Browsing by Subject "INVOLVEMENT"

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  • Pitkänen, H. H.; Kärki, M.; Niinikoski, H.; Tanner, L.; Näntö-Salonen, K.; Pikta, M.; Kopatz, W. F.; Zuurveld, M.; Meijers, J. C. M.; Brinkman, H. J. M.; Lassila, R. (2018)
    Introduction: Lysinuric protein intolerance (LPI), a rare autosomal recessive transport disorder of cationic amino acids lysine, arginine and ornithine, affects intestines, lungs, liver and kidneys. LPI patients may display potentially life-threatening bleeding events, which are poorly understood. Aims: To characterize alterations in haemostatic and fibrinolytic variables associated with LPI. Methods: We enrolled 15 adult patients (8 female) and assessed the clinical ISTH/ SSC-BAT bleeding score (BS). A variety of metabolic and coagulation assays, including fibrin generation test derivatives, clotting time (CT) and clot lysis time (CLT), thromboelastometry (ROTEM), and PFA-100 and Calibrated Automated Thrombogram (CAT), were used. Results: All patients had mild-to-moderate renal insufficiency, and moderate bleeding tendency (BS 4) without spontaneous bleeds. Mild anaemia and thrombocytopenia occurred. Traditional clotting times were normal, but in contrast, CT in fibrin generation test, and especially ROTEM FIBTEM was abnormal. The patients showed impaired primary haemostasis in PFA, irrespective of normal von Willebrand factor activity, but together with lowered fibrinogen and FXIII. Thrombin generation (TG) was reduced in vitro, according to CAT-derived endogenous thrombin potential, but in vivo TG was enhanced in the form of circulating prothrombin fragment 1 and 2 values. Very high D-dimer and plasmin-alpha 2-antiplasmin (PAP) complex levels coincided with shortened CLT in vitro. Conclusions: Defective primary haemostasis, coagulopathy, fibrin abnormality (FIBTEM, CT and CLT), low TG in vitro and clearly augmented fibrinolysis (PAP and D-dimer) in vivo were all detected in LPI. Altered fibrin generation and hyperfibrinolysis were associated with the metabolic and renal defect, suggesting a pathogenetic link in LPI.
  • Hakulinen, Christian; Jokela, Markus (2019)
    Background. Personality has been associated with alcohol use, but less is known about how alcohol use may influence long-term personality trait change. Methods. The present study examines associations between alcohol use and change in the five major personality traits across two measurement occasions (mean follow-up of 5.6 years). A total of 39 722 participants (54% women) were pooled from six cohort studies for an individual-participant meta-analysis. Alcohol use was measured as (1) average alcohol consumption, (2) frequency of binge drinking, (3) symptoms of alcohol use disorder, and (4) a global indicator of risky alcohol use. Changes in the five major personality traits (extraversion, emotional stability, agreeableness, conscientiousness, and openness to experience) were used as outcomes. Results. Risky alcohol use was associated with increasing extraversion [0.25 T-scores over the mean follow-up of 5.6 years; 95% confidence interval (CI) 0.07-0.44] and decreasing emotional stability (-0.28; 95% CI -0.48 to -0.08), agreeableness (-0.67; 95% CI -0.87 to -0.36), and conscientiousness (-0.58; 95% CI -0.79 to -0.38). Except the association between alcohol use and extraversion, these associations were consistent across cohort studies and across different measures of alcohol use. Conclusions. These findings suggest that alcohol use is associated with personality trait changes in adulthood.
  • Haaranen, Mia; Scuppa, Giulia; Tambalo, Stefano; Järvi, Vilja; Bertozzi, Sine M.; Armirotti, Andrea; Sommer, Wolfgang H.; Bifone, Angelo; Hyytiä, Petri (2020)
    The anterior insular cortex plays a key role in the representation of interoceptive effects of drug and natural rewards and their integration with attention, executive function, and emotions, making it a potential target region for intervention to control appetitive behaviors. Here, we investigated the effects of chemogenetic stimulation or inhibition of the anterior insula on alcohol and sucrose consumption. Excitatory or inhibitory designer receptors (DREADDs) were expressed in the anterior insula of alcohol-preferring rats by means of adenovirus-mediated gene transfer. Rats had access to either alcohol or sucrose solution during intermittent sessions. To characterize the brain network recruited by chemogenetic insula stimulation we measured brain-wide activation patterns using pharmacological magnetic resonance imaging (phMRI) and c-Fos immunohistochemistry. Anterior insula stimulation by the excitatory Gq-DREADDs significantly attenuated both alcohol and sucrose consumption, whereas the inhibitory Gi-DREADDs had no effects. In contrast, anterior insula stimulation failed to alter locomotor activity or deprivation-induced water drinking. phMRI and c-Fos immunohistochemistry revealed downstream activation of the posterior insula and medial prefrontal cortex, as well as of the mediodorsal thalamus and amygdala. Our results show the critical role of the anterior insula in regulating reward-directed behavior and delineate an insula-centered functional network associated with the effects of insula stimulation. From a translational perspective, our data demonstrate the therapeutic potential of circuit-based interventions and suggest that potentiation of insula excitability with neuromodulatory methods, such as repetitive transcranial magnetic stimulation (rTMS), could be useful in the treatment of alcohol use disorders.
  • Salonen, Anne H.; Castren, Sari; Raisamo, Susanna; Orford, Jim; Alho, Hannu; Lahti, Tuuli (2014)
    Background: Attitudes towards gambling influence gambling behaviour but also reflect the existing gambling policy in a society. However, studies examining general attitudes towards gambling at the population level are scarce. The first aim of this study was to investigate general attitudes of the Finnish population towards gambling. The second aim was to explore the association of socio-demographics, gambling behaviours, being a concerned significant other (CSO) of a problem gambler and perceived health and lifestyle with attitudes towards gambling among the Finnish population. Methods: A cross-sectional study was performed by structured telephone interview on a random sample of 15-74-year-old Finns between October 2011 and January 2012. The data (n = 4484) was weighted based on age, gender and region of residence. Attitudes towards gambling were measured with the eight-item version of the Attitude Towards Gambling Scale (ATGS-8). A factor analysis was performed to test the structure of the Finnish version of the ATGS-8. The data were analysed using one-way ANOVA test, t-test and multiple regression analysis. Results: On average, attitudes of Finns towards gambling were negative. The most significant factors associated with positive attitudes towards gambling were male gender, young age, 12 years or more education and net income more than 2000(sic), low score on gambling severity, being a non-CSO of a problem gambler and high alcohol consumption Conclusions: The association between young age, male gender, high net income and risky alcohol consumption, and favourable gambling attitudes was strong, and also reflects risky gambling behaviour. Experiencing gambling-related harms caused by one's own or significant other's excessive gambling seems to indicate unfavourable attitudes towards gambling.
  • Kaartinen, I.; Sunela, K.; Alanko, J.; Hukkinen, K.; Karjalainen-Lindsberg, M. -L.; Svarvar, C. (2017)
    Breast lymphomas comprise a rare group of malignant breast tumors. Among these, a new entity has emerged as a potentially under diagnosed disease. Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) most often manifests as a late periprosthetic effusion between 1 and 10 years after the implantation of silicone or saline-filled breast prostheses. BI-ALCL is an anaplastic lymphoma kinase-negative T-cell lymphoma that has a distinctively different clinical course than other breast lymphomas or ALCLs. Diagnosis is based on aspiration of the effusion around the implant and CD30 positivity of the sample. Every periprosthetic effusion after breast augmentation or reconstruction using implants should be considered as potential BI-ALCL until proven otherwise. The majority of cases at diagnosis are in the in situ stage, i.e., confined to the lumen around the prosthesis. Most patients have an excellent prognosis when complete removal of the capsule and prosthesis with negative margins is achieved surgically. Some patients, however, develop infiltrative disease with a potentially life-threatening clinical course. Treatment planning regarding the extent of surgery and role of adjuvant therapy, especially in advanced cases, requires further investigation. (c) 2017 Elsevier Ltd, BASO-The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
  • Halonen, Pia; Jakobsson, Maija; Heikinheimo, Oskari; Riska, Annika; Gissler, Mika; Pukkala, Eero (2018)
    The association between Lichen planus (LP) and cancer has been under debate for decades. We studied the connection via population-based Finnish register data. All women with the diagnosis of LP (n=13,100) were identified from the Finnish Hospital Discharge Registry from 1969-2012. These patients were linked with subsequent cancer diagnoses from the Finnish Cancer Registry until 2014. Standardized incidence ratios (SIRs) were counted for different cancers by dividing the observed numbers of cancers by expected numbers, which were based on national cancer incidence rates. In total, 1,520 women with LP were diagnosed with cancer (SIR 1.15, 95% confidence interval [CI] 1.09-1.20). LP was associated with an increased risk of cancer of lip (SIR 5.17, 95% CI 3.06-8.16), cancer of tongue (SIR 12.4, 95% CI 9.45-16.0), cancer of oral cavity (SIR 7.97, 95% CI 6.79-9.24), cancer of esophagus (SIR 1.95, 95% CI 1.17-3.04), cancer of larynx (SIR of 3.47, 95% CI 1.13-8.10) and cancer of vulva (SIR 1.99, 95% CI 1.18-3.13). The risk of cancer was not increased in other locations where LP manifests (pharynx and skin). Patients with diagnosed LP have an increased risk of developing cancer of lip, tongue, oral cavity, esophagus, larynx and vulva. These data are important when considering treatment and follow-up of patients with LP diagnosis. What's new?Lichen planus (LP) is a chronic disease of the skin and mucous membranes that is likely autoimmune in origin. Owing to its inflammatory nature, it is also suspected of causing certain cancers. Whether LP possesses malignant potential, however, remains uncertain. Here, in a cohort of 13,100 women diagnosed with LP between 1969 and 2012 in Finland, some 1,520 were eventually diagnosed with cancer. Malignancies with significant increases in incidence in LP patients included those of the lip, tongue, oral cavity, esophagus, larynx and vulva. The findings suggest that LP patients could benefit from multidisciplinary approaches to care.
  • Mauramo, Matti; Rohde, Luzius; Ramseier, Adrian M.; Rovo, Alicia; Waltimo, Tuomas (2017)
    The aetiology of hyposalivation in haematopoietic stem cell transplantation (HSCT) recipients is not fully understood. This study examined the effects of treatment-related aetiological factors, particularly medications, on stimulated salivary flow in HSCT recipients. Adult HSCT recipients (N = 118, 66 males, 27 autologous and 91 allogeneic transplants) were examined. Stimulated whole salivary flow rates (SWSFR) were measured before HSCT and at 6 and 12 months post-HSCT. Linear regression models were used to analyse the associations of medications and transplant-related factors with salivary flow rates, which were compared to salivary flow rates of generally healthy controls (N = 247). The SWSFR of recipients were lower pre-HSCT (mean +/- standard deviation, 0.88 +/- 0.56 ml/min; P <0.001), 6 months post-HSCT (0.84 +/- 0.61; P <0.001) and 12 months post-HSCT (1.08 +/- 0.67; P = 0.005) than the SWSFR of controls (1.31 +/- 0.65). In addition, hyposalivation (<0.7 ml/min) was more frequent among HSCT recipients pre-HSCT (P <0.001), 6 months post-HSCT (P <0.001) and 12 months post-HSCT (P = 0.01) than among controls. The SWSFR was observed to improve over time being significantly higher 12 months post-HSCT compared to pre-HSCT (P <0.001). The observed decrease of salivary flow could not be explained by the examined transplant-related factors and medications. Decreased stimulated salivary flow rates could not be explained by the examined factors alone; these findings indicate that hyposalivation in HSCT recipients exhibits a multifactorial aetiology. All HSCT recipients should be considered to be at high risk of hyposalivation and consequent oral diseases, and they should be treated accordingly.
  • Hillbom, Matti; Saloheimo, Pertti; Fujioka, Shinsuke; Wszolek, Zbigniew K.; Juvela, Seppo; Leone, Maurizio A. (2014)
  • Hikmat, Omar; Naess, Karin; Engvall, Martin; Klingenberg, Claus; Rasmussen, Magnhild; Tallaksen, Chantal M. E.; Brodtkorb, Eylert; Fiskerstrand, Torunn; Isohanni, Pirjo; Uusimaa, Johanna; Darin, Niklas; Rahman, Shamima; Bindoff, Laurence A. (2018)
    Objective: Epilepsy is common in individuals with mutations in POLG, the gene encoding the catalytic subunit of the mitochondrial DNA polymerase gamma. Early recognition and aggressive seizure management are crucial for patient survival. Disruption of the blood-brain barrier (BBB) is implicated in various neurological disorders including epilepsy. The aim of this study was to assess whether POLG-related disease is associated with BBB dysfunction and what clinical implications this has for patients. Methods: Our retrospective study used data from 83 patients with pathogenic POLG mutations from 4 countries-Norway, Sweden, Finland, and the United Kingdom. Data were collected using a structured questionnaire. We used the presence of raised cerebrospinal fluid (CSF) protein and a raised CSF/serum ratio of albumin (Q-alb) to evaluate the integrity of the blood-CSF bather. Results: Raised CSF protein was found in 70% of patients (n = 58/83) and appeared to be associated with the most severe phenotypes. In those in whom it was measured, the Q-alb ratio was markedly elevated (n = 18). The majority of those with epilepsy (n = 50/66, 76%) had raised CSF protein, and this preceded seizure debut in 75% (n = 15/20). The median survival time from symptom onset for those with raised CSF protein was decreased (13 months) compared to those with normal CSF protein (32 months). Significance: Our results indicate that there is disruption of the BBB in POLG-related disease, as evidenced by a raised CSF protein and Q-alb ratio. We also find that raised CSF protein is a common finding in patients with POLG disease. Our data suggest that the presence of BBB dysfunction predicts a poorer outcome, and elevated CSF protein may therefore be an additional biomarker both for early diagnosis and to identify those at high risk of developing epilepsy.
  • Palmio, Johanna; Leonard-Louis, Sarah; Sacconi, Sabrina; Savarese, Marco; Penttilä, Sini; Semmler, Anna-Lena; Kress, Wolfram; Mozaffar, Tahseen; Lai, Tim; Stojkovic, Tanya; Berardo, Andres; Reisin, Ricardo; Attarian, Shahram; Urtizberea, Andoni; Cobo, Ana Maria; Maggi, Lorenzo; Kurbatov, Sergei; Nikitin, Sergei; Milisenda, Jose C.; Fatehi, Farzad; Raimondi, Monika; Silveira, Fernando; Hackman, Peter; Claeys, Kristl G.; Udd, Bjarne (2019)
    ObjectiveHereditary myopathy with early respiratory failure (HMERF) is caused by titin A-band mutations in exon 344 and considered quite rare. Respiratory insufficiency is an early symptom. A collection of families and patients with muscle disease suggestive of HMERF was clinically and genetically studied.MethodsAltogether 12 new families with 19 affected patients and diverse nationalities were studied. Most of the patients were investigated using targeted next-generation sequencing; Sanger sequencing was applied in some of the patients and available family members. Histological data and muscle MRI findings were evaluated.ResultsThree families had several family members studied while the rest were single patients. Most patients had distal and proximal muscle weakness together with respiratory insufficiency. Five heterozygous TTN A-band mutations were identified of which two were novel. Also with the novel mutations the muscle pathology and imaging findings were compatible with the previous reports of HMERF.ConclusionsOur collection of 12 new families expands mutational spectrum with two new mutations identified. HMERF is not that rare and can be found worldwide, but maybe underdiagnosed. Diagnostic process seems to be complex as this study shows with mostly single patients without clear dominant family history.
  • Levinthal, Cristiana; Kuusisto, Elina; Tirri, Kirsi (2021)
    The current educational reforms in Finland and Portugal require a holistic engagement of parents with learning, bringing parents and teachers together as partners. This qualitative study, which interviewed Finnish (N = 10) and Portuguese (N = 9) parents, aimed to explore parents’ views on the role of teachers in supporting parent–teacher partnerships and parental engagement with the school. Inductive content analysis was performed to analyze the interviews. From a general standpoint, three patterns were found in the parents’ narratives about the role of teachers in supporting partnership and engagement: communication, professionalism, and invitations to active parental participation. From a cross-cultural standpoint, Finnish parents evidenced partnerships and engagement grounded in little face-to-face contact but consistent online communication with the teacher, as well as trust in their professionalism and independent work. The Portuguese parents revealed rather frequent active participation within the school premises, more recurrent face-to-face communication with the teacher, and appreciation for teachers’ timely responses and support. Recommendations for a holistic approach of engagement and partnerships were brought forward within the context of teacher education, such as the need to maintain simple but regular communication with parents and the relevance of reconsidering the frequency of parental activities in the school.
  • Rytkönen, Sari H.; Kulmala, Petri; Autio-Harmainen, Helena; Arikoski, Pekka; Enden, Kira; Kataja, Janne; Karttunen, Tuomo; Nuutinen, Matti; Jahnukainen, Timo (2018)
    Tubulointerstitial nephritis (TIN) is an inflammatory disease of unknown pathogenesis. To evaluate a possible role of regulatory T cells (Tregs) in the pathophysiology of TIN with (TINU) and without uveitis, we investigated the presence and quantity of FOXP3(+) T regulatory lymphocytes in diagnostic kidney biopsies from pediatric patients. A total of 33 patients (14 TIN and 19 TINU) were enrolled. The quantity of CD4(+), FOXP3(+) and double-positive T cells in formalin-fixed kidney biopsies was determined using double label immunohistochemistry with anti-human CD4 and FOXP3 antibodies. FOXP3 staining was successful in all 33 patients. In patients with chronic uveitis, the density of FOXP3(+) cells was significantly lower (p = 0.046) than in TIN patients without uveitis or with uveitis lasting <3 months. CD4(+) staining was successful in 23 patients. The density of all lymphocytes (CD4(+), CD4(+)FOXP3(+) and FOXP3(+) cells) was significantly lower (p = 0.023) in patients with chronic uveitis than in other patients. FOXP3(+) T cells are present in kidney biopsy samples from TIN and TINU patients. In patients with chronic uveitis, the density of FOXP3(+) T cells is significantly lower than in other patients, suggesting a different pathomechanism for these clinical conditions.
  • Jayanti, Anuradha; Neuvonen, Markus; Wearden, Alison; Morris, Julie; Foden, Philip; Brenchley, Paul; Mitra, Sandip; BASIC-HHD Study Grp (2015)
    Background: Medical decision-making is critical to patient survival and well-being. Patients with end stage renal disease (ESRD) are faced with incrementally complex decision-making throughout their treatment journey. The extent to which patients seek involvement in the decision-making process and factors which influence these in ESRD need to be understood. Methods: 535 ESRD patients were enrolled into the cross-sectional study arm and 30 patients who started dialysis were prospectively evaluated. Patients were enrolled into 3 groups-'predialysis' (group A), 'in-centre' haemodialysis (HD) (group B) and self-care HD (93 % at home-group C) from across five tertiary UK renal centres. The Autonomy Preference Index (API) has been employed to study patient preferences for information-seeking (IS) and decision-making (DM). Demographic, psychosocial and neuropsychometric assessments are considered for analyses. Results: 458 complete responses were available. API items have high internal consistency in the study population (Cronbach's alpha > 0.70). Overall and across individual study groups, the scores for information-seeking and decision-making are significantly different indicating that although patients had a strong preference to be well informed, they were more neutral in their preference to participate in DM (p <0.05). In the age, education and study group adjusted multiple linear regression analysis, lower age, female gender, marital status; higher API IS scores and white ethnicity background were significant predictors of preference for decision-making. DM scores were subdivided into tertiles to identify variables associated with high (DM > 70: and low DM ( Conclusion: ESRD patients prefer to receive information, but this does not always imply active involvement in decision-making. By understanding modifiable and non-modifiable factors which affect patient preferences for involvement in healthcare decision-making, health professionals may acknowledge the need to accommodate individual patient preferences to the extent determined by the individual patient factors.
  • Mustonen, Tuuli; Sivonen, Ville; Atula, Sari; Kiuru-Enari, Sari; Sinkkonen, Saku T. (2021)
    Background: Gelsolin amyloidosis (AGel amyloidosis) is a hereditary form of systemic amyloidosis featuring ophthalmological, neurological and cutaneous symptoms. Previous studies based mainly on patients’ self-reporting have indicated that hearing impairment might also be related to the disease, considering the progressive cranial neuropathy characteristic for AGel amyloidosis. In order to deepen the knowledge of possible AGel amyloidosis-related hearing problems, a clinical study consisting of the Speech, Spatial and Qualities of Hearing Scale (SSQ) questionnaire, clinical examination, automated pure-tone audiometry and a speech-in-noise test was designed. Results: Of the total 46 patients included in the study, eighteen (39%) had self-reported hearing loss. The mean scores in the SSQ were 8.2, 8.3 and 8.6 for the Speech, Spatial and Qualities subscales, respectively. In audiometry, the mean pure tone average (PTA) was 17.1 (SD 12.2) and 17.1 (SD 12.3) dB HL for the right and left ears, respectively, with no difference to gender- and age-matched, otologically normal reference values. The average speech reception threshold in noise (SRT) was − 8.2 (SD 1.5) and − 8.0 (SD 1.7) dB SNR for the right and left ears, respectively, which did not differ from a control group with a comparable range in PTA thresholds. Conclusion: Although a significant proportion of AGel amyloidosis patients experience subjective difficulties in hearing there seems to be no peripheral or central hearing impairment at least in patients up to the age of 60 years.
  • Bompada, Pradeep; Atac, David; Luan, Cheng; Andersson, Robin; Omella, Judit Domenech; Laakso, Emilia Ottosson; Wright, Jason; Groop, Leif; De Marinis, Yang (2016)
    Thioredoxin-interacting protein (TXNIP) has been shown to be associated with glucose-induced deterioration of pancreatic beta cell function in diabetes. However, whether epigenetic mechanisms contribute to the regulation of TXNIP gene expression by glucose is not clear. Here we studied how glucose exerts its effect on TXNIP gene expression via modulation of histone acetylation marks. To achieve this, we applied clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) to knock out his tone acetyltransferase (HAT) p300 in a rat pancreatic beta cell line INS1 832/13. We also treated the cells and human islets with chemical inhibitors of HAT p300 and histone deacetylase (HDAC). In human islets, diabetes and high glucose resulted in elevated TXNIP and EP300 expression, and glucose-induced TXNIP expression could be reversed by p300 inhibitor C646. In INS1 832/13 cells, Ep300 knock-out by CRISPR/Cas9 elevated glucose-induced insulin secretion and greatly reduced glucose-stimulated Txnip expression and cell apoptosis. This effect could be ascribed to decrease in histone marks H3K9ac and H4ac at the promoter and first coding region of the Txnip gene. Histone marks H3K9ac and H4ac in the Txnip gene in the wild-type cells was inhibited by HDAC inhibitor at high glucose, which most likely was due to enhanced acetylation levels of p300 after HDAC inhibition; and thereby reduced p300 binding to the Txnip gene promoter region. Such inhibition was absent in the Ep300 knock-out cells. Our study provides evidence that histone acetylation serves as a key regulator of glucose-induced increase in TXNIP gene expression and thereby glucotoxicity-induced apoptosis. (C) 2016 Elsevier Ltd. All rights reserved.
  • Levinthal, Cristiana; Kuusisto, Elina; Tirri, Kirsi (2021)
    The purpose of this qualitative study was to explore parental engagement in the home-learning environment, and parents’ implicit beliefs about learning underlying such engagement. Nineteen parents of elementary school children between seven and twelve years old were interviewed in two different cultural contexts, Finland (N = 10) and Portugal (N = 9). The interviews were subjected to inductive and deductive content analysis. Forms of parental engagement at home were similar in both countries, divided between two main categories: engagement with the child’s holistic development and engagement with the child’s schooling process. Parental narratives about engagement were, for the most part, embedded in a growth mindset (or an incremental meaning system). The most common actualizations of engagement included considering the child’s learning contexts and emotions; encouraging effort, persistence and practice; approaching difficulties as a natural part of learning and suggesting strategies for overcoming them. Parental practices of engagement were combined with the actualization of their implicit beliefs to create engagement–mindset parental profiles. Twelve parents were classified as having a Growth mindset to support the child’s holistic development profile, and the other seven were distributed amongst the three remaining profiles. The study contributes to the growing interest on the association between parental engagement and their learning-related implicit beliefs, giving clear first-person illustrations of how both occur and interact in the home-learning environment. Implications for practice are discussed.
  • Kuitunen, Hanne; Kaprio, Elina; Karihtala, Peeter; Makkonen, Ville; Kauppila, Saila; Haapasaari, Kirsi-Maria; Kuusisto, Milla; Jantunen, Esa; Turpeenniemi-Hujanen, Taina; Kuittinen, Outi (2020)
    Although overall survival in diffuse large B cell lymphomas (DLBCL) has improved, central nervous system (CNS) relapse is still a fatal complication of DLBCL. For this reason, CNS prophylaxis is recommended for patients at high risk of CNS disease. However, no consensus exists on definition of high-risk patient and optimal CNS prophylaxis. Systemic high-dose methotrexate in combination with R-CHOP has been suggested as a potential prophylactic method, since methotrexate penetrates the blood-brain barrier and achieves high concentration in the CNS. In this retrospective analysis, we report treatment outcome of 95 high-risk DLBCL/FL grade 3B patients treated with R-CHOP or its derivatives with (N = 57) or without (N = 38) CNS prophylaxis. At a median follow-up time (51 months), CNS relapses were detected in twelve patients (12.6%). Ten out of twelve (83%) of CNS events were confined to CNS system only. Median overall survival after CNS relapse was 9 months. Five-year isolated CNS relapse rates were 5% in the prophylaxis group and 26% in the group without prophylaxis. These findings suggest that high-dose methotrexate-containing prophylaxis decreases the risk of CNS failure.
  • Stevanovic, Melisa; Valkeapää, Taina; Weiste, Elina; Lindholm, Camilla (2022)
    Using both statistical methods and conversation analysis, we examined how support workers in a mental health rehabilitation community encourage clients to participate in joint decision-making processes. Drawing on video-recordings of 29 community meetings as data, we considered support workers’ proposals (N = 449) and clients’ responsiveness to them. Support workers’ proposals were coded for their linguistic and other features and clients’ responsiveness was assessed by three independent raters. Multiple linear regression (MLR) analysis was carried out. A significant regression equation with seven predictor variables accounted for 24% of the variance in the data. Four variables predicted a higher level of client responsiveness: the use of explicit recipient address term, “quasi-open” proposal form, support worker’s long work experience, and the average level of client participation during a session. Three variables predicted a lower level of client responsiveness: grammatical complexity of proposal form, modal declarative proposal form, and the presence of only one support worker in a session. The qualitative conversation-analytic investigation highlighted the advantages of the careful fine-tuning of openness vs. closedness of proposal form, the reflexive awareness of which, we argue, may help mental health professionals to encourage clients’ responsiveness in joint decision-making processes and thereby their participation in communal life.
  • Mennesson, Marie; Rydgren, Emilie; Lipina, Tatiana; Sokolowska, Ewa; Kulesskaya, Natalia; Morello, Francesca; Ivakine, Evgueni; Voikar, Vootele; Risbrough, Victoria; Partanen, Juha; Hovatta, Iiris (2019)
    NETO1 and NETO2 are auxiliary subunits of kainate receptors (KARs). They interact with native KAR subunits to modulate multiple aspects of receptor function. Variation in KAR genes has been associated with psychiatric disorders in humans, and in mice, knockouts of the Grik1 gene have increased, while Grik2 and Grik4 knockouts have reduced anxiety-like behavior. To determine whether the NETO proteins regulate anxiety and fear through modulation of KARs, we undertook a comprehensive behavioral analysis of adult Neto1(-/-) and Neto2(-/-) mice. We observed no differences in anxiety-like behavior. However, in cued fear conditioning, Neto2(-/-), but not Neto1(-/-) mice, showed higher fear expression and delayed extinction compared to wild type mice. We established, by in situ hybridization, that Neto2 was expressed in both excitatory and inhibitory neurons throughout the fear circuit including the medial prefrontal cortex, amygdala, and hippocampus. Finally, we demonstrated that the relative amount of synaptosomal KAR GLUK2/3 subunit was 20.8% lower in the ventral hippocampus and 36.5% lower in the medial prefrontal cortex in Neto2(-/-) compared to the Neto2(+/+) mice. The GLUK5 subunit abundance was reduced 23.8% in the ventral hippocampus and 16.9% in the amygdala. We conclude that Neto2 regulates fear expression and extinction in mice, and that its absence increases conditionability, a phenotype related to post-traumatic stress disorder and propose that this phenotype is mediated by reduced KAR subunit abundance at synapses of fear-associated brain regions.
  • Malmberg, Markus; Palomäki, Antti; Sipilä, Jussi O. T.; Rautava, Päivi; Gunn, Jarmo; Kytö, Ville (2021)
    Background: Patients with rheumatoid arthritis (RA) have increased risk of developing cardiovascular disease and events. Little is, however, known about the influence of RA to the outcomes after surgical aortic valve replacement (SAVR). Methods: In a retrospective, nationwide, multicenter cohort study, RA patients (n = 109) were compared to patients without RA (n = 1090) treated with isolated SAVR for aortic valve stenosis. Propensity score-matching adjustment for baseline features was used to study the outcome differences in a median follow-up of 5.6 years. Results: Patients with RA had higher all-cause mortality (HR 1.76; CI 1.21-2.57; p = 0.003), higher incidence of major adverse cardiovascular events (HR 1.63; CI 1.06-2.49; p = 0.025), and they needed more often coronary artery revascularization for coronary artery disease (HR 3.96; CI 1.21-12.90; p = 0.027) in long-term follow-up after SAVR. As well, cardiovascular mortality rate was higher in patients with RA (35.7% vs. 23.4%, p = 0.023). There was no difference in 30-day mortality (2.8% vs. 1.8%, p = 0.518) or in the need for aortic valve reoperations (3.7% vs. 4.0%, p = 0.532). Conclusions: Patients with rheumatoid arthritis had impaired long-term results and increased cardiovascular mortality after SAVR for aortic valve stenosis. Special attention is needed to improve outcomes of aortic valve stenosis patients with RA after SAVR.