Preventing Pediatric Opioid Poisoning: Unusual Sources and Scenarios.

This retrospective study analyzed 230 pediatric opioid exposures from a statewide poison control center over a 5-year period. Most exposures involved pharmaceutical opioids and children below 2-years-old. Narrative details were reviewed to identify uncommon sources of opioids involved in poisoning and highlight the need for tailored prevention strategies and guidance.

Systemic inflammatory Th1 cytokines during Trypanosoma cruzi infection disrupt the typical anatomical cell distribution and phenotypic/functional characteristics of various cell subsets within the thymus.

The thymus plays a crucial role in T cell differentiation, a complex process influenced by various factors such as antigens, the microenvironment and thymic architecture. The way the thymus resolves infections is critical, as chronic persistence of microbes or inflammatory mediators can obstruct the differentiation. Here, we illustrate that following inflammatory T helper 1 infectious processes like those caused by Candida albicans or Trypanosoma cruzi, single positive thymocytes adopt a mature phenotype. Further investigations focused on T. cruzi infection, reveal a substantial existence of CD44+ cells in both the cortical and medullary areas of the thymus at the onset of infection. This disturbance coincides with heightened interferon gamma (IFNγ) production by thymocytes and an increased cytotoxic capacity against T. cruzi-infected macrophages. Additionally, we observe a reduced exportation capacity in T. cruzi-infected mice. Some alterations can be reversed in IFNγ knockout mice (KO). Notably, the majority of these effects can be replicated by systemic expression of interleukin (IL)-12+IL-18, underlining the predominantly inflammatory rather than pathogen-specific nature of these phenomena. Understanding the mechanisms through which systemic inflammation disrupts normal T cell development, as well as subsequent T cell exportation to secondary lymphoid organs (SLO) is pivotal for comprehending susceptibility to diseases in different pathological scenarios.

Exploring the immunomodulatory role of virtual memory CD8+ T cells: Role of IFN gamma in tumor growth control.

Virtual memory CD8+ T cells (TVM) have been described as cells with a memory-like phenotype but without previous antigen (Ag) exposure. TVM cells have the ability to respond better to innate stimuli rather than by TCR engagement, producing large amounts of interferon gamma (IFNγ) after stimulation with interleukin (IL)-12 plus IL-18. As a result of the phenotypic similarity, TVM cells have been erroneously included in the central memory T cell subset for many years. However, they can now be discriminated via the CD49d receptor, which is up-regulated only on conventional memory T cells (TMEM) and effector T cells (TEFF) after specific cognate Ag recognition by a TCR. In this work we show that systemic expression of IL-12 plus IL-18 induced an alteration in the normal TVM vs TMEM/TEFF distribution in secondary lymphoid organs and a preferential enrichment of TVM cells in the melanoma (B16) and the pancreatic ductal adenocarcinoma (KPC) tumor models. Using our KPC bearing OT-I mouse model, we observed a significant increase in CD8+ T cell infiltrating the tumor islets after IL-12+IL-18 stimulation with a lower average speed when compared to those from control mice. This finding indicates a stronger interaction of T cells with tumor cells after cytokine stimulation. These results correlate with a significant reduction in tumor size in both tumor models in IL-12+IL-18-treated OT-I mice compared to control OT-I mice. Interestingly, the absence of IFNγ completely abolished the high antitumor capacity induced by IL-12+IL-18 expression, indicating an important role for these cytokines in early tumor growth control. Thus, our studies provide significant new information that indicates an important role of TVM cells in the immune response against cancer.

Factors related to mammography adherence among women in Brazil: A scoping review.

AIM: To explore and synthesize the literature on factors related to mammography screening adherence among women in Brazil. DESIGN: A scoping review. METHODS: We searched 11 databases for studies published between 2006-January 2020. All identified articles were screened, and data were extracted from eligible studies. We used the UK Government Social Research Service weight of evidence appraisal tool to appraise the quality of the included study. RESULTS: From a total of 1,384 identified articles, 22 were retained. All included studies used quantitative, non-experimental methods and all but two studies used cross-sectional data. Quality of evidence varied across studies. We identified 41 factors that were investigated across the set of studies. Demographic and socio-economic factors were the most commonly investigated, with older age, urban residence, living in the southeast of Brazil, higher level of education, higher income and private health insurance most consistently associated with mammography adherence.

The Revised Champion's Health Belief Model Scale: Predictive Validity Among Brazilian Women.

Mammography screening is provided free of charge for the recommended target population in Brazil but participation rates have remained low, and breast cancer mortality has continued to increase. Thus, it is important to identify factors that are associated with poor participation in mammography screening so that service providers can target health promotion messages and screening programs more effectively. Objective: To evaluate the predictive validity of the Revised Champion's Health Belief Model scale (RCHBMS) for identifying women at high risk of not adhering to national guidelines for mammography screening in Brazil. Methods: We used a longitudinal survey design with a 1-year follow-up data from 194 women living in northeastern Brazil, in the city of Fortaleza, Ceará, participants completed the RCHBMS at baseline, and mammography uptake was measured 1 year later. Hierarchical logistic regression was used to determine the predictive validity of the RCHBMS for identifying women who had not adhered to recommendations for mammography screening, after accounting for the women's sociodemographic and clinical characteristics. The sensitivity and specificity of various cut-off points were calculated to determine the optimal cut-off point for identifying women at high risk of not adhering to mammography screening guidelines. Results: Two subscales of the RCHBMS uniquely predicted nonadherence: susceptibility and barriers, along with race and family history of cancer. The total scale score (with barriers reverse coded) was also highly predictive. For our sample, using only the RCHBMS with a cutoff of ≤ 3.67 (out of a total possible range of 1-5) yielded a high sensitivity and specificity for predicting nonadherence. Conclusion: Study findings support the validity and clinical utility of the RCHBM for identifying women at risk of not adhering to national guidelines for mammography screening in Brazil.

Thymic expression of IL-4 and IL-15 after systemic inflammatory or infectious Th1 disease processes induce the acquisition of "innate" characteristics during CD8+ T cell development.

Innate CD8+ T cells express a memory-like phenotype and demonstrate a strong cytotoxic capacity that is critical during the early phase of the host response to certain bacterial and viral infections. These cells arise in the thymus and depend on IL-4 and IL-15 for their development. Even though innate CD8+ T cells exist in the thymus of WT mice in low numbers, they are highly enriched in KO mice that lack certain kinases, leading to an increase in IL-4 production by thymic NKT cells. Our work describes that in C57BL/6 WT mice undergoing a Th1 biased infectious disease, the thymus experiences an enrichment of single positive CD8 (SP8) thymocytes that share all the established phenotypical and functional characteristics of innate CD8+ T cells. Moreover, through in vivo experiments, we demonstrate a significant increase in survival and a lower parasitemia in mice adoptively transferred with SP8 thymocytes from OT I-T. cruzi-infected mice, demonstrating that innate CD8+ thymocytes are able to protect against a lethal T. cruzi infection in an Ag-independent manner. Interestingly, we obtained similar results when using thymocytes from systemic IL-12 + IL-18-treated mice. This data indicates that cytokines triggered during the acute stage of a Th1 infectious process induce thymic production of IL-4 along with IL-15 expression resulting in an adequate niche for development of innate CD8+ T cells as early as the double positive (DP) stage. Our data demonstrate that the thymus can sense systemic inflammatory situations and alter its conventional CD8 developmental pathway when a rapid innate immune response is required to control different types of pathogens.

Modular assembly of transposable element arrays by microsatellite targeting in the guayule and rice genomes.

BACKGROUND: Guayule (Parthenium argentatum A. Gray) is a rubber-producing desert shrub native to Mexico and the United States. Guayule represents an alternative to Hevea brasiliensis as a source for commercial natural rubber. The efficient application of modern molecular/genetic tools to guayule improvement requires characterization of its genome. RESULTS: The 1.6 Gb guayule genome was sequenced, assembled and annotated. The final 1.5 Gb assembly, while fragmented (N50 = 22 kb), maps > 95% of the shotgun reads and is essentially complete. Approximately 40,000 transcribed, protein encoding genes were annotated on the assembly. Further characterization of this genome revealed 15 families of small, microsatellite-associated, transposable elements (TEs) with unexpected chromosomal distribution profiles. These SaTar (Satellite Targeted) elements, which are non-autonomous Mu-like elements (MULEs), were frequently observed in multimeric linear arrays of unrelated individual elements within which no individual element is interrupted by another. This uniformly non-nested TE multimer architecture has not been previously described in either eukaryotic or prokaryotic genomes. Five families of similarly distributed non-autonomous MULEs (microsatellite associated, modularly assembled) were characterized in the rice genome. Families of TEs with similar structures and distribution profiles were identified in sorghum and citrus. CONCLUSION: The sequencing and assembly of the guayule genome provides a foundation for application of current crop improvement technologies to this plant. In addition, characterization of this genome revealed SaTar elements with distribution profiles unique among TEs. Satar targeting appears based on an alternative MULE recombination mechanism with the potential to impact gene evolution.

Metronidazole vaginal gel 1.3% in the treatment of bacterial vaginosis: a dose-ranging study.

OBJECTIVE: Metronidazole vaginal gel (MVG) 0.75% is a US Food and Drug Administration-approved, 5-day treatment for bacterial vaginosis (BV). This study tested the hypothesis that a shorter treatment course at a higher dose (MVG 1.3%) would yield similar efficacy to 5 days of MVG 0.75%. MATERIALS AND METHODS: This phase 2, multicenter, randomized, controlled, investigator-blinded, dose-ranging study enrolled women with a clinical diagnosis of BV. Patients were assigned to MVG 1.3% once daily for 1, 3, or 5 days or MVG 0.75% once daily for 5 days. The therapeutic cure rate, requiring clinical and bacteriological cure, at the end-of-study visit was determined for the per-protocol population. A Kaplan-Meier analysis was used to estimate median time-to-symptom resolution. RESULTS: In total, 255 women (mean age = 35 y) were enrolled. The per-protocol population included 189 patients. The therapeutic cure rate was higher in the 1-day (13/43, 30.2%), 3-day (12/48, 25.0%), and 5-day (16/49, 32.7%) MVG 1.3% groups versus the MVG 0.75% group (10/49, 20.4%). Median time-to-resolution of fishy odor was shorter in the 3 MVG 1.3% groups versus the MVG 0.75% group. The 5-day MVG 1.3% group had the lowest rate of symptom return. No clinically important differences were observed in adverse events across treatment groups; most events were mild or moderate in intensity and considered unrelated to treatment. Similar results were found in the modified intent-to-treat population. CONCLUSIONS: Metronidazole vaginal gel 1.3% applied once daily for 1, 3, or 5 days showed similar efficacy, safety, and tolerability as MVG 0.75% once daily for 5 days.

Serum urate levels and the risk of hip fractures: data from the Cardiovascular Health Study.

PURPOSE: Uric acid inhibits vitamin D activation experimentally and higher serum urate levels are associated with higher parathyroid hormone levels in humans suggesting a link between uric acid and bone health. We hypothesized that hyperuricemia may increase the risk of fractures in older adults. METHODS: 1963 men and 2729 women ≥65 years of age who participated in the Cardiovascular Health Study and had baseline serum urate levels were included in the study. The primary outcome was incident hip fracture, assessed prospectively through June, 2008 by inpatient and outpatient records. The analysis was stratified by sex a priori. RESULTS: There was a U-shaped relationship between serum urate levels and hip fractures in men. Men in the lowest and the highest urate quartiles (<4.88 and ≥6.88 mg/dL respectively) had a significantly higher rate of fractures in unadjusted analysis. However, upon multivariate adjustment, only the HR for hip fracture in highest quartile versus the reference remained significant (HR 1.9; 95% C.I. 1.1, 3.1; p value 0.02). High serum urate levels were not associated with hip fractures in women. CONCLUSION: In this large prospective cohort of community-dwelling older adults, increased serum urate levels were associated with an increased risk of hip fractures in men. Further studies are needed to confirm these findings and to understand the mechanisms that underlie them.

Abrogation of TNFα production during cancer immunotherapy is crucial for suppressing side effects due to the systemic expression of IL-12.

For more than a decade, the cytokine interleukin-12 (IL-12) has been utilized, either alone or in combination with other drugs, as a treatment for cancer. The numerous anti-tumor properties of IL-12 still generate interest in the clinical use of this cytokine, even though it has demonstrated toxicity when administrated systemically. As an approach to overcome this toxicity, numerous laboratories have attempted to induce IL-12 expression at the site of the tumor. However for tumors that are difficult to remove surgically or for the treatment of disseminated metastases, systemic expression of this cytokine still remains as the most efficient method of administration. Nevertheless, finding alternative approaches for the use of IL-12 in the treatment of cancer and unraveling the basis of IL-12-side effects remain a challenge. In the present work we demonstrate that systemic expression of IL-12 through hydrodynamic injection of IL-12 cDNA is able to induce different types of liver lesions associated with a toxic pathology. However we report here that hepatic toxicity is diminished and survival of mice enhanced in the absence of tumor necrosis factor alpha (TNFα). This observation is in contrast to several murine models and clinical trials that postulate interferon gamma (IFNγ) as the main cytokine responsible for IL-12 toxicity. Moreover, our work demonstrates that when IL-12 cDNA is co-injected with IL-18 cDNA or when mice are pre-treated with a low dose of IL-12 cDNA prior to receiving a high dose of IL-12 cDNA, systemic levels of TNFα are almost completely abrogated, resulting in improved survival and less hepatic damage. Importantly, abrogation of TNFα signaling does not affect the strong anti-tumor activity of IL-12. Thus, neutralizing TNFα with antagonists already approved for human use offers a promising approach to abrogate IL-12 side effects during the use of this cytokine for the treatment of cancer.

Diagnostic approach in allergic and irritant contact dermatitis.

Contact dermatitis is a highly frequent disease with a significant impact on the quality of life of the affected patients and a relevant socioeconomic impact. According to the pathophysiological mechanisms involved, two major types of contact dermatitis may be recognized: irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). The two types may, and often do, coexist. Differentiating between ICD and ACD is often difficult in the clinical setting. The basis for a diagnosis of either ICD or ACD is mainly established by a comprehensive clinical history and physical examination, as well as by performing appropriate diagnostic patch testing. The only useful and reliable method for the diagnosis of ACD remains the patch test. Positive patch test results, the current and/or past relevance of which has to be assessed, are confirmative of contact sensitization. Additional tests, such as the repeated open application test or the provocative use test, are sometimes necessary to confirm a causal relationship. This algorithmic diagnostic approach will allow the adoption of rational measures of allergen or irritant avoidance and the implementation of realistic patient information and education.

Respiratory tract toxicity in rats exposed to Mexico City air.

The rat has been used extensively as a health sentinel, indicator, or monitor of environmental health hazards, but this model has not been directly validated against human exposures. Humans in Mexico City show upper respiratory tract lesions and evidence of pulmonary damage related to their environmental inhalation exposure. In this study, male and female F344 rats were exposed (23 hr/day) in Mexico City to local Mexico City air (MCA)* for up to seven weeks. Controls were maintained at the same location under filtered air. Prior to these exposures, several steps were taken. First, the nasal passages of normal male rats shipped from the United States and housed in Mexico City were examined for mycoplasma infection; no evidence of infection was found. In addition, a mobile exposure and monitoring system was assembled and, with an ozone (O3) exposure atmosphere, was tested along with supporting histopathology techniques and analysis of rat nasal and lung tissues. Last, the entire exposure model (equipment and animals) was transported to Mexico City and validated for a three-week period. During the seven-week study there were 18 one-hour intervals during which the average O3 concentration of MCA in the exposure chamber exceeded the US National Ambient Air Quality Standard (NAAQS) of 0.120 ppm 03 (hourly average, not to be exceeded more than once per year). This prolonged exposure of healthy F344 rats to MCA containing episodically low to moderate concentrations of 03 (as well as other urban air pollutants) did not induce inflammatory or epithelial lesions in the nasal airways or lung as measured by qualitative histologic techniques or quantitative morphometric techniques. These findings agree with those of previous controlled O3 inhalation studies, but they are in contrast to reports indicating that O3-polluted MCA causes significant nasal mucosal injury in adults and children living in southwestern Mexico City. Taken together, these findings may suggest that human airways are markedly more susceptible to the toxic effects of MCA than are the airways of the F344 rat.

Petroleum asphaltenes: generated problematic and possible biodegradation mechanisms.

Petroleum asphaltenes are hydrocarbons that present an extremely complex molecular structure. They are conformed by different proportions of nitrogen, sulfur and oxygen. These compounds cause diverse problems like the blockage of crude oil extraction and transport pipes, the reduction of their economic use and the pollution of ecosystems. Biodegradation of asphaltenes is an important process that can eliminate these compounds and reduce the problems they cause. However, it is a process that occurs naturally in very reduced proportions. The purpose of this revision is to show the chemical structure of these compounds, the problems they cause and to represent their possible biodegradation mechanisms, based on the processes known for other hydrocarbons of complex structure. Elimination of the micelar structure, through the application of non-polar solvents, and fragmentation of the asphaltenes through photooxidation are the initial processes necessary to be able to degrade these compounds. The produced structures, such as the heteropolyaromatic and aromatic, lineal and ramified hydrocarbons, could be degraded in this order through biochemical reactions, such as omega oxidations, beta oxidations and aromatic oxidations respectively. These processes are distributed in an important variety of microorganisms. The elimination period's length can vary from one week, for the simplest structures, to 990 days for those with several condensed aromatic rings.

[Biological flow tracers: growth and survival of Bacillus subtilis 65-8 under environmental stress]. / Trazadores biológicos de flujos: crecimiento y sobrevivencia de Bacillus subtilis 65-8 bajo estrés ambiental.

Microbial flow tracers are presently limited to a strain of Bacillus globigii and a few highly specific bacteriophages. Bacillus subtilis 65-8 produces a black pigment as part of the primary metabolism under minimal nutritional conditions, with glucose as the sole carbon and energy source. This work shows that Bacillus subtilis 65-8 spores are thermostable (55 degrees C during 150 días), halotolerant (they germinate and grow in an enriched medium with up to 12% NaCl), persistent in a system of sand-soil and sewage, even in the presence of added commercial oil derivatives (kerosene, leaded gasoline and unleaded diesel), they are capable to move through porous systems even as the liquids, viscous as they may be, move through. Moreover, spores were resistant to the presence of autochtonous microorganisms in sewage, where we did not detect any other organism with differential characteristics like our strain (black pigment production in minimal medium) which could interfere with the identification of our biological flow tracer. The characteristics of Bacillus subtilis 65-8 make it a suitable biological flow tracer.

[Classification of Klebsiella strains with lectins]. / Clasificación de cepas de Klebsiella con lectinas.

Fourteen different plant seeds were used to obtain lectins which in turn were used to agglutinate 72 different serological strains of Klebsiella. The results were used to design a scheme which distinguishes 62 serotypes (91.6%) with a unique agglutination pattern with lectins. Two pairs of strains as well as two sets of three strains gave the same patterns. This procedure is useful as an alternative in the identification of strains for epidemiological purposes.

Mercury in yellow perch from adirondack drainage lakes (New York, U. S.)

Yellow perch (Perca flavescens) were collected from 12 drainage lakes located in the Adirondack Park, New York, U.S. in order to better document mercury concentrations in fish in this region. The fish were aged and tissue samples analyzed for mercury concentration by the New York State Department of Envimnmental Conservation laboratory at Hale Creek and by Syracuse University. Water chemistry data collected by the Adirondack Lakes Survey Corporation were used to relate fish mercury concentration to lake surface water chemistry. Mercury levels were found to exceed the New York State guidelines of 1 ppm in several large perch from three of the lakes. Using age 4 + yellow perch, among-lake comparisons showed that pH, acid neutralizing capacity, dissolved inorganic carbon, calcium, conductivity, and magnesium were the water quality variables direetly correlated with mercury concentrations. Air-equilibrated pH was the best single predictor of mercury concentrations in age 4+ yellow perch (r2 = 0.61) and in perch 200 to 300 mm in total length (r2 = 0.49). Within an individual lake, fish age, length, and weight were directly related to the mercury level in the muscle tissue of the fish. Air-equilibrated pH of the Iake surface water and total length of the fish were used to create a model predicting mercury concentrations in yellow perch from Adirondack drainage lakes.

Algunos aspectos relevantes de la enfermedad de Chagas en Chile / Chaga's disease in Chile

La infección por T. cruzi (enfermedad de Chagas) constituye un problema de salud pública en Chile. tiene carácter endemo-enzoótico en sectores rurales y periféricos de las siete primeras regiones político-administrativas del país. Se registra una poporción significativa de infección por el parásito en habitantes de ciudades ubicadas en las regiones antes mencionadas, debido muy posiblemente a migración rural - urbana. 2.- El T. infestans es el vector domiciliario practicamente único de la parasitosis. Las tasas de infestación domiciliaria, cuyo promedio es de 29,4%, varían entre 9,3% y 65,2%, siendo en general más altas en las regiones III y IV. 3.- La infección promedia por T. cruzi de los T. infestans es de 18,7%, variando entre 6,4% y 47,6% registrándose los porcentajes más latos en las regiones II y III. Las tasas de infección de los triatominos, ocn un promedio de 19,6%, van en aumento según su edad, desde un 5,8% en los estadios II - III hasta un 25,4% en los imagos. Las fuentes de alimentación de los triatomídeos están constituídas principalmente por sangre de mamíferos y aves, alcanzando a un 90,8%, en la de los primeros, correspondiendo al hombre el 68,4%. Como era de esperar, las tasas deinfección por T. cruzi de los triatomas, fueron mayores en aquellos que se alimentaron con sangre de mamíferos. 4.- La infección chagásica humana, diagnosticada por medio de la RHAI correspondiente, fue en general de 16,9%, oscilando entre un 7,0% y un 33,2%, siendo las regiones III y IV las con más altos índices de infección. Las tasas de infección fueron similares para hombres y mujeres con un 17,7% y un 16,3% respectivamente. como es natural, se registró un incrmento progresivo de los valores de dichas tasas desde los grupos de menor edad (5,7%) hasta los grupos de mayores de 60 años (35,8%)...