Mitigation measures against Coronavirus Disease 2019 (COVID-19) in overnight faith-based camps: summer 2021.

OBJECTIVE: In this study, we describe community-based nonpharmaceutical interventions (NPIs) incorporated into COVID-19 mitigation protocols, and SARS-CoV-2 incidence at five faith-based summer camps in the US. STUDY DESIGN: Retrospective cohort study. METHODS: Six southeastern states within the United States (13 sites) were assessed from May 30 to August 14, 2021 (13 sites; N = 13,132; May-August 2021). Camp mitigation policies and NPIs (including masking, vaccinations, meal arrangements, physical distancing, pre-arrival testing, symptom screening, quarantine/isolation, and ventilation upgrades), and SARS-CoV-2 infections were tracked at each site. RESULTS: The symptomatic primary case attack rate was 24.7 (range: 0.0-120.0) cases per 100,000 people per week. Fewer infections were observed in camps with greater mitigation protocols. CONCLUSION: These findings suggest that nonpharmaceutical mitigation can promote stable access to youth programs for historically vaccine-hesitant subgroups. Policy recommendations for nonpharmaceutical interventions to prevent respiratory viral transmission in overnight youth faith-based camp settings may include outdoor activities, accessible symptomatic tests, prearrival testing, indoor mask use, small cohorts, physical distancing, and protocols to minimize staff exposures during time off.

Adolescent preferences and reactions to language about body weight.

Over 30% of youth and adolescents have overweight or obesity, and health care providers are increasingly discussing weight-based health with these patients. Stigmatizing language in provider-patient communication about obesity is well documented and could be particularly detrimental to youth and adolescents. Although some research has examined preferences for weight-based terminology among adults, no studies have addressed these issues in youth populations. This study represents a preliminary and systematic investigation of weight-based language preferences among adolescents with overweight and obesity enrolled in a summer weight loss camp. Participants (N=50) indicated preferences for weight-based language and emotional responses to words that their family members used in reference to their body weight. Weight neutral terminology ('weight', 'body mass index') were most preferred, although some differences in word preferences emerged by the participants' gender. Boys preferred having their weight described as 'overweight' and 'heavy', while girls preferred the word 'curvy'. A large proportion of participants, particularly girls, reported experiencing sadness, shame, and embarrassment if parents used certain words to describe their body weight, which highlights the importance of considering the emotional impact of weight-based terminology. Providers may consider asking youth and adolescents for their preferences when discussing weight-based health.

Clinical and pathological features of dilated cardiomyopathy in Holstein-Friesian cattle.

Dilated cardiomyopathy is a primary disease of the heart muscle that has been reported in Holstein-Friesian cattle worldwide in the past 20 years. Nine cases of the condition were compared in terms of their clinical and pathological characteristics with nine unaffected animals matched for age, sex and breed. Their clinical signs included right-sided heart failure with severe subcutaneous oedema, ascites and/or hydrothorax and distended jugular veins. There were no characteristic biochemical or haematological changes. Postmortem, the affected hearts were enlarged with all the chambers dilated and walls of variable thickness. In most cases the kidneys were pale with a pitted surface. Histologically there was marked perimysial and endomysial fibrosis, extensive loss of cardiomyocytes by coagulative or colliquative necrosis, increased variation in the cross-sectional area of the myocardial fibres, and multifocal disarray and vacuolation of myocytes. Scanning electron microscopy showed that in all cases there was a mild myocardial inflammatory infiltrate, either diffuse or multifocal, which was identified by immunohistochemical labelling as T cells.

Ischemic loss of sarcolemmal dystrophin and spectrin: correlation with myocardial injury.

Sarcolemmal blebbing and rupture are prominent features of irreversible ischemic myocardial injury. Dystrophin and spectrin are sarcolemmal structural proteins. Dystrophin links the transmembrane dystroglycan complex and extracellular laminin receptors to intracellular F-actin. Spectrin forms the backbone of the membrane skeleton conferring an elastic modulus to the sarcolemmal membrane. An ischemic loss of membrane dystrophin and spectrin, in ischemically pelleted rabbit cardiomyocytes or in vivo 30--45 min permanently ischemic, LAD-ligated hearts, was detected by immunofluorescence with monoclonal antibodies. Western blots of light and heavy microsomal vesicles and Triton-extracted membrane fractions from ischemic myocytes demonstrated a rapid loss of dystrophin coincident with sub-sarcolemmal bleb formation, subsequent to a hypotonic challenge. The loss of spectrin from purified sarcolemma of autolysed rabbit heart, and both isolated membrane vesicles and Triton solubilized membrane fractions of ischemic cardiomyocytes correlated linearly with the onset of osmotic fragility as assessed by membrane rupture, subsequent to a hypotonic challenge. In contrast to the ischemic loss of dystrophin and spectrin from the membrane, the dystrophin-associated proteins, alpha-sarcoglycan and beta-dystroglycan and the integral membrane protein, sodium-calcium exchanger, were maintained in the membrane fraction of ischemic cells as compared to oxygenated cells. Preconditioning protected cells, but did not significantly alter ischemic dystrophin or spectrin translocation. This previously unrecognized loss of sarcolemmal dystrophin and spectrin may be the molecular basis for sub-sarcolemmal bleb formation and membrane fragility during the transition from reversible to irreversible ischemic myocardial injury.

Sarcolemmal blebs and osmotic fragility as correlates of irreversible ischemic injury in preconditioned isolated rabbit cardiomyocytes.

The hypothesis that irreversible ischemic injury is related to sub-sarcolemmal blebbing and an inherent osmotic fragility of the blebs was tested by subjecting isolated control and ischemically preconditioned (IPC) or calyculin A (CalA)-pretreated (protected) rabbit cardiomyocytes to ischemic pelleting followed by resuspension in 340, 170 or 85 mosmol medium containing trypan blue. At time points from 0-240 min, osmotic fragility was assessed by the percentage of trypan blue permeable cells. Membrane blebs were visualized with India ink preparations. Bleb formation, following acute hypo-osmotic swelling, developed by 75 min and increased with longer periods of ischemia. Osmotic fragility developed only after 75 min. Cells resuspended in 340 mosmol media did not form blebs and largely retained the ability to exclude trypan blue, even after 240 min ischemia. Although the latent tendency for osmotic blebbing preceded the development of osmotic fragility, most osmotically fragile cells became permeable without evident sarcolemmal bleb formation. The onset of osmotic fragility was delayed in protected cells, but protection did not reduce the bleb formation. It is concluded that blebbing and osmotic fragility are independent manifestations of ischemic injury. The principal locus of irreversible ischemic injury and the protection provided by IPC may lie within the sarcolemma rather than at sarcolemmal attachments to underlying adherens junctions.

The Williams syndrome cognitive profile.

Williams syndrome is a rare neurodevelopmental disorder caused by a hemizygous deletion of approximately 1.5 megabases on chromosome 7q11.23. In this article, we outline a Williams Syndrome Cognitive Profile (WSCP) that operationalizes the cognitive characteristics of the syndrome using measures of absolute and relative performance on subtests of the Differential Abilities Scales (Elliot, 1990a). Testing confirmed excellent sensitivity and specificity scores for the WSCP. Seventy-four of 84 individuals with Williams syndrome fit the WSCP while only 4 participants in a contrast group met all of the WSCP criteria. It was also found that the WSCP does not vary greatly with chronological age or overall level of cognitive ability for individuals with Williams syndrome. Possible applications for the WSCP include psychoeducational evaluation and empirical research such as the search for genotype/phenotype relations in this genetically based syndrome.

Differential translocation or phosphorylation of alpha B crystallin cannot be detected in ischemically preconditioned rabbit cardiomyocytes.

Alpha B Crystallin (alpha BC) is a putative effector protein of ischemic preconditioning (IPC), that is phosphorylated on Ser 45 by ERK1/2 and Ser 59 by the p38 MAPK substrate, MAPKAPK-2. Translocation and phosphorylation of alpha BC was determined in cytosolic and cytoskeletal fractions by 1D SDS-PAGE and IEF, or using Ser 45 and Ser 59 phospho-specific antibodies in: (1) control rabbit cardiomyocytes; (2) cells preconditioned by 10 min in vitro ischemia; or after pre-treatment with specific inhibitors of (3) Ser/Thr protein phosphatase 1/2A (calyculin A); (4) p38 MAPK (SB203580); or (5) ERK 1/2 (PD98059); all prior to 180 min ischemia. Ischemia induced a cytosolic to cytoskeletal translocation of alpha BC, which was similar in all the groups. Highly phosphorylated isoforms (D1/2) of alpha BC were present in cytosolic but not cytoskeletal fractions at 0 min ischemia. By 60-90 min ischemia, D1/2 isoforms had translocated to the cytoskeletal fraction. Calyculin A maintained D1/2 levels throughout prolonged ischemia. SB203580 decreased alpha BC phosphorylation. Neither PD98059 nor IPC altered alpha BC phosphorylation during prolonged ischemia. It is concluded that alpha BC phosphorylation during ischemia is regulated by p38 MAPK but not by ERK 1/2. The inability to detect a correlation between IPC protection and either alpha BC translocation or phosphorylation suggests that the proteins in the highly phosphorylated isoform bands of alpha BC quantitated in this study are not protective end effectors of classical IPC.

Phosphorylation state of hsp27 and p38 MAPK during preconditioning and protein phosphatase inhibitor protection of rabbit cardiomyocytes.

Small heat shock proteins (hsp) have been implicated in mediation of classic preconditioning in the rabbit, Hsp27 is a terminal substrate of the p38 MAPK cascade. One and 2D gel electrophoresis and immunoblotting of cell fractions was used to determine p38 MAPK and hsp27 phosphorylation levels, respectively, during in vitro ischemia in control, calyculin A (Cal A)-treated (protein phosphatase inhibitor), SB203580-treated (p38MAPK inhibitor) and preconditioned (IPC) isolated adult rabbit cardiomyocytes. The dual phosphorylation of p38 MAPK was increased by early ischemia (30-60 min), after which there was a loss of total cytosolic p38 MAPK. The ischemic increase of p38 MAPK dual phosphorylation was enhanced by IPC. Cal A strongly activated dual phosphorylation of p38 MAPK in oxygenated cells and this was maintained into early ischemia, SB203580 inhibited the dual phosphorylation of p38 MAPK and attenuated the loss of total cytosolic p38 MAPK. In each protocol, ischemia translocated hsp27 from the cytosolic fraction to the cytoskeletal fraction at similar rates and extents, Hsp27 phosphorylation was quantitated as the fraction of diphosphorylated hsp27, based on IEF mobility shifts of hsp27 phosphorylation isoforms. In oxygenated control cells, cytosolic and cytoskeletal hsp27 was highly phosphorylated. After 90 min ischemia, cytoskeletal hsp27 was markedly dephosphorylated. Cal A slightly increased control cytoskeletal hsp27 phosphorylation. During ischemic incubation, Cal A blocked ischemic dephosphorylation, SB203580 accelerated ischemic hsp27 dephosphorylation and injury, IPC insignificantly decreased the initial rate of ischemic dephosphorylation of hsp27, but not the extent of dephosphorylation in later ischemia. Phosphorylation is regulated by both kinase and phosphatase activities. IPC protection was not correlated with a significant increase in cytosolic or cytoskeletal hsp27 phosphorylation levels during prolonged (> 60-90 min) ischemia.

Fostriecin, an inhibitor of protein phosphatase 2A, limits myocardial infarct size even when administered after onset of ischemia.

BACKGROUND: The role of protein phosphatases (PPs) during ischemic preconditioning in the rabbit heart was examined. METHODS AND RESULTS: Fostriecin, a potent inhibitor of PP2A, was administered to isolated rabbit hearts starting either 15 minutes before or 10 minutes after the onset of a 30-minute period of regional ischemia and continuing until the onset of reperfusion. After 2 hours of reperfusion, infarct size was measured with triphenyltetrazolium chloride. In a second study with isolated rabbit cardiomyocytes, the effect of fostriecin pretreatment was assessed by measuring changes in cell osmotic fragility during simulated ischemia. PP1 and PP2A activities of isolated control and ischemically preconditioned cells were also measured. In a third series of experiments, left ventricular biopsies of isolated rabbit hearts were obtained before and at selected times during 60 minutes of global ischemia, and the tissue was assayed for PP1 and PP2A activities. In isolated hearts pretreated with fostriecin, only 8% of the ischemic zone infarcted, significantly less than that in untreated control hearts (33%; P<0.001) but comparable to that in ischemically preconditioned hearts (9%; P<0.001 versus control). Significant protection was also observed in the hearts treated only after the onset of ischemia (18% infarction; P<0.05 versus control). In isolated myocytes, fostriecin also provided protection comparable to that produced by metabolic preconditioning. Preconditioning had no apparent effect on the activity of either PP1 or PP2A in isolated ventricular myocytes or ventricular tissue obtained from heart biopsies. CONCLUSIONS: Fostriecin, a potent inhibitor of PP2A, can protect the rabbit heart from infarction even when administered after the onset of ischemia. But inhibition of either PP1 or PP2A does not appear to be the mechanism of protection from ischemic preconditioning.

Protein phosphatase inhibitors calyculin A and fostriecin protect rabbit cardiomyocytes in late ischemia.

Calcium-tolerant rabbit cardiomyocytes were isolated using retrograde aortic perfusion with a nominally calcium-free, collagenase buffer. In vitro ischemic preconditioning was induced by a 10-min episode of ischemic pelleting, followed by a 15-min post-incubation and a prolonged period of ischemic pelleting. Injury was assessed by determination of cell contracture and trypan blue permeability following hypotonic swelling and correlated with metabolic assays of lactate and adenine nucleotides. The protein phosphatase PP1/2A inhibitor calyculin A and PP2A-selective fostriecin protected isolated rabbit cardiomyocytes from lethal injury after a 10-min pre-incubation and when added late into ischemic pellets after a delay of 75 min. At the time of late drug addition, cells were severely ATP-depleted and in rigor contracture. Protection with Calyculin A from 1 nM to 1 microM was dose-related. Cells pre-incubated with 10 nM to 10 microM fostriecin 10 min prior to ischemic pelleting were protected with an EC50 approximating 71 nM, implying protection at a PP2A-selective dose. The selective protein kinase C inhibitor, calphostin C, blocked ischemic preconditioning protection but not protection from 1 microM calyculin A. Protection of severely ischemic cardiomyocytes following protein phosphatase inhibition appears not to require PKC activity or ATP conservation. Pre-incubation of cells with calyculin A induced high levels of phosphorylation in p38 mitogen activated protein kinase (MAPK), as compared to the ischemia-induced phosphorylation observed in the untreated group only at 30 min of ischemia, providing evidence of protein phosphatase activity in cardiomyocytes. Pharmacological protection in late ischemia has been demonstrated, but the mechanism of protection is undetermined.