Unexpectedly High Prevalence of Common Variable Immunodeficiency in Finland

Background: Common variable immunodeficiency (CVID) is the most common primary immunodeficiency. Prevalence varies greatly between countries and studies. Most diagnostic criteria include hypogammaglobulinemia and impaired vaccine response. Aim: To evaluate the minimum prevalence as well as the clinical and immunological phenotypes of CVID in Southern Finland. Methods: We performed a cross-sectional study to assess all adult CVID patients followed up in three hospital districts in Southern and South-Eastern Finland between April 2007 and August 2015. CVID diagnosis was based, with a minor modification, on the ESID/PAGID criteria for primary CVID. Antipolysaccharide responses to Pneumovax (R) were defined as impaired only if 50% or more of the serotypes did not reach a level of 0.35 mu g/mL after vaccination. We further characterized the patients' B cell phenotypes and complications associated with CVID. Results: In total, 9 patients were excluded due to potential secondary causes before diagnosis. ESID/PAGID criteria were met by 132 patients (males 52%), of whom, 106 had "probable" and 26 "possible CVID." Based on the population statistics in the three hospital districts, the minimum adult prevalence per 100,000 inhabitants in Finland for all CVID ("probable CVID," respectively) patients was 6.9 (5.5). In the highest prevalence district (Helsinki and Uusimaa), the prevalence was 7.7 (6.1). CVID patients suffer from frequent complications. Ten patients died during follow-up. Of probable CVID patients, 73% had more than one clinical phenotype. Intriguingly, gradual B cell loss from peripheral blood during follow-up was seen in as many as 16% of "Xprobable CVID" patients. Patients with possible CVID displayed somewhat milder clinical and laboratory phenotypes than probable CVID patients. We also confirm that large granular lymphocyte lymphoproliferation is a CVID-associated complication. Conclusion: The prevalence of CVID in Finland appears the highest recorded, likely reflecting the genetic isolation and potential founder effects in the Finnish population. Studies to discover potential gene variants responsible for the high prevalence in Finland thus seem warranted. Increased awareness of CVID among physicians would likely lead to earlier diagnosis and improved quality of care.Peer reviewe

Characterization of MOSFET dosimeters for low-dose measurements in maxillofacial anthropomorphic phantoms

Peer reviewe

Lung macrophage scavenger receptor SR-A6 (MARCO) is an adenovirus type-specific virus entry receptor

<div><p>Macrophages are a diverse group of phagocytic cells acting in host protection against stress, injury, and pathogens. Here, we show that the scavenger receptor SR-A6 is an entry receptor for human adenoviruses in murine alveolar macrophage-like MPI cells, and important for production of type I interferon. Scavenger receptors contribute to the clearance of endogenous proteins, lipoproteins and pathogens. Knockout of SR-A6 in MPI cells, anti-SR-A6 antibody or the soluble extracellular SR-A6 domain reduced adenovirus type-C5 (HAdV-C5) binding and transduction. Expression of murine SR-A6, and to a lower extent human SR-A6 boosted virion binding to human cells and transduction. Virion clustering by soluble SR-A6 and proximity localization with SR-A6 on MPI cells suggested direct adenovirus interaction with SR-A6. Deletion of the negatively charged hypervariable region 1 (HVR1) of hexon reduced HAdV-C5 binding and transduction, implying that the viral ligand for SR-A6 is hexon. SR-A6 facilitated macrophage entry of HAdV-B35 and HAdV-D26, two important vectors for transduction of hematopoietic cells and human vaccination. The study highlights the importance of scavenger receptors in innate immunity against human viruses.</p></div

Common data elements for clinical research in mitochondrial disease: a National Institute for Neurological Disorders and Stroke project

Objectives The common data elements (CDE) project was developed by the National Institute of Neurological Disorders and Stroke (NINDS) to provide clinical researchers with tools to improve data quality and allow for harmonization of data collected in different research studies. CDEs have been created for several neurological diseases; the aim of this project was to develop CDEs specifically curated for mitochondrial disease (Mito) to enhance clinical research. Methods Nine working groups (WGs), composed of international mitochondrial disease experts, provided recommendations for Mito clinical research. They initially reviewed existing NINDS CDEs and instruments, and developed new data elements or instruments when needed. Recommendations were organized, internally reviewed by the Mito WGs, and posted online for external public comment for a period of eight weeks. The final version was again reviewed by all WGs and the NINDS CDE team prior to posting for public use

A controlled follow-up study of adolescents exposed to a school shooting - Psychological consequences after four months

Background: In November 2007, a student shot eight people and himself at Jokela High School, Finland. This study aims to evaluate the long-term effects of exposure to a school shooting among adolescents. Method: Associations between psychological outcomes and background factors were analysed and compared with "comparison students" four months after the incident. A questionnaire including Impact of Event Scale (IES) and General Health Questionnaire (GHQ-36) was used. Results: Half of the females and a third of the males suffered from posttraumatic distress. High level of posttraumatic distress (IES >= 35), predicting PTSD, was observed in 27% of the females and 7% of the males. The odds ratio was 6.4 (95% confidence interval 3.5-10.5) for having high levels of posttraumatic distress. Severe or extreme exposure and female gender were found to increase the risk. Forty-two percent of the females and 16% of the males had psychiatric disturbance (GHQ >= 9). Severe or extreme exposure, older age and female gender increased the risk. Perceived support from family and friends was found to be protective. Conclusions: The observed risk and protective factors were similar to earlier studies. Follow-up will be essential in identifying factors predicting persisting trauma-related symptoms in adolescence. (C) 2010 Elsevier Masson SAS. All rights reserved.Peer reviewe

Dental health in patients with and without HPV-positive oropharyngeal and tongue cancer

BackgroundHuman papilloma virus is associated with oral and oropharyngeal cancer. Our aim was to examine oral health in patients with oropharyngeal (OPSCC) and oral tongue cancer (OTSCC), expecting better oral health among OPSCC patients.Material and methodsFifty-five OPSCC patients with known HPV status and 59 OTSCC patients were randomly selected from a list of consecutive patients of the Helsinki University Hospital, Finland. Oral health was assessed from panoramic jaw radiographs. Total Dental Index (TDI) summarizing the dental health status was calculated and Finnish population study data were used for comparison. Descriptive statistics were used for analyses.ResultsPatients with HPV-positive OPSCC had higher periapical lesion index compared with HPV-negative OPSCC patients or with OTSCC patients. Residual roots were more common among OPSCC patients compared with OTSCC patients, because of their higher occurrence among HPV-negative OPSCC patients compared with OTSCC patients. Similarly, modified TDI score was significantly higher among OPSCC patients than among OTSCC patients, because of higher TDI score among HPV-negative OPSCC patients compared with OTSCC patients. OPSCC patients more often used a removable prosthesis than OTSCC patients. Dental health of the cancer patients was poorer when compared with the population data.ConclusionsOur study hypothesis was only partly confirmed. Periapical lesions were more prevalent among HPV-positive OPSCC patients, compared with the other groups. The number of residual roots was higher among HPV-negative subgroup. Thus, OPSCC patients had worse oral health parameters than OTSCC patients.Peer reviewe

Yeast : the soul of beer’s aroma—a review of flavour-active esters and higher alcohols produced by the brewing yeast

Among the most important factors influencing beer quality is the presence of well-adjusted amounts of higher alcohols and esters. Thus, a heavy body of literature focuses on these substances and on the parameters influencing their production by the brewing yeast. Additionally, the complex metabolic pathways involved in their synthesis require special attention. More than a century of data, mainly in genetic and proteomic fields, has built up enough information to describe in detail each step in the pathway for the synthesis of higher alcohols and their esters, but there is still place for more. Higher alcohols are formed either by anabolism or catabolism (Ehrlich pathway) of amino acids. Esters are formed by enzymatic condensation of organic acids and alcohols. The current paper reviews the up-to-date knowledge in the pathways involving the synthesis of higher alcohols and esters by brewing yeasts. Fermentation parameters affecting yeast response during biosynthesis of these aromatic substances are also fully reviewed.Eduardo Pires gratefully acknowledges the Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) for the PhD fellowship support (SFRH/BD/61777/2009). The financial contributions of the EU FP7 project Ecoefficient Biodegradable Composite Advanced Packaging (EcoBioCAP, grant agreement no. 265669) as well as of the Grant Agency of the Czech Republic (project GACR P503/12/1424) are also gratefully acknowledged. The authors thank the Ministry of Education, Youth and Sports of the Czech Republic (MSM 6046137305) for their financial support

Isolation of dental stem cell-enriched populations from continuously growing mouse incisors

Continuous growth of the rodent incisor is enabled by epithelial and mesenchymal stem cells (ESCs and MSCs) which unceasingly replenish enamel and dentin, respectively, that wear by persistent animal gnawing. Lineage tracing studies have provided evidence that ESCs contribute to all epithelial lineages of the tooth in vivo. Meanwhile, in the mouse incisor, MSCs continuously contribute to odontoblast lineage and tooth growth. However, in vitro manipulation of ESCs has shown little progress, mainly due to lack of appropriate protocol to successfully isolate, culture, expand, and differentiate ESCs in vitro without using the co-culture system. In this chapter we describe the isolation of the Sox2-GFP+ cell population that is highly enriched in ESCs. Isolated cells can be used for various types of analyses, including in vitro culture, single cell-related analyses, etc. Furthermore, we describe ways to obtain populations enriched in the incisor MSCs using FACS sorting of antibody-labeled cells. Easily accessible FACS sorting enables easy and relatively fast isolation of the cells labeled by the fluorescent protein. © Springer Science+Business Media, LLC, part of Springer Nature 2019.Peer reviewe

Varied Responses to a High m.3243A>G Mutation Load and Respiratory Chain Dysfunction in Patient-Derived Cardiomyocytes

The m.3243A>G mutation in mitochondrial tRNA-Leu(UUR) is one of the most common pathogenic mitochondrial DNA mutations in humans. The clinical manifestations are highly heterogenous and the causes for the drastic clinical variability are unknown. Approximately one third of patients suffer from cardiac disease, which often increases mortality. Why only some patients develop cardiomyopathy is unknown. Here, we studied the molecular effects of a high m.3243A>G mutation load on cardiomyocyte functionality, using cells derived from induced pluripotent stem cells (iPSC-CM) of two different m.3243A>G patients, only one of them suffering from severe cardiomyopathy. While high mutation load impaired mitochondrial respiration in both patients’ iPSC-CMs, the downstream consequences varied. mtDNA mutant cells from a patient with no clinical heart disease showed increased glucose metabolism and retained cellular ATP levels, whereas cells from the cardiac disease patient showed reduced ATP levels. In this patient, the mutations also affected intracellular calcium signaling, while this was not true in the other patient’s cells. Our results reflect the clinical variability in mitochondrial disease patients and show that iPSC-CMs retain tissue specific features seen in patients

Arts-Aided Recognition of Citizens' Perceptions for Urban Open Space Management

Urban open spaces of local natural environments can promote the health and well-being of both ecosystems and humans, and the management of the urban spaces can benefit from knowledge of individuals’/citizens’ perceptions of such environments. However, such knowledge is scarce and contemporary inquiries are often limited to cognitive observations and focused on built environmental elements rather than encouraged to recognize and communicate comprehensive perceptions. This paper investigates whether arts-based methods can facilitate recognition and understanding perceptions of urban open spaces. Two arts-based methods were used to capture perceptions: drifting, which is a walking method, and theatrical images, which is a still image method and three reflective methods to recognize and communicate the perceptions. The results show related sensations and perceptions enabled by arts-based methods comparing them to a sticker map method. The main findings were perceptions, which included information about human–environment interaction, about relations to other people and about ‘sense of place’ in urban open spaces. The hitherto unidentified perceptions about urban open space were associations, metaphors and memories. The methods used offer initial practical implications for future use