The Impact of COVID-19 and Pandemic Mitigation Measures on Persons With Sensory Impairment.

PURPOSE: To assess the impact of the COVID-19 pandemic and associated mitigation measures on persons with sensory impairments (SI), including visual impairments (VI) and hearing impairments (HI). DESIGN: Cross-sectional survey. METHODS: Adults with VI (best-corrected visual acuity <20/60 in the better-seeing eye), HI (International Classification of Diseases, Tenth Revision, codes), and age- and sex-matched controls (n = 375) were recruited from the University of Michigan. The 34-item Coronavirus Disability Survey was administered. Both χ2 tests and logistic regression were used to compare survey responses between groups. RESULTS: All groups reported high levels of disruption of daily life, with 80% reporting "a fair amount" or "a lot" of disruption (VI: 76%, HI: 83%, CT: 82%, P = .33). Participants with VI had greater difficulty with day-to-day activities and were more likely to cite the following reasons: caregiver was worried about COVID-19 (odds ratio [OR]VI = 7.2, 95% CI = 3.5-14.4, P < .001) and decreased availability of public transportation (ORVI = 5.0, 95% CI = 1.5-15.6, P = .006). Participants with VI, but not HI, showed a trend toward increased difficulty accessing medical care (ORVI = 2.0, 95% CI = 0.99-4.0, P = .052) and began relying more on others for day-to-day assistance (ORVI = 3.1, 95% CI = 1.6-5.7, P < .001). Overall, 30% reported difficulty obtaining trusted information about the pandemic. Those with VI reported more difficulty seeing or hearing trusted information (ORVI = 6.1, 95% CI = 1.6-22.1, P = .006). Employed participants with HI were more likely to report a reduction in wages (ORHI = 2.5, 95% CI = 1.2-5.3, P = .02). CONCLUSIONS: Individuals with VI have experienced increased disruption and challenges in daily activities related to the pandemic. People with SI may benefit from targeted policy approaches to the current pandemic and future stressors. Minimal differences in some survey measures may be due to the large impact of the pandemic on the population as a whole. The SARS-CoV-2 (COVID-19) pandemic and public health mitigation measures have had an exceedingly large impact around the globe. As of the time of writing, more than 114 million global cases (28 million US) had been diagnosed, and there had been more than 2.5 million fatalities attributed to COVID-19 (517,000 US).1,2.

Vision-related quality of life in adults with severe peripheral vision loss: a qualitative interview study.

BACKGROUND: Existing patient-reported outcome (PRO) measures may not be relevant to the full range of functional and vision-related quality of life (VR-QOL) concerns of individuals with vision impairment due to severe peripheral field loss (PFL). Measurement of VR-QOL in severe PFL is important in order to determine the effectiveness of vision rehabilitation interventions for this population. The purpose of this study was to characterize the impact of severe PFL due to retinitis pigmentosa (RP) and glaucoma on VR-QOL as the initial phase in the development of a novel PRO measure. METHODS: Individuals with severe PFL due to RP or glaucoma were recruited from the Kellogg Eye Center and the Association for the Blind and Visually Impaired. Participants completed semi-structured qualitative interviews, the Impact of Vision Impairment (IVI) questionnaire and the RAND 36-Item Health Survey. Interviews were analyzed by two coders using thematic analysis. A matrix analysis was conducted to compare VR-QOL by cause of severe PFL. Sample size was determined by thematic saturation. RESULTS: The study included 37 participants (19 RP, 18 glaucoma). Median best-corrected visual acuity for those with RP and glaucoma was 20/40 and 20/27.5, while Pelli-Robson contrast sensitivity was 1.2 log contrast sensitivity (logCS) and 1.1 logCS, respectively. Median domain scores on the IVI (reading, mobility, well-being) ranged from a low of - 0.2 to a high of 0.7 logits in those with RP and from 0.5 to 1.2 logits in those with glaucoma. Qualitative interviews identified six VR-QOL themes relevant across participants with both RP and glaucoma, including activity limitations, driving, emotional well-being, reading, mobility, and social function. VR-QOL concerns were largely consistent among those with severe PFL due to RP and glaucoma. These overarching themes contained content relevant to specific challenges related to severe PFL. CONCLUSIONS: There are commonly occurring VR-QOL concerns among individuals with severe PFL due to RP and glaucoma. The outlined themes will serve as the basis for development of the Low Vision Severely Constricted Peripheral Eyesight (LV-SCOPE) Questionnaire.

Cardiovascular Programming During and After Diabetic Pregnancy: Role of Placental Dysfunction and IUGR.

Intrauterine growth restriction (IUGR) is a condition whereby a fetus is unable to achieve its genetically determined potential size. IUGR is a global health challenge due to high mortality and morbidity amongst affected neonates. It is a multifactorial condition caused by maternal, fetal, placental, and genetic confounders. Babies born of diabetic pregnancies are usually large for gestational age but under certain conditions whereby prolonged uncontrolled hyperglycemia leads to placental dysfunction, the outcome of the pregnancy is an intrauterine growth restricted fetus with clinical features of malnutrition. Placental dysfunction leads to undernutrition and hypoxia, which triggers gene modification in the developing fetus due to fetal adaptation to adverse utero environmental conditions. Thus, in utero gene modification results in future cardiovascular programming in postnatal and adult life. Ongoing research aims to broaden our understanding of the molecular mechanisms and pathological pathways involved in fetal programming due to IUGR. There is a need for the development of effective preventive and therapeutic strategies for the management of growth-restricted infants. Information on the mechanisms involved with in utero epigenetic modification leading to development of cardiovascular disease in adult life will increase our understanding and allow the identification of susceptible individuals as well as the design of targeted prevention strategies. This article aims to systematically review the latest molecular mechanisms involved in the pathogenesis of IUGR in cardiovascular programming. Animal models of IUGR that used nutrient restriction and hypoxia to mimic the clinical conditions in humans of reduced flow of nutrients and oxygen to the fetus will be discussed in terms of cardiac remodeling and epigenetic programming of cardiovascular disease. Experimental evidence of long-term fetal programming due to IUGR will also be included.

Stigma, self-blame, and satisfaction with care among patients with lung cancer.

OBJECTIVE: We sought to understand the experiences of patients with lung cancer and to see if attitudes varied by demographic factors. METHODS: We administered a 63-question survey by phone or online among 174 patients with lung cancer. Factor analysis was used to identify two groups of questions with a conceptual relationship and high Cronbach's alphas, stigma and satisfaction with care. We used a multivariable analysis to identify predictors of self-blame and the factors of stigma and satisfaction with care. RESULTS: Patients were satisfied with the quality of their care and treatment choices but did not feel that there is enough public support for or research in lung cancer. Predictors of lower satisfaction with care were never being a smoker, lack of college education, not living in a rural location, refusing to report income, and not knowing/not being sure of stage. Self-blame was modest; in multivariable analysis, predictors of self-blame were believing that smoking was a cause of their lung cancer, younger age, male sex, living in a suburban location, and not knowing/not being sure of the stage of the cancer. Reported stigma was low and the only predictor for stigma was being married. Despite low scores on their personal experience of stigma, patients reported a high degree of stigmatization of lung cancer in general. Smoking was a significant predictor of personal stigma. CONCLUSION: Despite satisfaction with their treatment and care, lung cancer patients feel that society stigmatizes them as a general population. Patients who smoke are more likely to report that they have personally experienced stigma.

GPR41 modulates insulin secretion and gene expression in pancreatic ß-cells and modifies metabolic homeostasis in fed and fasting states.

Insulin secretion by pancreatic ß-cells is primarily regulated by glucose; however, hormones and additional nutrients, such as long-chain fatty acids, also play an important role in adjusting insulin output to physiologic needs. To examine the role of short-chain fatty acids (SCFAs) in ß-cell function, we analyzed mouse models of gain and loss of function of GPR41 (FFAR3), a receptor for SCFAs, vs. wild-type control mice. GPR41 gain of function [GPR41-overexpressing transgenic (41 Tg) model] and GPR41 loss of function [GPR41-knockout (KO 41) model] resulted in complementary changes in glucose tolerance, without significant effects on insulin sensitivity. KO 41 mice showed fasting hypoglycemia, which was consistent with increased basal and glucose-induced insulin secretion by islets in vitro Mirroring this, 41 Tg islets showed impaired glucose responsiveness in vitro Microarray analysis of islets from 41 Tg mice indicated significant alterations in gene expression patterns; several of the altered genes were chosen for further analysis and were also observed to change upon incubation of islets and cultured ß-cells with SCFAs in a GPR41-dependent manner. Taken together, our results indicate that GPR41 and its ligands, SCFAs, may play an important role in the fine-tuning of insulin secretion in fed and fasting states.-Veprik, A., Laufer, D., Weiss, S., Rubins, N., Walker, M. D. GPR41 modulates insulin secretion and gene expression in pancreatic ß-cells and modifies metabolic homeostasis in fed and fasting states.

Gene flow, population growth and a novel substitution rate estimate in a subtidal rock specialist, the black-faced blenny Tripterygion delaisi (Perciformes, Blennioidei, Tripterygiidae) from the Adriatic Sea.

Population histories depend on the interplay between exogeneous and endogeneous factors. In marine species, phylogeographic and demographic patterns are often shaped by sea level fluctuations, water currents and dispersal ability. Using mitochondrial control region sequences (n = 120), we infer phylogeographic structure and historic population size changes of a common littoral fish species, the black-faced blenny Tripterygion delaisi (Perciformes, Blennioidei, Tripterygiidae) from the north-eastern Adriatic Sea. We find that Adriatic T. delaisi are differentiated from conspecific populations in the remaining Mediterranean, but display little phylogeographic structure within the Adriatic basin. The pattern is consistent with passive dispersal of planktonic larvae along cyclonic currents within the Adriatic Sea, but limited active dispersal of adults. Demographic reconstructions are consistent with recent population expansion, probably triggered by rising sea levels after the last glacial maximum (LGM). Placing the onset of population growth between the LGM and the warming of surface waters (18 000-13 000 years BP) and employing a novel expansion dating approach, we inferred a substitution rate of 2.61-3.61% per site per MY. Our study is one of only few existing investigations of the genetic structure of animals within the Adriatic basin and is the first to provide an estimate for mitochondrial control region substitution rates in blennioid fishes.

Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism.

Rho-associated kinase 2 (ROCK2) regulates the secretion of proinflammatory cytokines and the development of autoimmunity in mice. Data from a phase 1 clinical trial demonstrate that oral administration of KD025, a selective ROCK2 inhibitor, to healthy human subjects down-regulates the ability of T cells to secrete IL-21 and IL-17 by 90% and 60%, respectively, but not IFN-γ in response to T-cell receptor stimulation in vitro. Pharmacological inhibition with KD025 or siRNA-mediated inhibition of ROCK2, but not ROCK1, significantly diminished STAT3 phosphorylation and binding to IL-17 and IL-21 promoters and reduced IFN regulatory factor 4 and nuclear hormone RAR-related orphan receptor γt protein levels in T cells derived from healthy subjects or rheumatoid arthritis patients. Simultaneously, treatment with KD025 also promotes the suppressive function of regulatory T cells through up-regulation of STAT5 phosphorylation and positive regulation of forkhead box p3 expression. The administration of KD025 in vivo down-regulates the progression of collagen-induced arthritis in mice via targeting of the Th17-mediated pathway. Thus, ROCK2 signaling appears to be instrumental in regulating the balance between proinflammatory and regulatory T-cell subsets. Targeting of ROCK2 in man may therefore restore disrupted immune homeostasis and have a role in the treatment of autoimmunity.

Speeding up social waves. Propagation mechanisms of shimmering in giant honeybees.

Shimmering is a defence behaviour in giant honeybees (Apis dorsata), whereby bees on the nest surface flip their abdomen upwards in a Mexican wave-like process. However, information spreads faster than can be ascribed to bucket bridging, which is the transfer of information from one individual to an adjacent one. We identified a saltatoric process that speeds up shimmering by the generation of daughter waves, which subsequently merge with the parental wave, producing a new wave front. Motion patterns of individual "focus" bees (n = 10,894) and their shimmering-active neighbours (n = 459,558) were measured with high-resolution video recording and stereoscopic imaging. Three types of shimmering-active surface bees were distinguished by their communication status, termed "agents": "Bucket-bridging" agents comprised 74.98% of all agents, affected 88.17% of their neighbours, and transferred information at a velocity of v = 0.317±0.015 m/s. "Chain-tail" agents comprised 9.20% of the agents, were activated by 6.35% of their neighbours, but did not motivate others to participate in the wave. "Generator agents" comprised 15.82% of agents, showed abdominal flipping before the arrival of the main wave front, and initiated daughter waves. They affected 6.75% of their neighbourhood and speeded up the compound shimmering process compared to bucket bridging alone by 41.5% to v = 0.514±0.019 m/s. The main direction of shimmering was reinforced by 35.82% of agents, whereas the contribution of the complementing agents was fuzzy. We discuss that the saltatoric process could enable the bees to instantly recruit larger cohorts to participate in shimmering and to respond rapidly to changes in flight direction of preying wasps. A third, non-exclusive explanation is that at a distance of up to three metres from the nest the acceleration of shimmering could notably contribute to the startle response in mammals and birds.

How to join a wave: decision-making processes in shimmering behavior of Giant honeybees (Apis dorsata).

Shimmering is a collective defence behaviour in Giant honeybees (Apis dorsata) whereby individual bees flip their abdomen upwards, producing Mexican wave-like patterns on the nest surface. Bucket bridging has been used to explain the spread of information in a chain of members including three testable concepts: first, linearity assumes that individual "agent bees" that participate in the wave will be affected preferentially from the side of wave origin. The directed-trigger hypothesis addresses the coincidence of the individual property of trigger direction with the collective property of wave direction. Second, continuity describes the transfer of information without being stopped, delayed or re-routed. The active-neighbours hypothesis assumes coincidence between the direction of the majority of shimmering-active neighbours and the trigger direction of the agents. Third, the graduality hypothesis refers to the interaction between an agent and her active neighbours, assuming a proportional relationship in the strength of abdomen flipping of the agent and her previously active neighbours. Shimmering waves provoked by dummy wasps were recorded with high-resolution video cameras. Individual bees were identified by 3D-image analysis, and their strength of abdominal flipping was assessed by pixel-based luminance changes in sequential frames. For each agent, the directedness of wave propagation was based on wave direction, trigger direction, and the direction of the majority of shimmering-active neighbours. The data supported the bucket bridging hypothesis, but only for a small proportion of agents: linearity was confirmed for 2.5%, continuity for 11.3% and graduality for 0.4% of surface bees (but in 2.6% of those agents with high wave-strength levels). The complimentary part of 90% of surface bees did not conform to bucket bridging. This fuzziness is discussed in terms of self-organisation and evolutionary adaptedness in Giant honeybee colonies to respond to rapidly changing threats such as predatory wasps scanning in front of the nest.

Adult day health center participation and health-related quality of life.

PURPOSE: The purpose of this study was to assess the association between Adult Day Health Center (ADHC) participation and health-related quality of life. DESIGN AND METHODS: Case-controlled prospective study utilizing the Medical Outcomes Survey Form 36 (SF-36) to compare newly enrolled participants from 16 ADHC programs with comparable community-dwelling older adults who did not attend an ADHC. Assessments were conducted at study enrollment, 6 and 12 months. RESULTS: ADHC participants (n = 57) and comparison group subjects (n = 67) were similar at baseline in age, ethnic diversity, medical conditions, depression, cognition, immigration history, education, income, and marital status. Significantly more comparison group subjects lived alone (p = .002). One year after enrollment, the SF-36 domains role physical and role emotional improved significantly. Adjusted role physical scores for ADHC participants improved (23 vs. 36) but declined for the comparison group (38 vs. 26, time by group interaction p = .01), and role emotional scores improved for ADHC participants (62 vs.70) but declined for the comparison group (65 vs. 48, time by group interaction p = .02). Secondary analyses revealed that changes in daily physical functioning, depressed affect, or cognitive functioning did not explain the improvements found in role physical and role emotional scores for ADHC participants. No significant differences in trends for the 2 groups occurred for the SF-36 domains physical functioning, social functioning, and mental health. IMPLICATIONS: ADHC participation may enhance older adults' quality of life. Quality of life may be a key measure to inform care planning, program improvement, and policy development of ADHC.

Identification of a phytotoxic photo-transformation product of diclofenac using effect-directed analysis.

The pharmaceutical diclofenac (DCF) is released in considerably high amounts to the aquatic environment. Photo-transformation of DCF was reported as the main degradation pathway in surface waters and was found to produce metabolites with enhanced toxicity to the green algae Scenedesmus vacuolatus. We identified and subsequently confirmed 2-[2-(chlorophenyl)amino]benzaldehyde (CPAB) as a transformation product with enhanced toxicity using effect-directed analysis. The EC(50) of CPAB (4.8 mg/L) was a factor of 10 lower than that for DCF (48.1 mg/L), due to the higher hydrophobicity of CPAB (log K(ow) = 3.62) compared with DCF (log D(ow) = 2.04) at pH 7.0.

Augmenting the Cartesian medical discourse with an understanding of the person's lifeworld, lived body, life story and social identity.

Using three paradigm cases of persons living with Parkinson's Disease (PD) the authors make a case for augmenting and enriching a Cartesian medical account of the pathophysiology of PD with an enriched understanding of the lived body experience of PD, the lived implications of PD for a particular person's concerns and coping with the illness. Linking and adding a thick description of the lived experience of PD can enrich caregiving imagination and attunement to the patient's possibilities, concerns and constraints. The work of Merleau-Ponty is used to articulate the middle terms of the lived experience of dwelling in a lifeworld. Examining lived experience of embodied intentionality, skilled bodily capacities as highlighted in Merleau-Ponty's non-mechanistic physiology opens new therapeutic, coping and caregiving possibilities. Matching temporal rhythms can decrease the stress of being assisted with activities of daily living. For example, caregivers and patients alike can be taught strategies for extending their lived bodily capacities by altering rhythms, by shifting hyperactivity to different parts of the body and other strategies that change the perceptual experience associated with walking in different environment. A medical account of the pathophysiology of PD is nessessary and useful, but not sufficient for designing caregiving in ways that enrich and extend the existential skills of dwelling of persons with PD. The dominance of mechanistic physiology makes caregivers assume that it is the 'real discourse' about the disease, causing researchers and caregivers alike to overlook the equally real lived experience of the patient which requires different descriptive discourses and different sources of understanding. Lack of dialogue between the two discourses is tragic for patients because caregivers need both in order to provide attuned, effective caregiving.

Economism, efficiency, and the moral ecology of good nursing practice.

The free-market rhetoric dominating health-policy discussions today frames health-care goods and services as commodities that consumers will or will not buy at a given price. Health-care systems are being redesigned and hospitals restructured with a view to increased efficiency and productivity. Drawing on the experiences of clinical nurses in the United States, this paper shows how the application of economism to nursing may severely disrupt the ecology of good practice, leading to difficulties in meeting minimal standards of nursing care and severely constraining the acts of compassion called for by the human experiences of illness, loss, and death. Concerns about moral responsibility and conflicts between institutional and nursing goals are described. Increasing mistrust of health-care systems on the part of practitioners, patients, and families suggests that it is time to attend closely to the moral ecology of caring practices.

Regulation of the GPR40 locus: towards a molecular understanding.

GPR40 {FFAR1 [non-esterified ('free') fatty acid receptor 1]} is a G-protein-coupled receptor expressed preferentially in pancreatic beta-cells. GPR40 functions as a receptor for medium and long-chain fatty acids, and has been implicated in mediating both physiological and pathological effects of fatty acids on beta-cells. The GPR40 gene is encoded at an interesting chromosomal locus that contains several genes: at the 5'-end of the locus, located approximately 4 kb upstream of GPR40, is CD22, a gene encoding a receptor expressed selectively in lymphocytes and involved in B-lymphocyte maturation and function. At the 3'-end of the locus are the GPR41 (FFAR3) and GPR43 (FFAR2) genes encoding receptors activated by short-chain fatty acids. The intergenic region between CD22 and GPR40 contains several evolutionarily conserved sequence blocks, among them HR2 and HR3. beta-Cell-specific expression of GPR40 is controlled at the transcriptional level through HR2, a potent beta-cell-specific enhancer. The mechanisms controlling cell-specific expression of the remaining genes in the cluster are unknown. Given the divergent modes of expression of the genes within the locus and their demonstrated physiological significance, it is important to analyse further the locus with a view to fully understanding the basis for transcriptional regulation of the encoded genes.

PPAR-gamma activation fails to provide myocardial protection in ischemia and reperfusion in pigs.

Peroxisome proliferator-activated receptor (PPAR)-gamma modulates substrate metabolism and inflammatory responses. In experimental rats subjected to myocardial ischemia-reperfusion (I/R), thiazolidinedione PPAR-gamma activators reduce infarct size and preserve left ventricular function. Troglitazone is the only PPAR-gamma activator that has been shown to be protective in I/R in large animals. However, because troglitazone contains both alpha-tocopherol and thiazolidinedione moieties, whether PPAR-gamma activation per se is protective in myocardial I/R in large animals remains uncertain. To address this question, 56 pigs were treated orally for 8 wk with troglitazone (75 mg x kg(-1) x day(-1)), rosiglitazone (3 mg x kg(-1) x day(-1)), or alpha-tocopherol (73 mg x kg(-1) x day(-1), equimolar to troglitazone dose) or received no treatment. Pigs were then anesthetized and subjected to 90 min of low-flow regional myocardial ischemia and 90 min of reperfusion. Myocardial expression of PPAR-gamma, determined by ribonuclease protection assay, increased with troglitazone and rosiglitazone compared with no treatment. Rosiglitazone had no significant effect on myocardial contractile function (Frank-Starling relations), substrate uptake, or expression of proinflammatory cytokines during I/R compared with untreated pigs. In contrast, preservation of myocardial contractile function and lactate uptake were greater and cytokine expression was attenuated in pigs treated with troglitazone or alpha-tocopherol compared with untreated pigs. Multivariate analysis indicated that presence of an alpha-tocopherol, but not a thiazolidinedione, moiety in the test compound was significantly related to greater contractile function and lactate uptake and lower cytokine expression during I/R. We conclude that PPAR-gamma activation is not protective in a porcine model of myocardial I/R. Protective effects of troglitazone are attributable to its alpha-tocopherol moiety. These findings, in conjunction with prior rat studies, suggest interspecies differences in the response to PPAR-gamma activation in the heart.

Economism, efficiency, and the moral ecology of good nursing practice.

The free-market rhetoric dominating health-policy discussions today frames health-care goods and services as commodities that consumers will or will not buy at a given price. Health-care systems are being redesigned and hospitals restructured with a view to increased efficiency and productivity. Drawing on the experiences of clinical nurses in the United States, this paper shows how the application of economism to nursing may severely disrupt the ecology of good practice, leading to difficulties in meeting minimal standards of nursing care and severely constraining the acts of compassion called for by the human experiences of illness, loss, and death. Concerns about moral responsibility and conflicts between institutional and nursing goals are described. Increasing mistrust of health-care systems on the part of practitioners, patients, and families suggests that it is time to attend closely to the moral ecology of caring practices.