Biomedical Publications ABOUT PR

Injury-Related Emergency Department Visits After Hurricane Maria in a Southern Puerto Rico Hospital.

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Injury-Related Emergency Department Visits After Hurricane Maria in a Southern Puerto Rico Hospital.

Disaster Med Public Health Prep. 2019 Aug 28;:1-8

Authors: Frasqueri-Quintana VM, Oliveras García CA, Adams LE, Torres-Figueroa X, Iriarte RI, Ryff K, Sánchez-González L, Pérez Gómez V, Pérez-Rodríguez NM, Alvarado LI, Paz-Bailey G

Abstract
OBJECTIVE: The aim of this study was to describe individuals seeking care for injury at a major emergency department (ED) in southern Puerto Rico in the months after Hurricane Maria on September 20, 2017.
METHODS: After informed consent, we used a modified version of the Natural Disaster Morbidity Surveillance Form to determine why patients were visiting the ED during October 16, 2017-March 28, 2018. We analyzed visits where injury was reported as the primary reason for visit and whether it was hurricane-related.
RESULTS: Among 5 116 patients, 573 (11%) reported injury as the primary reason for a visit. Of these, 10% were hurricane-related visits. The most common types of injuries were abrasions, lacerations, and cuts (43% of all injury visits and 50% of hurricane-related visits). The most common mechanisms of injury were falls, slips, trips (268, 47%), and being hit by/or against an object (88, 15%). Most injury visits occurred during the first 3 months after the hurricane.
CONCLUSIONS: Surveillance after Hurricane Maria identified injury as the reason for a visit for about 1 in 10 patients visiting the ED, providing evidence on the patterns of injuries in the months following a hurricane. Public health and emergency providers can use this information to anticipate health care needs after a disaster.

PMID: 31455463 [PubMed - as supplied by publisher]

Entomological Investigation of Aedes aegypti In Neighborhoods With Confirmed Human Arbovirus Infection In Puerto Rico.

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Entomological Investigation of Aedes aegypti In Neighborhoods With Confirmed Human Arbovirus Infection In Puerto Rico.

J Am Mosq Control Assoc. 2018 Sep;34(3):233-236

Authors: Felix GE, Barrera R, Vazquez J, Ryff KR, Munoz-Jordan JL, Matias KY, Hemme RR

Abstract
The exotic arboviruses chikungunya (CHIKV) and Zika (ZIKV) recently caused large outbreaks and continue to circulate in Puerto Rico, prompting entomological investigations at 9 locations with confirmed CHIKV- or ZIKV-infected human cases. Adult mosquitoes were collected using the Centers for Disease Control and Prevention autocidal gravid ovitraps over a 14-day period at each site. Mean female Aedes aegypti captured per trap-week ranged from 13.47 per trap-week to 1.27 per trap-week. Arbovirus-positive pools were detected at 7 of the 9 sampling sites. We investigated vertical transmission by collecting Ae. aegypti eggs in a single location where ZIKV was found in adult mosquitoes. We discuss the relationship between vector density and infection rates and its implications for determining mosquito density thresholds of novel invasive arboviruses such as CHIKV and ZIKV.

PMID: 31442166 [PubMed - in process]

Hypoxia Has a Lasting Effect on Fast-Startle Behavior of the Tropical Fish Haemulon plumieri.

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Hypoxia Has a Lasting Effect on Fast-Startle Behavior of the Tropical Fish Haemulon plumieri.

Biol Bull. 2019 Aug;237(1):48-62

Authors: Sánchez-García MA, Zottoli SJ, Roberson LM

Abstract
Anthropogenic activities and climate change have resulted in an increase of hypoxic conditions in nearshore ecosystems worldwide. Depending on the persistence of a hypoxic event, the survival of aquatic animals can be compromised. Temperate fish exposed to hypoxia display a reduction in the probability of eliciting startle responses thought to be important for escape from predation. Here we examine the effect of hypoxia on the probability of eliciting fast-startle responses (fast-starts) of a tropical fish, the white grunt (Haemulon plumieri), and whether hypoxia has a prolonged impact on behavior once the fish are returned to normoxic conditions. White grunts collected from the San Juan Bay Estuary in Puerto Rico were exposed to an oxygen concentration of 2.5 mg L-1 (40% dissolved oxygen). We found a significant reduction in auditory-evoked fast-starts that lasted for at least 24 hours after fish were returned to normoxic conditions. Accessibility to the neuronal networks that underlie startle responses was an important motivator for this study. Mauthner cells are identifiable neurons found in most fish and amphibians, and these cells are known to initiate fast-starts in teleost fishes. The assumption that most of the short-latency responses in this study are Mauthner cell initiated provided the impetus to characterize the white grunt Mauthner cell. The identification of the cell provides a first step in understanding how low oxygen levels may impact a single cell and its circuit and the behavior it initiates.

PMID: 31441698 [PubMed - in process]

Epidemiology of Dengue, Chikungunya, and Zika Virus Disease in the U.S. States and Territories, 2017.

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Epidemiology of Dengue, Chikungunya, and Zika Virus Disease in the U.S. States and Territories, 2017.

Am J Trop Med Hyg. 2019 Aug 19;:

Authors: Adams LE, Martin SW, Lindsey NP, Lehman JA, Rivera A, Kolsin J, Landry K, Staples JE, Sharp TM, Paz-Bailey G, Fischer M

Abstract
Dengue, chikungunya, and Zika viruses, primarily transmitted by Aedes species mosquitoes, have caused large outbreaks in the Americas, leading to travel-associated cases and local mosquito-borne transmission in the United States. We describe the epidemiology of dengue, chikungunya, and noncongenital Zika virus disease cases reported from U.S. states and territories in 2017, including 971 dengue cases, 195 chikungunya cases, and 1,118 Zika virus disease cases. Cases of all three diseases reported from the territories were reported as resulting from local mosquito-borne transmission. Cases reported from the states were primarily among travelers, with only seven locally acquired mosquito-transmitted Zika virus disease cases reported from Texas (n = 5) and Florida (n = 2). In the territories, most dengue cases (n = 508, 98%) were reported from American Samoa, whereas the majority of chikungunya (n = 39, 100%) and Zika virus disease (n = 620, 93%) cases were reported from Puerto Rico. Temporally, the highest number of Zika virus disease cases occurred at the beginning of the year, followed by a sharp decline, mirroring decreasing case numbers across the Americas following large outbreaks in 2015 and 2016. Dengue and chikungunya cases followed a more seasonal pattern, with higher case numbers from July through September. Travelers to the United States and residents of areas with active virus transmission should be informed of both the ongoing risk from dengue, chikungunya, and Zika virus disease and personal protective measures to lower their risk of mosquito bites and to help prevent the spread of these diseases.

PMID: 31436154 [PubMed - as supplied by publisher]

Environmental phthalate exposure and preterm birth in the PROTECT birth cohort.

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Environmental phthalate exposure and preterm birth in the PROTECT birth cohort.

Environ Int. 2019 Aug 17;132:105099

Authors: Ferguson KK, Rosen EM, Rosario Z, Feric Z, Calafat AM, McElrath TF, Vélez Vega C, Cordero JF, Alshawabkeh A, Meeker JD

Abstract
BACKGROUND: Preterm birth is a global public health issue and rates in Puerto Rico are consistently among the highest in the USA. Exposures to environmental contaminants might be a contributing factor.
METHODS: In a preliminary analysis from the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort (n = 1090), we investigated the association between urinary phthalate metabolite concentrations measured at three study visits (targeted at 20, 24, and 28 weeks of gestation) individually and averaged over pregnancy with gestational age at delivery and preterm birth. We additionally assessed differences in associations by study visit and among preterm births with a spontaneous delivery.
RESULTS: Compared to women in the general USA population, urinary concentrations of metabolites of di-n-butyl phthalate (DBP) and di-isobutyl phthalate (DiBP) were higher among pregnant women in Puerto Rico. Interquartile range (IQR) increases in pregnancy-averages of urinary metabolites of DBP and DiBP were associated with shorter duration of gestation and increased odds of preterm birth. An IQR increase in mono-n-butyl phthalate (MBP), a metabolite of DBP, was associated with 1.55 days shorter gestation (95% confidence interval [CI] = -2.68, -0.42) and an odds ratio (OR) of 1.42 (95% confidence interval [CI]: 1.07, 1.88) for preterm birth. An IQR increase in mono-isobutyl phthalate (MiBP), a metabolite of DiBP, was associated with 1.16 days shorter gestation (95% CI = -2.25, -0.08) and an OR of 1.32 (95% CI: 1.02, 1.71) for preterm birth. Associations were greatest in magnitude for urinary concentrations measured at the second study visit (median 23 weeks gestation). DiBP metabolite associations were greatest in magnitude in models of spontaneous preterm birth. No associations were detected with other phthalate metabolites, including those of di-2-ethylhexyl phthalate.
CONCLUSION: Among pregnant women in the PROTECT cohort, DBP and DiBP metabolites were associated with increased odds of preterm birth. These exposures may be contributing to elevated rates of preterm birth observed in Puerto Rico.

PMID: 31430608 [PubMed - as supplied by publisher]

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

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

Disaster Med Public Health Prep. 2019 Aug 20;:1-9

Authors: Jiménez Chávez JC, Viruet Sánchez E, Rosario Maldonado FJ, Ramos Lucca AJ, Barros Cartagena B

Abstract
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.

PMID: 31429397 [PubMed - as supplied by publisher]

Informing Data to Care: Contacting Persons Sampled for the Medical Monitoring Project.

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Informing Data to Care: Contacting Persons Sampled for the Medical Monitoring Project.

J Acquir Immune Defic Syndr. 2019 Sep 01;82 Suppl 1:S6-S12

Authors: Beer L, Bosh KA, Chowdhury PP, Craw J, Nyaku MA, Luna-Gierke RE, Sanders CC, Shouse RL

Abstract
BACKGROUND: Data to care (D2C) is a public health strategy that uses HIV surveillance and other data to identify persons in need of HIV medical care. The Medical Monitoring Project (MMP), which uses similar methods to contact and recruit HIV-positive persons, may inform predictors of successful contact for D2C programs.
SETTING: MMP is a Centers for Disease Control and Prevention-funded surveillance system that collects nationally representative data on adults with diagnosed HIV in the United States and Puerto Rico.
METHODS: Using MMP's 2016 data collection cycle, we present contact rates (ie, proportion of HIV-positive persons successfully contacted for MMP) by the age of contact information and age of laboratory test results available from HIV surveillance data.
RESULTS: Nationally, 27.6% of eligible persons did not have a recorded laboratory test performed within the past year (project area range: 10.8%-54.6%). The national contact rate among persons with laboratory tests older than 1 year was 37.0% (project area range: 16.5%-67.1%). Higher contact rates were found among persons with more recent laboratory tests. Similar results were found by the age of contact information. Nationally, the most common reason for MMP ineligibility was that the person was deceased; the most common reason for not being contacted was lack of correct contact information.
CONCLUSIONS: MMP findings suggest that D2C programs would benefit from efforts to improve the quality of HIV surveillance data and local surveillance practices-in particular, death ascertainment, the completeness of laboratory reporting, and the routine updating of contact information. Strengthening collaboration and integration with existing MMP programs may be beneficial.

PMID: 31425389 [PubMed - in process]

Comorbidities in a sample of adults with HIV in Puerto Rico: an exploratory study.

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Comorbidities in a sample of adults with HIV in Puerto Rico: an exploratory study.

HIV AIDS (Auckl). 2019;11:155-164

Authors: Rodríguez-Díaz CE, Santiago-Rodríguez EI, Jovet-Toledo GG, Santana-Bagur J, Ron-Suarez Y, Orengo JC, Arbelaez F, Monsanto H

Abstract
Background: Puerto Rico is among the areas with the highest estimated rates of people living with HIV in the United States. Despite the epidemiologic data available, there is limited real-world information that can help understand the comorbidities of people with HIV. In this study, we describe common comorbidities among adults with HIV attending treatment clinics in Puerto Rico.
Methods: An exploratory, retrospective, cross-sectional study was conducted at five HIV clinics in Puerto Rico. A random sample of medical records was reviewed. Descriptive statistics were used to summarize patient demographics, morbidity, and clinical characteristics. Multivariate analyses were conducted to explore comorbidities by age and sex.
Results: A total of 250 (179 men; 71 women) medical records were reviewed. Participants' mean age was 47.9 years and on average they had been living with HIV for 9 years. Most (97.6%) had at least one comorbidity. The most common comorbidities were dyslipidemia and hypertension. Men were more likely to have been diagnosed with alcohol misuse while women were more likely to have been diagnosed with obesity, human papillomavirus (HPV), hypothyroidism, and osteoporosis. Participants younger than 50 years of age were more likely to have history of alcohol misuse while older individuals (50 years and old) were more likely to have been diagnosed with dyslipidemia, hypertension, and diabetes. Adjusting by sex and age, women were more likely to have been diagnosed with obesity and depression and those older than 50 years were more likely to have had a diagnosis of dyslipidemia, hypertension, HPV, and diabetes.
Conclusions: This is one of the few studies assessing comorbidities among adults with HIV in Puerto Rico, among Latino/Hispanics within the United States, and Latin America. Consistent with other studies, cardiovascular diseases are common among adults with HIV in Puerto Rico. Findings support the need for awareness and real-world evidence about comorbidities among people with HIV when implementing screenings and prescribing drugs.

PMID: 31413642 [PubMed]

Acceptability of a text message-based intervention for obesity prevention in infants from Hawai'i and Puerto Rico WIC.

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Acceptability of a text message-based intervention for obesity prevention in infants from Hawai'i and Puerto Rico WIC.

BMC Pregnancy Childbirth. 2019 Aug 13;19(1):291

Authors: Gibby CLK, Palacios C, Campos M, Graulau RE, Banna J

Abstract
BACKGROUND: Low-income and minority children are at increased risk for obesity. Text messaging offers advantages for delivering education, but few studies have assessed the acceptability of text messaging in interventions aimed at preventing excessive weight gain in infants. This study investigated the acceptability of a text message-based intervention for prevention of excessive weight gain in infants from Hawai'i and Puerto Rico WIC clinics.
METHODS: The four-month text message based intervention designed to improve infant feeding practices and reduce excessive weight gain was a randomized controlled trial that included mothers with infants ages 0-2 months at baseline. Participants in the intervention arm received 18 text messages (1/week) promoting breastfeeding and appropriate complementary feeding. Acceptability of the intervention was assessed from participant retention, satisfaction, and evidence of behavior change in a sequential multimethod approach, quantitatively from questions sent via text and qualitatively during the in-person exit interview. The final analysis included 80 mother-infant pairs from the intervention arm.
RESULTS: When asked about messages liked and disliked the most, the majority of responses via text indicated that they liked all messages. From the qualitative analyses, most participants reported that all messages were useful and that the messages led them to make changes in the way they fed their infants. Participant retention was good at 78.4%.
CONCLUSIONS: The intervention was acceptable to participants based upon participant retention, measures of satisfaction, and reports of behavior change. Results may inform development of mobile health programs for minority childhood obesity prevention.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier; NCT02903186; September 16, 2016.

PMID: 31409286 [PubMed - in process]

Acute Zika virus infection in an asymptomatic blood donor at the onset of the Puerto Rico epidemic.

Acute Zika virus infection in an asymptomatic blood donor at the onset of the Puerto Rico epidemic.

Transfusion. 2019 Aug 13;:

Authors: Saa P, Chiu C, Grimm K, Yu G, Benjamin RJ, Corash L, Stramer SL

Abstract
BACKGROUND: Zika virus (ZIKV) spread to Puerto Rico likely originated from southeastern Brazil approximately 8.5 months earlier than blood donation screening for ZIKV was initiated, but the time of ZIKV introduction in the blood donor population remains unknown.
METHODS: To better understand when arboviral infections first appeared in the blood donor pool in Puerto Rico, we retrospectively screened for ZIKV RNA (as well as chikungunya [CHIKV] and dengue [DENV] viral RNA) a repository of 1186 linked blood donor and recipient samples collected from February 2015 to May 2016 as an endpoint efficacy measure following the introduction of platelet pathogen reduction (PR). Phylogenetic analysis identified relatedness of donor strain to other circulating strains, and molecular clock analysis identified the estimated time of introduction.
RESULTS: An asymptomatic donor collected in December 2015 was ZIKV RNA confirmed positive, 4 months BEFORE investigational nucleic acid testing (NAT) implementation in April 2016, coincident and related to the first reported autochthonous cases. No CHIKV RNA or DENV RNA reactives were identified in donors or recipients, and no adverse events were reported from PR use in recipients. Phylogenetic analysis confirmed the molecular relatedness of the donor ZIKV strain to the Puerto Rico lineage likely introduced approximately 4.5 months earlier.
CONCLUSION: This study identified an asymptomatic ZIKV infection in a blood donor occurring before those previously recognized by blood donation screening. NAT and PR continue to be used as acceptable strategies to prevent transfusion-transmitted arboviral infections worldwide; however, repeated arboviral outbreaks warrant consideration of PR as a more proactive approach.

PMID: 31407817 [PubMed - as supplied by publisher]

Onion and Garlic Intake and Breast Cancer, a Case-Control Study in Puerto Rico.

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Onion and Garlic Intake and Breast Cancer, a Case-Control Study in Puerto Rico.

Nutr Cancer. 2019 Aug 12;:1-10

Authors: Desai G, Schelske-Santos M, Nazario CM, Rosario-Rosado RV, Mansilla-Rivera I, Ramírez-Marrero F, Nie J, Myneni AA, Zhang ZF, Freudenheim JL, Mu L

Abstract
Studies show an inverse association between onion and garlic intake and risk of cancers of the lung, prostate, and stomach. There is limited evidence on the association between onion and garlic intake and breast cancer. We assessed this association in a population-based, case-control study in Puerto Rico. Incident, primary breast cancer cases (n = 314) were identified among women aged 30-79 from hospital and clinic records. Controls (n = 346) were women with no history of cancer other than nonmelanoma skin cancer, residents of the same area. Dietary intake was estimated using a food frequency questionnaire. Total onion and garlic intake included sofrito (a popular garlic- and onion-based condiment) intake frequency. Unconditional logistic regression assessed the association between onion and garlic consumption and breast cancer adjusting for age, education, parity, family history, body mass index, age at menarche, total energy, and smoking. Inverse associations with breast cancer were observed for moderate (OR (odds ratio) = 0.59, 95% CI (confidence interval): 0.35, 1.01) and high consumption (OR = 0.51, 95% CI: 0.30, 0.87) compared to low consumption of onion and garlic (Ptrend = 0.02). Results were similar when stratified by menopausal status. Study results suggest that high onion and garlic consumption is protective against breast cancer in this population.

PMID: 31402709 [PubMed - as supplied by publisher]

Normal Saline.

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Normal Saline.

AMA J Ethics. 2019 Aug 01;21(8):E699-700

Authors: Abrams HR

Abstract
In 2017, Hurricane Maria devastated Puerto Rico and prompted a shortage of normal saline in US health care organizations. This graphic narrative considers ethics and justice in the supply, demand, and allocation of intravenous fluids in clinical settings during this time.

PMID: 31397666 [PubMed - in process]

Use of a Blockade-of-Binding ELISA and Microneutralization Assay to Evaluate Zika Virus Serostatus in Dengue-Endemic Areas.

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Use of a Blockade-of-Binding ELISA and Microneutralization Assay to Evaluate Zika Virus Serostatus in Dengue-Endemic Areas.

Am J Trop Med Hyg. 2019 Aug 05;:

Authors: Nascimento EJM, Bonaparte MI, Luo P, Vincent TS, Hu B, George JK, Áñez G, Noriega F, Zheng L, Huleatt JW

Abstract
Zika virus (ZIKV) serological diagnostics are compromised in areas where dengue viruses (DENV) co-circulate because of their high levels of protein sequence homology. Here, we describe the characterization of a Zika blockade-of-binding ELISA (Zika BOB) and a Zika microneutralization assay (Zika MN) for the detection of ZIKV nonstructural protein 1 (NS1)-specific antibodies and ZIKV neutralizing antibodies, respectively. Zika BOB and Zika MN cutoffs were established as 10 and 100 endpoint titers, respectively, using samples collected pre- and post-virologically confirmed ZIKV infection from subjects living in DENV-endemic areas. Specificity of the assays was equally high, whereas sensitivity of Zika BOB was lower than that of Zika MN, especially in samples collected > 6 months post-infection. Immunosurveillance analysis, using combined results from both Zika BOB and Zika MN, carried out also in DENV-endemic regions in Colombia, Honduras, Mexico, and Puerto Rico before (2013-2014) and after (2017-2018) ZIKV introduction in the Americas suggests unapparent ZIKV seroprevalence rates ranged from 25% to 80% over the specified period of time in the regions investigated.

PMID: 31392955 [PubMed - as supplied by publisher]

International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol.

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International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol.

BMC Pregnancy Childbirth. 2019 Aug 07;19(1):282

Authors: Lebov JF, Arias JF, Balmaseda A, Britt W, Cordero JF, Galvão LA, Garces AL, Hambidge KM, Harris E, Ko A, Krebs N, Marques ETA, Martinez AM, McClure E, Miranda-Filho DB, Moreira MEL, Mussi-Pinhata MM, Ochoa TJ, Osorio JE, Scalabrin DMF, Schultz-Cherry S, Seage GR, Stolka K, Ugarte-Gil CA, Vega CMV, Welton M, Ximenes R, Zorrilla C

Abstract
BACKGROUND: Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes.
METHODS: At research sites in ZIKV endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and then followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age. Pregnant women with symptomatic ZIKV infection confirmed by presence of ZIKV RNA and/or IgM for ZIKV will also be enrolled, regardless of gestational age. Participants will be tested monthly for ZIKV infection; additional demographic, physical, laboratory and environmental data will be collected to assess the potential interaction of these variables with ZIKV infection. Delivery outcomes and detailed infant assessments, including physical and neurological outcomes, will be obtained.
DISCUSSION: With the emergence of ZIKV in the Americas and its association with adverse pregnancy outcomes in this region, a much better understanding of the spectrum of clinical outcomes associated with exposure to ZIKV during pregnancy is needed. This cohort study will provide information about maternal, fetal, and infant outcomes related to ZIKV infection, including congenital ZIKV syndrome, and manifestations that are not detectable at birth but may appear during the first year of life. In addition, the flexibility of the study design has provided an opportunity to modify study parameters in real time to provide rigorous research data to answer the most critical questions about the impact of congenital ZIKV exposure.
TRIAL REGISTRATION: NCT02856984 . Registered August 5, 2016. Retrospectively registered.

PMID: 31391005 [PubMed - in process]

Extending the stalk enhances immunogenicity of the influenza virus neuraminidase.

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Extending the stalk enhances immunogenicity of the influenza virus neuraminidase.

J Virol. 2019 Aug 02;:

Authors: Broecker F, Zheng A, Suntrongwong N, Sun W, Bailey MJ, Krammer F, Palese P

Abstract
Influenza viruses express two surface glycoproteins, the hemagglutinin (HA) and the neuraminidase (NA). Anti-NA antibodies protect from lethal influenza virus challenge in the mouse model and correlate inversely with virus shedding and symptoms in humans. Consequently, the NA is a promising target for influenza virus vaccine design. Current seasonal vaccines, however, poorly induce anti-NA antibodies, partly because of the immunodominance of the HA over the NA when both glycoproteins are closely associated. To address this issue, we here investigated whether extending the stalk domain of the NA could render it more immunogenic on virus particles. Two recombinant influenza viruses based on the H1N1 strain A/Puerto Rico/8/1934 (PR8) were rescued with NA stalk domains extended by 15 or 30 amino acids. Formalin-inactivated viruses expressing wild type NA or the stalk-extended NA variants were used to vaccinate mice. Compared to the wild type PR8 virus, the virus with the 30 amino acid stalk extension induced significantly higher anti-NA IgG responses characterized by increased in vitro antibody-dependent cellular cytotoxicity (ADCC) activity, while anti-HA IgG levels were unaffected. Similarly, extending the stalk domain of the NA of a recent H3N2 virus enhanced the induction of anti-NA IgGs in mice. Based on these results we hypothesize that the subdominance of the NA can be modulated if the protein is modified such that it surpasses the height of the HA on the viral membrane. Extending the stalk domain of NA may help to enhance its immunogenicity in influenza virus vaccines without compromising antibody responses to HA.IMPORTANCE The efficacy of influenza virus vaccines could be improved by enhancing the immunogenicity of the NA protein. One of the reasons for its poor immunogenicity is the immunodominance of the HA over the NA in many seasonal influenza virus vaccines. Here we demonstrate that, in the mouse model, extending the stalk domain of the NA protein can enhance its immunogenicity on virus particles and overcome the immunodominance of the HA without affecting antibody responses to the HA. The antibody repertoire is broadened by the extended NA and includes additional ADCC-active antibodies. Our findings may assist in the efforts towards more effective influenza virus vaccines.

PMID: 31375573 [PubMed - as supplied by publisher]

5-Chloro-2-thiophenyl-1,2,3-triazolylmethyldihydroquinolines as dual inhibitors of Mycobacterium tuberculosis and influenza virus: Synthesis and evaluation.

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5-Chloro-2-thiophenyl-1,2,3-triazolylmethyldihydroquinolines as dual inhibitors of Mycobacterium tuberculosis and influenza virus: Synthesis and evaluation.

Bioorg Med Chem Lett. 2019 Jul 24;:

Authors: Marvadi SK, Krishna VS, Sinegubova EO, Volobueva AS, Esaulkova YL, Muryleva AA, Tentler DG, Sriram D, Zarubaev VV, Kantevari S

Abstract
This study describes synthesis and evaluation of novel 5-Chloro-2-thiophenyl-1,2,3-triazolylmethyldihydroquinolines 7a-o as dual inhibitors of Mycobacterium tuberculosis and influenza virus. Huisgen's [3+2] dipolar cycloaddition of 6-(azidomethyl)-5-chloro-2-(thiophen-2-yl)-7,8-dihydroquinoline 5 with various alkynes 6a-o using sodium ascorbate and copper sulphate gave new dihydroquinoline-1,2,3-triazoles 7a-o in good to excellent yields. The new compounds were evaluated for in vitro antimycobacterial against M. tuberculosis H37Rv (Mtb) and antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1). Among the fifteen new analogs, compounds 7a (MIC: 3.12 µg/mL), 7j and 7k (MIC: 6.25 µg/mL) were identified as potent antitubercular agents. The virus-inhibiting activity of all the fifteen compounds was found to be moderate, and among them the compound 7l, bearing thiophene moiety appeared the most active with good selectivity index (IC50 = 19.5 µg/mL; SI = 15). The results presented here will help developing newer dual inhibitors of tuberculosis and influenza virus.

PMID: 31375291 [PubMed - as supplied by publisher]

Associations between socioeconomic status, psychosocial stress, and urinary levels of 8-iso-prostaglandin-F2α during pregnancy in Puerto Rico.

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Associations between socioeconomic status, psychosocial stress, and urinary levels of 8-iso-prostaglandin-F2α during pregnancy in Puerto Rico.

Free Radic Biol Med. 2019 Jul 29;:

Authors: Eick SM, Meeker JD, Brown P, Swartzendruber A, Rios-McConnell R, Shen Y, Milne GL, Velez-Vega C, Rosario Z, Alshawabkeh A, Cordero JF, Ferguson KK

Abstract
BACKGROUND: Lower socioeconomic status (SES) and psychosocial stress during pregnancy have been associated with adverse birth outcomes. While hypothalamic-pituitary-axis activation is thought to be the primary driver, oxidative stress may also be involved mechanistically. We used data from the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort (N=476) to examine associations between self-reported psychosocial stress measures, SES indicators, and urinary oxidative stress biomarker concentrations, hypothesizing that women with lower SES and increased psychosocial stress would have elevated oxidative stress biomarkers.
METHODS: Maternal age, education, marital status, insurance status, alcohol use and smoking status were obtained via self-reported questionnaires and were used as indicators of SES. Perceived stress, depression, negative life experiences, neighborhood perceptions, and social support were self-reported in questionnaires administered during pregnancy. Responses were grouped into tertiles for analysis, where the highest tertile corresponded to highest level of psychosocial stress. Urinary concentrations of 8-iso-prostaglandin F2α (8-iso-PGF2α) and its primary metabolite were measured at three study visits (median 18, 24, 28 weeks gestation) and averaged to reflect oxidative stress across pregnancy. Linear models were used to examine associations between SES indicators, tertiles of psychosocial stress and oxidative stress biomarkers.
RESULTS: Average levels of 8-iso-PGF2α and the 8-iso-PGF2α metabolite were higher among pregnant women who were younger, who had public compared to private insurance, and who were unemployed compared to employed. However, no associations were observed between psychosocial stress measures and biomarker concentrations in adjusted analyses.
CONCLUSIONS: Psychosocial stress during pregnancy, as indicated by self-reported questionnaire measures, was not associated with biomarkers of oxidative stress in the PROTECT study. However, results suggest that these biomarkers are elevated among women of lower SES, which is typically associated with stress. Notably, compared to other populations, self-reported psychosocial stress measures were lower in PROTECT compared to other populations.

PMID: 31369838 [PubMed - as supplied by publisher]

Intraspecific variation in traits and tree growth along an elevational gradient in a subtropical forest.

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Intraspecific variation in traits and tree growth along an elevational gradient in a subtropical forest.

Oecologia. 2019 Jul 31;:

Authors: Umaña MN, Swenson NG

Abstract
A conspicuous feature of natural communities is that individuals within species exhibit broad variation in their phenotype. While the phenotypic differences among species are prominent and have received considerable attention in earlier studies, recent findings suggest that about 40% of the trait variation is found within species. How this intraspecific variation is related to underlying environmental gradients and ultimately linked to performance is an outstanding question in ecology and evolution. Here, we study six broadly distributed species across an elevational gradient in a subtropical forest. We focused on five functional traits reflecting plant functional differentiation in stem transport, leaf architecture, and leaf resource acquisition. We found that leaf thickness, leaf toughness, and specific leaf area generally varied with elevation, while wood density and leaf area exhibited constrained variation. Results on multivariate trait axes also showed mixed evidence with the PC1 values (positively related to leaf toughness and negatively related to specific leaf area) shifting with elevation, while PC2 values (negatively related to wood density) did not change with elevation. We also found that, despite the important variation in some traits along the gradient, growth performance did not follow this same trend. This suggests that strong directional changes in traits along the gradient may result in similar levels of demographic performance. The results, therefore, challenge the simple expectation that a trait will correlate with a demographic rate. More nuanced approaches and additional mechanisms must be considered to advance understanding of the performance-trait relationships.

PMID: 31367911 [PubMed - as supplied by publisher]

Progress in trial registration in Latin America and the Caribbean, 2007-2013.

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Progress in trial registration in Latin America and the Caribbean, 2007-2013.

Rev Panam Salud Publica. 2017;41:e31

Authors: Rodríguez-Feria P, Cuervo LG

Abstract
This descriptive study identifies trends in clinical trial registration in the World Health Organization International Clinical Trial Registry Platform (ICTRP) for Latin America and the Caribbean (LAC), from 2007-2013, and provides adjusted estimates for registration rates by population and publications (2007-2011). Trends and data are presented by subregion and language in interactive graphs, including annual registration rates by population (2007-2011) and publications (LILACS and MEDLINE) listed in SCIENTI Network (Science and Technology Indicators). Of the 11 945 clinical trials involving LAC countries, 8 282 were in South America, with Brazil leading at 4 070 (49%); 2 421 in North and Central America, with Mexico leading at 1 886 (78%); and 1 242 in the Caribbean, with Puerto Rico leading at 857 (69%). After adjusting by population and publication rates Chile, Panama, Argentina, and Peru led registration rates per 1 million inhabitants. Variations in the number of trials per year are quite substantial. Clinical trial registration increased in a steady yet inconsistent way. The implementation of the Policy on Research for Health has been followed by an increase in countries that require registration and have established clinical trial registries. However, there is room for improvement in adherence throughout LAC. Trial registration is offered gratis by Brazilian, Cuban, Peruvian, and United States registries, among others.

PMID: 31363353 [PubMed]

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