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BackgroundThe COVID-19 pandemic has had a widespread impact on attendance in biomedical research and health care visits. ObjectiveThis study aimed to identify when and how American adults might feel comfortable about resuming in-person research and health care visits. MethodsCross-sectional questionnaire data were collected from 135 adults (age: median 48 years; women: n=113, 83.7%; White participants: n=92, 68.2%) who were engaged in health-related research. ResultsMore than half of the respondents (65/122, 53.3%) felt that the COVID-19 pandemic positively affected their desire to participate in research. Although 73.6% (95/129) of respondents also indicated a willingness to attend in-person health care visits while Centers for Disease Control and Prevention (CDC) guidelines are implemented, 85.8% (109/127) indicated a willingness to attend in-person, outdoor visits, and 92.2% (118/128) reported a willingness to attend drive-through visits (with CDC guidelines implemented during both visit types). Videoconferencing was the most preferred format for intervention visits; however, adults over the age of 65 years preferred this format less than younger adults (P=.001). ConclusionsResearchers and clinicians should continue to provide opportunities for continuing the conduction of remote-based interventions while enforcing CDC guidelines during in-person visits.

BackgroundPast studies examining barriers to patient portal adoption have been conducted with a small number of patients and health care settings, limiting generalizability. ObjectiveThis study had the following two objectives: (1) to assess the prevalence of barriers to patient portal adoption among nonadopters and (2) to examine the association between nonadopter characteristics and reported barriers in a nationally representative sample. MethodsData from this study were obtained from the 2019 Health Information National Trends Survey. We calculated descriptive statistics to determine the most prevalent barriers and conducted multiple variable logistic regression analysis to examine which characteristics were associated with the reported barriers. ResultsThe sample included 4815 individuals. Among these, 2828 individuals (58.73%) had not adopted a patient portal. Among the nonadopters (n=2828), the most prevalent barriers were patient preference for in-person communication (1810/2828, 64.00%), no perceived need for the patient portal (1385/2828, 48.97%), and lack of comfort and experience with computers (735/2828, 25.99%). Less commonly, individuals reported having no patient portal (650/2828, 22.98%), no internet access (650/2828, 22.98%), privacy concerns (594/2828, 21.00%), difficulty logging on (537/2828, 18.99%), and multiple patient portals (255/2828, 9.02%) as barriers. Men had significantly lower odds of indicating a preference for speaking directly to a provider compared with women (odds ratio [OR] 0.75, 95% CI 0.60-0.94; P=.01). Older age (OR 1.01, 95% CI 1.00-1.02; P

BackgroundAs the novel coronavirus disease (COVID-19) is widely spreading across the United States, there is a concern about the overloading of the nation’s health care capacity. The expansion of telehealth services is expected to deliver timely care for the initial screening of symptomatic patients while minimizing exposure in health care facilities, to protect health care providers and other patients. However, it is currently unknown whether US hospitals have the telehealth capacity to meet the increasing demand and needs of patients during this pandemic. ObjectiveWe investigated the population-level internet search volume for telehealth (as a proxy of population interest and demand) with the number of new COVID-19 cases and the proportion of hospitals that adopted a telehealth system in all US states. MethodsWe used internet search volume data from Google Trends to measure population-level interest in telehealth and telemedicine between January 21, 2020 (when the first COVID-19 case was reported), and March 18, 2020. Data on COVID-19 cases in the United States were obtained from the Johns Hopkins Coronavirus Resources Center. We also used data from the 2018 American Hospital Association Annual Survey to estimate the proportion of hospitals that adopted telehealth (including telemedicine and electronic visits) and those with the capability of telemedicine intensive care unit (tele-ICU). Pearson correlation was used to examine the relations of population search volume for telehealth and telemedicine (composite score) with the cumulative numbers of COVID-19 cases in the United States during the study period and the proportion of hospitals with telehealth and tele-ICU capabilities. ResultsWe found that US population–level interest in telehealth increased as the number of COVID-19 cases increased, with a strong correlation (r=0.948, P

Background: The association between obesity and cardiovascular disease (CVD) remains unclear, particularly for those with established CVD risk factors. We analyzed follow-up data from the Aichi Workers’ Cohort Study. We studied the association between the degree of obesity and risk of CVD and its subtypes specifically among individuals with hypertension, hyper-low-density lipoprotein (LDL)-cholesterolemia, or diabetes. Methods: Pooled data of 8972 adults (7076 men and 1896 women) who were recruited between 2002 and 2008 were used in the current analysis. We used multivariable Cox proportional hazard model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between the degree of obesity assessed with body mass index (BMI) and the risk of CVD and its subtypes, i.e., coronary heart disease (CHD) and stroke. Results: During a median of 12 years, there were 197 CVDs (80 CHDs and 117 strokes). BMI ≥ 27.5 compared to 21.0–22.9 kg/m2 was positively and significantly associated with the risks of CVD, CHD, and total stroke. Hypertension, hyper-LDL-cholesterolemia, and diabetes mediated 15.9%, 5.8%, and 8.7% of obesity-CVD associations, respectively, and 28.3% by their combination. In the stratified analyses by the presence of risk factors, BMI ≥ 25.0 (overweight/obesity) compared to BMI < 25 kg/m2 was associated with a higher risk of CVD in those with and without hypertension, but only with hyper-LDL-cholesterolemia, and without diabetes. Conclusions: Overweight/obesity was associated with the risk of CVD and its subtypes. About 30% of the risk was explained by hypertension, hyper-LDL-cholesterolemia, and diabetes, of which hypertension accounted for approximately the half of the explained risk. However, overweight/obesity increased the risk of CVD even in those without hypertension. These findings highlight the importance of controlling and preventing overweight/obesity regardless of chronic disease status.

OBJECTIVE: This study examined the longitudinal association of perceived stress, ikigai, and having someone one can count on in middle age with the advanced-level functional competency in older age, which is crucial for the maintenance of independent life among older adults. The issue is especially relevant in super-aged countries like contemporary Japan, where more and more older people live in a household consisting only of older people. METHODS: Data were collected in 2019 from a total of 1692 retirees of the Aichi Workers Cohort Study participants in which baseline survey including psychological factors was conducted during their employment in 2002. Japan Science and Technology Agency Index of Competence (JST-IC) was used to measure the advanced-level functional competency. Multivariable-adjusted odds ratios (ORs) were obtained for having low JST-IC in later life by the degrees of psychological factors reported in the middle age adjusting for the presence of depressive mood in 2019. RESULTS: Those who were not sure about ikigai (OR: 2.02, 95 % CI: 1.33 to 3.08) and who have no one to count on (OR: 2.19, 95 % CI: 1.52 to 3.16) in the middle age were significantly associated with low JST-IC after retirement. Having much stress was significantly inversely associated with a low JST-IC (OR: 0.69, 95 % CI: 0.50 to 0.97). CONCLUSION: Having ikigai and someone reliable, and stress during middle age might play a role in preventing impaired advanced-level functional competency. Improved ikigai and increased social interaction and support might improve functional competency. Further research might explore avenues for improving ikigai.

Coherent perfect absorption (CPA) has been studied in various fields, such as metasurface, photonics, and acoustics, because of its ability to perfectly absorb light at a specific wavelength. However, the narrow bandwidth of CPA makes its application to on-chip photonics challenging. This limitation can be overcome by using a broadband resonator. Here, we demonstrate the coherent perfect loss (CPL) with respect to a single and broadband resonator at photonic crystal nanobeam. By using the finite element method, both cases of the CPL were simulated and optimized for the single and broadband resonators. In the optimized structure, a CPL occurs for both resonators. These results confirm that the perfect loss region for the broadband resonator is wider than that for the single resonator. These results are experimentally verified by fabricating both cases of CPL cases on a silicon-on-insulator by using electron beam lithography. An almost perfect loss of more than 95 % is observed for both single and broadband CPLs. Furthermore, the almost perfect loss region at the broadband resonator broadens more than that at the single resonator. The optimized structure for CPL has the potential for easy applications to on-chip photonics, such as optical switches, modulators, sensors, and logic gates.

PurposeTo characterize and pharmacologically influence subconjunctival lymphatics in rabbit and mouse eyes.MethodsRabbits received subconjunctival injections of trypan blue or fixable fluorescent dextrans. Bleb-related outflow pathways were quantified. Immunofluorescence for vessel-specific markers (lymphatics [podoplanin and LYVE-1] and blood vessels [CD31]) were performed in native rabbit conjunctiva and after fixable fluorescent dextran injection. Vascular endothelial cell growth factor-C (VEGFC) was injected subconjunctivally in rabbits. mRNA and protein were assessed for the above markers using RT-PCR and Western blot. Alternatively, mouse studies used Prox1-tdTomato transgenic reporter mice. Subconjunctival injection conditions included: no injection, balanced salt solution (BSS), VEGFC, 5-fluorouracil (5FU) and two concentrations of mitomycin-C (MMC). Two mouse injection protocols (short and long) with different follow-up times and number of injections were performed. Mouse eyes were enucleated, flat mounts created, and subconjunctival branching and length assessed.ResultsRabbit eyes demonstrated clear bleb-related subconjunctival outflow pathways that were distinct from blood vessels and were without nasal/temporal predilection. Immunofluorescence against vessel-specific markers showed lymphatics and blood vessels in rabbit conjunctiva, and these lymphatics overlapped with bleb-related subconjunctival outflow pathways. Subconjunctival VEGFC increased lymphatic (P = 0.004-0.04) but not blood vessel (P = 0.77-0.84) mRNA or protein in rabbits. Prox1-tdTomato transgenic reporter mice demonstrated natively fluorescent lymphatics. Subconjunctival VEGFC increased murine lymphatic branching and length (P ≤ 0.001-0.004) while antimetabolites (P ≤ 0.001-0.043) did the opposite for the long protocol.DiscussionSubconjunctival lymphatics are pharmacologically responsive to both VEGFC and antimetabolites in two animal models studied using different methodologies. These results may be important for bleb-forming glaucoma surgeries or ocular drug delivery.

BackgroundMutations in PIEZO1 (Piezo type mechanosensitive ion channel component 1) cause human lymphatic malformations. We have previously uncovered an ORAI1 (ORAI calcium release-activated calcium modulator 1)-mediated mechanotransduction pathway that triggers lymphatic sprouting through Notch downregulation in response to fluid flow. However, the identity of its upstream mechanosensor remains unknown. This study aimed to identify and characterize the molecular sensor that translates the flow-mediated external signal to the Orai1-regulated lymphatic expansion.MethodsVarious mutant mouse models, cellular, biochemical, and molecular biology tools, and a mouse tail lymphedema model were employed to elucidate the role of Piezo1 in flow-induced lymphatic growth and regeneration.ResultsPiezo1 was found to be abundantly expressed in lymphatic endothelial cells. Piezo1 knockdown in cultured lymphatic endothelial cells inhibited the laminar flow-induced calcium influx and abrogated the flow-mediated regulation of the Orai1 downstream genes, such as KLF2 (Krüppel-like factor 2), DTX1 (Deltex E3 ubiquitin ligase 1), DTX3L (Deltex E3 ubiquitin ligase 3L,) and NOTCH1 (Notch receptor 1), which are involved in lymphatic sprouting. Conversely, stimulation of Piezo1 activated the Orai1-regulated mechanotransduction in the absence of fluid flow. Piezo1-mediated mechanotransduction was significantly blocked by Orai1 inhibition, establishing the epistatic relationship between Piezo1 and Orai1. Lymphatic-specific conditional Piezo1 knockout largely phenocopied sprouting defects shown in Orai1- or Klf2- knockout lymphatics during embryo development. Postnatal deletion of Piezo1 induced lymphatic regression in adults. Ectopic Dtx3L expression rescued the lymphatic defects caused by Piezo1 knockout, affirming that the Piezo1 promotes lymphatic sprouting through Notch downregulation. Consistently, transgenic Piezo1 expression or pharmacological Piezo1 activation enhanced lymphatic sprouting. Finally, we assessed a potential therapeutic value of Piezo1 activation in lymphatic regeneration and found that a Piezo1 agonist, Yoda1, effectively suppressed postsurgical lymphedema development.ConclusionsPiezo1 is an upstream mechanosensor for the lymphatic mechanotransduction pathway and regulates lymphatic growth in response to external physical stimuli. Piezo1 activation presents a novel therapeutic opportunity for preventing postsurgical lymphedema. The Piezo1-regulated lymphangiogenesis mechanism offers a molecular basis for Piezo1-associated lymphatic malformation in humans.

Background/Objectives: Plantar fasciitis (PF) is a common condition that causes heel pain. While various conservative treatment modalities for PF exist, no previous studies have investigated the effectiveness of shoe rotation (ShR) in patients with PF pain. This study aimed to compare the therapeutic effectiveness of ShR with that of two conventional treatments for PF—namely, foot orthosis (FO) and physical therapy (PT). Methods: Charts of 42 patients with heel pain were retrospectively reviewed. Participants were allocated to one of three treatment groups: the ShR group, the customized FO group, and the PT group. Pain and functional outcomes were assessed using the Visual Analog Scale (VAS), Digital Pain Scale (DPS), Foot Function Index (FFI), Foot Pain and Function Scale (FPFS), and American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS-AHS) at baseline and at 4 and 12 weeks after the intervention. Results: The ShR, FO, and PT groups all showed improvements, with statistically significant decreases in VAS, DPS, and FFI scores and significant increases in FPFS and AOFAS-AHS scores over time (p < 0.05). All three interventions resulted in significant improvements from baseline to 4 weeks and further to 12 weeks (p < 0.05). The ShR group exhibited a slightly larger effect on all measurements than the other groups. Conclusions: ShR, FO, and PT contributed to pain reduction and functional improvement, and alternating the shoes alleviated PF pain. These results suggest a new approach to managing PF and serve as a basis for providing convenient treatment for patients with PF.

AIM: Understanding the mechanism of fluid outflow by comparing the subconjunctival and subtenon spaces can lead to improved ocular therapeutics. The purpose of the current study is to evaluate subconjunctival vs subtenon lymphatic outflow by creating tracer-filled blebs in each location. METHODS: Porcine (n = 20) eyes received subconjunctival or subtenon injection(s) of fixable and fluorescent dextrans. Blebs were angiographically imaged using a Heidelberg Spectralis ([Heidelberg Retina Angiograph] HRA + OCT; Heidelberg Engineering) and bleb-related lymphatic outflow pathways were counted. Optical coherence tomography (OCT) imaging of these pathways was used to assess structural lumens and the presence of valve-like structures. Furthermore, a comparison between tracer injection locations (superior/inferior/temporal/nasal) was made. Histologic analyses for subconjunctival and subtenon outflow pathways were performed, to confirm tracer co-localization with molecular lymphatic markers. RESULTS: Subconjunctival blebs demonstrated a greater number of lymphatic outflow pathways compared to subtenon blebs in every quadrant [superior: 6.10 ± 1.18 (subconjunctival) vs 0.50 ± 0.27 (subtenon); temporal: 2.30 ± 0.40 vs 0.10 ± 0.10; nasal: 5.30 ± 0.60 vs 0.30 ± 0.21; inferior: 6.00 ±1.29 vs 0.1 ± 0.1; all comparisons p < 0.001]. For subconjunctival blebs, the temporal quadrant showed fewer lymphatic outflow pathways compared to the nasal side (p = 0.005). DISCUSSION: Subconjunctival blebs accessed greater lymphatic outflow compared to subtenon blebs. Furthermore, regional differences existed, with fewer lymphatic vessels temporal than at the other locations. CLINICAL SIGNIFICANCE: Aqueous humor drainage after glaucoma surgery is incompletely understood. The present manuscript adds to our understanding of how lymphatics might influence filtration bleb function. HOW TO CITE THIS ARTICLE: Lee JY, Strohmaier CA, Akiyama G, et al. Bleb-related Porcine Lymphatic Outflow Is Greater from Subconjunctival compared to Subtenon Blebs. J Curr Glaucoma Pract 2022;16(3):144-151.

Skull development coincides with the onset of cerebrospinal fluid (CSF) circulation, brain-CSF perfusion, and meningeal lymphangiogenesis, processes essential for brain waste clearance. How these processes are affected by craniofacial disorders such as craniosynostosis are poorly understood. We report that raised intracranial pressure and diminished CSF flow in craniosynostosis mouse models associate with pathological changes to meningeal lymphatic vessels that affect their sprouting, expansion, and long-term maintenance. We also show that craniosynostosis affects CSF circulatory pathways and perfusion into the brain. Further, craniosynostosis exacerbates amyloid pathology and plaque buildup in [Twist1.sup.+/-] :5xFAD transgenic Alzheimer's disease models. Treating craniosynostosis mice with Yoda1, a small molecule agonist for Piezo1, reduces intracranial pressure and improves CSF flow, in addition to restoring meningeal lymphangiogenesis, drainage to the deep cervical lymph nodes, and brain-CSF perfusion. Leveraging these findings, we show that Yoda1 treatments in aged mice with reduced CSF flow and turnover improve lymphatic networks, drainage, and brain-CSF perfusion. Our results suggest that CSF provides mechanical force to facilitate meningeal lymphatic growth and maintenance. Additionally, applying Yoda1 agonist in conditions with raised intracranial pressure and/or diminished CSF flow, as seen in craniosynostosis or with ageing, is a possible therapeutic option to help restore meningeal lymphatic networks and brain-CSF perfusion., Introduction Meningeal lymphatic vessels (MLVs) facilitate drainage of cerebrospinal fluid (CSF) from the head to help control CNS waste clearance, immune surveillance, and responses to injury (1). MLVs reside in [...]

PURPOSE: To uncover the mechanism of subconjunctival outflow in human patients. DESIGN: Cross-sectional study. SUBJECTS/PARTICIPANTS AND/OR CONTROLS: Fifteen subjects receiving subconjunctival anesthesia prior to intravitreal injection for routine clinical care. METHODS: Anterior segment OCT (AS-OCT) was performed in patients with various instances of conjunctival edema or subconjunctival fluid. Other subjects received a subconjunctival mixture of 0.005% indocyanine green and 2% lidocaine. After subconjunctival injection of the tracer/anesthetic mixture, blebs and associated outflow pathways were angiographically imaged and the time for appearance recorded. The pattern and structure of outflow pathways were studied using AS-OCT. Angiographic and AS-OCT results were compared to trabecular/conventional outflow imaging which demonstrates veins. MAIN OUTCOME MEASURES: Ocular surface lymphangiography and AS-OCT images. RESULTS: AS-OCT of the conjunctiva in a normal eye demonstrated thin non-edematous conjunctiva with absent intraconjunctival lumens or subconjunctival fluid. Subjects with a history of trabeculectomy, subconjunctival drug injection, or chemosis demonstrated thickened conjunctiva and intraconjunctival luminal pathways that contained valve-like structures. Tracer-based studies in patients demonstrated blebs with irregular subconjunctival bleb-related outflow patterns that arose in a time-dependent fashion. These angiographic pathways were luminal on OCT, sausage-shaped, and contained intraluminal valve-like structures. This was in contrast to trabecular/conventional outflow imaging where pathways were classically Y-shaped, of even-caliber, and lacked valve-like structures. DISCUSSION: Outflow pathways were seen in cases of conjunctival edema and after subconjunctival tracer injection. These pathways were lymphatic based upon pattern and structural study. Better understanding of bleb-related lymphatic outflow may lead to improved bleb-requiring glaucoma surgeries and subconjunctival drug delivery.

Despite many reports about pulmonary blood vessels in lung fibrosis, the contribution of lymphatics to fibrosis is unknown. We examined the mechanism and consequences of lymphatic remodeling in mice with lung fibrosis after bleomycin injury or telomere dysfunction. Widespread lymphangiogenesis was observed after bleomycin treatment and in fibrotic lungs of prospero homeobox 1-enhanced green fluorescent protein (Prox1-EGFP) transgenic mice with telomere dysfunction. In loss-of-function studies, blocking antibodies revealed that lymphangiogenesis 14 days after bleomycin treatment was dependent on vascular endothelial growth factor (Vegf) receptor 3 signaling, but not on Vegf receptor 2. Vegfc gene and protein expression increased specifically. Extensive extravasated plasma, platelets, and macrophages at sites of lymphatic growth were potential sources of Vegfc. Lymphangiogenesis peaked at 14 to 28 days after bleomycin challenge, was accompanied by doubling of chemokine (C-C motif) ligand 21 in lung lymphatics and tertiary lymphoid organ formation, and then decreased as lung injury resolved by 56 days. In gain-of-function studies, expansion of the lung lymphatic network by transgenic overexpression of Vegfc in club cell secretory protein (CCSP)/VEGF-C mice reduced macrophage accumulation and fibrosis and accelerated recovery after bleomycin treatment. These findings suggest that lymphatics have an overall protective effect in lung injury and fibrosis and fit with a mechanism whereby lung lymphatic network expansion reduces lymph stasis and increases clearance of fluid and cells, including profibrotic macrophages.

Three new mixed metal fluoride hydrates, M2+AlF5(H2O)7 (M2+ = Fe2+, Co2+, or Ni2+), were synthesized and characterized. The crystals of M2+AlF5(H2O)7 were obtained using a hydrothermal method with a CF3COOH aqueous solution. The crystal structures displayed polymorphisms in C2/m (No. 12) or P-1 (No. 2) space groups, depending on temperature variations. The observed polymorphisms in M2+AlF5(H2O)7 are associated with changes in the bonding environment of [M(H2O)6]2+ and [AlF5(H2O)]2− octahedra, along with changes in hydrogen bonds and unit cell volumes. Infrared spectra and thermogravimetric analyses confirmed the presence of water molecules. The ultraviolet–visible spectra of M2+AlF5(H2O)7 revealed distinctive absorption bands dependent on the [M(H2O)6]2+ complex. This work provides a detailed account of the synthetic procedure, crystal structures, and spectroscopic characterization of M2+AlF5(H2O)7.