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1.
Chem Rev ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959423

RESUMO

In recent years, powerful genetic code reprogramming methods have emerged that allow new functional components to be embedded into proteins as noncanonical amino acid (ncAA) side chains. In this review, we will illustrate how the availability of an expanded set of amino acid building blocks has opened a wealth of new opportunities in enzymology and biocatalysis research. Genetic code reprogramming has provided new insights into enzyme mechanisms by allowing introduction of new spectroscopic probes and the targeted replacement of individual atoms or functional groups. NcAAs have also been used to develop engineered biocatalysts with improved activity, selectivity, and stability, as well as enzymes with artificial regulatory elements that are responsive to external stimuli. Perhaps most ambitiously, the combination of genetic code reprogramming and laboratory evolution has given rise to new classes of enzymes that use ncAAs as key catalytic elements. With the framework for developing ncAA-containing biocatalysts now firmly established, we are optimistic that genetic code reprogramming will become a progressively more powerful tool in the armory of enzyme designers and engineers in the coming years.

2.
J Adolesc Health ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38878049

RESUMO

PURPOSE: Cross-sectional studies in adults have demonstrated associations between early life adversity (ELA) and reduced hippocampal volume, but the timing of these effects is not clear. The present study sought to examine whether ELA predicts changes in hippocampal volume over time in a large sample of early adolescents. METHODS: The Adolescent Brain Cognitive Development Study provides a large dataset of tabulated neuroimaging, youth-reported adverse experiences, and parent-reported financial adversity from a sample of children around the United States. Linear mixed effects modeling was used to determine the relationship between ELA and hippocampal volume change within youth (n = 7036) from ages 9-10 to 11-12 years. RESULTS: Results of the models indicated that the number of early adverse events predicted bilateral hippocampal volume change (ß = -0.02, t = -2.02, p < .05). Higher adversity was associated with lower hippocampal volume at Baseline (t = 5.55, p < .01) and at Year 2 (t = 6.14, p < .001). DISCUSSION: These findings suggest that ELA may affect hippocampal development during early adolescence. Prevention and early intervention are needed to alter the course of this trajectory. Future work should examine associations between ELA, hippocampal development, and educational and socioemotional outcomes.

3.
J Prim Care Community Health ; 15: 21501319241255542, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38769775

RESUMO

OBJECTIVE: To estimate and compare the proportion of foreign-born Middle Eastern/North African (MENA) children without health insurance, public, or private insurance to foreign- and US-born White and US-born MENA children. METHODS: Using 2000 to 2018 National Health Interview Survey data (N = 311 961 children) and 2015 to 2019 American Community Survey data (n = 1 892 255 children), we ran multivariable logistic regression to test the association between region of birth among non-Hispanic White children (independent variable) and health insurance coverage types (dependent variables). RESULTS: In the NHIS and ACS, foreign-born MENA children had higher odds of being uninsured (NHIS OR = 1.50, 95%CI = 1.10-2.05; ACS OR = 2.11, 95%CI = 1.88-2.37) compared to US-born White children. In the ACS, foreign-born MENA children had 2.11 times higher odds (95%CI = 1.83-2.45) of being uninsured compared to US-born MENA children. CONCLUSION: Our findings have implications for the health status of foreign-born MENA children, who are currently more likely to be uninsured. Strategies such as interventions to increase health insurance enrollment, updating enrollment forms to capture race, ethnicity, and nativity can aid in identifying and monitoring key disparities among MENA children.


Assuntos
Negro ou Afro-Americano , Seguro Saúde , Pessoas sem Cobertura de Seguro de Saúde , Humanos , Criança , Masculino , Feminino , Seguro Saúde/estatística & dados numéricos , Estados Unidos , Pré-Escolar , Adolescente , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Lactente , Negro ou Afro-Americano/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Oriente Médio/etnologia , Cobertura do Seguro/estatística & dados numéricos , África do Norte/etnologia , População Branca/estatística & dados numéricos , Modelos Logísticos , Recém-Nascido
4.
Artigo em Inglês | MEDLINE | ID: mdl-38668780

RESUMO

Timely clinical diagnosis of Alzheimer's disease and related dementias (ADRD) is important for resource allocation, mitigating safety concerns, and improving quality of life. While studies have examined ADRD diagnosis disparities by race/ethnicity, few include its intersection with nativity. Our aims were to (1) estimate the odds of diagnosed ADRD among US- and foreign-born racial/ethnic groups compared to US-born White older adults and (2) make comparisons by nativity within each racial/ethnic group. We linked 2000-2017 National Health Interview Survey (NHIS) and 2001-2018 Medical Expenditure Panel Survey (MEPS) data (65 + years; n = 38,033). Race/ethnicity and nativity were measured using NHIS data. Diagnosed ADRD was determined using ICD-9 (290/294/331/797) or ICD-10 (F01/F03/G30/G31) billing codes created from self-reports during MEPS household interviews. Bivariate and multivariable analyses were adjusted for covariates based on Anderson's behavioral model of health services use. US-born Black (OR = 1.74; 95% CI = 1.48-2.05), Hispanic (OR = 1.62; 95% CI = 1.14-2.29), and foreign-born Hispanic (OR = 1.63; 95% CI = 1.24-2.15) older adults, but not foreign-born Black or Asian older adults, had higher odds of diagnosed ADRD compared to US-born White older adults after adjusting for age and sex. After additional adjustment for education, health insurance, usual source of care, and chronic conditions, only US-born Black older adults continued to show higher odds (OR = 1.54; 95% CI = 1.27-1.87) of diagnosed ADRD compared to US-born White older adults. There were no differences in ADRD diagnosis by nativity within each racial/ethnic group. Findings highlight the need for including nativity in studies comparing racial/ethnic groups to Whites to fully capture the ADRD burden among US-born Black older adults.

5.
Nat Commun ; 15(1): 1956, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438341

RESUMO

Directed evolution of computationally designed enzymes has provided new insights into the emergence of sophisticated catalytic sites in proteins. In this regard, we have recently shown that a histidine nucleophile and a flexible arginine can work in synergy to accelerate the Morita-Baylis-Hillman (MBH) reaction with unrivalled efficiency. Here, we show that replacing the catalytic histidine with a non-canonical Nδ-methylhistidine (MeHis23) nucleophile leads to a substantially altered evolutionary outcome in which the catalytic Arg124 has been abandoned. Instead, Glu26 has emerged, which mediates a rate-limiting proton transfer step to deliver an enzyme (BHMeHis1.8) that is more than an order of magnitude more active than our earlier MBHase. Interestingly, although MeHis23 to His substitution in BHMeHis1.8 reduces activity by 4-fold, the resulting His containing variant is still a potent MBH biocatalyst. However, analysis of the BHMeHis1.8 evolutionary trajectory reveals that the MeHis nucleophile was crucial in the early stages of engineering to unlock the new mechanistic pathway. This study demonstrates how even subtle perturbations to key catalytic elements of designed enzymes can lead to vastly different evolutionary outcomes, resulting in new mechanistic solutions to complex chemical transformations.


Assuntos
Arginina , Histidina , Histidina/genética , Evolução Biológica , Catálise , Engenharia , Metilistidinas
6.
Innov Aging ; 8(3): igae025, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524244

RESUMO

Background and Objectives: Modifiable risk factors across the life course play a role in the development of Alzheimer's disease and related dementias (ADRD). Studies have identified racial and ethnic disparities in ADRD risk factors. Few studies have explored the epidemiology of ADRD risk among Middle Eastern and North African (MENA) Americans, largely due to their classification as White in US national health surveys. Our aim was to estimate ADRD risk factors among MENA immigrants compared to US- and foreign-born non-Hispanic White adults. Research Design and Methods: We linked cross-sectional 2000-2017 National Health Interview Survey and 2001-2018 Medical Expenditure Panel Survey data (N = 108 695; age ≥ 18 years). Modifiable risk factors for ADRD that were evaluated (yes or no) included less than ninth grade education, hearing loss, traumatic brain injury, hypertension, alcohol use, obesity, smoking, depressive symptoms, marital status, physical inactivity, and diabetes. Bivariate analysis and multivariable logistic regression were conducted. Regression models were adjusted by age and sex. Results: Compared to US-born White adults, MENA immigrants had higher odds of reporting less than 9th grade education (OR = 1.93; 95% CI = 1.17-3.21) and psychological health concerns (OR = 1.28; 95% CI = 1.06-1.56). Compared to foreign-born White adults, MENA immigrants had higher odds of diabetes (OR = 1.48; 95% CI = 1.06-2.08) and psychological health concerns (OR = 1.24; 95% CI = 1.01-1.54). Discussion and Implications: The findings provide the first comprehensive look at potentially modifiable risk factors for ADRD among MENA immigrants based on a life course model. Without a racial/ethnic identifier for MENA individuals on a national level, ADRD risk factors among US-born MENA adults and MENA immigrants cannot be examined. More research is needed to explore these risk factors by life stage (early, midlife, and late) to further determine ADRD risk and prevention strategies for MENA Americans.

7.
Matern Child Health J ; 28(4): 719-728, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38194128

RESUMO

INTRODUCTION: Few studies have evaluated the health of Middle Eastern and North African (MENA) women and children in the United States. Objectives were to determine the odds of well-visits, preventive behaviors during pregnancy, and low birthweight among foreign-born non-Hispanic MENA women and children compared to their US- and foreign-born non-Hispanic White counterparts after adjusting for covariates (hereafter, reported as MENA and White). METHODS: We analyzed 2000-2018 National Health Interview Survey data (411,709 women, 311,961 children). Outcomes included well-woman visits (past 12 months); dentist visits (past 6 months) and current smoking among pregnant women; and low, moderately low, and very low birthweight among children. Covariates included age, family income, and health insurance for children. Education and marital status were also evaluated among women. RESULTS: Over half (53.4%) of foreign-born MENA women were of childbearing age (ages 18-45) compared to 47.7% US-born and 43.2% foreign-born White women. The odds of completing a well-women visit were 0.73 times lower (95% CI = 0.38-0.89) among foreign-born MENA women compared to US-born White women after adjusting for age, education, and marital status. There was no statistically significant difference in dental visits between groups. No foreign-born MENA pregnant women reported current smoking. Foreign-born MENA children had higher odds of low (OR = 1.65; 95% CI = 1.16-2.35) and moderately low birthweight (OR = 1.78; 95% CI = 1.19-2.66) compared to US-born White children in adjusted models. DISCUSSION: MENA women and children are classified as White by the federal government. Our results highlight that the health of foreign-born MENA women and children differ from their White counterparts.


Assuntos
Etnicidade , População do Oriente Médio e Norte da África , Criança , Feminino , Humanos , Gravidez , Peso ao Nascer , Desigualdades de Saúde , População do Norte da África , Estados Unidos/epidemiologia , Brancos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , População Branca
8.
J Racial Ethn Health Disparities ; 11(1): 238-247, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36648623

RESUMO

Diabetes is one of the most common coexisting conditions among adults with cognitive limitations. Complexities of diabetes care present challenges for older adults and their caregivers. Few studies have evaluated disparities in the prevalence of coexisting diabetes among older adults with cognitive limitations by race/ethnicity and nativity. Our objectives were to (1) estimate the odds of coexisting diabetes among US- and foreign-born racial/ethnic groups compared to US-born non-Hispanic White older adults and (2) compare US- and foreign-born older adults within each racial/ethnic group. We linked and analyzed 2000-2017 National Health Interview Survey and 2001-2018 Medical Expenditure Panel Survey data among older adults with cognitive limitations (ages ≥ 65 years, n = 4688). The overall prevalence of coexisting diabetes among older adults with cognitive limitations was 30.3%. Among older adults with cognitive limitations and after adjusted for age, sex, education, and risk factors for diabetes and cognitive limitations, non-Hispanic Black (US-born OR = 1.56, 95%CI = 1.23-1.98; foreign-born OR = 2.69, 95%CI = 1.20-6.05) and Hispanic (US-born OR = 2.13, 95%CI = 1.34-3.40; foreign-born OR = 2.02, 95%CI = 1.49-2.72) older adults had higher odds of coexisting diabetes compared to US-born non-Hispanic Whites. There were no differences in the odds of coexisting diabetes among foreign-born non-Hispanic Black and Hispanic adults compared to US-born counterparts. Findings suggest a large potential burden of coexisting diabetes among this growing populations of US- and foreign-born racially/ethnically diverse older adults with cognitive limitations. Future studies are needed to examine how diabetes self-efficacy, treatment, and monitoring are impacted by cognitive limitations and determine ways to improve care in collaboration with caregivers and healthcare providers.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus , Etnicidade , Grupos Raciais , Idoso , Humanos , Cognição , Estados Unidos/epidemiologia
9.
Skin Health Dis ; 3(6): e294, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38047256

RESUMO

Background: The existing association between skin disease and psychiatric comorbidity has gained attention during the last decades. Stress and mental illness can directly or indirectly affect skin disease, while dermatological conditions, known to impair life quality and mental well-being, can promote psychiatric conditions. Objectives: The aim of this study was to assess the risk of developing psychiatric disease among adult dermatological patients over a period of time. The secondary objective was to see which psychiatric disorders developed most commonly, and which skin diseases posed the greatest risk for later mental health issues. Methods: Adult dermatological patients were followed for 9 years (2008-2016) using the Norwegian Patient Registry, for both outpatient and inpatient specialist healthcare services. Dermatological patients were identified during the first 2 years and were then followed for psychiatric comorbidity prospectively for the next 7 years.Cox regression models were applied to estimate the risks of psychiatric disorders among patients with skin diseases. Estimates were adjusted for age and gender differences. Hazard risk ratios (HR) with 95% CI are reported. Results: Dermatological patients developed depressive disorders most frequently (4.1% vs. 2.3% in non-dermatological participants), followed by anxiety disorders (3.3% vs. 1.8%), and adjustment disorders (2.6% vs. 1.5%). Developing depressive disorders showed the highest HR among dermatological patients, HR (95% CI) = 2.5 (2.4-2.5), followed by disorders related to alcohol use, HR (95% CI) = 2.2 (2.1-2.5), and anxiety disorders, HR (95% CI) = 2.1 (2.1-2.2). Papulosquamous disorders were the skin conditions with the highest HR for developing a mental health condition, with depressive disorder having HR (95% CI) = 2.6 (2.5-2.9); anxiety disorders at HR (95% CI) = 2.9 (2.7-3.1); and disorders related to alcohol use at HR (95% CI) = 3.2 (2.8-3.6). Conclusions: The study demonstrates that having a skin disease doubles to triples the risk of developing a psychiatric illness within 7 years, especially depression, anxiety, and alcohol use compared with the general population.

10.
Org Lett ; 25(49): 8787-8791, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38052021

RESUMO

The reduction of nitroarenes using KBH4 and I2 is described. BI3 is generated in situ and was shown to be the active reductant. Conditions were optimized for BI3 generation and then applied to a wide range of nitroarenes, including traditionally challenging substrates. The method constitutes a practical reduction option which produces low-toxicity boric acid and potassium iodide upon workup.

11.
Mater Today Bio ; 22: 100772, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37674781

RESUMO

Delignified wood (DW) offers a versatile platform for the manufacturing of composites, with material properties ranging from stiff to soft and flexible by preserving the preferential fiber directionality of natural wood through a structure-retaining production process. This study presents a facile method for fabricating anisotropic and mechanically tunable DW-hydrogel composites. These composites were produced by infiltrating delignified spruce wood with an aqueous gelatin solution followed by chemical crosslinking. The mechanical properties could be modulated across a broad strength and stiffness range (1.2-18.3 MPa and 170-1455 MPa, respectively) by varying the crosslinking time. The diffusion-led crosslinking further allowed to manufacture mechanically graded structures. The resulting uniaxial, tubular structure of the anisotropic DW-hydrogel composite enabled the alignment of murine fibroblasts in vitro, which could be utilized in future studies on potential applications in tissue engineering.

12.
J Am Chem Soc ; 145(37): 20672-20682, 2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37688545

RESUMO

Oxygenase and peroxygenase enzymes generate intermediates at their active sites which bring about the controlled functionalization of inert C-H bonds in substrates, such as in the enzymatic conversion of methane to methanol. To be viable catalysts, however, these enzymes must also prevent oxidative damage to essential active site residues, which can occur during both coupled and uncoupled turnover. Herein, we use a combination of stopped-flow spectroscopy, targeted mutagenesis, TD-DFT calculations, high-energy resolution fluorescence detection X-ray absorption spectroscopy, and electron paramagnetic resonance spectroscopy to study two transient intermediates that together form a protective pathway built into the active sites of copper-dependent lytic polysaccharide monooxygenases (LPMOs). First, a transient high-valent species is generated at the copper histidine brace active site following treatment of the LPMO with either hydrogen peroxide or peroxyacids in the absence of substrate. This intermediate, which we propose to be a CuII-(histidyl radical), then reacts with a nearby tyrosine residue in an intersystem-crossing reaction to give a ferromagnetically coupled (S = 1) CuII-tyrosyl radical pair, thereby restoring the histidine brace active site to its resting state and allowing it to re-enter the catalytic cycle through reduction. This process gives the enzyme the capacity to minimize damage to the active site histidine residues "on the fly" to increase the total turnover number prior to enzyme deactivation, highlighting how oxidative enzymes are evolved to protect themselves from deleterious side reactions during uncoupled turnover.


Assuntos
Cobre , Histidina , Oxigenases de Função Mista , Estresse Oxidativo , Catálise
13.
Soc Sci Med ; 336: 116260, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37769512

RESUMO

Studies of Middle Eastern immigrants using national data, with and without African immigrants, have provided important discoveries on the health of this group. However, they do not directly measure health among Arab immigrants. It is yet to be determined whether using a Middle Eastern and North African (MENA) classification can represent the health needs of Arab immigrants. The objective of this study was to assess if MENA immigrant health reflects the same patterns found in previous research focusing on Arab immigrant health. We used multiple years of data from the National Health Interview Survey in alignment with each former study methodology to compare our findings with four previous research studies. The independent variable was region of birth among non-Hispanic Whites. The dependent variables were chronic diseases, women's preventive health behaviors, men's preventive health behaviors, and cigarette smoking. Logistic regression was conducted to determine the odds of each outcome for MENA immigrants compared to US-born Whites. Then, adjusted 95% confidence intervals representing the more inclusive MENA immigrant categorization were compared to previous studies among Arab immigrants. Chronic conditions, women's and men's preventive health behaviors and cigarette smoking did not differ whether the MENA or Arab definition was used. However, statistically significant differences were observed between MENA and Arab immigrants regarding bachelor's degree or higher, not employed and years in the US. The MENA category reflects the Arab immigrant experience, even though it includes a wider set of origins, some of which are not Arab. Including a MENA identifier on future data collections will both represent Arab Americans, as well as identify this population as distinct from Whites to better represent and track health disparities.


Assuntos
Árabes , Emigrantes e Imigrantes , Necessidades e Demandas de Serviços de Saúde , População do Oriente Médio , Brancos , Feminino , Humanos , Masculino , Doença Crônica , População do Norte da África , Inquéritos e Questionários , Estados Unidos/epidemiologia , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Avaliação das Necessidades/estatística & dados numéricos
14.
Nat Commun ; 14(1): 5309, 2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37652918

RESUMO

Colloidal gels, commonly used as mesoporous intermediates or functional materials, suffer from brittleness, often showing small yield strains on the order of 1% or less for gelled colloidal suspensions. The short-range adhesive forces in most such gels are central forces-combined with the smooth morphology of particles, the resistance to yielding and shear-induced restructuring is limited. In this study, we propose an innovative approach to improve colloidal gels by introducing surface roughness to the particles to change the yield strain, giving rise to non-central interactions. To elucidate the effects of particle roughness on gel properties, we prepared thermoreversible gels made from rough or smooth silica particles using a reliable click-like-chemistry-based surface grafting technique. Rheological and optical characterization revealed that rough particle gels exhibit enhanced toughness and self-healing properties. These remarkable properties can be utilized in various applications, such as xerogel fabrication and high-fidelity extrusion 3D-printing, as we demonstrate in this study.

15.
Womens Health (Lond) ; 19: 17455057231178118, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37449491

RESUMO

BACKGROUND: Despite the high cost of low birth weight and the persistent challenge of racial inequities affecting the Arab American community, there has been limited research to identify and examine risk factors for these inequities with validated data on Arab American ethnicity and recent population stressors. OBJECTIVES: This study examined whether the 2016 presidential election is associated with low birth weight among non-Hispanic White, Arab American, Hispanic, and non-Hispanic Black women. DESIGN: This population-based study of singleton births in Michigan (2008-2017) used an algorithm to identify mothers who were of Arab descent. METHODS: We used logistic regression to estimate odds ratios and 95% confidence intervals for the association between race/ethnicity and the odds of low birth weight. We examined whether these associations differed before and after the 2016 presidential election and according to maternal education. RESULTS: There were 1,019,738 births, including 66,272 (6.5%) classified as low birth weight. The odds of having a low-birth-weight infant were higher among all minority women compared to non-Hispanic White women. The association was similar before and after the 2016 presidential election and stronger among women with higher levels of education. CONCLUSION: This is the first study to estimate low birth weight among Arab American women in the context of political events. There are opportunities for future studies to discuss this issue in depth.


Assuntos
Árabes , Recém-Nascido de Baixo Peso , Política , Estresse Psicológico , Feminino , Humanos , Recém-Nascido , Hispânico ou Latino , Michigan/epidemiologia , Brancos , Asiático , Negro ou Afro-Americano
16.
Acta Derm Venereol ; 103: adv6485, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37345973

RESUMO

Perceived stigmatization places a large psychosocial burden on patients with some skin conditions. Little is known about the experience of stigmatization across a wide range of skin diseases. This observational cross-sectional study aimed to quantify perceived stigmatization and identify its predictors among patients with a broad spectrum of skin diseases across 17 European countries. Self-report questionnaires assessing perceived stigmatization and its potential predictors were completed by 5,487 dermatology outpatients and 2,808 skin-healthy controls. Dermatological diagnosis, severity, and comorbidity were clinician-assessed. Patients experienced higher levels of perceived stigmatization than controls (p < 0.001, d = 0.26); patients with psoriasis, atopic dermatitis, alopecia, and bullous disorders were particularly affected. Multivariate regression analyses showed that perceived stigmatization was related to sociodemographic (lower age, male sex, being single), general health-related (higher body mass index, lower overall health), disease-related (higher clinician-assessed disease severity, presence of itch, longer disease duration), and psychological (greater distress, presence of suicidal ideation, greater body dysmorphic concerns, lower appearance satisfaction) variables. To conclude, perceived stigmatization is common in patients with skin diseases. Factors have been identified that will help clinicians and policymakers to target vulnerable patient groups, offer adequate patient management, and to ultimately develop evidence-based interventions.


Assuntos
Psoríase , Dermatopatias , Humanos , Masculino , Estereotipagem , Pacientes Ambulatoriais , Qualidade de Vida/psicologia , Dermatopatias/diagnóstico , Dermatopatias/psicologia , Psoríase/diagnóstico , Psoríase/psicologia , Inquéritos e Questionários
17.
J Immigr Minor Health ; 25(5): 1098-1107, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37351736

RESUMO

ADRD underdiagnosis among minority populations is well-established and known to be more prevalent among women. Yet, it remains unclear if these patterns exist among adults of Middle Eastern and North African (MENA) descent. We estimated ADRD underdiagnosis among adults of MENA descent and other US- and foreign-born non-Hispanic Whites and compared sex-stratified results. We linked 2000-2017 National Health Interview Survey and 2001-2018 Medical Expenditure Panel Survey data (ages > = 65 years, n = 23,981). Undiagnosed ADRD was suspected if participants reported cognitive limitations without corresponding ADRD diagnosis. Undiagnosed ADRD was highest among adults of MENA descent (15.8%) compared to non-Hispanic Whites (US-born = 8.1%; foreign-born = 11.8%). Women of MENA descent had 2.52 times greater odds (95% CI = 1.31-4.84) of undiagnosed ADRD compared to US-born White women after adjusting for risk factors. This study contributes the first national estimates of undiagnosed ADRD among adults of MENA descent. Continued research is needed to facilitate policy changes that more comprehensively address health disparities and related resource allocation.


Assuntos
Doença de Alzheimer , Emigrantes e Imigrantes , População do Oriente Médio , População do Norte da África , Doenças não Diagnosticadas , Feminino , Humanos , Masculino , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/etnologia , Emigrantes e Imigrantes/estatística & dados numéricos , População do Oriente Médio/estatística & dados numéricos , População do Norte da África/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Doenças não Diagnosticadas/diagnóstico , Doenças não Diagnosticadas/epidemiologia , Doenças não Diagnosticadas/etnologia , Estados Unidos/epidemiologia , Brancos/etnologia , Brancos/estatística & dados numéricos , Idoso
18.
Protein Sci ; 32(5): e4640, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37051694

RESUMO

The availability of an expanded genetic code opens exciting new opportunities in enzyme design and engineering. In this regard histidine analogues have proven particularly versatile, serving as ligands to augment metalloenzyme function and as catalytic nucleophiles in designed enzymes. The ability to genetically encode multiple functional residues could greatly expand the range of chemistry accessible within enzyme active sites. Here, we develop mutually orthogonal translation components to selectively encode two structurally similar histidine analogues. Transplanting known mutations from a promiscuous Methanosarcina mazei pyrrolysyl-tRNA synthetase (MmPylRSIFGFF ) into a single domain PylRS from Methanomethylophilus alvus (MaPylRSIFGFF ) provided a variant with improved efficiency and specificity for 3-methyl-L-histidine (MeHis) incorporation. The MaPylRSIFGFF clone was further characterized using in vitro biochemical assays and x-ray crystallography. We subsequently engineered the orthogonal MmPylRS for activity and selectivity for 3-(3-pyridyl)-L-alanine (3-Pyr), which was used in combination with MaPylRSIFGFF to produce proteins containing both 3-Pyr and MeHis. Given the versatile roles played by histidine in enzyme mechanisms, we anticipate that the tools developed within this study will underpin the development of enzymes with new and enhanced functions.


Assuntos
Aminoacil-tRNA Sintetases , Histidina , Histidina/genética , Lisina/química , RNA de Transferência/genética , RNA de Transferência/metabolismo , Aminoacil-tRNA Sintetases/química , Methanosarcina/genética , Methanosarcina/metabolismo
19.
Res Sq ; 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-36993201

RESUMO

Background ADRD underdiagnosis among minority populations is well-established and known to be more prevalent among women. Yet, it remains unclear if these patterns exist among Middle Eastern and North African (MENA) adults. We estimated ADRD underdiagnosis among MENA and other US- and foreign-born non-Hispanic Whites and compared sex-stratified results. Methods We linked 2000-2017 National Health Interview Survey and 2001-2018 Medical Expenditure Panel Survey data (ages > = 65 years, n = 23,981). Undiagnosed ADRD was suspected if participants reported cognitive limitations without corresponding ADRD diagnosis. Results Undiagnosed ADRD was highest among MENA adults (15.8%) compared to non-Hispanic Whites (US-born = 8.1%; foreign-born = 11.8%). MENA women had 2.52 times greater odds (95% CI = 1.31-4.84) of undiagnosed ADRD compared to US-born White women after adjusting for risk factors. Discussion This study contributes the first national estimates of undiagnosed ADRD among MENA adults. Continued research is needed to facilitate policy changes that more comprehensively address health disparities and related resource allocation.

20.
Front Psychiatry ; 14: 1067378, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36846241

RESUMO

Background: Single-session mental health interventions are frequently attended by children and young people (CYP) in both web-based and face-to-face therapy settings. The Session "Wants" and "Needs" Outcome Measure (SWAN-OM) is an instrument developed in a web-based therapy service to overcome the challenges of collecting outcomes and experiences of single-session therapies (SSTs). It provides pre-defined goals for the session, selected by the young person prior to the intervention, on which progress toward achievement is scored at the end of the session. Objective: The objective of this study was to evaluate the instrument's psychometric properties, including concurrent validity against three other frequently used outcome and experience measures, at a web-based and text-based mental health service. Methods: The SWAN-OM was administered for a period of 6 months to 1,401 CYP (aged 10-32 years; 79.3% white; 77.59% female) accessing SST on a web-based service. Item correlations with comparator measures and hierarchical logistic regressions to predict item selection were calculated for concurrent validity and psychometric exploration. Results: The most frequently selected items were "Feel better" (N = 431; 11.61%) and "Find ways I can help myself" (N = 411; 11.07%); unpopular items were "Feel safe in my relationships" (N = 53; 1.43%) and "Learn the steps to achieve something I want" (N = 58; 1.56%). The SWAN-OM was significantly correlated with the Experience of Service Questionnaire, particularly the item "Feel better" [rs(109) = 0.48, p < 0.001], the Youth Counseling Impact Scale, particularly the item "Learn the steps to achieve something I want" [rs(22) = 0.76, p < 0.001], and the Positive and Negative Affect Schedule, particularly the items "Learn how to feel better" [rs(22) = 0.72, p < 0.001] and "Explore how I feel" [rs(70) = -0.44, p < 0.001]. Conclusion: The SWAN-OM demonstrates good concurrent validity with common measures of outcome and experience. Analysis suggests that lesser-endorsed items may be removed in future iterations of the measure to improve functionality. Future research is required to explore SWAN-OM's potential to measure meaningful change in a range of therapeutic settings.

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