Clinical, radiological and histopathological features of patients with familial pulmonary fibrosis.

BACKGROUND: In familial pulmonary fibrosis (FPF) at least two biological relatives are affected. Patients with FPF have diverse clinical features. RESEARCH QUESTION: We aimed to characterize demographic and clinical features, re-evaluate high-resolution computed tomography (HRCT) scans and histopathology of surgical lung biopsies, assess survival and investigate the suitability of risk prediction models for FPF patients. STUDY DESIGN: A retrospective cohort study. METHODS: FPF data (n = 68) were collected from the medical records of Oulu University Hospital (OUH) and Oulaskangas District Hospital between 1 Jan 2000 and 11 Jan 2023. The inclusion criterion was pulmonary fibrosis (PF) (ICD 10-code J84.X) and at least one self-reported relative with PF. Clinical information was gathered from hospital medical records. HRCT scans and histology were re-evaluated. RESULTS: Thirty-seven (54.4%) of the patients were men, and 31 (45.6%) were women. The mean ages of the women and men were 68.6 and 61.7 years, respectively (p = 0.003). Thirty-seven (54.4%) patients were nonsmokers. The most common radiological patterns were usual interstitial pneumonia (UIP) (51/75.0%), unclassifiable (8/11.8%) and nonspecific interstitial pneumonia (NSIP) (3/4.4%). Pleuroparenchymal fibroelastosis (PPFE) was observed as a single or combined pattern in 13.2% of the patients. According to the 2022 guidelines for idiopathic pulmonary fibrosis (IPF), the patients were categorized as UIP (31/45.6%), probable UIP (20/29.4%), indeterminate for UIP (7/10.3%) or alternative diagnosis (10/14.7%). The histopathological patterns were UIP (7/41.2%), probable UIP (1/5.9%), indeterminate for UIP (8/47.2%) and alternative diagnosis (1/5.9%). Rare genetic variants were found in 9 patients; these included telomerase reverse transcriptase (TERT, n = 6), telomerase RNA component (TERC, n = 2) and regulator of telomere elongation helicase 1 (RTEL1, n = 1). Half of the patients died (n = 29) or underwent lung transplantation (n = 5), with a median survival of 39.9 months. The risk prediction models composite physiology index (CPI), hazard ratio (HR) 1.07 (95.0% CI 1.04-1.10), and gender-age-physiology index (GAP) stage I predicted survival statistically significantly (p<0.001) compared to combined stages II and III. CONCLUSIONS: This study confirmed the results of earlier studies showing that FPF patients' radiological and histopathological patterns are diverse. Moreover, radiological and histological features revealed unusual patterns and their combinations.

Re-hospitalisation predicts poor prognosis after acute exacerbation of interstitial lung disease.

BACKGROUND: Several markers have been identified to increase the risk for acute exacerbation of interstitial lung disease (AE-ILD) or mortality related to AE-ILD. However, less is known about the risk predictors of ILD patients who have survived AE. The aim of the study was to characterise AE-ILD survivors and investigate prognostic factors in this subpopulation. METHODS: All AE-ILD patients (n = 95) who had been discharged alive from two hospitals located in Northern Finland were selected from a population of 128 AE-ILD patients. Clinical data related to the hospital treatment and six-month follow-up visit were collected retrospectively from medical records. RESULTS: Fifty-three patients with idiopathic pulmonary fibrosis (IPF) and 42 patients with other ILD were identified. Two thirds of the patients had been treated without invasive or non-invasive ventilation support. The clinical features of six-month survivors (n = 65) and non-survivors (n = 30) did not differ in terms of medical treatment or oxygen requirements. Of the patients, 82.5% used corticosteroids at the six-month follow-up visit. Fifty-two patients experienced at least one non-elective respiratory re-hospitalisation before the six-month follow-up visit. In a univariate model, IPF diagnosis, high age and a non-elective respiratory re-hospitalisation increased the risk of death, although re-hospitalisation was the only independent risk factor in a multivariate model. In six-month survivors, there was no statistically significant decrease in pulmonary function test results (PFT) examined at the follow-up visit compared with earlier PFT examined near the time of AE-ILD. CONCLUSIONS: The AE-ILD survivors were a heterogeneous group of patients both clinically and in terms of their outcome. A non-elective respiratory re-hospitalisation was identified as a marker of poor prognosis among AE-ILD survivors.

NHLRC2 expression is increased in idiopathic pulmonary fibrosis.

BACKGROUND: Variants of NHL repeat-containing protein 2 (NHLRC2) have been associated with severe fibrotic interstitial lung disease in early childhood and NHLRC2 has been listed as a differentially expressed gene between rapidly and slowly progressing idiopathic pulmonary fibrosis (IPF) patients. However, its cell type-specific localization in human lung tissue is unknown. The aim of this study was to evaluate NHLRC2 mRNA and protein expression in different cell types of lung tissue samples and to investigate the effect of transforming growth factor (TGF)-ß1 exposure on NHLRC2 expression in vitro. METHODS: The NHLRC2 expression in lung tissue samples was studied by immunohistochemistry (50 IPF, 10 controls) and mRNA in situ hybridization (8 IPF, 3 controls). The immunohistochemical NHLRC2 expression was quantified with image analysis software and associated with the clinical and smoking data of the patients. NHLRC2 expression levels in primary stromal and small airway epithelial cell lines after exposure to TGF-ß1 was measured by quantitative reverse transcription polymerase chain reaction and Western blot analysis. RESULTS: NHLRC2 expression was detected especially in bronchiolar epithelial cells, type II pneumocytes and macrophages in normal lung. In the lungs of IPF patients, NHLRC2 was mainly expressed in hyperplastic alveolar epithelial cells lining fibroblast foci and honeycombs. NHLRC2 expression assessed by image analysis was higher in IPF compared to controls (p < 0.001). Ever-smokers had more prominent NHLRC2 staining than non-smokers (p = 0.037) among IPF patients. TGF-ß1 exposure did not influence NHLRC2 levels in lung cell lines. CONCLUSIONS: NHLRC2 expression was higher in IPF compared to controls being widely expressed in type II pneumocytes, macrophages, bronchiolar epithelium, and hyperplastic alveolar epithelium. Additionally, its expression was not regulated by the exposure to TGF-ß1 in vitro. Further studies are needed to clarify the role of NHLRC2 in IPF.

Survival of patients with asbestosis can be assessed by risk-predicting models.

OBJECTIVES: Our aim was to investigate the pulmonary function test (PFT) results of patients with asbestosis and determine whether baseline PFTs and the risk-predicting models such as gender, age and physiologic (GAP) variables model and composite physiologic index (CPI) would be useful in predicting survival in these patients. METHODS: Demographics and PFTs of 100 patients with asbestosis were evaluated. The survival difference between the GAP stages was determined with Kaplan-Meier survival curves with statistical significance analysed with log-rank test. The suitability of the risk-predicting models and baseline PFTs to predict the survival of patients was analysed with Cox regression. RESULTS: At baseline, the mean value of diffusion capacity for carbon monoxide (DLCO) was 65%; for forced vital capacity it was 81%, with restrictive lung function being the most common impairment. The median estimated survival of the patients was 124 months, that is, 171 months in GAP stage I, 50 months in stage II and 21 months in stage III (p<0.001). CPI, DLCO% predicted, age at baseline and GAP stage were significant predictors of mortality (all p values under 0.001). CONCLUSIONS: GAP and CPI as well as baseline DLCO% predicted were significant parameters in the evaluation of the prognosis of the patients with asbestosis; they may be useful in clinical practice when considering treatment strategies of individual patients.

Bronchoalveolar lavage differential cell count on prognostic assessment of patients with stable or acute interstitial lung disease: A retrospective real-life study.

BAL cell differential counts of 133 therapy naive ILD patients and 43 patients during acute exacerbation of ILD (AE-ILD) were retrospectively evaluated. In the 20 patients who underwent BAL both at baseline and during an AE-ILD, there was an increase in neutrophils but a decrease in macrophages and eosinophils in the BAL obtained during AE-ILD. A detectable number of basophils at the baseline was a novel risk factor for earlier death and the occurrence of AE-ILD. Total BAL cell count >160 × 109/L during AE-ILD was correlated with a more favorable prognosis. BAL cell counts <20% of lymphocytes or > 20% of neutrophils during AE-ILD were associated with shorter survival. AE-ILD exerted significant changes in BAL cell profiles in individual patients. Several BAL-parameters correlated with survival of ILD patients; of these, baseline basophils and total cell count during AE-ILD were novel prognostic markers.

National retrospective registry survey on the epidemiology of sarcoidosis in Finland 2002-2022.

BACKGROUND: The prevalence of sarcoidosis is known to be high in the Nordic countries. There are no recent research data on the incidence or prevalence of sarcoidosis in Finland. Our aim was to investigate the epidemiology of sarcoidosis in Finland through a retrospective registry-based study. METHODS: We made an information request to the Hilmo database on patients who had been treated in Finnish specialised care with a main diagnosis related to sarcoidosis. Data were requested for the period 1 January-31 December for the years 2002, 2012 and 2022. In addition, we examined the age and gender distribution and regional differences in these variables between the five university hospital districts covering the whole of Finland. RESULTS: The incidence of sarcoidosis was 17‒19/100 000/year throughout the follow-up period. The prevalence of sarcoidosis in the ≥18-year-old population had risen from 85/100 000 in 2002-106/100 000 in 2022. There were considerable differences between university hospital districts: The highest prevalence rate was 170/100 000 in the Tampere University Hospital district in 2022, which was twice as high as in the Helsinki University Hospital district (84/100 000). The proportion of pulmonary sarcoidosis in all sarcoidosis cases decreased from 62% to 45% while the proportion of multiorgan sarcoidosis (D86.8) increased from 11% to 34%. The incidence of sarcoidosis was 15/100 000 and the prevalence was 82/100 000 in the age groups of ≥60 years in 2002. In 2022, the incidence in this same age group had risen to 20/100 000 and the prevalence to 109/100 000. In the ≥60-year-old population, the proportion of D86.8 increased from 11% to 35%. CONCLUSIONS: Sarcoidosis was a more common disease in Finland than in previous studies. Multiorgan sarcoidosis among the elderly has increased over the past 20 years. This might be explained by changes in environmental factors associated with sarcoidosis. Significant regional differences in prevalence might be partly explained by familial clustering.

Comorbidities and Causes of Death of Patients With Asbestosis.

OBJECTIVE: Comorbidities are common and affect the prognosis of patients with interstitial lung diseases, but few previous studies have investigated patients with asbestosis. METHODS: We collected comorbidities and death causes of 116 patients with asbestosis treated in Oulu University Hospital. Causes of death were confirmed by autopsy in 68% of the cases. RESULTS: The most common comorbidities of asbestosis patients were pleural plaques (96%) and coronary artery disease (CAD; 67%). The prevalence of rheumatoid arthritis was 8.6%. The most common underlying causes of death were asbestosis (36%), CAD (24%), and lung cancer (LC) (10%). CAD and LC were associated with shorter survival in adjusted analyses. CONCLUSIONS: Patients with asbestosis have multiple comorbidities. Prevention and treatment of CAD and LC may influence the prognosis of asbestosis patients.

Virtual communication is commonly used in Finnish interstitial lung disease multidisciplinary meetings.

Multidisciplinary meeting (MDM) is a core element in the diagnosis of interstitial lung diseases (ILD). The aim of the study was to investigate the implementation and key elements related to ILD MDMs in Finnish specialized care, which is characterized by long travel distances and a large number of small centers treating patients suffering from ILDs. An electronic questionnaire was sent to ILD experts working at five academic centers of Finland regarding the implementation of ILD MDMs with the focus on utilization of virtual communication. Responses were received from all academic centers of Finland (n = 5) whose catchment areas cover all of Finland. ILD MDMs were organized in each center approximately every two weeks and the core participants included a radiologist, respiratory physicians, junior staff, pathologist and a rheumatologist. All non-academic centers could refer their patients to be evaluated in ILD MDM of an academic center. Virtual communication was utilized by all academic centers in the implementation of ILD MDMs, being most common among small centers located in Eastern and Northern Finland. Virtual access to ILD MDM of an academic center was available in most parts of Finland, enabling small centers to benefit from the ILD expertise of academic centers.

National data on prevalence of idiopathic pulmonary fibrosis and antifibrotic drug use in Finnish specialised care.

INTRODUCTION: The previous data concerning the prevalence of idiopathic pulmonary fibrosis (IPF) and the frequency of antifibrotic drug use in Finland were based on research registries and medical records whereas nationwide data on the number of patients with IPF in specialised care and those on antifibrotic treatment have not been published. METHODS: We made an information request to the Finnish National Hospital Discharge Register (Hilmo) covering the whole population of Finland to find out the annual numbers of patients with IPF treated in specialised care in 2016-2021. The numbers of the patients initiating and using pirfenidone and nintedanib were requested from the Social Insurance Institution of Finland (Kela) for the same time period. RESULTS: The estimated prevalence of IPF in specialised care was 36.0 per 100 000 in 2021, having increased since 2016. The number of antifibrotic drug users and their proportion of outpatients with IPF had also risen during the follow-up period. In 2021, 35% of the patients with IPF used pirfenidone or nintedanib. The number of inpatients treated in specialised care because of IPF had declined during 2016-2021. CONCLUSIONS: The prevalence of IPF was higher than expected in Finnish specialised care and had increased during the 6-year follow-up time. The increase in the number of patients with IPF using antifibrotic drugs might have diminished the need for IPF-related hospitalisations.

Decline in Mast Cell Density During Diffuse Alveolar Damage in Idiopathic Pulmonary Fibrosis.

Mast cells (MCs) are known to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF), although their role in acute exacerbations of IPF has not been investigated. The aims of the study were to evaluate the numbers of MCs in fibrotic and non-fibrotic areas of lung tissue specimens of idiopathic pulmonary fibrosis (IPF) patients with or without an acute exacerbation of IPF, and to correlate the MC density with clinical parameters. MCs of IPF patients were quantified from surgical lung biopsy (SLB) specimens (n = 47) and lung tissue specimens taken at autopsy (n = 7). MC density was higher in the fibrotic areas of lung tissue compared with spared alveolar areas or in controls. Female gender, low diffusion capacity for carbon monoxide, diffuse alveolar damage, and smoking were associated with a low MC density. MC densities of fibrotic areas had declined significantly in five subjects in whom both SLB in the stable phase and autopsy after an acute exacerbation of IPF had been performed. There were no correlations of MC densities with survival time or future acute exacerbations. The MC density in fibrotic areas was associated with several clinical parameters. An acute exacerbation of IPF was associated with a significant decline in MC counts. Further investigations will be needed to clarify the role of these cells in IPF and in the pathogenesis of acute exacerbation as this may help to identify some potential targets for medical treatment for this serious disease.

Importance of the left auditory areas in chord discrimination in music experts as demonstrated by MEG.

The brain basis behind musical competence in its various forms is not yet known. To determine the pattern of hemispheric lateralization during sound-change discrimination, we recorded the magnetic counterpart of the electrical mismatch negativity (MMNm) responses in professional musicians, musical participants (with high scores in the musicality tests but without professional training in music) and non-musicians. While watching a silenced video, they were presented with short sounds with frequency and duration deviants and C major chords with C minor chords as deviants. MMNm to chord deviants was stronger in both musicians and musical participants than in non-musicians, particularly in their left hemisphere. No group differences were obtained in the MMNm strength in the right hemisphere in any of the conditions or in the left hemisphere in the case of frequency or duration deviants. Thus, in addition to professional training in music, musical aptitude (combined with lower-level musical training) is also reflected in brain functioning related to sound discrimination. The present magnetoencephalographic evidence therefore indicates that the sound discrimination abilities may be differentially distributed in the brain in musically competent and naïve participants, especially in a musical context established by chord stimuli: the higher forms of musical competence engage both auditory cortices in an integrative manner.

Causes of acute respiratory hospitalizations predict survival in fibrosing interstitial lung diseases.

Acute exacerbation of ILD (AE-ILD) is a common reason for hospitalization; it is also associated with significant mortality. Less is known about the prognostic significance of other events causing acute, non-elective hospitalizations in ILD patients. ILD patients hospitalized due to acute respiratory worsening were collected from medical records. Reasons for respiratory deterioration were classified into AE-ILDs and other causes. Clinical features and survival data of idiopathic pulmonary fibrosis (IPF) and other types of ILDs were evaluated and compared. In all, 237 patients (138 with IPF and 99 with other ILD) fulfilled the inclusion criteria. Of the non-IPF ILD types, the most prevalent subgroups were connective tissue disease-associated ILD (n = 33) and asbestosis (n = 22). The most common cause for hospitalization was AE-ILD explaining 41% of hospitalizations. Lower respiratory tract infection (22%), subacute progression of ILD (12%) and cardiovascular causes (7.2%) were other common reasons for hospital treatment. Patients with a lower respiratory tract infection had a more favorable prognosis compared with patients with AE-ILD. AE-ILDs were less fatal than cardiovascular or concurrent non-ILD-related causes for hospitalizations in non-IPF patients. High Gender-Age-Physiology (GAP) index was a marker for shortened survival and earlier AE-ILDs in all patients. IPF patients had a significantly shorter overall and post-hospitalization survival time compared with other ILDs. Most respiratory hospitalizations in ILD patients were related to causes other than AE-ILD, which highlights the importance of accurate differential diagnosis in order to target the appropriate treatment for each ILD patient.

Prognosis and causes of death of patients with acute exacerbation of fibrosing interstitial lung diseases.

BACKGROUND: The aim of this study was to compare the clinical characteristics, causes of death and factors impacting on the prognosis of patients with idiopathic pulmonary fibrosis (IPF) and other fibrosing interstitial lung disease (FILD) with a history of acute exacerbation (AE) of IPF or FILD. METHODS: Retrospective data of hospital treatment periods caused by AE-IPF and AE-FILD were collected from medical records. Clinical features and survival data of IPF and non-IPF cases were evaluated and compared. The underlying and immediate causes of death were gathered from death certificates. RESULTS: A total of 128 patients fulfilled the criteria for inclusion. IPF (n=79/62%), rheumatoid arthritis-associated interstitial lung disease (RA-ILD; n=17/14%) and asbestosis (n=11/8.6%) were the most common FILD subgroups in the study. The median survival after hospitalisation in AE-IPF was 2.6 months compared with 21 months in other AE-FILDs (p<0.001). The survival difference was not explained by age, gender or pulmonary function test results at the time of hospitalisation. Patients with non-specific interstitial pneumonia and RA-ILD had the most favourable prognosis. ILD was the most common underlying cause of death in both patients with IPF and with other FILD accounting for 87% and 78% of deaths, respectively. CONCLUSIONS: We detected a significantly longer survival in AE of patients with non-IPF compared with that of AE-IPFs. The prognosis of patients was affected by the underlying lung disease since pulmonary fibrosis was the underlying cause of death in the majority of all patients with FILD having experienced an AE.

Association between angiotensin-converting enzyme insertion/deletion polymorphism and treatment response in type 2 diabetic patients.

BACKGROUND: Our objective was to determine whether the angiotensin-converting enzyme insertion-deletion (ACE I/D) polymorphism affects the treatment responses in type 2 diabetic patients. METHODS: A total of 117 type 2 diabetic patients with poor metabolic control were evaluated and their treatment intensified before re-evaluation after a mean follow-up of 16.0 months. New insulin treatment was started in 61% of patients, the majority of whom used a combination of insulin and tablets. Earlier insulin treatment was continued and intensified for 9% of patients, and 19% of patients used oral treatment only. As antihypertensive treatment, 34% of patients used diuretics, 27% ACE-inhibitors, 38% beta-blockers and 21% calcium-channel blockers during the follow-up. For dyslipidemia, 6% of patients used fibrates and none used statins. RESULTS: There was a decrease in glycohemoglobin A1 levels [-2.0 (0.3) (S.E.) %], plasma total cholesterol [-0.2 (0.1) mmol/l] and plasma triglycerides [-1.2 (0.4) mmol/l], and an increase in plasma HDL cholesterol [0.07 (0.02) mmol/l] and weight [2.1 (0.5) kg] in response to intensified treatment. The changes in glycohemoglobin A1 (GHbA1) levels and HDL cholesterol were significantly associated with the ACE I/D polymorphism. The patients with the ACE I/I genotype had a greater decrease [-3.0 (0.7)] in their GHbA1 levels than the patients with I/D [-2.1 (0.5)] or D/D [-1.8 (0.4)] genotypes (P<0.03). HDL cholesterol levels increased more among the subjects homozygous for the I allele [0.21 (0.05)] than the I/D [0.04 (0.03)] or D/D [0.04 (0.03)] subjects (P<0.03). CONCLUSIONS: The results suggest that the ACE I/D polymorphism is associated with treatment responses in type 2 diabetic patients.

Proteomic changes during B cell maturation: 2D-DIGE approach.

B cells play a pivotal role in adaptive immune system, since they maintain a delicate balance between recognition and clearance of foreign pathogens and tolerance to self. During maturation, B cells progress through a series of developmental stages defined by specific phenotypic surface markers and the rearrangement and expression of immunoglobulin (Ig) genes. To get insight into B cell proteome during the maturation pathway, we studied differential protein expression in eight human cell lines, which cover four distinctive developmental stages; early pre-B, pre-B, plasma cell and immature B cell upon anti-IgM stimulation. Our two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry based proteomic study indicates the involvement of large number of proteins with various functions. Notably, proteins related to cytoskeleton were relatively highly expressed in early pre-B and pre-B cells, whereas plasma cell proteome contained endoplasmic reticulum and Golgi system proteins. Our long time series analysis in anti-IgM stimulated Ramos B cells revealed the dynamic regulation of cytoskeleton organization, gene expression and metabolic pathways, among others. The findings are related to cellular processes in B cells and are discussed in relation to experimental information for the proteins and pathways they are involved in. Representative 2D-DIGE maps of different B cell maturation stages are available online at http://structure.bmc.lu.se/BcellProteome/.

Attention-related modulation of auditory-cortex responses to speech sounds during dichotic listening.

Event-related magnetic fields (ERFs) were measured with magnetoencephalography (MEG) in fifteen healthy right-handed participants listening to sequences of consonant-vowel syllable pairs delivered dichotically (one syllable presented to the left ear and another syllable simultaneously to the right ear). The participants were instructed to press a response button to occurrences of a particular target syllable. In a condition with no other instruction (the non-forced condition, NF), they showed the well-known right-ear advantage (REA), that is, the participants responded more often to target syllables delivered to the right ear than to targets delivered to the left ear. The same was true in the forced-right (FR) condition, where the participants were instructed to attend selectively to the right-ear syllables and respond only to targets among them. In the forced-left (FL) condition, where they were instructed to respond only to left-ear targets, they responded more often to targets in this ear than to targets in the right ear. At 300-500 ms from syllable pair onset, a sustained field (SF) in ERFs to the syllable pairs was stronger in the left auditory cortex than in the right auditory cortex in the NF and FR conditions, while the opposite was true in the FL condition. Thus selective attention during dichotic listening leads to stronger processing of speech sounds in the auditory cortex contralateral to the attended direction. Our results also suggest that the REA observed for dichotic speech may involve a bias of attention to the right side even when there is no instruction to do so. This supports Kinsbourne's (1970) model of attention bias as a general principle of laterality.

Nucleolar proteins with altered expression in leukemic cell lines.

The function of the nucleolus is intimately connected to cell proliferation, division and growth. Many cancer cells have enlarged nucleoli, and several nucleolar proteins have been linked to tumorigenesis. In order to find proteins whose expression is altered in the nucleoli of leukemic cells, we carried out two-dimensional difference gel electrophoresis (2-D DIGE) analyses. Prohibitin (PHB) and TAR-DNA-binding protein-43 (TDP-43) were strongly expressed in the nucleoli of the pre-B-ALL cell line MHH-CALL3. Our results demonstrate that leukemic cells have differences in their nucleolar protein composition, and suggest that it may be possible to exploit these differences in identification of leukemia subtypes.

Proteome analysis of B-cell maturation.

Proteins affected by anti-mIgM stimulation during B-cell maturation were identified using 2-DE-based proteomics. We investigated the proteome profiles of stimulated and nonstimulated Ramos B-cells at eight time points during 5 d and compared the obtained proteomic data to the corresponding data from DNA-microarray studies. Anti-mIgM stimulation of the cells resulted in significant differences (> or =twofold) in the protein abundance close to 100 proteins and differences in post-translational protein modifications. Forty-eight up- or down-regulated proteins were identified by mass spectrometric methods and database searches. The identities of a further nine proteins were revealed by comparing their positions to the known proteins in other lymphocyte 2-DE databases. Several of the proteins are directly related to the functional and morphological characteristics of B-cells, such as cytoskeleton rearrangement and intracellular signalling triggered by the crosslinking of B-cell receptors. In addition to proteins known to be involved in human B-cell maturation, we identified several proteins that were not previously linked to lymphocyte differentiation. The results provide deeper insights into the process of B-cell maturation and may lead to novel therapeutic strategies for immunodeficiencies. An interactive 2-DE reference map is available at http://bioinf.uta.fi/BcellProteome.

Magnetoencephalography is feasible for infant assessment of auditory discrimination.

Magnetoencephalography (MEG) detects the brain's magnetic fields as generated by neuronal electric currents arising from synaptic ion flow. It is noninvasive, has excellent temporal resolution, and it can localize neuronal activity with good precision. For these reasons, many scientists interested in the localization of brain functions have turned to MEG. The technique, however, is not without its drawbacks. Those reluctant to employ it cite its relative awkwardness among pediatric populations because MEG requires subjects to be fairly still during experiments. Due to these methodological challenges, infant MEG studies are not commonly pursued. In the present study, MEG was employed to study auditory discrimination in infants. We had two goals: first, to determine whether reliable results could be obtained from infants despite their movements; and second, to improve MEG data analysis methods. To get more reliable results from infants we employed novel hardware (real-time head-position tracking system) and software (signal space separation method, SSS) solutions to better deal with noise and movement. With these solutions, the location and orientation of the head can be tracked in real time and we were able to reduce noise and artifacts originating outside the helmet significantly. In the present study, these new methods were used to study the biomagnetic equivalents of event-related potentials (ERPs) in response to duration changes in harmonic tones in sleeping, healthy, full-term newborns. Our findings indicate that with the use of these new analysis routines, MEG will prove to be a very useful and more accessible experimental technique among pediatric populations.