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1.
Dev Dyn ; 253(4): 423-434, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37850829

RESUMO

BACKGROUND: Wnt/ß-catenin signaling plays a variety of roles in both the dental epithelium and mesenchyme at most stages of tooth development. In this study, we verified the roles of Hertwig's epithelial root sheath (HERS) breakdown in tooth root development. This breakdown results in formation of epithelial cell rests of Malassez (ERM). RESULTS: Following induction of ß-catenin stabilization in the epithelium of developing tooth at the moment of HERS breakdown, HERS failed to break down for ERM formation. HERS with stabilized ß-catenin was altered into a multicellular layer enveloping elongated root dentin with higher expression of junctional proteins such as Zo-1 and E-cadherin. Importantly, this impairment of HERS breakdown led to arrest of further root elongation. In addition, the portion of root dentin enveloped by the undissociated HERS remained in a hypomineralized state. The odontoblasts showed ectopically higher expression of pyrophosphate regulators including Ank and Npp1, whereas Tnap expression was unchanged. CONCLUSIONS: Our data suggest that Wnt/ß-catenin signaling is decreased in HERS for ERM formation during root development. Furthermore, ERM formation is important for further elongation and dentin mineralization of the tooth roots. These findings may provide new insight to understand the contribution of ERM to root formation.


Assuntos
Raiz Dentária , beta Catenina , beta Catenina/genética , beta Catenina/metabolismo , Células Epiteliais/metabolismo , Epitélio/metabolismo , Odontogênese , Diferenciação Celular
2.
J Cell Physiol ; 238(2): 447-458, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36598878

RESUMO

Cementum has been empirically regarded as an antiresorptive barrier against tooth roots. However, little is known about the factors of homeostasis and resistant mechanisms of tooth roots against resorption. Here, we investigated cementum factors and their interaction against resorption using transgenic mice exhibiting external cervical root resorption (ECRR). Ectopically thickened cervical cementum caused by functional inactivation of ectonucleotide pyrophosphotase/phosphodiesterase 1 (Enpp1) was susceptible to ECRR with aging. In addition, the inactivation of the suppressor of fused (Sufu), a Hedgehog signaling inhibitor, in cementoblasts led to ECRR. Interestingly, concurrent inactivation of Sufu and Enpp1 in cementoblasts remarkably exacerbated ECRR with higher Rankl expression. Cellular and molecular analyses using cementoblasts and bone marrow-derived macrophages indicated that Dickkopf-related protein 1 (Dkk1) induced by the inactivation of Sufu in cementoblasts has roles in the acceleration of ECRR triggered by Enpp1 inactivation. Using compound mutant mice for concurrent Wntless and Enpp1 inactivation, this synergistic cooperation of Dkk1 and Npp1 for resorption found in double mutant Sufu and Enpp1 mice was confirmed by the reproduction of amplified ECRR. On the basis of these findings, we conclude that proper Npp1 function and sustained Wnt activity in the cervical cementum are essential for the homeostasis of tooth roots against resorption in a physiological state.


Assuntos
Cemento Dentário , Reabsorção da Raiz , Camundongos , Animais , Proteínas Hedgehog , Camundongos Transgênicos , Transdução de Sinais , Proteínas Repressoras
3.
Mar Drugs ; 21(9)2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37755082

RESUMO

The protein extract of Ulva australis hydrolyzed with Alcalase and Flavourzyme was found to have multi-functional properties, including total antioxidant capacity (TAC), collagenase inhibitory, and antibacterial activities. The #5 fraction (SP5) and #7 fraction (SP7) of U. australis hydrolysate from cation-exchange chromatography displayed significantly high TAC, collagenase inhibitory, and antibacterial effects against Propionibacterium acnes, and only the Q3 fraction from anion-exchange chromatography displayed high multi-functional activities. Eight of 42 peptides identified by MALDI-TOF/MS and Q-TOF/MS/MS were selected from the results for screening with molecular docking on target proteins and were then synthesized. Thr-Gly-Thr-Trp (TGTW) displayed ABTS [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] radical scavenging activity. The effect of TAC as Trolox equivalence was dependent on the concentration of TGTW. Asn-Arg-Asp-Tyr (NRDY) and Arg-Asp-Arg-Phe (RDRF) exhibited collagenase inhibitory activity, which increased according to the increase in concentration, and their IC50 values were 0.95 mM and 0.84 mM, respectively. Peptides RDRF and His-Ala-Val-Tyr (HAVY) displayed anti-P. Acnes effects, with IC50 values of 8.57 mM and 13.23 mM, respectively. These results suggest that the U. australis hydrolysate could be a resource for the application of effective nutraceuticals and cosmetics.

4.
J Cell Physiol ; 236(7): 5387-5398, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33377198

RESUMO

ß-catenin, a key mediator of Wnt signaling, plays multiple roles in tooth development. However, the role of ß-catenin in Hertwig's epithelial root sheath (HERS) during root formation remains unclear. In this study, we generated inducible tissue-specific ß-catenin conditional knockout mice (Ctnnb1i∆shh ) to investigate how ß-catenin in HERS affects tooth root development. The inactivation of ß-catenin in HERS led to interrupted root elongation due to premature disruption of HERS. This phenotype was accompanied by reduced cell-cell adhesion and decreased expression of junctional proteins, as well as increased epithelial-to-mesenchymal transition of HERS cells upon ß-catenin depletion. Accordingly, stabilization of ß-catenin in HERS (Catnbi∆shh ) led to the formation of unfragmented HERS and resulted in the failure of HERS dissociation, with increased expression of junctional proteins. Our results suggest that fine control of ß-catenin is important for HERS to guide root formation through regulating its structural integrity.


Assuntos
Células Epiteliais/metabolismo , Odontogênese/fisiologia , Raiz Dentária/crescimento & desenvolvimento , Raiz Dentária/metabolismo , beta Catenina/metabolismo , Animais , Camundongos , Camundongos Knockout
5.
J Cosmet Sci ; 71(2): 65-76, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271709

RESUMO

Five-aminolevulinic acid (5-ALA)-photodynamic therapy combined with infrared radiation is an effective and safe therapy for facial acne. Although there are various available agents for treating acne, therapies for resistant or severe strains have been limited. The aim of this study was to investigate the inhibitory efficacy of ALACELL synthesized by combining 5-ALA with Y-G-G-F-L peptide against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Yersinia enterocolitica, as well as Cutibacterium acnes. Furthermore, other effects of ALACELL on human skin cells, melanin formation, intracellular tyrosinase activity, and Ultra Violet B (UVB)-irradiated cell death were measured by treatment of ALACELL in vitro. ALACELL particularly showed a growth inhibitory effect on C. acnes and no inhibitory effect on the four bacteria strains. ALACELL reduced melanin formation and intracellular tyrosinase activity by α-melanin cell-stimulating hormone (α-MSH) in B16F10 cells, with no cytotoxicity. ALACELL also improved cell viability in UVB-irradiated HaCaT cells. The results of the experiment show that ALACELL exhibits more efficacy than 5-ALA against antimicrobial activity, melanin formation, intracellular tyrosinase activity, and UVB-irradiated cell death. Therefore, ALACELL is recommended as a candidate for clinical application in the treatment of acne and skin aging and will be further investigated to study the mode of action and in actual situations.


Assuntos
Raios Ultravioleta , Ácido Aminolevulínico , Humanos , Melaninas , Monofenol Mono-Oxigenase
6.
Am J Hum Genet ; 99(5): 1199-1205, 2016 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-27843125

RESUMO

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders affecting tooth enamel. The affected enamel can be hypoplastic and/or hypomineralized. In this study, we identified ACPT (testicular acid phosphatase) biallelic mutations causing non-syndromic, generalized hypoplastic autosomal-recessive amelogenesis imperfecta (AI) in individuals from six apparently unrelated Turkish families. Families 1, 4, and 5 were affected by the homozygous ACPT mutation c.713C>T (p.Ser238Leu), family 2 by the homozygous ACPT mutation c.331C>T (p.Arg111Cys), family 3 by the homozygous ACPT mutation c.226C>T (p.Arg76Cys), and family 6 by the compound heterozygous ACPT mutations c.382G>C (p.Ala128Pro) and 397G>A (p.Glu133Lys). Analysis of the ACPT crystal structure suggests that these mutations damaged the activity of ACPT by altering the sizes and charges of key amino acid side chains, limiting accessibility of the catalytic core, and interfering with homodimerization. Immunohistochemical analysis confirmed localization of ACPT in secretory-stage ameloblasts. The study results provide evidence for the crucial function of ACPT during amelogenesis.


Assuntos
Fosfatase Ácida/genética , Amelogênese Imperfeita/genética , Proteínas do Esmalte Dentário/genética , Genes Recessivos , Mutação , Fosfatase Ácida/metabolismo , Amelogênese Imperfeita/diagnóstico , Criança , Esmalte Dentário/anormalidades , Proteínas do Esmalte Dentário/metabolismo , Éxons , Feminino , Homozigoto , Humanos , Masculino , Linhagem , Conformação Proteica , Alinhamento de Sequência , Turquia
7.
Biosci Biotechnol Biochem ; 83(7): 1197-1204, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30999820

RESUMO

In this study, skin cream containing ziyuglycoside I isolated from Sanguisorba officinalis was manufactured and examined the protective effects of the skin cream against UVB-induced hairless mice. UVB-induced hairless mice were topically treated with the skin cream once a day for 5 weeks. Application of the skin cream did not exhibit side effect on body growth showing normal body weight and food efficiency in the mice. The skin cream treatment also was inhibited mRNA expression of interleukin (IL)-1ß, matrix metalloproteinase (MMP)-2, MMP-9, and MMP-2 protein expression in the mice. Furthermore, the skin cream treatment inhibits epidermal wrinkle formation, wrinkle depth, wrinkle thickness, and collagen degradation in UVB-induced hairless mice. Therefore, the skin cream was able to play a role in the attenuation of photoaging caused by UVB irradiation via downregulation of mRNA expression of inflammatory cytokine IL-1ß, MMP-2, MMP-9, and suppression of MMP-2 proteins expression.


Assuntos
Sanguisorba/química , Saponinas/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Creme para a Pele/farmacologia , Raios Ultravioleta , Animais , Peso Corporal/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Interleucina-1beta/genética , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Camundongos , Camundongos Pelados , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
8.
Ann Behav Med ; 52(4): 309-318, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30084896

RESUMO

Background: Greater purpose in life is associated with lower rates of certain chronic diseases. Whether purpose in life can protect against development of prediabetes or type 2 diabetes is unknown. Purpose: To examine the association between purpose in life and blood glucose control among adults ≥50 years. Methods: We conducted a longitudinal cohort study of 3,907 participants of the Health and Retirement Study who at baseline did not have type 2 diabetes or prediabetes. Baseline purpose in life was measured using the Ryff and Keyes' Scales of Psychological Well-Being and grouped into tertiles (high, medium, and low). We used multivariable linear regression to examine the association between baseline purpose in life and HbA1c over 4 years. Multivariable logistic regression was used to examine the association between baseline purpose and incident prediabetes or type 2 diabetes over the same period. Results: After adjusting for sociodemographic factors, body mass index, physical activity, and physical and mental health factors, HbA1c was 0.07 percentage points lower among participants with high purpose than those with low purpose (95% confidence interval [CI] -0.12 to -0.02; p = .011). Participants with high purpose had lower odds of developing prediabetes or type 2 diabetes than those with low purpose (adjusted odds ratio 0.78; 95% CI 0.62 to 0.98; p = .037). Conclusions: Among older adults, greater purpose in life is associated with a lower incidence of prediabetes or type 2 diabetes. Strategies to promote greater purpose in life should be tested as a part of type 2 diabetes prevention efforts.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobinas Glicadas , Satisfação Pessoal , Estado Pré-Diabético/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/sangue , Feminino , Inquéritos Epidemiológicos , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estados Unidos/epidemiologia
9.
Ann Emerg Med ; 71(6): 746-754.e2, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28789804

RESUMO

STUDY OBJECTIVE: We characterize hospital admissions among older adults for any cause in the 30 days after a significant natural disaster in the United States. The main outcome was all-cause hospital admissions in the 30 days after natural disaster. Separate analyses were conducted to examine all-cause hospital admissions excluding the 72 hours after the disaster, ICU admissions, all-cause inhospital mortality, and admissions by state. METHODS: A self-controlled case series analysis using the 2011 Medicare Provider and Analysis Review was conducted to examine exposure to natural disaster by elderly adults located in zip codes affected by tornadoes during the 2011 southeastern superstorm. Spatial data of tornado events were obtained from the National Oceanic and Atmospheric Administration's Severe Report database, and zip code data were obtained from the US Census Bureau. RESULTS: All-cause hospital admissions increased by 4% for older adults in the 30 days after the April 27, 2011, tornadoes (incidence rate ratio 1.04; 95% confidence interval 1.01 to 1.07). When the first 3 days after the disaster that may have been attributed to immediate injuries were excluded, hospitalizations for any cause also remained higher than when compared with the other 11 months of the year (incidence rate ratio 1.04; 95% confidence interval 1.01 to 1.07). There was no increase in ICU admissions or inhospital mortality associated with the natural disaster. When data were examined by individual states, Alabama, which had the highest number of persons affected, had a 9% increase in both hospitalizations and ICU admissions. CONCLUSION: When all time-invariant characteristics were controlled for, this natural disaster was associated with a significant increase in all-cause hospitalizations. This analysis quantifies acute care use after disasters through examining all-cause hospitalizations and represents an important contribution to building models of resilience-the ability to recover from a disaster-and hospital surge capacity.


Assuntos
Hospitalização/estatística & dados numéricos , Desastres Naturais , Tornados , Idoso , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Estudos Retrospectivos , Sudeste dos Estados Unidos/epidemiologia , Tempo para o Tratamento
10.
Phytother Res ; 32(12): 2475-2479, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30187587

RESUMO

This study aimed to investigate in vitro the anti-influenza B/Lee/40 virus effect of sakuranetin and mode of its action. The sakuranetin exhibited potent antiviral activity against influenza B/Lee/40 virus, reducing the formation of a visible cytopathic effect, with a 50% inhibitory concentration (IC50 ) of 7.21 µg/ml and no cytotoxicity at a concentration of 100 µg/ml, and the derived therapeutic index (TI) was >13.87. Oseltamivir showed weak anti-influenza B/Lee/40 virus activity with IC50 of 80.74 µg/ml, 50% cytotoxicity concentration of >100 µg/ml, and TI of >1.24. Sakuranetin also showed effective inhibitory effects when added at the viral attachment, entry, and postentry steps. Moreover, sakuranetin effectively inactivated influenza B/Lee/40 virus infection in dose- and temperature-dependent manners. Sakuranetin indicated an inhibitory effect in viral RNA synthesis in the presence of 100 µg/ml of sakuranetin. Overall, this research revealed that sakuranetin could inhibit influenza B/Lee/40 virus replication and that sakuranetin may be involved in the virus attachment, entry, and postentry. Therefore, sakuranetin is a good candidate for a chemopreventive agent for influenza virus-related diseases.


Assuntos
Flavonoides/farmacologia , Vírus da Influenza B/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/farmacologia , Cães , Vírus da Influenza B/fisiologia , Concentração Inibidora 50 , Células Madin Darby de Rim Canino , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/virologia , Transdução de Sinais/efeitos dos fármacos
11.
Am J Public Health ; 107(5): 807-811, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28323472

RESUMO

OBJECTIVES: To estimate health insurance and health care utilization patterns among previously incarcerated men following implementation of the Affordable Care Act's (ACA's) Medicaid expansion and Marketplace plans in 2014. METHODS: We performed serial cross-sectional analyses using data from the National Survey of Family Growth between 2008 and 2015. Our sample included men aged 18 to 44 years with (n = 3476) and without (n = 8702) a history of incarceration. RESULTS: Uninsurance declined significantly among previously incarcerated men after ACA implementation (-5.9 percentage points; 95% confidence interval [CI] = -11.5, -0.4), primarily because of an increase in private insurance (6.8 percentage points; 95% CI = 0.1, 13.3). Previously incarcerated men accounted for a large proportion of the remaining uninsured (38.6%) in 2014 to 2015. Following ACA implementation, previously incarcerated men continued to be significantly less likely to report a regular source of primary care and more likely to report emergency department use than were never-incarcerated peers. CONCLUSIONS: Health insurance coverage improved among previously incarcerated men following ACA implementation. However, these men account for a substantial proportion of the remaining uninsured. Previously incarcerated men continue to lack primary care and frequently utilize acute care services.


Assuntos
Cobertura do Seguro/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde , Patient Protection and Affordable Care Act , Prisioneiros , Adolescente , Adulto , Estudos Transversais , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Medicaid/estatística & dados numéricos , Estados Unidos
12.
Ann Emerg Med ; 70(3): 288-299.e2, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28757228

RESUMO

STUDY OBJECTIVE: We undertake this study to understand patterns of pediatric asthma-related acute care use to inform interventions aimed at reducing potentially avoidable hospitalizations. METHODS: Hospital claims data from 3 Camden city facilities for 2010 to 2014 were used to perform cluster analysis classifying patients aged 0 to 17 years according to their asthma-related hospital use. Clusters were based on 2 variables: asthma-related ED visits and hospitalizations. Demographics and a number of sociobehavioral and use characteristics were compared across clusters. RESULTS: Children who met the criteria (3,170) were included in the analysis. An examination of a scree plot showing the decline in within-cluster heterogeneity as the number of clusters increased confirmed that clusters of pediatric asthma patients according to hospital use exist in the data. Five clusters of patients with distinct asthma-related acute care use patterns were observed. Cluster 1 (62% of patients) showed the lowest rates of acute care use. These patients were least likely to have a mental health-related diagnosis, were less likely to have visited multiple facilities, and had no hospitalizations for asthma. Cluster 2 (19% of patients) had a low number of asthma ED visits and onetime hospitalization. Cluster 3 (11% of patients) had a high number of ED visits and low hospitalization rates, and the highest rates of multiple facility use. Cluster 4 (7% of patients) had moderate ED use for both asthma and other illnesses, and high rates of asthma hospitalizations; nearly one quarter received care at all facilities, and 1 in 10 had a mental health diagnosis. Cluster 5 (1% of patients) had extreme rates of acute care use. CONCLUSION: Differences observed between groups across multiple sociobehavioral factors suggest these clusters may represent children who differ along multiple dimensions, in addition to patterns of service use, with implications for tailored interventions.


Assuntos
Antiasmáticos/uso terapêutico , Asma/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Educação em Saúde/organização & administração , Hospitalização/estatística & dados numéricos , Pais/educação , Doença Aguda , Adolescente , Asma/terapia , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , New Jersey/epidemiologia , Fatores de Risco , Meio Social , Fatores Socioeconômicos , População Urbana
13.
Cell Tissue Res ; 364(1): 95-103, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26547858

RESUMO

Odontoblasts differentiate from dental mesenchyme during dentin formation and mineralization. However, the molecular mechanisms controlling odontoblast differentiation remain poorly understood. Here, we show that expression of testicular acid phosphatase (ACPT) is restricted in the early stage of odontoblast differentiation in proliferating dental mesenchymal cells and secretory odontoblasts. ACPT is expressed earlier than tissue-nonspecific alkaline phosphatase (TNAP) and partly overlaps with TNAP in differentiating odontoblasts. In MDPC-23 odontoblastic cells, expression of ACPT appears simultaneously with a decrease in ß-catenin activity and is abolished with the expression of Phex and Dsp. Knockdown of ACPT in MDPC-23 cells stimulates cell proliferation together with an increase in active ß-catenin and cyclin D1. In contrast, the overexpression of ACPT suppresses cell proliferation with a decrease in active ß-catenin and cyclin D1. Expression of TNAP, Osx, Phex and Dsp is reduced by knockdown of ACPT but is enhanced by ACPT overexpression. When ACPT is blocked with IgG, alkaline phosphatase activity is inhibited but cell proliferation is unchanged regardless of ACPT expression. These findings suggest that ACPT inhibits cell proliferation through ß-catenin-mediated signaling in dental mesenchyme but elicits odontoblast differentiation and mineralization by supplying phosphate during dentin formation. Thus, ACPT might be a novel candidate for inducing odontoblast differentiation and mineralization for dentin regeneration.


Assuntos
Fosfatase Ácida/biossíntese , Calcificação Fisiológica/fisiologia , Diferenciação Celular/fisiologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Odontoblastos/enzimologia , Fosfatase Ácida/genética , Animais , Antígenos de Diferenciação/biossíntese , Antígenos de Diferenciação/genética , Linhagem Celular , Técnicas de Silenciamento de Genes , Masculino , Camundongos , Odontoblastos/citologia
15.
Am J Public Health ; 106(10): 1872-8, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27552280

RESUMO

OBJECTIVES: To describe, and provide a nomenclature and taxonomy for classifying, the economic sectors and functional assets that could be mobilized as partners in an intersectoral health system. METHODS: MAPSCorps (Meaningful, Active, Productive Science in Service to Community) employed local youths to conduct a census of all operating assets (businesses and organizations) on the South Side of Chicago, Illinois, in 2012. We classified assets by primary function into sectors and described asset and sector distribution and density per 100 000 population. We compared empirical findings with the Institute of Medicine's (IOM's) conceptual representation and description of intersectoral health system partners. RESULTS: Fifty-four youths mapped a 62-square-mile region over 6 weeks; we classified 8376 assets into 23 sectors. Sectors with the most assets were food (n = 1214; 230/100 000 population), trade services (n = 1113; 211/100 000), and religious worship (n = 974;185/100 000). Several large, health-relevant sectors (2499 assets) were identified in the region but not specified in the IOM's representation. Governmental public health, central to the IOM concept, had no physical presence in the region. CONCLUSIONS: Local youths identified several thousand assets across a broad diversity of sectors that could partner in an intersectoral health system. Empirically informed iteration of the IOM concept will facilitate local translation and propagation.


Assuntos
Planejamento de Cidades , Comércio/estatística & dados numéricos , Características de Residência , Saúde da População Urbana , Censos , Chicago , Coleta de Dados/métodos , Atenção à Saúde , Humanos
16.
Acta Crystallogr D Biol Crystallogr ; 71(Pt 10): 2054-65, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26457429

RESUMO

The selection of correct metal ions with high fidelity against competing cellular cations is crucial for the function of many metalloenzymes; however, the understanding of the principles that govern metal selectivity is still incomplete. In this study, the crystal structure of the Tm1162 protein from Thermotoga maritima, a metallo-ß-lactamase, is reported. Several crystal structures of wild-type Tm1162 and its mutants were solved. Homologues of Tm1162 are widely distributed in bacteria and archaea, including several human pathogens. The monomer possesses an αß/ßα fold, with the core ß-strands having the ß-sheet sandwich structure common to the metallo-ß-lactamase superfamily. Tm1162 exists as a trimer in the crystal and this trimeric unit is likely to be present in solution. In the trimer, three active sites reside at the interface between subunits, suggesting that the oligomeric assembly is crucial for catalysis. A new type of structurally encoded heterodinuclear site has been identified by confirming the identity of nickel-containing heteronuclear sites in Tm1162 via X-ray absorption spectroscopy and anomalous difference Fourier maps. The second coordination sphere, including His8 and Glu73, maintains the side-chain orientations of histidines and stabilizes the metal-binding site. Nickel coordination was crucial for the oligomerization of Tm1162. The nickel-dependent and manganese-dependent ß-lactamase and phosphodiesterase activities of Tm1162 have also been characterized.


Assuntos
Níquel/química , Thermotoga maritima/enzimologia , beta-Lactamases/química , Sequência de Aminoácidos , Sítios de Ligação , Cristalografia por Raios X , Modelos Moleculares , Dados de Sequência Molecular , Níquel/metabolismo , Alinhamento de Sequência , Thermotoga maritima/química , Thermotoga maritima/metabolismo , Espectroscopia por Absorção de Raios X , beta-Lactamases/metabolismo
17.
Clin Orthop Relat Res ; 473(8): 2479-86, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25518806

RESUMO

BACKGROUND: Available studies disagree regarding the influence of patient sex on mortality and complications after spine surgery. We sought to conduct a systematic review and pool the results of existing research to better understand this issue. QUESTIONS/PURPOSES: We performed a systematic review to address two questions: (1) Does sex (male versus female) influence mortality after spine surgery? (2) Does sex impact the development of postoperative complications after spine surgery? METHODS: This systematic review was performed through a query of PubMed using a structured search algorithm. Additional queries of Embase, SCOPUS, Web of Science, and the tables of contents of orthopaedic and neurosurgical journals were also conducted using search terms such as "sex factors", "male or female", "risk factors", and "spine surgery". Selected papers were independently abstracted by three of the authors (AJS, ENR, EIW) and pooling was performed. Our literature search returned 720 studies, of which 99 underwent full review. Of these, 50 were selected for final abstraction. The Cochrane Q test was used to assess study heterogeneity; significant study heterogeneity was present and so a random-effects model was used. A Harbord test was used to evaluate for the presence of publication bias; this analysis found no statistically significant evidence of publication bias. RESULTS: Males were at increased odds of mortality after spine surgery (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.35-1.97; p<0.001). No differences between the sexes were identified for the odds of complications (OR, 1.04; 95% CI, 0.95-1.13; p=0.42). CONCLUSIONS: Our results determined that males were at elevated odds of mortality but not of complications after spine surgery. These results should be used to inform preoperative discussion and decision-making at the time of surgical consent. Future work should be directed at determining the underlying factors responsible for increased mortality among males and prospective studies specifically designed to evaluate sex-based differences in outcomes after spine surgery. LEVEL OF EVIDENCE: Level III, therapeutic study.


Assuntos
Disparidades nos Níveis de Saúde , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/mortalidade , Complicações Pós-Operatórias/mortalidade , Coluna Vertebral/cirurgia , Feminino , Humanos , Masculino , Razão de Chances , Medição de Risco , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento
18.
Matern Child Health J ; 19(6): 1354-63, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25430802

RESUMO

To compare the association between neighborhood Latino immigrant concentration and infant mortality by maternal nativity among singleton births to Mexican-origin women in Los Angeles County. Information about births, infant deaths, and infant and maternal characteristics were obtained from geocoded Los Angeles County vital statistics records (2002-2005). Linked data on neighborhood characteristics (census tracts) were obtained from the 2000 census. Logistic regression models were used to predict infant mortality while accounting for spatial clustering by census tract. Two-thirds of births to Mexican-origin mothers were to foreign-born women. Foreign-born mothers were older, had less education, and were more likely to have delivery costs paid by Medicaid than US-born mothers. Infants born to foreign-born women had a lower infant mortality rates than infants born to US-born women (3.8/1,000 live births vs. 4.6, p = .002). Among infants of foreign-born mothers, the odds of infant mortality increased with increasing immigrant concentration (OR 1.29; 95 % CI 1.01-1.66). There was a similar pattern of association between immigrant concentration and mortality for infants of US-born mothers (OR 1.29; 95 % CI 0.99-1.67). In Los Angeles County, the odds of infant mortality among foreign-born Mexican-origin Latina were higher in higher-density immigrant neighborhoods, with a similar trend among US-born mothers. Thus, living in immigrant enclaves likely does not help to explain the lower than expected infant mortality rate among infants born to Latina women. Instead, higher neighborhood Latino immigrant concentration may indicate a neighborhood with characteristics that negatively impact maternal and infant health for Latinos.


Assuntos
Emigrantes e Imigrantes/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Mortalidade Infantil/etnologia , Americanos Mexicanos/estatística & dados numéricos , Características de Residência/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Escolaridade , Feminino , Humanos , Lactente , Modelos Logísticos , Los Angeles/epidemiologia , Adulto Jovem
19.
Ann Intern Med ; 161(10 Suppl): S13-22, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25402398

RESUMO

BACKGROUND: Health care centers serving low-income communities have scarce resources to support medication decision making among patients with poorly controlled diabetes. OBJECTIVE: To compare outcomes between community health worker use of a tailored, interactive, Web-based, tablet computer-delivered tool (iDecide) and use of print educational materials. DESIGN: Randomized, 2-group trial conducted from 2011 to 2013 (ClinicalTrials.gov: NCT01427660). SETTING: Community health center in Detroit, Michigan, serving a Latino and African American low-income population. PARTICIPANTS: 188 adults with a hemoglobin A1c value greater than 7.5% (55%) or those who reported questions, concerns, or difficulty taking diabetes medications. INTERVENTION: Participants were randomly assigned to receive a 1- to 2-hour session with a community health worker who used iDecide or printed educational materials and 2 follow-up calls. MEASUREMENTS: Primary outcomes were changes in knowledge about antihyperglycemic medications, patient-reported medication decisional conflict, and satisfaction with antihyperglycemic medication information. Also examined were changes in diabetes distress, self-efficacy, medication adherence, and hemoglobin A1c values. RESULTS: Ninety-four percent of participants completed 3-month follow-up. Both groups improved across most measures. iDecide participants reported greater improvements in satisfaction with medication information (helpfulness, P = 0.007; clarity, P = 0.03) and in diabetes distress compared with the print materials group (P < 0.001). The other outcomes did not differ between the groups. LIMITATIONS: The study was conducted at 1 health center during a short period. The community health workers were experienced in behavioral counseling, thereby possibly mitigating the need for additional support tools. CONCLUSION: Most outcomes were similarly improved among participants receiving both types of decision-making support for diabetes medication. Longer-term evaluations are necessary to determine whether the greater improvements in satisfaction with medication information and diabetes distress achieved in the iDecide group at 3 months translate into better longer-term diabetes outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality and National Institute of Diabetes and Digestive and Kidney Diseases.


Assuntos
Negro ou Afro-Americano/psicologia , Agentes Comunitários de Saúde , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hispânico ou Latino/psicologia , Hipoglicemiantes/uso terapêutico , Educação de Pacientes como Assunto/métodos , Participação do Paciente/métodos , Adulto , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Feminino , Hemoglobinas Glicadas/análise , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Folhetos , Pobreza , Telemedicina
20.
J Cardiovasc Nurs ; 30(4 Suppl 1): S35-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24978160

RESUMO

BACKGROUND: Many programs for patients with heart failure (HF) fail to improve clinical outcomes in part because of low rates of patient enrollment and engagement. A better understanding of patient characteristics associated with willingness to enroll and then engage in HF self-management programs will improve the design and targeting of programs. METHODS AND RESULTS: Analyses of screening, baseline, and engagement data from a randomized controlled effectiveness trial of an HF peer self-management support program were conducted. The median age of the 266 recently hospitalized HF patients who enrolled in the study was 69 years, 51% were female, and 26% were minorities (primarily African American). Of 135 randomized to the peer support intervention, only 39% engaged in either the group sessions or telephone peer support calls. Older white women who reported higher baseline health status, functioning, social support, and confidence in their ability to manage and less difficulty with the physical and emotional aspects of living with HF were the most likely to engage in program activities. Minority status and reporting a need for social support were both correlated with higher enrollment but lower engagement in the intervention. CONCLUSIONS: Although minority patients with poorer reported health status and social support were most likely to consent to participate in the study, participants who engaged in program activities were more likely to have higher baseline health status, functioning, and social support. Developing HF interventions that successfully engage participants most in need of HF self-management support remains a difficult challenge.


Assuntos
Insuficiência Cardíaca/terapia , Participação do Paciente , Grupo Associado , Autocuidado , Idoso , Feminino , Humanos , Masculino , Apoio Social
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