Publications by authors named "Laura Mendoza"

52 Publications

Genomic and evolutionary classification of lung cancer in never smokers.

Nat Genet 2021 Sep 6;53(9):1348-1359. Epub 2021 Sep 6.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Lung cancer in never smokers (LCINS) is a common cause of cancer mortality but its genomic landscape is poorly characterized. Here high-coverage whole-genome sequencing of 232 LCINS showed 3 subtypes defined by copy number aberrations. The dominant subtype (piano), which is rare in lung cancer in smokers, features somatic UBA1 mutations, germline AR variants and stem cell-like properties, including low mutational burden, high intratumor heterogeneity, long telomeres, frequent KRAS mutations and slow growth, as suggested by the occurrence of cancer drivers' progenitor cells many years before tumor diagnosis. The other subtypes are characterized by specific amplifications and EGFR mutations (mezzo-forte) and whole-genome doubling (forte). No strong tobacco smoking signatures were detected, even in cases with exposure to secondhand tobacco smoke. Genes within the receptor tyrosine kinase-Ras pathway had distinct impacts on survival; five genomic alterations independently doubled mortality. These findings create avenues for personalized treatment in LCINS.
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http://dx.doi.org/10.1038/s41588-021-00920-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432745PMC
September 2021

Revisiting the dengue epidemic of 2011 in Paraguay: molecular epidemiology of dengue virus in the Asuncion metropolitan area.

BMC Infect Dis 2021 Aug 7;21(1):769. Epub 2021 Aug 7.

Laboratory of Virology, Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirão Preto, Brazil.

Background: Dengue is one of the most important re-emerging viral diseases and the most common human arthropod-borne viral infection worldwide. Any of the four Dengue virus serotypes (DENV-1 to 4) can cause asymptomatic infections or clinical manifestations that range in severity from a mild, self-limited illness, to a severe disease characterized by a shock syndrome that can lead to death. Paraguay suffers periodic epidemic outbreaks of dengue since 1988 when the DENV-1 was introduced in the country. Epidemics caused by all four serotypes have been reported and the country. Although dengue is endemic in Paraguay, few studies have described the molecular epidemiology of DENV in the country, which is important to understand the local and global spread, as well as the evolution of this pathogen.

Methods: This was a cross-sectional study of a convenience sample. Suspected dengue patients of any age were recruited from the Emergency Laboratory of the Central Hospital of the Institute of Social Welfare, Asuncion, Paraguay, from February to June of 2011. A DENV antigen test was used to confirm the infection. The protein E gene sequences of isolated viruses were sequenced for phylogenetic analysis.

Results: Dengue was confirmed in 55.1% of the participants (n = 98/178). The most frequent clinical findings were fever, headache, and myalgia. Identity analyses of the protein E gene sequence of 56 viruses isolated showed the circulation of DENV-1 (n = 45) and DENV-2 (n = 11) in the Asuncion metropolitan area in 2011. Molecular epidemiology analyses suggest that DENV-1 was introduced into Paraguay from Argentina, while the DENV-2 from Brazil, replacing previous virus lineages.

Conclusions: We have analyzed the molecular epidemiology of DENV-1 and DENV-2 isolated in Paraguay in 2011. We found strong evidence that DENV-1 was introduced into Paraguay from Argentina, while the DENV-2 from Brazil, replacing previous virus lineages. Molecular epidemiology studies are of great interest to analyze the dynamic of DENV spread, which are useful for early implementation of containment measures to reduce the risk of explosive epidemics caused by this virus.
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http://dx.doi.org/10.1186/s12879-021-06487-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349040PMC
August 2021

Impact of Histology and Tumor Grade on Clinical Outcomes Beyond 5 Years of Follow-Up in a Large Cohort of Renal Cell Carcinomas.

Clin Genitourin Cancer 2021 Jul 10. Epub 2021 Jul 10.

Division of Cancer Epidemiology Genetics, National Cancer Institute, NIH, Bethesda, MD. Electronic address:

Introduction: The optimal length for clinical follow-up of renal cell carcinoma (RCC) patients is unclear. We evaluated the impact of ISUP/WHO tumor grade and histological subtype on short- and long-term survival and risk of recurrence/metastasis in a large cohort of RCC patients.

Patients And Methods: We studied 1679 RCC patients from a single referral center in Italy. Adjusted hazard ratios for overall survival were estimated using Cox regression models. Adjusted absolute risk of developing recurrence or metastasis was computed considering competing risks of mortality.

Results: During up to 13 years of follow-up, 175 (10.4%) RCC patients died, of whom 92% beyond 5 years. Hazard ratio of grade IV clear cell carcinomas (ccRCC) was 3.82 compared to grade II. Notably, 33% of recurrences and 56% of distant metastases occurred beyond 5 years of follow-up. The estimated probabilities of recurrence/metastasis were 15% and 45% within and beyond 5 years of follow-up, respectively. After 5 years, the absolute risk of recurrences increased also for papillary renal cell carcinoma type I (35.2%) and grade I ccRCC (17%).

Conclusion: After 5 years of follow-up, both risk of mortality and recurrences or metastases were high and were modified by histological types and tumor grade. These data strongly support histology- and grade-tailored surveillance strategies and long-term follow-up for RCC patients.
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http://dx.doi.org/10.1016/j.clgc.2021.07.003DOI Listing
July 2021

Multi-site clinical validation of Isothermal Amplification based SARS-COV-2 detection assays using different sampling strategies.

medRxiv 2021 Jul 6. Epub 2021 Jul 6.

Background: Isothermal amplification-based tests were developed as rapid, low-cost, and simple alternatives to real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests for SARS-COV-2 detection.

Methods: Clinical performance of two isothermal amplification-based tests (Atila Biosystems iAMP COVID-19 detection test and OptiGene COVID-19 Direct Plus RT-LAMP test) was compared to clinical RT-PCR assays using different sampling strategies. A total of 1378 participants were tested across four study sites.

Results: Compared to standard of care RT-PCR testing, the overall sensitivity and specificity of the Atila iAMP test for detection of SARS-CoV-2 were 76.2% and 94.9%, respectively, and increased to 88.8% and 89.5%, respectively, after exclusion of an outlier study site. Sensitivity varied based on the anatomic collected site. Sensitivity for nasopharyngeal was 65.4% (range across study sites:52.8%-79.8%), mid-turbinate 88.2%, saliva 55.1% (range across study sites:42.9%-77.8%) and anterior nares 66.7% (range across study sites:63.6%-76.5%). The specificity for these anatomic collection sites ranged from 96.7% to 100%. Sensitivity improved in symptomatic patients (overall 82.7%) and those with a higher viral load (overall 92.4% for ct≤25). Sensitivity and specificity of the OptiGene Direct Plus RT-LAMP test, conducted at a single study-site, were 25.5% and 100%, respectively.

Conclusions: The Atila iAMP COVID test with mid-turbinate sampling is a rapid, low-cost assay for detecting SARS-COV-2, especially in symptomatic patients and those with a high viral load, and could be used to reduce the risk of SARS-COV-2 transmission in clinical settings. Variation of performance between study sites highlights the need for site-specific clinical validation of these assays before clinical adoption.
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http://dx.doi.org/10.1101/2021.07.01.21259879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282105PMC
July 2021

Novel MAPK/AKT-impairing germline NRAS variant identified in a melanoma-prone family.

Fam Cancer 2021 Jul 3. Epub 2021 Jul 3.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, EPS 7106, Bethesda, MD, 20892, USA.

While several high-penetrance melanoma risk genes are known, variation in these genes fail to explain melanoma susceptibility in a large proportion of high-risk families. As part of a melanoma family sequencing study, including 435 families from Mediterranean populations we identified a novel NRAS variant (c.170A > C, p.D57A) in an Italian melanoma-prone family. This variant is absent in exomes in gnomAD, ESP, UKBiobank, and the 1000 Genomes Project, as well as in 11,273 Mediterranean individuals and 109 melanoma-prone families from the US and Australia. This variant occurs in the GTP-binding pocket of NRAS. Differently from other RAS activating alterations, NRAS D57A expression is unable to activate MAPK-pathway both constitutively and after stimulation but enhances EGF-induced PI3K-pathway signaling in serum starved conditions in vitro. Consistent with in vitro data demonstrating that NRAS D57A does not enrich GTP binding, molecular modeling suggests that the D57A substitution would be expected to impair Mg2 + binding and decrease nucleotide-binding and GTPase activity of NRAS. While we cannot firmly establish NRAS c.170A > C (p.D57A) as a melanoma susceptibility variant, further investigation of NRAS as a familial melanoma gene is warranted.
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http://dx.doi.org/10.1007/s10689-021-00267-9DOI Listing
July 2021

Physical Activity Levels and Associated Factors in a Latin American COPD Population of Patients. The LASSYC Study.

COPD 2021 Aug 28;18(4):393-400. Epub 2021 Jun 28.

Department of Pneumology. Hospital Universitari Vall d´Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus; CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.

Reduced physical activity (PA) is an independent risk factor for lung function decline, hospitalization and mortality in chronic obstructive pulmonary disease (COPD) and affects a large proportion of patients from Europe and the United States. However, little is known of the level of PA of COPD patients in Latin America. The aim of this study was to provide information of the level of PA and its determinants in COPD patients in Latin America. This is an observational, cross-sectional study on patients with COPD in seven Latin American countries. PA level was evaluated with the short version of the International Physical Activity Questionnaire (IPAQ) and the association between PA and other variables was investigated. Complete information of PA level was obtained in 734 COPD patients consecutively recruited from specialized outpatient clinics; 448 (61%) were men, with a mean age of 69.6 years (standard deviation [SD] = 8.7) and a mean FEV (% predicted) = 49.1% (17.5%). In 37.9% the level of PA was low, and the average sitting time was 36.1 h per week. Patients with low levels of PA were older, with higher levels of dyspnea and higher CAT scores. Additionally, we found that patients with low level of PA presented more symptoms during the day. Low levels of PA have been observed in a large proportion of COPD patients of Latin America, which is higher in women and older patients and it is related with worse functional and clinical characteristics.
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http://dx.doi.org/10.1080/15412555.2021.1937090DOI Listing
August 2021

Comparison of Anti-Dengue and Anti-Zika IgG on a Plasmonic Gold Platform with Neutralization Testing.

Am J Trop Med Hyg 2021 Mar 29. Epub 2021 Mar 29.

2Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia.

Antibody cross-reactivity confounds testing for dengue virus (DENV) and Zika virus (ZIKV). We evaluated anti-DENV and anti-ZIKV IgG detection using a multiplex serological platform (the pGOLD assay) in patients from the Asunción metropolitan area in Paraguay, which experiences annual DENV outbreaks but has reported few autochthonous ZIKV infections. Acute-phase sera were tested from 77 patients who presented with a suspected arboviral illness from January to May 2018. Samples were tested for DENV and ZIKV RNA by real-time reverse transcription-PCR, and for DENV nonstructural protein 1 with a lateral-flow immunochromatographic test. Forty-one patients (51.2%) had acute dengue; no acute ZIKV infections were detected. Sixty-five patients (84.4%) had anti-DENV-neutralizing antibodies by focus reduction neutralization testing (FRNT50). Qualitative detection with the pGOLD assay demonstrated good agreement with FRNT50 (kappa = 0.74), and quantitative results were highly correlated between methods (P < 0.001). Only three patients had anti-ZIKV-neutralizing antibodies at titers of 1:55-1:80, and all three had corresponding DENV-neutralizing titers > 1:4,000. Hospitalized dengue cases had significantly higher anti-DENV IgG levels (P < 0.001). Anti-DENV IgG results from the pGOLD assay correlate well with FRNT, and quantitative results may inform patient risk stratification.
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http://dx.doi.org/10.4269/ajtmh.20-1449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103464PMC
March 2021

Tracing Lung Cancer Risk Factors Through Mutational Signatures in Never-Smokers.

Am J Epidemiol 2021 06;190(6):962-976

Epidemiologic studies often rely on questionnaire data, exposure measurement tools, and/or biomarkers to identify risk factors and the underlying carcinogenic processes. An emerging and promising complementary approach to investigate cancer etiology is the study of somatic "mutational signatures" that endogenous and exogenous processes imprint on the cellular genome. These signatures can be identified from a complex web of somatic mutations thanks to advances in DNA sequencing technology and analytical algorithms. This approach is at the core of the Sherlock-Lung study (2018-ongoing), a retrospective case-only study of over 2,000 lung cancers in never-smokers (LCINS), using different patterns of mutations observed within LCINS tumors to trace back possible exposures or endogenous processes. Whole genome and transcriptome sequencing, genome-wide methylation, microbiome, and other analyses are integrated with data from histological and radiological imaging, lifestyle, demographic characteristics, environmental and occupational exposures, and medical records to classify LCINS into subtypes that could reveal distinct risk factors. To date, we have received samples and data from 1,370 LCINS cases from 17 study sites worldwide and whole-genome sequencing has been completed on 1,257 samples. Here, we present the Sherlock-Lung study design and analytical strategy, also illustrating some empirical challenges and the potential for this approach in future epidemiologic studies.
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http://dx.doi.org/10.1093/aje/kwaa234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316614PMC
June 2021

Reconstruction of the Neopulmonary Root After Coronary Button Harvest for Arterial Switch Operation Using 2-ply Extracellular Matrix (Tyke): A Post-Implant Histology.

Front Cardiovasc Med 2020 30;7:562136. Epub 2020 Oct 30.

Division of Pediatric Cardiothoracic Surgery, The Heart Institute, Joe DiMaggio Children's Hospital, Hollywood, FL, United States.

In children with Transposition of the Great Arteries (TGA), the pulmonary artery, and aorta are connected to the heart abnormally resulting in blue blood (deoxygenated) recirculating to the body and red blood (oxygenated) recirculating to the lungs. The arterial switch operation (ASO) is the standard of care for transposition of the great arteries (TGA), and given the low risk of early mortality and satisfactory long-term outcomes, focus is now on managing longer term complications such as neo-aortic root dilatation, and pulmonary artery stenosis. Since May 2016, we have used 2-ply extracellular matrix (ECM; Tyke) for reconstruction of the coronary button defects using a pantaloon patch. We present histology of implanted 2-ply ECM (Tyke) from a patient who went back to surgery for development of subaortic stenosis ~12 months after ASO.
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http://dx.doi.org/10.3389/fcvm.2020.562136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661546PMC
October 2020

Case Report: Gestational Melioidosis through Perinatal Transmission.

Am J Trop Med Hyg 2020 11;103(5):1838-1840

Clínica Colsanitas, Clínica Universitaria Colombia, Bogotá, Colombia.

is an emerging pathogen in the Americas. Cases of mother-to-child transmission of are rare and probably occur by placental or perinatal infection. We report the first case of native gestational and neonatal melioidosis in the Western hemisphere. The isolated strains in the mother and newborn were confirmed by whole-genome sequencing and identified as a novel sequence type ST1748. The comparison of both genomes revealed a nucleotide similarity of 100%. Melioidosis should be considered within the differential diagnosis of febrile illness or pneumonia in pregnant women and newborns from endemic areas of the Americas.
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http://dx.doi.org/10.4269/ajtmh.20-0223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646751PMC
November 2020

The Destiny of Postoperative Residual Ventricular Septal Defects After Surgical Repair in Infants and Children.

World J Pediatr Congenit Heart Surg 2020 07;11(4):438-443

Division of Pediatric Cardiothoracic Surgery, The Heart Institute, Joe DiMaggio Children's Hospital, Hollywood, FL, USA.

Purpose: Residual ventricular septal defects (rVSDs) of small size are commonly seen on transesophageal echocardiography after surgical repair. This study aimed to determine the destiny of rVSD found on intraoperative echocardiogram.

Methods: Patients undergoing surgical repair of VSD as the primary procedure with available intraoperative and discharge echocardiograms between 2007 and 2017 were reviewed. Presence of an rVSD on intraoperative echo triggered review of discharge echo and of subsequent follow-up echocardiograms.

Results: One hundred four patients were analyzed. The mean age and weight for the entire cohort were 1.4 ± 2.9 years (median, 5.4 months; range, 29 days to 14 years) and 8.8 ± 9.9 kg (median, 5.1 kg; range, 2.7-58 kg), respectively. Sixty (57%) patients had rVSD at discharge, with mean size of residual VSD of 1.38 ± 0.92 mm (mode, 0.6; median, 2.2 mm; range, 0.5-3.9 mm). The mean follow-up time was 3.7 ± 3.1 years (range, 1 month to 9.3 years). Among those with rVSD at discharge, a residual shunt persisted in 73% at one-month follow-up. On follow-up at three years postdischarge, of the 60 patients with early rVSD, 6 had a persistent rVSD (10%) with a mean diameter of 3.0 ± 0.8 mm (range, 2.4-3.9 mm).

Conclusions: Residual VSD after surgical repair is detected frequently on postoperative echocardiogram. The presence of rVSD was not associated with any preoperative, intraoperative, or postoperative factors. By three years of follow-up, only six patients continued to demonstrate rVSD with a mean diameter of 3 mm, suggesting that defects 3 mm or greater may be less likely to close spontaneously after three years.
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http://dx.doi.org/10.1177/2150135120918537DOI Listing
July 2020

Serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multi-national cohort.

PLoS Negl Trop Dis 2020 06 24;14(6):e0008203. Epub 2020 Jun 24.

E25Bio, Cambridge, Massachusetts, United States of America.

Background: Dengue virus (DENV) infections pose one of the largest global barriers to human health. The four serotypes (DENV 1-4) present different symptoms and influence immune response to subsequent DENV infections, rendering surveillance, risk assessments, and disease control particularly challenging. Early diagnosis and appropriate clinical management is critical and can be achieved by detecting DENV nonstructural protein 1 (NS1) in serum during the acute phase. However, few NS1-based tests have been developed that are capable of differentiating DENV serotypes and none are currently commercially available.

Methodology/principle Findings: We developed an enzyme-linked immunosorbent assay (ELISA) to distinguish DENV-1-4 NS1 using serotype-specific pairs of monoclonal antibodies. A total of 1,046 antibodies were harvested from DENV-immunized mice and screened for antigen binding affinity. ELISA clinical performance was evaluated using 408 polymerase chain reaction-confirmed dengue samples obtained from patients in Brazil, Honduras, and India. The overall sensitivity of the test for pan-DENV was 79.66% (325/408), and the sensitivities for DENV-1-4 serotyping were 79.1% (38/48), 80.41% (78/97), 100% (45/45), and 79.6% (98/123), respectively. Specificity reached 94.07-100%.

Significance: Our study demonstrates a robust antibody screening strategy that enabled the development of a serotype NS1-based ELISA with maximized specific and sensitive antigen binding. This sensitive and specific assay also utilized the most expansive cohort to date, and of which about half are from Latin America, a geographic region severely underrepresented in previous similar studies. This ELISA test offers potential enhanced diagnostics during the acute phase of infection to help guide patient care and disease control. These results indicate that this ELISA is a promising aid in early DENV-1-4 diagnosis and surveillance in regions of endemicity in addition to offer convenient monitoring for future vaccine interventions.
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http://dx.doi.org/10.1371/journal.pntd.0008203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351204PMC
June 2020

Delayed Diagnosis of Dengue in a Patient With Systemic Lupus Erythematosus.

J Clin Rheumatol 2020 Jun 10. Epub 2020 Jun 10.

Departamento de Producción Universidad Nacional de Asunción Instituto de Investigaciones en Ciencias de la Salud San Lorenzo, Paraguay. Departamento de Reumatología Universidad Nacional de Asunción Facultad de Ciencias Médicas Hospital de Clínicas San Lorenzo, Paraguay. Departamento de Salud Pública Universidad Nacional de Asunción Instituto de Investigaciones en Ciencias de la Salud San Lorenzo, Paraguay. Division of Infectious Diseases Department of Medicine Emory University School of Medicine Atlanta, GA. Departamento de Producción Universidad Nacional de Asunción Instituto de Investigaciones en Ciencias de la Salud San Lorenzo, Paraguay. Departamento de Salud Pública Universidad Nacional de Asunción Instituto de Investigaciones en Ciencias de la Salud San Lorenzo, Paraguay. Universidad Departamento de Salud Pública Nacional de Asunción Instituto de Investigaciones en Ciencias de la Salud San Lorenzo, Paraguay Departamento de Reumatología Universidad Nacional de Asunción Facultad de Ciencias Médicas Hospital de Clínicas San Lorenzo, Paraguay. Departamento de Producción Universidad Nacional de Asunción Instituto de Investigaciones en Ciencias de la Salud San Lorenzo, Paraguay

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http://dx.doi.org/10.1097/RHU.0000000000001359DOI Listing
June 2020

Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America: the ESTAMPA screening study protocol.

BMJ Open 2020 05 24;10(5):e035796. Epub 2020 May 24.

Instituto Nacional de Cancerología, Bogotá, Colombia.

Introduction: Human papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC.

Methods And Analysis: Women aged 30-64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre.

Ethics And Dissemination: The study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings.

Trial Registration Number: NCT01881659.
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http://dx.doi.org/10.1136/bmjopen-2019-035796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252979PMC
May 2020

Real-time RT-PCR for the detection and quantitation of Oropouche virus.

Diagn Microbiol Infect Dis 2020 Jan 9;96(1):114894. Epub 2019 Sep 9.

Emory University, Department of Medicine, Division of Infectious Diseases, Atlanta, GA, USA; Rollins School of Public Health, Department of Global Health, Atlanta, GA, USA. Electronic address:

Oropouche virus (OROV) causes an acute, systemic febrile illness, and in certain regions of South America, this represents the second most common human arboviral infection after dengue virus. A new real-time RT-PCR was developed for OROV and reassortant species. The new OROV rRT-PCR proved linear across 6-7 orders of magnitude with a lower limit of 95% detection of 5.6-10.8 copies/μL. Upon testing dilutions of OROV and Iquitos virus reference genomic RNA, all dilutions with >10 copies/μL were detected in both the OROV rRT-PCR and a comparator molecular assay, but the OROV rRT-PCR detected more samples with ≤10 copies/μL (8/14 vs 0/13, respectively, P = 0.002). In a set of 100 acute-phase clinical samples from Paraguay patients with a suspected arboviral illness, no patients tested positive for OROV RNA using either assay. The OROV rRT-PCR provides a sensitive molecular assay for the study of this important yet neglected tropical arboviral infection.
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http://dx.doi.org/10.1016/j.diagmicrobio.2019.114894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906250PMC
January 2020

Characterization of dengue cases among patients with an acute illness, Central Department, Paraguay.

PeerJ 2019 9;7:e7852. Epub 2019 Oct 9.

Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GA, United States of America.

Background: In 2018, Paraguay experienced a large dengue virus (DENV) outbreak. The primary objective of this study was to characterize dengue cases in the Central Department, where the majority of cases occur, and identify factors associated with DENV infection.

Methods: Patients were enrolled from January-May 2018 if they presented with a suspected arboviral illness. Acute-phase specimens (≤8 days after symptom onset) were tested using rRT-PCR, a rapid diagnostic test for DENV nonstructural protein 1 (NS1) and anti-DENV IgM and IgG, and ELISA for IgG against NS1 from Zika virus (ZIKV).

Results: A total of 231 patients were enrolled (95.2% adults) at two sites: emergency care and an outpatient clinical site. Patients included 119 (51.5%) dengue cases confirmed by rRT-PCR ( = 115, 96.6%) and/or the detection of NS1 and anti-DENV IgM ( = 4, 3.4%). DENV-1 was the predominant serotype (109/115, 94.8%). Epidemiologically, dengue cases and non-dengue cases were similar, though dengue cases were less likely to reside in a house/apartment or report a previous dengue case. Clinical and laboratory findings associated with dengue included red eyes, absence of sore throat, leucopenia and thrombocytopenia. At an emergency care site, 26% of dengue cases (26/100) required hospitalization. In univariate analysis, hospitalization was associated with increased viral load, anti-DENV IgG, and thrombocytopenia. Among dengue cases that tested positive for IgG against ZIKV NS1, the odds of DENV NS1 detection in the acute phase were decreased 10-fold (OR 0.1, 0.0-0.3).

Conclusions: Findings from a predominantly adult population demonstrate clinical and laboratory factors associated with DENV infections and the potential severity of dengue in this group. The combination of viral load and specific IgG antibodies warrant further study as a prognostic to identify patients at risk for severe disease.
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http://dx.doi.org/10.7717/peerj.7852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790102PMC
October 2019

Custodiol cardioplegia solution compared to cold blood cardioplegia in pediatric cardiac surgery: a single-institution experience.

Perfusion 2020 05 4;35(4):316-322. Epub 2019 Oct 4.

Joe DiMaggio Children's Hospital Heart Institute, Hollywood, FL, USA.

Objective: Custodiol is an intracellular, crystalloid cardioplegia solution that is a single-dose alternative to multi-dose cold blood cardioplegia; however, there is scarce data regarding its use in infants and children. The objective of this study was to compare its impact on myocardial function in infants.

Methods: Single-center retrospective review including 132 patients <12 months old undergoing biventricular repair. There were 106 patients who received single-dose Custodiol and 27 patients who received multi-dose blood cardioplegia. Demographic and echocardiographic data were compared between the two groups.

Results: Patients receiving Custodiol were slightly younger (100 ± 62 days) and lower weight (4.7 ± 1.3 kg) compared to 152 ± 86 days and 5.2 ± 1.3 kg for blood cardioplegia (p < 0.05). The Society of Thoracic Surgeons/European Association for Cardio-Thoracic Surgery Congenital Heart Surgery score was similar between both groups. Average cardiopulmonary bypass time was similar between both groups (Custodiol 93 ± 54 minutes vs. blood 81 ± 44 minutes, p = 0.46) as was aortic cross-clamp time (Custodiol 58 ± 33 minutes vs. cold blood 53 ± 33 minutes, p = 0.62). Pre-operative left ventricular ejection fraction was similar for blood 73 ± 8% versus Custodiol 70 ± 9%, p = 0.21. There was also no intergroup difference in left ventricular ejection fraction 24 hours post op (blood 64 ± 9% vs. Custodiol 65 ± 12%, p = 0.53) or at discharge (blood 66 ± 10% vs. Custodiol 66 ± 11%, p = 0.95). The pre-operative right ventricle function by fractional area change was also similar in blood cardioplegia (46 ± 13%) versus Custodiol (48 ± 9%, p = 0.38) and showed similar drops in parameters in the two groups 24 hours after surgery and at discharge.

Conclusion: Single-dose Custodiol is as safe as blood cardioplegia for myocardial protection in congenital cardiac surgery for the cross-clamp times evaluated in this study. Evaluation at longer cross-clamp times would be helpful to determine if there is a greater benefit to single-dose Custodiol versus more repeated doses of blood cardioplegia for longer cross-clamp times.
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http://dx.doi.org/10.1177/0267659119878006DOI Listing
May 2020

Factors associated with high-risk human papillomavirus infection and high-grade cervical neoplasia: A population-based study in Paraguay.

PLoS One 2019 27;14(6):e0218016. Epub 2019 Jun 27.

Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción (IICS-UNA), San Lorenzo, Paraguay.

Background: Cervical cancer (CC) is one of the leading causes of cancer mortality among women from Paraguay, with high incidence and mortality rates (31.2 and 16 per 100 000 women, respectively). Although the risk factors associated with high-risk human papillomavirus (hrHPV) infection and preneoplastic cervical lesions are widely studied, population-based characteristics of particular settings may influence the feasibility of HPV-based CC screening implementation. This study aimed to explore factors associated with hrHPV infection and high-grade cervical neoplasia in hrHPV-positive (hrHPV+) women from Paraguay.

Methods: A total of 5677 women aged 30-64 years from the Central Department of Paraguay were screened with HPV test (Hybrid Capture 2) and Pap smear. Sociodemographic and risk factor interviews were conducted. hrHPV+ women were referred to colposcopy and women with an abnormal colposcopy had a biopsy taken. The outcomes recorded were the hrHPV status and the presence of high-grade cervical intraepithelial neoplasia or worse (CIN2+) among hrHPV+ women. Associations were investigated using multivariate logistic regressions.

Results: hrHPV prevalence was 13.8% (95%CI 13.0-14.8). This value decreased with the age of women (p-trend<0.001) and increased with the lifetime number of sexual partners (p-trend<0.001) and number of previous female partners of their current male partner if women had had one lifetime sexual partner (p-trend<0.001), increasing from 3.06 (95%CI 0.073-20.9) if partners had had one previous female partner to 9.19 (95%CI 2.36-61.1) if they had had eight or more. In hrHPV+ women, CIN2+ prevalence was 10.7% (95%CI 8.58-13.2) and increased with time since the last Pap smear (p-trend<0.001) and with the increasing number of pregnancies (p-trend = 0.05).

Conclusion: In these settings, the sexual behavior of women and their male partners is associated with hrHPV infection. In hrHPV+ women, underscreening practices and multiple pregnancies are associated with CIN2+. This knowledge can contribute to public health policies for CC prevention and control in Paraguay.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218016PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597051PMC
February 2020

Relation Between New York Heart Association Functional Class and Objective Measures of Cardiopulmonary Exercise in Adults With Congenital Heart Disease.

Am J Cardiol 2019 06 15;123(11):1868-1873. Epub 2019 Mar 15.

Adult Congenital Heart Center, Memorial Healthcare System, Hollywood, Florida.

We aimed to compare New York Heart Association (NYHA) functional class in adult congenital heart disease (ACHD) patients with objectively measured cardiopulmonary exercise testing (CPET) parameters. This study included retrospective review of ACHD patients who underwent a CPET between August 2014 and April 2018 at our center. Patients were grouped according to severity of CHD, and NYHA class as recorded in their medical record or estimated from the clinical narrative. A total of 175 ACHD patients (mean age 30 ± 11 years) with NYHA class I-III enrolled in the study. The NYHA functional class was II or III in most complex CHD. There was a strong inverse relation between NYHA class and peak oxygen consumption, oxygen uptake efficiency slope, and the double product at peak exercise (product of heart rate and systolic blood pressure) (p<0.0001). There was no relation between NYHA class and ventilation efficiency slope (p = 0.37). In conclusion, NYHA functional class correlates with objective measures of CPET, however there is wide variability in measured exercise capacity in each NYHA classification. Therefore, whereas NYHA class of patients is a simple measure for assessment of functional status, CPET is an important tool to identify the source of exercise limitation in ACHD patients.
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http://dx.doi.org/10.1016/j.amjcard.2019.02.053DOI Listing
June 2019

[Severe poisoning with naphazoline: update from a therapeutic error].

Arch Argent Pediatr 2018 08;116(4):e626-e629

Servicio de Emergencias Pediátricas, Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires.

Naphazoline is a drug commonly used as a decongestant in adult patients. Its indication in Pediatrics is not frequent, being approved its use from the age of 12 for the toxic effects it possesses. Intoxication in children generates a potentially serious clinical picture. It is characterized by the immediate appearance of hypotonia, deterioration of the sensory, hypothermia and bradycardia of variable degree of clinical compromise. Although it is an infrequent intoxication, the anamnesis and the initial management of the patient are the key in the evolution. We present a 4-year-old boy who, as a therapeutic error, receives this drug, emphasizing the rapid and potentially severe establishment of the clinical picture.
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http://dx.doi.org/10.5546/aap.2018.e626DOI Listing
August 2018

Respiratory medication used in COPD patients from seven Latin American countries: the LASSYC study.

Int J Chron Obstruct Pulmon Dis 2018 11;13:1545-1556. Epub 2018 May 11.

Department of Pneumology, Hospital Universitari Vall d'Hebron, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.

Background: Limited information is available regarding medication use in COPD patients from Latin America. This study evaluated the type of medication used and the adherence to different inhaled treatments in stable COPD patients from the Latin American region.

Methods: This was an observational, cross-sectional, multinational, and multicenter study in COPD patients attended by specialist doctors from seven Latin American countries. Adherence to inhaled therapy was assessed using the Test of Adherence to Inhalers (TAI) questionnaire. The type of medication was assessed as: short-acting β-agonist (SABA) or short-acting muscarinic antagonist (SAMA) only, long-acting muscarinic antagonist (LAMA), long-acting β-agonist (LABA), LABA/LAMA, inhaled corticosteroid (ICS), ICS/LABA, ICS/LAMA/LABA, or other.

Results: In total, 795 patients were included (59.6% male), with a mean age of 69.5±8.7 years and post-bronchodilator FEV of 50.0%±18.6%. The ICS/LAMA/LABA (32.9%) and ICS/LABA (27.7%) combinations were the most common medications used, followed by LABA/LAMA (11.3%), SABA or SAMA (7.9%), LABA (6.4%), LAMA (5.8%), and ICS (4.3%). The types of medication most commonly used in each Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013 category were ICS/LABA (A: 32.7%; B: 19.8%; C: 25.7%; D: 28.2%) and ICS/LAMA/LABA (A: 17.3%; B: 30.2%; C: 33%; D: 41.1%). The use of long-acting bronchodilators showed the highest adherence (good or high adherence >50%) according to the TAI questionnaire.

Conclusion: COPD management in specialist practice in Latin America does not follow the current guideline recommendations and there is an overuse of ICSs in patients with COPD from this region. Treatment regimens including the use of long-acting bronchodilators are associated with the highest adherence.
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http://dx.doi.org/10.2147/COPD.S154097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955011PMC
October 2018

Alphaviruses: Serological Evidence of Human Infection in Paraguay (2012-2013).

Vector Borne Zoonotic Dis 2018 05 13;18(5):266-272. Epub 2018 Mar 13.

1 Research Institute in Health Sciences, National University of Asunción , San Lorenzo, Paraguay .

Introduction: Alphaviruses can produce febrile illness and encephalitis in dead-end hosts such as horses and humans. Within this genus, the Venezuelan Equine Encephalitis virus (VEEV) complex includes pathogenic epizootic subtypes and enzootic subtypes that are not pathogenic in horses (except subtype IE, Mexican strains), although they can cause febrile symptoms in humans. The Rio Negro virus (RNV-VEEV subtype VI) circulates in Argentina, where it was associated with undifferentiated febrile illness. Mayaro (MAYV) and Una (UNAV) viruses belong to a different group, the Semliki Forest virus complex, with confirmed circulation.

Objective: The present study aimed to determine RNV, MAYV, and UNAV seroprevalences by plaque reduction neutralization test in 652 samples of Paraguayan individuals mainly from the Central Department, between years 2012 and 2013.

Methods: Samples with antibodies titer >1:20 against RNV were also tested for Mosso das Pedras-subtype IF, subtype IAB, and Pixuna (PIXV)-subtype IV viruses that belongs to VEEV antigenic complex.

Results: The overall seroprevalence of RNV was 3.83%, and for UNAV it was 0.46%, and no neutralizing antibodies were detected against MAYV in the studied population. Two of the twenty-seven heterotypic samples were positive for PIXV. The 50.1% of neutralizing antibody titers against RNV were high (equal to or greater than 1/640), suggesting recent infections. The effect of age on the prevalence of RNV was negligible.

Conclusions: These results bring new information about neglected alphaviruses in South America, and these data will serve as the basis for future studies of seroprevalence of other VEEV, and studies to search potential hosts and vectors of these viruses in the region.
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http://dx.doi.org/10.1089/vbz.2017.2178DOI Listing
May 2018

Prevalence and impact of respiratory symptoms in a population of patients with COPD in Latin America: The LASSYC observational study.

Respir Med 2018 01 28;134:62-69. Epub 2017 Nov 28.

Hospital Universitario de Caracas, Universidad Central de Venezuela, Caracas, Venezuela.

Background: To analyse the relationship between symptoms at different times during the 24-hour day and outcomes in COPD.

Methods: Observational cross-sectional study in a patients from 7 Latin American countries. The frequency of symptoms in the morning, at night and during the day was explored by means of standardised and validated questionnaires, and the relationship between symptoms and exacerbations and quality of life were investigated.

Results: 734 patients (59.6% male, mean age 69.5 years, mean FEV 50% predicted normal) were recruited. The most frequent symptoms during the day were dyspnea (75% of patients, of which 94% mild-moderate) and cough (72.2%, of which 93.4% mild-moderate). Highly symptomatic patients had a greater impairment in FEV, more exacerbations and worse scores in COPD assessment test (CAT) and Body Mass Index, Obstruction, Dyspnoea and Exacerbations (BODEx) index (all p < 0.001). Morning symptoms were more frequent than night-time symptoms, particularly cough and dyspnoea (morning: 50.1% and 45.7%; night-time: 33.2% and 24.4%, respectively), and mostly rated as mild or moderate. Patients with morning or night-time symptoms presented with worse severity of daytime symptoms. There was a strong correlation between intensity of daytime with morning or night-time symptoms, as well as with CAT score (r = 0.715; p < 0.001), but a weak correlation with FEV (r = -0.205; p < 0.001).

Conclusion: Morning symptoms were more frequent than night-time symptoms, and having either morning and/or night-time symptoms was associated with worse severity of daytime symptoms. Increased symptoms were strongly associated with worse quality of life and more frequent exacerbations, but weakly associated with airflow limitation.

Clinical Trial Registration: NCT02789540.
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http://dx.doi.org/10.1016/j.rmed.2017.11.018DOI Listing
January 2018

Redefining Cut-Points for High Symptom Burden of the Global Initiative for Chronic Obstructive Lung Disease Classification in 18,577 Patients With Chronic Obstructive Pulmonary Disease.

J Am Med Dir Assoc 2017 Dec;18(12):1097.e11-1097.e24

Department of Research and Education, CIRO, Horn, The Netherlands.

Background: Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference.

Methods: After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, postbronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores.

Main Outcomes: Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points.

Findings: A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points.

Conclusions: The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed.
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http://dx.doi.org/10.1016/j.jamda.2017.09.003DOI Listing
December 2017

Adherence to inhaled therapies of COPD patients from seven Latin American countries: The LASSYC study.

PLoS One 2017 15;12(11):e0186777. Epub 2017 Nov 15.

Department of Pneumology, Hospital Universitari Vall d'Hebron, CIBER de Enfermedades Respiratorias (CIBERES) Barcelona, Spain.

Background: This study assessed the adherence profiles to inhaled therapies and the agreement between two patient self-report adherence methods in stable COPD lpatients from seven Latin American countries.

Methods: This observational, cross-sectional, multinational, multicenter study involved 795 COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity [FEV1/FVC] <0.70). Adherence to inhaled therapy was assessed using the specific Test of Adherence to Inhalers (10-item TAI) and the generic 8-item Morisky Medication Adherence Scale (MMAS-8) questionnaires. The percentage agreement and the kappa index were used to compare findings.

Results: 59.6% of patients were male (69.5±8.7 years); post-bronchodilator FEV1 percent predicted was 50.0±18.6%. Mean values for 10-item TAI and MMAS-8 questionnaires were 47.4±4.9 and 6.8±1.6, respectively. Based on the TAI questionnaire, 54.1% of patients had good, 26.5% intermediate, and 19.4% poor adherence. Using the MMAS-8 questionnaire, 51% had high, 29.1% medium, and 19.9% low adherence. According to both questionnaires, patients with poor adherence had lower smoking history, schooling but higher COPD Assessment Test score, exacerbations in the past-year and post-bronchodilator FEV1. The agreement between 10-item TAI and MMAS-8 questionnaires was moderate (Kappa index: 0.42; agreement: 64.7%).

Conclusion: Suboptimal adherence to medication was frequent in COPD patients from Latin America. Low adherence was associated with worse health status impairment and more exacerbations. There was inadequate agreement between the two questionnaires. Greater effort should be made to improve COPD patients' adherence to treatment, and assessment of adherence with more specific instruments, such as the TAI questionnaire, would be more convenient in these patients.

Clinical Trial Registration: NCT02789540.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186777PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687703PMC
December 2017

The boundaries of mild chronic obstructive pulmonary disease (COPD): design of the searching clinical COPD onset (SOON) study.

BMJ Open 2017 Aug 11;7(8):e015731. Epub 2017 Aug 11.

Department of Pulmonary Diseases, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago, Chile.

Introduction: Clinical onset of chronic obstructive pulmonary disease (COPD) is the point at which the disease is first identifiable by physicians. It is a poorly defined stage which seems to include both mild spirometric and non-spirometric disease, and could be described as early grade COPD, for practical purposes. While dyspnoea; chronic bronchitis and CT imaging evidence of emphysema and airway disease may be present very early, the lone significance of dyspnoea, the most relevant symptom in COPD in identifying these individuals, has been scarcely assessed.The Searching Clinical COPD Onset (SOON) Study was designed primarily to detect clinical, physiological and structural differences between dyspnoeic and non-dyspnoeic individuals with early grade COPD. It is hypothesised that presence of dyspnoea in early disease may identify a subtype of individuals with reduced exercise capacity, notwithstanding of their spirometry results. In addition, dyspnoeic individuals will share worse quality of life, lower physical activity, greater lung hyperinflation greater emphysema and airway thickness and reduced peripheral muscle mass than their non-dyspnoeic counterpart.

Methods And Analysis: SOON is a monocentric study, with a cross sectional design aimed at obtaining representative samples of current or ex-smoker-adults aged ≥45 and ≤80 years. Two hundred and forty participants will be enrolled into four strata, according to normal spirometry or mild spirometric obstruction and presence or not of dyspnoea modified Medical Research Council score ≥1. The primary outcome will be the difference between dyspnoeic and non-dyspnoeic individuals on the 6-min walk test performance, regardless of their spirometry results. To account for the confounding effect of heart failure on dyspnoea, stress echocardiography will be also performed. Secondary outcomes will include clinical (quality of life, physical activity), physiological (exercise testing) and structural characteristics (emphysema, airway disease and peripheral muscle mass by CT imaging).

Ethics And Dissemination: The Institutional Ethics Committee from Pontificia Universidad Católica de Chile has approved the study protocol and signed informed consent will be obtained from all participants. The findings of the trial will be disseminated through relevant peer-reviewed journals and international conference presentations.

Trial Registration Number: NCT03026439.
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http://dx.doi.org/10.1136/bmjopen-2016-015731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724156PMC
August 2017

Effects of practice variability on spinal manipulation learning.

J Chiropr Educ 2017 Oct 25;31(2):90-95. Epub 2017 Jan 25.

Objective: To evaluate the effects of practice variability on chiropractic students' capacity to deliver spinal manipulations (SMs) of a targeted peak force.

Methods: Forty students participated in an experimental session including either a variable or a constant practice protocol of 45 SMs. SMs were delivered on a computer-connected device that recorded force-time profiles. Ten SMs with a target peak force of 350-N were performed before practice, immediately following practice, and 2 days later. Mixed-design analyses of variance were used to assess the effect of practice type on SM biomechanical parameters and on the constant, the absolute error (AE), and the variable error (VE).

Results: The practice period led to significantly more accurate (F[2,76] = 6.17, p < .01) and consistent (F[2,76] = 3.90, p = .02) performances at the postintervention assessment regardless of practice type. Among biomechanical parameters, preload force was higher at the retention assessment than at baseline (F[2,76] = 6.53, p < .01), while rate of force application significantly decreased between the baseline and the retention assessment (F[2,76] = 4.10, p = .02).

Conclusion: This experimental study showed that 1 session of SM practice including feedback leads to an increase in SM peak force accuracy and consistency, whether or not the practice period included variable practice. The current results confirmed that short practice periods with feedback should be included in the chiropractic curriculum.
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http://dx.doi.org/10.7899/JCE-16-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656152PMC
October 2017

Synthesis of bimetallic trifluoroacetates through a crystallochemical investigation of their monometallic counterparts: the case of (A, A')(CFCOO)·nHO (A, A' = Mg, Ca, Sr, Ba, Mn).

Dalton Trans 2017 Jan;46(5):1420-1430

Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.

Owing to their potential as single-source precursors for compositionally complex materials, there is growing interest in the rational design of multimetallic compounds containing fluorinated ligands. In this work, we show that chemical and structural principles for a materials-by-design approach to bimetallic trifluoroacetates can be established through a systematic investigation of the crystal-chemistry of their monometallic counterparts. A(CFCOO)·nHO (A = Mg, Ca, Sr, Ba, Mn) monometallic trifluoroacetates were employed to demonstrate the feasibility of this approach. The crystal-chemistry of monometallic trifluoroacetates was mapped using variable-temperature single-crystal X-ray diffraction, powder X-ray diffraction, and thermal analysis. The evolution with temperature of the previously unknown crystal structure of Mg(CFCOO)·4HO was found to be identical to that of Mn(CFCOO)·4HO. More important, the flexibility of Mn(CFCOO)·4HO (x = 1, 3) to adopt two structures, one isostructural to Mg(CFCOO)·4HO, the other isostructural to Ca(CFCOO)·4HO, enabled the synthesis of Mg-Mn and Ca-Mn bimetallic trifluoroacetates. MgMn(CFCOO)·4HO was found to be isostructural to Mg(CFCOO)·4HO and exhibited isolated metal-oxygen octahedra with Mg and Mn nearly equally distributed over the metal sites (Mg/Mn: 45/55). CaMn(CFCOO)·4HO was isostructural to Ca(CFCOO)·4HO and displayed trimers of metal-oxygen corner-sharing octahedra; Ca and Mn were unequally distributed over the central (Ca/Mn: 96/4) and terminal (Ca/Mn: 38/62) octahedral sites.
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http://dx.doi.org/10.1039/c6dt04152cDOI Listing
January 2017

[Not Available].

Nutr Hosp 2016 Mar 25;33(2):122. Epub 2016 Mar 25.

Centro de Investigaciones Endocrino-Metabólicas Dr. Félix Gómez. Facultad de Medicina. Universidad del Zulia. Maracaibo, Estado Zulia. Venezuela. Departamento de Ciencias Fisiológicas. Facultad de Medicina. Universidad del Zulia. Maracaibo, Estado Zulia. Venezuela..

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http://dx.doi.org/10.20960/nh.122DOI Listing
March 2016

[Not Available].

Nutr Hosp 2016 Feb 16;33(1):47-53. Epub 2016 Feb 16.

.

It has been studied the effect of three kinds of supplements (whey, casein and maltodextrin, as control) in the regulation of food intake and satiety of 60 overweight women. After 10 weeks, significant differences (p < 0.001) were found with regard to reduction of weight, IMC, % fat and waist circumference in the whey group against casein and control groups. A higher decrease of energy intake (-383 kcal/day) was also found in women who ate whey supplements, while in the casein and control group the decrease was only -144 and -70 kcal/day respectively. Finally, satiety effect was more efficiently promoted by whey against casein and maltodextrins.
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http://dx.doi.org/10.20960/nh.v33i1.15DOI Listing
February 2016
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