Atherosclerosis is a progressive inflammatory disease that is characterized by the accumulation of lipids, infiltrated cells and fibrous elements in large arteries. This thesis focuses on the molecular mechanisms behind foam cell formation and inflammation, two central processes in the development of atherosclerosis. More specific, we studied the effects of proinflammatory cytokines on CXCL16 expression and its role as scavenger receptor on macrophages and smooth muscle cells in atherogenesis. CXCL16 is defined as a chemokine and a scavenger receptor, regulating adhesion and chemoattraction of CXCR6 expressing cells and uptake of oxLDL. We show that the expression of CXCL16 and its receptor CXCR6 are more pronounced in human atherosclerotic lesions compared with non-atherosclerotic vessels. Increased expression of CXCL16 was also seen in atherosclerotic aortas of apoE-/- mice compared with aortas of non-atherosclerotic, age-matched C57BL/6 mice. In vitro, IFN gamma induced CXCL16 expression in primary human monocytes and smooth muscle cells which resulted in an increased uptake of oxLDL. Treatment of mice with IFN gamma also induced CXCL16 expression in atherosclerotic lesions. Thus, we have demonstrated a role for IFN gamma in foam cell formation through upregulation of CXCL16. The expression of CXCR6 was defined to the same regions as for CXCL16 in the lesion, indicating the presence of cells able to respond to CXCL16. Consequently, CXCL16 could serve as a molecular link between lipid metabolism and immune activity in atherosclerotic lesion. CD137 belongs to the TNF family and mediates several important processes in inflammation. CD137 is involved in the activation of T cells, NK cells, B cells and monocytes and regulate cytokine production, proliferation and apoptosis in these cells. A limited number of studies have demonstrated CD137 expression on smooth muscle cells and endothelial cells. Our results show that CD137 mRNA is higher expressed in human atherosclerotic lesions compared with unaffected vessels. We found that endothelial cells express CD137 in atherosclerotic lesions and that cultured endothelial cells and smooth muscle cells express CD137 and CD137 ligand in vitro. CD137 was regulated differentially by proinflammatory cytokines (i.e. IFN gamma, TNF alpha, IL-1 beta) and bacterial lipopolysaccharide depending on cell type. Furthermore, we investigated the effects of CD137 signalling, demonstrating that binding of the CD137 ligand to its receptor increases proliferation and migration of smooth muscle cells. In summary, this thesis has focused on the expression, regulation and role of CXCL16 and CD137, two genes that have not been described earlier in the concept of atherosclerosis. The findings demonstrate some of the molecular mechanisms involved in vascular inflammation and may increase our knowledge about the development of atherosclerosis.

The purpose of this project was to evaluate the effectiveness of a practice-based dermoscopy training program for dermatology healthcare providers in order to improve their technique of performing clinical skin exams for the early detection of melanomas. The overall incidence of melanoma continues to rise. More than 75% of all skin cancer deaths are from melanoma. Advanced melanoma spreads to lymph nodes and internal organs and can result in death. One American dies from melanoma almost every hour (American Cancer Society [ACS], 2009). Early diagnosis and excision are essential to reduce morbidity and to improve patient survival. This one-group before-and-after study design utilized a convenience sample of three dermatology healthcare providers (DHPs). The primary investigator conducted a retrospective review of the pathology logs for each provider. The time frame for the review was a three-month period in 2010, which represented the same time frame that the study was conducted in 2011. The DHPs participated in a four-hour training workshop that included pattern analysis recognition using dermoscopy. Following the workshop, each DHP was given a DermLite 3Gen DL100 to use in practice when performing clinical skin examinations. All DHPs completed a data collection sheet to document their pattern of decision making with and without a DermLite. The outcome of interest was the use of dermoscopy by DHPs to demonstrate an increased detection of melanoma when compared to naked-eye examination. The outcome was evaluated 12 weeks post-workshop training. There were 120 evaluations made with the DermLite as compared to the naked eye. The overall agreement was 0.52, AC1 coefficient (95% CI) was 0.36 (0.30, 0.42), p < .001, and kappa coefficient (95% CI) was 0.27 (0.20, 0.43), p < .001. Overall, the risk of lesion under exam being suspicion for skin cancer was higher on 27.5% (33 out of 120) of the evaluations and lower on 20.8% (25 out of 120) evaluations. The risk of lesion was evaluated the same on 51.7% (62 out of 120) of the evaluations. This is an indication of “Poor” agreement between the two methods. The diagnosis and disposition made using DermLite compared to naked-eye results for both coefficients provided an “Intermediate to Good” agreement between the two methods in assigning diagnosis and disposition. This indicates that there is no difference between DermLite and naked-eye evaluations. More studies are needed in order to provide better evidence on the value of dermoscopy in clinical practice at the Dermatology and Laser Center. Future projects should be more explicit regarding the methods used and lesion selection in order to better understand the benefits of dermoscopy.

No description available.

Background: Financial constraints challenge evidence of the effectiveness of dermatological inpatient management. Objective: To evaluate the effectiveness of hospitalization in atopic dermatitis and psoriasis regarding initial and sustained benefits. Methods: Prospective study on adults with psoriasis vulgaris (n = 22) and atopic dermatitis (n = 14). At admission, discharge, and 3 months after discharge, validated outcomes of objective and subjective disease severity were assessed by trained investigators. Results: Hospitalization resulted in substantial benefit in quality of life and clinical disease severity. Looking at mean scores, the observed benefit appeared stable until 3-month follow-up. The analysis of individual patient data revealed significant changes in disease severity between discharge and 3-month follow-up with some patients relapsing, others further improving. Reasons for hospitalization and treatment performed were not related to sustained benefit. Conclusions: In psoriasis vulgaris and atopic dermatitis, hospitalization effectively improved quality of life and clinical disease severity. Further research should focus on prognostic factors for sustained improvement. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The Melanocyte Keratinocyte Transplantation Procedure (MKTP) is an effective surgical replacement of lost melanocytes in recalcitrant vitiligo and pigmentary skin disorders. However, it is only effective in stable vitiligo lesions because active autoimmunity destroys the newly transplanted melanocytes. Despite careful selection of candidates based on the reported clinical stability, the success of the procedure is still unpredictable. MKTP candidates with non-segmental, segmental, and mixed vitiligo, as well as hypopigmented scars and Piebaldism patients were enrolled to our studies. Our aim was first, to investigate the possible immunological mechanisms responsible for the unpredictable post- transplantation outcomes, including T cell subsets and inflammatory chemokines, by correlating these biomarkers with clinical phenotypes, duration of stability, and surgical outcomes. We used suction blister biopsy, a minimally invasive technique that we developed to sample human skin. Moreover, we quantified transplanted melanocytes in the suspension using flow cytometry. Following MKTP, we corelated these biomarkers to the repigmentation score. We found that CD8+ T cells remain in some clinically stable vitiligo lesions, correlate negatively with the post-surgical score of repigmentation, and inversely impact the durability of the responses. Interestingly, the number of transplanted melanocytes in the suspension and the duration of stability do not have prognostic roles. Based on our findings and in a second group of patients, we suppressed the activity of T cells to enhance the outcomes of MKTP. We used Ruxolitinib, JAK1/2 inhibitor, in a triple blinded randomized controlled within subject study, in comparison with Tacrolimus (a calcineurin inhibitor and the standard of care treatment in vitiligo) as well as placebo control. We found lower T cell infiltrate, lower chemokines, and better skin repigmentation in lesions treated with MKTP plus Ruxolitinib or Tacrolimus than in lesions treated with MKTP plus placebo. Lastly, we compared two different types of laser in preparation of the recipient skin for MKTP - ablative versus fractional Er:YAG laser. We found that the ablative laser is combined with minimal CD8+ T cell epidermal infiltrate and superior repigmentation score in comparison to more infiltrate and lower repigmentation score with the fractional laser. Taken together, these results from our studies provide novel insight to predict the optimal surgical candidates and will improve surgical outcomes. It advances the treatment of vitiligo by uncovering the impact of autoimmunity on the success of repigmentation and discovering new approaches to optimize the surgical treatment options in patients with vitiligo and pigmentary skin disorders.

Background: A landmark study suggested that wide excision of intermediate-thickness melanoma with sentinel lymph node biopsy (SLNB) and subsequent completion lymph node dissection (CLND) for regional disease may improve prognostication and disease-free survival (DFS) compared with those undergoing wide excision alone. However, these benefits were relatively small and not associated with an improvement in disease-specific survival (DSS). It remains unknown if SLNB and subsequent treatments are beneficial in elderly patients who have a decreased overall (OS) due to other causes. Methods: Adults ≥ 70 years of age, who underwent surgical intervention for intermediate-thickness cutaneous melanoma from 2000-2013 were identified from a prospectively-maintained database. Clinicopathologic variables measured included age, gender, anatomic site, histologic type, tumor thickness, ulceration, receipt and result of SLNB, completion of CLND, OS, and DFS. Results: Ninety-one patients underwent excision of an intermediate-thickness melanoma. Forty-nine patients (54%) received a SLNB. Seven of these biopsies (14%) were positive, and five patients went on to receive CLND. Five-year OS was 41% in patients who did not receive SLNB and 52% in patients who did receive SLNB (p=0.11). DFS was similar between groups independent of receipt of SLNB. Conclusion: Among elderly patients with intermediate-thickness melanoma, patients who received SLNB had similar 5-year OS and DFS compared with those who did not receive SLNB. Routine SLNB for intermediate-thickness melanoma patients may not significantly change outcomes for this age group, and clinical decision-making should consider individual patient comorbidities and goals of care.

Since more and more customers switch to online purchases, the last-mile delivery problemhas created a huge burden on companies and cities. The increasing parcel delivery leads toextra operational costs in logistics and congestion in cities. IKEA, the furniture retailcompany, is going to propose a project – IKEA Urban Multi Hub to solve this problem byallowing customers to carry back orders themselves. This study collaborates with IKEA toinvestigate and formulate a robust hub that customers are willing to visit. The aim of thisresearch is to identify appropriate locations for the hub and possible future mobility that thehub should provide. Moreover, develop concepts and strategies for two cities - Shanghai cityand New York City.Research and customer interview were fundamental parts of this project. The research partincludes literature review and background that helps to preliminary clarify urban conditions,possible future mobility, and travel behavior. The customer interview part investigatescustomers’ preferences in two selected cities which helps to realize their needs and gaininspiration. The results showed that clustering with metro stations and providingautonomous mobility may create a smooth customer self-delivery experience for IKEA UrbanMulti Hub. Besides, cooperating with logistic companies can reduce the operation risk of theHub and strengthen the business model. Further concepts and strategies developed for twoselected cities are described in the thesis.

São cada vez mais freqüentes as queixas cosméticas na sociedade contemporânea objetivando a perfeição das formas do corpo e da pele. Os dermatologistas e cirurgiões plásticos são frequentemente consultados para avaliar e tratar essas queixas. Sendo assim é importante conhecer o Transtorno Dismórfico Corporal, inicialmente chamado de dismorfofobia que foi pouco estudado até recentemente. Esse transtorno é relativamente comum, por vezes incapacitante, e envolve uma percepção distorcida da imagem corporal caracterizada pela preocupação exagerada com um defeito imaginário na aparência ou com um mínimo defeito corporal presente. A maioria dos pacientes apresenta algum grau de prejuízo no funcionamento social e ocupacional e como resultado de suas queixas obsessivas com a aparência podem desenvolver comportamentos compulsivos, em casos mais graves há risco de suicídio. O nível de juízo crítico é prejudicado, não reconhecem que seu defeito é mínimo ou inexistente e freqüentemente procuram tratamentos cosméticos para um transtorno psíquico. A prevalência do transtorno na população geral é de 1 a 2% e em pacientes dermatológicos e de cirurgia cosmética de 2,9 a 16%. Neste estudo investigou-se a prevalência do Transtorno Dismórfico Corporal em pacientes dermatológicos. Entrevistadores treinados avaliaram com questionários e entrevistas semi-estruturadas (SCID) pacientes que procuravam tratamentos cosméticos clínicos e cirúrgicos (grupo Cosmiatria, n=150), que procuravam a dermatologia em geral (grupo Geral, n=150) e grupo controle de 50 pacientes. Três psiquiatras independentes fizeram a melhor estimativa diagnóstica (best estimate diagnosis). Foram diagnosticados 32 pacientes (Cosmiatria 14%; Geral 6,7%; Controle 2%). As diferenças entre as prevalências nos três grupos foram significativas, bem como entre o grupo da Cosmiatria e o Controle. A regressão logística mostrou maior prevalência na Cosmiatria do que no grupo Geral e Controle, em indivíduos solteiros e com menor índice de massa corpórea. A gravidade foi moderada (em escala validada) e as obsessões foram mais significativas no grupo da Cosmiatria do que no Geral. A aplicação de escala de avaliação de crenças mostrou que o nível de juízo crítico estava mais prejudicado nos pacientes do grupo da Cosmiatria. Nenhum paciente havia sido diagnosticado previamente. As comorbidades psiquiátricas foram freqüentes, principalmente o Transtorno Depressivo Maior e o Transtorno Obsessivo Compulsivo. A comparação de subgrupos de pacientes que tinham o Transtorno Dismórfico Corporal ou este associado ao Transtorno Obsessivo-Compulsivo não mostrou diferenças significativas quanto às variáveis demográficas, comorbidades psiquiátricas, gravidade do transtorno ou nível de juízo crítico. As queixas dermatológicas mais freqüentes, em média duas, foram: discromias, acne, quanto à forma do corpo e ao envelhecimento. No grupo Cosmiatria a maioria dos pacientes já havia se submetido a tratamentos ou cirurgias cosméticas com resultados insatisfatórios. Os achados desse estudo apontam para uma maior prevalência em pacientes dermatológicos, principalmente nos que procuram tratamentos cosméticos, sugerindo que possam ser mais obsessivos e ter pior nível de juízo crítico em relação aos seus sintomas. Considerando a alta prevalência do Transtorno Dismórfico Corporal em pacientes dermatológicos e que os tratamentos cosméticos raramente melhoram seus sintomas, o treinamento dos profissionais para a investigação sistemática, diagnóstico e encaminhamento para tratamento psiquiátrico parece fundamental / Cosmetic concerns are increasingly pervading the contemporary societies, focusing on body shape and the skin perfection. Dermatologists and plastic surgeons are frequently consulted to evaluate and treat these concerns. Therefore it is important to be aware of the Body Dysmorphic Disorder, also known as dysmorphophobia, little studied until recently. This disorder is relatively common sometimes causing impairment involving a distorted perception of the body image characterized by an excessive preoccupation with an imagined or minimal appearance defect. Most of the patients experience some degree of impairment in social or occupational functioning and as a result, their obsessive thoughts, may lead to repetitive behaviors and in severe cases, to attempted suicide. Most individuals have poor insight and they do not acknowledge the defect is minimal or inexistent and seek out cosmetic treatments for a psychiatric disorder. The prevalence of this disorder among general population ranges from 1 to 2 % and in dermatological and cosmetic surgery patients ranges from 2, 9 to 16%. This study assessed the prevalence of Body Dysmorphic Disorder in dermatological patients. Trained interviewers used questionnaires (BDDQ) and semi-structured clinical interviews (SCID) to access patients seeking clinical or surgical cosmetic treatments (Cosmetic group, n=150), seeking dermatology in general (General group, n=150) and a control group of 50 subjects. Three independent psychiatrists assigned the best estimate diagnosis and 32 patients were diagnosed with the disorder (Cosmetic 14%, General 6, 7% and Control 2%). Prevalence differences in the three groups were significant, also for Cosmetic and Control groups. In the logistic regression a higher prevalence has been noticed in the Cosmetic group (when compared with General and Control groups), in patients that are not currently married and with less body mass index. The severity of the symptoms assessed by a validated scale (BDD-YBOCS) was moderate and the obsessions were significantly higher in the Cosmetic group as compared to the General one. Beliefs were assessed by a scale (BABS) and insight were significantly poorer in the Cosmetic group. None of the patients had been previously diagnosed. Psychiatric co-morbidities were frequent, mostly Major Depressive Disorder and Obsessive-Compulsive Disorder. Comparing two patients subgroups with just Body Dysmorphic Disorder and patients with Obsessive-Compulsive Disorder as comorbidity show no differences according to demographic variables, Axis I psychiatric comorbidity, symptoms severity and level of insight. The most frequent dermatological concerns were dyschromias, acne, the shape of the body and ageing. In the Cosmetical group most of the patients have performed clinical or surgical cosmetic treatments with poor results. Our findings provide further support for higher prevalence of Body Dysmorphic Disorder in dermatological patients, mainly those seeking cosmetic treatments and suggests that those patients might be more obsessive and having poorer insight into their symptoms. Taking into account the high prevalence of Body Dysmorphic Disorder in dermatological patients and cosmetic treatments that rarely improve symptoms there are compelling reasons for training professionals to systematically investigate, diagnose and refer these patients to adequate psychiatric treatment

São cada vez mais freqüentes as queixas cosméticas na sociedade contemporânea objetivando a perfeição das formas do corpo e da pele. Os dermatologistas e cirurgiões plásticos são frequentemente consultados para avaliar e tratar essas queixas. Sendo assim é importante conhecer o Transtorno Dismórfico Corporal, inicialmente chamado de dismorfofobia que foi pouco estudado até recentemente. Esse transtorno é relativamente comum, por vezes incapacitante, e envolve uma percepção distorcida da imagem corporal caracterizada pela preocupação exagerada com um defeito imaginário na aparência ou com um mínimo defeito corporal presente. A maioria dos pacientes apresenta algum grau de prejuízo no funcionamento social e ocupacional e como resultado de suas queixas obsessivas com a aparência podem desenvolver comportamentos compulsivos, em casos mais graves há risco de suicídio. O nível de juízo crítico é prejudicado, não reconhecem que seu defeito é mínimo ou inexistente e freqüentemente procuram tratamentos cosméticos para um transtorno psíquico. A prevalência do transtorno na população geral é de 1 a 2% e em pacientes dermatológicos e de cirurgia cosmética de 2,9 a 16%. Neste estudo investigou-se a prevalência do Transtorno Dismórfico Corporal em pacientes dermatológicos. Entrevistadores treinados avaliaram com questionários e entrevistas semi-estruturadas (SCID) pacientes que procuravam tratamentos cosméticos clínicos e cirúrgicos (grupo Cosmiatria, n=150), que procuravam a dermatologia em geral (grupo Geral, n=150) e grupo controle de 50 pacientes. Três psiquiatras independentes fizeram a melhor estimativa diagnóstica (best estimate diagnosis). Foram diagnosticados 32 pacientes (Cosmiatria 14%; Geral 6,7%; Controle 2%). As diferenças entre as prevalências nos três grupos foram significativas, bem como entre o grupo da Cosmiatria e o Controle. A regressão logística mostrou maior prevalência na Cosmiatria do que no grupo Geral e Controle, em indivíduos solteiros e com menor índice de massa corpórea. A gravidade foi moderada (em escala validada) e as obsessões foram mais significativas no grupo da Cosmiatria do que no Geral. A aplicação de escala de avaliação de crenças mostrou que o nível de juízo crítico estava mais prejudicado nos pacientes do grupo da Cosmiatria. Nenhum paciente havia sido diagnosticado previamente. As comorbidades psiquiátricas foram freqüentes, principalmente o Transtorno Depressivo Maior e o Transtorno Obsessivo Compulsivo. A comparação de subgrupos de pacientes que tinham o Transtorno Dismórfico Corporal ou este associado ao Transtorno Obsessivo-Compulsivo não mostrou diferenças significativas quanto às variáveis demográficas, comorbidades psiquiátricas, gravidade do transtorno ou nível de juízo crítico. As queixas dermatológicas mais freqüentes, em média duas, foram: discromias, acne, quanto à forma do corpo e ao envelhecimento. No grupo Cosmiatria a maioria dos pacientes já havia se submetido a tratamentos ou cirurgias cosméticas com resultados insatisfatórios. Os achados desse estudo apontam para uma maior prevalência em pacientes dermatológicos, principalmente nos que procuram tratamentos cosméticos, sugerindo que possam ser mais obsessivos e ter pior nível de juízo crítico em relação aos seus sintomas. Considerando a alta prevalência do Transtorno Dismórfico Corporal em pacientes dermatológicos e que os tratamentos cosméticos raramente melhoram seus sintomas, o treinamento dos profissionais para a investigação sistemática, diagnóstico e encaminhamento para tratamento psiquiátrico parece fundamental / Cosmetic concerns are increasingly pervading the contemporary societies, focusing on body shape and the skin perfection. Dermatologists and plastic surgeons are frequently consulted to evaluate and treat these concerns. Therefore it is important to be aware of the Body Dysmorphic Disorder, also known as dysmorphophobia, little studied until recently. This disorder is relatively common sometimes causing impairment involving a distorted perception of the body image characterized by an excessive preoccupation with an imagined or minimal appearance defect. Most of the patients experience some degree of impairment in social or occupational functioning and as a result, their obsessive thoughts, may lead to repetitive behaviors and in severe cases, to attempted suicide. Most individuals have poor insight and they do not acknowledge the defect is minimal or inexistent and seek out cosmetic treatments for a psychiatric disorder. The prevalence of this disorder among general population ranges from 1 to 2 % and in dermatological and cosmetic surgery patients ranges from 2, 9 to 16%. This study assessed the prevalence of Body Dysmorphic Disorder in dermatological patients. Trained interviewers used questionnaires (BDDQ) and semi-structured clinical interviews (SCID) to access patients seeking clinical or surgical cosmetic treatments (Cosmetic group, n=150), seeking dermatology in general (General group, n=150) and a control group of 50 subjects. Three independent psychiatrists assigned the best estimate diagnosis and 32 patients were diagnosed with the disorder (Cosmetic 14%, General 6, 7% and Control 2%). Prevalence differences in the three groups were significant, also for Cosmetic and Control groups. In the logistic regression a higher prevalence has been noticed in the Cosmetic group (when compared with General and Control groups), in patients that are not currently married and with less body mass index. The severity of the symptoms assessed by a validated scale (BDD-YBOCS) was moderate and the obsessions were significantly higher in the Cosmetic group as compared to the General one. Beliefs were assessed by a scale (BABS) and insight were significantly poorer in the Cosmetic group. None of the patients had been previously diagnosed. Psychiatric co-morbidities were frequent, mostly Major Depressive Disorder and Obsessive-Compulsive Disorder. Comparing two patients subgroups with just Body Dysmorphic Disorder and patients with Obsessive-Compulsive Disorder as comorbidity show no differences according to demographic variables, Axis I psychiatric comorbidity, symptoms severity and level of insight. The most frequent dermatological concerns were dyschromias, acne, the shape of the body and ageing. In the Cosmetical group most of the patients have performed clinical or surgical cosmetic treatments with poor results. Our findings provide further support for higher prevalence of Body Dysmorphic Disorder in dermatological patients, mainly those seeking cosmetic treatments and suggests that those patients might be more obsessive and having poorer insight into their symptoms. Taking into account the high prevalence of Body Dysmorphic Disorder in dermatological patients and cosmetic treatments that rarely improve symptoms there are compelling reasons for training professionals to systematically investigate, diagnose and refer these patients to adequate psychiatric treatment

<p>The principal aim was to study selected aspects of indoor environment in dwellings and their association with symptoms compatible with the sick building syndrome (SBS). A validated questionnaire was developed specifically for residential indoor investigations, using sociological principles and test procedures. The questionnaire was mailed to 14,243 multi-family dwellings in Stockholm, selected by stratified random sampling. Females, subjects with a history of atopy, those above 65 y, and those in new buildings reported more symptoms. Subjects owning their own dwelling had less symptoms. A multiple regression model was developed, to identify residential buildings with a higher than expected occurrence of SBS. In total, 28.5% reported at least one sign of building dampness in their home (condensation on windows, humidity in the bathroom, mouldy odour, water leakage). All indicators of dampness were related to symptoms, even when adjusting for demographic data, and other building characteristics (OR=2.9-6.0). Associations between symptoms and other building data was evaluated in older houses, built before 1961. Subjects in older buildings with a mechanical ventilation system had fewer symptoms. Heating by electric radiators, and wood heating was associated with an increase of most types of symptoms (OR=1.2-5.0). Multiple sealing measures (OR=1.3), and major reconstruction (OR=1.1-1.9), was associated with an increase of symptoms. The effect of seasonal adapted ventilation (SAV) was studied in a small experimental study. A 20% reduction of ventilation flow from 0.5-0.8 ac/h to 0.4-0.5 ACH during the heating season increased the perception of poor indoor air quality in the dwelling in general, and in the bedroom. In conclusion, low building age, and building dampness in the dwelling are associated with SBS. In older houses, mechanical ventilation is beneficial. The thesis did not support the view that energy saving measures in general is an important risk factor for SBS, but major reconstruction and multiple sealing measures can be risk factor for symptoms. Reducing the outdoor ventilation flow below the current Swedish ventilation standard (0.5 ACH) may increase the perception of impaired air quality. </p>