Showing papers by "National Autonomous University of Nicaragua published in 2021"

Arsenic in Latin America : New findings on source, mobilization and mobility in human environments in 20 countries based on decadal research 2010-2020

Abstract: Today (year 2020), the globally recognized problem of arsenic (As) contamination of water resources and other environments at toxic levels has been reported in all of the 20 Latin American countrie...

Three-year Efficacy and Safety of Takeda’s Dengue Vaccine Candidate (TAK-003)

Abstract: 1Hospital Maternidad Nuestra Senora de Altagracia, Santo Domingo, Dominican Republic; 2Takeda Vaccines, Inc., Boston, Massachusetts, USA; 3Hospital del Nino Dr. Jose Renan Esquivel, Sistema Nacional de Investigacion at SENACYT, Centro de Vacunacion Internacional (Cevaxin), Panama City, Panama; 4Centro de Atencion e Investigacion Medica, CAIMED, Bogota, Colombia; 5Centro de Estudios en Infectologia Pediatrica, Universidad del Valle and Centro Medico Imbanaco, Cali, Colombia; 6Research Institute For Tropical Medicine, Muntinlupa, Philippines; 7University of the Philippines Manila, Ermita, Philippines; 8Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 9Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; 10CAIMED, Dominicana, Santo Domingo, Dominican Republic; 11De La Salle Medical and Health Sciences Institute, Dasmarinas, Philippines; 12Phramongkutklao Hospital, Bangkok, Thailand; 13National Autonomous University of Nicaragua, Leon, Nicaragua; 14Nucleo de Doencas Infecciosas, Centro de Ciencias da Saude-UFES, Vitoria, Brazil; 15Centre for Clinical Management of Dengue & Dengue Haemorrhagic Fever, Negombo General Hospital, Negombo, Sri Lanka; 16University of Colombo, Colombo, Sri Lanka; 17Associacao Obras Sociais Irma Dulce Hospital Santo Antonio and Oswaldo Cruz Foundation, Bahia, Brazil; 18Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka; 19Faculty of Medical Sciences, University of Sri Jayawardenenpura, Colombo, Sri Lanka; 20Instituto de Medicina Tropical da Universidade Federal do Rio Grande do Norte, Natal, Brazil; 21Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil; 22Takeda Pharmaceuticals International AG, Zurich, Switzerland; and 23Philippines-Armed Forces Research Institute of Medical Sciences Virology Research Unit, Cebu City, Philippines

Neurodevelopmental Outcomes of Children Following In Utero Exposure to Zika in Nicaragua.

Abstract: BACKGROUND Neurodevelopmental outcomes of asymptomatic children exposed to Zika virus (ZIKV) in utero are not well characterized. METHODS We prospectively followed 129 newborns without evidence of congenital Zika syndrome (CZS) up to 24 months of age. Participants were classified as ZIKV exposed or ZIKV unexposed. The Mullen Scales of Early Learning (MSEL) was administered in the participants' homes at 6, 12, 15, 18, 21, and 24 months of age by trained psychologists. Sociodemographic data, medical history, and infant anthropometry at birth were collected at each home visit. Our primary outcome was the Mullen Early Learning Composite Score (ECL) at 24 months of age between our 2 exposure groups. Secondary outcomes were differences in MSEL subscales over time and at 24 months. RESULTS Of 129 infants in whom exposure status could be ascertained, 32 (24.8%) met criteria for in utero ZIKV exposure and 97 (75.2%) did not. There were no differences in maternal age, maternal educational attainment, birthweight, or gestational age at birth between the 2 exposure groups. The adjusted means and standard errors (SEs) for the ELC score between the ZIKV-exposed children compared to ZIKV-unexposed children were 91.4 (SE, 3.1) vs 96.8 (SE, 2.4) at 12 months and 93.3 (SE, 2.9) vs 95.9 (SE, 2.3) at 24 months. In a longitudinal mixed model, infants born to mothers with an incident ZIKV infection (P = .01) and low-birthweight infants (<2500 g) (P = .006) had lower composite ECL scores. CONCLUSIONS In this prospective cohort of children without CZS, children with in utero ZIKV exposure had lower neurocognitive scores at 24 months.

Risk Factors and Clinical Profile of Sapovirus-associated Acute Gastroenteritis in Early Childhood: A Nicaraguan Birth Cohort Study.

Abstract: Background Sapovirus is increasingly recognized as an important cause of acute gastroenteritis (AGE) in children. We identified risk factors and characterized the clinical profile of sapovirus AGE in a birth cohort in Leon, Nicaragua. Methods We conducted a case-control study nested within a birth cohort (n = 444). Fieldworkers conducted weekly household AGE surveillance. AGE stools were tested for sapovirus by reverse transcriptase quantitative polymerase chain reaction. For each first sapovirus episode, we selected 2 healthy age-matched controls and estimated independent risk factors of sapovirus AGE using conditional logistic regression. We compared clinical characteristics of sapovirus AGE episodes with episodes associated with other etiologies and identified co-infections with other enteric pathogens. Results From June 2017 to July 2019, we identified 63 first sapovirus AGE episodes and selected 126 controls. Having contact with an individual with AGE symptoms and vaginal delivery were independent risk factors for sapovirus AGE. All cases experienced diarrhea, lasting a median 6 days; 23% experienced vomiting. Compared to children with AGE due to another etiology, sapovirus AGE was similar in severity, with less reported fever. Most cases experienced co-infections and were more likely than controls to be infected with diarrheagenic Escherichia coli or astrovirus. Conclusions Sapovirus was a commonly identified AGE etiology in this Central American setting, and symptoms were similar to AGE associated with other etiologies. The association between vaginal delivery and sapovirus is a novel finding. Gut microbiome composition might mediate this relationship, or vaginal delivery might be a proxy for other risk factors. Further investigation into more specific biological mechanisms is warranted.

Secretor status strongly influences the incidence of symptomatic norovirus infection in a genotype-dependent manner in a Nicaraguan birth cohort.

Abstract: BACKGROUND The role of histo-blood group on the burden and severity of norovirus gastroenteritis in young infants has not been well documented. METHODS Norovirus gastroenteritis was assessed in 443 Nicaraguan children followed from birth until 3 years of age. Stool samples were tested for norovirus by RT-qPCR and histo-blood group antigens (HBGA) were determined by phenotyping of saliva and blood. Hazards ratios (95% CI) and predictors of norovirus AGE outcome stratified by HBGA were estimated using Cox proportional hazards models. RESULTS Of 1,353 AGE episodes experienced by children, 229 (17%) tested positive for norovirus with an overall incidence of 21.9/100 child-years. Secretor children were infected as early as 2 months old and had a higher incidence of norovirus GII compared to non-secretor children (15.4 vs 4.1/100 child-years, P = 0.006). Furthermore, all GII.4 AGE episodes occurred in secretor children. Children infected with GI (adjusted OR=0.09, 95% CI 0.02-0.33) or non-GII.4 viruses (adjusted OR=0.2, 95% CI: 0.07-0.6) were less likely to have severe AGE compared to GII.4 infected children. CONCLUSION Secretor status in children strongly influences the incidence of symptomatic norovirus infection in a genogroup or genotype-dependent manner and provides evidence that clinical severity in children depends on norovirus genotypes.

Prevalence and Factors Associated With Intimate Partner Violence Among Women in Haiti: Understanding Household, Individual, Partner, and Relationship Characteristics

Abstract: Intimate partner violence (IPV) is a significant public health issue with detrimental consequences for women’s reproductive, mental, and physical health. In Haiti, IPV is a major obstacle to women’...

The Relevance of Amyloid β-Calmodulin Complexation in Neurons and Brain Degeneration in Alzheimer's Disease.

Abstract: Intraneuronal amyloid β (Aβ) oligomer accumulation precedes the appearance of amyloid plaques or neurofibrillary tangles and is neurotoxic. In Alzheimer’s disease (AD)-affected brains, intraneuronal Aβ oligomers can derive from Aβ peptide production within the neuron and, also, from vicinal neurons or reactive glial cells. Calcium homeostasis dysregulation and neuronal excitability alterations are widely accepted to play a key role in Aβ neurotoxicity in AD. However, the identification of primary Aβ-target proteins, in which functional impairment initiating cytosolic calcium homeostasis dysregulation and the critical point of no return are still pending issues. The micromolar concentration of calmodulin (CaM) in neurons and its high affinity for neurotoxic Aβ peptides (dissociation constant ≈ 1 nM) highlight a novel function of CaM, i.e., the buffering of free Aβ concentrations in the low nanomolar range. In turn, the concentration of Aβ-CaM complexes within neurons will increase as a function of time after the induction of Aβ production, and free Aβ will rise sharply when accumulated Aβ exceeds all available CaM. Thus, Aβ-CaM complexation could also play a major role in neuronal calcium signaling mediated by calmodulin-binding proteins by Aβ; a point that has been overlooked until now. In this review, we address the implications of Aβ-CaM complexation in the formation of neurotoxic Aβ oligomers, in the alteration of intracellular calcium homeostasis induced by Aβ, and of dysregulation of the calcium-dependent neuronal activity and excitability induced by Aβ.

Association of Genetic Polymorphisms in DC-SIGN, Toll-Like Receptor 3, and Tumor Necrosis Factor α Genes and the Lewis-Negative Phenotype With Chikungunya Infection and Disease in Nicaragua.

Abstract: Background Chikungunya infections range from subclinical infection to debilitating arthralgia and to chronic inflammatory rheumatism. Tumor necrosis factor (TNF) α, DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin), Toll-like receptor (TLR) 3, and blood groups have been directly or indirectly implicated in the susceptibility and pathogenesis of chikungunya. Methods To test the hypothesis that polymorphisms in genes coding for these molecules determine clinical outcomes of chikungunya infection, a retrospective case-control study was performed in Leon, Nicaragua. The study included 132 case patients and 132 controls, matched for age, sex and neighborhood. Case patients had clinical symptoms of chikungunya, which was diagnosed by means of polymerase chain reaction. Controls were individuals not reporting abrupt presentation of clinical chikungunya-like symptoms. Polymorphisms were identified by TaqMan single-nucleotide polymorphism genotyping assays. Results After adjustment for sociodemographic risk factors, chikungunya disease was associated with polymorphism in DC-SIGN and TLR3 genes (odds ratios, 5.2 and 3.3, respectively), and TNF-α with reduced persistent joint pain (0.24). Persistent joint pain was also associated with age, female sex and other comorbid conditions. Most interestingly, the Lewis-negative phenotype was strongly associated with both symptomatic chikungunya and immunoglobulin G seropositivity (odds ratios, 2.7, and 3.3, respectively). Conclusion This study identified polymorphisms in DC-SIGN, TLR3, and TNF-α genes as well as Lewis-negative phenotype as risk factors for chikungunya infection and disease progression.

What the Flip: Embracing Flipped Learning as a Mediated Approach in Teacher Education

Abstract: Given the abrupt shift to online learning when schools closed down due to the COVID-19 pandemic, this chapter provides insights gained during the transition. The purpose of this chapter is to explore the use of flipped learning in teacher education courses as the courses transitioned to a virtual model. The authors discuss their participation in virtual professional learning communities (VPLCs) as well as efforts to engage students in VPLCs. This chapter offers perspectives of both instructors and students as well as insights gained while teaching in a teacher education program and while teaching at a Nicaraguan university. A primary focus within the chapter is the use of various technologies and the collaboration among colleagues in and out of the United States to instruct teachers candidates and practicing teachers from primary level through higher education programs. Practical guidance is offered to those looking to begin or further the virtual teaching and learning.

Serological Humoral Immunity Following Natural Infection of Children with High Burden Gastrointestinal Viruses.

Abstract: Acute gastroenteritis (AGE) is a major cause of morbidity and mortality worldwide, resulting in an estimated 440,571 deaths of children under age 5 annually. Rotavirus, norovirus, and sapovirus are leading causes of childhood AGE. A successful rotavirus vaccine has reduced rotavirus hospitalizations by more than 50%. Using rotavirus as a guide, elucidating the determinants, breath, and duration of serological antibody immunity to AGE viruses, as well as host genetic factors that define susceptibility is essential for informing development of future vaccines and improving current vaccine candidates. Here, we summarize the current knowledge of disease burden and serological antibody immunity following natural infection to inform further vaccine development for these three high-burden viruses.

Climate Change and Nephrology.

Abstract: Climate change should be of special concern for the nephrologist as the kidney has a critical role in protecting the host from dehydration, but is also a favorite target of heat stress and dehydration. Here we discuss how rising temperatures and extreme heat events may affect the kidney. The most severe presentation of heat stress is heat stroke, which can result in severe electrolyte disturbance and both acute and chronic kidney disease. However, lesser levels of heat stress also have multiple effects, including exacerbating kidney disease and precipitating cardiovascular events in subjects with established kidney disease. Heat stress can also increase the risk for kidney stones, cause multiple electrolyte abnormalities, and induce both acute and chronic kidney disease. Recently there have been multiple epidemics of chronic kidney disease of uncertain etiology in various regions of the world, including Mesoamerica, Sri Lanka, India and Thailand. There is increasing evidence that climate change and heat stress may have a contributory role in these conditions, although other causes including toxins could also be involved. As climate change worsens, the nephrologist should prepare for an increase in diseases associated with heat stress and dehydration.

MUSE Reveals Extended Circumnuclear Outflows in the Seyfert 1 NGC 7469

Abstract: NGC 7469 is a well known Luminous IR Galaxy, with a circumnuclear star formation ring ($\sim 830$ pc radius) surrounding a Seyfert 1 AGN. Nuclear unresolved winds were previously detected in X-rays and UV, as well as an extended biconical outflow in IR coronal lines. We search for extended outflows by measuring the kinematics of the $\mathrm{H\beta}$ and [O III] $\lambda 5007$ optical emission lines, in data of the VLT/MUSE integral field spectrograph. We find evidence of two outflow kinematic regimes: one slower regime extending across most of the star formation ring -- possibly driven by the massive star formation -- and a faster regime (with a maximum velocity of $-715 \ \mathrm{km \ s^{-1}}$), only observed in [O III], in the western region between the AGN and the massive star forming regions of the ring, likely AGN-driven. This work shows a case where combined AGN/star-formation feedback can be effectively spatially-resolved, opening up a promising path toward a deeper understanding of feedback processes in the central kiloparsec of AGN.

Binding of Amyloid β(1-42)-Calmodulin Complexes to Plasma Membrane Lipid Rafts in Cerebellar Granule Neurons Alters Resting Cytosolic Calcium Homeostasis.

Abstract: Lipid rafts are a primary target in studies of amyloid β (Aβ) cytotoxicity in neurons. Exogenous Aβ peptides bind to lipid rafts, which in turn play a key role in Aβ uptake, leading to the formation of neurotoxic intracellular Aβ aggregates. On the other hand, dysregulation of intracellular calcium homeostasis in neurons has been observed in Alzheimer's disease (AD). In a previous work, we showed that Aβ(1-42), the prevalent Aβ peptide found in the amyloid plaques of AD patients, binds with high affinity to purified calmodulin (CaM), with a dissociation constant ≈1 nM. In this work, to experimentally assess the Aβ(1-42) binding capacity to intracellular CaM, we used primary cultures of mature cerebellar granule neurons (CGN) as a neuronal model. Our results showed a large complexation of submicromolar concentrations of Aβ(1-42) dimers by CaM in CGN, up to 120 ± 13 picomoles of Aβ(1-42) /2.5 × 106 cells. Using fluorescence microscopy imaging, we showed an extensive co-localization of CaM and Aβ(1-42) in lipid rafts in CGN stained with up to 100 picomoles of Aβ(1-42)-HiLyteTM-Fluor555 monomers. Intracellular Aβ(1-42) concentration in this range was achieved by 2 h incubation of CGN with 2 μM Aβ(1-42), and this treatment lowered the resting cytosolic calcium of mature CGN in partially depolarizing 25 mM potassium medium. We conclude that the primary cause of the resting cytosolic calcium decrease is the inhibition of L-type calcium channels of CGN by Aβ(1-42) dimers, whose activity is inhibited by CaM:Aβ(1-42) complexes bound to lipid rafts.

Seroepidemiology of SARS-CoV-2 infections in an urban Nicaraguan population

Abstract: In a Nicaraguan population-based cohort, SARS-CoV-2 seroprevalence was 34%, with higher prevalence in children compared to adults. Having a seropositive household member was associated with a two-fold probability of individual seropositivity, suggesting a role for household transmission. Co-morbidities and preventive behaviors were not associated with SARS-CoV-2 seroprevalence.

Necesidades de investigación y transferencia de tecnologías sobre cambio climático en Nicaragua: Una oportunidad en la Bioeconomía

Abstract: This study focused on identifying the gaps that exist in relation to knowledge of climate change, its impacts and opportunities, as well as identifying its potentialities and restrictions as an alternative to the Bioeconomy. An interview model was developed, whose universe was aimed at selecting three types of populations: Private Companies, Institutions of Higher Education: Teachers and / or administrators and decision makers of these institutions, Public Institutions and Non-Governmental Organizations. The results showed that the private sector gives higher priority to reducing costs and increasing efficiency, increasing profitability and customer retention in relation to responding effectively to the threats and opportunities of climate change, indicating that there is a knowledge gap in relation to the impacts and opportunities offered by climate change, while in teaching it was observed that there is an abundant training of master's degrees related to environmental issues, however the courses taught in universities on climate change are very scarce and on the other hand, there is no national postgraduate training program on Climate change and only 58% of the teachers interviewed carry out research tasks. In public institutions and NGOs they believe that the frequency of access to scholarships to acquire knowledge about climate change is low and that at the national level the source of knowledge about climate change very frequently used by teachers and researchers is the Internet.

How Community and Individual Risk Factors Mutually Impact Youth's Perceived Safety: A Syndemic Analysis Using Structural Equation Modeling.

Abstract: The purpose of this study was to evaluate the mutual impact of community and individual factors on youth's perceptions of community safety, using structural equation modeling (SEM) conceptualized by syndemic theory. This study used survey data collected from a county wide sample of middle and high school students (N=25,147) in West Central Florida in 2015. The outcome variable was youth's perceptions of community safety. Predictors were latent individual and community factors constructed from 14 observed variables including gun accessibility, substance use, depressive symptoms, and multiple neighborhood disadvantage questions. Three structural equation models were conceptualized based on syndemic theory and analyzed in Mplus 8 using weighted least squares (WLS) estimation. Each model's goodness of fit was assessed. Approximately seven percent of youth reported feeling unsafe in their community. After model modifications, the final model showed a good fit of the data and adhered to the theoretical assumption. In the final SEM model, an individual latent factor was implied by individual predictors measuring gun accessibility without adult's permission (β=0.70), sadness and hopelessness (β=0.52), alcohol use (β=0.79), marijuana use (β=0.94), and illegal drug use (β=0.77). Meanwhile, a community latent factor was indicated by multiple community problems including public drinking (β=0.88), drug addiction (β=0.96), drug selling (β=0.97), lack of money (β=0.83), gang activities (β=0.90), litter and trash (β=0.79), graffiti (β=0.91), deserted houses (β=0.86), and shootings (β=0.93). A second-order syndemic factor that represented the individual and community factors showed a very strong negative association with youth's safe perception (β=-0.98). This study indicates that individual risk factors and disadvantaged community conditions interacted with each other and mutually affected youth's perceptions of community safety. To reduce these co-occurring effects and improve safe perceptions among youth, researchers and practitioners should develop and implement comprehensive strategies targeting both individual and community factors.

Relationships between CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 metabolic phenotypes and genotypes in a Nicaraguan Mestizo population.

Abstract: Interethnic variability in the drug-metabolizing capacity of CYP450 enzymes may lead to discrepancies in the relationship between genotypes and phenotypes worldwide. The present study was aimed to analyze for the first time whether there is a relationship between clinically relevant CYP450 genetic polymorphisms and their drug oxidation capacity (metabolic phenotype) in a population of healthy Nicaraguan volunteers. Two hundred and twelve participants were genotyped for CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, and their actual metabolic phenotype (evaluated by the Metabolic Ratio, MR) was analyzed by using the CEIBA cocktail approach. The results showed the wide interindividual variability in all the studied enzymes and a significant difference (p < 0.004) in the activity of CYP1A2 between male and female subjects. The number of CYP2C19 (p < 0.0001) and CYP2D6 (p < 0.0001) active alleles were shown inversely correlated with their corresponding MR, although there were marked genotype-phenotype discrepancies. There was an actual enzyme capacity overlapping (MR) between genotypically Poor (gPMs) and Extensive Metabolizers (gEMs) of 3.14% subjects for CYP2D6 and 0.94% for CYP2C9. Similarly, there was an overlapping for metabolic phenotypes of 11.48% of genotypically ultrarapid metabolizers (gUMs) for CYP2C19 and 2.09% for CYP2D6 and gEMs. Therefore, the current approach for metabolic phenotype prediction based just on genotype does not predict properly for all individuals within this Nicaraguan Mestizo population, thus representing a potential barrier for the clinical implementation of personalized medicine in this region. However, it is necessary to improve the prediction of phenotype from genotype in order to improve the pharmacogenetic implementation in populations with specific ethnic backgrounds.

Daily Rice Bran Consumption for 6 Months Influences Serum Glucagon-Like Peptide 2 and Metabolite Profiles without Differences in Trace Elements and Heavy Metals in Weaning Nicaraguan Infants at 12 Months of Age.

Abstract: Background Environmental enteric dysfunction (EED) is associated with chronic gut inflammation affecting nutrient absorption and development of children, primarily in low- and middle-income countries. Several studies have shown that rice bran (RB) supplementation provides nutrients and modulates gut inflammation, which may reduce risk for undernutrition. Objective The aim was to evaluate the effect of daily RB dietary supplementation for 6 mo on serum biomarkers in weaning infants and associated changes in serum and stool metabolites. Methods A 6-mo randomized-controlled dietary intervention was conducted in a cohort of weaning 6-mo-old infants in Leon, Nicaragua. Anthropometric indices were obtained at 6, 8, and 12 mo. Serum and stool ionomics and metabolomics were completed at the end of the 6-mo intervention using inductively coupled plasma MS and ultra-high performance LC-tandem MS. The ɑ1-acid glycoprotein, C-reactive protein, and glucagon-like peptide 2 (GLP-2) serum EED biomarkers were measured by ELISA. Results Twenty-four infants in the control group and 23 in the RB group successfully completed the 6-mo dietary intervention with 90% dietary compliance. RB participants had higher concentrations of GLP-2 as compared with control participants at 12 mo [median (IQR): 743.53 (380.54) pg/mL vs. 592.50 (223.59) pg/mL; P = 0.04]. Metabolite profiles showed significant fold differences of 39 serum metabolites and 44 stool metabolites from infants consuming RB compared with control, and with significant metabolic pathway enrichment scores of 4.7 for the tryptophan metabolic pathway, 5.7 for polyamine metabolism, and 5.7 for the fatty acid/acylcholine metabolic pathway in the RB group. No differences were detected in serum and stool trace elements or heavy metals following daily RB intake for 6 mo. Conclusions RB consumption influences a suite of metabolites associated with growth promotion and development, while also supporting nutrient absorption as measured by changes in serum GLP-2 in Nicaraguan infants. This clinical trial was registered at https://clinicaltrials.gov as NCT02615886.

Evidence-based medicine in neurosurgery: why and how?

Abstract: Since its inception, medical training and practice are based primarily on the clinical experience provided by the mentors of each of the medical schools. In the 1990s, the first steps were taken for the construction of what we now know as evidence-based medicine. Evidence-based medicine is the set of studies, methods, and principles for the prevention of medical diseases, management guidelines, and algorithms used in sources of evidence. Neurosurgery based on evidence has emerged thanks to advances in neuroscience and information technology that allows the globalization of current scientific information. The results of important reviews on the levels of evidence in neurosurgery are low in percentages of high-quality evidence in this field of medicine. Based on the above, the objective of this manuscript is to describe the application of evidence in neurosurgery, the current state of the art in evidence-based medicine, and the steps needed to create evidence of the best quality in neurosurgery.

IMPORTANCE trial: a provisional study-design of a single-center, phase II, double-blinded, placebo-controlled, randomized, 4-week study to compare the efficacy and safety of intranasal esketamine in chronic opioid refractory pain

Abstract: Background: Cancer is the second leading cause of death globally. Up to 86% of advanced cancer patients experience significant pain, while 10-20% live in chronic pain. Besides, increasing prescription of opioids resulted in 33,000 deaths in the US in 2015. Both reduce patients' functional status and quality of life. While cancer survival rates are increasing, therapeutic options for chronic opioid refractory pain are still limited. Esketamine is the s-enantiomer of ketamine, with superior analgesic effect and less psychotomimetic side effects. Intranasal esketamine was approved by the FDA for treatment-resistant depression. However, its use in chronic cancer pain has never been tested. Therefore, we propose a phase II, randomized, placebo-controlled trial to evaluate the efficacy and safety of intranasal esketamine in chronic opioid refractory cancer pain. Methods and analysis: We will recruit 120 subjects with chronic opioid refractory pain, defined as pain lasting more than 3 months despite optimal therapy with high dose opioids (>60 mg morphine equivalent dose/day) and optimal adjuvant therapy. Subjects will be randomized into two groups: intranasal esketamine (56mg) and placebo. Treatment will be administered twice a week for four consecutive weeks. The primary outcome is defined as reduction in the Numeric Pain Rating Scale (NPRS) after first application. Secondary outcomes include NPRS reduction after four weeks, the number of daily morphine rescue doses, functional status and satisfaction, and depression. Conclusion: This study may extend therapeutic options in patients with chronic pain, thus improving their quality of life and reducing opioid use. Trial registration: Clinical Trials.gov, NCT04666623. Registered on 14 December 2020.

Zika RNA and Flavivirus-Like Antigens in the Sperm Cells of Symptomatic and Asymptomatic Subjects.

Abstract: Zika virus (ZIKV) RNA has been found to remain in human semen for up to one year after infection, but the presence of Flavivirus antigens in the different compartments of semen has been largely unexplored. Following the introduction of ZIKV in Nicaragua (2016), a prospective study of patients with clinical symptoms consistent with ZIKV was conducted in Leon to investigate virus shedding in different fluids. ZIKV infection was confirmed in 16 male subjects (≥18 years of age) by RT-qPCR in either blood, saliva or urine. Of these, three provided semen samples at 7, 14, 21, 28, 60 and 180 days postsymptom onset (DPSO) for Flavivirus antigens and RNA studies. These cases were compared with 19 asymptomatic controls. Flavivirus antigens were examined by immunofluorescence (IF) using the 4G2 Mabs, and confocal microscopy was used to explore fluorescence patterns. The three (100%) symptomatic subjects and 3 (16%) of the 19 asymptomatic subjects had Flavivirus antigens and viral RNA in the spermatozoa fraction. The percentage of IF Flavivirus-positive spermatozoa cells ranged from 1.9% to 25% in specimens from symptomatic subjects, as compared with 0.8% to 3.8% in specimens from asymptomatic controls. A marked IF-pattern in the cytoplasmic droplets and tail of the spermatozoa was observed. The sperm concentrations (45 × 106/mL vs. 63.5 × 106/mL, p = 0.041) and the total motility percentage (54% vs. 75%, p = 0.009) were significantly lower in specimens from ZIKV-positive than in those of ZIKV-negative. In conclusion, this study demonstrated the presence of Flavivirus antigens and RNA within a time frame of 28 DPSO in sperm cells of symptomatic and asymptomatic subjects during the ZIKV epidemic. These findings have implications for public health, in terms of nonarthropod-born, silent transmission facilitated by sperm cells and potential transmission from asymptomatic males to pregnant women, with consequences to the fetus.

Anxiety and Depression Symptoms in Spanish Children and Adolescents: An Exploration of Comorbidity from the Network Perspective.

Abstract: The combination of depression and anxiety is among the most prevalent comorbidities of disorders leading to substantial functional impairment in children and adolescents. The network perspective offers a new paradigm for understanding and measuring psychological constructs and their comorbidity. The present study aims to apply network analysis to explore the comorbidity between depression and anxiety symptoms. Specifically, the study examines bridge symptoms, comorbidity, and shortest pathway networks and estimates the impact of the symptoms in the network's connectivity and structure. The findings show that "feeling lonely" and "feeling unloved" are identified as the most central bridge symptoms. The shortest path network suggests that the role of a mixed anxiety-depressive symptomatology, and specific and non-specific symptoms of clinical criteria, such as "worries," "feels depressed," "fears school," and "talks about suicide" could serve as a warning for comorbidity.

A Wild Animal Inside My House: An Analysis of the Children’s Picturebook Svenn the Otter and the Magic Rock by Espen Villseth and Anita Sletten

Abstract: Svenn, a wild otter, has become an Instagram celebrity with over 140,000 followers around the world. Svenn has his own YouTube channel and Facebook page. Moreover, in December 2020, NRK, an influential Norwegian TV channel, released a series entitled “Oteren Svenn” (Svenn, the Otter), consisting of ten episodes. In addition to all of this, Svenn has his own picturebook for children, which is entitled Svenn the Otter and the Magic Rock (Villseth & Sletten, 2020). This article presents the picturebook and analyzes three of its significant spreads. The aim is to uncover aspects of the sociocultural context in which Svenn – along with other characters – is portrayed by images and verbal language in the book, and to provide a short discussion of how the book may be used in English Language Teaching (ELT). Our analysis builds on tools from multimodal text analysis (Kress & van Leeuwen, 2005; van Leeuwen, 2005) and Narrative Intelligence (Mateas & Senger, 2003). The analysis focuses on the significance of the picturebook to represent participants in actions, the relationship between the book’s participants and the reader, and the value of presenting images and verbal text together. Our analysis also touches on some implications for ELT, on the potential that visual literacy can have in language teaching.

Modelo para la continuidad de la formación de grado en posgrado: UNAN-Managua

Abstract: The continuity of postgraduate undergraduate training has the goal of integrating university training, research and extension processes in a coherent sequence, of greater scope and continuity of skills from undergraduate to postgraduate, which allows the linkage and effective development of lines of research at both levels. Therefore, to achieve this, a constructive, recursive, systematic work methodology and inclusive participation of the actors involved is necessary. To do this, the construction of a model for the continuity of undergraduate and graduate training explains how undergraduate and graduate training can be linked is based on different foundations. Among these are: the methodology to build theoretical models, the country's legal framework, the mission, vision and values of the institution of higher education, as well as concepts and theories related to curricular models that favor the integral development of learning, of research and extension processes. The different levels of integration (level of integration in the undergraduate degree, level of integration in the integrating axis, research projects (intervention) and level of integration and link with postgraduate degrees), give coherence to the continuity process in which the they link training, research and extension. However, the model is finally materialized in a series of actions that culminate in the improvement of the training of postgraduate programs, taking as a basis the model to develop competencies.

Morphological descriptions of the nymph and adults of Ornithodoros clarki, the larva and nymph of Ornithodoros rondoniensis, with notes on their phylogenetic relationships.

Abstract: Based on tick specimens collected recently in Mexico, Nicaragua, Panama and Brazil, we provide morphological descriptions of the nymph and adults of Ornithodoros clarki Jones & Clifford, 1972 from the first three countries, and the larva and nymph of Ornithodoros rondoniensis (Labruna, Terassini, Camargo, Brandao, Ribeiro & Estrada-Pena, 2008) from Brazil. Also, an analysis of mitochondrial 16S rDNA sequences was performed to analyze the phylogenetic relationships of these tick species. Adults and nymphs of O. clarki and O. rondoniensis are unique among the Argasidae family by presenting exceptionally large spiracular plates with small goblets, and an integument with smooth polygonal mammillae. However, these two species are morphologically distinct based on specific patterns of coxal folds, idiosomal mammillae and pilosity, and female genital flap. In contrast, the larvae of O. clarki and O. rondoniensis are morphologically identical, except for a general larger size of the former species; this slight difference is corroborated by Principal Component Analysis (PCA) by using 40 morphometric variables. Phylogenetic analyses including 16S rDNA partial sequences of different Ornithodoros taxa from Central and South America indicate that O. rondoniensis from Brazil diverges from O. clarki from Mexico, Nicaragua and Panama. However, phylogenetic distance separating both alleged species is similar or slightly lower than the distances depicted for conspecific populations of a few other Ornithodoros species. Nonetheless, our primary criterion to maintain O. rondoniensis as a valid species is because its adult and nymphal stages do present distinct morphological traits that easily distinguish these postlarval stages from O. clarki.

Antibody response to SARS-CoV-2 infection over six months among Nicaraguan outpatients

Abstract: New information is emerging about SARS-CoV-2 epidemiology and immunity, but little of this information comes from low- and middle-income countries or from patients receiving care in the outpatient setting. The current study investigated the SARS-CoV-2 infection status and antibody responses in 157 patients seeking care for a respiratory disease suggestive of COVID-19 in private healthcare clinics during the first wave (June-October 2020) of infections in Nicaragua. We examined nasal swabs for the presence of viral RNA via RT-PCR and longitudinally collected sera for the changes in SARS-CoV-2 Spike antibody levels over six months. Among patients with confirmed SARS-CoV-2 infections, we evaluated if clinical symptoms were associated with age, hematological parameters and co-morbidities. The combination of PCR and paired serology identified 60 (38%) of the 157 outpatients as acute COVID-19. While both PCR and serology identified the majority (n = 38, 64%) of the acute infections, a notable number of outpatients were identified by RT-qPCR (n = 13, 22%) or by serology (n = 9, 14%) only. During the longitudinal study, we identified 6 new infections by serology among the 97 non-COVID-19 subjects. In conclusion, this study report that more than one third of the outpatients seeking care for acute respiratory disease during the first epidemic wave of SARS-CoV-2 in Nicaragua had an acute mild COVID-19 infection that correlate with prolonged humoral response. This immune response to the RBD antigen, more likely IgG dependent, significantly increased between the acute to convalescent and decay in the late convalescent but still remained seropositive.