Ecthyma gangrenosum in pediatric patients: 10-year experience at the National Institute of Pediatrics.

BACKGROUND: Ecthyma gangrenosum (EG) usually results from the hematogenous seeding of the skin in the setting of bacteremia, mostly by Pseudomonas aeruginosa, especially in immunocompromised patients. It presents as erythematous-violaceous macules, or plaques with surrounding erythema before rapidly progressing to bullae and necrotic-ulcerative eschars. METHODS: We performed a retrospective chart review of EG patients diagnosed at the National Institute of Pediatrics. Data included demographics, underlying disease, cutaneous lesions, location, evolution, microbiologic, histopathologic findings, and treatment. Data were analyzed by descriptive statistics; Mann-Whitney U test and Fisher's exact test were used to evaluate differences between groups. RESULTS: Seventeen patients with a mean age of 12.5 (6-16) years were included. The most common underlying disease was acute lymphoblastic leukemia (59%), three patients were not immunocompromised (17%). A total of 18 episodes of EG were recorded, 10 (55%) were disseminated at presentation. Systemic manifestations included fever (100%), pain (88.9%), asthenia and adynamia (22.2%). P. aeruginosa was isolated in 10 (55%) cases, followed by Staphylococcus aureus in four. Three patients had sepsis at onset (17%). A comparison between localized versus disseminated, pseudomonal versus nonpseudomonal, and bacteremic versus nonbacteremic EG was performed with no statistical difference between any of the groups, except for longer treatment time for pseudomonal EG, and longer hospitalization days for both pseudomonal EG and bacteremia. CONCLUSIONS: Fever and pain in the setting of rapidly evolving necrotic lesions should prompt the clinical suspicion of EG and the installment of empiric treatment pending culture results.

Trends in Inpatient Antibiotic Use Among Adults Hospitalized During the Coronavirus Disease 2019 Pandemic in Argentina, Brazil, and Chile, 2018-2021.

BACKGROUND: High rates of antibiotic use (AU) among inpatients with coronavirus disease 2019 (COVID-19) despite low rates of bacterial coinfection and secondary infection have been reported. We evaluated the impact of the COVID-19 pandemic on AU in healthcare facilities (HCFs) in South America. METHODS: We conducted an ecologic evaluation of AU in inpatient adult acute care wards in 2 HCFs each in Argentina, Brazil, and Chile. The AU rates for intravenous antibiotics were calculated as the defined daily dose per 1000 patient-days, using pharmacy dispensing records and hospitalization data from March 2018-February 2020 (prepandemic) and March 2020-February 2021 (pandemic). Differences in median AU were compared between the prepandemic and pandemic periods, using the Wilcoxon rank sum test to determine significance. Interrupted time series analysis was used to analyze changes in AU during the COVID-19 pandemic. RESULTS: Compared with the prepandemic period, the median difference in AU rates for all antibiotics combined increased in 4 of 6 HCFs (percentage change, 6.7%-35.1%; P < .05). In the interrupted time series models, 5 of 6 HCFs had significant increases in use of all antibiotics combined immediately at the onset of the pandemic (immediate effect estimate range, 15.4-268), but only 1 of these 5 HCFs experienced a sustained increase over time (change in slope, +8.13; P < .01). The effect of the pandemic onset varied by antibiotic group and HCF. CONCLUSIONS: Substantial increases in AU were observed at the beginning of the COVID-19 pandemic, suggesting the need to maintain or strengthen antibiotic stewardship activities as part of pandemic or emergency HCF responses.

Nanocaging Rose Bengal to Inhibit Aggregation and Enhance Photo-induced Oxygen Consumption†.

Photosensitized crosslinking of proteins in tissues has many medical applications including sealing wounds, strengthening tissues, and beneficially altering tissue properties. Rose Bengal (RB) is used most frequently as the photosensitizer but is not as efficient as would be desired for broad utilization in medicine. Aggregation of RB, at the high concentrations used for medical treatments, decreases the yield of singlet oxygen, which mediates protein crosslinking. We hypothesized that nanocages that sequester RB would inhibit self-association, increasing photosensitization efficiency. We tested cucurbituril and cyclodextrin nanocages, demonstrating that hydroxypropyl-functionalized cyclodextrins are most effective in inhibiting RB aggregation. For these RB/cyclodextrin solutions, we investigated the effect of nanocaging on the photobleaching and oxygen consumption kinetics under 530 nm LED light in aqueous phosphate-buffered solutions. At 100 µm RB, the initial oxygen consumption rates increased by 58% and 80% compared with uncaged RB for the ß and γ (2-hydroxypropyl) cyclodextrins, respectively. For 1 mm RB, the enhancement in these rates was much greater, about 200% and 300%, respectively. In addition, at 1 mm RB these two cyclodextrins increased the RB photobleaching rate by ~20% and ~75%. These results suggest that nanocages can minimize RB aggregation and may lead to higher-efficiency photo-medical therapies.

Impact of axenic and mixed starter cultures on metabolomic and sensory profiles of ripened Italian salami.

In this work, the synergistic/antagonistic impact of glucose and mixed starter cultures, namely Latilactobacillus sakei, Pediococcus pentosaceus, and Staphylococcus xylosus, was evaluated in Italian salami in terms of metabolomics and sensory profiles. As expected, Salami manufactured with 0.5 % glucose exhibited a substantial pH drop, showing values close to 5 at 12 days of ripening. Metabolomics revealed 1841 metabolites, mainly belonging to amino acids, peptides, glycerolipids, and nucleic acids, showing a greater hierarchical role of glucose addition when compared with inoculated microbial starters. Distinct metabolomic fingerprints could be observed across treatments, mainly concerning glutamyl peptides like gamma-glutamyl-glutamate (related to the kokumi taste), biogenic amines (spermine), and lipid oxidation products (i.e., the oxylipin 13S-hydroperoxylinolenic acid). Such differences may drive the differences in sensory profiles recorded among treatments. These findings indicate the need to select ad-hoc starter cultures to improve the safety, quality, and sensory traits of salami.

Metabolomics and gene-metabolite networks reveal the potential of Leuconostoc and Weissella strains as starter cultures in the manufacturing of bread without baker's yeast.

Lactic Acid Bacteria (LAB) could provide a valid alternative to S. cerevisiae as a starter culture for bakery products, avoiding yeast-related health problems while contributing to the technological and functional properties of bread. In this work, we evaluate the role of certain LABs (Leuconostoc citreum SB6, Weissella cibaria UC4051, Weissella confusa UC4051, and the commercial starter cultures Weissella cibaria, and Leuconostoc mesenteroides) in producing functional compounds (pro-technological, health-promoting, and postbiotic-like molecules). For this purpose, we analysed the genotypic and phenotypic features of strains, and we investigated dough fermentation from microbiological and metabolomics approaches. Results evidenced a clear discrimination between the metabolic activity of baker's yeast and LAB. The most discriminant metabolites derived from proteolysis and lipolysis, such as peptides, amino acids, and fatty acyls. Furthermore, we elucidated the different metabolism of these strains by building gene-metabolite interaction networks that pairwise compared the LAB strains of the same genus. While most of the networks showed a characteristic nucleotide metabolism, only the commercial W. cibaria exhibited an interaction network composed of amino acids and their related genes. In conclusion, our findings reveal that LAB strains under investigation, and particularly the commercial W. cibaria, can enhance the functional properties of bread.

Influence of Diet and Levels of Zonulin, Lipopolysaccharide and C-Reactive Protein on Cardiometabolic Risk Factors in Young Subjects.

A western diet and increased intestinal permeability may contribute to systemic inflammation and the development of cardio-metabolic alterations. The aim of this study was to assess the relationship between diet, biomarkers of intestinal permeability, and chronic low-grade inflammation on the cardiometabolic profile. A cross-sectional study was carried out in 238 young subjects aged 18-29 years, divided into two groups: with <3 cardiometabolic risk factors (CRF) and ≥3 risk factors. Anthropometric parameters, biochemical profile, and serum levels of zonulin, lipopolysaccharide (LPS), and high-sensitivity C-reactive protein (hs-CRP) were measured, and the macronutrient intake was evaluated. Interaction models showed elevated glucose levels in the presence of high biomarker levels: zonulin ≥51.6 ng/mL plus LPS ≥ 1.35 EU/mL (ß = 1.1, p = 0.006), and LPS ≥1.35 EU/mL plus hs-CRP ≥ 4.3 mg/L (ß = 1.2, p = 0.007). In addition, triglyceride levels increased in the presence of LPS ≥ 1.35 EU/mL and hs-CRP ≥ 4.3 mg/L (ß = 3.9, p = 0.01). Despite having increased biomarker levels, a higher consumption of water (≥2100 mL), polyunsaturated fatty acids (≥6.0 g), or fiber (≥30 g) decreased triglyceride (ß = -9.6, p = 0.03), total cholesterol (ß = -5.1, p = 0.01), and LDL-C levels (ß = -7.7, p = 0.01). These findings suggest that the increased consumption of water, PUFA and fiber may improve lipid profile in subjects with intestinal permeability dysfunction or low-grade systemic inflammation.

Strategies for Nitrite Replacement in Fermented Sausages and Effect of High Pressure Processing against Salmonella spp. and Listeria innocua.

The development of nitrite-free meat products is a current industrial concern. Many efforts have been attempted to replace the nitrite effect in cured meats colour formation and pathogens control. Our previous work evidenced that lactic acid and a cold ripening were the best hurdle technologies for nitrite-free fermented sausages from metabolomics. In the first part of this work, we investigated the effect of lactic acid compared with both two alternative additives (glucono-D-lactone and a mix of sodium di-acetate/sodium lactate) and with low-nitrite sausages, all of them following either cold or traditional ripening. For this purpose, microbiological analysis, pH, water activity (aw), and a sensory study were performed. All nitrite-free sausages (cold or traditional ripened) showed quality and safety traits similar to low-nitrite traditionally ripened ones used as control. In addition, sensory study revealed that sausages with lactic acid were the most preferred cold ripened samples, supporting that this is an optimal strategy for the production of nitrite-free sausages. We selected this product for further studies. Indeed, in the second part, we evaluated the impact of ripening, and other hurdle technologies as High Pressure Processing (HPP) and under-vacuum storage against Listeria innocua and Salmonella spp. by a challenge test. Maximal declines were obtained for ripening along with HPP (i.e., 4.74 and 3.83 log CFU/g for L. innocua and Salmonella spp., respectively), suggesting that HPP might guarantee nitrite-free sausages safety. Although the quality of raw materials remains essential, these hurdle strategies largely contributed to nitrite-free sausages safety, offering a promising tool for the meat industry.

Incidence of Tetracycline and Erythromycin Resistance in Meat-Associated Bacteria: Impact of Different Livestock Management Strategies.

The extensive use of antibiotics as growth promoters, or their continued abusive misuse to cure or prevent the onset of bacterial infections as occurs in the intensive farming, may have played a pivotal role in the spread of reservoirs of antibiotic resistance (AR) among food-associated bacteria including pathogens representing risks to human health. The present study compares the incidence of tetracycline and erythromycin resistances in lactic acid bacteria (LAB) and coagulase negative staphylococci (CNS) from fermented products manufacturing using meat from intensive animal husbandry (industrialized manufacturing Italian salami) and from extensive farms (artisanal sausages facilities pork and llama Argentinean sausages). A higher incidence of tetracycline resistance (TET-R) compared to erythromycin resistance (ERY-R) was observed among the 205 isolates. Unlike CNS strains, the LAB showed a significant correlation between the TET-R and the ERY-R phenotypes. Genotypic assessment shows a high correlation with tetK and tetM for the TET-R strains and with ermB and ermC for the ERY-R strains. Multiple correspondence analyses have highlighted the association between AR phenotypes and CNS species isolated from Italian salami, while the susceptible phenotypes were associated with the LAB species from Argentinean sausages. Since antibiotic resistance in meat-associated bacteria is a very complex phenomenon, the assessment of bacterial resistance in different environmental contexts with diverse farming practices and food production technologies will help in monitoring the factors influencing AR emergence and spread in animal production.

Exploring Coagulase-Negative Staphylococci Diversity from Artisanal Llama Sausages: Assessment of Technological and Safety Traits.

Llama sausage is still produced following artisanal procedures, with the autochthonous microbiota being mainly responsible for the fermentation process. In this work, the taxonomical identification and technological-safety criteria of coagulase-negative staphylococci (CNS) isolated from two different productions of llama sausages (P: pilot and A: artisanal) were investigated. Staphylococcus (S) equorum and S. saprophyticus were the species most frequently found in P production, followed by S. succinis and S. warneri; a wider species variability was observed in A factory being S. equorum, S. capitis, S. xylosus, S. pasteuri, S. epidermidis and S. saprophyticus as the main identified species. The technological characterization of 28 CNS strains showed their ability to hydrolyze gelatin and tributyrin together with a relevant nitrate reductase activity. Phenotypic and genotypic approaches were conducted to investigate the main safety traits. Llama's CNS strains exhibited weak decarboxylase and hemolytic activity and low biofilm production; additionally, no enterotoxin genes were detected. Correlation analysis between phenotypic and genotypic data showed low values for the biofilm parameters, while high correlation was observed for oxacillin, ampicillin, tetracycline and aminoglycosides resistance and their genetic determinants. Data obtained may contribute to broaden knowledge about the autochthonous strains of this poorly studied fermented product, thus helping to select an appropriate combination of potential starter cultures to improve llama sausage safety and quality.

Universal loop assembly: open, efficient and cross-kingdom DNA fabrication.

Standardized type IIS DNA assembly methods are becoming essential for biological engineering and research. These methods are becoming widespread and more accessible due to the proposition of a 'common syntax' that enables higher interoperability between DNA libraries. Currently, Golden Gate (GG)-based assembly systems, originally implemented in host-specific vectors, are being made compatible with multiple organisms. We have recently developed the GG-based Loop assembly system for plants, which uses a small library and an intuitive strategy for hierarchical fabrication of large DNA constructs (>30 kb). Here, we describe 'universal Loop' (uLoop) assembly, a system based on Loop assembly for use in potentially any organism of choice. This design permits the use of a compact number of plasmids (two sets of four odd and even vectors), which are utilized repeatedly in alternating steps. The elements required for transformation/maintenance in target organisms are also assembled as standardized parts, enabling customization of host-specific plasmids. Decoupling of the Loop assembly logic from the host-specific propagation elements enables universal DNA assembly that retains high efficiency regardless of the final host. As a proof-of-concept, we show the engineering of multigene expression vectors in diatoms, yeast, plants and bacteria. These resources are available through the OpenMTA for unrestricted sharing and open access.

Targeting antisense mitochondrial noncoding RNAs induces bladder cancer cell death and inhibition of tumor growth through reduction of survival and invasion factors.

Knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, supporting a selective therapy against different types of cancer. In this work, we evaluated the effects of knockdown of ASncmtRNAs on bladder cancer (BCa). We transfected the BCa cell lines UMUC-3, RT4 and T24 with the specific antisense oligonucleotide Andes-1537S, targeted to the human ASncmtRNAs. Knockdown induced a strong inhibition of cell proliferation and increase in cell death in all three cell lines. As observed in UMUC-3 cells, the treatment triggered apoptosis, evidenced by loss of mitochondrial membrane potential and Annexin V staining, along with activation of procaspase-3 and downregulation of the anti-apoptotic factors survivin and Bcl-xL. Treatment also inhibited cell invasion and spheroid formation together with inhibition of N-cadherin and MMP 11. In vivo treatment of subcutaneous xenograft UMUC-3 tumors in NOD/SCID mice with Andes-1537S induced inhibition of tumor growth as compared to saline control. Similarly, treatment of a high-grade bladder cancer PDX with Andes-1537S resulted in a strong inhibition of tumor growth. Our results suggest that ASncmtRNAs could be potent targets for bladder cancer as adjuvant therapy.

Niveles Plasmáticos de Citoquinas Proinflamatorias en Cáncer de Próstata / Serum levels of proinflammatory cytokines in prostate cancer

INTRODUCTION: Prostate cancer has become an important public health problem affecting millions of men worldwide every year. Like other malignant tumors, prostate cancer shows evidence of a strong inflammatory component that is dependent on the release of pro-inflammatory cytokines, which might play a major role in the development and progression of the tumor, helping in its early stage, progression and aggressiveness. AIMS: The goal of this study was to determine the relationships between the serum levels of pro-inflammatory cytokines and the different stages of prostate cancer. To this end, sera from patients enrolled by The Laboratory of Metabolic Diseases and Cancer of the Faculty of Pharmacy and Biochemistry at the University Juan Agustín Maza in Argentina, were analyzed through ELISA and their pro-inflammatory cytokines (IL-6, TNF-α and MCP-1) quantified. Patients were first classified into three groups (Control, at Risk, and Cancer subjects) and anthropometric, biochemical and histological parameters of prostate were then determined for all groups. RESULTS AND CONCLUSIONS: Despite displaying elevated serum concentrations of IL-6 and TNF-α in the Cancer and the Risk groups compared to the Control group, the differences did not reach significance. However, there was a positive correlation between these cytokines only in the Risk and Cancer groups, showing a general inflammatory behavior in these patients. The results obtained provide general data about the behavior of pro-inflammatory cytokines in prostate cancer. However, they do not demonstrate a direct correlation between serum levels and neoplastic progression. Nevertheless, these findings do not rule out a possible relationship between prostate cancer and serum levels of pro-inflammatory cytokines.

Evaluación de la transferencia de adolescentes desde una unidad de cardiología pediátrica a una de adultos / Transfering adolescents from pediatric to adult cardiology units: evaluation

Resumen: Objetivos: evaluar la transferencia de adolescentes desde Cardiología Pediátrica (CP) a Cardiología de Adultos (CA) en el Hospital Dr. Hernán Henríquez de Temuco (HHHT), determinando si recibieron su primera atención en CA en la fecha requerida y si los controles se ajustaron al plazo indicado. Evaluar si la complejidad de la cardiopatía y ruralidad se asocian al cumplimiento en ambos objetivos, en los pacientes sin seguimiento adecuado. Material y Método: revisión de fichas de pacientes atendidos en CP del HHHT que, cumplida la edad requerida, fueron transferidos a CA, entre Octubre 2014 - Julio de 2017. Resultados: De 53 pacientes transferidos de CPCA, 12 (22.6%) tuvo traspaso no efectivo; de ellos, 6 presentaban complejidad moderada-alta (66,6%) y 3 eran rurales (25%). De 28 pacientes ingresados a CA, 14 (50%) tenían seguimiento inefectivo; de ellos 13 (92.6%) tenían cardiopatías de moderada-alta complejidad y 3 (21.5%) provenían de áreas rurales. Conclusiones: la transferencia de CP - CA fue inefectiva en 22.6% de los pacientes; la complejidad de la cardiopatía no se asoció al resultado de la transferencia en este grupo. En CA el seguimiento fue inefectivo en la mitad de los pacientes; de ellos, 92.8% tenían cardiopatías de moderada-alta complejidad, lo que fue estadísticamente significativo respecto de la complejidad en todos los pacientes traspasados. El domicilio no estuvo asociado a la pérdida de pacientes en la transferencia ni en el seguimiento. Estos hallazgos nos permitieron tomar medidas de mejoría en la transferencia y los controles en CA que esperamos mejoren los resultados futuros.

Abstracts: Aim: To evaluate the transfer of adolescents from Pediatric Cardiology (PC) to Adult Cardiology (AC) at Hospital Dr. Hernán Henríquez de Temuco (HHHT). We determined whether they got their first care in AC on the required date and whether controls were performed on the period prescribed. Also, to evaluate whether the complexity of cardiac disease and the patient's place of residence influenced the accomplishment of the objectives, in patients without adequate following. Material and Method: Retrospective review of clinical records of patients that were treated in PC at HHHT who, having the required age were transferred to AC, between October 2014 and July 2017. Results: Of 53 patients that were transferred from PC to AC, 12 (22.6%) had an non effective transfer; 6 of them had moderate to high complexity cardiac lesions (66.6%) and 3 lived in rural areas (25%). Of 28 patients admitted to AC, 14 (50%) had a non effective follow up and 13 (92.8%) had moderate to high complexity forms of heart disease; 3 (21.5%) came from rural areas. Conclusions: Transfer of patients from PC to AC was not effective in 22.6% of patients. The complexity of the disease was not related to the results of transfer in this group. At AC the follow-up was not effective in half the patients; from these, 92.6% had moderate to high complexity heart disease, which was significantly different from the complexity of all patients transferred. The place of residence was not relates to transfer neither to follow-up. These findings allowed us to make improvement in the transfer processes and the follow up at AC.

Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model.

Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule. These studies showed inhibition of tumor growth and metastasis. Direct metastasis assessment by tail vein injection of RenCa cells also showed a drastic reduction in lung metastatic nodules. In vivo treatment reduces survivin, N-cadherin and P-cadherin levels, providing a molecular basis for metastasis inhibition. In consequence, the treatment significantly enhanced mouse survival in these models. Our results suggest that the ASncmtRNAs could be potent and selective targets for therapy against human renal cell carcinoma.

[Comparative evaluation of survival prognosis using MELD or Child-Pugh scores in patients with liver cirrhosis in Chile]. / Evaluación comparativa entre MELD y Child-Pugh como escalas pronósticas de sobrevida en pacientes con cirrosis hepática en Chile.

BACKGROUND: Currently, most liver units use the Child-Pugh (CP) or the Model for End-Stage Liver Disease (MELD) scores to establish survival prognosis among patients with liver cirrhosis. Which classification is superior, is not well defined. AIM: To compare CP and MELD classification scores to predict survival among adult patients with liver cirrhosis in Chile. MATERIAL AND METHODS: Follow-up of 137 consecutive adult patients with liver cirrhosis aged 59 ± 12 years (55% women). The diagnosis was reached by clinical, laboratory and image studies at three different centers of Santiago. Patients were staged with CP and MELD classification scores at baseline and followed over a period of 12 months. The predictive capacity of the scores for survival was analyzed using a multivariate statistical analysis (Kaplan-Meier curves). RESULTS: The most common etiology was alcohol (37.9%). The actuarial survival rate was 79.6% at 12 months of follow-up. When comparing groups with areas under curve of receiver operating characteristic curves (AUROC), there was no statistically significant difference in survival between less severe and advanced disease, assessed with both survival scales. The AUROC for MELD and CP were 0.80 and 0.81, respectively. CONCLUSIONS: This clinical study did not find a statistically significant difference between the two classifications for the prediction of 12 months survival in patients with cirrhosis.

Evaluación comparativa entre MELD y Child-Pugh como escalas pronósticas de sobrevida en pacientes con cirrosis hepática en Chile / Comparative evaluation of survival prognosis using MELD or Child-Pugh scores in patients with liver cirrhosis in Chile

Background: Currently, most liver units use the Child-Pugh (CP) or the Model for End-Stage Liver Disease (MELD) scores to establish survival prognosis among patients with liver cirrhosis. Which classification is superior, is not well defined. Aim: To compare CP and MELD classification scores to predict survival among adult patients with liver cirrhosis in Chile. Material and Methods: Follow-up of 137 consecutive adult patients with liver cirrhosis aged 59 ± 12 years (55% women). The diagnosis was reached by clinical, laboratory and image studies at three different centers of Santiago. Patients were staged with CP and MELD classification scores at baseline and followed over a period of 12 months. The predictive capacity of the scores for survival was analyzed using a multivariate statistical analysis (Kaplan-Meier curves). Results: The most common etiology was alcohol (37.9%). The actuarial survival rate was 79.6% at 12 months of follow-up. When comparing groups with areas under curve of receiver operating characteristic curves (AUROC), there was no statistically significant difference in survival between less severe and advanced disease, assessed with both survival scales. The AUROC for MELD and CP were 0.80 and 0.81, respectively. Conclusions: This clinical study did not find a statistically significant difference between the two classifications for the prediction of 12 months survival in patients with cirrhosis.