Activation of Adrenoceptor Alpha-2 (ADRA2A) Promotes Chemosensitization to Carboplatin in Ovarian Cancer Cell Lines.

Recurrence of ovarian cancer (OvCa) following surgery and standard carboplatin/paclitaxel first-line therapy signifies poor median progression-free survival (<24 months) in the majority of patients with OvCa. The current study utilized unbiased high-throughput screening (HTS) to evaluate an FDA-approved compound library for drugs that could be repurposed to improve OvCa sensitivity to carboplatin. The initial screen revealed six compounds with agonistic activity for the adrenoceptor alpha-2a (ADRA2A). These findings were validated in multiple OvCa cell lines (TYKnu, CAOV3, OVCAR8) using three ADRA2A agonists (xylazine, dexmedetomidine, and clonidine) and two independent viability assays. In all the experiments, these compounds enhanced the cytotoxicity of carboplatin treatment. Genetic overexpression of ADRA2A was also sufficient to reduce cell viability and increase carboplatin sensitivity. Taken together, these data indicate that ADRA2A activation may promote chemosensitivity in OvCa, which could be targeted by widely used medications currently indicated for other disease states.

Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development.

BACKGROUND & AIMS: There is a major unmet need to assess the prognostic impact of antifibrotics in clinical trials because of the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression. METHODS: A fibrosis progression signature (FPS) was defined to predict fibrosis progression within 5 years in patients with hepatitis C virus and nonalcoholic fatty liver disease (NAFLD) with no to minimal fibrosis at baseline (n = 421) and was validated in an independent NAFLD cohort (n = 78). The FPS was used to assess response to 13 candidate antifibrotics in organotypic ex vivo cultures of clinical fibrotic liver tissues (n = 78) and cenicriviroc in patients with nonalcoholic steatohepatitis enrolled in a clinical trial (n = 19, NCT02217475). A serum protein-based surrogate FPS was developed and tested in a cohort of compensated cirrhosis patients (n = 122). RESULTS: A 20-gene FPS was defined and validated in an independent NAFLD cohort (adjusted odds ratio, 10.93; area under the receiver operating characteristic curve, 0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacologic target using clinical liver tissues. Systematic ex vivo evaluation of 13 candidate antifibrotics identified rational combination therapies based on epigallocatechin gallate, which were validated for enhanced antifibrotic effect in ex vivo culture of clinical liver tissues. In patients with nonalcoholic steatohepatitis treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of the PPARα pathway was absent in patients without fibrosis improvement, suggesting a benefit of combining PPARα agonism to improve the antifibrotic efficacy of cenicriviroc. A 7-protein serum protein-based surrogate FPS was associated with the development of decompensation in cirrhosis patients. CONCLUSION: The FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform antifibrotic drug development.

Immature stages of Phloeosinus tacubayae (Curculionidae: Scolytinae): morphology and chaetotaxy of larva and pupa, sexual dimorphism of adults, and developmental time.

The current knowledge of morphology and chaetotaxy of the different developmental stages within the subfamily Scolytinae presents an information deficit that needs to be addressed. Thus, the objective of the present study was to describe, the chaetotaxy and morphology of larvae and pupae, and determine the number of larval instars, the sexual dimorphism in adults, and the development time in Phloeosinus tacubayae. The number of larval instars was determined using traditional morphometry of cephalic capsule and multivariate analysis; description of morphology and chaetotaxy of larvae and pupae, and sexual dimorphism in adults was based on light microscopy and scanning electron microscopy photographs; finally, we quantified development time by mean reviews of 10 gallery systems selected randomly in infested logs, in the laboratory. Morphometric analysis of the cephalic capsule allowed the recognition of 3 different instars. Our results showed that the larvae of P. tacubayae have unique attributes in the body that differentiate them from other genera of the subfamily for example the epicranial suture is not marked, and differentiated from Phloeosinus canadensis, such as a smaller number of setae in the maxillae and without a tergal plate. The pupa had a smaller number of setae on the whole body. The most useful morphological characters to identify a sexual dimorphism in adults were found in the shape and relative position of the seventh and eighth tergites; development time lasted 40 days in total, being the pupal stage the one that took the longest to complete.

Melatonin Prevents Depression but Not Anxiety-like Behavior Produced by the Chemotherapeutic Agent Temozolomide: Implication of Doublecortin Cells and Hilar Oligodendrocytes.

Melatonin is a hormone synthesized by the pineal gland with neuroprotective and neurodevelopmental effects. Also, melatonin acts as an antidepressant by modulating the generation of new neurons in the dentate gyrus of the hippocampus. The positive effects of melatonin on behavior and neural development may suggest it is used for reverting stress but also for the alterations produced by chemotherapeutic drugs influencing behavior and brain plasticity. In this sense, temozolomide, an alkylating/anti-proliferating agent used in treating brain cancer, is associated with decreased cognitive functions and depression. We hypothesized that melatonin might prevent the effects of temozolomide on depression- and anxiety-like behavior by modulating some aspects of the neurogenic process in adult Balb/C mice. Mice were treated with temozolomide (25 mg/kg) for three days of two weeks, followed by melatonin (8 mg/kg) for fourteen days. Temozolomide produced short- and long-term decrements in cell proliferation (Ki67-positive cells: 54.89% and 53.38%, respectively) and intermediate stages of the neurogenic process (doublecortin-positive cells: 68.23% and 50.08%, respectively). However, melatonin prevented the long-term effects of temozolomide with the increased number of doublecortin-positive cells (47.21%) and the immunoreactivity of 2' 3'-Cyclic-nucleotide-3 phosphodiesterase (CNPase: 82.66%), an enzyme expressed by mature oligodendrocytes, in the hilar portion of the dentate gyrus. The effects of melatonin in the temozolomide group occurred with decreased immobility in the forced swim test (45.55%) but not anxiety-like behavior. Thus, our results suggest that melatonin prevents the harmful effects of temozolomide by modulating doublecortin cells, hilar oligodendrocytes, and depression-like behavior tested in the forced swim test. Our study could point out melatonin's beneficial effects for counteracting temozolomide's side effects.

Optimization of the Extraction of Antioxidant Compounds from Roselle Hibiscus Calyxes (Hibiscus sabdariffa), as a Source of Nutraceutical Beverages.

Secondary metabolites from Hibiscus sabdariffa have been used to prevent different diseases. Roselle Hibiscus is known for being rich in phenolic bioactive compounds. The extraction conditions are directly related to the chemical composition and then to the overall bioactivity of the extract. In this study, a Box-Behnken experimental design has been used to optimize the antioxidant activity, considering four variables: ethanol:water ratio, temperature, extraction time, and solvent:solid ratio. The experiment comprises 27 experiments and 3 repetitions at the central point. The results are described by surface response analysis and a second-degree polynomial equation. The model explains 87% of the variation in the response. The maximum antioxidant activity is yielded when 1% solids are extracted in 35.5% ethanol at 60 °C for 33 min. Finally, a nutritional functional supplement of 495 µmol Trolox Equivalent (TE) antioxidant capacity was prepared with the optimized extract.

The utility of the Edmonton Obesity Staging System for the prediction of COVID-19 outcomes: a multi-centre study.

BACKGROUND: Patients with obesity have an increased risk for adverse COVID-19 outcomes. Body mass index (BMI) does not acknowledge the health burden associated this disease. The performance of the Edmonton Obesity Staging System (EOSS), a clinical classification tool that assesses obesity-related comorbidity, is compared with BMI, with respect to adverse COVID-19 outcomes. METHODS: 1071 patients were evaluated in 11 COVID-19 hospitals in Mexico. Patients were classified into EOSS stages. Adjusted risk factors for COVID-19 outcomes were calculated and survival analysis for mechanical ventilation and death was carried out according to EOSS stage and BMI category. RESULTS: The risk for intubation was higher in patients with EOSS stages 2 and 4 (HR 1.42, 95% CI 1.02-1.97 and 2.78, 95% CI 1.83-4.24), and in patients with BMI classes II and III (HR 1.71, 95% CI 1.06-2.74, and 2.62, 95% CI 1.65-4.17). Mortality rates were significantly lower in patients with EOSS stages 0 and 1 (HR 0.62, 95% CI 0.42-0.92) and higher in patients with BMI class III (HR 1.58, 95% CI 1.03-2.42). In patients with a BMI ≥ 25 kg/m2, the risk for intubation increased with progressive EOSS stages. Only individuals in BMI class III showed an increased risk for intubation (HR 2.24, 95% CI 1.50-3.34). Mortality risk was increased in EOSS stages 2 and 4 compared to EOSS 0 and 1, and in patients with BMI class II and III, compared to patients with overweight. CONCLUSIONS: EOSS was associated with adverse COVID-19 outcomes, and it distinguished risks beyond BMI. Patients with overweight and obesity in EOSS stages 0 and 1 had a lower risk than patients with normal weight. BMI does not adequately reflect adipose tissue-associated disease, it is not ideal for guiding chronic-disease management.

Predicting of excess body fat in children.

PURPOSE OF REVIEW: Approximately 370 million children and adolescents worldwide showed overweight or obesity in 2016. The risk of developing severe comorbidities depends on the age of onset and the duration of obesity. This review discusses available methodologies to detect excess body fat in children as well as the early life factors that predict excess body fat and its development. RECENT FINDINGS: Factors, such as parental nutritional status, maternal weight gain during pregnancy, maternal malnutrition, maternal smoking during pregnancy, low and high birth weight, rapid weight gain, and short infant sleep duration have been independently and positively associated with neonatal, infant, and children adiposity. Early detection of excess body fat in children through the use of various tools is the first step in preventing nutrition-related diseases in adulthood. SUMMARY: The early detection of excess body fat and the implementation of efficient interventions to normalize the weight of children and adolescents at obesity risk are essential to prevent diseases in adult life.

Environmental Enrichment Differentially Activates Neural Circuits in FVB/N Mice, Inducing Social Interaction in Females but Agonistic Behavior in Males.

Environmental enrichment induces behavioral and structural modifications in rodents and influences the capability of mice to cope with stress. However, little is understood about hippocampal neurogenesis and the appearance of social/agonistic (aggressive) behavior upon activation of different neuronal circuits in FVB/N mice. Thus, in this study we hypothesized that environmental enrichment differentially regulates neurogenesis, neural circuit activation and social/agonistic behavior in male and female FVB/N mice. We explored the (1) neurogenic process as an indicative of neuroplasticity, (2) neuronal activation in the limbic system, and (3) social behavior using the resident-intruder test. On postnatal day 23 (PD23), mice were assigned to one of two groups: Standard Housing or Environmental Enrichment. At PD53, rodents underwent the resident-intruder test to evaluate social behaviors. Results revealed that environmental enrichment increased neurogenesis and social interaction in females. In males, environmental enrichment increased neurogenesis and agonistic behavior. Enriched male mice expressed higher levels of agonistic-related behavior than female mice housed under the same conditions. Neural circuit analysis showed lower activation in the amygdala of enriched males and higher activation in enriched females than their respective controls. Enriched females also showed higher activation in the frontal cortex without differences in male groups. Moreover, the insular cortex was less activated in females than in males. Thus, our results indicate that environmental enrichment has different effects on neuroplasticity and social/agonistic behavior in FVB/N mice, suggesting the relevance of sexual dimorphism in response to environmental stimuli.

An Indicator of environmental enrichment to measure physical, social and cognitive activities in human daily life.

BACKGROUND: The concept of environmental enrichment (EE) encompasses complex physical, social, cognitive, motor, and somatosensory stimuli to which individuals are differentially exposed. An indicator of EE comprising these elements would facilitate the study of the impact of EE in diverse clinical settings by allowing an easy and comparable measurement. This study aimed to create and test such an EE indicator based on the Florida Cognitive Activities Scale (FCAS), the Multidimensional Social Integration in Later Life Scale (SILLS), and the International Physical Activity Questionnaire (IPAQ). METHODS: Participants with major depression and control subjects were recruited in this cross-sectional comparative study. Depressive symptom severity was assessed with the Hamilton Depression Rating Scale (HAM-D). The EE indicator was used to evaluate cognitive, social, and physical activity. We divided the sample into three levels of cognitive and social activities to construct an EE indicator and compared the obtained scores between participants with major depression and control subjects. RESULTS: 40 patients suffering from major depression and 50 control subjects were included. Higher HAM-D scores were associated with lower EE levels. Cognitive and social items exhibited adequate reliability. Control subjects reported higher scores in all three activities evaluated, except for some items of physical activities. This indicator of EE clearly differentiated between participants with major depression from control subjects. CONCLUSIONS: FCAS, SILLS, and IPAQ used together are valid to evaluate EE. This EE indicator may be a useful tool during clinical practice. The cross-sectional design and the small sample size are limitations of the present study.

Fat-free/lean body mass in children with insulin resistance or metabolic syndrome: a systematic review and meta-analysis.

BACKGROUND: Lean / Fat Free Body Mass (LBM) is metabolically involved in active processes such as resting energy expenditure, glucose uptake, and myokine secretion. Nonetheless, its association with insulin sensitivity / resistance / glucose tolerance and metabolic syndrome remains unclear in childhood. METHODS: The current investigation aimed to examine the differences in fat-free mass /lean body mass according to the presence of insulin sensitivity/insulin resistance/glucose tolerance/metabolic syndrome in children. A systematic search was carried out in Medline/PubMed, Embase, Scopus, Web of Science, and SciELO, covering the period from each database's respective start to 21 June 2021. Two researchers evaluated 7111 studies according to the inclusion criteria: original human studies, written in English or Spanish, evaluating fat-free mass/lean body mass in children and adolescents including both with and without insulin sensitivity/insulin resistance /glucose tolerance and metabolic syndrome and reported the differences between them in terms of fat free mass/lean body mass. The results of the studies were combined with insulin sensitivity, insulin, resistance, glucose tolerance and metabolic syndrome. The standardized mean difference (SMD) in each study was calculated and combined using the random-effects model. Heterogeneity between studies was tested using the index of heterogeneity (I2), leave-one-out sensitivity analyses were performed, and publication bias was assessed using the Egger and Begg tests. RESULTS: Finally, 15 studies which compared groups defined according to different glucose homeostasis criteria or metabolic syndrome out of 103 eligible studies were included in this systematic review and 12 studies in the meta-analysis. Meta-analysis showed lower fat-free mass/lean body mass percentage in participants with insulin resistance/glucose tolerance/metabolic syndrome (SMD -0.47; 95% CI, - 0.62 to - 0.32) while in mass units (kg), higher values were found in the same group (SMD, 1.01; 95% CI, 0.43 to 1.60). CONCLUSIONS: Our results identified lower values of fat-free mass/lean body mass (%) in children and adolescents with insulin resistance/glucose tolerance/metabolic syndrome and higher values of fat-free mass/lean body mass when these are expressed in kg. The evidence of the impact of lean mass on children's glucose homeostasis or metabolic syndrome is limited, so future studies research should focus on explaining the effect of fat-free mass/lean body mass on different metabolic outcomes. Moreover, it may be interesting to evaluate the quality (muscle density) or functional (muscle strength) outcomes in addition to both absolute (kg) and relative (%) values in future studies. The systematic review was prospectively registered at PROSPERO (registration number CRD42019124734; available at: http://www.crd.york.ac.uk/prospero [accessed: 05 April 2019]).

Associations between Spanish children's physical activity and physical fitness with lean body mass: The CALINA study.

The present study investigated the associations between physical activity (PA) and physical fitness (PF) with lean body mass (LBM) and evaluated whether PA mediates the association between PF and LBM. 279 children (150 boys) aged 7.5 ± 0.3 years participated in the study. PA was assessed by accelerometry and PF with handgrip and the standing long jump test. Total lean soft tissue mass index (TLSTMI), muscle cross-sectional area index (MCSAI), and fat-free mass index (FFMI) were evaluated using dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and bioimpedance analysis, respectively.Total (ß = 0.247) and vigorous PA (ß = 0.143) were associated with TLSTMI in girls. In boys, total (ß = 0.337), light (ß = 0.290), vigorous (ß = 0.200), and moderate-vigorous PA (ß = 0.189) were associated with TLSTMI. Total PA was associated with FFMI (ß = 0.299). Handgrip strength does not mediate the relationship between total PA and TLSTMI. Positive associations were found between handgrip strength and TLSTMI, MCSAI, and FFMI in both girls and boys.In children, there is a positive association between total and vigorous PA with TLSTMI. Handgrip strength does not mediate the relationship between total PA and TLSTMI. It was associated with TLSTMI, MCSAI, and FFMI.

Bioguided Phytochemical Study of Ipomoea cairica Extracts with Larvicidal Activity against Aedes aegypti.

Vector-borne diseases, such as those transmitted by Aedes aegypti, are a constant threat to inhabitants of tropical regions of the planet. Synthetic chemicals are commonly used as a strategy to control them; however, these products are known to persist in ecosystems and drive the appearance of resistance genes in arthropod vectors. Thus, the use of natural products has emerged as an environmentally friendly alternative in integrated vector control strategies. The present bioguided study investigated the larvicidal potential of Ipomoea cairica extracts, fractionated using thin-layer and open-column chromatography, because this species has been shown to exert larvicidal effects on the genus Aedes. The objective of this study was to evaluate the nonvolatile components in ethanolic extract of I. cairica stems as a potential natural larvicidal, and coumarins, such as 7-hydroxy-6-methoxychromen-2-one (scopoletin) and 7-hydroxychromen-2-one (umbelliferone), were identified as major compounds; however, they were not shown to be responsible for the larvicidal activity. Based on the results of the larvicidal action tests, these coumarins are not directly responsible for the larvicidal activity, but this activity might be attributed to a synergistic effect of all the compounds present in the most active secondary fraction, called F.DCM, which had an LC50 value of 30.608 mg/L. This type of study has yet not been conducted in the region; therefore, it is an important contribution to recognizing a natural and easy-to-cultivate source of vector control, such I. cairica.

Clinical, endoscopic and histological characteristics of Mexican adult patients with eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) has high prevalence/incidence in Western Europe, Canada, United States of America and Australia where it has significantly increased over the past three decades to the extent that some consider it an epidemic.

Management experience of pediatric meningioma in a Mexican reference center.

OBJECTIVE: Determine the histopathological and clinical characteristics of patients diagnosed with meningiomas and to establish the frequency of these tumors in the pediatric population Mexican. Determine the NF1/2 frequency in meningioma pediatric. METHODS: Samples from the histopathology file were reviewed, and from the complete clinical file the following patient data was reviewed: age, gender, diagnosis, diagnosis year, surgical resection, location, tumor size, symptoms, and family background. The frequency of NF1/2 in pediatric meningioma was reviewed in literature. RESULTS: Forty-four de novo cases were collected from pediatric patients; 19 were female patients and 25 males. The most frequent histological subtype was transitional meningioma. Of all the cases, 75% had a supratentorial localization and 20% had an extramedullary intrarachidian localization. Some clinical manifestations included seizures, paresis, headache, and visual disturbances. CONCLUSION: There is a low incidence of meningiomas in the pediatric population, more than 70% are Grade I, and they have supratentorial localization.

Quantitative peripheral computed tomography to measure muscle area and assess lean soft tissue mass in children.

BACKGROUND: Skeletal muscle is one of the main components of lean soft tissue mass (LSTM). Low levels in children affect locomotion, posture, and increase the risk of metabolic syndrome. AIM: (1) To evaluate the association between muscle cross-sectional area (MCSA) of the lower left leg measured by peripheral quantitative computed tomography (pQCT) and total LSTM; namely, total left leg and left lower leg LSTM assessed by dual-energy X-ray absorptiometry (DXA) in a group of children, (2) to examine if MCSA is a predictor of LSTM, (3) to determine the ability of pQCT to identify children with low LSTM. SUBJECTS AND METHODS: Lower left leg MCSA and LSTM were measured using pQCT and DXA, respectively, in 396 children. RESULTS: Statistically significant positive correlations were found between the lower leg MCSA - total LSTM (r² = 0.789), total leg LSTM (r² = 0.79), and lower leg LSTM (r² = 0.791) (p < .01). MCSA explained 64-68% of the variance in LSTM. Receiver operator characteristic (ROC) curves determined the capacity of the lower left leg MCSA to identify low LSTM in girls (AUC 0.95) and boys (AUC 0.87). CONCLUSIONS: Our results showed that lower left leg MCSA, measured using pQCT, could be a tool to predict low LSTM in children.

Environmental Exposure during Pregnancy: Influence on Prenatal Development and Early Life: A Comprehensive Review.

Preconception and prenatal exposure to environmental contaminants may affect future health. Pregnancy and early life are critical sensitive windows of susceptibility. The aim of this review was to summarize current evidence on the toxic effects of environment exposure during pregnancy, the neonatal period, and childhood. Alcohol use is related to foetal alcohol spectrum disorders, foetal alcohol syndrome being its most extreme form. Smoking is associated with placental abnormalities, preterm birth, stillbirth, or impaired growth and development, as well as with intellectual impairment, obesity, and cardiovascular diseases later in life. Negative birth outcomes have been linked to the use of drugs of abuse. Pregnant and lactating women are exposed to endocrine-disrupting chemicals and heavy metals present in foodstuffs, which may alter hormones in the body. Prenatal exposure to these compounds has been associated with pre-eclampsia and intrauterine growth restriction, preterm birth, and thyroid function. Metals can accumulate in the placenta, causing foetal growth restriction. Evidence on the effects of air pollutants on pregnancy is constantly growing, for example, preterm birth, foetal growth restriction, increased uterine vascular resistance, impaired placental vascularization, increased gestational diabetes, and reduced telomere length. The advantages of breastfeeding outweigh any risks from contaminants. However, it is important to assess health outcomes of toxic exposures via breastfeeding. Initial studies suggest an association between pre-eclampsia and environmental noise, particularly with early-onset pre-eclampsia. There is rising evidence of the negative effects of environmental contaminants following exposure during pregnancy and breastfeeding, which should be considered a major public health issue.

Short Daily Exposure to Environmental Enrichment, Fluoxetine, or Their Combination Reverses Deterioration of the Coat and Anhedonia Behaviors with Differential Effects on Hippocampal Neurogenesis in Chronically Stressed Mice.

Depression is a neuropsychiatric disorder with a high impact on the worldwide population. To overcome depression, antidepressant drugs are the first line of treatment. However, pre-clinical studies have pointed out that antidepressants are not entirely efficacious and that the quality of the living environment after stress cessation may play a relevant role in increasing their efficacy. As it is unknown whether a short daily exposure to environmental enrichment during chronic stress and antidepressant treatment will be more effective than just the pharmacological treatment, this study analyzed the effects of fluoxetine, environmental enrichment, and their combination on depressive-associated behavior. Additionally, we investigated hippocampal neurogenesis in mice exposed to chronic mild stress. Our results indicate that fluoxetine reversed anhedonia. Besides, fluoxetine reversed the decrement of some events of the hippocampal neurogenic process caused by chronic mild stress. Conversely, short daily exposure to environmental enrichment changed the deterioration of the coat and anhedonia. Although, this environmental intervention did not produce significant changes in the neurogenic process affected by chronic mild stress, fluoxetine plus environmental enrichment showed similar effects to those caused by environmental enrichment to reverse depressive-like behaviors. Like fluoxetine, the combination reversed the declining number of Ki67, doublecortin, calretinin cells and mature newborn neurons. Finally, this study suggests that short daily exposure to environmental enrichment improves the effects of fluoxetine to reverse the deterioration of the coat and anhedonia in chronically stressed mice. In addition, the combination of fluoxetine with environmental enrichment produces more significant effects than those caused by fluoxetine alone on some events of the neurogenic process. Thus, environmental enrichment improves the benefits of pharmacological treatment by mechanisms that need to be clarified.

The Ventilator Management Team: Repurposing Anesthesia Workstations and Personnel to Combat COVID-19.

The coronavirus disease 2019 pandemic resulted in unprecedented numbers of patients with respiratory failure requiring ventilatory support. The number of patients who required critical care quickly outpaced the availability of intensive care unit (ICU) beds. Consequently, health care systems had to creatively expand critical care services into alternative hospital locations with repurposed staff and equipment. Deploying anesthesia workstations to the ICU to serve as mechanical ventilators requires equipment preparation, multidisciplinary planning, and targeted education. We aim to contextualize this process, highlighting major differences between anesthesia workstations and ICU ventilators, and to share the insights gained from our experiences creating an anesthesia provider-based ventilator management team.

Quality improvement in tracheostomy care: A multidisciplinary approach to standardizing tracheostomy care to reduce complications.

PURPOSE: Develop a model for quality improvement in tracheostomy care and decrease tracheostomy-related complications. METHODS: This study was a prospective quality improvement project at an academic tertiary care hospital. A multidisciplinary team was assembled to create institutional guidelines for clinical care during the pre-operative, intra-operative, and post-operative periods. Baseline data was compiled by retrospective chart review of 160 patients, and prospective tracking of select points over 8 months in 73 patients allowed for analysis of complications and clinical parameters. RESULTS: Implementation of a quality improvement team was successful in creating guidelines, setting baseline parameters, and tracking data with run charts. Comparison of pre- and post-guideline data showed a trend toward decreased rate of major complications from 4.38% to 2.74% (p = 0.096). Variables including time to tracheotomy for prolonged intubation, surgical technique, day of first tracheostomy tube change, and specialty performing surgery did not show increased risk of complications. There were increased tracheostomy-related complications in cold months (p = 0.04). CONCLUSIONS: An interdisciplinary quality improvement team can improve tracheostomy care by identifying system factors, standardizing care among specialties, and providing continuous monitoring of select data points.

Melatonin Modulates Dendrite Maturation and Complexity in the Dorsal- and Ventral- Dentate Gyrus Concomitantly with Its Antidepressant-Like Effect in Male Balb/C Mice.

Adult neurogenesis occurs in the dentate gyrus (DG) of the hippocampus. New neurons help to counteract the effects of stress and several interventions including antidepressant drugs, environmental modifications and internal factors act pro-neurogenic with consequences in the dorsal and ventral DG. Melatonin, the main product synthesized by the pineal gland, induces antidepressant-like effects and modulates several events of the neurogenic process. However, the information related to the capability of melatonin to modulate dendrite maturation and complexity in the dorsal and ventral regions of the DG and their correlation with its antidepressant-like effect is absent. Thus, in this study, we analyzed the impact of melatonin (0, 0.5, 1, 2.5, 5 or 10 mg/kg) administered daily for fourteen days on the number, dendrite complexity and distribution of doublecortin (DCX)-cells in the dorsal-ventral regions of the DG in male Balb/C mice. Doublecortin is a microtubule-associated protein that is expressed during the course of dendritic maturation of newborn neurons. Also, we analyzed the impact of melatonin on despair-like behavior in the forced swim test. We first found a significant increase in the number and higher dendrite complexity, mainly with the doses of 2.5, 5 and 10 mg/kg of melatonin (81%, 122%, 78%). These cells showed more complex dendritic trees in the ventral- and the dorsal- DG. Concomitantly, the doses of 5 and 10 mg/kg of melatonin decreased depressant-like behavior (76%, 82%). Finally, the data corroborate the antidepressant-like effect of melatonin and the increasing number of doublecortin-associated cells. Besides, the data indicate that melatonin favors the number and dendrite complexity of DCX-cells in the dorsal- and ventral- region of the DG, which may explain part of the antidepressant-like effect of melatonin.