Browsing by Subject "ADULT"

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  • Sorsa, Timo; Alassiri, Saeed; Grigoriadis, Andreas; Räisänen, Ismo T.; Pärnänen, Pirjo; Nwhator, Solomon O.; Gieselmann, Dirk-Rolf; Sakellari, Dimitra (2020)
    The aim of this study was to investigate the utility of incorporating active matrix metalloproteinase-8 (aMMP-8) as a biomarker into the new periodontitis classification system (stage/grade) presented in 2018. This study included 150 Greek adults aged 25-78, of whom 74 were men and 76 women. Participants were tested with an aMMP-8 point-of-care mouthrinse test, after which a full-mouth clinical examination was performed to assess their periodontal and oral health. The aMMP-8 levels in mouthrinse were significantly lower among healthy patients compared with patients in more severe periodontitis stages and grades (Kruskal-Wallis test and Dunn-Bonferroni test for pairwise post-hoc comparisons; p <0.01 and p <0.05, respectively). Furthermore, aMMP-8 levels were less correlated with plaque levels than bleeding on probing (BOP) (Spearman's rho = 0.269, p <0.001; Spearman's rho = 0.586, p <0.001); respectively). Thus, aMMP-8 was more robust to the confounding effects of oral hygiene than traditional periodontal parameter bleeding on probing. The aMMP-8 point-of-care mouthrinse test can be utilized as an adjunctive and preventive diagnostic tool to identify periodontal disease, classified by stage and grade, and ongoing periodontal breakdown chairside in clinical practice in only 5 min. Overall, integrating aMMP-8 into the new periodontitis classification system seems beneficial.
  • Tapiovaara, Laura; Back, Leif; Aro, Katri (2017)
    Possible airway compromise further complicates treatment of deep neck infections (DNI). Airway management is crucial, but factors affecting the method of choice are unclear. We retrospectively evaluated adult DNIs in a single tertiary center covering 10 years, with special attention on airway management. Patient data were retrieved from electronic data files from 2007 to 2016, and included adult patients with DNI operated through the neck. Of the 202 patients, 127 (63%) were male, with a median age of 47 years. Odontogenic (n = 74; 35%) infection was the most common etiology. Intubation was the most common method of airway management (n = 165; 82%), and most patients (n = 102; 50%) were extubated immediately after surgery. Tracheotomy was performed primarily for 35 (17%) patients, and secondarily for 25 (15%). Two patients were managed in local anesthesia. Altogether 80 (40%) patients required care in the intensive care unit for a median of 7 days. Median hospital stay was 6 days for intubated patients and 10 days for primarily tracheotomized (p = 0.036). DNI extended to the mediastinal space in 25 (12%) patients, most of whom with odontogenic infection (48%), and necrotizing fasciitis (32%). Odontogenic infection was the most common etiology for DNI with increased risk for mediastinal involvement. Intubation was most common type of airway management with high success in immediate extubation after surgery. The need for tracheotomy seemed to lead to a longer hospital care and was associated with a more severe clinical course.
  • Anttonen, Mikko; Pihlajoki, Marjut; Andersson, Noora; Georges, Adrien; L'Hote, David; Vattulainen, Sanna; Farkkila, Anniina; Unkila-Kallio, Leila; Veitia, Reiner A.; Heikinheimo, Markku (2014)
  • Balboa, Diego; Prasad, Rashmi B.; Groop, Leif; Otonkoski, Timo (2019)
    Understanding the molecular mechanisms behind beta cell dysfunction is essential for the development of effective and specific approaches for diabetes care and prevention. Physiological human beta cell models are needed for this work. We review the possibilities and limitations of currently available human beta cell models and how they can be dramatically enhanced using genome-editing technologies. In addition to the gold standard, primary isolated islets, other models now include immortalised human beta cell lines and pluripotent stem cell-derived islet-like cells. The scarcity of human primary islet samples limits their use, but valuable gene expression and functional data from large collections of human islets have been made available to the scientific community. The possibilities for studying beta cell physiology using immortalised human beta cell lines and stem cell-derived islets are rapidly evolving. However, the functional immaturity of these cells is still a significant limitation. CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9) has enabled precise engineering of specific genetic variants, targeted transcriptional modulation and genome-wide genetic screening. These approaches can now be exploited to gain understanding of the mechanisms behind coding and non-coding diabetes-associated genetic variants, allowing more precise evaluation of their contribution to diabetes pathogenesis. Despite all the progress, genome editing in primary pancreatic islets remains difficult to achieve, an important limitation requiring further technological development.
  • Vermeulen, Eric; van den Anker, John N.; Della Pasqua, Oscar; Hoppu, Kaarlo; van der Lee, Johanna H.; GRiP (2017)
    Objectives In children, there is often lack of sufficient information concerning the pharmacokinetics (PK) and pharmacodynamics (PD) of a study drug to support dose selection and effective evaluation of efficacy in a randomised clinical trial (RCT). Therefore, one should consider the relevance of relatively small PKPD studies, which can provide the appropriate data to optimise the design of an RCT. Methods Based on the experience of experts collaborating in the EU-funded Global Research in Paediatrics consortium, we aimed to inform clinician-scientists working with children on the design of investigator-initiated PKPD studies. Key findings The importance of the identification of an optimal dose for the paediatric population is explained, followed by the differences and similarities of dose-ranging and efficacy studies. The input of clinical pharmacologists with modelling expertise is essential for an efficient dose-finding study. Conclusions The emergence of new laboratory techniques and statistical tools allows for the collection and analysis of sparse and unbalanced data, enabling the implementation of (observational) PKPD studies in the paediatric clinic. Understanding of the principles and methods discussed in this study is essential to improve the quality of paediatric PKPD investigations, and to prevent the conduct of paediatric RCTs that fail because of inadequate dosing.
  • Forsgård, Richard A. (2019)
    Globally, similar to 70% of adults are deficient in intestinal lactase, the enzyme required for the digestion of lactose. In these individuals, the consumption of lactose-containing milk and dairy products can lead to the development of various gastrointestinal (GI) symptoms. The primary solution to lactose intolerance is withdrawing lactose from the diet either by eliminating dairy products altogether or substituting lactose-free alternatives. However, studies have shown that certain individuals erroneously attribute their GI symptoms to lactose and thus prefer to consume lactose-free products. This has raised the question whether consuming lactose-free products reduces an individual's ability to absorb dietary lactose and if lactose-absorbers should thus avoid these products. This review summarizes the current knowledge regarding the acclimatization of lactose processing in humans. Human studies that have attempted to induce intestinal lactase expression with different lactose feeding protocols have consistently shown lack of enzyme induction. Similarly, withdrawing lactose from the diet does not reduce intestinal lactase expression. Evidence from cross-sectional studies shows that milk or dairy consumption is a poor indicator of lactase status, corroborating the results of intervention studies. However, in lactase-deficient individuals, lactose feeding supports the growth of lactose-digesting bacteria in the colon, which enhances colonic lactose processing and possibly results in the reduction of intolerance symptoms. This process is referred to as colonic adaptation. In conclusion, endogenous lactase expression does not depend on the presence of dietary lactose, but in susceptible individuals, dietary lactose might improve intolerance symptoms via colonic adaptation. For these individuals, lactose withdrawal results in the loss of colonic adaptation, which might lower the threshold for intolerance symptoms if lactose is reintroduced into the diet.
  • Piirtola, Maarit; Kaprio, Jaakko; Waller, Katja; Heikkila, Kauko; Koskenvuo, Markku; Svedberg, Pia; Silventoinen, Karri; Kujala, Urho M.; Ropponen, Annina (2017)
    Background: We investigated the stability and change of leisure-time physical inactivity in adult men and women during a 35-year follow-up. We also analysed the impact of long-term physical inactivity on the development of body mass index (BMI). Methods: In this population-based cohort study, 5254 Finnish twin individuals (59% women) participated in four surveys in 1975, 1981, 1990 and 2011. Mean age at baseline was 23.9 years. Individual long-term leisure-time physical activity (LTPA) was categorized into seven classes varying from 'persistently inactive' to 'persistently active'. We used the multivariate multilevel mixed-effects linear regression model and paired-sample t-test in the analyses. Co-twin control design was used for examining within-pair associations. Results: Of men 11%, and of women 8%, were persistently inactive. Among both sexes, the mean BMI slope trajectories were steeper among the persistently inactive and those who became inactive than among those who were persistently active. Overall, the inactive participants gained 1.4 kg/m(2) [95% confidence interval (CI) 1.2 to 1.7] more in weight than did the active participants from 1975 to 2011. Among twin pairs discordant for LTPA, the corresponding difference was 1.4 kg/m(2) (95% CI 0.83 to 2.0) in dizygotic pairs and 0.68 kg/m(2) (95% CI 0.05 to1.3) in monozygotic pairs. Conclusions: Over a 35-year time span from young adulthood, persistently inactive participants and those who had become inactive had greater weight increases than those who were persistently active. This association was also found in twin-pair analyses, although attenuated in monozygotic pairs. This may support the importance of LTPA in weight management, although further causal inference is required.
  • Juhila, Juuso; Sipila, Tessa; Icay, Katherine; Nicorici, Daniel; Ellonen, Pekka; Kallio, Aleksi; Korpelainen, Eija; Greco, Dario; Hovatta, Iiris (2011)
  • Varshney, Mukesh Kumar; Yu, Nancy Yiu-Lin; Katayama, Shintaro; Li, Xin; Liu, Tianyao; Wu, Wan-Fu; Tohonen, Virpi; Krjutskov, Kaarel; Kere, Juha; Fan, Xiaotang; Inzunza, Jose; Gustafsson, Jan-Ake; Nalvarte, Ivan (2020)
    Background: Male estrogen receptor beta (ER beta) knockout (BERKO) mice display anxiety and aggression linked to, among others, altered serotonergic signaling in the basolateral amygdala and dorsal raphe, impaired cortical radial glia migration, and reduced GABAergic signaling. The effects on primary motor cortex (M1 cortex) and locomotor activity as a consequence of ER beta loss have not been investigated. Objective: The aim of this study was to determine whether locomotor activity is altered as a consequence of the changes in the M1 cortex. Methods: The locomotor activity of male wild-type (WT) and BERKO mice was evaluated using the open-field and rotarod tests. Molecular changes in the M1 cortex were analyzed by RNA sequencing, electron microscopy, electrophysiology, and immunohistological techniques. In addition, we established oligodendrocyte (OL) cultures from WT and BERKO mouse embryonic stem cells to evaluate OL function. Results: Locomotor profiling revealed that BERKO mice were more active than WT mice but had impaired motor coordination. Analysis of the M1 cortex pointed out differences in synapse function and myelination. There was a reduction in GABAergic signaling resulting in imbalanced excitatory and inhibitory neurotransmission as well as a defective OL differentiation accompanied by myelin defects. The effects of ER beta loss on OL differentiation were confirmed in vitro. Conclusion: ER beta is an important regulator of GABAergic interneurons and OL differentiation, which impacts on adult M1 cortex function and may be linked to increased locomotor activity and decreased motor coordination in BERKO mice.
  • Elmadani, Manar; Khan, Suleiman; Tenhunen, Olli; Magga, Johanna; Aittokallio, Tero; Wennerberg, Krister; Kerkelä, Risto (2019)
    Background-Small molecule kinase inhibitors (KIs) are a class of agents currently used for treatment of various cancers. Unfortunately, treatment of cancer patients with some of the KIs is associated with cardiotoxicity, and there is an unmet need for methods to predict their cardiotoxicity. Here, we utilized a novel computational method to identify protein kinases crucial for cardiomyocyte viability. Methods and Results-One hundred forty KIs were screened for their toxicity in cultured neonatal cardiomyocytes. The kinase targets of KIs were determined based on integrated data from binding assays. The key kinases mediating the toxicity of KIs to cardiomyocytes were identified by using a novel machine learning method for target deconvolution that combines the information from the toxicity screen and from the kinase profiling assays. The top kinases identified by the model were phosphoinositide 3-kinase catalytic subunit alpha, mammalian target of rapamycin, and insulin-like growth factor 1 receptor. Knockdown of the individual kinases in cardiomyocytes confirmed their role in regulating cardiomyocyte viability. Conclusions-Combining the data from analysis of KI toxicity on cardiomyocytes and KI target profiling provides a novel method to predict cardiomyocyte toxicity of KIs.
  • Räisänen, Ismo T.; Heikkinen, Anna Maria; Nwhator, Solomon O.; Umeizudike, Kehinde A.; Tervahartiala, Taina; Sorsa, Timo (2019)
    This study investigated the diagnostic utility of mouthrinse and saliva in aMMP-8 measurements to analyze patients' risk for active periodontal tissue destruction and progression of periodontal disease among 47 adolescents. Results show that measurements from mouthrinse produce better discrimination and should be used instead of saliva measurements. (C) 2019 Elsevier Inc. All rights reserved.
  • Bjorn, Annika; Pudas-Tahka, Sanna-Mari; Salantera, Sanna; Axelin, Anna (2017)
    Aim: To evaluate the impact of video education on critical care nurses' knowledge and skills in using a behavioural pain assessment tool for intensive care patients and to explore the nurses' experiences with video education. Methods: Forty-eight nurses in one intensive care unit watched an educational video on the use of the Critical-Care Pain Observation Tool, then assessed pain in two patients with the tool and took a knowledge test. The researcher made parallel pain assessments. Interrater reliability of patients' pain assessment between nurses and the researcher was determined to examine nurses' skills in using the tool after education. Twenty nurses were interviewed about their experiences with the video education. Interviews were analysed with deductive thematic analysis. Results: The knowledge test scores indicated that the nurses learned the principles of how to use the tool. The interrater reliability of pain assessments reached a moderate level of agreement during the painful procedure, with a weighted kappa coefficient value of 0.48, CL [0.37, 0.58]. The nurses perceived video education positively, but requested additional interaction. Conclusions: Video education is useful in teaching the principles of using a pain assessment tool. Additional clinical training is required for nurses to reach adequate skills in using the tool. (C) 2017 Elsevier Ltd. All rights reserved.