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Non-muscle myosin II (NMII) plays a role in many fundamental cellular processes including cell adhesion, migration, and cytokinesis. However, its role in mammalian vascular function is not well understood. Here, we investigated the function of NMII in the biomechanical and signalling properties of mouse aorta. We found that blebbistatin, an inhibitor of NMII, decreases agonist-induced aortic stress and stiffness in a dose-dependent manner. We also specifically demonstrate that in freshly isolated, contractile, aortic smooth muscle cells, the non-muscle myosin IIA (NMIIA) isoform is associated with contractile filaments in the core of the cell as well as those in the non-muscle cell cortex. However, the non-muscle myosin IIB (NMIIB) isoform is excluded from the cell cortex and colocalizes only with contractile filaments. Furthermore, both siRNA knockdown of NMIIA and NMIIB isoforms in the differentiated A7r5 smooth muscle cell line and blebbistatin-mediated inhibition of NM myosin II suppress agonist-activated increases in phosphorylation of the focal adhesion proteins FAK Y925 and paxillin Y118. Thus, we show in the present study, for the first time that NMII regulates aortic stiffness and stress and that this regulation is mediated through the tension-dependent phosphorylation of the focal adhesion proteins FAK and paxillin.
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Citoesqueleto/metabolismo , Adesões Focais/genética , Adesões Focais/metabolismo , Miosina Tipo II/genética , Rigidez Vascular/genética , Actinas/metabolismo , Animais , Biomarcadores , Células Cultivadas , Imunofluorescência , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Imuno-Histoquímica , Masculino , Camundongos , Contração Muscular/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miosina Tipo II/metabolismo , Fosforilação , Ligação Proteica , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Multimerização Proteica , Estresse MecânicoRESUMO
The Mekong Delta is host to a large number of freshwater species, including a unique group of facultative air-breathing Anabantiforms. Of these, the striped snakehead (Channa striata), the climbing perch (Anabas testudineus), the giant gourami (Osphronemus goramy) and the snakeskin gourami (Trichogaster pectoralis) are major contributors to aquaculture production in Vietnam. The gastrointestinal responses to feeding in these four species are detailed here. Relative intestinal length was lowest in the snakehead, indicating carnivory, and 5.5-fold greater in the snakeskin, indicating herbivory; climbing perch and giant gourami were intermediate, indicating omnivory. N-waste excretion (ammonia-N + urea-N) was greatest in the carnivorous snakehead and least in the herbivorous snakeskin, whereas the opposite trend was observed for net K+ excretion. Similarly, the more carnivorous species had a greater stomach acidity than the more herbivorous species. Measurements of acid-base flux to water indicated that the greatest postprandial alkaline tide occurred in the snakehead and a potential acidic tide in the snakeskin. Additional findings of interest were high levels of both PCO2 (up to 40 mmHg) and HCO3 - (up to 33 mM) in the intestinal chyme of all four of these air-breathing species. Using in vitro gut sac preparations of the climbing perch, it was shown that the intestinal net absorption of fluid, Na+ and HCO3 - was upregulated by feeding but not net Cl- uptake, glucose uptake or K+ secretion. Upregulated net absorption of HCO3 - suggests that the high chyme (HCO3 - ) does not result from secretion by the intestinal epithelium. The possibility of ventilatory control of PCO2 to regulate postprandial acid-base balance in these air-breathing fish is discussed.
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Comportamento Alimentar/fisiologia , Peixes/fisiologia , Trato Gastrointestinal/fisiologia , Amônia/metabolismo , Animais , Água Doce , Mucosa Intestinal/metabolismo , Íons/metabolismo , Período Pós-Prandial , Sódio/metabolismo , Ureia/metabolismo , VietnãRESUMO
Mammals in hibernation retain a relatively constant blood plasma pH (extracellular pH; pHe) that is typically alkaline relative to the pH of neutral water (pHnw). Given that pHnw increases as temperature falls, however, a constant pHe in hibernation represents a reduction in the relative degree of alkalinity (i.e. a relative acidosis) of plasma and extracellular fluids. The manner in which this is achieved during entrance into, and arousal from hibernation, however, is not straightforward and has implications for the control of ventilation. Furthermore, intracellular pH (pHi) changes in different ways in different tissues during hibernation. The dominant buffers involved in pH regulation are the imidazole buffer groups of histidyl residues of proteins and polypeptides. As a result, changes in the dissociation ratio of this buffer group (alpha imidazole; αim) directly affect the net electric charge of all functional proteins. The pKa of the imidazole ring on histidine is close to pHnw at 37⯰C and increases with decreasing temperature with an almost identical slope to that seen for pHnw. As a result, it has been suggested that the metabolic activity of tissues in which changes in pHi parallel changes in pHnw should be sustained while tissues in which changes in pHi parallel changes in pHe become relatively acidic and that this may contribute to metabolic suppression during hibernation. In this review we explore these implications.
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Equilíbrio Ácido-Base/fisiologia , Álcalis/metabolismo , Hibernação/fisiologia , Mamíferos/fisiologia , Acidose/metabolismo , Acidose/patologia , Animais , Temperatura Corporal , Dióxido de Carbono/metabolismo , Homeostase , Concentração de Íons de Hidrogênio , Imidazóis/metabolismo , Líquido Intracelular/metabolismo , Mamíferos/metabolismo , Músculos/metabolismo , Músculos/fisiologiaRESUMO
The American Academy of Pediatrics recommends annual testing in children beginning at 3 years of age to detect vision problems and prevent amblyopia. However, rates of vision testing in children from non-English primary language (NEPL) households are not well delineated. This study analyzed the 2018-2020 National Survey of Children's Health to examine patterns and predictors of vision testing among children from NEPL households. In this nationally representative cohort of 89,697 children 3-17 years of age, 70.9% of children received vision testing during the previous 12 months. Children from non-English-speaking households were less likely to undergo vision testing (64.3% vs 72.0%; aOR [95% CI] = 0.83 [0.72-0.95], P = 0.008). Decreased vision testing among children from NEPL households was driven by lower rates of testing at school (16.1% vs 21.0%; 0.72 [0.57-0.89], P = 0.009) or from an ophthalmologist or optometrist (49.0% vs 54.0%; 0.72 [0.61-0.85], P = 0.0004), whereas children from NEPL households were more likely to receive vision testing at health clinics (14.4% vs 3.1%; 3.25 [2.40-4.39], P < 0.0001). No differences were observed in rates of testing by a pediatrician (41.1% vs 44.0%; 1.05 [0.89-1.23], P = 0.69). Interventions to improve language services and health literacy are warranted to increase rates of vision testing among children from NEPL households.
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Ambliopia , Seleção Visual , Criança , Humanos , Estados Unidos/epidemiologia , Idoso , Idioma , Instituições AcadêmicasRESUMO
Purpose: To examine the prevalence and predictors of patient awareness of their disease in adults with age-related macular degeneration (AMD). Methods: This study analyzed 5553 adults 40 years or older in the 2005-2008 National Health and Nutrition Examination Survey who underwent retinal imaging. AMD was determined based on retinal images. Patient awareness of their AMD was assessed by a self-reported AMD diagnosis. Multivariable logistic regression models were constructed to examine the association of patient awareness of their AMD with sociodemographic characteristics and specific AMD lesion types on retinal imaging. Results: AMD was identified in 425 of the adults surveyed (6.5%) (95% confidence interval [CI], 5.5%-7.5%), including 87.7% (95% CI, 82.9%-92.5%) with early AMD and 12.3% (95% CI, 7.5%-17.1%) with late AMD. Among adults with either type of AMD on retinal imaging, 17.5% (95% CI, 13.1%-22.0%) were aware of their disease, which included 11.6% (95% CI, 8.4%-14.9%) with early AMD and 59.2% (95% CI, 43.1%-75.3%) with late AMD (P < .0001). In the same group, those aged 60 years or older (odds ratio [OR], 33.46; 95% CI, 7.67-146.03) and with a best-corrected visual acuity of 20/40 or worse (OR, 4.63; 95% CI, 2.95-7.26) had higher awareness of their AMD diagnosis, whereas Hispanic (OR, 0.28; 95% CI, 0.09-0.88) vs White adults and those who did not speak English at home (OR, 0.05; 95% CI, 0.01-0.41) had lower awareness of their diagnosis. Conclusions: Fewer than 1 in 5 adults with AMD were aware of their personal diagnosis, including fewer than 3 in 5 adults with late AMD. Older adults and those with worse vision were more likely to know they have AMD, whereas Hispanic adults and those who did not speak English at home were less likely. Efforts to increase patients' awareness of their AMD may improve rates of follow-up and prevent vision loss.
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Chronic diseases of aging are increasingly common. Dementia, often due to multiple etiologies including Alzheimer disease (AD), is at the forefront. Previous studies have reported higher rates of dementia among persons with diabetes, yet less is known about how insulin resistance relates to cognition. This article reviews recently published data on the relationship of insulin resistance to cognition and AD, and remaining knowledge gaps in the field are discussed. A structured review of studies was conducted over a 5-year period, investigating insulin and cognitive function in adults with a baseline mean age of ≥65 years. This search yielded 146 articles, of which 26 met the predetermined inclusion and exclusion criteria. Among the nine studies that specifically examined insulin resistance and cognitive dysfunction and/or decline, eight studies suggest an association, but some only in subanalyses. Results are mixed in studies relating insulin to structural and functional changes on brain imaging, and data on intranasal insulin for cognition remain unclear. Future avenues are proposed to elucidate the impact of insulin resistance on brain structure and function, including cognition, in persons with and without AD.
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Doença de Alzheimer , Disfunção Cognitiva , Resistência à Insulina , Humanos , Idoso , Doença de Alzheimer/etiologia , Doença de Alzheimer/psicologia , Cognição , InsulinaRESUMO
INTRODUCTION: Decreased public transit, novisitor policies, and other restrictions to reduce the spread of COVID19 may limit healthcare access for vision impaired adults. This study aimed to assess rates of healthcare delayed or forgone due to COVID19 among adults with low vision. METHODS: Data were analyzed from the 2021 National Health Interview Survey, a representative sample of US adults. Vision and hearing impairment were determined by selfreport. The primary study outcome was delayed or canceled medical care due to COVID19. Multivariable logistic regression models adjusted for gender, age, race, education, insurance, income, region, and chronic comorbidities were constructed to examine associations of medical care delayed due to COVID19. RESULTS: Overall, 1.6% (n=457) of adults had vision impairment and 1.6% (n=438) had hearing impairment. Vision impairment was not associated with having taken a COVID19 test (P=0.34) or previous COVID19 infection (P=0.46). Adults with vs without low vision had higher rates of delayed (30.7% vs 19.2%, 1.86 [1.43-2.42], P<.0001) and cancelled care due to COVID-19 (23.9% vs 12.2%, 2.21 [1.66-2.94], P<.0001). Even compared to adults with hearing impairment, those with vision impairment were more likely to report canceled medical care due to COVID19 (1.20 [1.02-1.41], P=0.03). CONCLUSION: Adults with low vision had increased risk of delayed and canceled medical care due to COVID19, with increased rates of canceled medical care even when compared to those with hearing impairment. These results suggest COVID19 and interventions to limit its spread have had a disproportionate impact on adults with low vision and place them at risk of poor health outcomes.
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COVID-19 , Pessoas com Deficiência , Perda Auditiva , Baixa Visão , Humanos , Adulto , COVID-19/epidemiologia , Baixa Visão/epidemiologia , Acessibilidade aos Serviços de SaúdeRESUMO
Hirsutism is a common condition characterized by excess hair growth and may lead to psychosocial distress and substantial mental health (MH) burden. These psychosocial manifestations may lead to MH emergencies and hospitalization. However, the prevalence and predictors of MH hospitalization associated with hirsutism are not well-understood. The objective of this study was to determine the likelihood and associations of MH hospitalization among females in the US with hirsutism. Data were analyzed from female inpatients in the 2005-2014 National Inpatient Sample, a representative sample of US hospitalizations. Multivariable logistic regression models were constructed to examine the association of MH hospitalization and comorbidities with hirsutism diagnosis. Patients with hirsutism were more likely to also have a comorbid MH disorder, compared to those without hirsutism (49.5% vs 27.5%, odds ratio [95% CI]: 3.33 [3.14-3.54]), including higher odds of having 14 of the 15 MH disorders studied. Moreover, those with hirsutism had higher odds of hospitalization for a MH disorder in multivariable logistic regression models adjusted for sex, age, and insurance coverage (14.0% vs 3.6%, 3.84 [3.50-4.21]). The mean length of hospital stay (LOS) for a MH disorder was greater among inpatients with vs without hirsutism (12.8 vs 7.1 days, ß [95% CI]: 5.71 [4.24-7.18]). There were two-way interactions of hirsutism and MH hospitalization as predictors of longer LOS. Among female inpatients with hirsutism, MH hospitalization was associated with younger age, having health insurance, and longer LOS, and inversely associated with elective admission. In conclusion, female inpatients with hirsutism have higher odds of comorbid MH disorders and MH hospitalizations, with much longer LOS. Patients may benefit from increased access to outpatient follow-up, as poor disease control may contribute to worse MH outcomes and more frequent hospitalization.
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Transtornos Mentais , Saúde Mental , Humanos , Feminino , Hirsutismo , Hospitalização , Tempo de Internação , Transtornos Mentais/epidemiologiaRESUMO
Purpose: To assess the accessibility and content of surgical and medical retina fellowship websites. Methods: The websites of all surgical and medical retina fellowship programs were examined. Each program's website was evaluated based on information available on 10 recruitment and 10 training criteria. The presence of the criteria was summed to calculate a total content score (range, 0-20). Also examined were the differences in website content score by number of fellows, geographic location, and Association of University Professors of Ophthalmology (AUPO) compliance. Results: This study identified 102 surgical and 25 medical retina programs. Overall, 91.2% of surgical and 88.0% of medical retina programs had an accessible website. The surgical retina program website contained a mean of 9.8 of the total criteria, including 4.9 recruitment criteria and 5.2 training criteria, with no significant differences by number of fellows, geography, or AUPO status. Medical retina websites contained a mean of 9.3 total criteria, including 4.5 recruitment criteria and 4.9 training criteria. Website content scores for medical retina programs were associated with geography and AUPO status, which was consistent when stratifyed by recruitment and training criteria. Conclusions: Most surgical and medical retina fellowships have an accessible program website. However, there are opportunities to improve the completeness and consistency of information on these websites. Improved websites can help programs attract well-suited candidates and might address multiple inefficiencies in the application process.
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Background Fellowship program Web sites are a crucial source of information for prospective pediatric ophthalmology applicants, especially in light of the restrictions on in-person interactions due to the coronavirus disease 2019 pandemic. Objective This study examined all pediatric ophthalmology fellowship Web sites for availability and presented recruitment and training content. Methods A full list of all pediatric ophthalmology and strabismus (POAS) fellowship programs were compiled from the Association of University Professors of Ophthalmology (AUPO) directory and the San Francisco Match (SFMatch) application listing. Each fellowship was queried by Google Internet search to identify the program's corresponding Web site. The content of Web sites was evaluated using 20 predetermined recruitment and training criteria. All data were collected in February 2022. Kruskal-Wallis and Mann-Whitney U tests were constructed to examine differences by geographic location, program size, number of teaching faculty, and affiliation with a top ophthalmology residency program. Results There were 45 pediatric ophthalmology fellowships identified from the AUPO and SFMatch. All pediatric ophthalmology fellowships had an available program Web site. However, there was significant variability in content, and the average Web site had approximately half of the evaluated criteria. POAS Web sites reported a greater number of recruitment criteria than program training criteria. There were no differences by program size, number of faculty, affiliation with a top residency program, or geographic location in the number of observed criteria. Conclusions This study provides data to drive efforts to improve pediatric ophthalmology fellowship Web sites. Pediatric ophthalmology fellowship Web sites are missing important information, and there are opportunities to improve program Web sites, regardless of program size, number of faculty, affiliation with a top residency, and geographic location. Informative, accurate Web sites may attract qualified candidates, and as a result, elevate the likelihood that interviewed candidates are well-suited to the program. As such, improvements to fellowship Web sites can streamline the application process and increase a program's success rate in the match.
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PURPOSE: To examine the association of childhood strabismus with functional limitation to identify particular domains of impairment. METHODS: The authors analyzed 201 children ages 5 to 17 years with strabismus enrolled in the 1996-2015 Medical Expenditure Panel Surveys, representative annual surveys of the U.S. POPULATION: Functional impairment was assessed using the Columbia Impairment Scale (CIS), a validated measure of behavioral and psychosocial functioning. A CIS score of 16 or greater defined clinically significant functional impairment. Multivariate regression models adjusted for age, sex, race, ethnicity, household income, geographic location, and insurance type were constructed to examine the association of strabismus diagnosis with overall impairment and individual domains of function. RESULTS: Children diagnosed as having strabismus had higher rates of clinically significant functional impairment compared to those without strabismus (15.1% vs 9.1%, adjusted odds ratio [95% CI]: 1.82 [1.11 to 2.97], P = .02). Moreover, strabismus diagnosis was associated with higher rates of problems with getting along with their mother (1.70 [1.21 to 2.40], P = .003) and father (1.66 [1.16 to 2.38], P = .006), getting along with other children (1.67 [1.16 to 2.40], P = .006), behavior at home (1.94 [1.37 to 2.74], P = .0002), staying out of trouble (1.52 [1.04 to 2.23], P = .03), nervousness (1.49 [1.05 to 2.11], P = .02), and getting involved with sports and hobbies (1.55 [1.03 to 2.34], P = .04). CONCLUSIONS: Childhood strabismus is associated with 1.8-fold greater odds of clinically significant functional impairment, with greater dysfunction in specific relationship and behavioral domains. Functional burden may be an important consideration in management decisions. [J Pediatr Ophthalmol Strabismus. 2023;60(4):268-276.].
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Background: Previous studies have found the increasing use of patient satisfaction scores by patients and insurance payers. Less is known about how patient mental health affects health care satisfaction. Objective: To examine the association between baseline mental health and health care satisfaction among adults with alopecia. Methods: We examined 543 adults with alopecia in the 2004-2016 Medical Expenditure Panel Survey. Mental health burden was assessed by the 6-item Kessler Psychological Distress Scale (K6) and 2-item Patient Health Questionnaire (PHQ2). Patient satisfaction was determined using the Consumer Assessment of Healthcare Providers and Systems survey. Results: Adults with versus without alopecia had higher rates of positive PHQ2 (adjusted odds ratio [95% CI], 1.37 [1.05-1.78]); positive K6 (1.57 [1.02-2.41]), and comorbid anxiety (1.85 [1.30-2.63]) and depression (1.68 [1.19-2.39]). Positive PHQ2 (2.15 [1.13, 4.11]) and positive K6 (6.04 [2.60, 14.05]) were associated with low patient satisfaction. Whereas, there were no differences in the rates of low patient satisfaction associated with comorbid anxiety (0.74 [0.33-1.67]) and depression (1.42 [0.72-2.78]). Limitations: Data are unavailable on alopecia areata phenotypes and treatment. Conclusions: Adults with alopecia and greater mental health symptoms report lower patient satisfaction. Clinicians may wish to adapt their communication style to support these patients and improve overall health care satisfaction.
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PRCIS: We assessed the readability of online glaucoma patient education materials using seven validated instruments. Overall, glaucoma materials were written at a 10th to 11th grade level, above the recommended seventh grade reading level. PURPOSE: Online health information is increasingly used by patients, yet previous studies show online patient education materials are often difficult to understand. As such, the American Medical Association recommends that patient education materials are written at or below a seventh grade reading level. This study aimed to assess the readability of online glaucoma patient education materials. METHODS: Glaucoma was entered into the Google search engine, and the first 30 search results were assessed for readability using seven validated readability instruments. Scientific articles, forums, and dictionary entries were excluded. Single sample t tests were used to assess whether online glaucoma materials were written above the recommended seventh grade level. RESULTS: Overall, glaucoma materials were written at a mean grade level of 10.33 (SD: 2.02). Across 6 grade level readability instruments, these patient education materials were written above the recommended seventh grade reading level (P<0.0001 for all). Glaucoma education materials only on the first page of Google search results were of a similar reading level: mean 10.56 (SD: 2.13). The readability instruments used in this study showed strong consistency. CONCLUSIONS: Glaucoma patient education materials are written above the recommended reading level to promote accessibility of education materials. This may contribute to lower patient engagement, worse clinical outcomes, and greater racial and ethnic disparities in glaucoma management. There is a need for reliable, simple glaucoma information to improve patient outcomes.
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Glaucoma , Letramento em Saúde , Compreensão , Letramento em Saúde/métodos , Humanos , Pressão Intraocular , Educação de Pacientes como Assunto , Estados UnidosRESUMO
BACKGROUND: Study participants, patients, and care partners are key stakeholders in research and have asked for greater inclusion in the dissemination of scientific learning. However, the participation of general audiences in scientific conferences dedicated to Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) is not widely supported or studied. OBJECTIVE: Our objectives were to evaluate the interest, level of engagement, and impact of including general audiences in a virtual dementia conference. METHODS: A diverse group of lay participants, identified via community-based health advocacy groups and research centers, were invited to attend the 2021 Alzheimer's Association International Conference (AAIC), with optional small-group discussions. Participants received complimentary access to all scientific sessions and were supported via navigation tips, recommended sessions, and a glossary of frequently used terms and acronyms. RESULTS: Lay participants demonstrated a high level of engagement, even among those that were research-naïve, attending virtual sessions for an average of 11.7 hours across the five days and recommending a variety of sessions to each other on topics extending from prevention of dementia to new therapies and care. Most participants said they would attend the conference again and rated the quality of interaction as high, while requesting more opportunities to engage directly with researchers. CONCLUSION: General audiences, in particular research participants, are advocating for greater participation in scientific conferences. This program can serve as a model to accomplish inclusion; thereby acknowledging their invaluable contribution to science.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/terapiaRESUMO
Burrowing rodents have a blunted ventilatory response to CO2 in comparison to non-burrowing rodents. Non-burrowing rats display a period during development where ventilatory responses to hypercarbia become transiently blunted. This study examined the ventilatory responses to CO2 of rats, hamsters and ground squirrels through neonatal development to determine whether the blunted adult response of burrowing species is a retention of the blunting period seen in rats or present from birth. All three species increased ventilation in response to hypercarbia on the day of birth (70-170% in response to 5% CO2; 100-250% in response to 7% CO2). Rats in our study exhibited the triphasic ventilatory response (when expressed as %Δ) to CO2 previously described. In golden-Syrian hamsters, the ventilatory response slowly and progressively waned to a blunted adult response while in the 13-lined ground squirrels, the early ventilatory response to CO2 decreased within days and remained attenuated through development. Our study shows three distinct developmental patterns in the hypercarbic ventilatory response.