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1.
Allergy ; 78(10): 2698-2711, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37571876

RESUMO

BACKGROUND: Viruses may drive immune mechanisms responsible for chronic rhinosinusitis with nasal polyposis (CRSwNP), but little is known about the underlying molecular mechanisms. OBJECTIVES: To identify epigenetic and transcriptional responses to a common upper respiratory pathogen, rhinovirus (RV), that are specific to patients with CRSwNP using a primary sinonasal epithelial cell culture model. METHODS: Airway epithelial cells were collected at surgery from patients with CRSwNP (cases) and from controls without sinus disease, cultured, and then exposed to RV or vehicle for 48 h. Differential gene expression and DNA methylation (DNAm) between cases and controls in response to RV were determined using linear mixed models. Weighted gene co-expression analysis (WGCNA) was used to identify (a) co-regulated gene expression and DNAm signatures, and (b) genes, pathways, and regulatory mechanisms specific to CRSwNP. RESULTS: We identified 5585 differential transcriptional and 261 DNAm responses (FDR <0.10) to RV between CRSwNP cases and controls. These differential responses formed three co-expression/co-methylation modules that were related to CRSwNP and three that were related to RV (Bonferroni corrected p < .01). Most (95%) of the differentially methylated CpGs (DMCs) were in modules related to CRSwNP, whereas the differentially expressed genes (DEGs) were more equally distributed between the CRSwNP- and RV-related modules. Genes in the CRSwNP-related modules were enriched in known CRS and/or viral response immune pathways. CONCLUSION: RV activates specific epigenetic programs and correlated transcriptional networks in the sinonasal epithelium of individuals with CRSwNP. These novel observations suggest epigenetic signatures specific to patients with CRSwNP modulate response to viral pathogens at the mucosal environmental interface. Determining how viral response pathways are involved in epithelial inflammation in CRSwNP could lead to therapeutic targets for this burdensome airway disorder.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Humanos , Rhinovirus , Sinusite/metabolismo , Doença Crônica , Células Epiteliais/metabolismo , Epigênese Genética
2.
Alzheimer Dis Assoc Disord ; 37(2): 128-133, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36989106

RESUMO

BACKGROUND: The associations between cognitive domains and odor identification are well established, but how sociodemographic variables affect these relationships is less clear. PURPOSE: Using the survey-adapted Montreal Cognitive Assessment instrument (MoCA-SA), we assess how age, sex, race, and education shape these relationships. METHODS: We first used cluster analysis and multidimensional scaling to empirically derive distinct cognitive domains from the MoCA-SA as it is unclear whether the MoCA-SA can be disaggregated into cognitive domains. We then used ordinal logistic regression to test whether these empirically derived cognitive domains were associated with odor identification and how sociodemographic variables modified these relationships. STUDY POPULATION: Nationally representative sample of community-dwelling US older adults. RESULTS: We identified 5 out of the 6 theoretical cognitive domains, with the language domain unable to be identified. Odor identification was associated with episodic memory, visuospatial ability, and executive function. Stratified analyses by sociodemographic variables reveal that the associations between some of the cognitive domains and odor identification varied by age, sex, or race, but not by education. CONCLUSIONS: These results suggest that (1) the MoCA-SA can be used to identify cognitive domains in survey research and (2) the performance of smell tests as a screener for cognitive decline may potentially be weaker in certain subpopulations.


Assuntos
Cognição , Disfunção Cognitiva , Humanos , Idoso , Odorantes , Testes Neuropsicológicos , Função Executiva
3.
Int Arch Occup Environ Health ; 96(4): 621-628, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36719485

RESUMO

OBJECTIVE: Exposure to particulate matter of 10 µm or less in diameter (PM10) has been implicated in pulmonary and cardiovascular diseases. However, the effect of PM10 on olfaction has not been well established. We estimated individual acute and chronic PM10 exposure levels in a large Brazilian cohort and related them to the ability to identify odors. METHODS: Adults from São Paulo (n = 1358) were recruited from areas with different levels of air pollution. To verify individual exposure to air pollution, the averages of 30, 60, 90, 180 and 364 days of PM10 were interpolated to subjects' zip codes using the kriging method. Olfactory identification performance was tested using the University of Pennsylvania Smell Identification Test (UPSIT®). Multiple linear regressions were used to calculate the effect of air pollution on olfactory identification performance, controlling for demographic and other variables that affect the sense of smell. RESULTS: Acute exposures to PM10 were related to worse UPSIT® scores, including 30- (ß = - 0.94, 95% Confidence Interval [CI] - 0.98, - 0.89), 60- (ß = - 1.09, 95% CI = - 1.13, - 1.04) and 90-day intervals (ß = - 1.06, 95% CI - 1.10, - 1.02) (reference for ß: 1 µm/m3 increase in PM10 exposure per point decrease in UPSIT® score). Chronic exposures were also associated with worse olfaction for both 180- (ß = - 1.06, 95% CI - 1.10, - 1.03) and 364-day (ß = - 0.87, 95% CI - 0.90, - 0.84) intervals. As in prior work, men, older, low-income, and low-schooling people demonstrated worse olfactory performance. CONCLUSION: Acute and chronic exposure to PM10 is strongly associated with olfactory identification performance in Brazilian adults. Understanding the mechanisms which underlie these relationships could help to improve chemosensory function with a large public health impact.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Masculino , Adulto , Humanos , Olfato , Estudos Transversais , Brasil/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Material Particulado/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise
4.
ORL J Otorhinolaryngol Relat Spec ; 85(6): 312-320, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37062268

RESUMO

BACKGROUND: Definitions are essential for effective communication and discourse, particularly in science. They allow the shared understanding of a thought or idea, generalization of knowledge, and comparison across scientific investigation. The current terms describing olfactory dysfunction are vague and overlapping. SUMMARY: As a group of clinical olfactory researchers, we propose the standardization of the terms "dysosmia," "anosmia," "hyposmia," "normosmia," "hyperosmia," "olfactory intolerance," "parosmia," and "phantosmia" (or "olfactory hallucination") in olfaction-related communication, with specific definitions in this text. KEY MESSAGES: The words included in this paper were determined as those which are most frequently used in the context of olfactory function and dysfunction, in both clinical and research settings. Despite widespread use in publications, however, there still exists some disagreement in the literature regarding the definitions of terms related to olfaction. Multiple overlapping and imprecise terms that are currently in use are confusing and hinder clarity and universal understanding of these concepts. There is a pressing need to have a unified agreement on the definitions of these olfactory terms by researchers working in the field of chemosensory sciences. With the increased interest in olfaction, precise use of these terms will improve the ability to integrate and advance knowledge in this field.


Assuntos
Transtornos do Olfato , Olfato , Humanos , Anosmia , Transtornos do Olfato/diagnóstico , Alucinações
5.
Alzheimers Dement ; 19(4): 1479-1490, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35899859

RESUMO

INTRODUCTION: Longitudinal multivariable analyses are needed to determine if the rate of olfactory decline during normal cognition predicts subsequent Alzheimer's disease (AD) diagnoses and brain dysmorphology. METHODS: Older adults (n = 515) were assessed annually for odor identification, cognitive function and dementia clinical diagnosis (max follow-up 18 years). Regional gray matter volumes (GMV) were quantified (3T MRI) in a cross-sectional subsample (n = 121). Regression models were adjusted for APOE-ε4 genotype, dementia risk factors and demographics. RESULTS: Faster olfactory decline during periods of normal cognition predicted higher incidence of subsequent MCI or dementia (OR 1.89, 95% CI: 1.26, 2.90, p < 0.01; comparable to carrying an APOE-ε4 allele) and smaller GMV in AD and olfactory regions (ß = -0.11, 95% CI -0.21, -0.00). DISCUSSION: Rapid olfactory decline during normal cognition, using repeated olfactory measurement, predicted subsequent cognitive impairment, dementia, and smaller GMVs, highlighting its potential as a simple biomarker for early AD detection. HIGHLIGHTS: Rate of olfactory decline was calculated from olfactory testing over ≥3 time points. Rapid olfactory decline predicted impaired cognition and higher risk of dementia. Neurodegeneration on 3T magnetic resonance imaging was identical in those with olfactory decline and Alzheimer's disease.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Substância Cinzenta/patologia , Estudos Transversais , Encéfalo/patologia , Disfunção Cognitiva/etiologia , Envelhecimento , Apolipoproteínas E/genética , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo
6.
Chem Senses ; 472022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36469055

RESUMO

Little attention has been paid to olfactory changes during pregnancy with contemporary studies limited in number and sample size. We examined whether pregnancy is associated with differences in olfactory performance and if there were any specific gestational ages at which these differences occur through a comprehensive systematic review and meta-analysis of the current literature. An initial electronic database search identified 234 citations, which were screened at the abstract level. Twenty-three citations were germane for full-text review, and 13 met criteria for inclusion. Our review assessed 5 olfactory measures of interest: odor identification (n = 11 articles), threshold (n = 8), discrimination (n = 5), hedonics (n = 6), and intensity (n = 5). Nine of these 13 studies contained sufficient data for meta-analysis, and these studies included a total of 523 pregnant women and 365 non-pregnant controls. Despite previous subjective and objective reports of odor intolerances and odor hypersensitivity, we did not find any significant differences between pregnant and non-pregnant women in odor discrimination, thresholds, or hedonics. However, meta-analysis of 506 cases and 333 controls showed worse odor identification in pregnant women compared to controls in a random-effects model. Thus, we demonstrate worse performance at odor identification during pregnancy. In this review, we discuss the current evidence (and lack thereof) regarding olfaction in pregnancy as well as highlight current knowledge gaps in this field.


Assuntos
Transtornos do Olfato , Olfato , Gravidez , Humanos , Feminino , Odorantes
7.
Alzheimers Dement ; 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35770850

RESUMO

INTRODUCTION: Variants in the tau gene (MAPT) region are associated with breast cancer in women and Alzheimer's disease (AD) among persons lacking apolipoprotein E ε4 (ε4-). METHODS: To identify novel genes associated with tau-related pathology, we conducted two genome-wide association studies (GWAS) for AD, one among 10,340 ε4- women in the Alzheimer's Disease Genetics Consortium (ADGC) and another in 31 members (22 women) of a consanguineous Hutterite kindred. RESULTS: We identified novel associations of AD with MGMT variants in the ADGC (rs12775171, odds ratio [OR] = 1.4, P = 4.9 × 10-8 ) and Hutterite (rs12256016 and rs2803456, OR = 2.0, P = 1.9 × 10-14 ) datasets. Multi-omics analyses showed that the most significant and largest number of associations among the single nucleotide polymorphisms (SNPs), DNA-methylated CpGs, MGMT expression, and AD-related neuropathological traits were observed among women. Furthermore, promoter capture Hi-C analyses revealed long-range interactions of the MGMT promoter with MGMT SNPs and CpG sites. DISCUSSION: These findings suggest that epigenetically regulated MGMT expression is involved in AD pathogenesis, especially in women.

8.
J Aging Phys Act ; 30(4): 572-580, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34611055

RESUMO

Multisensory, physical, and cognitive dysfunction share age-related physiologic disturbances and may have common health effects. We determined whether the effect of multisensory impairment on physical activity (PA) is explained by physical (timed up and go) or cognitive (Short Portable Mental Status Questionnaire) dysfunction. A National Social Life, Health, and Aging Project participant subset (n = 507) underwent objective sensory testing in 2005-2006 and wrist accelerometry in 2010-2011. We related multisensory impairment to PA using multivariate mixed-effects linear regression and compared the effect magnitude after adjusting for physical then cognitive dysfunction. Worse multisensory impairment predicted lower PA across three scales (Global Sensory Impairment: ß = -0.04, 95% confidence interval [-0.07, -0.02]; Total Sensory Burden: ß = -0.01, 95% confidence interval [-0.03, -0.003]; and Number of Impaired Senses: ß = -0.02, 95% confidence interval [-0.04, -0.004]). Effects were similar after accounting for physical and cognitive dysfunction. Findings suggest that sensory, physical, and cognitive dysfunction have unique mechanisms underlying their PA effects.


Assuntos
Disfunção Cognitiva , Exercício Físico , Acelerometria , Envelhecimento , Humanos
9.
Chem Senses ; 462021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34673938

RESUMO

Age-related olfactory dysfunction, or presbyosmia, is a common sensory impairment in aging adults. People in this demographic group with comorbid conditions or exposure to viral, traumatic, or environmental insults remain at the greatest risk for impairment. Several methods for assessing olfaction exist, but they are only available in special settings and require consideration of age, sex, ancestry, and cognition. Perhaps most importantly, olfactory dysfunction has been suggested as an early sign of Alzheimer's and Parkinson's disease and therefore may serve as a tool in the diagnosis and prognosis of these neurodegenerative conditions. Outside of this context, olfactory loss also impacts nutrition, safety, and social relationships, and even predicts mortality itself. This review covers the detection and manifestations of olfactory decline in aging individuals and the myriad ways in which olfactory impairment is connected to their health and well-being.


Assuntos
Doenças Neurodegenerativas , Transtornos do Olfato , Adulto , Envelhecimento , Anosmia , Humanos , Transtornos do Olfato/diagnóstico , Olfato
10.
Chem Senses ; 462021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33197253

RESUMO

Neuroanatomic connections link the olfactory and limbic systems potentially explaining an association between olfactory dysfunction and depression. Some previous studies have demonstrated that olfactory dysfunction is associated with increased depressive symptoms. However, these studies were cross-sectional and unable to establish which develops first. We used longitudinal data to determine if impaired odor identification increased subsequent depressive symptoms or vice versa. We assessed olfaction and depression in the National Social Life, Health, and Aging Project, a nationally representative, 15-year longitudinal study of older US adults. Olfaction was measured using a validated odor identification test (Sniffin' Sticks). Depressive symptoms were measured using a modified version of the validated Center for Epidemiological Studies Depression Scale. Multivariable logistic regression models examined the temporal relationships between developing olfactory dysfunction and depression while accounting for demographics, disease comorbidities, alcohol use, smoking, and cognition. Older adults with olfactory dysfunction had concurrent frequent depressive symptoms (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.00-1.43). Among healthy adults at baseline, those who had olfactory dysfunction were more likely to develop frequent depressive symptoms 5 or 10 years later (OR = 2.22, 95% CI = 1.13-4.37). Conversely, those with frequent depressive symptoms at baseline were not more likely to develop olfactory dysfunction 5 or 10 years later. We show for the first time that olfactory dysfunction predicts subsequent development of depression in older US adults. These data support screening for depression in older adults with chemosensory impairment and set the stage for disentangling the relationship between olfaction and depression.


Assuntos
Depressão/fisiopatologia , Transtornos do Olfato/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Razão de Chances , Olfato
11.
J Sex Med ; 18(2): 295-302, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33423973

RESUMO

BACKGROUND: Sensory function declines with age and may impact sexual function in older adults. Indeed, the sense of smell plays a uniquely strong role in sexual motivation. Therefore, olfactory dysfunction in older adults may be intimately linked to changes in sexual desire and satisfaction. AIM: To test whether impaired olfactory function is associated with decreased sexual activity and motivation in older adults. METHODS: Cross-sectional analysis of a nationally representative sample of community-dwelling older U.S. adults from the National Social Life, Health, and Aging Project. OUTCOMES: 2 modalities of olfactory function were measured (sensitivity to n-butanol and odor identification) via validated methods (Sniffin' Sticks). Respondents answered survey questions about frequency of sexual thoughts (motivation) and sexual activity, and satisfaction with their most recent sexual relationship. A wide range of demographic, health, and social information were also collected. RESULTS: Decreased olfactory function in older U.S. adults was associated with decreased sexual motivation (odds ratio 0.93, P = .03) and less emotional satisfaction with sex (odds ratio 0.89, P = .04), but not decreased frequency of sexual activity or physical pleasure, in analyses that were adjusted for age, gender, race, education, cognition, comorbidities, and depression. CLINICAL IMPLICATIONS: Olfactory dysfunction may affect sexuality in older adults. Potentially treatable causes of sensory loss should be addressed by clinicians to improve quality of life. STRENGTHS & LIMITATIONS: These results rely on validated olfactory testing, detailed measures of sexual attitudes and behaviors, and extensive demographic, health, and social history in a nationally representative sample of older U.S. adults. Owing to the cross-sectional nature of these analyses, we cannot determine causality. CONCLUSIONS: Olfactory dysfunction in older U.S. adults is associated with decreased sexual motivation and emotional satisfaction, potentially due to evolutionarily-conserved neurological links between olfaction and sexuality. Siegel JK, Kung SY, Wroblewski KE, et al. Olfaction Is Associated With Sexual Motivation and Satisfaction in Older Men and Women. J Sex Med 2021;18:295-302.


Assuntos
Motivação , Olfato , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação Pessoal , Qualidade de Vida , Comportamento Sexual
12.
Allergy ; 75(4): 911-920, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31713250

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) epidemiology has been largely studied using symptom-based case definitions, without assessment of objective sinus findings. OBJECTIVE: To describe radiologic sinus opacification and the prevalence of CRS, defined by the co-occurrence of symptoms and sinus opacification, in a general population-based sample. METHODS: We collected questionnaires and sinus CT scans from 646 participants selected from a source population of 200 769 primary care patients. Symptom status (CRSS ) was based on guideline criteria, and objective radiologic inflammation (CRSO ) was based on the Lund-Mackay (L-M) score using multiple L-M thresholds for positivity. Participants with symptoms and radiologic inflammation were classified as CRSS+O . We performed negative binomial regression to assess factors associated with L-M score and logistic regression to evaluate factors associated with CRSS+O . Using weighted analysis, we calculated estimates for the source population. RESULTS: The proportion of women with L-M scores ≥ 3, 4, or 6 (CRSO ) was 11.1%, 9.9%, and 5.7%, respectively, and 16.1%, 14.6%, and 8.7% among men. The respective proportion with CRSS+O was 1.7%, 1.6%, and 0.45% among women and 8.8%, 7.5%, and 3.6% among men. Men had higher odds of CRSS+O compared to women. A greater proportion of men (vs women) had any opacification in the frontal, anterior ethmoid, and sphenoid sinuses. CONCLUSION: In a general population-based sample in Pennsylvania, sinus opacification was more common among men than in women and opacification occurred in different locations by sex. Male sex, migraine headache, and prior sinus surgery were associated with higher odds of CRSS+O .


Assuntos
Seios Paranasais , Rinite , Sinusite , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Seios Paranasais/diagnóstico por imagem , Pennsylvania , Rinite/diagnóstico por imagem , Rinite/epidemiologia , Sinusite/diagnóstico por imagem , Sinusite/epidemiologia , Adulto Jovem
13.
Chem Senses ; 45(4): 321-330, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32406505

RESUMO

The ability to identify odors predicts morbidity, mortality, and quality of life. It varies by age, gender, and race and is used in the vast majority of survey and clinical literature. However, odor identification relies heavily on cognition. Other facets of olfaction, such as odor sensitivity, have a smaller cognitive component. Whether odor sensitivity also varies by these factors has not been definitively answered. We analyzed data from the National Social Life, Health, and Aging Project, a nationally representative study of older US adults (n = 2081). Odor identification was measured using 5 validated odors presented with Sniffin' Stick pens as was odor sensitivity in a 6-dilution n-butanol constant stimuli detection test. Multivariate ordinal logistic regression modeled relationships between olfaction and age, gender, race, cognition, education, socioeconomic status, social network characteristics, and physical and mental health. Odor sensitivity was worse in older adults (P < 0.01), without gender (P = 0.56) or race (P = 0.79) differences. Odor identification was also worse in older adults, particularly men (both P ≤ 0.01), without differences by race. Decreased cognitive function was associated with worse odor identification (P ≤ 0.01) but this relationship was weaker for odor sensitivity (P = 0.02) in analyses that adjusted for other covariates. Odor sensitivity was less strongly correlated with cognitive ability than odor identification, confirming that it may be a more specific measure of peripheral olfactory processing. Investigators interested in associations between olfaction and health should consider both odor sensitivity and identification when attempting to understand underlying neurosensory mechanisms.


Assuntos
Cognição , Odorantes , Fatores Etários , Idoso , Estudos Transversais , Fatores Econômicos , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Qualidade de Vida , Fatores Raciais , Fatores Sexuais , Olfato , Rede Social , Inquéritos e Questionários , Estados Unidos
14.
Chem Senses ; 45(5): 407-414, 2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32369568

RESUMO

Inflammation has been implicated in physical frailty, but its role in sensory impairment is unclear. Given that olfactory impairment predicts dementia and mortality, determining the role of the immune system in olfactory dysfunction would provide insights mechanisms of neurosensory decline. We analyzed data from the National Social Life, Health and Aging Project, a representative sample of home-dwelling older US adults. Plasma levels of 18 cytokines were measured using standard protocols (Luminex xMAP). Olfactory function was assessed with validated tools (n-butanol sensitivity and odor identification, each via Sniffin' Sticks). We tested the association between cytokine profiles and olfactory function using multivariate ordinal logistic regression, adjusting for age, gender, race/ethnicity, education level, cognitive function, smoking status, and comorbidity. Older adults with the IL-1Rahigh-IL-4low-IL-13low cytokine profile had worse n-butanol odor sensitivity (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.19-2.17) and worse odor identification (OR = 1.42, 95% CI 1.11-1.80). Proinflammatory, Th1, or Th2 cytokine profiles were not associated with olfactory function. Moreover, accounting for physical frailty did not alter the main findings. In conclusion, we identified a plasma cytokine signature-IL-1Rahigh-IL-4low-IL-13low-that is associated with olfactory dysfunction in older US adults. These data implicate systemic inflammation in age-related olfactory dysfunction and support a role for immune mechanisms in this process, a concept that warrants additional scrutiny.


Assuntos
Citocinas/sangue , Proteína Antagonista do Receptor de Interleucina 1/sangue , Interleucina-13/sangue , Interleucina-4/sangue , Transtornos do Olfato/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Feminino , Humanos , Modelos Logísticos , Masculino , Razão de Chances , Transtornos do Olfato/sangue , Transtornos do Olfato/epidemiologia , Olfato/fisiologia , Estados Unidos/epidemiologia
15.
Chem Senses ; 45(7): 493-502, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-32556127

RESUMO

The chemical senses of taste and smell play a vital role in conveying information about ourselves and our environment. Tastes and smells can warn against danger and also contribute to the daily enjoyment of food, friends and family, and our surroundings. Over 12% of the US population is estimated to experience taste and smell (chemosensory) dysfunction. Yet, despite this high prevalence, long-term, effective treatments for these disorders have been largely elusive. Clinical successes in other sensory systems, including hearing and vision, have led to new hope for developments in the treatment of chemosensory disorders. To accelerate cures, we convened the "Identifying Treatments for Taste and Smell Disorders" conference, bringing together basic and translational sensory scientists, health care professionals, and patients to identify gaps in our current understanding of chemosensory dysfunction and next steps in a broad-based research strategy. Their suggestions for high-yield next steps were focused in 3 areas: increasing awareness and research capacity (e.g., patient advocacy), developing and enhancing clinical measures of taste and smell, and supporting new avenues of research into cellular and therapeutic approaches (e.g., developing human chemosensory cell lines, stem cells, and gene therapy approaches). These long-term strategies led to specific suggestions for immediate research priorities that focus on expanding our understanding of specific responses of chemosensory cells and developing valuable assays to identify and document cell development, regeneration, and function. Addressing these high-priority areas should accelerate the development of novel and effective treatments for taste and smell disorders.


Assuntos
Transtornos do Olfato/terapia , Distúrbios do Paladar/terapia , Congressos como Assunto , Terapia Genética , Humanos , Transtornos do Olfato/patologia , Medicina Regenerativa , Bibliotecas de Moléculas Pequenas/uso terapêutico , Transplante de Células-Tronco , Células-Tronco/citologia , Células-Tronco/metabolismo , Distúrbios do Paladar/patologia
16.
Chem Res Toxicol ; 33(5): 1145-1162, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32349469

RESUMO

A variety of imaging and analytical methods have been developed to study nanoparticles in cells. Each has its benefits, limitations, and varying degrees of expense and difficulties in implementation. High-resolution analytical scanning transmission electron microscopy (HRSTEM) has the unique ability to image local cellular environments adjacent to a nanoparticle at near atomic resolution and apply analytical tools to these environments such as energy dispersive spectroscopy and electron energy loss spectroscopy. These tools can be used to analyze particle location, translocation and potential reformation, ion dispersion, and in vivo synthesis of second-generation nanoparticles. Such analyses can provide in depth understanding of tissue-particle interactions and effects that are caused by the environmental "invader" nanoparticles. Analytical imaging can also distinguish phases that form due to the transformation of "invader" nanoparticles in contrast to those that are triggered by a response mechanism, including the commonly observed iron biomineralization in the form of ferritin nanoparticles. The analyses can distinguish ion species, crystal phases, and valence of parent nanoparticles and reformed or in vivo synthesized phases throughout the tissue. This article will briefly review the plethora of methods that have been developed over the last 20 years with an emphasis on the state-of-the-art techniques used to image and analyze nanoparticles in cells and highlight the sample preparation necessary for biological thin section observation in a HRSTEM. Specific applications that provide visual and chemical mapping of the local cellular environments surrounding parent nanoparticles and second-generation phases are demonstrated, which will help to identify novel nanoparticle-produced adverse effects and their associated mechanisms.


Assuntos
Nanoestruturas/efeitos adversos , Nanoestruturas/análise , Especificidade de Órgãos , Microscopia Eletrônica de Transmissão
17.
Ann Intern Med ; 170(10): 673-681, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31035288

RESUMO

Background: Poor olfaction is common among older adults and has been linked to higher mortality. However, most studies have had a relatively short follow-up and have not explored potential explanations. Objective: To assess poor olfaction in relation to mortality in older adults and to investigate potential explanations. Design: Community-based prospective cohort study. Setting: 2 U.S. communities. Participants: 2289 adults aged 71 to 82 years at baseline (37.7% black persons and 51.9% women). Measurements: Brief Smell Identification Test in 1999 or 2000 (baseline) and all-cause and cause-specific mortality at 3, 5, 10, and 13 years after baseline. Results: During follow-up, 1211 participants died by year 13. Compared with participants with good olfaction, those with poor olfaction had a 46% higher cumulative risk for death at year 10 (risk ratio, 1.46 [95% CI, 1.27 to 1.67]) and a 30% higher risk at year 13 (risk ratio, 1.30 [CI, 1.18 to 1.42]). Similar associations were found in men and women and in white and black persons. However, the association was evident among participants who reported excellent to good health at baseline (for example, 10-year mortality risk ratio, 1.62 [CI, 1.37 to 1.90]) but not among those who reported fair to poor health (10-year mortality risk ratio, 1.06 [CI, 0.82 to 1.37]). In analyses of cause-specific mortality, poor olfaction was associated with higher mortality from neurodegenerative and cardiovascular diseases. Mediation analyses showed that neurodegenerative diseases explained 22% and weight loss explained 6% of the higher 10-year mortality among participants with poor olfaction. Limitation: No data were collected on change in olfaction and its relationship to mortality. Conclusion: Poor olfaction is associated with higher long-term mortality among older adults, particularly those with excellent to good health at baseline. Neurodegenerative diseases and weight loss explain only part of the increased mortality. Primary Funding Source: National Institutes of Health and Michigan State University.


Assuntos
Vida Independente , Transtornos do Olfato/mortalidade , Idoso , Doenças Cardiovasculares/mortalidade , Causas de Morte , Feminino , Humanos , Masculino , Doenças Neurodegenerativas/mortalidade , Pennsylvania/epidemiologia , Estudos Prospectivos , Fatores de Risco , Tennessee/epidemiologia
18.
J Sex Med ; 15(4): 502-509, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29501426

RESUMO

BACKGROUND: The sexual experience is shaped by sensory function; with aging, sensory dysfunction may interfere with sexuality and sexual behavior between partners. Specifically, older adults with age-related sensory dysfunction may have less sexual activity than those with better sensory function. In addition, since sexual desire and attraction rests in part upon sensory function, sensory dysfunction may also be associated with less sexual motivation. AIM: To test the association between sexual activity and motivation in older adults and their sensory dysfunction. METHODS: Sensory dysfunction was measured both by global sensory impairment (a validated measure of dysfunction shared among the 5 classic senses: olfaction, vision, taste, touch, hearing) and by total sensory burden (cumulative sensory loss). Sexual activity was quantified by frequency and type of sexual behavior. Sexual motivation was measured by the frequency of sexual ideation and the importance of sex to the respondent. We used cross-sectional data from a nationally representative sample of community-dwelling older adults (aged 57-85 years) in the United States (National Social Life, Health, and Aging Project, N = 3,005) in logistic regression analyses. OUTCOMES: Sexual activity, sexual motivation, and satisfaction with the sexual relationship were self-reported. RESULTS: Older adults with sensory dysfunction were less likely to be sexually active-an association that persisted when accounting for other factors that also affected sexual activity (age, gender, partnered status, mental and physical health, and relationship satisfaction). Nonetheless, sensory dysfunction did not impair sexual motivation, nor affect the physical and emotional satisfaction with the sexual relationship. Among currently sexually active older adults, sensory dysfunction did not affect the frequency of sex or the type of sexual activity (foreplay, vaginal intercourse, or oral sex). These results were the same for 2 different measures of sensory dysfunction. CLINICAL TRANSLATION: This is the first nationally representative study of sexuality and multisensory dysfunction in community-dwelling older adults. 4 of the 5 classic senses were measured with objective tests, and hearing was rated by interviewers in the context of their conversation. Medical and health care interventions that can reduce the burden of sensory dysfunction may improve older adults' sexual experience. CONCLUSIONS: Sensory dysfunction is associated with sexual inactivity, but not with sexual motivation. Among those who are sexually active, sensory dysfunction did not interfere with sexual expression. Improving the sexual experience of older adults requires a focus on sensory dysfunction as an impediment to sexual activity given that older adults remain sexually motivated. Zhong S, Pinto JM, Wroblewski KE, et al. Sensory Dysfunction and Sexuality in the U.S. Population of Older Adults. J Sex Med 2018;15:502-509.


Assuntos
Envelhecimento , Comportamento Sexual , Disfunções Sexuais Fisiológicas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Motivação , Autorrelato , Disfunções Sexuais Fisiológicas/etiologia , Inquéritos e Questionários , Estados Unidos/epidemiologia
19.
Alzheimer Dis Assoc Disord ; 32(3): 207-213, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29334499

RESUMO

BACKGROUND: The Montreal Cognitive Assessment (MoCA) has not been administered to a representative national sample, precluding comparison of patient scores to the general population and for risk factor identification. METHODS: A validated survey-based adaptation of the MoCA (MoCA-SA) was administered to a probability sample of home-dwelling US adults aged 62 to 90, using the National Social Life, Health, and Aging Project (n=3129), yielding estimates of prevalence in the United States. The association between MoCA-SA scores and sociodemographic and health-related risk factors were determined. RESULTS: MoCA-SA scores decreased with age, and there were substantial differences among sex, education, and race/ethnicity groups. Poor physical health, functional status, and depression were also associated with lower cognitive performance; current health behaviors were not. Using the recommended MoCA cut-point score for Mild Cognitive Impairment (MoCA score <26; MoCA-SA score <17), 72% (95% confidence interval, 69% to 74%) of older US adults would be classified as having some degree of cognitive impairment. CONCLUSIONS: Our results provide an important national estimate for interpreting MoCA scores from individual patients, and establish wide variability in cognition among older home-dwelling US adults. Care should be taken in applying previously-established MoCA cut-points to the general population, especially when evaluating individuals from educationally and ethnically diverse groups.


Assuntos
Cognição/fisiologia , Avaliação Geriátrica/estatística & dados numéricos , Vida Independente , Atividades Cotidianas , Idoso , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Fatores de Risco , Inquéritos e Questionários
20.
Med Sci Monit ; 24: 1887-1893, 2018 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-29603712

RESUMO

BACKGROUND The apnea-hypopnea index (AHI) and the mean apnea-hypopnea duration (MAD) are used to measure the severity of the symptoms of obstructive sleep apnea (OSA). The aim of this study was to compare the use of the MAD with the AHI as indicators of clinical and demographic parameters, blood oxygenation, and sleep parameters in patients diagnosed with OSA by polysomnography (PSG). MATERIAL AND METHODS A retrospective study included 511 patients with OSA diagnosed by PSG and who had the AHI and the MAD measured according to the guidelines from the American Academy of Sleep Medicine (AASM). The patients were divided into two groups: patients with a short MAD and with a long MAD, according to median duration, and using the inter-quartile range (IQR), as the data were not normally distributed. Clinical and demographic parameters were recorded. Pulse oximetry was used to measure blood oxygen saturation during sleep, sleep structure was recorded, and the Epworth Sleepiness Scale (ESS) questionnaire was used to measure daytime sleepiness. RESULTS In all 511 patients with OSA, the MAD was significantly, but weakly, correlated with the AHI (r=0.17, P<0.01), but showed no significant associations with patient age (r=0.08, P=0.06), body weight (r=0.014, P=0.75), and height (r=0.06, P=0.16). Patients with a long MAD or severe OSA (n=260) had significantly worse blood oxygen levels and sleep parameters. CONCLUSIONS For patients with severe OSA, this study showed that the MAD was a useful indicator of blood oxygenation and sleep parameters.


Assuntos
Apneia/metabolismo , Síndromes da Apneia do Sono/metabolismo , Apneia Obstrutiva do Sono/complicações , Adulto , Idoso , Apneia/sangue , Pressão Sanguínea/fisiologia , Feminino , Humanos , Hipertensão/complicações , Hipóxia/metabolismo , Masculino , Pessoa de Meia-Idade , Oximetria/métodos , Oxigênio/sangue , Polissonografia/métodos , Taxa Respiratória , Estudos Retrospectivos , Sono/fisiologia , Síndromes da Apneia do Sono/sangue , Fases do Sono/fisiologia
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