Impact of urban farming on health: a systematic review.

BACKGROUND: Urban farms are spaces designated for the cultivation of plants for food security, medicinal and curative purposes. Since the turn of the century, they have become more widespread and health benefits have been claimed; however, no consensus exists regarding this information. Hence, this study aims to provide information about the health effects of urban farming. METHODS: Protocol register number CRD42023448001. We followed the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Studies addressing urban farming interventions in any population group were included without age limitation of publication from PubMed, DOAJ, CAB Abstracts and NIH. Risk of bias was assessed using the Risk of Bias In Non-randomized Studies - of Interventions tool, and data were narratively synthesized. RESULTS: The search retrieved 2578 manuscripts, reduced to seven after screening. Urban farming's impact on health has been reflected in the physical domain by increasing self-reported health levels, physical activity, perceived general health, healthy eating and decreasing drug use. Parasites' presence has also been reported. In the mental aspect, urban farming is associated with relaxation and stress reduction. From a social perspective, urban farms provide a sense of belonging, personal growth and happiness. CONCLUSIONS: The benefits of urban farming outweigh the disadvantages. Further research should be conducted to clarify the potential benefits of this practice.

Antitumor activity of a hydrogel loaded with lipophilic bismuth nanoparticles on cervical, prostate, and colon human cancer cells.

The objective of this study was to analyze the antitumor activity of a hydrogel loaded with lipophilic bismuth nanoparticles on human cervical, prostate, and colon cancer cell lines. The effect of lipophilic bismuth nanoparticles on the viability of cancer cell lines (HeLa, DU145, and HCT-116) and non-cancer lung fibroblasts (HLF; LL 47[MaDo]) was determined with the MTT cell viability assay and compared with known antineoplastic drugs. The biocompatibility at an organismal level was verified in a murine model by histological examination. A lipophilic bismuth nanoparticle hydrogel at 50 µM time-dependently inhibited the growth of the three cancer cell lines, in a time-dependent way. A 1-hour exposure to 250 µM lipophilic bismuth nanoparticle hydrogel, inhibited the growth of the three cancer cell lines. The in-vitro efficacy of lipophilic bismuth nanoparticle was similar to the one of docetaxel and cisplatin, but without inhibiting the growth of non-cancer control cells. Histology confirmed the biocompatibility of lipophilic bismuth nanoparticles as there were no signs of cytotoxicity or tissue damage in any of the evaluated organs (kidney, liver, brain, cerebellum, heart, and jejunum). In conclusion, a lipophilic bismuth nanoparticle hydrogel is an innovative, low-cost alternative for the topical treatment of cervicouterine, prostate, and colon human cancers.

Quantification of missing prescriptions in commercial claims databases: results of a cohort study.

PURPOSE: This study aims to quantify the magnitude of missed dispensings in commercial claims databases. METHODS: A retrospective cohort study has been used linking PharMetrics, a commercial claims database, to a prescription database (LRx) that captures pharmacy dispensings independently of payment method, including cash transactions. We included adults with dispensings for opioids, diuretics, antiplatelet medications, or anticoagulants. To determine the degree of capture of dispensings, we calculated the number of subjects with the following: (1) same number of dispensings in both databases; (2) at least one dispensing, but not all dispensings, missed in PharMetrics; and (3) all dispensings missing in PharMetrics. Similar analyses were conducted using dispensings as the unit of analysis. To assess whether a dispensing in LRx was in PharMetrics, the dispensing in PharMetrics had to be for the same medication class and within ±7 days in LRx. RESULTS: A total of 1 426 498 subjects were included. Overall, 68% of subjects had the same number of dispensings in both databases. In 13% of subjects, PharMetrics identified ≥1 dispensing but also missed ≥1 dispensing. In 19% of the subjects, PharMetrics missed all the dispensings. Taking dispensings as the unit of analysis, 25% of the dispensings present in LRx were not captured in PharMetrics. These patterns were similar across all four classes of medications. Of the dispensings missing in PharMetrics, 48% involved a subject who had >1 health insurance plan. CONCLUSIONS: Commercial claims databases provide an incomplete picture of all prescriptions dispensed to patients. The lack of capture goes beyond cash transactions and potentially introduces substantial misclassification bias. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

Involvement of the cellular phosphatase DUSP1 in vaccinia virus infection.

Poxviruses encode a large variety of proteins that mimic, block or enhance host cell signaling pathways on their own benefit. It has been reported that mitogen-activated protein kinases (MAPKs) are specifically upregulated during vaccinia virus (VACV) infection. Here, we have evaluated the role of the MAPK negative regulator dual specificity phosphatase 1 (DUSP1) in the infection of VACV. We demonstrated that DUSP1 expression is enhanced upon infection with the replicative WR virus and with the attenuated VACV viruses MVA and NYVAC. This upregulation is dependent on early viral gene expression. In the absence of DUSP1 in cultured cells, there is an increased activation of its molecular targets JNK and ERK and an enhanced WR replication. Moreover, DUSP1 knock-out (KO) mice are more susceptible to WR infection as a result of enhanced virus replication in the lungs. Significantly, MVA, which is known to produce non-permissive infections in most mammalian cell lines, is able to grow in DUSP1 KO immortalized murine embryo fibroblasts (MEFs). By confocal and electron microscopy assays, we showed that in the absence of DUSP1 MVA morphogenesis is similar as in permissive cell lines and demonstrated that DUSP1 is involved at the stage of transition between IVN and MV in VACV morphogenesis. In addition, we have observed that the secretion of pro-inflammatory cytokines at early times post-infection in KO mice infected with MVA and NYVAC is increased and that the adaptive immune response is enhanced in comparison with WT-infected mice. Altogether, these findings reveal that DUSP1 is involved in the replication and host range of VACV and in the regulation of host immune responses through the modulation of MAPKs. Thus, in this study we demonstrate that DUSP1 is actively involved in the antiviral host defense mechanism against a poxvirus infection.

An association between liraglutide treatment and reduction in excessive daytime sleepiness in obese subjects with type 2 diabetes.

BACKGROUND: The main purpose of the present study is to evaluate whether treatment with long-acting human glucagon-like peptide-1 liraglutide was associated with an improvement of excessive daytime sleepiness (EDS) in obese subjects with type-2 diabetes. METHODS: This single-centre retrospective study included 158 obese (body mass index [BMI] ≥ 30 kg/m(2)) adult subjects with type-2 diabetes who were initiated with liraglutide treatment at least 3 months before study inclusion. Data of the Epworth Sleepiness Scale (ESS), anthropometric parameters, glucose-control and metabolic parameters were collected at liraglutide initiation (baseline) and at months 1 and 3 after liraglutide initiation. RESULTS: Significant reductions in ESS score were achieved at months 1 (-1.3 ± 2.8, p < 0.001) and 3 (-1.5 ± 3.0, p < 0.001) after liraglutide introduction. After 3 months of treatment with liraglutide, significant changes in body weight (p < 0.001), BMI (p < 0.001), waist (p < 0.001) and neck circumferences (p < 0.005), HbA1c (p < 0.001), mean blood glucose (p < 0.001), fasting plasma glucose (p < 0.001), triglycerides (p < 0.01) and total cholesterol (p < 0.001) were achieved. CONCLUSIONS: After 3 months of treatment with liraglutide a significant reduction in EDS was observed in obese subjects with type-2 diabetes. Besides this, significant changes in body weight and metabolic parameters of diabetes control were also accomplished. Further investigation is required to determine whether liraglutide could improve other abnormal sleep patterns and obstructive sleep apnoea.

Effect of Opioids on Testosterone Levels: Cross-Sectional Study using NHANES.

OBJECTIVE: Opioids can suppress gonadal hormone production, which may result in low testosterone levels. To date, there have been no large-scale population-based studies examining the extent to which opioid use may contribute to changes in testosterone levels. DESIGN: Cross-sectional study. SETTING: 2011-2012 National Health and Nutrition Examination Survey. SUBJECTS: Participants 17 years and older who had data on prescription medication usage and serum testosterone levels available. Participants were divided in two groups, opioid exposed and unexposed. METHODS: Testosterone levels of participants who responded that they had been exposed (n = 320) to prescription opioids in the past 30 days were compared with those who were unexposed (n = 4909). The number of participants with low testosterone levels was calculated and unadjusted and adjusted analyses were performed. RESULTS: Participants on opioids had higher odds of having low testosterone levels than those unexposed, odd ratio (OR) = 1.40, 95% confidence interval (CI) (1.07-1.84). After controlling for opioid exposure, as the age and the number of comorbidities increased, the odds of having low testosterone levels significantly increased in all categories. Compared with participants between 17 and 45 years of age, participants >70 years had OR = 1.70, 95% CI (1.16-2.50). Compared with participants with no comorbidities, participants with >2 comorbidities had OR = 1.69 95% CI (1.24-2.30). CONCLUSION: When assessing the impact of opioids on testosterone, the effects of age and medical conditions should be considered.

High, broad, polyfunctional, and durable T cell immune responses induced in mice by a novel hepatitis C virus (HCV) vaccine candidate (MVA-HCV) based on modified vaccinia virus Ankara expressing the nearly full-length HCV genome.

A major goal in the control of hepatitis C infection is the development of a vaccine. Here, we have developed a novel HCV vaccine candidate based on the highly attenuated poxvirus vector MVA (referred to as MVA-HCV) expressing the nearly full-length (7.9-kbp) HCV sequence, with the aim to target almost all of the T and B cell determinants described for HCV. In infected cells, MVA-HCV produces a polyprotein that is subsequently processed into the structural and nonstructural HCV proteins, triggering the cytoplasmic accumulation of dense membrane aggregates. In both C57BL/6 and transgenic HLA-A2-vaccinated mice, MVA-HCV induced high, broad, polyfunctional, and long-lasting HCV-specific T cell immune responses. The vaccine-induced T cell response was mainly mediated by CD8 T cells; however, although lower in magnitude, the CD4(+) T cells were highly polyfunctional. In homologous protocol (MVA-HCV/MVA-HCV) the main CD8(+) T cell target was p7+NS2, whereas in heterologous combination (DNA-HCV/MVA-HCV) the main target was NS3. Antigenic responses were also detected against other HCV proteins (Core, E1-E2, and NS4), but the magnitude of the responses was dependent on the protocol used. The majority of the HCV-induced CD8(+) T cells were triple or quadruple cytokine producers. The MVA-HCV vaccine induced memory CD8(+) T cell responses with an effector memory phenotype. Overall, our data showed that MVA-HCV induced broad, highly polyfunctional, and durable T cell responses of a magnitude and quality that might be associated with protective immunity and open the path for future considerations of MVA-HCV as a prophylactic and/or therapeutic vaccine candidate against HCV.

The Burden of Cardiovascular Disease in the Post-COVID Era.

In 2019, before the COVID-19 pandemic, cardiovascular disease (CVD) was the leading cause of death. Since 2020, the pandemic has had far-reaching effects on the landscape of health care including CVD prevention and management. Recent decreases in life expectancy in the United States could potentially be explained by issues related to disruptions in CVD prevention and control of CVD risk factors from the COVID-19 pandemic. This article reviews the effects of the SARS-CoV-2 virus and the accompanying pandemic on CVD risk factor prevention and management in the United States. Potential solutions are also proposed for these patients.

Application of Robotics in Orthodontics: A Systematic Review.

Robotics has various applications in dentistry, particularly in orthodontics, although the potential use of these technologies is not yet clear. This review aims to summarize the application of robotics in orthodontics and clarify its function and scope in clinical practice. Original articles addressing the application of robotics in any area of orthodontic practice were included, and review articles were excluded. PubMed, Google Scholar, Scopus, and DOAJ were searched from June to August 2023. The risk of bias was established using the risk of bias in non-randomized studies (ROBINS) and certainty assessment tools following the grading of recommendations, assessment, development, and evaluation (GRADE) guidelines. A narrative synthesis of the data was generated and presented according to its application in surgical and non-surgical orthodontics. The search retrieved 2,106 articles, of which 16 articles were selected for final data synthesis of research conducted between 2011 and 2023 in Asia, Europe, and North America. The application of robotics in surgical orthodontics helps guide orthognathic surgeries by reducing the margin of error, but it does not replace the work of a clinician. In non-surgical orthodontics, robotics assists in performing customized bending of orthodontic wires and simulating orthodontic movements, but its application is expensive. The articles collected for this synthesis exhibited a low risk of bias and high certainty, and the results indicated that the advantages of the application of robotics in orthodontics outweigh the disadvantages. This project was self-financed, and a previous protocol was registered at the PROSPERO site (registration number: CRD42023463531).

Status of ambulatory blood pressure monitoring and home blood pressure monitoring for the diagnosis and management of hypertension in the US: an up-to-date review.

The diagnosis and management of hypertension has been based on the measurement of blood pressure (BP) in the office setting. However, data have demonstrated that BP may substantially differ when measured in the office than when measured outside the office setting. Higher out-of-office BP is associated with increased cardiovascular risk independent of office BP. Ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM) are validated approaches for out-of-office BP measurement. In the 2015 and 2021 United States Preventive Services Task Force (USPSTF) reports on screening for hypertension, ABPM was recommended as the reference standard for out-of-office BP monitoring and for confirming an initial diagnosis of hypertension. This recommendation was based on data from more published studies of ABPM vs. HBPM on the predictive value of out-of-office BP independent of office BP. Therefore, HBPM was recommended as an alternative approach when ABPM was not available or well tolerated. The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP guideline recommended ABPM as the preferred initial approach for detecting white-coat hypertension and masked hypertension among adults not taking antihypertensive medication. In contrast, HBPM was recommended as the preferred initial approach for detecting the white-coat effect and masked uncontrolled hypertension among adults taking antihypertensive medication. The current review provides an overview of ABPM and HBPM in the US, including best practices, BP thresholds that should be used for the diagnosis and treatment of hypertension, barriers to widespread use of such monitoring, US guideline recommendations for ABPM and HBPM, and data supporting HBPM over ABPM.

Use of Different Blood Pressure Thresholds to Reduce the Number of Home Blood Pressure Monitoring Days Needed for Detecting Hypertension.

BACKGROUND: Home blood pressure (BP) monitoring over a 7-day period is recommended to confirm the diagnosis of hypertension. METHODS: We determined upper and lower home BP thresholds with >90% positive predictive value and >90% negative predictive value using 1 to 6 days of monitoring to identify high home BP (systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg) based on 7 days of home BP monitoring. The sample included 361 adults from the Improving the Detection of Hypertension Study who were not taking antihypertensive medication. We used two 7-day periods, at least 3 days apart, the first being a sampling period and the second a reference period. For each number of days in the sampling period, we determined the percentage of participants who had a high likelihood of having (>90% positive predictive value) or not having (>90% negative predictive value) high BP and would not need to continue home BP monitoring. Only the participants in an uncertain category (ie, positive predictive value ≤90% and negative predictive value ≤90%) after each day were carried forward to the next day of home BP monitoring. RESULTS: Of the 361 participants (mean [SD] age of 41.3 [13.2] years; 60.4% women), 38.0% had high home BP during the reference period. There were 63.7%, 17.1%, 10.5%, 3.3%, 3.6%, and 1.4% participants who would not need to continue after 1, 2, 3, 4, 5, and 6 days of monitoring. CONCLUSIONS: In most people, high home BP can be identified or excluded with a high degree of confidence with 3 days or less of monitoring.

Cumulative antitumor effect of bismuth lipophilic nanoparticles and cetylpyridinium chloride in inhibiting the growth of lung cancer.

OBJECTIVE: To determine the combined antitumor effect of bismuth lipophilic nanoparticles (BisBAL NP) and cetylpyridinium chloride (CPC) on human lung tumor cells. MATERIAL AND METHODS: The human lung tumor cells A549 were exposed to 1-100 µM BisBAL NP or CPC, either separately or in a 1:1 combination. Cell viability was measured with the PrestoBlue assay, the LIVE/DEAD assay, and fluorescence microscopy. The integrity and morphology of cellular microtubules were analyzed by immunofluorescence. RESULTS: A 24-h exposure to 1 µM solutions reduced A549 growth with 21.5% for BisBAL NP, 70.5% for CPC, and 92.4% for the combination (p < 0.0001), while a 50 µM BisBAL NP/CPC mixture inhibited cell growth with 99% (p < 0.0001). BisBAL NP-curcumin conjugates were internalized within 30 min of exposure and could be traced within the nucleus of tumor cells within 2 h. BisBAL NP, but not CPC, interfered with microtubule organization, thus interrupting cell replication, similar to the action mechanism of docetaxel. CONCLUSION: The growth inhibition of A549 human tumor cells by BisBAL NP and CPC was cumulative as of 1 µM. The BisBAL NP/CPC combination may constitute an innovative and cost-effective alternative for treating human lung cancer.

Evaluating novel approaches for estimating awake and sleep blood pressure: design of the Better BP Study - a randomised, crossover trial.

INTRODUCTION: For many people, blood pressure (BP) levels differ when measured in a medical office versus outside of the office setting. Out-of-office BP has a stronger association with cardiovascular disease (CVD) events compared with BP measured in the office. Many BP guidelines recommend measuring BP outside of the office to confirm the levels obtained in the office. Ambulatory BP monitoring (ABPM) can assess out-of-office BP but is not available in many US practices and some individuals find it uncomfortable. The aims of the Better BP Study are to (1) test if unattended office BP is closer to awake BP on ABPM compared with attended office BP, (2) assess if sleep BP assessed by home BP monitoring (HBPM) agrees with sleep BP from a full night of ABPM and (3) compare the strengths of associations of unattended versus attended office BP, unattended office BP versus awake BP on ABPM and sleep BP on HBPM versus ABPM with markers of end-organ damage. METHODS AND ANALYSIS: We are recruiting 630 adults not taking antihypertensive medication in Birmingham, Alabama, and New York, New York. Participants are having their office BP measured with (attended) and without (unattended) a technician present, in random order, using an automated oscillometric office BP device during each of two visits within one week. Following these visits, participants complete 24 hours of ABPM and one night of HBPM, in random order. Psychosocial factors, anthropometrics, left ventricular mass index and albumin-to-creatinine ratio are also being assessed. ETHICS AND DISSEMINATION: This study was approved by the University of Alabama at Birmingham and the Columbia University Medical Center Institutional Review Boards. The study results will be disseminated at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04307004.

Neuroprotective and Neurotoxic Effects of Glial-Derived Exosomes.

Exosomes derived from glial cells such as astrocytes, microglia, and oligodendrocytes can modulate cell communication in the brain and exert protective or neurotoxic effects on neurons, depending on the environmental context upon their release. Their isolation, characterization, and analysis under different conditions in vitro, in animal models and samples derived from patients has allowed to define the participation of other molecular mechanisms behind neuroinflammation and neurodegeneration spreading, and to propose their use as a potential diagnostic tool. Moreover, the discovery of specific molecular cargos, such as cytokines, membrane-bound and soluble proteins (neurotrophic factors, growth factors, misfolded proteins), miRNA and long-non-coding RNA, that are enriched in glial-derived exosomes with neuroprotective or damaging effects, or their inhibitors can now be tested as therapeutic tools. In this review we summarize the state of the art on how exosomes secretion by glia can affect neurons and other glia from the central nervous system in the context of neurodegeneration and neuroinflammation, but also, on how specific stress stimuli and pathological conditions can change the levels of exosome secretion and their properties.

Cetylpyridinium chloride inhibits human breast tumor cells growth in a no-selective way.

OBJECTIVE: Analyze the antitumor capacity of cetylpyridinium chloride (CPC) on human breast tumor cells, and the possible action mechanism. MATERIAL AND METHODS: The human breast tumor cells MCF-7 and no-tumor breast cells MCF-10A were exposed to CPC under various condition (concentration and duration). Cell viability was measured with MTT assay, the LIVE/DEAD assay, and fluorescence microscopy. Membrane permeability after CPC exposure was evaluated by Calcein AM assay, mitochondrial morphology with a MitoView staining, and genotoxicity with the comet assay and fluorescence microscopy. RESULTS: CPC was cytotoxic to both MCF-7 and MCF-10A as of a 24-h exposure to 0.1 µM. Cytotoxicity was dose-dependent and reached 91% for MCF-7 and 78% for MCF-10A after a 24-h exposure to 100 µM CPC, which outperformed the positive control doxorubicin in effectiveness and selectivity. The LD50 of CPC on was 6 µM for MCF-7 and 8 µM for MCF-10A, yielding a selectivity index of 1.41. A time response analysis revealed 64% dead cells after only 5 min of exposure to 100 µM CPC. With respect to the action mechanisms, the comet assay did not reveal genome fragmentation. On the other hand, membrane damage was dose-dependent and may also affect mitochondrial morphology. CONCLUSION: Cetylpyridinium chloride inhibits MCF-7 cell growing in a non-selective way as of 5 min of exposure. The action mechanism of CPC on tumor cells involves cell membrane damage without change neither mitochondrial morphology nor genotoxicity.

Antimicrobial potential of AH Plus supplemented with bismuth lipophilic nanoparticles on E. faecalis isolated from clinical isolates.

The objective of this study was to determine the antimicrobial potential of AH plus supplemented with bismuth lipophilic nanoparticles (BisBAL NPs) on the growth of Enterococcus faecalis isolated from patients with endodontic infections. BisBAL NPs, synthesized with the colloidal method, were characterized, in its pure form or AH Plus-absorbed, by energy-dispersive X-ray spectroscopy and scanning electron microscopy (EDS-SEM). Antimicrobial activity was evaluated with disc diffusion assays, and antibiofilm activity with fluorescence microscopy. BisBAL NP-supplemented AH Plus had a 4.9 times higher antimicrobial activity than AH Plus alone (p = 0.0001). In contrast to AH Plus alone, AH Plus supplemented with BisBAL NP inhibited E. faecalis biofilm formation. The sealing properties of AH plus were not modified by the incorporation of BisBAL NPs, which was demonstrated by a 12-day split-chamber leakage assay with daily inoculation, which was used to evaluate the possible filtration of E. faecalis. Finally, BisBAL NP-supplemented AH plus-BisBAL NPs was not cytotoxic for cultured human gingival fibroblasts. Their viability was 83.7% to 89.9% after a 24-h exposure to AH Plus containing 50 and 10 µM BisBAL NP, respectively. In conclusion, BisBAL NP-supplemented AH Plus constitutes an innovative nanomaterial to prevent re-infection in endodontic patients without cytotoxic effects.

Correlation Between CD133+ Stem Cells and Clinical Improvement in Patients with Autism Spectrum Disorders Treated with Intrathecal Bone Marrow-derived Mononuclear Cells.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental pathologies characterized by social and communication deficits, for which treatments are limited. Cell therapies, including intrathecal (IT) administration of bone marrow (BM) mononuclear cells (BM-MNC), improves symptoms in patients with ASD. Twenty-four patients diagnosed with ASD, according to the Diagnostic and Statistical Manual of Mental Disorders Text Revision Fourth Edition (DSM-IV-TR) criteria, were autologously treated with IT BM-MNC, and the clinical effect was evaluated using the Childhood Autism Rating Scale (CARS) on Days 30 (n=24) and 180 (n=14) post-treatment. IT BM-MNC improved clinical outcomes by Day 30 (p=0.0039), and those benefits remained and were further accentuated by Day 180 post-treatment (n=14; p=<0.0001). Clinical benefit at Days 30 (p=0.001; r= -0.51) and 180 (p=0.01; r= -0.60) posttreatment positively correlated with the enrichment of a putative BM stem cell population expressing the cluster of differentiation 133+ (CD133+) surface marker.

Bismuth Lipophilic Nanoparticles (BisBAL NP) Inhibit the Growth of Tumor Cells in a Mouse Melanoma Model.

AIM: The objective of this study was to analyze the antitumor effect of BisBAL NP in a mouse melanoma model. MATERIALS AND METHODS: The antitumor activity of BisBAL NP on murine B16-F10 melanoma cells was determined both in vitro (PrestoBlue cell viability assay and Live/Dead fluorescence) and in vivo, in a mouse model, with the following 15-day treatments: BisBAL NP, negative control (PBS), and cell-death control (docetaxel; DTX). Mouse survival and weight, as well as the tumor volume, were recorded daily during the in vivo study. RESULTS: BisBAL NP were homogeneous in size (mean diameter, 14.7 nm) and bismuth content. In vitro, 0.1 mg/mL BisBAL NP inhibited B16-F10 cell growth stronger (88%) than 0.1 mg/mL DTX (82%) (*p<0.0001). In vivo, tumors in mice treated with BisBAL NP (50 mg/kg/day) or DTX (10 mg/kg/day) were 76% and 85% smaller than the tumors of negative control mice (*p<0.0001). The average weight of mice was 18.1 g and no statistically significant difference was detected among groups during the study. Alopecia was only observed in all DTX-treated mice. The survival rate was 100% for the control and BisBAL NP groups, but one DTX- treated mouse died at the end of the treatment period. The histopathological analysis revealed that exposure to BisBAL NP was cytotoxic for tumor tissue only, without affecting the liver or kidney. CONCLUSION: BisBAL NP decreased the tumor growing in a mouse melanoma model without secondary effects, constituting an innovative low-cost alternative to treat melanoma.

Antimicrobial Effect of Calcium Hydroxide Combined with Electrolyzed Superoxidized Solution at Neutral pH on Enterococcus faecalis Growth.

OBJECTIVE: To evaluate the effect of the combination of calcium hydroxide (Ca(OH)2) and a novel electrolyzed superoxidized solution at neutral pH, known as OxOral® on Enterococcus faecalis growth in root canals. METHODS: Sixty human teeth were used, from which root canals were infected and randomly divided into the following treatment groups: saline solution, saline solution plus Ca(OH)2, OxOral®, and OxOral® plus Ca(OH)2. RESULTS: A permanent reduction in bacterial growth was observed at days 1, 6, 12, and 18 after OxOral® plus Ca(OH)2 treatment from 4.4 ± 0.074 log10 CFU/mL to 0.0 ± 0.001 log10 CFU/mL. In addition, alkaline conditions maintenance was observed from application time (pH = 12.2 ± 0.033) to 18 d posttreatment (pH = 12.6 ± 0.083). CONCLUSION: The combination of OxOral® and Ca(OH)2 provides an alkaline pH and inhibits E. faecalis growth into the root canals. Our study opens the possibility for further research on the use of OxOral® in endodontic therapy.

Dose patterns in commercially insured subjects chronically exposed to opioids: a large cohort study in the United States.

BACKGROUND: Little data exist on how opioid doses vary with the length of exposure among chronic opioid users. METHODS: To characterize the change in the dosage of opioids over time, a retrospective cohort study using the PharMetrics database for the years 1999 through 2008 was conducted. Individuals exposed to opioids in 2000 who had 2 opioid dispensings at least 6 months apart and were opioid naive (did not receive any opioid 6 month before their exposure in 2000) were included. The date of the first dispensing in 2000 was defined as the index date and the dispensing had to be for a strong and full agonist opioid. All opioid doses were converted to oral morphine equivalent doses. Exposure was classified as continuous or intermittent. Mean, median, interquartile range, and 95th percentile of opioid dose over 6-month periods, as well as the percentage of subjects who ever received a high or very high opioid dose, were calculated. RESULTS: Among the 48,986 subjects, the mean age was 44.5 years and 54.5% were women. Intermittent exposure was observed in 99% of subjects; continuous exposure was observed in 1% of subjects. The mean duration of exposure for the subjects who were continuously exposed to opioids was 477 days. In subjects with no cancer diagnosis who were continuously exposed to opioids, the mean, 25th, 50th, and 75th percentile of dose was stable during the first 2 years of use, but the 95th percentile increased. Seven percent of them were exposed to doses of 180 mg or more of morphine at some point. CONCLUSIONS: Dose escalation is uncommon in subjects with intermittent exposure to opioids. For subjects with continuous exposure to opioids who have cancer, doses rise substantially with time. For those without cancer, doses remain relatively stable for the first 2 years of use, but subsequently increase. Seven percent of subjects with no cancer diagnosis will be exposed to daily doses of 180 mg or more of morphine equivalent at some point.