Same-day testing with initiation of antiretroviral therapy or tuberculosis treatment versus standard care for persons presenting with tuberculosis symptoms at HIV diagnosis: A randomized open-label trial from Haiti.

BACKGROUND: Same-day HIV testing and antiretroviral therapy (ART) initiation is being widely implemented. However, the optimal timing of ART among patients with tuberculosis (TB) symptoms is unknown. We hypothesized that same-day treatment (TB treatment for those diagnosed with TB; ART for those not diagnosed with TB) would be superior to standard care in this population. METHODS AND FINDINGS: We conducted an open-label trial among adults with TB symptoms at initial HIV diagnosis at GHESKIO in Haiti; participants were recruited and randomized on the same day. Participants were randomized in a 1:1 ratio to same-day treatment (same-day TB testing with same-day TB treatment if TB diagnosed; same-day ART if TB not diagnosed) versus standard care (initiating TB treatment within 7 days and delaying ART to day 7 if TB not diagnosed). In both groups, ART was initiated 2 weeks after TB treatment. The primary outcome was retention in care with 48-week HIV-1 RNA <200 copies/mL, with intention to treat (ITT) analysis. From November 6, 2017 to January 16, 2020, 500 participants were randomized (250/group); the final study visit occurred on March 1, 2021. Baseline TB was diagnosed in 40 (16.0%) in the standard and 48 (19.2%) in the same-day group; all initiated TB treatment. In the standard group, 245 (98.0%) initiated ART at median of 9 days; 6 (2.4%) died, 15 (6.0%) missed the 48-week visit, and 229 (91.6%) attended the 48-week visit. Among all who were randomized, 220 (88.0%) received 48-week HIV-1 RNA testing; 168 had <200 copies/mL (among randomized: 67.2%; among tested: 76.4%). In the same-day group, 249 (99.6%) initiated ART at median of 0 days; 9 (3.6%) died, 23 (9.2%) missed the 48-week visit, and 218 (87.2%) attended the 48-week visit. Among all who were randomized, 211 (84.4%) received 48-week HIV-1 RNA; 152 had <200 copies/mL (among randomized: 60.8%; among tested: 72.0%). There was no difference between groups in the primary outcome (60.8% versus 67.2%; risk difference: -0.06; 95% CI [-0.15, 0.02]; p = 0.14). Two new grade 3 or 4 events were reported per group; none were judged to be related to the intervention. The main limitation of this study is that it was conducted at a single urban clinic, and the generalizability to other settings is uncertain. CONCLUSIONS: In patients with TB symptoms at HIV diagnosis, we found that same-day treatment was not associated with superior retention and viral suppression. In this study, a short delay in ART initiation did not appear to compromise outcomes. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov NCT03154320.

CRISPR/Cas9-mediated genome editing of Schistosoma mansoni acetylcholinesterase.

CRISPR/Cas9-mediated genome editing shows cogent potential for the genetic modification of helminth parasites. We report successful gene knock-in (KI) into the genome of the egg of Schistosoma mansoni by combining CRISPR/Cas9 with single-stranded oligodeoxynucleotides (ssODNs). We edited the acetylcholinesterase (AChE) gene of S. mansoni targeting two guide RNAs (gRNAs), X5 and X7, located on exon 5 and exon 7 of Smp_154600, respectively. Eggs recovered from livers of experimentally infected mice were transfected by electroporation with a CRISPR/Cas9-vector encoding gRNA X5 or X7 combining with/ without a ssODN donor. Next generation sequencing analysis of reads of amplicon libraries spanning targeted regions revealed that the major modifications induced by CRISPR/Cas9 in the eggs were generated by homology directed repair (HDR). Furthermore, soluble egg antigen from AChE-edited eggs exhibited markedly reduced AChE activity, indicative that programed Cas9 cleavage mutated the AChE gene. Following injection of AChE-edited schistosome eggs into the tail veins of mice, an significantly enhanced Th2 response involving IL-4, -5, -10, and-13 was detected in lung cells and splenocytes in mice injected with X5-KI eggs in comparison to control mice injected with unmutated eggs. A Th2-predominant response, with increased levels of IL-4, -13, and GATA3, also was induced by X5 KI eggs in small intestine-draining mesenteric lymph node cells when the gene-edited eggs were introduced into the subserosa of the ileum of the mice. These findings confirmed the potential and the utility of CRISPR/Cas9-mediated genome editing for functional genomics in schistosomes.

Microbiome is not linked to clinical disease severity of familial Mediterranean fever in an international cohort of children.

OBJECTIVES: The severity of familial Mediterranean fever (FMF) may vary in different areas, suggesting a role for environmental factors. We analysed the composition of gut microbiota among children with FMF and healthy controls from Turkey and the USA and determined its effect on disease severity. METHODS: Children with FMF with pathogenic MEFV mutations and healthy controls from Turkey and the USA were enrolled. FMF disease activity was evaluated with the Autoinflammatory Disease Activity Index (AIDAI). Gut bacterial diversity was assessed by sequencing 16S rRNA gene libraries. RESULTS: We included 36 children from Turkey (28 patients with FMF, 8 healthy controls), and 21 patients and 6 controls from the USA. In the Turkish group, 28.6% of patients had severe disease, while 13.3% of US group patients had severe disease. As expected, we observed substantial differences between the gut microbiota of children from the two geographic regions, with Turkish patients and controls exhibiting higher relative abundances of Bacteriodia, while US patients and controls exhibited higher relative abundances of Clostridia. Alpha- and betadiversity did not differ significantly between FMF patients and controls, and neither was predictive of disease severity within each geographic region. We observed differences between FMF patients and controls in the relative abundance of some bacterial taxa at the amplicon sequence variant (ASV) level, but these differences received mixed statistical support. CONCLUSIONS: Among an international cohort of children with FMF, we did not find a strong effect of gut microbiota composition on disease severity. Other environmental or epigenetic factors may be operative.

#FlavorsSaveLives: An Analysis of Twitter Posts Opposing Flavored E-cigarette Bans.

BACKGROUND: Starting in 2019 policies restricting the availability of flavored e-cigarette products were proposed or implemented in the United States to curb vaping by youth. People took to Twitter to voice their opposition, referencing the phrase "Flavors Save Lives." This study documented the emerging themes pertaining to "Flavors Saves Lives" over a 12-month period. METHODS: The study period was from May 1, 2019, to May 1, 2020. A stratified sampling procedure supplied 2500 tweets for analysis. Posts were classified by one or more of the following themes: (1) Political Referendum; (2) Institutional Distrust; (3) Individual Rights; (4) Misinformation; (5) THC Vaping is the Real Problem; (6) Smoking Cessation; (7) Adult Use; and (8) Not a Bot. The temporal pattern of tweets over the year was examined. RESULTS: Political Referendum (76.5%) and Institutional Distrust (31.3%) were the most prominent themes, followed by Not a Bot (11.0%), Individual Rights (10.4%), Adult Use (8.0%), Smoking Cessation (6.6%), Misinformation (5.9%), and THC Vaping is the Real Problem (3.5%). Total tweet frequencies increased in September 2019 and peaked in November 2019 before returning to relatively low numbers. Political Referendum and Institutional Distrust were consistently the most prevalent themes over time. CONCLUSION: Twitter posts with the phrase "Flavors Save Lives" commonly discussed voting against political incumbents and mentioned distrust of government representatives. Findings demonstrated the possibility of near real-time Twitter monitoring of public opposition to flavor bans. These data may be valuable for designing tobacco control information campaigns in the future. IMPLICATIONS: (a) Starting in 2019 policies restricting the availability of flavored e-cigarette products were proposed or implemented in the United States to curb vaping by youth. (b) This study content analyzed Twitter posts with the phrase "Flavors Save Lives" from a 12-month period to understand opposition to flavor restrictions. (c) Twitter posts commonly discussed voting against political incumbents and mentioned distrust of government representatives. (d) Findings demonstrated the possibility of near real-time Twitter monitoring of public opposition to flavor bans, and contribute to a more comprehensive assessment of different sub-population's responses to current and proposed tobacco control information policies.

Environment, phylogeny, and photosynthetic pathway as determinants of leaf traits in savanna and forest graminoid species in central Brazil.

Leaf traits are closely linked to plant responses to the environment and can provide important information on adaptation and evolution. These traits may also result from common ancestry, so phylogenetic relationships also play an important role in adaptive evolution. We evaluated the effects of the closed forest environment (gallery forest) and the open savanna environment (cerrado) on the selection of leaf traits of graminoid species. The two plant communities differ in light, nutrients, and water availability, which are important drivers in the selection and differentiation of these traits. We also investigated the functional structure and the role of phylogeny in the functional organization of species, considering leaf traits. Patterns of leaf trait variation differed between forest and savanna species suggesting habitat specialization. Wider and longer leaves, with higher values of specific leaf area, chlorophyll, and nitrogen, seem to be an advantage for graminoid species growing in forest environments, while thicker leaves, with higher values of leaf dry-matter content and carbon, benefit species growing in savanna environments. We found few phylogenetic signals related to leaf traits in each environment. Therefore, the functional similarity that the gallery forest and cerrado graminoid species share within their group is independent of their phylogenetic proximity. Environmental filters affect the functional structure of communities differently, generating communities with trait values that are more distant than expected by chance in cerrado (functional dispersion), and closer than expected by chance in the gallery forest (functional convergence).

Leading Topics in Twitter Discourse on JUUL and Puff Bar Products: Content Analysis.

BACKGROUND: In response to the recent government restrictions, flavored JUUL products, which are rechargeable closed-system electronic cigarettes (e-cigarettes), are no longer available for sale. However, disposable closed-system products such as the flavored Puff Bar e-cigarette continues to be available. If e-cigarette consumers simply switch between products during the current government restrictions limited to 1 type of product over another, then such restrictions would be less effective. A step forward in this line of research is to understand how the public discusses these products by examining discourse referencing both Puff Bar and JUUL in the same conversation. Twitter data provide ample opportunity to capture such early trends that could be used to help public health researchers stay abreast of the rapidly changing e-cigarette marketplace. OBJECTIVE: The goal of this study was to examine public discourse referencing both Puff Bar and JUUL products in the same conversation on Twitter. METHODS: We collected data from Twitter's streaming application programming interface between July 16, 2019, and August 29, 2020, which included both "Puff Bar" and "JUUL" (n=2632). We then used an inductive approach to become familiar with the data and generate a codebook to identify common themes. Saturation was determined to be reached with 10 themes. RESULTS: Posts often mentioned flavors, dual use, design features, youth use, health risks, switching 1 product for the other, price, confusion over the differences between products, longevity of the products, and nicotine concentration. CONCLUSIONS: On examining the public's conversations about Puff Bar and JUUL products on Twitter, having described themes in posts, this study aimed to help the tobacco control community stay informed about 2 popular e-cigarette products with different device features, which can be potentially substituted for one another. Future health communication campaigns may consider targeting the health consequences of using multiple e-cigarette products or dual use to reduce exposure to high levels of nicotine among younger populations.

Use of kinase inhibitors against schistosomes to improve and broaden praziquantel efficacy.

Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ. Here we tested the in vitro efficacy of 15 selective and non-selective CaMK inhibitors against Schistosoma mansoni and showed that PZQ efficacy was improved against refractory juvenile parasites when combined with these CaMK inhibitors. By measuring CaMK activity and the mobility of adult S. mansoni, we identified two non-selective CaMK inhibitors, Staurosporine (STSP) and 1Naphthyl PP1 (1NAPP1), as promising candidates for further study. The impact of STSP and 1NAPP1 was investigated in mice infected with S. mansoni in the presence or absence of a sub-lethal dose of PZQ against 2- and 7-day-old schistosomula and adults. Treatment with STSP/PZQ induced a significant (47-68%) liver egg burden reduction compared with mice treated with PZQ alone. The findings indicate that the combination of STSP and PZQ dosages significantly improved anti-schistosomal activity compared to PZQ alone, demonstrating the potential of selective and non-selective CaMK/kinase inhibitors as a combination therapy with PZQ in treating schistosomiasis.

The Haiti cardiovascular disease cohort: study protocol for a population-based longitudinal cohort.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality among Haitians, having surpassed HIV in the last decade. Understanding the natural history of CVD in Haitians, including the age of onset, prevalence, incidence, and role of major risk factors and social determinants, is urgently needed to develop prevention and treatment interventions. Aim 1: Establish a population-based cohort of 3000 adults from Port-au-Prince and assess the prevalence of CVD risk factors and diseases and their association with social and environmental determinants. Aim 2: Determine the incidence of CVD risk factors and CVD during 2-3.5 years of follow-up and their association with social and environmental determinants. METHODS: The Haiti CVD Cohort is a longitudinal observational study of 3000 adults > 18 years in Port-au-Prince (PAP), Haiti. The study population is recruited using multistage random sampling from census blocks. Adults receive blood pressure (BP) measurements in the community and those with elevated BP are referred to the Groupe Haitien d'Etude Sarcome de Kaposi et des Infections Opportunistes Clinic for care. After informed consent, participants undergo a clinical exam with medical history. BP, electrocardiogram, echocardiogram, a study questionnaire on health behaviors, and laboratory specimens. Every 6 months, BP is remeasured. At 12 and 24 months, clinical exams and questionnaires are repeated. Labs are repeated at 24 months. Adjudicated study outcomes include the prevalence and incidence of CVD risk factors (hypertension, diabetes, obesity, dyslipidemia, kidney disease, inflammation, poor diet, smoking, and physical inactivity) and events (myocardial infarction, heart failure, stroke, and CVD mortality). We also measure social determinants including poverty. Depression, stress, social isolation, food insecurity, and lead exposure. Blood, urine, and stool samples are biobanked at study enrollment. DISCUSSION: The Haiti CVD Cohort is the largest population-based cohort study evaluating CVD risk factors and CVD among adults in urban Haiti with the goal of understanding the drivers of the CVD epidemic in Haiti. Study outcomes are comparable with existing international cohorts, and the biobank will provide important data for future research. Our goal is to translate findings from this study into pragmatic prevention and treatment interventions to fight the CVD epidemic in Haiti.

Live imaging of collagen deposition during experimental hepatic schistosomiasis and recovery: a view on a dynamic process.

Hepatic fibrosis is the central cause of chronic clinical pathology resulting from infection by the blood flukes Schistosoma japonicum or S. mansoni. Much has been elucidated regarding the molecular, cellular and immunological responses that correspond to the formation of the granulomatous response to trapped schistosome eggs. A central feature of this Th2 response is the deposition of collagen around the periphery of the granuloma. To date, traditional histology and transcriptional methods have been used to quantify the deposition of collagen and to monitor the formation of the hepatic granuloma during experimental animal models of schistosomiasis. We have investigated the dynamic nature of granuloma formation through the use of a transgenic mouse model (B6.Collagen 1(A) luciferase mice (B6.Coll 1A-luc+)). With this model and whole-animal bioluminescence imaging, we followed the deposition of collagen during an active schistosome infection with Chinese and Philippines geographical strains of S. japonicum and after clearance of the adult parasites by the drug praziquantel. Individual mice were re-imaged over the time course to provide robust real-time quantitation of the development of chronic fibrotic disease. This model provides an improved method to follow the course of hepatic schistosomiasis-induced hepatic pathology and effectively supports the current dogma of the formation of hepatic fibrosis, originally elucidated from static traditional histology. This study demonstrates the first use of the B6.Coll 1A-luc+ mouse to monitor the dynamics of disease development and the treatment of pathogen-induced infection with the underlying pathology of fibrosis.

High Burden of Non-communicable Diseases among a Young Slum Population in Haiti.

The objective of this study was to characterize the demographics and population health of four slum communities in Port-au-Prince, Haiti, including population density and the burden of communicable and non-communicable diseases. Four urban slums were surveyed using a population-representative design between July and October 2016. A multistage cluster area random sampling process was used to identify households and individuals for the survey. Household surveys included rosters of residents, household characteristics, adult and child deaths in the past year, child health, and healthcare access and utilization. Individual surveys of two randomly sampled adults from each household included sociodemographic data, maternal health, and adult health. Additionally, blood pressure, height, weight, and psychological distress were measured by study staff. Data were weighted for complex survey design and non-response. A total of 525 households and 894 individuals completed the survey (96% household and 90% individual response rate, respectively). The estimated population density was 58,000 persons/km2. Across slums, 55% of all residents were female, and 38% were adolescents and youth 10-24 years. Among adults, 58% were female with median age 29 years (22-38). The most common adult illnesses were severe psychological distress (24%), hypertension (20%), history of physical injury/trauma (10%), asthma (7%), history of cholera (4%), and history of tuberculosis (3%). Ten percent of adults had obesity (BMI > 30 kg/m2), and 7% currently smoked. The most common under-5 diseases during the last 3 months were respiratory and gastrointestinal illnesses (50% and 28%, respectively). One-third of households reported needing medical care for a child in the past year but not being able to access it, largely due to financial constraints. Unique features of these slums are a population structure dominated by adolescents and youth, a high proportion of females, and a high burden of non-communicable diseases including hypertension and psychological distress. Screening, diagnostic, and disease management interventions are urgently needed to protect and promote improved population health outcomes in these slum communities.

T cell-mediated immunity in CBA mice during Schistosoma japonicum infection.

Characterisation of the cellular immune response to schistosomiasis is well established for Schistosoma mansoni but a comprehensive description of T cell-mediated immune responses against S. japonicum infection is lacking. Accordingly, 20 CBA mice were infected with cercariae of S. japonicum and the immune response at different time points was determined. Mouse spleen and liver lymphocytes were isolated from the mice and stimulated with schistosomal adult worm antigen preparation (SWAP) and schistosomal soluble egg antigen (SEA). There was a relatively higher Th1 immune response to SWAP compared to SEA at the early phase of infection (up to week 5 post challenge). However, a Th2 immune response directed against SEA was dominant at week 6 post-infection, a time point when the highest IgG response against both SWAP and, especially, SEA was generated. The regulatory immune response was highest at the early phase of the immune response (up to week 5 post challenge) followed by a rapid decline at week 6-post infection. Before egg-laying, S. japonicum induced a regulatory T cell immune response which may limit the early Th1-mediated immune response that is believed to be protective in murine schistosomiasis. Following egg laying, the immune response was polarized to a Th2 immune response mainly directed against the eggs and this may contribute to parasite survival.

The FANMI ("my FAMILY" in Creole) study to evaluate community-based cohort care for adolescent and young women living with HIV in Haiti: protocol for a randomized controlled trial.

BACKGROUND: Adolescent girls and young women living with HIV in resource-limited settings have the poorest health outcomes of any age group, due in part to poor retention in care. Differentiated models of HIV care that target the specific challenges of young people living with HIV are urgently needed. METHODS: The FANMI study is an unblinded randomized controlled trial designed to evaluate the efficacy of an adolescent-specific model of HIV care in Port-au-Prince, Haiti. The FANMI intervention places newly young women living with HIV who are not currently on ART or on ART ≤ 3 months, in cohorts of 5-10 peers to receive monthly group HIV care in a community location. In contrast, participants in the standard care arm receive routine HIV care and individual counseling each month in GHESKIO's Adolescent Clinic. A total of 160 participants ages 16-23 years old are being randomized on a 1:1 basis. The primary outcome is retention in HIV care defined as being alive and in care at 12 months after enrollment. Secondary outcomes include viral suppression at 12 months, sexual risk behaviors, acceptability of the FANMI intervention, and health care utilization and costs. DISCUSSION: The FANMI study evaluates a novel community-based cohort model of HIV care aimed at improving retention in care and reducing risk behaviors for HIV transmission among adolescent girls and young women living with HIV. Specifically, the FANMI model of care addresses social isolation by placing participants in cohorts of 5-10 peers to provide intensified peer support and makes HIV health management a group norm; reduces stigma and improves convenience by providing care in a community setting; and integrates clinical care and social support by the same providers to streamline care and promote long-term patient-provider relationships. If shown to be effective, the FANMI intervention may serve as a model of HIV care for improving retention among hard-to-reach adolescents and young adults in Haiti and could be adapted for other high-risk groups globally. TRIAL REGISTRATION: Identifier: NCT03286504, Registered September 18, 2017.

Protective Immune Responses Generated in a Murine Model Following Immunization with Recombinant Schistosoma japonicum Insulin Receptor.

There is a pressing need to develop vaccines for schistosomiasis given the current heavy dependency on praziquantel as the only available drug for treatment. We previously showed the ligand domain of the Schistosoma japonicum insulin receptor 1 and 2 (rSjLD1 and 2) fusion proteins conferred solid protection in mice against challenge infection with S. japonicum. To improve vaccine efficacy, we compared the immunogenicity and protective efficacy of rSjLD1 on its own and in combination with S. japonicum triose-phosphate isomerase (SjTPI), formulated with either of two adjuvants (QuilA and montanide ISA 720VG) in murine vaccine trials against S. japonicum challenge. The level of protection was higher in mice vaccinated only with rSjLD1 formulated with either adjuvant; rSjTPI or the rSjTPI-rSjLD1 combination resulted in a lower level of protection. Mirroring our previous results, there were significant reductions in the number of female worms (30⁻44%), faecal eggs (61⁻68%), liver eggs (44⁻56%), intestinal eggs (46⁻48%) and mature intestinal eggs (58⁻63%) in the rSjLD1-vaccinated mice compared with the adjuvant only groups. At 6-weeks post-cercarial challenge, a significantly increased production of interferon gamma (IFNγ) in rSjLD1-stimulated splenic CD4⁺ T cells was observed in the rSjLD1-vaccinated mice suggesting a Th1-type response is associated with the generated level of protective efficacy.

Suppression of Schistosoma japonicum Acetylcholinesterase Affects Parasite Growth and Development.

To further investigate the importance of Schistosoma japonicum acetylcholinesterase (SjAChE) in cholinergic signaling for parasite growth and development, we used RNA interference (RNAi) to knock-down its expression in adults and eggs in vitro. This resulted in its reduced transcription but also expression of other important genes involved both in cholinergic signaling and glucose uptake were impacted substantially. Significant decreases in AChE protein expression, AChE enzymatic activity, and glucose uptake were observed in the SjAChE-knockdown parasites compared with luciferase controls. In vaccine/challenge experiments, we found that immunization of mice with recombinant SjAChE (rSjAChE) expressed in Escherichia coli elicited reductions in male worm numbers (33%), liver granuloma density (41%), and reduced numbers of mature intestinal eggs (73%) in the vaccinated group compared with the control group. These results indicate AChE plays an important role in the metabolism of male worms, and impacts indirectly on female fecundity leading to increased numbers of immature eggs being released and reduced sizes of liver granulomas. Furthermore, cytokine analysis showed that immunization of mice with rSjAChE elicited a predominantly Th1-type immune response characterized by increased production of IFNγ in splenic CD4⁺ T cells of vaccinated mice. The study confirms the potential of SjAChE as a vaccine/drug candidate against zoonotic schistosomiasis japonica.

Secreted and Tissue miRNAs as Diagnosis Biomarkers of Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor that originates in the pleura, is diagnosed in advanced stages and has a poor prognosis. Accurate diagnosis of MPM is often difficult and complex, and the gold standard diagnosis test is based on qualitative analysis of markers in pleural tissue by immunohistochemical staining. Therefore, it is necessary to develop quantitative and non-subjective alternative diagnostic tools. MicroRNAs are non-coding RNAs that regulate essential cellular mechanisms at the post-transcriptional level. Recent evidence indicates that miRNA expression in tissue and body fluids is aberrant in various tumors, revealing miRNAs as promising diagnostic biomarkers. This review summarizes evidence regarding secreted and tissue miRNAs as biomarkers of MPM and the biological characteristics associated with their potential diagnostic value. In addition to studies regarding miRNAs with potential diagnostic value for MPM, studies that aimed to identify the miRNAs involved in molecular mechanisms associated with MPM development are described with an emphasis on relevant aspects of the experimental designs that may influence the accuracy, consistency and real diagnostic value of currently reported data.

Preventive Care Screening in the Puerto Rican Geriatric Population: A Formative Evaluation of Patient Knowledge.

OBJECTIVE: This study was meant to be the first step in bridging a gap in the literature concerning Puerto Rican geriatric patients' levels of knowledge concerning 4 preventive care screening tests: mammography, bone densitometry, colonoscopy, and lipid panels. METHODS: Patients 65 years old and older were interviewed at the University of Puerto Rico (UPR), Medical Sciences Campus, primary care clinics. Fisher's exact test was used to assess knowledge status for each screening test. RESULTS: Fifty-three participants, 53% being women, took part in the study. All the women (100%) reported having knowledge about mammography screening as well as about bone densitometry scans (71%); 91% of the participants reported having knowledge concerning colonoscopy. Only 34% understood what information results from a lipid panel. The majority of the participants were not aware of precisely when each of the screening tests under discussion should be undertaken. For all the screenings, level of education and provider recommendation were associated with increased levels of knowledge (though statistically significant only for bone densitometry and lipid panels). CONCLUSION: Elderly Puerto Ricans appear to have knowledge about screening tests; however, there is an overall lack of knowledge about the timing of screening. Risk factors for this lack of knowledge are having a relatively lower level of education, the lack of healthcare-provider recommendation, and the lack of patient education. Understanding when to have tests is vital for interventions, in order to improve patient outcomes, which can include death from treatable conditions or diseases. Future research should include larger samples as well as studies of outcomes associated with these screening tests. These will help researchers and policymakers better understand this issue and aid in the development and implementation of interventions for both patients and physicians.

Origins and recent radiation of Brazilian Eupatorieae (Asteraceae) in the eastern Cerrado and Atlantic Forest.

The remarkable diversity of Eupatorieae in the Brazilian flora has received little study, despite the tribe's very high levels of endemism and importance in the threatened Cerrado and the Atlantic Forest biodiversity hotspots. Eupatorieae are one of the largest tribes in Asteraceae with 14 of 19 recognized subtribes occurring in Brazil. We constructed the largest phylogeny of Brazilian Eupatorieae to date that sampled the nrITS and ETS, chloroplast ndhI and ndhF genes, and the ndhI-ndhG intergenic spacer for 183 species representing 77 of the 85 Brazilian genera of the tribe. Maximum likelihood and Bayesian phylogenetic analyses showed that these species are not collectively monophyletic, so their distribution reflects multiple introductions into Brazil. A novel clade was found that includes 75% of the genera endemic to Brazil (Cerrado-Atlantic Forest Eupatorieae, "CAFE" clade). This radiation of at least 247 species concentrated in the Cerrado and Atlantic Forest biomes of central eastern Brazil is <7 my old and exhibits several ecologically diverse life forms. Eight subtribes of Brazilian Eupatorieae (Ageratinae, Alomiinae, Ayapaninae, Critoniinae, Disynaphiinae, Eupatoriinae, Gyptidinae and Hebecliniinae) and 16 genera (Ageratum, Agrianthus, Austroeupatorium, Bejaranoa, Chromolaena, Critonia, Disynaphia, Grazielia, Hatschbachiella, Heterocondylus, Koanophyllon, Lasiolaena, Neocabreria, Praxelis, Stylotrichium, and Symphyopappus) were found to be polyphyletic. We attribute incongruities between the molecular phylogenetic results and the current classification of the tribe mostly to convergent evolution of morphological characters traditionally used in the classification of the tribe. We used these phylogenetic results to suggest changes to the classification of some subtribes and genera of Eupatorieae that occur in Brazil.

Developmental exposure to bisphenol A (BPA) alters sexual differentiation in painted turtles (Chrysemys picta).

Environmental chemicals can disrupt endocrine signaling and adversely impact sexual differentiation in wildlife. Bisphenol A (BPA) is an estrogenic chemical commonly found in a variety of habitats. In this study, we used painted turtles (Chrysemys picta), which have temperature-dependent sex determination (TSD), as an animal model for ontogenetic endocrine disruption by BPA. We hypothesized that BPA would override TSD and disrupt sexual development. We incubated farm-raised turtle eggs at the male-producing temperature (26°C), randomly assigned individuals to treatment groups: control, vehicle control, 17ß-estradiol (E2, 20ng/g-egg) or 0.01, 1.0, 100µgBPA/g-egg and harvested tissues at hatch. Typical female gonads were present in 89% of the E2-treated "males", but in none of the control males (n=35). Gonads of BPA-exposed turtles had varying amounts of ovarian-like cortical (OLC) tissue and disorganized testicular tubules in the medulla. Although the percentage of males with OLCs increased with BPA dose (BPA-low=30%, BPA-medium=33%, BPA-high=39%), this difference was not significant (p=0.85). In all three BPA treatments, SOX9 patterns revealed disorganized medullary testicular tubules and ß-catenin expression in a thickened cortex. Liver vitellogenin, a female-specific liver protein commonly used as an exposure biomarker, was not induced by any of the treatments. Notably, these results suggest that developmental exposure to BPA disrupts sexual differentiation in painted turtles. Further examination is necessary to determine the underlying mechanisms of sex reversal in reptiles and how these translate to EDC exposure in wild populations.

Diagnosing Alzheimer's disease: Which dementia screening test to use in elderly Puerto Ricans with mild cognitive impairment and early Alzheimer's disease?

Typically, Alzheimer's disease (AD) diagnosis is not made at its earliest period, for instance, at mild cognitive impairment (MCI) and early AD (E-AD). Our study aims to demonstrate a correlation between the screening tools, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating (CDR), and the biological biomarkers in the cerebrospinal fluid (CSF) amyloid beta 1-42 (Aß42), phosphorylated tau (p-tau) proteins and total tau (t-tau)/Aß42 ratio in Puerto Ricans > 55 years old with MCI and E-AD. We evaluated 30 participants, including demographics, memory scales, and CSF biomarkers. Twenty-eight CSF biomarkers (Aß42, p-tau protein, and t-tau/Aß42 ratio) were analyzed using the Meso Scale Discovery Platform (MSD). Associations between memory scales (MoCA, MMSE, CDR) and CSF markers were performed using Spearman rho correlation. Our study revealed a statistical association favoring a direct relationship between MMSE and MoCA with t-tau/Aß42 ratio in CSF (P = 0.022, P = 0.035, respectively). We found a trend toward significance with an inverse relationship with MMSE and Aß42 (P = 0.069) and a direct relationship with MMSE and p-tau (P = 0.098). MMSE and MoCA screening tests were identified with a statistically significant association with the CSF biomarkers, specifically t-tau/Aß42 ratio, in elderly Puerto Ricans with MCI and E-AD. Puerto Ricans > 55 years old with MCI and E-AD could be screened confidently with MMSE and MoCA for a higher likelihood of earlier detection and, thus, initiation of disease-modifying treatment and prompt non-pharmacological interventions.