Molecular characterization of antibiotic resistant Salmonella enterica across the poultry production chain in Costa Rica: A cross-sectional study.

Antibiotic resistant Salmonella enterica are on the increase, worldwide. Given the scarcity of data, this study aimed to investigate its occurrence, virulence, and antibiotic resistance in Costa Rica's food chain. In total, 65 chicken meat- and 171 chicken caecal samples were collected and examined for Salmonella. High frequencies of Salmonella were found in chicken meat (58.5 %, n/N = 38/65) and poultry farms (38.0 %, n/N = 65/171). The majority of Salmonella from chicken meat (89.5 %, n/N = 34/38) and caecum samples (93.6 %, n/N = 59/63) exhibited multidrug resistance (MDR). Serovar Infantis was the most prevalent (94 %, n/N = 67/71), followed by serovars Anatum and Kentucky (3 %, n/N = 2/71). A pESI-like plasmid (92 %, n/N = 65/71) containing virulence and resistance markers was found in S. Infantis. Given the high prevalence of MDR Salmonella, this study emphasizes the need to enhance surveillance systems for foodborne pathogens and antimicrobial resistance in Costa Rica's food production chain.

Sucralose: From Sweet Success to Metabolic Controversies-Unraveling the Global Health Implications of a Pervasive Non-Caloric Artificial Sweetener.

Sucralose is a food additive initially used to mitigate glycemic peaks and calorie intake in patients with diabetes and obesity. Although sucralose has been considered safe for human consumption, the World Health Organization (WHO) issued a global alert in 2023 concerning the potential health implications of this artificial sweetener. This review aims to comprehensively explore the effects of sucralose intake on human health by understanding sucralose absorption, metabolism, and excretion. We also outline the role of the sweet taste 1 receptor 3 (T1R3) in mediating sucralose-dependent signaling pathways that regulate satiety, incretin release, and insulin response. Finally, we discuss the impact of sucralose on microbiome dysbiosis, inflammatory response origin, liver damage, and toxicity. Gaining a deeper understanding of the manifold effects of sucralose on human physiology will help promote further studies to ensure its consumption is deemed safe for a broader population, including children, adolescents, and pregnant women.

Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations.

SARS-CoV-2 causes COVID-19, which has claimed millions of lives. This virus can infect various cells and tissues, including the brain, for which numerous neurological symptoms have been reported, ranging from mild and non-life-threatening (e.g., headaches, anosmia, dysgeusia, and disorientation) to severe and life-threatening symptoms (e.g., meningitis, ischemic stroke, and cerebral thrombosis). The cellular receptor for SARS-CoV-2 is angiotensin-converting enzyme 2 (ACE2), an enzyme that belongs to the renin-angiotensin system (RAS). RAS is an endocrine system that has been classically associated with regulating blood pressure and fluid and electrolyte balance; however, it is also involved in promoting inflammation, proliferation, fibrogenesis, and lipogenesis. Two pathways constitute the RAS with counter-balancing effects, which is the key to its regulation. The first axis (classical) is composed of angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and angiotensin type 1 receptor (AT1R) as the main effector, which -when activated- increases the production of aldosterone and antidiuretic hormone, sympathetic nervous system tone, blood pressure, vasoconstriction, fibrosis, inflammation, and reactive oxygen species (ROS) production. Both systemic and local classical RAS' within the brain are associated with cognitive impairment, cell death, and inflammation. The second axis (non-classical or alternative) includes ACE2, which converts Ang II to Ang-(1-7), a peptide molecule that activates Mas receptor (MasR) in charge of opposing Ang II/AT1R actions. Thus, the alternative RAS axis enhances cognition, synaptic remodeling, cell survival, cell signal transmission, and antioxidant/anti-inflammatory mechanisms in the brain. In a physiological state, both RAS axes remain balanced. However, some factors can dysregulate systemic and local RAS arms. The binding of SARS-CoV-2 to ACE2 causes the internalization and degradation of this enzyme, reducing its activity, and disrupting the balance of systemic and local RAS, which partially explain the appearance of some of the neurological symptoms associated with COVID-19. Therefore, this review aims to analyze the role of RAS in the development of the neurological effects due to SARS-CoV-2 infection. Moreover, we will discuss the RAS-molecular targets that could be used for therapeutic purposes to treat the short and long-term neurological COVID-19-related sequelae.

Blood-brain Barrier Damage is Pivotal for SARS-CoV-2 Infection to the Central Nervous System.

Transsynaptic transport is the most accepted proposal to explain the SARS-CoV-2 infection of the CNS. Nevertheless, emerging evidence shows that neurons do not express the SARS-CoV-2 receptor ACE2, which highlights the importance of the blood-brain barrier (BBB) in preventing virus entry to the brain. In this study, we examine the presence of SARS-CoV-2 messenger ribonucleic acid (mRNA) and the cytokine profile in cerebrospinal fluids (CSF) from two patients with a brain tumor and COVID-19. To determine the BBB damage, we evaluate the Q- albumin index, which is an indirect parameter to assess the permeability of this structure. The Q-albumin index of the patient with an intraventricular brain tumor suggests that the BBB is undamaged, preventing the passage of SARS-CoV-2 and pro-inflammatory molecules. The development of brain tumors that disrupt the BBB (measured by the Q-albumin index), in this case, a petroclival meningioma (Case 1), allows the free passage of the SARS-CoV-2 virus and probably lets the free transit of pro-inflammatory molecules to the CNS, which leads to a possible activation of the microglia (astrogliosis) and an exacerbated immune response represented by IL-13, IFN-γ, and IL-2 trying to inhibit both the infection and the carcinogenic process.

In Vitro Exposure of Primary Human T Cells and Monocytes to Polyclonal Stimuli Reveals a Basal Susceptibility to Display an Impaired Cellular Immune Response and Develop Severe COVID-19.

The contribution of the cellular immune response to the severity of coronavirus disease 2019 (COVID-19) is still uncertain because most evidence comes from patients receiving multiple drugs able to change immune function. Herein, we conducted a prospective cohort study and obtained blood samples from 128 unvaccinated healthy volunteers to examine the in vitro response pattern of CD4+ and CD8+ T cells and monocyte subsets to polyclonal stimuli, including anti-CD3, anti-CD28, poly I:C, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) recombinant spike S1 protein, and lipopolysaccharide. Then, we started a six-month follow-up and registered 12 participants who got SARS-CoV-2 infection, from whom we retrospectively analyzed the basal immune response pattern of T cells and monocytes. Of the 12 participants infected, six participants developed mild COVID-19 with self-limiting symptoms such as fever, headache, and anosmia. Conversely, six other participants developed severe COVID-19 with pneumonia, respiratory distress, and hypoxia. Two severe COVID-19 cases required invasive mechanical ventilation. There were no differences between mild and severe cases for demographic, clinical, and biochemical baseline characteristics. In response to polyclonal stimuli, basal production of interleukin-2 (IL-2) and interferon (IFN-) gamma significantly decreased, and the programmed cell death protein 1 (PD-1) increased in CD4+ and CD8+ T cells from participants who posteriorly developed severe COVID-19 compared to mild cases. Likewise, CD14++CD16- classical and CD14+CD16+ non-classical monocytes lost their ability to produce IFN-alpha in response to polyclonal stimuli in participants who developed severe COVID-19 compared to mild cases. Of note, neither the total immunoglobulin G serum titers against the virus nor their neutralizing ability differed between mild and severe cases after a month of clinical recovery. In conclusion, using in vitro polyclonal stimuli, we found a basal immune response pattern associated with a predisposition to developing severe COVID-19, where high PD-1 expression and low IL-2 and IFN-gamma production in CD4+ and CD8+ T cells, and poor IFN-alpha expression in classical and non-classical monocytes are linked to disease worsening. Since antibody titers did not differ between mild and severe cases, these findings suggest cellular immunity may play a more crucial role than humoral immunity in preventing COVID-19 progression.

High Incidence Rate of SARS-CoV-2 Infection in Health Care Workers at a Dedicated COVID-19 Hospital: Experiences of the Pandemic from a Large Mexican Hospital.

Health care workers (HCW) are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The incidence of SARS-CoV-2 infection in HCW has been examined in cross-sectional studies by quantitative polymerase chain reaction (qPCR) tests, which may lead to underestimating exact incidence rates. We thus investigated the incidence of SARS-CoV-2 infection in a group of HCW at a dedicated coronavirus disease 2019 (COVID-19) hospital in a six-month follow-up period. We conducted a prospective cohort study on 109 participants of both sexes working in areas of high, moderate, and low SARS-CoV-2 exposure. qPCR tests in nasopharyngeal swabs and anti-SARS-CoV-2 IgG serum antibodies were assessed at the beginning and six months later. Demographic, clinical, and laboratory parameters were analyzed according to IgG seropositivity by paired Student's T-test or the chi-square test. The incidence rate of SARS-CoV-2 infection was considerably high in our cohort of HCW (58%), among whom 67% were asymptomatic carriers. No baseline risk factors contributed to the infection rate, including the workplace. It is still necessary to increase hospital safety procedures to prevent virus transmissibility from HCW to relatives and non-COVID-19 patients during the upcoming waves of contagion.

Molecular characterization of the S1 gene in GI-17 and GI-13 type isolates of avian infectious bronchitis virus (IBV) in Costa Rica, from 2016 to 2019.

Avian infectious bronchitis is one of the most important respiratory diseases affecting poultry production worldwide. The etiological agent of this disease is the avian infectious bronchitis virus (IBV). We analyzed 14 isolates of IBV obtained from poultry farms in Costa Rica, from 2016 through 2019. We sequenced the S1 region of the genome and the sequences obtained were submitted to GenBank. Phylogenetic analyses showed that the isolates obtained during 2016-2017 belong to the GI-17 lineage and are related to the Georgia 13-type Ga-13/14255/14 and CK/CR/1160/16 variants, with a 96.90-100% nucleotide sequence identity and a 92.25-100% amino acid sequence identity. The main differences were detected in the RBD and HVR-3 regions, where a series of mutations eliminate an N-glycosylation site in 10 out of 11 isolates. The isolates obtained during 2018-2019 belong to the GI-13 lineage and are closely related to the 4/91 vaccine variant, with over 98% sequence identity at the nucleotide and amino acids levels. Variations were detected in the RBD and HVR regions, with a possible N-glycosylation site detected in isolate CK/CR/0632/19. These results indicate that a GA13-like pathogenic variant circulated during the 2016-2017 period and that the 4/91 variant was detected after the introduction of the vaccine. The variations shown in both the GA13-like and 4/91 isolates examined, reveal the need for continuous surveillance of IBV in Costa Rica, to detect new variants that may be introduced to the country or develop during outbreaks. This information is highly relevant for vaccination planning and disease management programs. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-022-00762-2.

Ten-Week Sucralose Consumption Induces Gut Dysbiosis and Altered Glucose and Insulin Levels in Healthy Young Adults.

Sucralose consumption alters microbiome and carbohydrate metabolism in mouse models. However, there are no conclusive studies in humans. Our goals were to examine the effect of sucralose consumption on the intestinal abundance of bacterial species belonging to Actinobacteria, Bacteroidetes, and Firmicutes and explore potential associations between microbiome profiles and glucose and insulin blood levels in healthy young adults. In this open-label clinical trial, volunteers randomly drank water, as a control (n = 20), or 48 mg sucralose (n = 20), every day for ten weeks. At the beginning and the end of the study, participants were subjected to an oral glucose tolerance test (OGTT) to measure serum glucose and insulin every 15 min for 3 h and provided fecal samples to assess gut microbiota using a quantitative polymerase chain reaction. Sucralose intake altered the abundance of Firmicutes without affecting Actinobacteria or Bacteroidetes. Two-way ANOVA revealed that volunteers drinking sucralose for ten weeks showed a 3-fold increase in Blautia coccoides and a 0.66-fold decrease in Lactobacillus acidophilus compared to the controls. Sucralose consumption increased serum insulin and the area under the glucose curve compared to water. Long-term sucralose ingestion induces gut dysbiosis associated with altered insulin and glucose levels during an OGTT.

The Combined Use of Cytokine Serum Values with Laboratory Parameters Improves Mortality Prediction of COVID-19 Patients: The Interleukin-15-to-Albumin Ratio.

Laboratory parameters display limited accuracy in predicting mortality in coronavirus disease 2019 (COVID-19) patients, as with serum albumin. Emerging evidence suggests that cytokine serum values may enhance the predictive capacity of albumin, especially interleukin (IL)-15. We thus investigated whether the use of the IL-15-to-albumin ratio enables improving mortality prediction at hospital admission in a large group of COVID-19 patients. In this prospective cross-sectional study, we enrolled and followed up three hundred and seventy-eight patients with a COVID-19 diagnosis until hospital discharge or death. Two hundred and fifty-five patients survived, whereas one hundred and twenty-three died. Student's T-test revealed that non-survivors had a significant two-fold increase in the IL-15-to-albumin ratio compared to survivors (167.3 ± 63.8 versus 74.2 ± 28.5), a difference that was more evident than that found for IL-15 or albumin separately. Likewise, mortality prediction considerably improved when using the IL-15-to-albumin ratio with a cut-off point > 105.4, exhibiting an area under the receiver operating characteristic curve of 0.841 (95% Confidence Interval, 0.725-0.922, p < 0.001). As we outlined here, this is the first study showing that combining IL-15 serum values with albumin improves mortality prediction in COVID-19 patients.

Immunometabolic bases of type 2 diabetes in the severity of COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 and type 2 diabetes (T2D) have now merged into an ongoing global syndemic that is threatening the lives of millions of people around the globe. For this reason, there is a deep need to understand the immunometabolic bases of the main etiological factors of T2D that affect the severity of COVID-19. Here, we discuss how hyperglycemia contributes to the cytokine storm commonly associated with COVID-19 by stimulating monocytes and macrophages to produce interleukin IL-1ß, IL-6, and TNF-α in the airway epithelium. The main mechanisms through which hyperglycemia promotes reactive oxygen species release, inhibition of T cell activation, and neutrophil extracellular traps in the lungs of patients with severe SARS-CoV-2 infection are also studied. We further examine the molecular mechanisms by which proinflammatory cytokines induce insulin resistance, and their deleterious effects on pancreatic ß-cell exhaustion in T2D patients critically ill with COVID-19. We address the effect of excess glucose on advanced glycation end product (AGE) formation and the role of AGEs in perpetuating pneumonia and acute respiratory distress syndrome. Finally, we discuss the contribution of preexisting endothelial dysfunction secondary to diabetes in the development of neutrophil trafficking, vascular leaking, and thrombotic events in patients with severe SARS-CoV-2 infection. As we outline here, T2D acts in synergy with SARS-CoV-2 infection to increase the progression, severity, and mortality of COVID-19. We think a better understanding of the T2D-related immunometabolic factors that contribute to exacerbate the severity of COVID-19 will improve our ability to identify patients with high mortality risk and prevent adverse outcomes.

Molecular characterization of an avian GA13-like infectious bronchitis virus full-length genome from Costa Rica.

We describe the first whole-genome sequence of a GA13-like isolate of avian infectious bronchitis virus CK/CR/1160/16 (MN757859), obtained in 2016 in the province of Alajuela, Costa Rica. This virus caused an outbreak with great economic impact to the local poultry industry. The genome sequence is 27 696 bp in length, with the following genome organization 5'-UTR-Pol-S-3a-3b-E-4b-4c-M-5a-5b-N-6b-3'-UTR. The complete genome sequence has the highest sequence identity (94.03%) with DMV/1639/GA9977/2019 (MK878536) from Georgia, USA, and the lowest identity (86.03%) with ck/CH/LHLJ/08-6 (KX252788), from China. Analysis of the S1 subunit indicates that the Costa Rican isolate belongs to genotype I, lineage 17 (GI-17) and displays 96.89% identity with the S1 subunit of Ga-13/14255/14 (KM087780) (USA). Possible recombination events in genes S, E, M, 4b y 4c were detected, with Massachusetts, Connecticut, Arkansas and MA5 as potential parental types. This study highlights the importance of the epidemiological and molecular surveillance of avian infectious bronchitis.

Implicaciones clínicas de la enfermedad diverticular del apéndice. Experiencia en los últimos 10 años / Clinical implications of diverticular disease of the appendix. Experience over the past 10 years

INTRODUCCIÓN: La enfermedad diverticular del apéndice es infrecuente, con una incidencia que varía desde 0,004 a 2,1%. Suele presentarse entre la cuarta o quinta década de vida, con ausencia de síntomas gastrointestinales y dolor abdominal insidioso. Los pacientes habitualmente consultan de forma tardía, con el consiguiente aumento de morbimortalidad. El objetivo de este estudio fue determinar las características clínicas de la enfermedad diverticular del apéndice. MÉTODOS: Se realizó un estudio retrospectivo de todos los pacientes operados de apendicectomía en un hospital terciario desde septiembre de 2003 hasta septiembre de 2013. RESULTADOS: Durante este periodo se realizaron 7.044 apendicectomías, encontrándose 42 casos de enfermedad diverticular del apéndice, que representa una incidencia de 0,59%. De ellos, 27 pacientes fueron de sexo masculino. La edad media fue de 46,6 ± 21 años. El promedio de la estancia hospitalaria fue de 4,5 días. El 46% de los casos presentaban perforación del apéndice. En el 80% de los casos se realizó una prueba de imagen complementaria. La incidencia de neoplasia asociada a enfermedad diverticular fue de 7,1%. CONCLUSIONES: La enfermedad diverticular del apéndice es un hallazgo incidental. En la fase aguda presenta síntomas indiferenciables de la apendicitis aguda. El tratamiento de elección es la apendicectomía. Presenta una mayor probabilidad de desarrollar neoplasias del apéndice

BACKGROUND: Diverticular disease of the appendix is an uncommon condition, with an incidence from 0.004 to 2.1%. It usually occurs between the fourth or fifth decades of life, does not present gastrointestinal symptoms but only insidious abdominal pain. Patients usually delay consultation, leading to increased morbidity and mortality. The aim of this study was to determine the clinical features of diverticular disease of the appendix. METHODS: A retrospective study of all patients undergoing appendectomy in a tertiary hospital between September 2003 and September 2013 was performed. RESULTS: During this period, 7,044 appendectomies were performed, and 42 cases of diverticular disease of the appendix were found, which represents an incidence of 0.59%. A total of 27 patients were male. The mean age was 46.6 ± 21 years. The average hospital stay was 4.5 days. A perforated appendix was identified in 46% of patients. In 80% of the cases, a complementary imaging test was performed. The incidence of neoplastic disease with diverticulum of the appendix was 7.1%. CONCLUSIONS: Diverticular disease of the appendix is an incidental finding. In its acute phase, it presents as an acute appendicitis. The treatment of choice is appendectomy. It presents a higher risk of developing neoplastic disease of the appendix

Clinical implications of diverticular disease of the appendix. Experience over the past 10 years.

BACKGROUND: Diverticular disease of the appendix is an uncommon condition, with an incidence from 0.004 to 2.1%. It usually occurs between the fourth or fifth decades of life, does not present gastrointestinal symptoms but only insidious abdominal pain. Patients usually delay consultation, leading to increased morbidity and mortality. The aim of this study was to determine the clinical features of diverticular disease of the appendix. METHODS: A retrospective study of all patients undergoing appendectomy in a tertiary hospital between September 2003 and September 2013 was performed. RESULTS: During this period, 7,044 appendectomies were performed, and 42 cases of diverticular disease of the appendix were found, which represents an incidence of 0.59%. A total of 27 patients were male. The mean age was 46.6±21 years. The average hospital stay was 4.5 days. A perforated appendix was identified in 46% of patients. In 80% of the cases, a complementary imaging test was performed. The incidence of neoplastic disease with diverticulum of the appendix was 7.1%. CONCLUSIONS: Diverticular disease of the appendix is an incidental finding. In its acute phase, it presents as an acute appendicitis. The treatment of choice is appendectomy. It presents a higher risk of developing neoplastic disease of the appendix.

Salmonella contamination risk points in broiler carcasses during slaughter line processing.

Salmonella is one of the foodborne pathogens most commonly associated with poultry products. The aim of this work was to identify and analyze key sampling points creating risk of Salmonella contamination in a chicken processing plant in Costa Rica and perform a salmonellosis risk analysis. Accordingly, the following examinations were performed: (i) qualitative testing (presence or absence of Salmonella), (ii) quantitative testing (Salmonella CFU counts), and (iii) salmonellosis risk analysis, assuming consumption of contaminated meat from the processing plant selected. Salmonella was isolated in 26% of the carcasses selected, indicating 60% positive in the flocks sampled. The highest Salmonella counts were observed after bleeding (6.1 log CFU per carcass), followed by a gradual decrease during the subsequent control steps. An increase in the percentage of contamination (10 to 40%) was observed during evisceration and spray washing (after evisceration), with Salmonella counts increasing from 3.9 to 5.1 log CFU per carcass. According to the prevalence of Salmonella -contaminated carcasses released to trade (20%), we estimated a risk of 272 cases of salmonellosis per year as a result of the consumption of contaminated chicken. Our study suggests that the processes of evisceration and spray washing represent a risk of Salmonella cross-contamination and/ or recontamination in broilers during slaughter line processing.

Split ex situ e in situ: técnica y resultados / No disponible

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