Corrigendum: Implementing a provisional overarching intervention for COVID-19 monitoring and control in the Brazil-Colombia-Peru frontier.

[This corrects the article DOI: 10.3389/fpubh.2023.1330347.].

First case of Oropouche fever detected in the international border region of the Colombian Amazon: clinical characteristics and molecular diagnosis.

OBJECTIVES: We report the first case of Oropouche fever detected in the border region of Colombia. METHODS: Using a multiplex real-time polymerase chain reaction (PCR), genetic sequencing and clinical characteristics during the dengue epidemic in 2019, a total of 175 samples were analysed, from cases notified to the system epidemiological surveillance such as dengue. FINDINGS: The Oropouche virus (OROV) isolate from Leticia belongs to lineage 2 according to both M and S genome segments maximum likelihood (ML) analysis, shares a common ancestor with samples obtained in Esmeraldas, Ecuador and Turbaco, Colombia. The patient: a woman resident in the border neighbourhood of the municipality of Leticia had the following symptoms: fever, headache, retro-orbital pain and myalgias. MAIN CONCLUSION: This cross-border surveillance can be useful to give an alert about the entry or exit of arboviruses circulation in the region, which are often underreported in public health surveillance systems.

First case of Oropouche fever detected in the international border region of the Colombian Amazon: clinical characteristics and molecular diagnosis

OBJECTIVES We report the first case of Oropouche fever detected in the border region of Colombia. METHODS Using a multiplex real-time polymerase chain reaction (PCR), genetic sequencing and clinical characteristics during the dengue epidemic in 2019, a total of 175 samples were analysed, from cases notified to the system epidemiological surveillance such as dengue. FINDINGS The Oropouche virus (OROV) isolate from Leticia belongs to lineage 2 according to both M and S genome segments maximum likelihood (ML) analysis, shares a common ancestor with samples obtained in Esmeraldas, Ecuador and Turbaco, Colombia. The patient: a woman resident in the border neighbourhood of the municipality of Leticia had the following symptoms: fever, headache, retro-orbital pain and myalgias. MAIN CONCLUSION This cross-border surveillance can be useful to give an alert about the entry or exit of arboviruses circulation in the region, which are often underreported in public health surveillance systems.

A multistrain probiotic increases the serum glutamine/glutamate ratio in patients with cirrhosis: a metabolomic analysis.

To explore the potential mechanisms underlying the effects of a probiotic in cirrhotic patients, we analyzed the blood metabolome using proton nuclear magnetic resonance (1H-NMR) spectroscopy in 32 patients with cirrhosis and cognitive dysfunction or falls. Patients were randomized to receive a multistrain probiotic or placebo for 12 weeks. Among the 54 metabolites identified, the only significant changes in the probiotic group were an increase in glutamine, a decrease in glutamate, and an increase in the glutamine/glutamate ratio. In the placebo group, glutamate increased and the glutamine/glutamate ratio decreased. Our results suggest the multistrain probiotic could influence glutamine/glutamate metabolism, increasing the capacity of ammonia detoxification.

Implementing a provisional overarching intervention for COVID-19 monitoring and control in the Brazil-Colombia-Peru frontier.

Introduction: he challenge was to provide comprehensive health resources to a remote and underserved population living in the Brazil-Colombia-Peru border, amid the most disruptive global crisis of the century. Methods: In August 2021, Fundação Oswaldo Cruz Amazonia (FIOCRUZ Amazônia) and partner collaborators implemented an overarching provisional program for SARS-CoV-2 detection and lineages characterization, training of laboratory personnel and healthcare providers, donation of diagnostic supplies and personal protective equipment, and COVID-19 vaccination. The expedition was conducted at the Port of Tabatinga, a busy terminal with an intense flux of people arriving and departing in boats of all sizes, located in the Amazon River basin. Local government, non-profit organizations, private companies, and other stakeholders supported the intervention. Results: The expedition was accomplished in a convergence point, where migrant workers, traders, army personnel, people living in urban areas, and people from small villages living in riversides and indigenous territories are in close and frequent contact, with widespread cross-border movement. Using a boat as a provisional lab and storage facility, the intervention provided clinical and laboratory monitoring for 891 participants; vaccination for 536 individuals; personal protective equipment for 200 healthcare providers; diagnostic supplies for 1,000 COVID-19 rapid tests; training for 42 community health agents on personal protection, rapid test execution, and pulse oximeter management; and hands-on training for four lab technicians on molecular diagnosis. Discussion: Our experience demonstrates that multilateral initiatives can counterweigh the scarcity of health resources in underserved regions. Moreover, provisional programs can have a long-lasting effect if investments are also provided for local capacity building.

STARS: Un instrumento útil para evaluar la ansiedad a la estadística / STARS: A useful tool to evaluate anxiety to statistics

Resumen. La ansiedad a la estadística se define como un conjunto de reacciones emocionales que generan incomodidad en el individuo, como preocupación excesiva, ideas intrusivas y tensión al asistir a una asignatura que involucre estadística o análisis estadísticos. Para su medición, se han diseñado distintos instrumentos; el más usado es la Statistical Anxiety Rating Scale (STARS). El objetivo del presente estudio fue adaptar y validar la escala STARS en una muestra colombiana para explorar sus propiedades psicométricas. Participaron 357 estudiantes universitarios con edades entre los 18 y 36 años (M= 19.19, DE = 1.87). Los resultados evidencian que las subescalas de la STARS muestran excelentes niveles de fiabilidad; el análisis factorial confirma la estructura de seis dimensiones y se reporta una validez concurrente importante. Se recomienda su uso para investigación y como herramienta para la toma de decisiones en procesos de acompañamiento académico en universidades.

Abstract. Statistics anxiety is defined as a set of emotional reactions that generate discomfort in the students, such as excessive worry, intrusive ideas and tension when they attending a course that involves statistics or statistical analysis. For its measurement, different instruments have been designed; the most used is the Statistical Anxiety Rating Scale (STARS). The objective of the present study was to adapt and validate the STARS in a Colombian sample to explore its psychometric properties. A total of 357 university students with ages between 18 and 36 years participated (X = 19.19, D.E. = 1.87). The results show that the subscales of the STARS show excellent levels of reliability; factor analysis confirms the six-dimensional structure and important concurrent validity is reported. It is recommended for research and as a tool for decision making in academic support processes in universities.

Dispositional mindfulness is associated with less cognitive fusion and better effortful control in young people: The mediating role of repetitive negative Thinking / Mindfulness disposicional se asocia con menor fusión cognitiva y mejor control del esfuerzo en personas jóvenes: El rol mediador del pensamiento negativo repetitivo

Abstract Introduction: The scientific community is taking an increasing interest in mindful ness due to its positive association with physical and psychological health indicators. However, there is still ongoing debate as to whether there could be other explanations for these effects. Aim: This study explores the relationships between dispositional mindfulness, cognitive fusion, effortful control and repetitive negative thinking (RNT). RNT was chosen as a potential me diating variable due to its presence in multiple psychological disorders. Method: A mediation analysis was performed using the bootstrap method with 5000 replications on data collected from a non-clinical sample of 415 young adults who completed a battery of online questionnai res. Results: Dispositional mindfulness is negatively associated with measures of RNT, effortful control and cognitive fusion. The analyses indicate that the effect that dispositional mindful ness has on cognitive fusion in young people can be partially mediated with medium effect size by RNT. Conclusion: RNT may play a central role as an underlying process in the link between mindfulness and different psychological aspects.

Resumen Introducción: Mindfulness ha ganado interés dentro de la comunidad científica dada su asociación con resultados positivos sobre indicadores de salud física y psicológica. Sin embargo, el debate sigue abierto sobre cuáles son los procesos que podrían mediar estas re laciones. Objetivo: Explorar en una muestra de 415 jóvenes, las relaciones entre mindfulness disposicional, fusión cognitiva, control del esfuerzo y pensamiento negativo repetitivo (PNR). El PNR se propone como potencial variable mediadora debido a que se es común en múltiples trastornos psicológicos. Método: Los análisis de mediación realizados a través de Bootstrap ping con 5000 replicaciones, indicaron que el efecto que genera el mindfulness disposicional sobre la fusión cognitiva puede estar mediado parcialmente por el PNR en personas jóvenes con un tamaño del efecto medio. Conclusiones: Mindfulness disposicional se relaciona de manera negativa con las medidas de PNR, control del esfuerzo y fusión cognitiva. Por tanto, el PNR podría desempeñar un papel importante como proceso subyacente entre mindfulness y diferentes aspectos psicológicos.

Use of checkpoint inhibitors in patients with lymphoid malignancies receiving allogeneic cell transplantation: a review.

Monoclonal antibodies against checkpoint receptors or its ligands have demonstrated high response rates and durable remissions in patients with relapsed Hodgkin lymphoma (HL) and other lymphoid malignancies. However, most patients will eventually progress on therapy and may benefit from further treatments including allogenic hematopoietic cell transplantation (allo-HCT). Furthermore, the use of checkpoint inhibitors (CPI) has emerged as a treatment option for patients relapsing after allo-HCT. The immune effects of the checkpoint blockade leading to a T-cell activation have raised some concerns on the safety of these therapies used either before or after allo-HCT, due to the potential risk of graft-versus-host disease (GVHD). Furthermore, CPI might also induce other immune toxicities, that can affect almost any organ, as a result of the dysregulation on the immune system balance. This review aims to focus on the evidence behind the use of CPI in patients with lymphoma who undergo allo-HCT. We summarize the clinical data generated to date about the use of CPI in HL and other lymphoid malignancies, the mechanisms of checkpoint inhibition in the context of allo-HCT as well as the clinical and biological observations of different GVHD prophylaxis in this setting. Furthermore, we discuss the evidence from retrospective series and early clinical trials on the feasibility and safety of the use of CPI in patients who relapsed after allo-HCT.

Effect of a Multistrain Probiotic on Cognitive Function and Risk of Falls in Patients With Cirrhosis: A Randomized Trial.

Probiotics can modulate gut microbiota, intestinal permeability, and immune response and could therefore improve cognitive dysfunction and help avoid potential consequences, such as falls, in patients with cirrhosis. The aim of this study was to evaluate the effect of a multistrain probiotic on cognitive function, risk of falls, and inflammatory response in patients with cirrhosis. Consecutive outpatients with cirrhosis and cognitive dysfunction (defined by a Psychometric Hepatic Encephalopathy Score [PHES] < -4) and/or falls in the previous year were randomized to receive either a sachet of a high-concentration multistrain probiotic containing 450 billion bacteria twice daily for 12 weeks or placebo. We evaluated the changes in cognitive function (PHES); risk of falls (Timed Up and Go [TUG] test, gait speed, and incidence of falls); systemic inflammatory response; neutrophil oxidative burst; intestinal barrier integrity (serum fatty acid-binding protein 6 [FABP-6] and 2 [FABP-2] and zonulin and urinary claudin-3); bacterial translocation (lipopolysaccharide-binding protein [LBP]); and fecal microbiota. Thirty-six patients were included. Patients treated with the probiotic (n = 18) showed an improvement in the PHES (P = 0.006), TUG time (P = 0.015) and gait speed (P = 0.02), and a trend toward a lower incidence of falls during follow-up (0% compared with 22.2% in the placebo group [n = 18]; P = 0.10). In the probiotic group, we observed a decrease in C-reactive protein (P = 0.01), tumor necrosis factor alpha (P = 0.01), FABP-6 (P = 0.009), and claudin-3 (P = 0.002), and an increase in poststimulation neutrophil oxidative burst (P = 0.002). Conclusion: The multistrain probiotic improved cognitive function, risk of falls, and inflammatory response in patients with cirrhosis and cognitive dysfunction and/or previous falls.

Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites.

AIM: To assess the relationship between the presence of toll-like receptor 4 (TLR4) polymorphisms and bacterial infections in cirrhotic patients with ascites. METHODS: We prospectively included consecutive patients with cirrhosis and ascites hospitalized during a 6-year period. Patients with human immunodeficiency virus (HIV) infection or any other immunodeficiency, patients with advanced hepatocellular carcinoma (beyond Milan's criteria) or any other condition determining poor short-term prognosis, and patients with a permanent urinary catheter were excluded. The presence of D299G and/or T399I TLR4 polymorphisms was determined by sequencing and related to the incidence and probability of bacterial infections, other complications of cirrhosis, hepatocellular carcinoma, and mortality during follow-up. A multivariate analysis to identify predictive variables of mortality in the whole series was performed. RESULTS: We included 258 patients: 28 (10.8%) were carriers of D299G and/or T399I TLR4 polymorphisms (polymorphism group) and 230 patients were not (wild-type group). The probability of developing any bacterial infection at one-year follow-up was 78% in the polymorphism group and 69% in the wild-type group (P = 0.54). The one-year probability of presenting infections caused by gram-negative bacilli (51% vs 44%, P = 0.68), infections caused by gram-positive cocci (49% vs 40%, P = 0.53), and spontaneous bacterial peritonitis (29% vs 34%, respectively, P = 0.99) did not differ between the two groups. The one-year probability of transplant-free survival was 55% in the polymorphism group and 66% in the wild-type group (P = 0.15). Multivariate analysis confirmed that age, Child-Pugh score, active alcohol intake, previous hepatic encephalopathy, hepatocellular carcinoma and serum creatinine were associated with a higher risk of death during follow-up. CONCLUSION: Genetic polymorphisms D299G and/or T399I of TLR4 do not seem to play a relevant role in the predisposition of cirrhotic patients with ascites to bacterial infections.

CSF-1 regulates the function of monocytes in Crohn's disease patients in remission.

During the flare-ups of Crohn's disease (CD) patients, circulating leukocytes actively migrate toward the inflamed sites. During the remission, the lack of symptoms does not necessarily imply immunological remission. To decipher inflammatory mechanisms still operating during CD remission, we compared the expression of chemokine receptors on monocytes from CD and healthy donors (HD), and how these differences could modulate monocyte maturation and cytokine production. Flow cytometry analysis showed a higher expression of CCR5 on monocytes from CD patients than those from HD after 24 h. This CCR5 upregulation was associated with the spontaneous production of CSF-1 and IL-10. The higher expression of CCR5 on CD monocytes increased their migratory pattern in response to CCL5. Signaling through CCR5/CCL5 increased CD163 and HLA-DR expression and diminished TLR4-induced TNF-α and IL-6 secretion during monocyte differentiation. When we analyzed clinical parameters, patients treated with azathioprine had the highest CSF-1 levels and CCR5 expression. Our results suggest that monocytes from CD patients in remission produced high levels of CSF-1 that upregulate CCR5 expression. Consequently, monocytes differentiated in these conditions had a characteristic phenotype and lower production of inflammatory cytokines. The treatment with azathioprine could be responsible for this anti-inflammatory profile of monocytes.

Alteration of the serum microbiome composition in cirrhotic patients with ascites.

The progression of cirrhosis is associated with alterations in the composition of the gut microbiome. To assess microbial translocation, we compared the serum microbial composition of patients with and without ascites and characterized the ascitic fluid microbiome using 16S rDNA high-throughput sequencing data. A complex and specific microbial community was detected in the serum and ascitic fluid of patients with cirrhosis but barely detectable in the serum of healthy controls. The serum microbiome of patients with ascites presented higher levels of lipopolysaccharide binding protein, a marker of microbial translocation, associated with higher diversity and relative abundance of Clostridiales and an unknown genus belonging to the Cyanobacteria phylum compared to patients without ascites. The composition of the fecal microbiome was also more altered in patients with than without ascites, confirming previous studies on fecal microbiome. We propose that alteration of the serum and fecal microbiome composition be considered indicators of cirrhosis progression.

Impaired innate immune response of leukocytes from ascitic fluid of patients with spontaneous bacterial peritonitis.

An ascitic microenvironment can condition the immune response of cells from cirrhotic patients with spontaneous bacterial peritonitis. To characterize this response, we determined the cytokine concentrations in ascitic fluid and analyzed the phenotype and function of ascitic leukocytes at diagnosis and after antibiotic-induced resolution in sterile ascites and ascitic fluid of 2 spontaneous bacterial peritonitis variants: positive and negative bacteriological culture. At diagnosis, a high concentration was found of IL-6 and IL-10 in the ascitic fluid from negative and positive bacteriological culture. The IL-6 concentration correlated with the percentage of neutrophils (R = 0.686, P < 0.001). In this context, positive and negative culture neutrophils had an impaired oxidative burst, and, after the antibiotic, the negative culture spontaneous bacterial peritonitis burst was fully recovered. Higher concentrations of IL-6 and IL-10 correlated with the presence of low granular CD 14(low) macrophages (R = -0.436, P = 0.005 and R = 0.414, P = 0.007, respectively). Positive culture spontaneous bacterial peritonitis macrophages expressed the lowest levels of CD16, CD86, CD11b and CD206, and HLA-DR, suggesting an impaired global function. Treatment increased all markers on the positive culture macrophages and CD11b and CD86 on negative culture macrophages. In negative culture spontaneous bacterial peritonitis, this increase was accompanied by phagocytic function recovery. The antibiotics then reverted the marker levels on positive and negative culture macrophages to the levels on sterile ascitis macrophages and restored ascitic negative culture cell function.

Cytokine production in patients with cirrhosis and TLR4 polymorphisms.

AIM: To analyze the cytokine production by peripheral blood cells from cirrhotic patients with and without TLR4 D299G and/or T399I polymorphisms. METHODS: The study included nine patients with cirrhosis and TLR4 D299G and/or T399I polymorphisms, and 10 wild-type patients matched for age, sex and degree of liver failure. TLR4 polymorphisms were determined by sequence-based genotyping. Cytokine production by peripheral blood cells was assessed spontaneously and also after lipopolysaccharide (LPS) and lipoteichoic acid (LTA) stimulation. RESULTS: Patients with TLR4 polymorphisms had a higher incidence of previous hepatic encephalopathy than wild-type patients (78% vs 20%, P = 0.02). Spontaneous production of interleukin (IL)-6 and IL-10 was lower in patients with TLR4 polymorphisms than in wild-type patients [IL-6: 888.7 (172.0-2119.3) pg/mL vs 5540.4 (1159.2-26053.9) pg/mL, P < 0.001; IL-10: 28.7 (6.5-177.1) pg/mL vs 117.8 (6.5-318.1) pg/mL, P = 0.02]. However, the production of tumor necrosis factor-α, IL-6 and IL-10 after LPS and LTA stimulation was similar in the two groups. CONCLUSION: TLR4 polymorphisms were associated with a distinctive pattern of cytokine production in cirrhotic patients, suggesting that they play a role in the development of cirrhosis complications.

Interleukin-19 impairment in active Crohn's disease patients.

The exact function of interleukin-19 (IL-19) on immune response is poorly understood. In mice, IL-19 up-regulates TNFα and IL-6 expression and its deficiency increases susceptibility to DSS-induced colitis. In humans, IL-19 favors a Th2 response and is elevated in several diseases. We here investigate the expression and effects of IL-19 on cells from active Crohn's disease (CD) patient. Twenty-three active CD patients and 20 healthy controls (HC) were included. mRNA and protein IL-19 levels were analyzed in monocytes. IL-19 effects were determined in vitro on the T cell phenotype and in the production of cytokines by immune cells. We observed that unstimulated and TLR-activated monocytes expressed significantly lower IL-19 mRNA in active CD patients than in HC (logFC = -1.97 unstimulated; -1.88 with Pam3CSK4; and -1.91 with FSL-1; p<0.001). These results were confirmed at protein level. Exogenous IL-19 had an anti-inflammatory effect on HC but not on CD patients. IL-19 decreased TNFα production in PBMC (850.7 ± 75.29 pg/ml vs 2626.0 ± 350 pg/ml; p<0.01) and increased CTLA4 expression (22.04 ± 1.55% vs 13.98 ± 2.05%; p<0.05) and IL-4 production (32.5 ± 8.9 pg/ml vs 13.5 ± 2.9 pg/ml; p<0.05) in T cells from HC. IL-10 regulated IL-19 production in both active CD patients and HC. We observed that three of the miRNAs that can modulate IL-19 mRNA expression, were up-regulated in monocytes from active CD patients. These results suggested that IL-19 had an anti-inflammatory role in this study. Defects in IL-19 expression and the lack of response to this cytokine could contribute to inflammatory mechanisms in active CD patients.

Randomized pilot study: effects of an exercise programme and leucine supplementation in patients with cirrhosis.

BACKGROUND: Physical exercise could improve functional limitations, muscle mass, and health-related quality of life (HRQoL) in patients with cirrhosis. AIM: The purpose of this study was to evaluate the efficacy and safety of an exercise programme and leucine supplementation to increase exercise capacity, muscle mass, and HRQoL in patients with cirrhosis. PATIENTS AND METHODS: Seventeen outpatients with cirrhosis were randomized to an exercise group (n = 8) or a control group (n = 9) in a pilot study. The programme of moderate exercise was performed for 12 weeks under supervision of a physiotherapist. All patients received oral leucine (10 g/day) during the study. At baseline and at the end of the study, we determined exercise capacity (6-min walk and 2-min step tests), anthropometric measurements, and HRQoL by Short Form-36 (SF-36) questionnaire. We also analyzed safety regarding complications of cirrhosis, liver and renal function, inflammatory response and oxidative stress. RESULTS: In the exercise group, exercise capacity improved, as shown by the increase in the 6-min walk test from 365 (160-420) to 445 m (250-500) (p = 0.01), and in the 2-min step test (p = 0.02). Lower thigh circumference also increased, from 41 (34-53) to 46 cm (36-56) (p = 0.02), and the domains of SF-36 general health (p = 0.03), vitality (p = 0.01) and social function (p = 0.04) improved significantly. In the control group, no statistically significant changes were observed in any of the parameters. We did not observe complications of cirrhosis in either group during the study. CONCLUSIONS: A programme of moderate physical exercise together with leucine supplements in patients with cirrhosis is safe and improves exercise capacity, leg muscle mass and HRQoL.