Cardiovascular tolerance and safety of intravenous lidocaine in the broiler chicken (Gallus gallus domesticus)

Lidocaine, an amide local anesthetic agent, is commonly used in mammals, including humans. There is a general assumption that birds are more sensitive to lidocaine than mammals. Relatively low doses of lidocaine have been suggested to cause toxic effects in birds. While this information appears to be anecdotal, it has been perpetuated in the literature. The overall objective of this thesis research was to determine the tolerance and safety of intravenous lidocaine in broiler chickens. To assess the cardiovascular effects of lidocaine, relative changes on heart rate and mean blood pressure were calculated. Clinically significant cardiovascular effects were defined as relative decrease of heart rate and/or mean blood pressure equal to or greater than 30%. On the first study, doses below the reported toxic dose were assessed. The effects of 2.5, 3.0, 3.5 mg/kg intravenous lidocaine were compared with a control (saline) group. Each dose was used in 2 randomly selected animals. No significant cardiovascular effects were detected; therefore, higher doses were investigated. On a 2nd study, using an up-and-down study design, a total of 11 subjects were evaluated. The up-and-down method is a sequential design with binary response variables within a certain population which allows the determination of an effective dose to 50% of the population (ED50). The ED50 was defined as the dose that would cause clinically insignificant cardiovascular depression to 50% of the population. Using two statistical methods, the ED50 of cardiovascular function was 6.3 mg/kg and 6.22 mg/kg (95% confidence interval, 5.3 – 7.13 mg/kg). The safety of this dose was then tested in a new group of broiler chickens. The dose of 6 mg/kg was administered to 6 animals. No clinically significant cardiovascular effects were detected in any animal. In conclusion, the 3 studies performed for this thesis indicates that the reported toxic dose of lidocaine appears to be erroneous. Furthermore, this thesis determined the highest tolerable dose and its safety in a specific group of broiler chickens. Further studies assessing analgesia and anesthetic effects of lidocaine are necessary, both in chickens and other avian species

Activation of PI3K Is Indispensable for Interleukin 7–mediated Viability, Proliferation, Glucose Use, and Growth of T Cell Acute Lymphoblastic Leukemia Cells

Interleukin (IL)-7 is essential for normal T cell development. Previously, we have shown that IL-7 increases viability and proliferation of T cell acute lymphoblastic leukemia (T-ALL) cells by up-regulating Bcl-2 and down-regulating the cyclin-dependent kinase inhibitor p27kip1. Here, we examined the signaling pathways via which IL-7 mediates these effects. We investigated mitogen-activated protein kinase (MEK)–extracellular signal-regulated kinase (Erk) and phosphatidylinositol-3-kinase (PI3K)–Akt (protein kinase B) pathways, which have active roles in T cell expansion and have been implicated in tumorigenesis. IL-7 induced activation of the MEK–Erk pathway in T-ALL cells; however, inhibition of the MEK–Erk pathway by the use of the cell-permeable inhibitor PD98059, did not affect IL-7–mediated viability or cell cycle progression of leukemic cells. IL-7 induced PI3K-dependent phosphorylation of Akt and its downstream targets GSK-3, FOXO1, and FOXO3a. PI3K activation was mandatory for IL-7–mediated Bcl-2 up-regulation, p27kip1 down-regulation, Rb hyperphosphorylation, and consequent viability and cell cycle progression of T-ALL cells. PI3K signaling was also required for cell size increase, up-regulation of CD71, expression of the glucose transporter Glut1, uptake of glucose, and maintenance of mitochondrial integrity. Our results implicate PI3K as a major effector of IL-7–induced viability, metabolic activation, growth and proliferation of T-ALL cells, and suggest that PI3K and its downstream effectors may represent molecular targets for therapeutic intervention in T-ALL

Climate Change Impacts on Microbiota in Beach Sand and Water : Looking Ahead

Beach sand and water have both shown relevance for human health and their microbiology have been the subjects of study for decades. Recently, the World Health Organization recommended that recreational beach sands be added to the matrices monitored for enterococci and Fungi. Global climate change is affecting beach microbial contamination, via changes to conditions like water temperature, sea level, precipitation, and waves. In addition, the world is changing, and humans travel and relocate, often carrying endemic allochthonous microbiota. Coastal areas are amongst the most frequent relocation choices, especially in regions where desertification is taking place. A warmer future will likely require looking beyond the use of traditional water quality indicators to protect human health, in order to guarantee that waterways are safe to use for bathing and recreation. Finally, since sand is a complex matrix, an alternative set of microbial standards is necessary to guarantee that the health of beach users is protected from both sand and water contaminants. We need to plan for the future safer use of beaches by adapting regulations to a climate-changing world.Peer reviewe

Prevalencia de sobrepeso y obesidad en la infancia en las instituciones educativas: públicas vs. privadas

Introduction: epidemiological data indicate that childhood obesity is increasing in Brazil and is identified as a risk factor for early development of chronic diseases. Obesity has been characterized by increased adipose tissue and body weight. Objective: to diagnose and compare the prevalence of overweight and obesity in schoolchildren from public (EPU) and private (EPR) schools. Methods: anthropometrics variables (BMI and DOC [skin folds]) were evaluated in boys (n=91) and girls (n=109) between 8 and 10 years old. There was a higher prevalence of overweight in boys (19.6%) and girls (25.5%) of the EPR compared to boys (6.7%) and girls (8.1%) of the EPU. the obesity level was higher in boys (34.8%) and girls (31.9%) of the EPR compared to boys (6.7%) and girls (6.5%) of the EPU. Positive correlation was obtained between the variables BMI and % body fat in boys (r=0.82) and girls (r=0.85). Results: the results suggest that despite the increase in all social classes, overweight and obesity prevalence were more present in those with higher economic status, confirming therefore a socioeconomic relationship. This finding may lead to a health condition closest to the negative pole. Conclusion: the BMI analysis proved to be an index for efficient determination of overweight and obesity in children.Univ Sao Judas Tadeu, Programa Posgrad Stricto Sensu Educ Fis, BR-03221100 São Paulo, SP, BrazilUniv Fed Sergipe, Aracaju, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Microbes in beach sands : integrating environment, ecology and public health

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Reviews in Environmental Science and Bio/Technology 13 (2014): 329-368, doi:10.1007/s11157-014-9340-8.Beach sand is a habitat that supports many microbes, including viruses, bacteria, fungi and protozoa (micropsammon). The apparently inhospitable conditions of beach sand environments belie the thriving communities found there. Physical factors, such as water availability and protection from insolation; biological factors, such as competition, predation, and biofilm formation; and nutrient availability all contribute to the characteristics of the micropsammon. Sand microbial communities include autochthonous species/phylotypes indigenous to the environment. Allochthonous microbes, including fecal indicator bacteria (FIB) and waterborne pathogens, are deposited via waves, runoff, air, or animals. The fate of these microbes ranges from death, to transient persistence and/or replication, to establishment of thriving populations (naturalization) and integration in the autochthonous community. Transport of the micropsammon within the habitat occurs both horizontally across the beach, and vertically from the sand surface and ground water table, as well as at various scales including interstitial flow within sand pores, sediment transport for particle-associated microbes, and the large-scale processes of wave action and terrestrial runoff. The concept of beach sand as a microbial habitat and reservoir of FIB and pathogens has begun to influence our thinking about human health effects associated with sand exposure and recreational water use. A variety of pathogens have been reported from beach sands, and recent epidemiology studies have found some evidence of health risks associated with sand exposure. Persistent or replicating populations of FIB and enteric pathogens have consequences for watershed/beach management strategies and regulatory standards for safe beaches. This review summarizes our understanding of the community structure, ecology, fate, transport, and public health implications of microbes in beach sand. It concludes with recommendations for future work in this vastly under-studied area.2015-05-0

The decline of dengue in the Americas in 2017: discussion of multiple hypotheses

OBJECTIVE: Since the 1980s, dengue incidence has increased 30-fold. However, in 2017, there was a noticeable reduction in reported dengue incidence cases within the Americas, including severe and fatal cases. Understanding the mechanism underlying dengue's incidence and decline in the Americas is vital for public health planning. We aimed to provide plausible explanations for the decline in 2017. METHODS: An expert panel of representatives from scientific and academic institutions, Ministry of Health officials from Latin America and PAHO/WHO staff met in October 2017 to propose hypotheses. The meeting employed six moderated plenary discussions in which participants reviewed epidemiological evidence, suggested explanatory hypotheses, offered their expert opinions on each and developed a consensus. RESULTS: The expert group established that in 2017, there was a generalised decreased incidence, severity and number of deaths due to dengue in the Americas, accompanied by a reduction in reported cases of both Zika and chikungunya virus infections, with no change in distribution among age groups affected. This decline was determined to be unlikely due to changes in epidemiological surveillance systems, as similar designs of surveillance systems exist across the region. Although sudden surveillance disruption is possible at a country or regional level, it is unlikely to occur in all countries simultaneously. Retrospective modelling with epidemiological, immunological and entomological information is needed. Host or immunological factors may have influenced the decline in dengue cases at the population level through immunity; however, herd protection requires additional evidence. Uncertainty remains regarding the effect on the outcome of sequential infections of different dengue virus (DENV) types and Zika virus (ZIKV), and vice versa. Future studies were recommended that examine the epidemiological effect of prior DENV infection on Zika incidence and severity, the epidemiological effect of prior Zika virus infection on dengue incidence and severity, immune correlates based on new-generation ELISA assays, and impact of prior DENV/other arbovirus infection on ZIKV immune response in relation to number of infections and the duration of antibodies in relation to interval of protection. Follow-up studies should also investigate whether increased vector control intensification activities contributed to the decline in transmission of one or more of these arboviruses. Additionally, proposed studies should focus on the potential role of vector competence when simultaneously exposed to various arboviruses, and on entomological surveillance and its impact on circulating vector species, with a goal of applying specific measures that mitigate seasonal occurrence or outbreaks. CONCLUSIONS: Multifactorial events may have accounted for the decline in dengue seen in 2017. Differing elements might explain the reduction in dengue including elements of immunity, increased vector control, and even vector and\or viruses changes or adaptations. Most of the results of this expert consensus group meeting are hypothetical and based on limited evidence. Further studies are needed

Minimizing Errors in RT-PCR Detection and Quantification of SARS-CoV-2 RNA for Wastewater Surveillance

Wastewater surveillance for pathogens using the reverse transcription-polymerase chain reaction (RT-PCR) is an effective, resource-efficient tool for gathering additional community-level public health information, including the incidence and/or prevalence and trends of coronavirus disease-19 (COVID-19). Surveillance of SARS-CoV-2 in wastewater may provide an early-warning signal of COVID-19 infections in a community. The capacity of the world’s environmental microbiology and virology laboratories for SARS-CoV-2 RNA characterization in wastewater is rapidly increasing. However, there are no standardized protocols nor harmonized quality assurance and quality control (QA/QC) procedures for SARS-CoV-2 wastewater surveillance. This paper is a technical review of factors that can lead to false-positive and -negative errors in the surveillance of SARS-CoV-2, culminating in recommendations and strategies that can be implemented to identify and mitigate these errors. Recommendations include, stringent QA/QC measures, representative sampling approaches, effective virus concentration and efficient RNA extraction, amplification inhibition assessment, inclusion of sample processing controls, and considerations for RT-PCR assay selection and data interpretation. Clear data interpretation guidelines (e.g., determination of positive and negative samples) are critical, particularly during a low incidence of SARS-CoV-2 in wastewater. Corrective and confirmatory actions must be in place for inconclusive and/or potentially significant results (e.g., initial onset or reemergence of COVID-19 in a community). It will also be prudent to perform inter-laboratory comparisons to ensure results are reliable and interpretable for ongoing and retrospective analyses. The strategies that are recommended in this review aim to improve SARS-CoV-2 characterization for wastewater surveillance applications. A silver lining of the COVID-19 pandemic is that the efficacy of wastewater surveillance was demonstrated during this global crisis. In the future, wastewater will play an important role in the surveillance of a range of other communicable diseases.Highlights: Harmonized QA/QC procedures for SARS-CoV-2 wastewater surveillance are lacking; Wastewater analysis protocols are not optimized for trace analysis of viruses; False-positive and -negative errors have consequences for public health responses; Inter-laboratory studies utilizing standardized reference materials and protocols are needed.info:eu-repo/semantics/publishedVersio

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049