The Association Between Tobacco Use and Risk of COVID-19 Infection and Clinical Outcomes in Sweden: A Population-Based Study.

Background: The association between tobacco use and COVID-19 is controversial. During the early course of the pandemic, limited testing prevented studying a wide spectrum of clinical manifestations. Objective: To examine the potential causal association between tobacco use and COVID-19 during the second wave (1 October 2020-30 June 2021) of the pandemic in Stockholm, Sweden. Methods: A population-based cohort study was conducted in the Stockholm region of Sweden, with information on tobacco use collected prior to the pandemic. Adjusted relative risks (RR) of COVID-19 and 95% confidence intervals (CI) were calculated, contrasting current smokers and snus users to non-users of tobacco. Results: Compared with non-users of tobacco, current smokers had a lower risk of COVID-19 (RR 0.78, 95% CI = 0.75-0.81) and of hospitalisation for the disease. Current snus users had a higher risk of COVID-19. Heavy smokers and snus users had longer hospital stays than non-users of tobacco. Conclusion: Tobacco use may have a different impact on the risk of being infected with SARS-CoV-2 and the risk of developing severe clinical manifestations. Further research is needed to determine the underlying mechanisms.

Current tobacco use and COVID-19 diagnoses in a cohort of adult clients of public dental clinics in Sweden.

Smoking has been linked with both increased and decreased risk of COVID-19, prompting the hypothesis of a protective role of nicotine in the pathogenesis of the disease. Studies of the association between use of smokeless tobacco and COVID-19 would help refining this hypothesis. We analysed data from 424,386 residents in the Stockholm Region, Sweden, with information on smoking and smokeless tobacco (snus) use prior to the pandemic obtained from dental records. Diagnoses of COVID-19 between February and October 2020 were obtained from health-care registers. We estimated the risk of receiving a diagnosis of COVID-19 for current smokers and for current snus users relative to non-users of tobacco, adjusting for potential confounders (aRR). The aRR of COVID -19 was elevated for current snus users (1.09 ;95%CI = 0.99-1.21 among men and 1.15; 95%CI = 1.00-1.33 among women). The risk for women consuming more than 1 can/day was twice as high as among non-users of tobacco. Current smoking was negatively associated with risk of COVID-19 (aRR = 0.68; 95% CI = 0.61-0.75); including hospital admission (aRR = 0.60; 95% CI = 0.47-0.76) and intensive care (aRR = 0.43; 95% CI = 0.21-0.89). The hypothesis of a protective effect of tobacco nicotine on COVID-19 was not supported by the findings. The negative association between smoking and COVID-19 remains unexplained.

The associations of indoor environment and psychosocial factors on the subjective evaluation of Indoor Air Quality among lower secondary school students: a multilevel analysis.

Subjective evaluation of Indoor Air Quality (subjective IAQ) reflects both building-related and psychosocial factors, but their associations have rarely been studied other than on the individual level in occupational settings and their interactions have not been assessed. Therefore, we studied whether schools' observed indoor air problems and psychosocial factors are associated with subjective IAQ and their potential interactions. The analysis was performed with a nationwide sample (N = 195 schools/26946 students) using multilevel modeling. Two datasets were merged: (i) survey data from students, including information on schools' psychosocial environment and subjective IAQ, and (ii) data from school principals, including information on observed indoor air problems. On the student level, school-related stress, poor teacher-student relationship, and whether the student did not easily receive help from school personnel, were significantly associated with poor subjective IAQ. On the school level, observed indoor air problem (standardized ß = -0.43) and poor teacher-student relationship (standardized ß = -0.22) were significant predictors of poor subjective IAQ. In addition, school-related stress was associated with poor subjective IAQ, but only in schools without observed indoor air problem (standardized ß = -0.44).

European S3-guidelines on the systemic treatment of psoriasis vulgaris.

Of the 131 studies on monotherapy or combination therapy assessed, 56 studies on the different forms of phototherapy fulfilled the criteria for inclusion in the guidelines. Approximately three-quarters of all patients treated with phototherapy attained at least a PASI 75 response after 4 to 6 weeks, and clearance was frequently achieved (levels of evidence 2 and 3). Phototherapy represents a safe and very effective treatment option for moderate to severe forms of psoriasis vulgaris. The onset of clinical effects occurs within 2 weeks. Of the unwanted side effects, UV erythema from overexposure is by far the most common and is observed frequently. With repeated or long-term use, the consequences of high, cumulative UV doses (such as premature aging of the skin) must be taken into consideration. In addition, carcinogenic risk is associated with oral PUVA and is probable for local PUVA and UVB. The practicability of the therapy is limited by spatial, financial, human, and time constraints on the part of the physician, as well as by the amount of time required by the patient. From the perspective of the cost-bearing institution, phototherapy has a good cost-benefit ratio. However, the potentially significant costs for, and time required of, the patient must be considered.

Neurofibromatosis type 1 tumour suppressor gene expression is deficient in psoriatic skin in vivo and in vitro: a potential link to increased Ras activity.

BACKGROUND: Neurofibromatosis type 1 (NF1) protein (neurofibromin) accelerates the inactivation of Ras-GTP in various cell types. Somatic mutations of the NF1 gene may lead to malignant transformation and uncontrolled proliferation. We have previously shown that NF1 protein expression is downregulated in psoriasis in vivo. OBJECTIVES: To study the functional expression and distribution of NF1 mRNA and protein in vivo and in psoriatic and normal keratinocyte cultures. METHODS: Immunohistochemistry and in situ hybridization were used to study NF1 gene and protein expression in psoriasis in vivo. Furthermore, Northern and in situ hybridizations, immunoblot and localization analyses were utilized to study NF1 mRNA and protein in vitro in keratinocyte cultures. RESULTS: NF1 tumour suppressor gene expression was reduced in lesional psoriatic skin compared with perilesional and normal skin in vivo. The in vitro results showed that the levels of NF1 mRNA and protein were reduced in cultured psoriatic keratinocytes during cellular differentiation even after multiple passaging of the cells. Moreover, cultured nonlesional psoriatic keratinocytes were almost equally defective as lesional cells with respect to NF1 expression. CONCLUSIONS: Our findings demonstrate that psoriatic keratinocytes maintain an altered phenotype and gene expression profile even when isolated from interaction with lymphocytes and fibroblasts, which are known to increase proliferation of keratinocytes. As NF1 protein is regarded as a Ras proto-oncogene regulator, the aberrant expression and distribution of NF1 protein and mRNA found in the present study may be causative to the previously described increased activation of Ras in psoriatic lesions, and relate to altered cellular behaviour.

Immunohistological distribution of the tight junction components ZO-1 and occludin in regenerating human epidermis.

BACKGROUND: Molecular characterization of tight junction proteins during the past few years has provided novel methods for studying these specialized junctions. Tight junctions have recently been characterized in the granular cell layer of human epidermis, and the role of these junctions in the epidermal barrier is now being re-evaluated. OBJECTIVES: To investigate the expression of tight junction components during the re-epithelialization of suction blisters and the regeneration of the corneal layer after tape stripping. METHODS: Suction blisters were induced in eight healthy volunteers, and skin biopsies were taken 4 or 6 days afterwards. The restoration of epidermal barrier function was evaluated by measuring water evaporation (WE) from the wound area. Tape stripping was performed on three volunteers to remove the corneal layer. The tissues were immunolabelled using indirect immunofluorescence or the avidin-biotin method. RESULTS: Prior to the biopsies, WE from the blister wounds was markedly elevated in comparison with normal skin. In the epidermis surrounding the blister, occludin and ZO-1 were expressed in the granular cell layer only. In the hyperproliferative zone adjacent to the border of the blister, the expression of ZO-1 was redistributed into several spinous cell layers, while occludin expression was restricted to the upper epidermis. In the leading edge of migrating keratinocytes, both proteins were expressed exclusively in the most superficial layer of keratinocytes. Double labelling for ZO-1 and involucrin showed expression of both proteins in the same layers of hyperproliferative keratinocytes, while the expression patterns were clearly different in the migrating keratinocytes. CONCLUSIONS: Tight junctions of regenerating epidermis may provide a functional barrier prior to regeneration of the corneal layer.

Epidermal tight junctions: ZO-1 and occludin are expressed in mature, developing, and affected skin and in vitro differentiating keratinocytes.

This study demonstrates the presence of tight junction antigens in adult and developing human epidermis. Indirect immunofluorescence labeling and immunoelectron microscopy with antibodies to ZO-1 and occludin localized tight junction components ZO-1 and occludin to a narrow zone of the granular cells of adult epidermis. Double immunolabeling for tight junction components with adherens junction or desmosome proteins suggested that occludin is more specific for tight junctions than ZO-1, which may also be associated with adherens junctions. In developing skin, tight junctions interconnected the peridermal cells, and after the fetal stratification localized to the granular cell layer. Immunolabeling of psoriasis, lichen planus, and ichthyosis vulgaris, representing aberrant differentiation of the epidermis, showed that these conditions were associated with relocation of ZO-1 and occludin to the spinous cells. Cultures of epidermal keratinocytes, which offer a useful model for the formation of cellular contacts, revealed that tight junction components, ZO-1 and occludin, displayed a marked degree of colocalization relatively late during the process when the fusion zone had assumed a linear appearance. This suggests that the formation of adherens junctions and desmosomes precedes that of tight junctions. We speculate that the epidermal barrier, isolating the human body from the external environment, is in part formed by tight junctions of stratum granulosum.

Household educational level as a determinant of consumption of raw vegetables among male and female adolescents.

BACKGROUND: This study aimed to examine the association between household educational level and consumption of raw vegetables among adolescents and to assess the influence of other determinants on the association, such as family factors, school achievement, health behavior, meal pattern, and weight-related factors. A further aim was to investigate whether the associations were the same for male and female adolescents. METHODS: The study is based on data from the School Health Promotion Survey 1997-1998. Data were collected by a classroom-administered questionnaire, which was completed by 76,201 secondary school pupils. The study recorded the consumption of raw vegetables, but not the consumption of cooked vegetables. Multivariate logistic regressions were used in the analyses. RESULTS: A clear positive association between educational level of the household and daily consumption of raw vegetables was found among adolescents. The adolescent's own school achievement explained part of the association between household educational level and consumption of raw vegetables. Other factors explained the association to a small degree, with meal pattern and weight factors having no effect. The associations were similar for both genders. CONCLUSIONS: Educational level in the household is an important determinant of consumption of raw vegetables. A household with a high educational level will also presumably contain adolescents who have good school achievement, another strong predictor of frequent consumption of raw vegetables.

Occult neurofibroma and increased S100 protein in the skin of patients with neurofibromatosis type 1: new insight to the etiopathomechanism of neurofibromas.

BACKGROUND: Neurofibromas represent proliferation of the connective tissue cells of peripheral nerves and deposition of collagenous extracellular matrix. There is evidence that the appearance and growth of neurofibromas may be associated with prior or ongoing mechanical trauma in patients with neurofibromatosis type 1 (NF1). OBJECTIVE: To study the histologic characteristics of apparently healthy skin of patients with NF1. DESIGN: The histologic features of healthy-looking skin of patients with NF1 were analyzed. SETTING: University hospital. PATIENTS: Ten patients who fulfilled the criteria for NF1. INTERVENTIONS: Punch biopsy specimens of healthy-looking skin of the forearm from 9 volunteer patients and of the upper eyelid during cosmetic operation from 1 volunteer patient were obtained. MAIN OUTCOME MEASURES: The main outcomes were not predicted, and the hypothesis was formulated during data collection. RESULTS: Apparently unaffected skin of 5 patients with NF1 was studied by routine histologic testing with respect to expression of S100 protein. Unexpectedly, analysis of the samples revealed the presence of a small neurofibroma tumor in one of the samples. The tumor was located in deep dermis around a hair follicle. In addition, neurofibromatous tissue not large enough to be called a tumor was found on the same anatomical location in another patient. In further studies, 10 punch biopsy specimens of apparently healthy skin from patients with NF1 were similarly sectioned and analyzed. No tumors were found in these additional samples. In 4 patients, however, abundant S100 protein-positive cells were located within collagenous extracellular matrix surrounding hair follicles. CONCLUSIONS: The skin of patients with NF1 might be more widely affected than previously thought and occult neurofibromas are not rare.

Patterns of health-related behaviour and their cross-cultural validity--a comparative study on two populations of young people.

The study aimed at exploring health-related behaviour patterns among young people. The approach was cross-cultural and the study was focused on identifying culturally valid behaviour patterns in two countries, Finland (F) and Switzerland (CH). Data came from two surveys and included 16- and 18-year-old respondents (F: study year 1993, n = 280, CH: study year 1992/3, n = 272). Three intake behaviours--eating, drinking and smoking--were analysed by means of cluster and logistic regression analyses. Three cross-culturally valid behaviour clusters emerged: a healthy, an unhealthy and a mixed pattern where unhealthy eating behaviours were combined with non-smoking and low alcohol use. The determinants of the patterns were tested by comparing the two countries in relation to the socio-demographic characteristics of the young people that belonged in the same cluster. In both countries the structure of the determinants was almost identically indicating high cross-cultural stability. The study suggests that among young people of this age there is clear and cross-culturally consistent patterning of health-related behaviours.

Psoriasis and altered calcium metabolism: downregulated capacitative calcium influx and defective calcium-mediated cell signaling in cultured psoriatic keratinocytes.

Intracellular calcium plays an important part in the regulation of proliferation and differentiation of keratinocytes. Detached from their in vivo environment, cultured psoriatic keratinocytes were investigated by monitoring free intracellular calcium concentration, which was measured using fura-2/AM as a calcium-sensitive probe. The mean increase in intracellular calcium of psoriatic keratinocytes was significantly reduced compared with control keratinocytes when intracellular calcium stores were mobilized from endoplasmic reticulum with thapsigargin. This finding suggests defective capacitative calcium influx of psoriatic cells. Intracellular calcium stores were similar in psoriatic and control keratinocytes, when extracellular calcium was chelated with ethyleneglycol-bis(beta-aminoethyl ether)-N,N,N',N',-tetraacetic acid and intracellular calcium was depleted with thapsigargin. Mechanical wounding of keratinocyte monolayer resulted in a significantly reduced rise in intracellular calcium of psoriatic cells in low (< 0.1 mM) and high (1.8 mM) extracellular calcium suggesting defective intercellular coupling of psoriatic keratinocytes. Blocking of gap-junctions with heptanol in wounded keratinocytes did not affect the intracellular calcium response in psoriatic keratinocytes in contrast to healthy keratinocytes. Adding adenosine triphosphate to culture medium resulted in a more pronounced intracellular calcium increase than thapsigargin in psoriatic keratinocytes, suggesting that inositol triphosphate-mediated, P2-purinergic signaling was enhanced in these cells. Moreover, psoriatic keratinocytes maintained their defective responses up to at least fifth passage suggesting that psoriatic keratinocytes have an inborn error in calcium metabolism, rather than a localized defect in response to altered extracellular calcium gradient observed in vivo.

New function for NF1 tumor suppressor.

The expression and subcellular localization of neurofibromatosis type 1 tumor suppressor was studied in keratinocytes induced to differentiate by increased Ca2+ concentration of the culture medium. Differentiating keratinocytes became intensely immunoreactive for neurofibromatosis type 1 protein, which was apparently associated with cellular fibrils. Double immunolabeling with antibodies to cytokeratin 14 and neurofibromatosis type 1 protein suggested an association of intermediate type cytoskeleton and neurofibromatosis type 1 protein. The presence of neurofibromatosis type 1 protein in cell preparations treated with cytoskeletal buffer indicated a high affinity interaction between intermediate filaments and neurofibromatosis type 1 protein. Further studies utilizing double immunolabelings revealed that the intense neurofibromatosis type 1 tumor suppressor signal on intermediate filaments was temporally limited to the period in keratinocyte differentiation in which the formation of desmosomes takes place. Keratinocytes were also cultured from nine patients with type 1 neurofibromatosis and were studied with respect to cell morphology, and association of neurofibromatosis type 1 protein with intermediate cytoskeleton. The results showed that keratinocytes cultured from patients with neurofibromatosis type 1 displayed a highly variable cell size and morphology compared to controls. The latter findings represent predicted alterations in a situation where cytoskeletal organization is disturbed. Furthermore, differentiating neurofibromatosis type 1 keratinocytes were characterized by a reduced number of cytokeratin bundles that were decorated neurofibromatosis type 1 protein. The results of this study suggest that neurofibromatosis type 1 tumor suppressor exerts its effects in part by controlling organization of cytoskeleton during the formation of cellular contacts.

Individual differences in adolescent religiosity in Finland: familial effects are modified by sex and region of residence.

Data from 16-year-old Finnish twin pairs were used to estimate familial effects on religiosity and the modification of those effects by sex and residential region. The sample of 2265 twin boys and 2521 twin girls formed 779 monozygotic and 1614 dizygotic pairs, 785 of the same sex and 829 of opposite sex. We compared religiosity scores of twins living in more rural and traditional northern Finland with those living in the more urban and secular southern region. Girls had higher religiosity scores than did boys, and twins living in northern Finland had higher religiosity scores than those resident in southern Finland. Correlations for monozygotic twins were slightly higher than those for dizygotic twins, and covariance modeling found modest heritability of religiosity [11% (95% CI 0-24) for girls; 22% (95% CI 6-38) for boys], and substantial shared environmental effects [60% (95% CI 49-69) and 45% (95% CI 31-57)] among girls and boys, respectively. The correlation between shared environmental effects in boys and girls was estimated to be 0.84 (95% CI 0.73-0.99). In analyses distinguishing region of residence, girls living in southern Finland were found to have significantly higher unshared environmental effects than girls in northern Finland, while boys living in the urban south appeared to have lower shared environmental effects, and higher additive genetic effects, than boys living in the rural north.

Social mobility and health related behaviours in young people.

STUDY OBJECTIVE: To assess the influences related to social mobility, particularly health related behaviours, as one potential explanation for the social class variation in health among adults. DESIGN: The study is based on questionnaire data from the Adolescent Health and Lifestyle Surveys of 1985, 1987, and 1989. SETTING: The whole of Finland. PARTICIPANTS: A representative sample of 8355 adolescents. The response rate was 79%. MEASUREMENT AND MAIN RESULTS: The relation between social mobility and health related behaviours among 16 and 18 year old young people was studied. The measure of social mobility was based on a combination of the social class of origin and achieved social position measured by the present educational status, educational attainment, and labour market position. Three mobility groups were constructed: the downwardly mobile, the upwardly mobile and the stable. Health related behaviours in an upwardly or downwardly mobile group were compared with a stable group from the same social class of origin by calculating relative risks (RR). RRs were assessed by calculating age and sex adjusted rate ratios approximating a Mantel-Haenszel estimate. In logistic regression analyses the independent effects of the social class of origin and the achieved social position were investigated. Most of the nine behaviours studied (smoking, alcohol use, heavy intoxication, coffee drinking, tooth brushing, consumption of sweets, lack of physical exercise, choice of bread spread, and consumption of milk) were related to the direction of mobility so that health compromising behaviours were more frequent among downwardly mobile and less frequent among upwardly mobile young people than their stable peers. Achieved social position proved to determine health related behaviours more strongly than class of origin, thus emphasising the way education facilitates both health values and behaviours as well as the future social position. CONCLUSIONS: The close relation between social mobility and health related behaviours is concluded to be a part of an explanation of social class differences in health observed among adults.

Increased prevalence of vitiligo, but no evidence of premature ageing, in the skin of patients with bp 3243 mutation in mitochondrial DNA in the mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome (MELAS).

The MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) belongs to the category of mitochondrial disorders. The most common molecular aetiology of the syndrome is a mutation at base pair (bp) 3243 in the mitochondrial genome (mtDNA). The phenotype is varied and, apart from central nervous system involvement, the patients with this mutation may present with neurosensory hearing loss, diabetes mellitus and cardiomyopathy. These phenotypes suggest that organs dependent on aerobic metabolism suffer most. We investigated the possible clinical and physiological manifestations of impaired energy metabolism in the skin of 28 patients with the bp 3243 mutation in mtDNA. Non-invasive sonography and laser Doppler flowmetry were used to measure skin thickness and the blood flow of the skin. Skin collagen synthesis was assayed from suction blister fluid. Evaporimetry was used to assess the re-epithelialization rate of suction blister wounds. Histochemistry and immunohistochemistry were used to evaluate the melanocytes and pigment in the skin. Vitiligo was found in three of the 28 patients (11%), which was markedly more than in the general population. Histological findings showed an absence of pigment, but an apparently normal distribution of melanocytes in the dermoepidermal junction. Seborrhoeic eczema and atopy were also somewhat more frequent. No features of premature ageing, such as a marked decrease in skin thickness, blood flow, collagen synthesis or re-epithelialization rate, were demonstrated.

Developmental regulation of NF1 tumor suppressor gene in human peripheral nerve.

Mutations of the NF1 tumor suppressor gene cause type 1 neurofibromatosis, characterized by multiple tumors of the peripheral nerves, as well as other tumor types. The NF1 protein, neurofibromin, is intricately linked to the cell growth regulatory signalling pathways, e.g. by possessing RAS-GTPase activity. The regulation and role of neurofibromin are not known in normal human development. We addressed this issue by studying the regulation of neurofibromin in normal human peripheral nerves, from early fetal development to adulthood. The barely detectable neurofibromin immunosignal in peripheral nerves during the first trimester of gestation contrasted dramatically to its increase in Schwann cells, perineurial cells, and axons during the second and third trimesters. Interestingly, the type I and II isoforms of neurofibromin, differing in their RAS oncoprotein inactivation capacity, displayed clearly different expression profiles throughout these periods. This suggests distinct cellular functions for these neurofibromin isoforms. The results also revealed distinct species-specific differences in neurofibromin expression, potentially bearing relevance to the lack of human neurofibromatosis-like disorders in other species.

Urban small area variation in adolescents' health behaviour.

Our previous study indicated that region plays a relatively small role in adolescents' health behaviour. Here, the regional patterning of health behaviour is studied further by shifting the focus to small areas. First, we test whether small area socioeconomic, demographic and housing characteristics correlate with health behaviour. The analysis then turns to the relationship between these characteristics and their individual level correlates. We wish to ascertain if behaviour is related to small area characteristics similarly for both genders and for adolescents' socioeconomic characteristics. The Adolescent Health and Lifestyle Survey data from 1989-1995 (16- and 18-year-olds, n = 1048, response rate 71%) were linked with data describing 33 subareas of Helsinki, the capital of Finland. Smoking, alcohol use, abstention from dietary fat and physical activity were used as lifestyle indicators. Gender apparently influences the extent to which the area plays a role. Logistic regression demonstrated that prolonged unemployment predicted low prevalence of abstention from dietary fat (traditional dietary patterns) among girls and heavy drinking among boys. High total rate of unemployment predicted lower physical activity among girls. Also owner-occupied housing correlated positively with girls' physical activity. Although the individual level socioeconomic characteristics were not as strongly related to health behaviour as the small area factors, a low level of education predicted smoking and alcohol use and, among girls, decreased physical activity. We conclude that small area characteristics, especially the level of unemployment of the area, may be even more strongly related to health behaviour than individual socioeconomic characteristics.