One year of COVID-19 in dental health services in Norway: psychological impact, risk perceptions and vaccination status.

BACKGROUND: Increased psychological pressure on oral healthcare professionals (OHP) due to COVID-19 has been shown, yet little is known about the long-term psychological impacts. We aimed to study the psychological impact of COVID-19 and associated factors including perceived risk and preparedness and vaccination status among OHP in the first year after the lockdown period in Norway. METHODS: A structured questionnaire sent electronically to dentists, dental hygienists and dental assistants inquired experiences and perceptions during the second year following the outbreak in Norway. The questionnaire comprised a COVID-19 fear scale and questions about risk perception, preparedness and vaccination status. Exploratory factor analysis (EFA) and Structural Equation Modeling (SEM) were used to assess psychological impact, perception of risk and preparedness according to vaccination status of the respondents. RESULTS: The majority of the 708 respondents were female (92.8%), had ten or more years of work experience (67.1%), and worked in public dental clinics (95.9%). Fears and concerns related to COVID-19 were common, 72.6% feared getting infected and 85.4% feared infecting others. Of the 642 respondents who agreed that their workplaces handled the situation well, 55.6% were fully vaccinated. Three factors were retrieved from EFA: Insecurity, Instability and Infection. SEM showed that females were more concerned with Infection, and respondents with long clinical experience were less likely to express fear about Instability. Fully vaccinated individuals felt more insecure about becoming infected, and those agreeing that their workplaces handled the current situation well were concerned with Insecurity. CONCLUSIONS: Despite widespread perception of adequate preparedness and high vaccine coverage, a considerable psychological impact and high levels of fear of COVID-19 were observed among the majority of OHP. Fully vaccinated individuals had a larger psychological burden than not fully vaccinated and those with unknown vaccination status. These findings can inform means and interventions to reduce negative impacts of fear in populations with a high psychological burden.

Method to characterize inorganic particulates in lung tissue biopsies using field emission scanning electron microscopy.

Humans accumulate large numbers of inorganic particles in their lungs over a lifetime. Whether this causes or contributes to debilitating disease over a normal lifespan depends on the type and concentration of the particles. We developed and tested a protocol for in situ characterization of the types and distribution of inorganic particles in biopsied lung tissue from three human groups using field emission scanning electron microscopy (FE-SEM) combined with energy dispersive spectroscopy (EDS). Many distinct particle types were recognized among the 13 000 particles analyzed. Silica, feldspars, clays, titanium dioxides, iron oxides and phosphates were the most common constituents in all samples. Particles were classified into three general groups: endogenous, which form naturally in the body; exogenic particles, natural earth materials; and anthropogenic particles, attributed to industrial sources. These in situ results were compared with those using conventional sodium hypochlorite tissue digestion and particle filtration. With the exception of clays and phosphates, the relative abundances of most common particle types were similar in both approaches. Nonetheless, the digestion/filtration method was determined to alter the texture and relative abundances of some particle types. SEM/EDS analysis of digestion filters could be automated in contrast to the more time intensive in situ analyses.

Patterns of adaptation to children's food allergies.

BACKGROUND: Families with food allergy (FA) are at risk of reduced quality of life and elevated anxiety. A moderate level of anxiety may be beneficial to sustain vigilance for food avoidance; however, excessive anxiety may increase risk for burden and maladjustment. The current study presents a framework for understanding the patterns of adaptation to FA across families and to identify typologies of families that would benefit from intervention. METHODS: Participants included 57 children, 6-12 years old with documented FA, and their mothers. Families were assessed using the Food Allergy Management and Adaptation Scale. Families also completed measures of quality of life, anxiety, FA management, and psychosocial impairment. RESULTS: A hierarchical cluster analysis revealed that 56 of the 57 families of food-allergic children were categorized into four groups that differed on their adequacy of family FA management, levels of anxiety, and balanced psychosocial functioning: balanced responders (n = 23; 41%), high responders (n = 25; 45%), and low responders (n = 3; 5%). The fourth group, anxious high responders (n = 5; 9%), was characterized by extremely high maternal FA anxiety scores and low scores for balanced integration of FA management and psychosocial functioning. Families in clusters differed across illness and psychosocial outcome variables. CONCLUSION: Families with FA were characterized by patterns of FA management, anxiety, and ability to integrate FA demands into daily life. Identified adaptation patterns correspond with clinical impressions and provide a framework for identifying families in need of intervention.

Cardiopulmonary correlates of cognition in systemic lupus erythematosus.

OBJECTIVE: We aimed to evaluate the relationship between cognitive dysfunction and lung function, exercise endurance, and self-reported activity levels in patients with systemic lupus erythematosus (SLE). BACKGROUND: Cognitive dysfunction is present in 20%-60% of SLE patients. No studies to date have investigated the inter-relationships between cardiopulmonary factors and cognition in this population. METHODS: Thirty-seven SLE patients without overt neuropsychiatric histories and 16 healthy controls completed neuropsychological testing, measures of lung function, exercise capacity (distance walked during a timed walk test,(1) maximal oxygen uptake(2)), and exercise questionnaires. RESULTS: Thirty-two percent of SLE patients demonstrated cognitive impairment. Cognitive impairment was correlated with Six-Minute Walk Distance (6MWD) (r = 0.37, p = 0.02) and certain measures of lung function. Also, in SLE patients, self-reported physical activity was correlated with 6MWD (p = 0.012), but none of the more complex measures of physical activity (VO2max). CONCLUSIONS: Patients with mild SLE disease activity have cognitive dysfunction associated with certain objective markers of exercise capacity and activity levels. The lack of associations between self-report activity and VO2max suggests the possibility that multiple factors mediate the relationships between perceived and actual physical ability. Additional studies are needed to better understand the relationship between cognition and physical activity in patients with SLE.

Regression calibration with instrumental variables for longitudinal models with interaction terms, and application to air pollution studies.

In this paper, we derive forms of estimators and associated variances for regression calibration with instrumental variables in longitudinal models that include interaction terms between two unobservable predictors and interactions between these predictors and covariates not measured with error; the inclusion of the latter interactions generalize results we previously reported. The methods are applied to air pollution and health data collected on children with asthma. The new methods allow for the examination of how the relationship between health outcome leukotriene E4 (LTE4, a biomarker of inflammation) and two unobservable pollutant exposures and their interaction are modified by the presence or absence of upper respiratory infections. The pollutant variables include secondhand smoke and ambient (outdoor) fine particulate matter. Simulations verify the accuracy of the proposed methods under various conditions.

The cardiokine secreted Frizzled-related protein 3, a modulator of Wnt signalling, in clinical and experimental heart failure.

OBJECTIVES: Experimental studies have shown involvement of Wnt signalling in heart failure (HF). We hypothesized that secreted frizzled-related protein 3 (sFRP3), a modulator of Wnt signalling, is related to the progression of HF. DESIGN: Circulating sFRP3 was measured in 153 HF patients and compared with 25 healthy controls. The association of sFRP3 with mortality was evaluated in 1202 patients (GISSI-HF trial). sFRP3 mRNA expression was assessed in failing human and murine left ventricles (LV), and cellular localization was determined after fractioning of myocardial tissue. In vitro studies were carried out in cardiac fibroblasts subjected to cyclic mechanical stretch. RESULTS: (i) Heart failure patients had significantly raised serum sFRP3 levels compared with controls, (ii) during a median follow-up of 47 months, 315 patients died in the GISSI-HF substudy. In univariable Cox regression, tertiles of baseline sFRP3 concentration were significantly associated with all-cause and cardiovascular mortality. After adjustment for demographic and clinical variables, but not for CRP and NT-proBNP, the associations with mortality remained significant for the third tertile (all-cause, HR 1.45, P = 0.011; cardiovascular, HR 1.66, P = 0.003), (iii) sFRP3 mRNA expression was increased in failing human LV, with a decline following LV assist device therapy. LV from post-MI mice showed an increased sFRP3 mRNA level, particularly in cardiac fibroblasts, and (iv) mechanical stretch enhanced sFRP3 expression and release in myocardial fibroblasts. CONCLUSION: There is an association between increased sFRP3 expression and adverse outcome in HF, suggesting that the failing myocardium itself contributes to an increase in circulating sFRP3.

Impact of virtual simulation vs. Video refresher training on NRP simulation performance: a randomized controlled trial.

OBJECTIVE: To assess the impact of NRP virtual simulations (eSim™), video or no refresher training, on simulation performance, six months after a provider course; and to evaluate eSim™ acceptability. STUDY DESIGN: In this multi-site randomized controlled trial, NRP providers from four U.S. institutions were randomized to receive refreshers every two months with NRP eSim™, NRP resuscitation video, or no refresher (control). Simulation performance was assessed immediately after an NRP course and six months later. RESULT: 248 participants completed the baseline simulation and 148 completed the six-month follow-up simulation. The majority (71%) of subjects had a decline in resuscitation skills at 6 months. There were no differences in performance between the study groups, but participants who reported using either the video or eSim™ had less decline in performance at the 6-month follow-up (p < 0.05). CONCLUSION: NRP refreshers with either eSim™ or NRP video may mitigate the decline in resuscitation skills after training.

Fissure Sealants or Fluoride Varnish? A Randomized Pragmatic Split-Mouth Trial.

This study aimed to compare the clinical effectiveness of resin-based fissure sealants (FS) and fluoride varnish (FV) in children at high caries risk. A practice-based split-mouth randomized clinical trial was conducted at 9 Public Dental Service (PDS) clinics in Norway. In total, 409 children age 6 to 10 y at high caries risk (d3mft > 0) meeting inclusion criteria were recruited by dentists and dental hygienists during routine examination. Eligibility criteria were 2 fully erupted first permanent molars (FPMs) in the same jaw, with sound occlusal surfaces or with initial caries. Participation was voluntary, caregivers and eligible children were informed about the study, and written parental consent was obtained. FS and FV were randomly applied on contralateral FPMs in the same jaw, with each participant serving as their own control. FS was applied at baseline and thereafter maintained according to clinicians' conventional procedures, whereas FV was applied at baseline, 6 mo, and 12 mo. The study outcome was success, with no need for invasive treatment (caries control), while failure was defined as dentin carious lesion or restoration. Two-level mixed-effects logistic regression analysis was used to compare FS and FV groups. Of 409 recruited children, 369 (90%) children/tooth pairs were examined after 36 mo. Intention-to-treat analysis showed 94.1% adjusted predicted probability (aPP) of success (95% confidence interval [CI] 91.7 to 96.4) in the FS group and 89.6% aPP (95% CI 86.5 to 92.7) in the FV group. In the adjusted analysis, the FV group had a lower OR for success compared with the FS group (OR 0.54, 95% CI 0.24 to 0.87). In the population studied, the clinical effectiveness of FS was statistically significantly higher compared with FV but below the estimated minimal clinically important difference of 10%.

Blood mRNA biomarkers for detection of treatment response in acute pulmonary exacerbations of cystic fibrosis.

BACKGROUND: Acute pulmonary exacerbations accelerate pulmonary decline in cystic fibrosis (CF). There is a critical need for better predictors of treatment response. OBJECTIVE: To test whether expression of a panel of leucocyte genes directly measured from whole blood predicts reductions in sputum bacterial density. METHODS: A previously validated 10-gene peripheral blood mononuclear cell (PBMC) signature was prospectively tested in PBMC and whole blood leucocyte RNA isolated from adult subjects with CF at the beginning and end of treatment for an acute pulmonary exacerbation. Gene expression was simultaneously quantified from PBMCs and whole blood RNA using real-time PCR amplification. Test characteristics including sensitivity, specificity, positive and negative predictive values were calculated and receiver operating characteristic curves determined the best cut-off to diagnose a microbiological response. The findings were then validated in a smaller independent sample. RESULTS: Whole blood transcript measurements are more accurate than forced expiratory volume in 1 s (FEV(1)) or C reactive protein (CRP) alone in identifying reduction of airway infection. When added to FEV(1), the whole blood gene panel improved diagnostic accuracy from 64% to 82%. The specificity of the test to detect reduced infection was 88% and the positive predictive value for the presence of persistent infection was 86%. The area under the curve for detecting treatment response was 0.81. Six genes were the most significant predictors for identifying reduction in airway bacterial load beyond FEV(1) or CRP alone. The high specificity of the test was replicated in the validation cohort. CONCLUSIONS: The addition of blood leucocyte gene expression to FEV(1) and CRP enhances specificity in predicting reduced pulmonary infection and may bolster the assessment of CF treatment outcomes.

Phage loss and the breakdown of a defensive symbiosis in aphids.

Terrestrial arthropods are often infected with heritable bacterial symbionts, which may themselves be infected by bacteriophages. However, what role, if any, bacteriophages play in the regulation and maintenance of insect-bacteria symbioses is largely unknown. Infection of the aphid Acyrthosiphon pisum by the bacterial symbiont Hamiltonella defensa confers protection against parasitoid wasps, but only when H. defensa is itself infected by the phage A. pisum secondary endosymbiont (APSE). Here, we use a controlled genetic background and correlation-based assays to show that loss of APSE is associated with up to sevenfold increases in the intra-aphid abundance of H. defensa. APSE loss is also associated with severe deleterious effects on aphid fitness: aphids infected with H. defensa lacking APSE have a significantly delayed onset of reproduction, lower weight at adulthood and half as many total offspring as aphids infected with phage-harbouring H. defensa, indicating that phage loss can rapidly lead to the breakdown of the defensive symbiosis. Our results overall indicate that bacteriophages play critical roles in both aphid defence and the maintenance of heritable symbiosis.

The viral envelope glycoprotein of murine leukemia virus and the pathogenesis of immune complex glomerulonephritis of New Zealand mice.

The use of monospecific antisera for the analysis by radioimmunoassay and immunofluorescence study of two major viral proteins, gp69/71 and p30 of murine leukemia virus, that could be of significance in the pathogenesis of immune complex glomerulonephritis of mice, particularly NZB and B/WF(1) hybrid mice, yielded the following conclusions. A remarkably high concentration of viral envelope glycoprotein, gp69/71, was detected in the spleen and serum of New Zealand mice (NZB, NZW, B/WF(1), and W/BF(1)); the concentration in the spleen was 10-fold greater than that found in AKR mice and 30-fold greater than that present in C57BL/6 mice. The gp69/71 was deposited along with bound immunoglobulins, apparently as an immune complex, in the diseased kidneys of mice, and the glomerular site and extent of deposition of gp69/71 was related to the severity of the glomerulonephritis. This study suggests that the pathogenesis of immune complex glomerulonephritis (and vasculitis) in mice is related to the expression of this specific viral envelope glycoprotein and to the host immune response to this protein.

Phenotypically plastic traits regulate caste formation and soldier function in polyembryonic wasps.

Polyembryonic encyrtid wasps are parasitoids that have evolved a clonal form of embryogenesis and a caste system where some progeny become reproducing wasps whereas others develop into a sterile soldier caste. Theory based on the biology of Copidosoma floridanum predicts that the primary role of soldier larvae is to mediate conflict over sex ratio, which also favours female-biased soldier production. Other data, however, suggest that female-biased soldier production reflects a developmental constraint. Here, we assessed whether female-biased soldier function by polyembryonic wasps reflects sex-specific adaptation or constraint by conducting comparative studies with Copidosoma bakeri, a species that produces clutch sizes similar to C. floridanum yet rarely produces broods associated with sex ratio conflict. Our results indicate that the oviposition behaviour of adults, development of progeny and function of soldier larvae differ greatly between C. bakeri and C. floridanum. These findings indicate that caste formation and soldier function in polyembryonic encyrtid wasps are regulated by phenotypically plastic traits. Our results further suggest that the primary function of the soldier caste in some species is defence of host resources from competitors whereas in others it is the resolution of sex ratio conflict.

Risk of eating disorders in international adoptees: a cohort study using Swedish national population registers.

AIMS: Compared to the general population, adoptees are more often referred to specialist psychiatric treatment, exhibit increased risk of suicide and display more symptoms of attention-deficit/hyperactivity-disorder. However, little is known about the impact of being an adoptee on the risk of developing an eating disorder. The aim of the present study was to assess whether international adoptees have a higher risk for eating disorders than native Swedes. METHODS: In the present retrospective cohort study, data from the Swedish total population registers on individuals born between 1979 and 2005 were used to assess whether international adoptees residing in Sweden (n = 25 287) have a higher risk for anorexia nervosa (AN) and other eating disorders (OED) than non-adoptees with Swedish-born parents from the general population (n = 2 046 835). The patterns of these results were compared to those for major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and anxiety disorders to determine whether any observed effects were unique to eating disorders or reflected a more general impact on mental health outcomes. RESULTS: A survival analysis adjusting for relevant demographic covariates revealed an elevated risk of all examined psychiatric disorders in international adoptees: hazard ratios (95% confidence intervals) are 1.21 (1.04-1.41) for AN, 1.60 (1.44-1.79) for OED, 1.90 (1.81-2.00) for MDD, 1.25 (1.09-1.44) for OCD, and 1.69 (1.60-1.78) for anxiety disorders. CONCLUSIONS: Elevated risk of eating disorders as well as of MDD, OCD, and anxiety disorders was found in international adoptees. A parallel pattern between AN and OCD was observed, which both display less elevated rates than the other diagnoses. A considerable number of biological, environmental, and societal factors have been suggested to explain the observed differences in mental health between adoptees and non-adoptees, but they remain primarily theoretical.

Tumor imaging with radioactive metal chelates conjugated to monoclonal antibodies.

High-resolution gamma camera images of mouse erythroid tumors were obtained by use of leukemia cell-specific monoclonal antibodies labeled with bifunctional radioactive metal chelates. Small tumors (200 to 300 milligrams) were visible without subtraction or enhancement 1 to 5 hours after injection of antibody. Chelate-derivitized monoclonal antibodies permit targeting of a broad spectrum of radioisotopes, including those that are optimum for agamma for gamma camera imaging or positron tomography, as well as those that are tumoricidal.

Infection by a symbiotic polydnavirus induces wasting and inhibits metamorphosis of the moth Pseudoplusia includens.

Insect pathogens and parasites often affect the growth and development of their hosts, but understanding of these processes is fragmentary. Among the most species-rich and important mortality agents of insects are parasitoid wasps that carry symbiotic polydnaviruses (PDVs). Like many PDV-carrying wasps, Microplitis demolitor inhibits growth and pupation of its lepidopteran host, Pseudoplusia includens, by causing host hemolymph juvenile hormone (JH) titers to remain elevated and preventing ecdysteroid titers from rising. Here we report these alterations only occurred if P. includens was parasitized prior to achieving critical weight, and were fully mimicked by infection with only M. demolitor bracovirus (MdBV). Metabolic assays revealed that MdBV infection of pre-critical weight larvae caused a rapid and persistent state of hyperglycemia and reduced nutrient stores. In vitro ecdysteroid assays further indicated that prothoracic glands from larvae infected prior to achieving critical weight remained in a refractory state of ecdysteroid release, whereas infection of post-critical weight larvae had little or no effect on ecdysteroid release by prothoracic glands. Taken together, our results suggest MdBV causes alterations in metabolic physiology, which prevent the host from achieving critical weight. This in turn inhibits the endocrine events that normally trigger metamorphosis.

55,000-dalton, retrovirus-associated, cell membrane glycoprotein: purification and quantitative measurements of expression in viruses, cells, and tissues.

We have purified to homogeneity and characterized a 55,000-dalton rat cell membrane glycoprotein, gp55. This protein was originally identified in preparations of a defective pseudotype of the Kirsten sarcoma virus and shown to be present in several rodent retrovirus particles. The gp55 was purified from this defective virus by concanavalin A and heparin affinity chromatography, as well as by preparative sodium dodecyl sulfate-gel electrophoresis. Both preparations displayed similar purity and antigenic characteristics. The 125I-labeled gp55 was precipitated by antisera against rodent retroviruses, but not by monospecific antisera against purified type C virus structural proteins, thus indicating that gp55 was retrovirus associated, but unrelated to known retrovirus structural proteins. Competition radioimmunoassay with an anti-rat virus serum which recognized rodent group-specific antigens on gp55 indicated: the presence of gp55 antigens in 15 rodent cell lines, but not 10 nonrodent cell lines; no effect of viral infection or cell transformation on the amount of gp55 expressed; up to 100-fold increases in the concentration of the gp55 antigens in nine rodent retroviruses, but not in five nonrodent viruses, as compared to cells; the presence of gp55 in rodent sera, especially of the NZB mouse, where anti-gp55 antibody was also detected; a lymphoid and epithelial tissue distribution of gp55 in rats and mice. Additional competition radioimmunoassays with a broad-reacting antivirus serum also detected the presence of gp55 in nonrodent, mink, and human cells and thus distinguished rat type, rodent group, and interspecies antigenic determinants on gp55. In conclusion, gp55 is a cell membrane glycoprotein associated in high concentration with retroviruses.

Characterization of hemocytes from the mosquitoes Anopheles gambiae and Aedes aegypti.

Hemocytes are an essential component of the mosquito immune system but current knowledge of the types of hemocytes mosquitoes produce, their relative abundance, and their functions is limited. Addressing these issues requires improved methods for collecting and maintaining mosquito hemocytes in vitro, and comparative data that address whether important vector species produce similar or different hemocyte types. Toward this end, we conducted a comparative study with Anopheles gambiae and Aedes aegypti. Collection method greatly affected the number of hemocytes and contaminants obtained from adult females of each species. Using a collection method called high injection/recovery, we concluded that hemolymph from An. gambiae and Ae. aegypti adult females contains three hemocyte types (granulocytes, oenocytoids and prohemocytes) that were distinguished from one another by a combination of morphological and functional markers. Significantly more hemocytes were recovered from An. gambiae females than Ae. aegypti. However, granulocytes were the most abundant cell type in both species while oenocytoids and prohemocytes comprised less than 10% of the total hemocyte population. The same hemocyte types were collected from larvae, pupae and adult males albeit the absolute number and proportion of each hemocyte type differed from adult females. The number of hemocytes recovered from sugar fed females declined with age but blood feeding transiently increased hemocyte abundance. Two antibodies tested as potential hemocyte markers (anti-PP06 and anti-Dox-A2) also exhibited alterations in staining patterns following immune challenge with the bacterium Escherichia coli.

Leukemic cell targeting and therapy by monoclonal antibody in a mouse model system.

A monoclonal antibody prepared against the Rauscher virus envelope glycoprotein with a molecular weight of 70,000 targeted to neoplastic cells and cured the Rauscher leukemia virus-induced erythroleukemia in BALB/c mice. This antibody, 103A, specifically reacted with the Rauscher and Friend erythroleukemia viruses and erythroleukemic cells but did not react with other murine ecotropic or xenotropic viruses or feline leukemia virus or with normal spleen cells, thymocytes, or fibroblasts, as measured by radioimmunoassays. P3, a control antibody of the same immunoglobulin G1 subclass, did not bind to any of these cells or viruses. This specificity was maintained in vivo. 125I-Labelled 103A injected into mice targeted to leukemic spleen cells but not to normal cells. Mean uptake ratios of binding to leukemic over normal spleen cells ranged from greater than 70 at 7 hr after injection to less than 10 at 40 hr later. The control antibody showed no binding in vivo. A single small dose of 103A was able to cure leukemic mice as assayed by spleen focus formation on Day 8 or splenomegaly on Day 20. The 50% effective dose was 1.5 micrograms when injected 72 hr after onset of leukemia. The therapeutic potencies of drugs, toxins, and cytotoxic radioisotopes conjugated to antibodies can be quantitatively compared using the established dose-response curve. Such quantitative comparisons showed that 131-labeled 103A immunoglobulin G was no more potent than unlabeled 103A immunoglobulin G in this system.

Stability, targeting, and biodistribution of scandium-46- and gallium-67-labeled monoclonal antibody in erythroleukemic mice.

Using a monoclonal antibody specific for the Mr 70,000 glycoprotein of Rauscher erythroleukemia virus, we have determined the optimal conditions for conjugation with the cyclic anhydride of diethylene triamine pentaacetic acid and subsequent labeling with 46Sc. The conjugates were shown to retain their specificity and activity in vitro and to target specifically to virus-infected spleen cells in vivo. The stability of the 46Sc:diethylene triamine pentaacetic acid-antibody conjugates in vivo was studied using immunoaffinity chromatography; 25% of the isotope bound to transferrin, and 75% remained bound to the antibody conjugates. These results are discussed with respect to the potential for labeling antibodies with 47Sc for use in imaging and therapy. Studies with 111In-labeled antibody were used for comparison. Labeling with 67Ga was also performed; these labeled conjugates showed adventitious binding of isotope to the antibody and lack of stability of diethylene triamine pentaacetic acid-chelated gallium. Free EDTA was shown to stably incorporate 67Ga.