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1.
J Vis Exp ; (155)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32065158

RESUMO

Major adverse cardiovascular events (MACEs) negatively impact the cardiovascular prognosis of patients undergoing coronary angioplasty due to coronary ischemic injury. The extent of coronary damage and the mechanisms of vascular repair are factors influencing the future development of MACEs. Intrinsic vascular features like the plaque characteristics and coronary artery complexity have demonstrated prognostic information for MACEs. However, the use of intracoronary circulating biomarkers has been postulated as a convenient method for the early identification and prognosis of MACEs, as they more closely reflect dynamic mechanisms involving coronary damage and repair. Determination of coronary circulating biomarkers during angioplasty, such as the number of subpopulations of mononuclear progenitor cells (MPCs) as well as the concentration of soluble molecules reflecting inflammation, cell adhesion, and repair, allows for assessment of future developments and the prognosis of MACEs 6 months post coronary angioplasty. This method is highlighted by its translational nature and better performance than peripheral blood circulating biomarkers regarding prediction of MACEs and its effect on the cardiovascular prognosis, which may be applied for risk stratification of patients with coronary artery disease undergoing angioplasty.

2.
Microb Pathog ; 140: 103953, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31904447

RESUMO

PURPOSE: To report the characterization and analysis of the biofilm formation in mixed keratitis induced by the coinfection of Staphylococcus aureus and Fusarium falciforme in a novel murine model. METHODS: Clinical ocular microbial isolates and female BALB/c mice were used to develop the murine model. Immunosuppression was achieved with cyclophosphamide and methylprednisolone. A corneoscleral lesion was performed with a micro-pocket technique. Mice received an inoculum with a concentration of 1 × 105 conidia of F. falciforme and S. aureus with 1 × 105 UFC/ml. Mice were sacrificed at 72 h after induction of infection, the right eye was enucleated and preserved in 10% formaldehyde to perform the PAS staining. In addition, cuts were obtained for the labeling with the fluorophores propidium iodide and Calcofluor White, and other eye cuts were processed to transmission microscopy. RESULTS: F. falciforme and S. aureus were able to developed mono and mixed biofilm in vitro. Keratitis of F. falciforme, S. aureus and mixed, were established at immunosuppressed mice. Clinical symptoms were observed at murine cornea. Histological analysis by special stains identified bacterial, fungal and mixed biofilm structures at epithelial and stromal level. Extracellular matrix was observed surrounded clusters of bacterial, fungi and mixed by fluorescence and transmission electronic microscopy. CONCLUSION: This study provides direct evidence of the establishment and formation of mixed biofilm in vitro, as well as in vivo on the corneal surface of mice in an experimentally induced S. aureus and F. falciforme mixed keratitis infection.

3.
J Interpers Violence ; : 886260519898423, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31994433

RESUMO

The aim of this study was to determine whether the experiences of direct or subtle forms of discrimination and violence are associated with mental health in Mexican gay, homosexual, and bisexual (GHB) men. A cross-sectional survey was conducted online; the sample consisted of 4,827 GHB men. Ten forms of overt and subtle sexual orientation-based discrimination and violence (SO-DV) were assessed. Linear and logistic regression models were used to evaluate the association between SO-DV experiences and mental health outcomes. Physical violence was reported less frequently than the other forms of SO-DV. As the number of settings in which SO-DV were experienced increased, a stronger association with negative mental health outcomes was observed. Experiences of subtle SO-DV were associated with increased distress, lower vitality, and increased risk of suicidal ideation. Disapproval of gender nonconformity was associated with negative mental health outcomes independently of violence based on sexual orientation. Subtle forms of SO-DV are more common than direct and overt forms. Both types of SO-DV could negatively affect mental health. Studies investigating these negative experiences are required to gain an understanding of the health inequalities faced by non-heterosexual populations.

4.
J Plant Physiol ; 246-247: 153114, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31958684

RESUMO

Aluminium (Al) water pollution is an increasing environmental problem and comprehensive analysis of toxic responses of aquatic primary producer organisms is imperative. We characterized the antioxidant response of Scenedesmus sp. microalga to Al-induced oxidative stress. After 72 h of exposure to Al (0, 10, and 100 µM) in a modified Bold Basal Medium (pH 5.0), we observed cell aggregation and alterations in the subcellular structure, strong lipid peroxidation and oxidative stress induction (detected with the fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate) in parallel with Al accumulation in cells. At the same time, Al toxicity caused depletion of important macronutrients like Ca, which is important for cell-wall structure. Analysis of antioxidant enzymatic activities in Al-treated Scenedesmus cells revealed that catalase, ascorbate peroxidase, as well as different isoforms of superoxide dismutase were inhibited especially at the highest Al dose (100 µM), cells that accumulated the highest concentration of Al. On the other hand, glutathione reductase activity increased at that Al concentration. Immunodetection after Western-blotting confirmed that only ascorbate peroxidase inhibition was apparently due to a decrease in enzyme levels. However, the inhibition of catalase and activation of glutathione reductase activities seemed related with post-translational modifications in protein function as protein expression decreased or increased, respectively under Al stress. Our results may help to understand toxic mechanisms triggered by Al in freshwater microalgae, which in turn could aid to select suitable biomarkers of Al contamination in aquatic ecosystems.

5.
Life Sci ; 245: 117348, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31981633

RESUMO

AIMS: Haloperidol is a neuroleptic drug with high affinity towards the σ1 receptor (σ1R), acting as antagonist that decreases neuropathic pain, but has CNS side effects. This work describes the design and synthesis of a novel analog N­(1­benzylpiperidin­4-yl)­4­fluorobenzamide (LMH-2), which produced antihyperalgesic and antiallodynic effects in rats with neuropathy induced by chronic constriction injury of the sciatic nerve (CCI), being more active than gabapentin (The most widely used drug for the treatment of neuropathic pain). MAIN METHODS: LMH-2 was designed as haloperidol analog. Its structure was characterized by spectroscopic (1H and 13C NMR) and spectrometric mass (electronic impact) techniques. Additionally, in silico predictions of pharmacokinetic, pharmacodynamic and toxicological properties were obtained, with promising results. A competitive binding assay using radioligands was employed to evaluate the in vitro affinity for σ1R, whereas in vivo antihyperalgesic and antiallodynic activities were investigated using Wistar rats with CCI. KEY FINDINGS: LMH-2 showed high affinity for σ1R in an in vitro binding assay, with a Ki = 6.0 nM and a high σ1R/σ2R selectivity ratio. Molecular docking studies were carried out to determine the binding energy and to analyze LMH-2-protein interactions. Through an in silico pharmacological consensus analysis, LMH-2 was considered safe for in vivo evaluation. Thus, LMH-2 had dose-dependent antiallodynic and antihyperalgesic activities; its efficacy was comparable to that of gabapentin, but its potency was 2-times higher than this drug. SIGNIFICANCE: LMH-2 administration produced antihyperalgesic and antiallodynic effects by the antagonism of σ1R, suggesting its potential use as an analgesic drug for neuropathic pain.

6.
Physiother Theory Pract ; 36(1): 241-248, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29873592

RESUMO

Background and purpose: Conservative therapies for complex regional pain syndrome (CRPS) have traditionally focused on exercise and desensitization techniques targeted at the involved extremity. The primary purpose of this case series is to report on the potential benefit of utilizing manual therapy to the lumbar spine in conjunction with traditional conservative care when treating patients with lower extremity CRPS.Case description: Two patients with the diagnosis of lower extremity CRPS were treated with manual therapy to the lumbar spine in conjunction with education, exercise, desensitization, and soft tissue techniques for the extremity.Outcomes: Patient 1 received 13 sessions over 6 weeks resulting in a 34-point improvement in oswestry disability index (ODI) and 35-point improvement in lower extremity functional scale (LEFS). Patient 2 received 21 sessions over 12 weeks resulting in a 28-point improvement in ODI and a 41-point improvement in LEFS.Discussion: Both patients exhibited reductions in pain and clinically meaningful improvements in function. Manual therapies when applied to the lumbar spine in these patients as part of a comprehensive treatment plan resulted in improved spinal mobility, decreased pain, and reduction is distal referred symptoms. Although one cannot infer a cause and effect relationship from a case series, this report identifies meaningful clinical outcomes potentially associated with manual physical therapy to the lumbar spine for two patients with complex regional pain syndrome type 1.

7.
Sci Total Environ ; 708: 134592, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31780144

RESUMO

Dry feed for dogs and cats sold in Europe are mostly formulated with cereals and cereal by-products, so the contamination of this food with mycotoxins represents a potential risk for these pets. We analyzed a representation of the best-selling feed brands in Spain. The presence of Aflatoxins (B1, B2, G1, and G2), Ochratoxin A, T-2 and HT-2 toxins, Deoxynivalenol, Zearalenone, and Fumonisins (B1 and B2) was quantified, using immunoaffinity columns and LC-MS/MS. In general, mycotoxins were frequently and simultaneously (6-11) detected, with AFB1, FB1, FB2, Deoxynivalenol, and HT-2 detected in 100% of the samples. However, the concentrations of most of them are among the lowest reported so far. Fumonisins were the exception since we report the highest concentrations to date, particularly in cat feed. We practically found no significant differences in the level of mycotoxin contamination in relation to the presumed quality of the feed. We also calculated the daily exposure, and evaluated the acute and chronic health risk posed by these feeds. None of the brands analyzed presented acute risk for any of the mycotoxins. However, the high levels of fumonisins found in some samples could become problematic, if there are hidden forms of them. This is also evident in relation to long-term risk, since in the case of fumonisins the level of exposure exceeds the tolerable daily intake level in 3.5 and 12 times, for dogs and cats respectively. The exposure levels to zearalenone and deoxynivalenol could also be of long-term concern, especially considering the possibility that the continuous exposure to several mycotoxins simultaneously might produce potentiated toxic effects as a result of their synergistic action. Further research on the potential adverse health effects deriving from chronic exposure to low doses of multi-mycotoxin mixtures in pets is needed.

8.
Pharmacoeconomics ; 38(1): 69-84, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31552601

RESUMO

BACKGROUND: Vedolizumab (VDZ) was approved by the Japanese Ministry of Health, Labor and Welfare in 2018 for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The comparative cost-effectiveness of VDZ compared with other biologics is unknown in Japan. This information could be useful for decision makers at the time of repricing biologics for the treatment of patients with moderate-to-severe UC. OBJECTIVE: The aim was to assess the cost-effectiveness of VDZ versus other branded biologics for the treatment of patients with moderate-to-severe UC who were anti-tumor necrosis factor (TNF)-naïve, from the Japanese public healthcare payer perspective. METHODS: A hybrid decision tree/Markov model was developed to predict the number of patients who achieved response and remission at the end of the induction phase and sustained it during the maintenance phase, translating this into quality-adjusted life-years (QALYs) and costs. Treatment-related adverse events, discontinuation and surgery, and their impact on QALYs and costs were also modeled. A systematic literature review and network meta-analysis were conducted to estimate the comparative efficacy of each treatment versus placebo. Rates of adverse events, surgery, surgery complications, and utilities were from the literature. Costs (2018 Japanese yen) were obtained from the Japanese National Health Insurance drug price list and medical fee table and local claims databases. Clinical and economic outcomes were projected over a lifetime and discounted at 2% annually. RESULTS: Over a lifetime, VDZ yielded greater QALYs and cost savings compared with golimumab and was cost-effective compared with adalimumab and infliximab (incremental cost-effectiveness ratios ¥4,821,940 and ¥4,687,692, respectively). Deterministic and probabilistic analyses supported the robustness of the findings in the base-case analysis, indicating that VDZ was either dominant or cost-effective in most scenarios and replications. The main limitations of this analysis include excluding tofacitinib and infliximab biosimilar as comparators, health-state utility estimates were obtained from population studies in the United Kingdom, and the impact of subsequent (i.e., second-line) biologic treatment was not evaluated. CONCLUSION: Our analysis suggests that VDZ is dominant or cost-effective compared with other branded biologics for the treatment of anti-TNF-naïve patients with moderate-to-severe UC in Japan.

9.
PLoS Negl Trop Dis ; 13(12): e0007919, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31790401

RESUMO

Current knowledge of the piRNA pathway is based mainly on studies on Drosophila melanogaster where three proteins of the Piwi subclade of the Argonaute family interact with PIWI-interacting RNAs to silence transposable elements in gonadal tissues. In mosquito species that transmit epidemic arboviruses such as dengue and chikungunya viruses, Piwi clade genes underwent expansion, are also expressed in the soma and cross-talk with proteins of recognized antiviral function cannot be excluded for some Piwi proteins. These observations underscore the importance of expanding our knowledge of the piRNA pathway beyond the model organism D. melanogaster. Here we focus on the emerging arboviral vector Aedes albopictus and we couple traditional approaches of expression and adaptive evolution analyses with most current computational predictions of protein structure to study evolutionary divergence among Piwi clade proteins. Superposition of protein homology models indicate possible high structure similarity among all Piwi proteins, with high levels of amino acid conservation in the inner regions devoted to RNA binding. On the contrary, solvent-exposed surfaces showed low conservation, with several sites under positive selection. Analysis of the expression profiles of Piwi transcripts during mosquito development and following infection with dengue serotype 1 or chikungunya viruses showed a concerted elicitation of all Piwi transcripts during viral dissemination of dengue viruses while maintenance of infection relied on expression of primarily Piwi5. Opposite, establishment of persistent infection by chikungunya virus is accompanied by increased expression of all Piwi genes, particularly Piwi4 and, again, Piwi5. Overall these results are consistent with functional specialization and a general antiviral role for Piwi5. Experimental evidences of sites under positive selection in Piwi1/3, Piwi4 and Piwi6, that have complex expression profiles, provide useful knowledge to design tailored functional experiments.

10.
Mutagenesis ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793639

RESUMO

Chagas disease, caused by the protozoan Trypanosoma cruzi, has increased in the world due to migration, travelling and climate change; at present, the principal problem is that common trypanocidal agents have resulted in toxic or inconvenient side effects. We tested for genotoxicity in the standard (ST) and high bioactivation (HB) crosses of Drosophila wing somatic mutation and recombination test, four novel trypanocidal agents derived from 2, 4, 6-triaminquinazoline (TAQ): 2,4-diamino-6 nitro-1,3 diazonaftalene (S-1QN2-1), 2,4-diacetamino-6-amino 1,3 diazonaftalene (D-1), N6-(4,methoxybenzyl)quinazoline-2,4,6-triamine (GHPM) and N6-[4-(trifluoromethoxy)benzyl]quinazoline-2,4,6-triamine (GHPMF) at 1.9, 3.9, 7.9 and 15 µM, respectively. Also, high-pressure liquid chromatography (HPLC) analysis was run to determine the remanence of either drug in flare, and Oregon R(R)-flare flies emerged from treated larvae. S-1QN2-1 showed genotoxicity only in the ST cross, increasing the small, large and total spot frequencies at all concentrations and twin spots only at 1.9 µM; D-1 and GHPM showed significant increments of large spots only at 15 µM in the ST cross; GHPMF was not genotoxic at any concentration or either cross. In the mwh clones accumulated distribution frequencies analysis, associated with disrupted cell division, S-1QN2-1 caused alterations in the ST cross at all concentrations but only at 15 µM in the HB cross; D-1 caused alterations at 3.9, 7.9 and 15 µM in the ST cross and at 1.9 and 15 µM in the HB cross; GHPM caused alterations at 7.9 and 15 µM in the ST cross and also at 1.9, 3.9 and 7.9 µM in the HB cross; GHPMF caused those alterations at all concentrations in the ST cross and at 1.9, 3.9 and 7.9 µM in the HB cross. The HPLC results indicated no traces of either agent in the flare and Oregon R(R)-flare flies. We conclude that S-1QN2-1 is clearly genotoxic, D-1 and GHPM have an unclear genotoxicity and GHPMF was not genotoxic; all quinazoline derivatives disrupted cell division. GHPMF is a good candidate to be tested in other genotoxicity and cytotoxic bioassays. The differences in the genotoxic activity of these trypanocidal agents are correlated with differences in their chemical structure.

11.
Chem Pharm Bull (Tokyo) ; 67(12): 1293-1300, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31787656

RESUMO

Based on our previous research on cysticidal drugs, we report the synthesis and evaluation of three new benzimidazole derivatives. In these compounds, the amido group was used as a bioisosteric replacement of the ester group. The molecular docking on ß-tubulin revealed that the derivatives interacted through hydrogen bonding with N165, E198 and V236. All compounds showed in vitro activity against Taenia crassiceps cysts. Among them, benzimidazole 3 was found to be the most potent of the series (EC50 0.86 µM). This compound also exhibited the highest probability of binding and the lowest binding free energy score and was therefore selected for in vivo evaluation. Results indicated that the efficacy of compound 3 was comparable to that of the reference drug, albendazole (50.39 vs. 47.16% parasite reduction). Animals treated with compound 3 seemed to tolerate this benzimidazole well, with no changes in behavior, or food and water consumption. These findings are consistent with the in silico prediction results, which indicated low toxicity risks. The pharmacokinetic study showed that the half-life and mean residence time (6.06 and 11.9 h, respectively) were long after oral administration. Together, these results indicate that this new benzimidazole derivative represents a promising structure with cysticidal activity.


Assuntos
Amebicidas/farmacologia , Benzimidazóis/farmacologia , Cisticercose/tratamento farmacológico , Simulação de Acoplamento Molecular , Taenia/efeitos dos fármacos , Amebicidas/síntese química , Amebicidas/química , Animais , Benzimidazóis/síntese química , Benzimidazóis/química , Relação Dose-Resposta a Droga , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Relação Estrutura-Atividade
12.
Animals (Basel) ; 9(12)2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31835365

RESUMO

Humic substances (HS) from different sources have been evaluated to replace or reduce the use of growth promoter antibiotics (GPA) in the feeds of broiler chickens. The objective was to evaluate the growth performance, tibia measurements, nutrient balance, meat quality, and microbiological status of broiler fed with an HS extract (EHS) under ad libitum (ADLIB) or feed restriction (REST). Individually caged broilers (n = 180, 14-35 day of age) were assigned to a factorial arrangement of three dietary treatments: (1) positive control with bacitracin methylene disalicylate (BMD) and salinomycin; (2) negative control without BMD nor salinomycin, and (3) same as negative control with 0.25% EHS, and two feeding regimens 1) ADLIB or REST for 24 h on d 1, 7, and 14. Results were subjected to ANOVA. Positive control and EHS-fed broilers showed higher carcass yield (p < 0.05) and lower oocyst excretion (p < 0.01) compared to negative control birds. Lactic acid bacteria (LAB) and Clostridium perfringens (C. perfringens) were higher in negative control and EHS-broilers compared to positive control (p < 0.01). In conclusion, higher carcass yield, lower C. perfringens and oocyst excretion were found in positive control and higher carcass yield, higher LAB and lower oocyst excretion were found in EHS-fed broilers. Broilers subjected to REST had reduced growth performance and meat quality. In conclusion, EHS could be used to increase the carcass yield and beneficial LAB in broilers.

13.
Clin Chem ; 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31811001

RESUMO

BACKGROUND: One of the objectives for the liquid biopsy is to become a surrogate to tissue biopsies in diagnosis of cancer as a minimally invasive method, with clinical utility in real-time follow-ups of patients. To achieve this goal, it is still necessary to achieve a better understanding of the mechanisms of cancer and the biological principles that govern its behavior, particularly with regard to circulating tumor cells (CTCs). CONTENT: The isolation, enumeration, detection, and characterization of CTCs have already proven to provide relevant clinical information about patient prognosis and treatment prediction. Moreover, CTCs can be analyzed at the genome, proteome, transcriptome, and secretome levels and can also be used for functional studies in in vitro and in vivo models. These features, taken together, have made CTCs a very valuable biosource. SUMMARY: To further advance the field and discover new clinical applications for CTCs, several studies have been performed to learn more about these cells and better understand the biology of metastasis. In this review, we describe the recent literature on the topic of liquid biopsy with particular focus on the biology of CTCs.

14.
Int J Environ Health Res ; : 1-14, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674203

RESUMO

Inorganic elements have been associated with brain tumours for long. The blood concentration of 47 elements was assessed by ICP-MS in 26 brain tumour patients and 21 healthy subjects from Bucharest (Romania). All 47 elements were detected in the brain tumour tissue, and 22 were detected in > 80% of samples; this implies that these elements can cross the blood-brain barrier. Median blood levels of cadmium, lead, and nickel were higher than the reference values (1.14, 53.3, and 2.53 ng/mL). Gadolinium and tantalum showed significantly higher concentrations among cases. We observed considerable differences and different profiles of the presence of inorganic elements between the tumour and non-tumour brain tissue and between tissue from the primary tumour and tissue from brain metastasis. Our data suggest that similar to heavy metals, other elements - commonly used in high tech devices and rare earth elements - can also influence brain tumour.

15.
Water Sci Technol ; 80(5): 911-919, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31746798

RESUMO

In this work, we describe the morphological, electronic and catalytic properties of support TiO2-CeO2-ZrO2, prepared by sol-gel method, which was impregnated with copper at 5 and 10% by weight, in order to obtain efficient catalysts in the catalytic wet air oxidation (CWAO) of 2-cp. The catalysts were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM-EDS), UV-Vis diffuse reflectance spectroscopy (DRS) and nitrogen physisorption by the Brunauer-Emmett-Teller (BET) method. The activity of the materials used in this study revealed that without the presence of Cu, the SCO2 is low and with a content of 10% this metal shows the best catalytic behaviour; conversely, a reaction mechanism is proposed that describes the complete oxidation of 2-cp in this case.


Assuntos
Clorofenóis , Cobre , Catálise , Oxirredução
16.
J Clin Med ; 8(10)2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31627485

RESUMO

In neurodegenerative diseases, microglia-mediated neuroinflammation and oxidative stress are central events. Recent genome-wide transcriptomic analyses of microglial cells under different disease conditions have uncovered a new subpopulation named disease-associated microglia (DAM). These studies have challenged the classical view of the microglia polarization state's proinflammatory M1 (classical activation) and immunosuppressive M2 (alternative activation). Molecular signatures of DAM and proinflammatory microglia (highly pro-oxidant) have shown clear differences, yet a partial overlapping gene profile is evident between both phenotypes. The switch activation of homeostatic microglia into reactive microglia relies on the selective activation of key surface receptors involved in the maintenance of brain homeostasis (a.k.a. pattern recognition receptors, PRRs). Two relevant PRRs are toll-like receptors (TLRs) and triggering receptors expressed on myeloid cells-2 (TREM2), whose selective activation is believed to generate either a proinflammatory or a DAM phenotype, respectively. However, the recent identification of endogenous disease-related ligands, which bind to and activate both TLRs and TREM2, anticipates the existence of rather complex microglia responses. Examples of potential endogenous dual ligands include amyloid ß, galectin-3, and apolipoprotein E. These pleiotropic ligands induce a microglia polarization that is more complicated than initially expected, suggesting the possibility that different microglia subtypes may coexist. This review highlights the main microglia polarization states under disease conditions and their leading role orchestrating oxidative stress.

17.
Metabolites ; 9(10)2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31569489

RESUMO

(1) Background: Disruption of insulin production by native or transplanted pancreatic islets caused by auto/allo-immunity leads to hyperglycemia, a serious health condition and important therapeutic challenge due to the lifelong need for exogeneous insulin administration. Early metabolic biomarkers can prompt timely interventions to preserve islet function, but reliable biomarkers are currently lacking. We explored the feasibility of "localized metabolomics" where initial biomarker discovery is made in aqueous humor samples for further validation in the circulation. (2) Methods: We conducted non-targeted metabolomic studies in parallel aqueous humor and plasma samples from diabetic and nondiabetic mice. Metabolite levels and associated pathways were compared in both compartments as well as to an earlier longitudinal dataset in hyperglycemia-progressor versus non-progressor non-obese diabetic (NOD) mice. (3) Results: We confirmed that aqueous humor samples can be used to assess metabolite levels. About half of the identified metabolites had well-correlated levels in the aqueous humor and plasma. Several plasma metabolites were significantly different between diabetic and nondiabetic animals and between males and females, and many of them were correlated with the aqueous humor. (4) Conclusions: This study provides proof-of-concept evidence that aqueous humor samples enriched with islet-related metabolites and representative of the immediate islet microenvironment following intraocular islet transplant can be used to assess metabolic changes that could otherwise be overlooked in the general circulation. The findings support localized metabolomics, with and without intraocular islet transplant, to identify biomarkers associated with diabetes and islet allograft rejection.

18.
Sensors (Basel) ; 19(19)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31554194

RESUMO

Microelectromechanical systems (MEMS) microphone sensors have significantly improved in the past years, while the readout electronic is mainly implemented using switched-capacitor technology. The development of new battery powered "always-on" applications increasingly requires a low power consumption. In this paper, we show a new readout circuit approach which is based on a mostly digital Sigma Delta ( Σ Δ ) analog-to-digital converter (ADC). The operating principle of the readout circuit consists of coupling the MEMS sensor to an impedance converter that modulates the frequency of a stacked-ring oscillator-a new voltage-controlled oscillator (VCO) circuit featuring a good trade-off between phase noise and power consumption. The frequency coded signal is then sampled and converted into a noise-shaped digital sequence by a time-to-digital converter (TDC). A time-efficient design methodology has been used to optimize the sensitivity of the oscillator combined with the phase noise induced by 1 / f and thermal noise. The circuit has been prototyped in a 130 nm CMOS process and directly bonded to a standard MEMS microphone. The proposed VCO-based analog-to-digital converter (VCO-ADC) has been characterized electrically and acoustically. The peak signal-to-noise and distortion ratio (SNDR) obtained from measurements is 77.9 dB-A and the dynamic range (DR) is 100 dB-A. The current consumption is 750 µ A at 1.8 V and the effective area is 0.12 mm 2 . This new readout circuit may represent an enabling advance for low-cost digital MEMS microphones.

19.
Health Promot Perspect ; 9(3): 198-206, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508340

RESUMO

Background: Guided by an ecological systems theory (EST) framework, the purpose of the present study was to investigate how multiple micro, mezzo, and macro factors influence the suicidality continuum from suicidal ideation to suicide attempt among Latinx LGB (lesbian, gay, and bisexual) youth living in the United States. Methods: Data for this cross sectional-study included 451 participants who self-identified as Latinx LGB on the 2017-National Youth Risk Behavioral Survey. The analysis explored micro, mezzo, and macro-level factors' association with three suicidality outcomes (ideation, planning, and attempt) at the bivariate and multivariate level. Since the outcome variables were dichotomized, univariate logistic regressions and backward elimination logistic regressions were used. Results: The most commonly reported suicidal behavior was ideation (n = 173; 40%), followed by planning (n = 150; 34%), and then attempt (n = 64; 21%). Findings from the backward elimination logistic regression on suicidal ideation suggest the best set of independent variables are being bullied at school (odds ratio [OR] = 2.81; CI: 1.61-4.89), experiencing sexual assault(OR = 2.32; CI: 1.32-4.07), experiencing depressive symptoms (OR = 1.99; CI: 1.07- 3.69),being cannabis use (OR = 1.76; CI: 1.08-2.89), and being female (OR = 1.72; CI: 1.01-2.93).For suicide planning the model suggested, experiencing depressive symptoms (OR = 3.21; CI:1.74-5.91), cannabis use (OR = 2.46; CI: 1.49-4.07), being bullied at school (OR = 2.04; CI:1.17-3.58), and experiencing sexual assault (OR = 1.88; CI: 1.07-3.31) exhibited the strongest relationships. Suicide attempt was significantly associated with cannabis use (OR = 3.12; CI:1.60-6.08), experiencing depression (OR= 2.89; CI: 1.30-6.43), experiencing sexual assault (OR = 2.77; CI: 1.34-5.71), and being bullied at school (OR = 2.34; CI: 1.12-4.91). Conclusion: Given the findings of this study, it is essential that tailored suicide prevention efforts be established that uniquely address the intersections of race/ethnicity and sexual orientation and how this intersection influences micro, mezzo, and macro factors associated with suicide ideation, planning, and attempt among Latinx LGB adolescents.

20.
Bol Med Hosp Infant Mex ; 76(5): 225-236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31536044

RESUMO

Background: Active commuting (walking or cycling) is associated with benefits to health; thus, it is required to identify factors that promote it. The objective of this study was to analyze the relationship between the transport modes used by Mexican pediatric population to commute to school with sociodemographic and socioeconomic individual characteristics and public insecurity at the state level. Methods: The frequency of transport modes used by schoolchildren and adolescents to commute to school (walking, cycling, private car and public transport) were estimated using the database of the Encuesta Intercensal 2015. In an ecological analysis (i.e., states as observation units) correlations with food insecurity, urbanization level, and violent deaths statistics at state-level were obtained. Results: The most frequent transportation mode was walking (66.2%), followed by car (16.2%) and public transportation (15.3%). Active commuting (walking or cycling) was more frequent in males, schoolchildren, low socioeconomic status, living in rural or southern areas and those who spent <15 min to commute. Passive commute was more frequent among females, adolescents, high socioeconomic status, and living in urban areas. In the more urbanized states, active transportation was less frequent, but motorized transportation was more prevalent. Public insecurity was negatively related to cycling. Conclusions: Maintaining or increasing active commuting among Mexican pediatric population is necessary through public policies aimed to improve physical and social environment.

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