhoods with a substantial number of confirmed COVID-19 cases.

Saliva is a reliable and accessible source for the detection of SARS-CoV-2.

OBJECTIVES: The aim of this study was to investigate the feasibility of saliva sampling as a non-invasive and safer tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to compare its reproducibility and sensitivity with nasopharyngeal swab samples (NPS). The use of sample pools was also investigated. METHODS: A total of 2107 paired samples were collected from asymptomatic healthcare and office workers in Mexico City. Sixty of these samples were also analyzed in two other independent laboratories for concordance analysis. Sample processing and analysis of virus genetic material were performed according to standard protocols described elsewhere. A pooling analysis was performed by analyzing the saliva pool and the individual pool components. RESULTS: The concordance between NPS and saliva results was 95.2% (kappa 0.727, p = 0.0001) and 97.9% without considering inconclusive results (kappa 0.852, p = 0.0001). Saliva had a lower number of inconclusive results than NPS (0.9% vs 1.9%). Furthermore, saliva showed a significantly higher concentration of both total RNA and viral copies than NPS. Comparison of our results with those of the other two laboratories showed 100% and 97% concordance. Saliva samples are stable without the use of any preservative, and a positive SARS-CoV-2 sample can be detected 5, 10, and 15 days after collection when the sample is stored at 4 °C. CONCLUSIONS: The study results indicate that saliva is as effective as NPS for the identification of SARS-CoV-2-infected asymptomatic patients. Sample pooling facilitates the analysis of a larger number of samples, with the benefit of cost reduction.

Outcomes of visceral leishmaniasis in pregnancy: A retrospective cohort study from South Sudan.

INTRODUCTION: Visceral leishmaniasis (VL) is endemic in South Sudan, where outbreaks occur frequently. Because of changes in the immune system during pregnancy, pregnant women are considered particularly vulnerable for developing complications of VL disease, including opportunistic infections. There is limited evidence available about clinical aspects and treatment outcomes of VL in pregnancy. We describe characteristics, maternal and pregnancy outcomes from a cohort of pregnant women with VL. METHODS: We conducted a retrospective analysis using routine programme data from a MSF health facility in Lankien, Jonglei State, South Sudan, between Oct 2014 and April 2018. Records were extracted of women diagnosed with VL while pregnant, and those symptomatic during pregnancy but diagnosed during the first two weeks postpartum. Records were matched with a random sample of non-pregnant women of reproductive age (15-45 years) with VL from the same period. RESULTS: We included 113 women with VL in pregnancy, and 223 non-pregnant women with VL. Women with VL in pregnancy presented with more severe anaemia, were more likely to need blood transfusion (OR 9.3; 95%CI 2.5-34.2) and were more often prescribed antibiotics (OR 6.0; 95%CI 3.4-10.6), as compared to non-pregnant women with VL. Adverse pregnancy outcomes, including miscarriage and premature delivery, were reported in 20% (16/81) where VL was diagnosed in pregnancy, and 50% 13/26) where VL was diagnosed postpartum. Postpartum haemorrhage was common. Pregnant women were more likely to require extension of treatment to achieve cure (OR 10.0; 95%CI 4.8-20.9), as compared to non-pregnant women with VL. Nevertheless, overall initial cure rates were high (96.5%) and mortality was low (1.8%) in this cohort of pregnant women with VL. CONCLUSION: This is the largest cohort in the literature of VL in pregnancy. Our data suggest that good maternal survival rates are possible in resource-limited settings, despite the high incidence of complications.

Promoting Integrated Mental Health Care Services in Disaster Response Programs: Lessons Learned After the Impact of Hurricane María in Puerto Rico.

Meteorological and even human-made disasters are increasing every year in frequency and magnitude. The passage of a disaster affects a society without distinction, but groups with social vulnerability (low socioeconomic status, chronic medical, or psychological conditions, limited access to resources) face the most significant impact. As a result, psychological and behavioral symptoms (eg, depression and anxiety) can ensue, making the immediate response of mental health services crucial. Secondary data from a database of a temporary healthcare unit were analyzed. A total of 54 records were reviewed to collect information; univariate and bivariate analyses were done. The purpose of this article is to present our experience regarding the incorporation of a mental health services model, with its respective benefits and challenges, into a temporary healthcare unit, after Hurricane Maria in 2017.

Self-reported health problems among travelers visiting Cuzco: a Peruvian Airport survey.

Travel related illnesses are a concern among travelers visiting developing countries. These illnesses affect the travelers' plans and the local tourism industry. Few data on travel related illnesses are available from tourist destinations. Foreign travelers answered a self-administered questionnaire on health issues at the departures area of Cuzcos' International Airport between August and November 2002. Self-reported travel related illnesses that occurred during the travelers stay in Cuzco were compared with demographic and risk factors. The total number of participants was 5988. Their mean age was 35.4 years (SD 11.4), and slightly over half were female. The most common countries of residence were the United States (23.5%) and the United Kingdom (20%). The median length of stay in Cuzco was 5 days (IQR: 4-7 days). Pre-travel advice was received by 93.6% of the participants. Half (47.6%) of the participants became ill while in Cuzco. The most common illnesses reported were diarrhea (49.8%), altitude sickness (43.2%), and upper respiratory infections (21.7%). Most participants who reported an illness treated themselves (75.5%), and only 22.1% sought medical attention. It is concluded that a significant burden of disease is observed in travelers to Cuzco. Self-medication is very common and apparently preferred over formal medical attention.

Assessing Acceptability, Feasibility, and Preliminary Effectiveness of a Community-Based Participatory Research Curriculum for Community Members: A Contribution to the Development of a Community-Academia Research Partnership.

Purpose: The community-based participatory research approach has been identified as a great asset in reducing health disparities through the integration of community members in all phases of the research process. It is essential to provide skills to community members to achieve successful research partnerships. The purpose of this study is to evaluate the feasibility, acceptability, and preliminary efficacy of the community-based participatory research training curriculum for community members. Methods: Using mixed-methods, noncomparative design, eight workshops were developed and tested. Workshops covered topics such as community-based participatory research principles, health disparities, ethics in community-based participatory research, and fundamentals of research methodology. A total of 25 community leaders were trained. Pre-/post-test knowledge (unpaired t-test), retention rate, workshop satisfaction, and cognitive debriefing sessions were used to assess knowledge gained and acceptability and feasibility of the curriculum. Results: A retention rate of 100% and an average satisfaction of 92.68% were obtained. Preliminary effectiveness results indicate that there was an overall significant change in participant's knowledge before and after the curriculum (p<0.001). In the cognitive debriefing, participants were satisfied with the organization and structure and found the curriculum feasible. Furthermore, participants identified the skills acquired to aid in being more effective in their communities and work with academic researchers. The following changes were recommended: workshops' order, time, practical activities, and level of language. Discussion: Findings from this study suggest that the curriculum was acceptable and feasible to community leaders and that it might provide skills to actively incorporate community members in research activities. A large randomized clinical trial (RCT) study to evaluate curriculum effectiveness is recommended.

Oxigenoterapia de alto flujo y ventilación no invasiva en pacientes extubados por COVID-19 y riesgo de reintubación / High-flow oxygen therapy and non-invasive ventilation in extubated patients with COVID-19 and risk of reintubation

RESUMEN Introducción: La oxigenoterapia de alto flujo (OAF) y la ventilación no invasiva (VNI) son sistemas no invasivos que se administran post-extubación en pacientes COVID-19 para evitar la reintubación. Sin embargo, la evidencia sobre la elección de alguno de estos dispositivos no está muy clara. El objetivo fue determinar si el grupo que recibió OAF comparado con el grupo que recibió VNI se asocia a menor riesgo de reintubación en adultos con destete difícil y extubados por COVID-19. Material y métodos: Estudio cohorte retrospectivo en 206 registros de pacientes en destete difícil de ventilación mecánica en la Unidad de Cuidados Intensivos (UCI). El resultado primario fue reintubación en pacientes que fracasaron con OAF o VNI post-extubación y los resultados secundarios fueron estancia hospitalaria en UCI y mortalidad a los 90 días. Resultados: Doscientos seis pacientes cumplieron los criterios de inclusión, 102 pacientes en el grupo OAF y 104 pacientes en el grupo VNI. Durante el seguimiento de 72 horas, la tasa de reintubación en el grupo OAF fue mayor [n=24 (64,9%)] comparado con el grupo VNI [n=13 (35,1%)], mostrando en el análisis de Kaplan-Meier diferencias significativas (Log-Rank-Test p=0,005). La regresión de COX mostró mayor riesgo de reintubación en el grupo de OAF frente a VNI (HR 2,74; IC95% 1,42-5,68; p=0,007). No hubo diferencias en los días de hospitalización UCI (p=0,913) ni en mortalidad a los 90 días (Log-Rank-Test p=0,49). Conclusión: Este estudio observacional retrospectivo sugirió que la OAF frente al VNI se asoció a mayor riesgo de reintubación, pero no a mortalidad a los 90 días.

ABSTRACT Introduction: High flow oxygen therapy (HFO) and non-invasive ventilation (NIV) are non-invasive systems that are administered post-extubation in COVID-19 patients to avoid reintubation. However, the evidence on the choice of any of these devices is not very clear. The objective was to determine if the group that received OAF compared to the group that received NIV is associated with a lower risk of reintubation in adults with difficult weaning and extubated due to COVID-19. Material and methods: Retrospective cohort study in 206 records of patients in difficult weaning from mechanical ventilation in the Intensive Care Unit (ICU). The primary outcome was reintubation in patients who failed HFO or post-extubation NIV, and the secondary outcomes were ICU hospital stay and 90-day mortality. Results: Two hundred and six patients met the inclusion criteria, 102 patients in the OAF group and 104 patients in the NIV group. During the 72-h follow-up, the reintubation rate in the HFO group was higher [n=24 (64,9%)] compared to the NIV group [n=13 (35,1%)], showing in the analysis of Kaplan-Meier significant differences (Log-Rank-Test p=0,005). COX regression showed a higher risk of reintubation in the HFO group compared to NIV (HR 2,74; 95%CI 1,42-5,68; p=0,007). There were no differences in ICU hospitalization days (p=0,913) or in 90-day mortality (Log-Rank-Test p=0,49). Conclusion: This retrospective observational study suggested that HFO versus NIV was associated with a higher risk of reintubation, but not with 90-day mortality.

Sexual behavior, knowledge of STI prevention, and prevalence of serum markers for STI among tour guides in Cuzco/Peru.

BACKGROUND: Sexual behavior during travel has increasingly become a focus of travel medicine research. The perceived freedom when away from home can lead to increased casual sexual activities, often unprotected. Local sexual partners, particularly those who are in close contact with tourists due to their occupation, need to be considered more in research. The purpose of this study was to explore the sexual behavior, knowledge of STI prevention, and prevalence of serum markers of selected STIs in tour guides in Cuzco/Peru. METHODS: In this cross-sectional study, 161 tour guides completed a questionnaire consisting of information on demographics, sexual behavior, and knowledge about STI prevention. Blood samples of the participants were tested for antibodies against HSV2, Chlamydia trachomatis, and Treponema pallidum using commercial enzyme-linked immunosorbent assay kits. RESULTS: The majority of guides (65%) were sexually active during the year prior to the study and 10% had foreign partners. Consistent condom use was reported by 38.1%, but almost 42% did not use condoms. In total, 27.6% reported symptoms compatible with STI. Three quarters of the participants had previously received information on STI prevention, predominantly from health professionals. In total, 22% considered themselves at high risk for STI. Antibodies against C trachomatis were prevalent in 15%, while 88.2% were against HSV2. None had antibodies against T pallidum. CONCLUSIONS: There is an inconsistency in reported sexual behavior and reported knowledge about STI prevention. Because of the tour guides' bridging position between potential STI carriers in tourists and the local population, the reported nonuse of condoms is of concern. The prevalence of serum markers supports this concern, which is aggravated by the potential of noncurable infections. Current sexual health education strategies seem unsatisfactory, and major modifications are highly recommended.

Risk factors associated with diarrhea among international visitors to Cuzco, Peru.

The objective of this study was to determine the risk factors for travelers' diarrhea (TD) reported by visitors to Cuzco, Peru. In this cross-sectional study, self-administered questionnaires looking at perceived occurrence of health problems and pre-travel health advice were obtained from departing travelers at Cuzco's International Airport between August and November 2002. A total of 5,988 travelers participated in the study. The mean age was 35 years, and 51% were women. The prevalence of TD was 24%. Factors associated with TD in the multivariable analysis were use of antibiotic prophylaxis (OR: 3.20), vaccination against cholera (OR: 1.44), history of advice for safe food and water consumption (OR: 1.46), being younger than 35 years of age (OR: 1.37), being a resident of the United States (OR: 1.28), not staying in hotels in Cuzco (OR: 1.13), and number of unsafe food or beverages consumed (OR: 1.04). Remaining in Cuzco < 1 week was a protective factor (OR: 0.58). TD is common among travelers to Cuzco. This study suggests that conventional recommendations are not invariably effective at decreasing TD.

BUB1 and SURVIVIN proteins are not degraded after a prolonged mitosis and accumulate in the nuclei of HCT116 cells.

Spindle poisons activate the spindle assembly checkpoint and prevent mitotic exit until cells die or override the arrest. Several studies have focused on spindle poison-mediated cell death, but less is known about consequences in cells that survive a mitotic arrest. During mitosis, proteins such as CYCLIN B, SECURIN, BUB1 and SURVIVIN are degraded in order to allow mitotic exit, and these proteins are maintained at low levels in the next interphase. In contrast, exit from a prolonged mitosis depends only on degradation of CYCLIN B; it is not known whether the levels of other proteins decrease or remain high. Here, we analyzed the levels and localization of the BUB1 and SURVIVIN proteins in cells that escaped from a paclitaxel-mediated prolonged mitosis. We compared cells with a short arrest (HCT116 cells) with cells that spent more time in mitosis (HT29 cells) after paclitaxel treatment. BUB1 and SURVIVIN were not degraded and remained localized to the nuclei of HCT116 cells after a mitotic arrest. Moreover, BUB1 nuclear foci were observed; BUB1 did not colocalize with centromere proteins. In HT29 cells, the levels of BUB1 and SURVIVIN decreased during the arrest, and these proteins were not present in cells that reached the next interphase. Using time-lapse imaging, we observed morphological heterogeneity in HCT116 cells that escaped from the arrest; this heterogeneity was due to the cytokinesis-like mechanism by which the cells exited mitosis. Thus, our results show that high levels of BUB1 and SURVIVIN can be maintained after a mitotic arrest, which may promote resistance to cell death.

MAD2γ, a novel MAD2 isoform, reduces mitotic arrest and is associated with resistance in testicular germ cell tumors.

BACKGROUND: Prolonged mitotic arrest in response to anti-cancer chemotherapeutics, such as DNA-damaging agents, induces apoptosis, mitotic catastrophe, and senescence. Disruptions in mitotic checkpoints contribute resistance to DNA-damaging agents in cancer. MAD2 has been associated with checkpoint failure and chemotherapy response. In this study, a novel splice variant of MAD2, designated MAD2γ, was identified, and its association with the DNA damage response was investigated. METHODS: Endogenous expression of MAD2γ and full-length MAD2 (MAD2α) was measured using RT-PCR in cancer cell lines, normal foreskin fibroblasts, and tumor samples collected from patients with testicular germ cell tumors (TGCTs). A plasmid expressing MAD2γ was transfected into HCT116 cells, and its intracellular localization and checkpoint function were evaluated according to immunofluorescence and mitotic index. RESULTS: MAD2γ was expressed in several cancer cell lines and non-cancerous fibroblasts. Ectopically expressed MAD2γ localized to the nucleus and reduced the mitotic index, suggesting checkpoint impairment. In patients with TGCTs, the overexpression of endogenous MAD2γ, but not MAD2α, was associated with resistance to cisplatin-based chemotherapy. Likewise, cisplatin induced the overexpression of endogenous MAD2γ, but not MAD2α, in HCT116 cells. CONCLUSIONS: Overexpression of MAD2γ may play a role in checkpoint disruption and is associated with resistance to cisplatin-based chemotherapy in TGCTs.

Pretravel health advice among international travelers visiting Cuzco, Peru.

BACKGROUND: Cuzco, a Peruvian city of historical interest located 3,326 m above sea level, is a frequent destination for tourists. We conducted a descriptive study to assess the extent and sources of pretravel health advice received by international travelers before their arrival to Cuzco. METHODS: Data were collected as part of a health survey among travelers. Between August and November 2002, travelers between 15 and 65 years old were invited to fill out a questionnaire in the departing area of Cuzco's international airport. RESULTS: A total of 5,988 travelers participated. The mean age was 35.4 years (SD 11.4 yr); 50.6% were female and 50.8% were single. Tourism was the reason for traveling in 90.2% of the participants, and 89.3% of them were traveling with companions. Pretravel health information was received by 93.6%. The median number of information sources was two, with books (41.5%), travel medicine clinics (38.8%), the Internet (23.3%), and general practitioners (22.7%) as the main sources. Most frequently received recommendations were about safe food and water consumption (85%), use of insect repellents (66.0%), sunburn protection (64.4%), and condom use (22%). Only 16.5% took medication to prevent altitude sickness, and 14.2% took medication to prevent traveler's diarrhea. Variables independently associated with receiving pretravel health information from a health care professional were female gender, country of residence other than the United States, length of stay in Cuzco > 7 days, length of stay in other Peruvian cities > 7 days, tourism as the main reason for visiting Cuzco, traveling with companions, and consulting of more than one source of information. CONCLUSIONS: Most travelers arriving to Cuzco had received pretravel health information, and the majority obtained it from more than one source. Recommendations addressed for specific health risks, such as altitude sickness prophylaxis, were received by few travelers.