Browsing by Subject "RESPONSIVENESS"

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  • Piirila, Päivi L.; Nordman, Henrik; Korhonen, Olli; Winblad, Ilkka (1996)
    Objectives In 1977, nine men were accidentally exposed to sulfur dioxide in an explosion in a pyrite mine. The lung function of seven men was followed after the accident. A four-year follow-up has been published previously. The greatest decrease in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1.0)), and maximal midexpiratory flow (MMEF) was observed one week after the accident, after which all these parameters improved without reaching the preaccident level. Reversible bronchial obstruction was still present in three patients, and a positive reaction In the histamine challenge test was found for four. In the present paper, the lung function follow-up 13 years after the accident is reported for six men. Methods The patients' clinical condition, chest X-ray, spirometry, and histamine challenge test were studied 13 years after the incident. Results Spirometry was normal in one worker, two displayed obstruction, and three had a combined obstructive and restrictive, mainly obstructive, ventilatory impairment. In the histamine challenge test, four patients showed bronchial hyperreactivity, one with a nearly significant reaction. Because of bronchial obstruction one patient could not perform the challenge test. Conclusions This 13-year follow-up showed that acute inflammatory obstruction caused by exposure to sulfur dioxide left, as sequelae, obstructive impairment of ventilatory function and permanent bronchial hyperreactivity. The clinical picture displayed by these patients was named the ''reactive airways dysfunction syndrome'' (RADS) in 1985. Four of the patients also showed symptoms of chronic bronchitis.
  • Malmström, Kristiina; Lohi, Jouko; Malmberg, Leo Pekka; Kotaniemi-Syrjänen, Anne; Lindahl, Harry; Sarna, Seppo; Pelkonen, Anna S.; Mäkelä, Mika J. (2020)
    Abstract Background The relationship of airway hyperresponsiveness to airway remodeling and inflammation in infants with wheeze is unclear. Objective To investigate airway hyperresponsiveness, remodeling and inflammation in infants with wheeze and troublesome breathing. Methods Inclusion criteria: full-term, 3-23 months of age; doctor diagnosed wheeze and persistent recurrent troublesome breathing; without obvious structural defect, suspicion of ciliary dyskinesia, cystic fibrosis, immune deficiency or specified use of corticosteroids. Airway hyperresponsiveness (AHR) was evaluated by performing a methacholine bronchial challenge test combined with whole body pletysmography and rapid thoracoabdominal compression. Endobronchial biopsies were analyzed for remodeling (thickness of reticular basement membrane and amount of airway smooth muscle) and for inflammation (numbers of inflammatory cells). Correlation analyses were performed. Results Forty-nine infants fulfilled the inclusion criteria for the present study. Median age was 1.06 years (IQR 0.6; 1.5). Lung function was impaired in 39/49 (80%) children, at the median age of 1.1 years. Methacholine challenge was successfully performed in 38/49 children. Impaired baseline lung function correlated with AHR (p=0.047, Spearman). In children with the most sensitive quartile of AHR, the percentage of median bronchial airway smooth muscle % and the number of bronchial mast cells in airway smooth muscle were not significantly higher compared to others (p=0.057 and 0.056 respectively). No association was found between AHR and thickness of reticular basement membrane or inflammatory cells. Only a small group of children with both atopy and AHR (the most reactive quartile) had thicker airway smooth muscle area than non-atopics with AHR (p=0.031). Conclusions & Clinical Relevance These findings don not support the concept that AHR in very young children with wheeze is determined by eosinophilic inflammation or clear-cut remodeling although it is associated with impaired baseline lung function. The possible association of increased airway smooth muscle area among atopic children with AHR remains to be confirmed.
  • Leskinen, Heidi; Tringham, Maaria; Karjalainen, H.; Iso-Touru, T.; Hietaranta-Luoma, Hanna-Leena; Marnila, P.; Pihlava, J.-M.; Hurme, T.; Puolijoki, H.; Åkerman, K.; Mäkinen, Sari; Sandell, Mari; Vähäkangas, K.; Tahvonen, R.; Rokka, Susanna; Hopia, Anu (2022)
    Introduction: The APOE ε4 allele predisposes to high cholesterol and increases the risk for lifestyle-related diseases such as Alzheimer’s disease and cardiovascular diseases (CVDs). The aim of this study was to analyse interrelationships of APOE genotypes with lipid metabolism and lifestyle factors in middle-aged Finns among whom the CVD risk factors are common. Methods: Participants (n = 211) were analysed for APOE ε genotypes, physiological parameters, and health- and diet-related plasma markers. Lifestyle choices were determined by a questionnaire. Results: APOE genotypes ε3/ε4 and ε4/ε4 (ε4 group) represented 34.1% of the participants. Genotype ε3/ε3 (ε3 group) frequency was 54.5%. Carriers of ε2 (ε2 group; ε2/ε2, ε2/ε3 and ε2/ε4) represented 11.4%; 1.9% were of the genotype ε2/ε4. LDL and total cholesterol levels were lower (p < 0.05) in the ε2 carriers than in the ε3 or ε4 groups, while the ε3 and ε4 groups did not differ. Proportions of plasma saturated fatty acids (SFAs) were higher (p < 0.01), and omega-6 fatty acids lower (p = 0.01) in the ε2 carriers compared with the ε4 group. The ε2 carriers had a higher (p < 0.05) percentage of 22:4n-6 and 22:5n-6 and a lower (p < 0.05) percentage of 24:5n-3 and 24:6n-3 than individuals without the ε2 allele. Conclusions: The plasma fatty-acid profiles in the ε2 group were characterized by higher SFA and lower omega-6 fatty-acid proportions. Their lower cholesterol values indicated a lower risk for CVD compared with the ε4 group. A novel finding was that the ε2 carriers had different proportions of 22:4n-6, 22:5n-6, 24:5n-3, and 24:6n-3 than individuals without the ε2 allele. The significance of the differences in fatty-acid composition remains to be studied.
  • Päivinen, Marja; Keskinen, Kari; Putus, Tuula; Kujala, Urho M.; Kalliokoski, Pentti; Tikkanen, Heikki O. (2021)
    Background Respiratory symptoms are common in competitive swimmers. However, among these and in swimmers at other activity levels the swimming distance, the total spent time in swimming halls and their medical background varies. Our objectives were, first, to assess their medical histories and the associations with respiratory symptoms among swimmers in different activity groups and then second, to study the pulmonary function findings and related medications in competitive swimmers who exercise in swimming hall environments the most. Methods First, 1118 participants consisting of 133 competitive-, 734 fitness- and 251 occasional swimmers answered questionnaires concerning their medical background, their respiratory symptoms in connection to swimming distance and their amount of time spent in swimming halls. Secondly, in 130 competitive swimmers, pulmonary function was tested by spirometry and a specific questionnaire was used to assess respiratory symptoms, medical histories and prescribed medication. Results Respiratory symptoms were reported by 18% of the studied swimmers. Competitive swimmers had significantly more symptoms than fitness- and occasional swimmers. Naturally competitive swimmers swum more than 2000 m and stayed by the pool more than 90 min, longer than the other activity groups of swimmers. Spirometry testing showed airway obstruction in 15 swimmers, which was 12% of the 130 competitive swimmers. 21 of them, had physician-diagnosed asthma and 16 of these individuals had prescribed medication for it. Conclusions Competitive swimmers had the highest swimming hall exposure and reported significantly more respiratory symptoms. A high prevalence of airway obstruction findings in competitive swimmers with asthma and allergies suggests a need for future recommendations for regular testing and special medical care for competitive swimmers.
  • Paloneva, Juha; Koskela, Sanna; Kautiainen, Hannu; Vanhala, Mauno; Kiviranta, Ilkka (2013)
  • Hulkkonen, S.; Repo, J. P.; Häkkinen, A.; Karppinen, J.; Ryhänen, J. (2020)
    Background and Aims: Michigan Hand Outcomes Questionnaire is a widely used patient-reported outcome measure in hand surgery. The aim of this study was to translate and validate the Michigan Hand Outcomes Questionnaire into Finnish for Finnish patients with hand problems following international standards and guidelines. Material and Methods: The original English Michigan Hand Outcomes Questionnaire was translated into Finnish. Altogether, 115 patients completed the Finnish Michigan Hand Outcomes Questionnaire, and reference outcomes: Disabilities of the Arm and Shoulder, EQ-5D 3L and pain intensity on a visual analog scale. Grip and key pinch forces were measured. After 1-2 weeks, 63 patients completed the Finnish Michigan Hand Outcomes Questionnaire the second time. The Michigan Hand Outcomes Questionnaire was analyzed for internal consistency, repeatability, correlations with the reference outcomes, and factor analysis. Results: Cronbach's alpha ranged from 0.90 to 0.97 in all the Michigan Hand Outcomes Questionnaire subscales, showing high internal consistency. The intraclass correlation coefficient showed good to excellent test-retest reliability ranging from 0.66 to 0.91 in all the Michigan Hand Outcomes Questionnaire subscales. In factor analysis, the structure with six subscales was not confirmed. All the subscales correlated with Disabilities of the Arm and Shoulder score, and five subscales correlated with EQ-5D index. Conclusion: The Finnish version of the Michigan Hand Outcomes Questionnaire showed similar properties compared to the original English version and thus can be used as patient-reported outcome measure for Finnish patients with hand problems.
  • Sousa-Pinto, Bernardo; Azevedo, Luis Filipe; Jutel, Marek; Agache, Ioana; Canonica, G. Walter; Czarlewski, Wienczyslawa; Papadopoulos, Nikolaos G.; Bergmann, Karl-Christian; Devillier, Philippe; Laune, Daniel; Klimek, Ludger; Anto, Aram; Anto, Josep M.; Eklund, Patrik; Almeida, Rute; Bedbrook, Anna; Bosnic-Anticevich, Sinthia; Brough, Helen A.; Brussino, Luisa; Cardona, Victoria; Casale, Thomas; Cecchi, Lorenzo; Charpin, Denis; Chivato, Tomas; Costa, Elisio M.; Cruz, Alvaro A.; Dramburg, Stephanie; Durham, Stephen R.; De Feo, Giulia; van Wijk, Roy Gerth; Fokkens, Wystke J.; Gemicioglu, Bilun; Haahtela, Tari; Illario, Maddalena; Carlos Ivancevich, Juan; Kvedariene, Violeta; Kuna, Piotr; Larenas-Linnemann, Desiree E.; Makris, Michael; Mathieu-Dupas, Eve; Melen, Erik; Morais-Almeida, Mario; Moesges, Ralph; Mullol, Joaquim; Nadeau, Kari C.; Nhan Pham-Thi; O'Hehir, Robyn; Regateiro, Frederico S.; Reitsma, Sietze; Samolinski, Boleslaw; Sheikh, Aziz; Stellato, Cristiana; Todo-Bom, Ana; Tomazic, Peter Valentin; Toppila-Salmi, Sanna; Valero, Antonio; Valiulis, Arunas; Ventura, Maria Teresa; Wallace, Dana; Waserman, Susan; Yorgancioglu, Arzu; Vries, Govert; Eerd, Michiel; Zieglmayer, Petra; Zuberbier, Torsten; Pfaar, Oliver; Fonseca, Joao Almeida; Bousquet, Jean (2022)
    Background Validated combined symptom-medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real-life data from the MASK-air(R) app to generate and validate hypothesis- and data-driven CSMSs. Methods We used MASK-air(R) data to assess the concurrent validity, test-retest reliability and responsiveness of one hypothesis-driven CSMS (modified CSMS: mCSMS), one mixed hypothesis- and data-driven score (mixed score), and several data-driven CSMSs. The latter were generated with MASK-air(R) data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK-air(R), and Work Productivity and Activity Impairment: Allergy Specific [WPAI-AS]), (ii) quality-of-life (EQ-5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]). Results We assessed 317,176 days of MASK-air(R) use from 17,780 users aged 16-90 years, in 25 countries. The mCSMS and the factor analyses-based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate-to-strong correlations with the tested comparators, high test-retest reliability and moderate-to-large responsiveness. Among data-driven CSMSs, a better performance was observed for cluster analyses-based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC-ROC = 0.904) and for the mixed CSMS (AUC-ROC = 0.820). Conclusion The mixed CSMS and the cluster-based CSMSs presented medium-high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials.
  • Malmberg, Leo Pekka; Malmström, Kristiina; Kotaniemi-Syrjänen, Anne; Lohi, Jouko; Pelkonen, Anna S.; Sarna, Seppo; Mäkelä, Mika J. (2020)
  • Cecconi, Maurizio; Hofer, Christoph; Teboul, Jean-Louis; Pettila, Ville; Wilkman, Erika; Molnar, Zsolt; Della Rocca, Giorgio; Aldecoa, Cesar; Artigas, Antonio; Jog, Sameer; Sander, Michael; Spies, Claudia; Lefrant, Jean-Yves; De Backer, Daniel; FENICE Investigators; ESICM Trial Grp (2015)
    Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC. This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC. 2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500-1000). The median time was 24 min (40-60 min), and the median rate of FC was 1000 [500-1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57-61 %). In 43 % (CI 41-45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34-37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20-24 %). No safety variable for the FC was used in 72 % (CI 70-74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response. The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account.
  • Perner, Anders; Hjortrup, Peter B.; Pettila, Ville (2017)
  • Tuorila, Katri; Ollila, Meri-Maija; Järvelin, Marjo-Riitta; Tapanainen, Juha S.; Franks, Stephen; Puukka, Katri; Piltonen, Terhi T.; Morin-Papunen, Laure (2021)
    Context: The role of androgen excess as a contributing factor to abnormal glucose metabolism (AGM) and insulin resistance in women remains controversial. Objective: To investigate whether hyperandrogenemia (HA) estimated by serum testosterone (T) level and free androgen index (FAI) at ages 31 and 46 years is associated with insulin resistance, insulin secretion and AGM by age 46. Design: Prospective study including 5889 females followed at ages 31 and 46 years. Setting: General community. Participants: Women with HA were compared with normoandrogenic women at ages 31 and 46 years. Intervention: None. Main outcome measurements: AGM, including prediabetes and type 2 diabetes mellitus, homeostatic model assessments of insulin resistance (HOMA-IR) and of pancreatic beta-cell function (HOMA-B). Results: At age 31 years, HA women displayed increased HOMA-IR (P = 0.002), HOMA-B (P = 0.007), and higher fasting insulin (P = 0.03) than normoandrogenic women after adjusting for body mass index (BMI). At age 46 years, there was a nonsignificant trend toward higher fasting glucose (P = 0.07) and glycated hemoglobin A1 (P = 0.07) levels in HA women. Women in the highest T quartile (odds ratio [OR] = 1.80; 95%CI, 1.15-2.82) at age 31 years and in the 2 highest FAI quartiles at ages 31 (Q4: OR = 3.76; 95% CI, 2.24-6.32) and 46 (Q4: OR = 2.79; 95% CI, 1.74-4.46) years had increased risk for AGM, independently of BMI, when compared with women in Q1. SHBG was inversely associated with AGM (at age 31 years: Q4: OR = 0.37; 95% CI, 0.23-0.60, at age 46 years: Q4: OR = 0.28; 95% CI, 0.17-0.44). Conclusion: Hyperandrogenemia and low SHBG in early and middle age associates with AGM independently of BMI.
  • PLATO Investigators; Franchi, Francesco; James, Stefan K.; Lakic, Tatevik Ghukasyan; Lassila, Riitta (2019)
    Background-There are limited data on how the combination of diabetes mellitus (DM) and chronic kidney disease (CKD) affects cardiovascular outcomes as well as response to different P2Y(12) receptor antagonists, which represented the aim of the present investigation. Methods and Results-In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM+/CKD+ (n=1058), DM+/CKD- (n=2748), DM-/CKD+ (n=2160), and DM-/CKD- (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM+/CKD+ patients had a higher incidence of the primary end point compared with DM-/CKD- patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88-2.63; P Conclusions-In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD, with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD.
  • Lassmann-Klee, Paul G.; Sundblad, Britt-Marie; Malmberg, Leo P.; Sovijarvi, Anssi R. A.; Piirilä, Päivi (2020)
    Clinical testing of bronchial hyperreactivity (BHR) provides valuable information in asthma diagnostics. Nevertheless, the test results depend to a great extent on the testing procedure: test substance, apparatus and protocol. In Nordic countries, three protocols predominate in the testing field: Per Malmberg, Nieminen and Sovijarvi methods. However, knowledge of their equivalence is limited. We aimed to find equivalent provocative doses (PD) to obtain similar bronchoconstrictive responses for the three protocols. We recruited 31 patients with suspected asthma and health care workers and performed BHR testing with methacholine according to Malmberg and Nieminen methods, and with histamine according to Sovijarvi. We obtained the individual response-dose slopes for each method and predicted equivalent PD values. Applying a mixed-model, we found significant differences in the mean (standard error of mean) response-dose (forced expiratory volume in one second (FEV1)%/mg): Sovijarvi 7.2 (1.5), Nieminen 13.8 (4.2) and Malmberg 26 (7.3). We found that the earlier reported cut-point values for moderate BHR and marked BHR between the Sovijarvi (PD15) and Nieminen (PD20) methods were similar, but with the Malmberg method a significant bronchoconstrictive reaction was measured with lower PD20 values. We obtained a relationship between slope values and PD (mg) between different methods, useful in epidemiological research and clinical practice.
  • Stjernberg-Salmela, Susanna; Karjalainen, Teemu; Juurakko, Joona; Toivonen, Pirjo; Waris, Eero; Taimela, Simo; Ardern, Clare L.; Järvinen, Teppo L.N.; Jokihaara, Jarkko (2022)
    Background: The Numerical Rating Scale (NRS) and Patient-rated wrist/hand evaluation (PRWHE) are patient-reported outcomes frequently used for evaluating pain and function of the wrist and hand. The aim of this study was to determine thresholds for minimal important difference (MID) and patient acceptable symptom state (PASS) for NRS pain and PRWHE instruments in patients with base of thumb osteoarthritis. Methods: Fifty-two patients with symptomatic base of thumb osteoarthritis wore a splint for six weeks before undergoing trapeziectomy. NRS pain (0 to 10) and PRWHE (0 to 100) were collected at the time of recruitment (baseline), after splint immobilization prior to surgery, and at 3, 6, 9 and 12 months after surgery. Four anchor-based methods were used to determine MID for NRS pain and PRWHE: the receiver operating characteristics (ROC) curve, the mean difference of change (MDC), the mean change (MC) and the predictive modelling methods. Two approaches were used to determine PASS for NRS pain and PRWHE: the 75th percentile and the ROC curve methods. The anchor question for MID was the change perceived by the patient compared with baseline; the anchor question for PASS was whether the patient would be satisfied if the condition were to stay similar. The correlation between the transition anchor at baseline and the outcome at all time points combined was calculated using the Spearman’s rho analysis. Results: The MID for NRS pain was 2.5 using the ROC curve method, 2.0 using the MDC method, 2.8 using the MC method, and 2.5 using the predictive modelling method. The corresponding MIDs for PRWHE were 22, 24, 10, and 20. The PASS values for NRS pain and PRWHE were 2.5 and 30 using the ROC curve method, and 2.0 and 22 using the 75th percentile method, respectively. The area under curve (AUC) analyses showed excellent discrimination for all measures. Conclusion: We found credible MID estimates for NRS and PRWHE (including its subscales), although the MID estimates varied depending on the method used. The estimates were 20-30% of the range of scores of the instruments. The cut-offs for MID and PASS showed good or excellent discrimination, lending support for their use in future studies. Trial registration: This clinimetrics study was approved by the Helsinki University ethical review board (HUS1525/2017).
  • Hao, Qiukui; Devji, Tahira; Zeraatkar, Dena; Wang, Yuting; Qasim, Anila; Siemieniuk, Reed A. C.; Vandvik, Per Olav; Lähdeoja, Tuomas; Carrasco-Labra, Alonso; Agoritsas, Thomas; Guyatt, Gordon (2019)
    Objectives To identify credible anchor-based minimal important differences (MIDs) for patient-reported outcome measures (PROMs) relevant to a BMJ Rapid Recommendations addressing subacromial decompression surgery for shoulder pain. Design Systematic review. Outcome measures Estimates of anchor-based MIDs, and their credibility, for PROMs judged by the parallel BMJ Rapid Recommendations panel as important for informing their recommendation (pain, function and health-related quality of life (HRQoL)). Data sources MEDLINE, EMBASE and PsycINFO up to August 2018. Study selection and review methods We included original studies of any intervention for shoulder conditions reporting estimates of anchor-based MIDs for relevant PROMs. Two reviewers independently evaluated potentially eligible studies according to predefined selection criteria. Six reviewers, working in pairs, independently extracted data from eligible studies using a predesigned, standardised, pilot-tested extraction form and independently assessed the credibility of included studies using an MID credibility tool. Results We identified 22 studies involving 5562 patients that reported 74 empirically estimated anchor-based MIDs for 10 candidate instruments to assess shoulder pain, function and HRQoL. We identified MIDs of high credibility for pain and function outcomes and of low credibility for HRQoL. We offered median estimates for the systematic review team who applied these MIDs in Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence summaries and in their interpretations of results in the linked systematic review addressing the effectiveness of surgery for shoulder pain. Conclusions Our review provides anchor-based MID estimates, as well as a rating of their credibility, for PROMs for patients with shoulder conditions. The MID estimates inform the interpretation for a linked systematic review and guideline addressing subacromial decompression surgery for shoulder pain, and could also prove useful for authors addressing other interventions for shoulder problems.
  • Salmela, Heli; Harwood, Gyan P.; Munch, Daniel; Elsik, Christine G.; Herrero-Galan, Elias; Vartiainen, Maria K.; Amdam, Gro (2022)
    Vitellogenin (Vg) is a conserved protein used by nearly all oviparous animals to produce eggs. It is also pleiotropic and performs functions in oxidative stress resistance, immunity, and, in honey bees, behavioral development of the worker caste. It has remained enigmatic how Vg affects multiple traits. Here, we asked whether Vg enters the nucleus and acts via DNA-binding. We used cell fractionation, immunohistology, and cell culture to show that a structural subunit of honey bee Vg translocates into cell nuclei. We then demonstrated Vg-DNA binding theoretically and empirically with prediction software and chromatin immunoprecipitation with sequencing (ChIP-seq), finding binding sites at genes influencing immunity and behavior. Finally, we investigated the immunological and enzymatic conditions affecting Vg cleavage and nuclear translocation and constructed a 3D structural model. Our data are the first to show Vg in the nucleus and suggest a new fundamental regulatory role for this ubiquitous protein.
  • Malmberg, Maiju; Malmberg, L. Pekka; Pelkonen, Anna S.; Makela, Mika J.; Kotaniemi-Syrjänen, Anne (2021)
    Background The objective of this study was to evaluate the role of body mass index with regard to exercise performance, exercise-induced bronchoconstriction (EIB), and respiratory symptoms in 7- to 16-year-old children. Methods A total of 1120 outdoor running exercise challenge test results of 7- to 16-year-old children were retrospectively reviewed. Lung function was evaluated with spirometry, and exercise performance was assessed by calculating distance per 6 minutes from the running time and distance. Respiratory symptoms in the exercise challenge test were recorded, and body mass index modified for children (ISO-BMI) was calculated for each child from height, weight, age, and gender according to the national growth references. Results Greater ISO-BMI and overweight were associated with poorer exercise performance (P <.001). In addition, greater ISO-BMI was independently associated with cough (P = .002) and shortness of breath (P = .012) in the exercise challenge. However, there was no association between ISO-BMI and EIB or with wheeze during the exercise challenge. Conclusion Greater ISO-BMI may have a role in poorer exercise performance and appearance of respiratory symptoms during exercise, but not in EIB in 7- to 16-year-old children.
  • Lajunen, Katariina Tytti; Malmberg, Leo Pekka; Kalliola, Satu; Kotaniemi-Syrjänen, Anne; Pelkonen, L. Anna Susanna; Mäkelä, Mika Juhani (2020)
    Abstract Background Airway hyperresponsiveness (AHR) is a common feature in asthma. The use of AHR in predicting active asthma or the persistence of AHR in childhood is poorly understood. By analyzing longitudinal connections including different measures of AHR, lung function, and inflammation markers, we sought to identify the best available method for predicting persistence of AHR and identification of later active asthma. Methods We tested 105 asthmatic children aged 3-7 years with fractional exhaled nitric oxide (FeNO), impulse oscillometry (IOS), and AHR evaluated by indirect methods (hypertonic saline and exercise challenge). Ten years later, 64 children participated in the follow-up visit and were tested with FeNO, IOS, spirometry, and methacholine challenge. At both study visits, blood samples were collected, and a questionnaire was completed. Results Asthma was in remission in 66% of patients at adolescence. AHR measured by hypertonic saline challenge at preschool age was associated with asthma symptoms (OR 10.2; 95%CI 2.8, 37.3) but not with AHR estimated with methacholine challenge 10 years later. AHR measured by exercise challenge was not associated with AHR or recent asthma symptoms in adolescence. Preschool eosinophilia continued until adolescence in 87% of patients but was not associated with AHR or subjective signs of asthma 10 years later. Wheezy preschoolers with atopy had a higher risk for AHR in adolescence (OR 4.1; 95%CI 1.0, 16.2). Conclusion Results from hypertonic saline challenge are associated with persistent asthma symptoms even after a decade. AHR measured by indirect methods at preschool age did not predict AHR in adolescence.
  • Parkkinen, Markus; Lindahl, Jan; Mäkinen, Tatu J.; Koskinen, Seppo K.; Mustonen, Antti; Madanat, Rami (2018)
    Purpose: To determine factors influencing the development of posttraumatic osteoarthritis (OA) following medial tibial plateau fractures and to evaluate concomitant injuries associated with these fractures. Materials and methods: A chart review of patients with operatively treated medial tibial plateau fractures admitted to our Level I trauma centre from 2002 to 2008 was performed. Of 63 patients, 41 participated in a clinical and radiographic examination. The mean age was 47 years (range 16-78) and the mean follow-up time was 7.6 (range 4.7-11.7) years. All patients had preoperative computed tomography (CT) scans and postoperative radiographs. At the end of follow-up, standing radiographs, mechanical axis, and CT scans were evaluated. Results: Of the 41 patients, 24 had no or mild (Kellgren-Lawrence grade 0-2) OA and 17 had severe (grade 3-4) OA. Initial articular depression measured from preoperative CT scans was a significant predictor of OA (median 1.8 mm vs 4.5 mm, p = 0.009). Fracture line extension to the lateral plateau (p = 0.68) or fracture comminution (p = 0.21) had no effect on the development of posttraumatic OA, nor did articular depression at the end of follow-up (p = 0.68) measured from CT scans. Mechanical axis >4 degrees of varus and >= 2 mm articular depression or step-off were associated with worse WOMAC pain scores, but did not affect other functional outcome scores. Six patients (10%) had permanent peroneal nerve dysfunction. Ten patients (16%) required LCL reconstruction and nine (14%) ACL avulsions were treated at the time of fracture stabilisation. Conclusions: The amount of articular depression measured from preoperative CT scans seems to predict the development of posttraumatic OA, probably reflecting the severity of chondral injury at the time of fracture. Restoration of mechanical axis and articular congruence are important in achieving a good clinical outcome. (C) 2017 Elsevier Ltd. All rights reserved.