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1.
Toxics ; 12(5)2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38787151

RESUMO

E-liquids contain combinations of chemicals, with many enhancing the sensory attractiveness of the product. Studies are needed to understand and characterize e-liquid ingredients, particularly flavorings, to inform future research and regulations of these products. We identified common flavor ingredients in a convenience sample of commercial e-liquids using gas chromatography-mass spectrometry. E-liquid flavors were categorized by flavor descriptors provided on the product packaging. A Flavor Ingredient Wheel was developed to link e-liquid flavor ingredients with flavor categories. An analysis of 109 samples identified 48 flavor ingredients. Consistency between the labeled flavor and ingredients used to produce such flavor was found. Our novel Flavor Ingredient Wheel organizes e-liquids by flavor and ingredients, enabling efficient analysis of the link between ingredients and their flavor profiles and allowing for quick assessment of an e-liquid ingredient's flavor profile. Investigating ingredient profiles and identifying and classifying commonly used chemicals in e-liquids may assist with future studies and improve the ability to regulate these products.

2.
PLoS One ; 18(11): e0289183, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37963142

RESUMO

Clostridium novyi has demonstrated selective efficacy against solid tumors largely due to the microenvironment contained within dense tumor cores. The core of a solid tumor is typically hypoxic, acidic, and necrotic-impeding the penetration of current therapeutics. C. novyi is attracted to the tumor microenvironment and once there, can both lyse and proliferate while simultaneously re-activating the suppressed immune system. C. novyi systemic toxicity is easily mitigated by knocking out the phage DNA plasmid encoded alpha toxin resulting in C. novyi-NT; but, after intravenous injection spores are quickly cleared by phagocytosis before accomplishing significant tumor localization. C. novyi-NT could be designed to accomplish intravenous delivery with the potential to target all solid tumors and their metastases in a single dose. This study characterizes CRISPR/Cas9 modified C. novyi-NT to insert the gene for RGD, a tumor targeting peptide, expressed within the promoter region of a spore coat protein. Expression of the RGD peptide on the outer spore coat of C. novyi-NT indicates an increased capacity for tumor localization of C. novyi upon intravenous introduction based on the natural binding of RGD with the αvß3 integrin commonly overexpressed on the epithelial tissue surrounding a tumor, and lead to immune stimulation.


Assuntos
Clostridium botulinum , Neoplasias Pancreáticas , Humanos , Esporos Bacterianos/genética , Clostridium/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Oligopeptídeos/metabolismo , Microambiente Tumoral
3.
J Strength Cond Res ; 37(12): 2484-2490, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37639680

RESUMO

ABSTRACT: McGrath, R, FitzSimmons, S, Andrew, S, Black, K, Bradley, A, Christensen, BK, Collins, K, Klawitter, L, Kieser, J, Langford, M, Orr, M, and Hackney, KJ. Prevalence and trends of weakness among middle-aged and older adults in the United States. J Strength Cond Res 37(12): 2484-2490, 2023-Muscle weakness, which is often determined with low handgrip strength (HGS), is associated with several adverse health conditions; however, the prevalence and trends of weakness in the United States is not well-understood. We sought to estimate the prevalence and trends of weakness in Americans aged at least 50 years. The total unweighted analytic sample included 22,895 Americans from the 2006-2016 waves of the Health and Retirement Study. Handgrip strength was measured with a handgrip dynamometer. Men with weakness were below at least one of the absolute or normalized (body mass, body mass index) cut points: <35.5 kg, <0.45 kg/kg, <1.05 kg/kg/m 2 . The presence of any weakness in women was also identified as being below one of the absolute or normalized HGS cut points: <20.0 kg, <0.34 kg/kg, or <0.79 kg/kg/m 2 . There was an increasing trend in the prevalence of any weakness over time ( p < 0.001). The prevalence of weakness was 45.1% (95% confidence interval [CI]: 44.0-46.0) in the 2006-2008 waves and 52.6% (CI: 51.5-53.7) in the 2014-2016 waves. Weakness prevalence was higher for older (≥65 years) Americans (64.2%; CI: 62.8-65.5) compared with middle-aged (50-64 years) Americans (42.2%; CI: 40.6-43.8) in the 2014-2016 waves. Moreover, the prevalence of weakness in the 2014-2016 waves was generally higher in women (54.5%; CI: 53.1-55.9) than in men (50.4%; CI: 48.7-52.0). Differences existed in weakness prevalence across races and ethnicities. The findings from our investigation suggest that the prevalence of weakness is overall pronounced and increasing in Americans. Efforts for mitigating and better operationalizing weakness will elevate in importance as our older American population grows.


Assuntos
Força da Mão , Aposentadoria , Masculino , Pessoa de Meia-Idade , Humanos , Feminino , Estados Unidos/epidemiologia , Idoso , Força da Mão/fisiologia , Prevalência , Debilidade Muscular/epidemiologia , Índice de Massa Corporal
4.
Influenza Other Respir Viruses ; 17(5): e13152, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37246149

RESUMO

BACKGROUND: Highly pathogenic avian H5 influenza viruses have spread and diversified genetically and antigenically into multiple clades and subclades. Most isolates of currently circulating H5 viruses are in clade 2.3.2.1 or 2.3.4.4. METHODS: Panels of murine monoclonal antibodies (mAbs) were generated to the influenza hemagglutinin (HA) of H5 viruses from the clade 2.3.2.1 H5N1 vaccine virus A/duck/Bangladesh/19097/2013 and the clade 2.3.4.4 H5N8 vaccine virus A/gyrfalcon/Washington/41088-6/2014. Antibodies were selected and characterized for binding, neutralization, epitope recognition, cross-reactivity with other H5 viruses, and the ability to provide protection in passive transfer experiments. RESULTS: All mAbs bound homologous HA in an ELISA format; mAbs 5C2 and 6H6 were broadly binding for other H5 HAs. Potently neutralizing mAbs were identified in each panel, and all neutralizing mAbs provided protection in passive transfer experiments in mice challenged with a homologous clade influenza virus. Cross-reacting mAb 5C2 neutralized a wide variety of clade 2.3.2.1 viruses, as well as H5 viruses from other clades, and also provided protection against heterologous H5 clade influenza virus challenge. Epitope analysis indicated that the majority of mAbs recognized epitopes in the globular head of the HA. The mAb 5C2 appeared to recognize an epitope below the globular head but above the stalk region of HA. CONCLUSIONS: The results suggested that these H5 mAbs would be useful for virus and vaccine characterization. The results confirmed the functional cross-reactivity of mAb 5C2, which appears to bind a novel epitope, and suggest the therapeutic potential for H5 infections in humans with further development.


Assuntos
Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A Subtipo H5N8 , Vírus da Influenza A , Vacinas contra Influenza , Influenza Humana , Humanos , Animais , Camundongos , Anticorpos Monoclonais , Anticorpos Neutralizantes , Hemaglutininas , Anticorpos Antivirais , Testes de Neutralização , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Epitopos/química , Camundongos Endogâmicos BALB C
5.
Environ Sci Technol ; 57(22): 8225-8235, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37220346

RESUMO

Plastic cutting boards are a potentially significant source of microplastics in human food. Thus, we investigated the impact of chopping styles and board materials on microplastics released during chopping. As chopping progressed, the effects of chopping styles on microplastic release became evident. The mass and number of microplastics released from polypropylene chopping boards were greater than polyethylene by 5-60% and 14-71%, respectively. Chopping on polyethylene boards was associated with a greater release of microplastics with a vegetable (i.e., carrots) than chopping without carrots. Microplastics showed a broad, bottom-skewed normal distribution, dominated by <100 µm spherical-shaped microplastics. Based on our assumptions, we estimated a per-person annual exposure of 7.4-50.7 g of microplastics from a polyethylene chopping board and 49.5 g of microplastics from a polypropylene chopping board. We further estimated that a person could be exposed to 14.5 to 71.9 million polyethylene microplastics annually, compared to 79.4 million polypropylene microplastics from chopping boards. The preliminary toxicity study of the polyethylene microplastics did not show adverse effects on the viability of mouse fibroblast cells for 72 h. This study identifies plastic chopping boards as a substantial source of microplastics in human food, which requires careful attention.


Assuntos
Microplásticos , Poluentes Químicos da Água , Animais , Camundongos , Humanos , Plásticos , Polipropilenos , Poluentes Químicos da Água/análise , Polietileno/análise , Monitoramento Ambiental
6.
Biol Open ; 11(12)2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36318109

RESUMO

Plasticity in hatching time allows embryos to maximize fitness by balancing the benefits and costs of remaining bound within the chorion against the benefits and costs of emerging as a free-swimming larva. Here, in the first experiment, we exposed zebrafish (Danio rerio) embryos to either chemical cues from crushed embryos (simulating egg predation) or to blank water control. Embryos exposed to alarm cues hatched sooner, and had shorter body lengths and underdeveloped fins, relative to larvae from the water treatment. Burst swimming speed was significantly slower for larvae that hatched from the alarm cue treatment than for larvae from the water treatment. In a second 2×2 experiment, we exposed zebrafish embryos to either chemical alarm cues from conspecific embryos, mechanical disturbance (magnetic stir bar) to simulate a predator probing the substrate for developing embryos, both chemical and mechanical indicators of risk, or neither (control). We found similar effects in terms of earlier time to hatch at an earlier stage of development and poorer swimming performance of hatchling larvae. In the second experiment, these effects occurred in response to mechanical disturbance with or without the presence of chemical alarm cues. Alarm cues alone produced no effects in the second experiment. Taken together, these data indicate that zebrafish embryos demonstrate a facultative trade-off between risk of predation acting on two stages of their life history.


Assuntos
Comportamento Predatório , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Larva , Natação , Sinais (Psicologia)
7.
Front Genet ; 13: 849839, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360846

RESUMO

Over the past several decades in the United States, incidence of pancreatic cancer (PCa) has increased, with the 5-year survival rate remaining extremely low at 10.8%. Typically, PCa is diagnosed at an advanced stage, with the consequence that there is more tumor heterogeneity and increased probability that more cells are resistant to treatments. Risk factors for PCa can serve as a way to select a high-risk population and develop biomarkers to improve early detection and treatment. We focus on blood-based methylation as an approach to identify a marker set that can be obtained in a minimally invasive way (through peripheral blood) and could be applied to a high-risk subpopulation [those with recent onset type 2 diabetes (DM)]. Blood samples were collected from 30 patients, 15 had been diagnosed with PCa and 15 had been diagnosed with recent onset DM. HumanMethylationEPIC Beadchip (Illumina, CA, United States) was used to quantify methylation of approximately 850,000 methylation sites across the genome and to analyze methylation markers associated with PCa or DM or both. Exploratory analysis conducted to propose importance of top CpG (5'-C-phosphate-G-3') methylation site associated genes and visualized using boxplots. A methylation-based age predictor was also investigated for ability to distinguish disease groups from controls. No methylation markers were observed to be significantly associated with PCa or new onset diabetes compared with control the respective control groups. In our exploratory analysis, one methylation marker, CpG04969764, found in the Laminin Subunit Alpha 5 (LAMA5) gene region was observed in both PCa and DM Top 100 methylation marker sets. Modification of LAMA5 methylation or LAMA5 gene function may be a way to distinguish those recent DM cases with and without PCa, however, additional studies with larger sample sizes and different study types (e.g., cohort) will be needed to test this hypothesis.

10.
Public Health Nurs ; 38(5): 879-884, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33938043

RESUMO

OBJECTIVE: To determine compliance with North Dakota's smoke-free law in vape shops and other tobacco specialty shops selling electronic nicotine delivery systems (ENDS) or e-liquids. DESIGN: In this 2019 descriptive study, shops (n = 35) were assessed for compliance with the smoke-free law by observation of indoor and outdoor areas for smoking or vaping, or evidence of such activity in prohibited areas, and the presence of required no-smoking signs. RESULTS: Only two shops (5.7%) were fully compliant with the smoke-free law. Full compliance for indoor and outdoor environments was 8.5% and 42.8%, respectively. Vaping occurred inside five shops (14.3%), and smoking occurred outdoors within required smoke-free areas in two (5.7%) shops. Four (11.4%) and 17 (48.6%) shops complied with indoor and outdoor signage requirements, respectively. CONCLUSIONS: Overall compliance remained low, although much of the noncompliance was related to signage. Use or evidence of ENDS use occurred both indoors and outdoors where prohibited by law. Classifying ENDS as tobacco products would require tobacco licensure of shops selling ENDS and e-liquids, aiding in identification of the shops for education and enforcement efforts to ensure compliance with the law and to improve public health protection.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Política Antifumo , Produtos do Tabaco , Poluição por Fumaça de Tabaco , Vaping , Humanos , North Dakota , Nicotiana , Poluição por Fumaça de Tabaco/prevenção & controle
11.
J Pediatr Nurs ; 59: 45-54, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33460879

RESUMO

PURPOSE: To expand on our 2015 study of the nicotine content accuracy of e-liquids, including salts, and the presence of child-resistant packaging. We also describe compounding in shop (CIS). DESIGN AND METHODS: We analyzed samples from 35 shops. CIS processing was observed. Descriptive statistics summarized the data, and inference was performed. RESULTS: Actual nicotine content was significantly less than the identified content, on average, with a mean percent deviation 34.0% below the identified content. Only 3.8% of the samples' actual nicotine content was within 10% of the identified content; the maximum deviation was 213.2%. Of eight uniquely packaged samples, including designs resembling pop cans, ice cream cones, etc., the mean percent deviation was -39.6%; none were within 10% of the identified content. Eight shops compounded samples. After removing outlier values, significant differences were found in the percent deviations between the CIS and non-CIS free-base samples. A significantly higher percentage of CIS samples had nicotine content > 10% above the identified content, and none were within 10%. One shop visually estimated the nicotine quantities to add, e-liquids were not always relabeled to reflect new nicotine levels, and protective materials were not always worn during compounding. Child-resistant packaging was not present for one third of the samples. CONCLUSIONS: Labeling of nicotine content in e-liquids remains inaccurate, child-resistant packaging is inconsistent, and CIS is problematic. Effective e-liquid regulation is needed to protect public health. PRACTICE IMPLICATIONS: Nurses should educate families about the serious health risks of e-liquids and advocate for increased e-liquid regulations.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Nicotina , Humanos , Rotulagem de Produtos , Embalagem de Produtos
12.
J Am Pharm Assoc (2003) ; 61(1): 20-26, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33012670

RESUMO

OBJECTIVES: The use of e-cigarettes is becoming more common in the United States. E-cigarettes are often refilled with nicotine-containing solutions of various concentrations purchased in local shops or on the Internet. There is evidence that the nicotine content in these solutions is often mislabeled; thus, we reviewed the available literature on this topic. DATA SOURCES: We conducted a systematic review of peer-reviewed articles published worldwide on e-liquid nicotine content accuracy using the databases CAB Direct, Cochrane Central Register of Controlled Trials, PubMed, and SPORTDiscus (EBSCO). STUDY SELECTION: Initial screening of titles and abstracts was conducted to determine relevancy for inclusion. Full-article reviews of studies involving the purchase and chemical analysis of nicotine content in refillable e-liquids were conducted for final inclusion. DATA EXTRACTION: Data extraction included e-liquid sample size, whether the samples were labeled to contain nicotine, whether the samples were purchased in retail shops or online, and the number and percentage of samples where the analyzed nicotine content fell outside 10% of the labeled nicotine content. RESULTS: Twenty articles described cross-sectional studies of purchased samples containing nicotine. The number of nicotine-containing e-liquid samples obtained in each study varied from 2 to 71. The percentage of samples with an analyzed nicotine concentration of more than 10% above or below the labeled nicotine concentration ranged from 0% to 100% (277/574 or 48.3%; median 46.85%). A large percentage of the samples deviated by 10% from the labeled nicotine concentrations in both U.S. and non-U.S. samples, with U.S. samples having a higher percentage. CONCLUSION: Our review shows that actual nicotine concentrations in e-liquids may vary considerably from labeled concentrations. Pharmacists should warn patients to be wary of the contents of e-cigarettes, and explain the dangers of using these products.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Nicotina , Estudos Transversais , Humanos , Marketing , Estados Unidos
13.
Mol Pharm ; 18(1): 87-100, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33231464

RESUMO

Pancreatic ductal adenocarcinoma (PDAC), a metabolic disorder, remains one of the leading cancer mortality sources worldwide. An initial response to treatments, such as gemcitabine (GEM), is often followed by emergent resistance reflecting an urgent need for alternate therapies. The PDAC resistance to GEM could be due to ERK1/2 activity. However, successful ERKi therapy is hindered due to low ligand efficiency, poor drug delivery, and toxicity. In this study, to overcome these limitations, we have designed pH-responsive nanoparticles (pHNPs) with a size range of 100-150 nm for the simultaneous delivery of ERKi (SCH 772984) and GEM with tolerable doses. These pHNPs are polyethylene glycol (PEG)-containing amphiphilic polycarbonate block copolymers with tertiary amine side chains. They are systemically stable and capable of improving in vitro and in vivo drug delivery at the cellular environment's acidic pH. The functional analysis indicates that the nanomolar doses of ERKi or GEM significantly decreased the 50% growth inhibition (IC50) of PDAC cells when encapsulated in pHNPs compared to free drugs. The combination of ERKi with GEM displayed a synergistic inhibitory effect. Unexpectedly, we uncover that the minimum effective dose of ERKi significantly promotes GEM activities on PDAC cells. Furthermore, we found that pHNP-encapsulated combination therapy of ERKi with GEM was superior to unencapsulated combination drug therapy. Our findings, thus, reveal a simple, yet efficient, drug delivery approach to overcome the limitations of ERKi for clinical applications and present a new model of sensitization of GEM by ERKi with no or minimal toxicity.


Assuntos
Proliferação de Células/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Portadores de Fármacos/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Nanopartículas/química , Neoplasias Pancreáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Carcinoma Ductal Pancreático/tratamento farmacológico , Linhagem Celular Tumoral , Desoxicitidina/administração & dosagem , Desoxicitidina/química , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Camundongos Nus , Polietilenoglicóis/química , Polímeros/química , Inibidores de Proteínas Quinases/química , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Gencitabina
14.
Cancers (Basel) ; 12(6)2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32526885

RESUMO

Glutathione S-transferase pi-1 (GSTP1) plays an important role in regulating oxidative stress by conjugating glutathione to electrophiles. GSTP1 is overexpressed in breast, colon, lung, and prostate tumors, where it contributes to tumor progression and drug resistance; however, the role of GSTP1 in pancreatic ductal adenocarcinoma (PDAC) is not well understood. Using shRNA, we knocked down GSTP1 expression in three different PDAC cell lines and determined the effect on cell proliferation, cell cycle progression, and reactive oxygen species (ROS) levels. Our results show GSTP1 knockdown reduces PDAC cell growth, prolongs the G0/G1 phase, and elevates ROS in PDAC cells. Furthermore, GSTP1 knockdown results in the increased phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun and the decreased phosphorylation of extracellular signal-regulated kinase (ERK), p65, the reduced expression of specificity protein 1 (Sp1), and the increased expression of apoptosis-promoting genes. The addition of the antioxidant glutathione restored cell viability and returned protein expression levels to those found in control cells. Collectively, these data support the working hypothesis that the loss of GSTP1 elevates oxidative stress, which alters mitogen-activated protein (MAP) kinases and NF-κB signaling, and induces apoptosis. In support of these in vitro data, nude mice bearing orthotopically implanted GSTP1-knockdown PDAC cells showed an impressive reduction in the size and weight of tumors compared to the controls. Additionally, we observed reduced levels of Ki-67 and increased expression of cleaved caspase-3 in GSTP1-knockdown tumors, suggesting GSTP1 knockdown impedes proliferation and upregulates apoptosis in PDAC cells. Together, these results indicate that GSTP1 plays a significant role in PDAC cell growth and provides support for the pursuit of GSTP1 inhibitors as therapeutic agents for PDAC.

15.
J Child Neurol ; 35(9): 585-590, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32429785

RESUMO

INTRODUCTION: In young children, excessive cow's milk intake causes iron-deficiency anemia, which is associated with hypercoagulable states. We present a case series of 4 toddlers with excessive milk intake iron-deficiency anemia and cerebral sinovenous thrombosis. METHODS: Retrospective chart review of 4 patients was performed for patients with cerebral sinovenous thrombosis and iron-deficiency anemia secondary to excessive milk intake. Iron-deficiency anemia was defined as hemoglobin <11 mg/dL, mean corpuscular volume <70 fL, and serum ferritin <12 µg/L. Excessive milk intake was defined as consumption of >24 oz daily. Clinical, laboratory, and radiographic features were reviewed. RESULTS: Age ranged from 12 to 24 months. Average hemoglobin, hematocrit, mean corpuscular volume, and ferritin levels were 6.1 g/dL, 22.7 g/dL, 52.7 fL, and 3.2 ng/mL, respectively. Daily milk consumption ranged from 40 to 60 oz. All patients presented with focal neurologic deficits, including seizures in 3. The location of cerebral sinovenous thrombosis varied, and 3 patients had venous infarcts, one of them hemorrhagic. All patients had a limited diet and were described as "picky eaters" by their parents, and only 1 had transitioned of a bottle. All patients were treated with anticoagulation, iron supplementation, and extensive dietary counseling to reduce cow's milk intake. CONCLUSION: Iron-deficiency anemia due to excessive milk intake is an important and preventable etiology of pediatric cerebral sinovenous thrombosis. Focused anticipatory guidance is necessary for at-risk groups to prevent this neurologic emergency.


Assuntos
Anemia Ferropriva/etiologia , Transtornos Cerebrovasculares/etiologia , Leite/efeitos adversos , Trombose/etiologia , Anemia Ferropriva/terapia , Animais , Transfusão de Sangue , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/terapia , Pré-Escolar , Feminino , Heparina/uso terapêutico , Humanos , Lactente , Ferro/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Masculino , Estudos Retrospectivos , Trombose/diagnóstico por imagem , Trombose/terapia
16.
Front Microbiol ; 10: 2689, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31849864

RESUMO

Vasoactive intestinal peptide (VIP) is crucial for gastrointestinal tract (GIT) health. VIP sustains GIT homeostasis through maintenance of the intestinal epithelial barrier and acts as a potent anti-inflammatory mediator that contributes to gut bacterial tolerance. Based on these biological functions by VIP, we hypothesized that its deficiency would alter gut microbial ecology. To this end, fecal samples from male and female VIP+/+, VIP+/-, and VIP-/- littermates (n = 47) were collected and 16S rRNA sequencing was conducted. Our data revealed significant changes in bacterial composition, biodiversity, and weight loss from VIP-/- mice compared to VIP+/+ and VIP+/- littermates, irrespective of sex. The gut bacteria compositional changes observed in VIP-/- mice was consistent with gut microbial structure changes reported for certain inflammatory and autoimmune disorders. Moreover, predicted functional changes by PICRUSt software suggested an energy surplus within the altered microbiota from VIP-/- mice. These data support that VIP plays an important role in maintaining microbiota balance, biodiversity, and GIT function, and its genetic removal results in significant gut microbiota restructuring and weight loss.

17.
Chiropr Man Therap ; 26: 45, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30534361

RESUMO

Background: Tobacco use remains a leading cause of death and disability in the United States. Health professionals need to address the use of tobacco products by their patients, but chiropractic clinical systems often remain unsupported and underappreciated in their role to facilitate tobacco use cessation. Methods: This pilot study tested an intervention to assist a chiropractic community to implement sustainable health systems changes for tobacco use based on U.S. Public Health Service guidelines. Chiropractors were educated on the Ask, Advise, Refer (AAR) approach, provided with ongoing guidance, and followed for six months to assess systems change. The study was conducted from March 2016 to July 2017. Results: Evidence of a systematic process in place to conduct AAR was present in all clinics by the end of the fourth month of the intervention period. Although no clinic had sustained health system change for full AAR, all six of the clinics made progress in the individual AAR components. Furthermore, five clinics achieved sustained system change for the Ask component, as after systems change was achieved, the rate of tobacco user identifications did not drop below 50%. For the Advise component, five clinics succeeded in having individual months of ≥50% of tobacco users being advised, and three clinics achieved the formal definition of systems change. For the Refer component, no clinic achieved system change, although four had individual months of ≥50% of tobacco users being referred. The patient quit rate was 13.3% (n = 15) for the 30-day follow-up and 16.7% (n = 6) for the three-month follow-up. Conclusions: This study demonstrates the feasibility of implementing a health systems change in the chiropractic setting to identify tobacco users, to advise them to quit, and to refer users for cessation services.


Assuntos
Quiroprática , Aconselhamento , Pessoal de Saúde/educação , Encaminhamento e Consulta , Abandono do Hábito de Fumar/métodos , Fumar , Uso de Tabaco , Adulto , Instituições de Assistência Ambulatorial , Terapias Complementares , Estudos de Viabilidade , Feminino , Fidelidade a Diretrizes , Comportamentos Relacionados com a Saúde , Promoção da Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Abandono do Uso de Tabaco/métodos , Tabagismo/prevenção & controle , Estados Unidos
18.
Oncotarget ; 9(12): 10457-10469, 2018 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-29535819

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers due to a late diagnosis and poor response to available treatments. There is a need to identify complementary treatment strategies that will enhance the efficacy and reduce the toxicity of currently used therapeutic approaches. We investigated the ability of a known ROS inducer, piperlongumine (PL), to complement the modest anti-cancer effects of the approved chemotherapeutic agent gemcitabine (GEM) in PDAC cells in vitro and in vivo. PDAC cells treated with PL + GEM showed reduced cell viability, clonogenic survival, and growth on Matrigel compared to control and individually-treated cells. Nude mice bearing orthotopically implanted MIA PaCa-2 cells treated with both PL (5 mg/kg) and GEM (25 mg/kg) had significantly lower tumor weight and volume compared to control and single agent-treated mice. RNA sequencing (RNA-Seq) revealed that PL + GEM resulted in significant changes in p53-responsive genes that play a role in cell death, cell cycle, oxidative stress, and DNA repair pathways. Cell culture assays confirmed PL + GEM results in elevated ROS levels, arrests the cell cycle in the G0/G1 phase, and induces PDAC cell death. We propose a mechanism for the complementary anti-tumor effects of PL and GEM in PDAC cells through elevation of ROS and transcription of cell cycle arrest and cell death-associated genes. Collectively, our results suggest that PL has potential to be combined with GEM to more effectively treat PDAC.

19.
Stat Appl Genet Mol Biol ; 16(5-6): 291-312, 2017 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-29077555

RESUMO

RNA-Seq is a developing technology for generating gene expression data by directly sequencing mRNA molecules in a sample. RNA-Seq data consist of counts of reads recorded to a particular gene that are often used to identify differentially expressed (DE) genes. A common statistical method used to analyze RNA-Seq data is Significance Analysis of Microarray with emphasis on RNA-Seq data (SAMseq). SAMseq is a nonparametric method that uses a resampling technique to account for differences in sequencing depths when identifying DE genes. We propose a modification of this method that takes into account asymmetry in the distribution of the effect sizes by taking into account the sign of the test statistics. Through simulation studies, we showthat the proposed method, comparedwith the traditional SAMseqmethod and other existing methods provides better power for identifying truly DE genes or more sufficiently controls FDR in most settings where asymmetry is present. We illustrate the use of the proposed method by analyzing an RNA-Seq data set containing C57BL/6J (B6) and DBA/2J (D2) mouse strains samples.


Assuntos
Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Análise de Sequência de RNA , Algoritmos , Simulação por Computador , Computadores , Modelos Estatísticos , Análise de Sequência de RNA/métodos
20.
J Community Health ; 41(6): 1242-1248, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27271783

RESUMO

Many children are not being properly restrained in motor vehicles, resulting in unnecessary injury and fatalities. Health care provider (HCP) education is effective at increasing proper child restraint within vehicles. However, differences exist by HCP specialty in regards to frequency of child passenger safety (CPS) counseling. This study of a sample of 255 HCPs examined differences in CPS counseling by HCP specialty (pediatric vs. non-pediatric). HCPs from several upper Midwest states were surveyed about how frequently they provide CPS counseling in their practice by patient age and their attitudes toward CPS-related issues. Pediatric HCPs were twice as likely as non-pediatric HCPs to always provide CPS counseling to parents/guardians of children aged 5 or older. Non-pediatric HCPs were more likely than pediatric HCPs to feel that counseling is ineffective at increasing child seat/booster (p = 0.001) or seat belt use (p = 0.006). Non-pediatric HCPs were more likely than pediatric HCPs to feel there is inadequate time to provide CPS counseling in their practice setting (p = 0.001), and were less likely to know where to refer patients if they have questions regarding CPS issues (0.0291). The differences in HCP attitudes toward CPS counseling provision and the resulting differences in counseling frequency by patient age may contribute to disparities for patients who have limited or no access to pediatric HCPs. Additional research is needed to investigate the rationale for counseling differences seen by HCP specialty and patient age, and the potential effect on child motor vehicle injuries and fatalities.


Assuntos
Acidentes de Trânsito , Atitude do Pessoal de Saúde , Aconselhamento , Pessoal de Saúde/psicologia , Medicina , Segurança , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Cintos de Segurança/estatística & dados numéricos , Inquéritos e Questionários
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