Covid-19 shelter-at-home and work, lifestyle and well-being in desk workers.

BACKGROUND: Emerging cross-sectional reports find that the COVID-19 pandemic and related social restrictions negatively affect lifestyle behaviours and mental health in general populations. AIMS: To study the longitudinal impact of COVID-19 on work practices, lifestyle and well-being among desk workers during shelter-at-home restrictions. METHODS: We added follow-up after completion of a clinical trial among desk workers to longitudinally measure sedentary behaviour, physical activity, sleep, diet, mood, quality of life and work-related health using validated questionnaires and surveys. We compared outcomes assessed before and during COVID-19 shelter-at-home restrictions. We assessed whether changes in outcomes differed by remote working status (always, changed to or never remote) using analysis of covariance (ANCOVA). RESULTS: Participants (N = 112; 69% female; mean (SD) age = 45.4 (12.3) years; follow-up = 13.5 (6.8) months) had substantial changes to work practices, including 72% changing to remote work. Deleterious changes from before to during shelter-at-home included: 1.3 (3.5)-h increase in non-workday sedentary behaviour; 0.7 (2.8)-point worsening of sleep quality; 8.5 (21.2)-point increase in mood disturbance; reductions in five of eight quality of life subscales; 0.5 (1.1)-point decrease in work-related health (P < 0.05). Other outcomes, including diet, physical activity and workday sedentary behaviour, remained stable (P ≥ 0.05). Workers who were remote before and during the pandemic had greater increases in non-workday sedentary behaviour and stress, with greater declines in physical functioning. Wake time was delayed overall by 41 (61) min, and more so in workers who changed to remote. CONCLUSIONS: Employers should consider supporting healthy lifestyle and well-being among desk workers during pandemic-related social restrictions, regardless of remote working status.

IgE autoantibodies in serum and skin of non-bullous and bullous pemphigoid patients.

BACKGROUND: Non-bullous pemphigoid (NBP) is a pemphigoid variant which frequently resembles other pruritic skin diseases. In contrast with bullous pemphigoid (BP), blisters are absent. In BP, previous studies showed that IgE autoantibodies may be involved in its pathogenesis. IgE-activated mast cells, basophils and eosinophils may participate in BP by inducing pruritus and possibly blister formation, although the differential role of IgE in NBP compared with BP has not yet been described. OBJECTIVE: To assess IgE in serum and skin of NBP and BP patients. METHODS: We examined total IgE and pemphigoid-specific IgE in the serum of 68 NBP and 50 BP patients by enzyme-linked immunosorbent assay (ELISA). Sera of 25 pemphigus patients and 25 elderly patients with pruritus were included as controls. Skin biopsies of 14 NBP and 14 BP patients with the highest IgE titres to NC16A were stained for IgE by immunofluorescence techniques. RESULTS: Total IgE was elevated in 63% of NBP and 60% of BP patients, and in 20% of pemphigus controls, as well as 60% of elderly controls. IgE ELISAs were more frequently positive in BP than in NBP (NC16A 18% vs. 9%, P = 0.139; BP230 34% vs. 22%, P = 0.149). IgE ELISAs for NC16A and BP230 were positive in 8% and 20% of elderly controls, respectively, while all pemphigus controls were negative. Two of 28 biopsies (7%; one NBP, one BP) showed linear IgE along the basement membrane zone, while in most biopsies (71% NBP; 86% BP) IgE was bound to dermal cells. CONCLUSION: Since IgE was present in the serum and skin of both NBP and BP patients, this supports IgE-dependent mechanisms common to both diseases, such as pruritus. However, it remains to be elucidated whether IgE contributes to blister formation in BP.

Neurological disorders are associated with bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease with an increased incidence particularly among the elderly. Several studies have recently reported an association between BP and neurological disorders. OBJECTIVE: To evaluate the association between BP and neurological disorders in a single centre in Germany. METHODS: We retrospectively assessed 183 patients with BP (diagnosed between 2011 and 2015) and 348 age- and sex-matched controls for neurological disorders. The latter were confirmed either by a neurologist or psychiatrist. RESULTS: Overall, there was a highly statistically significant association between BP and neurological disorders (P < 0.0001). These included dementia (P < 0.0001), Parkinson`s disease (P = 0.0434), stroke (P = 0.0015) and other neurological disorders but not Alzheimer's diseases, which was more common among patients in the control group. CONCLUSION: Our cohort of bullous pemphigoid and neurological disorders demonstrates a significant association between bullous pemphigoid and neurological disorders, including dementia, Parkinson's disease and stroke. These observations support the need for future studies in order to elucidate the immunological mechanisms responsible for these comorbidities.

Important and specific role for basophils in acute allergic reactions.

IgE-mediated allergic reactions involve the activation of effector cells, predominantly through the high-affinity IgE receptor (FcεRI) on mast cells and basophils. Although the mast cell is considered the major effector cell during acute allergic reactions, more recent studies indicate a potentially important and specific role for basophils and their migration which occurs rapidly upon allergen challenge in humans undergoing anaphylaxis. We review the evidence for a role of basophils in contributing to clinical symptoms of anaphylaxis and discuss the possibility that basophil trafficking during anaphylaxis might be a pathogenic (to target organs) or protective (preventing degranulation in circulation) response. Finally, we examine the potential role of basophils in asthma exacerbations. Understanding the factors that regulate basophil trafficking and activation might lead to new diagnostic and therapeutic strategies in anaphylaxis and asthma.

[Neurophysiology of atopic pruritus]. / Neurophysiologie des atopischen Pruritus.

Pruritus is one of the major symptoms of inflammatory skin diseases and strongly affects the quality of life in patients. Although the perception of pruritus and pain are closely intertwined, pruritus represents a distinct sensation, which is also significantly different to pain at a neurophysiological level. The pathophysiological basis of chronic and acute pruritus is not fully understood. Besides histamine, a plethora of different neuromediators of itch, including neurotrophins, neuropeptides and their corresponding receptors, have been identified. In atopic dermatitis the release of these mediators leads to an activation of immune cells, such as mast cells and eosinophilic granulocytes, which in turn release neuromediators and cytokines that activate peripheral neurons. This review focuses on the neurophysiological interactions which regulate pruritus and summarizes the function of neurological and inflammatory mediators in atopic pruritus.

Effects of supervised and unsupervised physical activity programmes for weight loss.

OBJECTIVES: Physical activity is important for weight management. However, it remains unclear what type of physical activity prescription/programme is optimal for increasing physical activity during a standard behavioural weight loss intervention. This study examined changes in physical activity after a 12-week supervised programme prescribed in minutes per week (SUP-PA), an unsupervised programme prescribed in minutes per week (UNSUP-PA) and an unsupervised programme prescribed in steps per day (STEP). METHODS: Fifty-two adults who were overweight or obese (age: 43.5 ± 10.1 years, BMI: 31.5 ± 3.5 kg·m-2) were randomized to STEP (n = 18), UNSUP-PA (n = 17) and SUP-PA (n = 17). Subjects attended weekly in-person group intervention sessions and were prescribed a calorie-restricted diet (1,200-1,800 kcals·day-1) combined with increased physical activity (150 min·week-1 or 10,000 steps·day-1 with 2,500 brisk steps·day-1). RESULTS: All three groups significantly increased moderate-to-vigorous physical activity (STEP: 80.6 ± 218.5 min·week-1, UNSUP-PA: 112.9 ± 180.4 min·week-1 and SUP-PA: 151.1 ± 174.0 min·week-1, p < 0.001) with no differences between groups (p = 0.94) or group by time interaction (p = 0.81). In addition, there were no significant differences in weight loss between the groups (p = 0.81). CONCLUSIONS: In this short-term study, all three physical activity programmes increased physical activity and elicited modest weight loss when combined with a standard behavioural weight loss intervention.

Human basophils are a source of - and are differentially activated by - IL-31.

BACKGROUND: Basophils are important effector cells involved in the pathogenesis of inflammatory skin diseases including chronic urticaria which is associated by increased IL-31 serum levels. So far the effects of IL-31 on human basophils are unknown. OBJECTIVE: To analyse the functional role of IL-31 in basophil biology. METHODS: IL-31 expression was evaluated in skin samples derived from chronic spontaneous urticaria patients. Oncostatin M receptor (OSMR), IL-31 receptor A (RA) and IL-31 protein expressions were analysed on human basophils from healthy donors. Basophil responses to IL-31 were assessed for chemotaxis, externalization of CD63 and CD203c as well as the release of histamine, IL-4 and IL-13. RESULTS: IL-31RA and OSMR were expressed on human basophils. IL-31 was strongly expressed in the skin of patients with chronic spontaneous urticaria and was released from isolated basophils following either anti-IgE, IL-3 or fMLP stimulation. IL-31 induced chemotaxis and the release of IL-4 and IL-13 which was specifically inhibited by anti-IL-31RA and anti-OSMR. Conversely, IL-31 had no effect on CD63 and CD203c externalization or histamine release. CONCLUSIONS AND CLINICAL RELEVANCE: Human basophils are a source of -and are activated by - IL-31 with the release of pro-inflammatory cytokines and the induction of chemotaxis indicating an important novel function of IL-31 in basophil biology.

Energy expenditure of deskwork when sitting, standing or alternating positions.

BACKGROUND: Recent guidelines recommend accruing 2-4h of standing or light activity during the working day. Use of sit-stand desks could achieve this goal, but whether standing can meaningfully increase energy expenditure (EE) is unclear. AIMS: To study EE, heart rate, feelings and productivity during deskwork while sitting, standing or alternating positions. METHODS: We measured EE by indirect calorimetry in working adults over three randomly ordered 60-min conditions while performing deskwork: continuous sitting (SIT), 30min of each standing and sitting (STAND-SIT) and continuous standing (STAND). We also assessed heart rate, productivity and self-reported energy, fatigue and pain. Linear mixed models compared minute-by-minute EE and heart rate across conditions. Non-parametric tests compared remaining outcomes across conditions. RESULTS: The study group comprised 18 working adults. Compared with SIT, STAND-SIT engendered an additional 5.5±12.4 kcal/h (7.8% increase) and STAND engendered an additional 8.2±15.9 kcal/h (11.5% increase) (both P < 0.001). Alternating positions to achieve the recommended 4h/day of standing could result in an additional 56.9 kcal/day for an 88.9kg man and 48.3 kcal/day for a 75.5kg woman. STAND-SIT and STAND also increased heart rate over SIT by 7.5±6.8 and 13.7±8.8 bpm, respectively (both P < 0.001). We observed no meaningful differences in feelings or productivity. CONCLUSIONS: Desk-based workers could increase EE without added discomfort by using a sit-stand desk. These findings inform future research on sit-stand desks as a part of workplace interventions to increase EE and potentially improve health.

Applying a technology-based system for weight loss in adults with obesity.

OBJECTIVE: The aim of this study was to compare an in-person, group-based behavioral weight loss intervention to technology-based interventions in adults with obesity. METHODS: Adults (N = 39; body mass index: 39.5 ± 2.8 kg m-2; age: 39.9 ± 11.5 years) participated in a 6-month program with randomization to one of three intervention groups: standard behavioral weight loss, a technology-based system combined with a monthly intervention telephone call (TECH) or an enhanced technology-based system combined with a monthly intervention telephone call (EN-TECH). All groups were prescribed an energy-restricted diet and physical activity. Assessments occurred at 0, 3 and 6 months. Separate mixed-effects models using unstructured dependence structure were fit to the outcomes. RESULTS: Weight loss (least square means ± standard error) at 6 months was -6.57 ± 1.65 kg in standard behavioral weight loss, -5.18 ± 1.72 kg in TECH and -6.25 ± 1.95 kg in EN-TECH (p-value for time effect ≤ 0.0001). A similar pattern was observed for change in body mass index, waist circumference and percent body fat. There was a decrease in total energy intake (p = 0.0005) and percent dietary fat intake (p = 0.0172), and physical activity increased (p = 0.0003). CONCLUSIONS: Findings provide initial information on the use of technology-based interventions that include wearable devices combined with brief monthly telephone calls for weight loss in adults with obesity.

Socioeconomic status, infant feeding practices and early childhood obesity.

BACKGROUND: Children from low socioeconomic households are at greater risk of obesity. As breastfeeding can protect against child obesity, disadvantaged infants are less likely to breastfeed relative to more advantaged children. Whether infant feeding patterns, as well as other maternal characteristics mediate the association between social class and obesity has not been established in available research. OBJECTIVES: Examine the impact of infant feeding practices on child obesity and identify the mechanisms that link socioeconomic status (SES) with child obesity. METHODS: Based on a nationally representative longitudinal survey (ECLS-B) of early childhood (n = 8030), we examine how breastfeeding practices, the early introduction of solid foods and putting an infant to bed with a bottle mediate the relationship between social class and early childhood obesity relative to the mediating influence of other maternal characteristics (BMI, age at birth, smoking, depression and daycare use). RESULTS: Infants predominantly fed formula for the first 6 months were about 2.5 times more likely to be obese at 24 months of age relative to infants predominantly fed breast milk. The early introduction of solid foods (< 4 months) and putting the child to bed with a bottle also increased the likelihood of obesity. Unhealthy infant feeding practices were the primary mechanism mediating the relationship between SES and early childhood obesity. Results are consistent across measures of child obesity although the effect size of infant feeding practices varies. CONCLUSIONS: The encouragement and support of breastfeeding and other healthy feeding practices are especially important for low socioeconomic children who are at increased risk of early childhood obesity. Targeting socioeconomically disadvantaged mothers for breastfeeding support and for infant-led feeding strategies may reduce the negative association between SES and child obesity. The implications are discussed in terms of policy and practice.

Uncertainties in predicting structure-borne sound power input into buildings.

There has been a steady development of methods of measurement and prediction of structure-borne noise in buildings, particularly over the last two decades. In proposing and evaluating these methods, a major consideration has been the likely trade-off between accuracy and simplicity. Structure-borne sound transmission is a more complicated process than airborne sound transmission, but practitioners seek methods of prediction for the former, which are as straightforward as for the latter. In this paper a description is given of a study of multi-contact sources in buildings. The study concentrates on measurement and calculation procedures for sources and calculation procedures for receiver structures, particularly lightweight building elements. Although the study is not exhaustive, the findings point to the limitations of simplified methods, specifically the uncertainties likely as a result of reducing the data sets and computational effort, and the discrepancies resulting from simplifying assumptions.

IgE-mediated basophil tumour necrosis factor alpha induces matrix metalloproteinase-9 from monocytes.

BACKGROUND: IgE-mediated activation of mast cells has been reported to induce the release of tumour necrosis alpha (TNF-α), which may display autocrine effects on these cells by inducing the generation of the tissue remodelling protease matrix metalloproteinase-9 (MMP-9). While mast cells and basophils have been shown to express complementary and partially overlapping roles, it is not clear whether a similar IgE/TNF-α/MMP-9 axis exists in the human basophil. The purpose of this study was thus to investigate whether IgE-mediated activation of human basophils induces TNF-α and MMP-9 release. METHODS: Human peripheral blood mononuclear cells (PBMC), isolated basophils and monocytes were stimulated up to 21 h with anti-IgE. Mediator releases were assessed by ELISA, and surface expressions of mediators were detected by flow cytometry. Upregulation of cytokine production was detected by Western blot and polymerase chain reaction (PCR). RESULTS: IgE-mediated activation of basophils induced the synthesis and release of both TNF-α and MMP-9 from PBMC. In contrast, IgE-mediated activation of purified basophils induced the release and cellular expression of TNF-α but not MMP-9. Isolated monocytes did not release MMP-9 upon anti-IgE stimulation, but MMP-9 release was induced by stimulating monocytes with supernatants from activated basophils, and this release was inhibited by anti-TNF-α neutralizing antibodies. CONCLUSION: Our results strongly indicate that human basophils release TNF-α following IgE-dependent activation and that this cytokine subsequently stimulates MMP-9 release from monocytes. These findings support a direct involvement of basophils in inflammation as well as suggesting a role for the basophil in tissue remodelling.

Longitudinal assessment of cardiac diastolic function in HIV-infected patients.

Asymptomatic isolated diastolic dysfunction (DD), with normal left ventricular systolic function, may be the first indication of underlying cardiac disease in HIV-negative populations. We previously reported a high prevalence (37%) of DD among asymptomatic HIV-infected patients at low risk for AIDS and cardiovascular disease (CVD). We performed a longitudinal assessment of interval echocardiographic changes in this cohort over a four-year period. Repeat transthoracic echocardiograms (TTEs) utilized standard techniques. Sixty (of the original 91) HIV-infected patients, predominately men, underwent repeat TTE (median follow-up 3.7 years, interquartile range [IQR] 3.5, 4.0). Cohort characteristics (median; IQR) include age 42.0 (36.5, 46.0) years, HIV duration 16.4 years (8.1, 18.9), current CD4 count 572.0 cells/mm(3) (436.5, 839.0), antiretroviral therapy (ART) duration 8.1 years (4.8, 13.4) and Framingham risk score 1.0 (0.0, 2.0). DD was observed in 28/60 patients on re-evaluation (47%, 95% confidence interval [CI] 34%, 60%); 31% (11/36) of patients had new onset DD for an overall incidence of 8.2/100 person-years. On follow-up, subjects with DD were older, had a trend towards higher body mass index, hypertension and longer duration of HIV infection compared with subjects without DD. We confirmed a high prevalence of DD (47%) in asymptomatic HIV-infected patients at low risk for AIDS and CVD.

The role of basophils in the pathogenesis of allergic disease.

There has been much controversy surrounding the importance of basophils in allergy. These cells are, after all, comparatively rare and yet they display remarkable potential to contribute to the symptoms of allergic inflammation. Furthermore, by virtue of their ability to rapidly elaborate T helper type 2 (Th2)-type cytokines, they are well endowed to support ongoing allergic immunity. Despite this, basophils have often been regarded as redundant in this function as in murine models of allergy, their more numerous tissue-fixed mast cell counterparts also display Th2-type cytokine-releasing potential, which is rather different in most human mast cells. Surprisingly, it is from murine models that the basophil has re-surfaced as a key orchestrator of Th2-type immunity and chronic allergic inflammation, a property that has long been hypothesized by researchers into human basophil function but never demonstrated. Moreover, murine experimental models also highlighted the ability of basophils to take up and present antigens in an MHC-dependent manner. Controversy regarding basophils, however, has remained as recent methods for depleting these cells in murine models of allergy and parasitic infection have yielded conflicting results, where the role for this cell oscillates from essential antigen-presenting cells to mere supporting functions in controlling Th2 responses. This review highlights the recent advances in understanding the role of this rather enigmatic cell in allergy.

Shea meal and cotton stalk as potential fuels for co-combustion with coal.

The efficient management of waste biomass is an important environmental problem in agricultural countries. Often land-fill is the main disposal route with ramifications including CH(4) release having 21 times greater global warming potential per molecule than CO(2). Biomasses are considered to be CO(2)-neutral fuels when combusted. Moreover, they are renewable and covered by the renewable obligation scheme and eligible for certificates in the UK. The overall objective of the investigation is to assess the performance of selected biomass and coal co-firing under two different modes of operation, air-staging and fuel-staging with the benefit of reduced-NO(x) and SO(2) emissions in power plant. The biomasses chosen for the study, shea meal (SM) and cotton stalk (CS) have very different cellulose/lignin compositions and different reported thermal behaviour. A series of experiments have been carried out in a 20 kW, down fired combustor using coal, shea meal-coal and cotton stalk-coal blends under un-staged, air-staged and fuel-staged co-combustion configurations. For air-staging, an optimum value of primary zone stoichiometry SR(1)=0.9 was found. Keeping it fixed, the shea meal and cotton stalk content in the coal-biomass blends was set to 5%, 10% and 15% on thermal basis. NO reductions of 51% and 60% were achieved using SM and CS, respectively, with an optimum thermal biomass blending ratio (BBR) of 10%. The results obtained were compared with un-staged and air-staged results for coal without the addition of biomass. Similarly for fuel-staging, keeping the length of the reburn and burnout zone fixed, SM and CS were evaluated as reductive fuel using different reburn fuel fractions (R(ff)) of 5%, 10%, 15% and 20%. NO reductions of 83% and 84% were obtained with an optimum R(ff) of 15% with an optimum reburn zone stoichiometry of SR(2)=0.8 for both SM and CS, respectively. SO(2) reduction and char burnout efficiency were also evaluated. It was found that addition of biomass coupled with air and fuel-staging techniques reduced-NO(x) and SO(2) simultaneously while at the same time improving the char burnout efficiency.

HIV positivity, protease inhibitor exposure and subclinical atherosclerosis: a systematic review and meta-analysis of observational studies.

CONTEXT: Patients with HIV may have increased risk of atherosclerotic cardiovascular disease owing to multiple biological mechanisms. OBJECTIVE: To evaluate the evidence for subclinical atherosclerosis among patients with HIV. DESIGN: Systematic review of observational studies. DATA SOURCES: We searched Medline, Cochrane DSR, ACP Journal Club, DARE, CMR, HTA, NHSEED, Embase and the Cochrane Controlled Trials Register for studies published before November 2008. STUDY SELECTION: Eligible studies were cross-sectional, cohort, or case-control studies reporting carotid ultrasound intima-media thickness (CIMT), focal plaque incidence, or coronary artery calcium (CAC), as determined by HIV positivity or protease inhibitor (PI) exposure. DATA EXTRACTION: Two independent reviewers abstracted data using a standardised form. The primary outcome was weighted mean difference (WMD) for CIMT comparing HIV positive versus negative patients. Other outcomes included WMD by PI exposure and the odds ratio (OR) for a focal carotid plaque or CAC. Data from six cross-sectional, seven case-control and 13 cohort studies were included, involving 5456 HIV positive and 3600 HIV negative patients. RESULTS: The weighted mean CIMT was 0.04 mm thicker among patients with HIV than among non-HIV patients (95% CI 0.02 to 0.06; p<0.001). HIV positivity was not associated with carotid plaque or CAC. PI exposure did not significantly affect CIMT, carotid plaque, or CAC. There was evidence of publication bias and stratified analysis and meta-regression showed outcomes were influenced by study design, age, gender and smoking. However, HIV positivity slightly increased CIMT even after sensitivity analyses. CONCLUSIONS: HIV infection and PI exposure are not strong independent risk factors for subclinical atherosclerosis. Confounding may contribute to overestimation of the risk associated with HIV and PI exposure.