Browsing by Subject "INDUCTION"

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  • Pascual, Jesus; Rahikainen, Moona; Angeleri, Martina; Alegre, Sara; Gossens, Richard; Shapiguzov, Alexey; Heinonen, Arttu; Trotta, Andrea; Durian, Guido; Winter, Zsofia; Sinkkonen, Jari; Kangasjarvi, Jaakko; Whelan, James; Kangasjärvi, Saijaliisa (2021)
    Mitochondria are tightly embedded within metabolic and regulatory networks that optimize plant performance in response to environmental challenges. The best-known mitochondrial retrograde signaling pathway involves stress-induced activation of the transcription factor NAC DOMAIN CONTAINING PROTEIN 17 (ANAC017), which initiates protective responses to stress-induced mitochondrial dysfunction in Arabidopsis (Arabidopsis thaliana). Posttranslational control of the elicited responses, however, remains poorly understood. Previous studies linked protein phosphatase 2A subunit PP2A-B'gamma, a key negative regulator of stress responses, with reversible phosphorylation of ACONITASE 3 (ACO3). Here we report on ACO3 and its phosphorylation at Ser91 as key components of stress regulation that are induced by mitochondrial dysfunction. Targeted mass spectrometry-based proteomics revealed that the abundance and phosphorylation of ACO3 increased under stress, which required signaling through ANAC017. Phosphomimetic mutation at ACO3-Ser91 and accumulation of ACO3(S91D)-YFP promoted the expression of genes related to mitochondrial dysfunction. Furthermore, ACO3 contributed to plant tolerance against ultraviolet B (UV-B) or antimycin A-induced mitochondrial dysfunction. These findings demonstrate that ACO3 is both a target and mediator of mitochondrial dysfunction signaling, and critical for achieving stress tolerance in Arabidopsis leaves.
  • Hänninen, Arno; Toivonen, Raine; Pöysti, Sakari; Belzer, Clara; Plovier, Hubert; Ouwerkerk, Janneke P.; Emani, Rohini; Cani, Patrice D.; De Vos, Willem M. (2018)
    Objective Intestinal microbiota is implicated in the pathogenesis of autoimmune type 1 diabetes in humans and in non-obese diabetic (NOD) mice, but evidence on its causality and on the role of individual microbiota members is limited. We investigated if different diabetes incidence in two NOD colonies was due to microbiota differences and aimed to identify individual microbiota members with potential significance. Design We profiled intestinal microbiota between two NOD mouse colonies showing high or low diabetes incidence by 16S ribosomal RNA gene sequencing and colonised the high-incidence colony with the microbiota of the low-incidence colony. Based on unaltered incidence, we identified a few taxa which were not effectively transferred and thereafter, transferred experimentally one of these to test its potential significance. Results Although the high-incidence colony adopted most microbial taxa present in the low-incidence colony, diabetes incidence remained unaltered. Among the few taxa which were not transferred, Akkermansia muciniphila was identified. As A. muciniphila abundancy is inversely correlated to the risk of developing type 1 diabetes-related autoantibodies, we transferred A. muciniphila experimentally to the high-incidence colony. A. muciniphila transfer promoted mucus production and increased expression of antimicrobial peptide Reg3., outcompeted Ruminococcus torques from the microbiota, lowered serum endotoxin levels and islet toll-like receptor expression, promoted regulatory immunity and delayed diabetes development. Conclusion Transfer of the whole microbiota may not reduce diabetes incidence despite a major change in gut microbiota, but single symbionts such as A. muciniphila with beneficial metabolic and immune signalling effects may reduce diabetes incidence when administered as a probiotic.
  • Zhu, Ya-Di; Pang, Hui-Lin; Zhou, Qi-Hang; Qin, Zi-Fei; Jin, Qiang; Finel, Moshe; Wang, Yi-Nan; Qin, Wei-Wei; Lu, Yin; Wang, Dan-Dan; Ge, Guang-Bo (2020)
    The human UDP-glucuronosyltransferase 1A1 (UGT1A1), one of the most essential conjugative enzymes, is responsible for the metabolism and detoxification of bilirubin and other endogenous substances, as well as many different xenobiotic compounds. Deciphering UGT1A1 relevance to human diseases and characterizing the effects of small molecules on the activities of UGT1A1 requires reliable tools for probing the function of this key enzyme in complex biological matrices. Herein, an easy-to-use assay for highly-selective and sensitive monitoring of UGT1A1 activities in various biological matrices, using liquid chromatography with fluorescence detection (LC-FD), has been developed and validated. The newly developed LC-FD based assay has been confirmed in terms of sensitivity, specificity, precision, quantitative linear range and stability. One of its main advantages is lowering the limits of detection and quantification by about 100-fold in comparison to the previous assay that used the same probe substrate, enabling reliable quantification of lower amounts of active enzyme than any other method. The precision test demonstrated that both intra- and inter-day variations for this assay were less than 5.5%. Furthermore, the newly developed assay has also been successfully used to screen and characterize the regulatory effects of small molecules on the expression level of UGT1A1 in living cells. Overall, an easy-to-use LC-FD based assay has been developed for ultra-sensitive UGT1A1 activities measurements in various biological systems, providing an inexpensive and practical approach for exploring the role of UGT1A1 in human diseases, interactions with xenobiotics, and characterization modulatory effects of small molecules on this conjugative enzyme. (c) 2020 Xi'an Jiaotong University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • Talja, Ija; Kubo, Anna-Liisa; Veijola, Riitta; Knip, Mikael; Simell, Olli; Ilonen, Jorma; Vaha-Makila, Mari; Sepp, Epp; Mikelsaar, Marika; Utt, Meeme; Uibo, Raivo (2014)
  • Kakkola, L.; Denisova, O. V.; Tynell, J.; Viiliainen, J.; Ysenbaert, T.; Matos, R. C.; Nagaraj, A.; Öhman, Tiina; Kuivanen, S.; Paavilainen, H.; Feng, L.; Yadav, B.; Julkunen, I.; Vapalahti, O.; Hukkanen, V.; Stenman, J.; Aittokallio, T.; Verschuren, E. W.; Ojala, P. M.; Nyman, T.; Saelens, X.; Dzeyk, K.; Kainov, D. E. (2013)
  • Pohjanvirta, Raimo; Mahiout, Selma (2019)
    Previous studies have shown that several aryl hydrocarbon receptor (AHR) agonists, including β-naphthoflavone (BNF), elicit avoidance of novel food items in rodents, with this behavioral response displaying a similar doseresponse to hepatic induction of CYP1A1. The avoidance has been found to bear substantial similarity to conditioned taste avoidance/aversion (CTA). The present study set out to confirm the indispensability of AHR in the avoidance response, to verify whether vagal afferent fibers are involved in it, and to see if AHR signaling might interfere with the effect of the classic trigger of CTA, LiCl. To this end, globally AHR deficient (AHRKO) or vagotomized wildtype rats were treated by gavage with 60 mg/kg BNF or ip with 0.15M LiCl (4 ml/kg), and presented with chocolate which was either novel or familiar to them. Both the avoidance response and Cyp1a1 induction were missing in AHRKO rats. In contrast, Ahr+/− rats exhibited them in full, save for a single outlier. Total subdiaphragmatic vagotomy failed to interfere with the avoidance of novel or familiar chocolate or induction of Cyp1a1. After LiCl administration, male AHRKO rats showed a significantly mitigated suppression of chocolate consumption compared with wildtype animals (~60% vs. ~10% of control chocolate intake, respectively). A similar tendency was seen in females, but they were less responsive to LiCl. These findings corroborate AHR as a prerequisite of the BNF-induced novel food avoidance, prove vagal afferents unlikely mediators of this response, and imply an unforeseen involvement of AHR signaling in the thoroughly-characterized CTA instigated by LiCl.
  • Nohynek, Hanna; Jokinen, Jukka; Partinen, Markku; Vaarala, Outi; Kirjavainen, Turkka; Sundman, Jonas; Himanen, Sari-Leena; Hublin, Christer; Julkunen, Ilkka; Olsen, Paivi; Saarenpaa-Heikkila, Outi; Kilpi, Terhi (2012)
  • Kruit, Heidi; Tolvanen, Jenna; Eriksson, Jasmin; Place, Katariina; Nupponen, Irmeli; Rahkonen, Leena (2020)
    Introduction To investigate the safety of balloon catheter for cervical ripening in women with term pre-labor rupture of membranes (PROM) and to compare the incidence of maternal and neonatal infections in women with PROM and women with intact membranes undergoing cervical ripening with a balloon catheter. Material and methods This retrospective cohort study of 1923 women with term singleton pregnancy and an unfavorable cervix undergoing cervical ripening with a balloon catheter was conducted in Helsinki University Hospital between January 2014 and December 2018. For each case of PROM, two controls were assigned. The main outcome measures were the rates of maternal and neonatal infections. Statistical analyses were performed by SPSS. Results In all, 641 (33.3%) women following PROM and 1282 (66.6%) women with intact amniotic membranes underwent labor induction. The rates of intrapartum infection (3.7% vs 7.7%; P = .001) and neonatal infection (1.7% vs 3.8%; P = .01) were not increased in women induced by balloon catheter following PROM. Intrapartum infections were associated with nulliparity (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.6-6.5), history of previous cesarean section (OR 2.8, 95% CI 1.2-6.4), extended gestational age >= 41 weeks (OR 1.9, 95% CI 1.2-3.0) and an induction to delivery interval of 48 hours or more (OR 2.0, 95% CI 1.2-3.3). The risk of neonatal infection was associated with nulliparity (OR 3.3, 95% CI 1.4-8.0), gestational age >= 41 weeks (OR 1.9, 95% CI 1.09-3.36) and induction to delivery interval of 48 hours or more (OR 3.4, 95% CI 1.9-6.0). Conclusions Use of balloon catheter in women with term PROM appears safe and was not associated with increased maternal or neonatal infectious morbidity.
  • White, Brian S.; Khan, Suleiman A.; Mason, Mike J.; Ammad-ud-din, Muhammad; Potdar, Swapnil; Malani, Disha; Kuusanmäki, Heikki; Druker, Brian J.; Heckman, Caroline; Kallioniemi, Olli; Kurtz, Stephen E.; Porkka, Kimmo; Tognon, Cristina E.; Tyner, Jeffrey W.; Aittokallio, Tero; Wennerberg, Krister; Guinney, Justin (2021)
    The FDA recently approved eight targeted therapies for acute myeloid leukemia (AML), including the BCL-2 inhibitor venetoclax. Maximizing efficacy of these treatments requires refining patient selection. To this end, we analyzed two recent AML studies profiling the gene expression and ex vivo drug response of primary patient samples. We find that ex vivo samples often exhibit a general sensitivity to (any) drug exposure, independent of drug target. We observe that this "general response across drugs" (GRD) is associated with FLT3-ITD mutations, clinical response to standard induction chemotherapy, and overall survival. Further, incorporating GRD into expression-based regression models trained on one of the studies improved their performance in predicting ex vivo response in the second study, thus signifying its relevance to precision oncology efforts. We find that venetoclax response is independent of GRD but instead show that it is linked to expression of monocyte-associated genes by developing and applying a multi-source Bayesian regression approach. The method shares information across studies to robustly identify biomarkers of drug response and is broadly applicable in integrative analyses.
  • Kolehmainen, Sara; Ylisaukko-Oja, Tero; Jokelainen, Jari; Koivusalo, Mirkka; Jokiranta, T. Sakari; Sipponen, Taina (2021)
    Objectives We set out to determine the reasons for serum vedolizumab (VDZ) trough concentration (TC) measurements in inflammatory bowel disease (IBD) patients and to evaluate treatment modifications after therapeutic drug measurement (TDM). We also evaluated the effect of increased dosing on patients' response to VDZ therapy. Methods We performed a retrospective cohort study of IBD patients who received VDZ therapy at Helsinki University Hospital and whose VDZ levels were measured between June 2014 and December 2018. Results Altogether, 90 patients (32 Crohn's disease and 58 ulcerative colitis) and 141 VDZ TC measurements were included. 24.1% of measurements took place during induction and 75.9% during the maintenance phase. During induction, 64.7% reached the target TC >20 mu g/ml. During maintenance therapy, 82.2% of VDZ TCs were within or exceeded the suggested target range of 5-15 mu g/ml. Reasons for TDM were: secondary nonresponse (44.0%), assessment of adequate VDZ TC (25.5%), primary nonresponse (12.8%), adverse events (6.4%), and other (11.3%). No treatment changes occurred after 60.3% of VDZ measurements. Increased dose frequency was used after 25.5% of VDZ measurements and 33.3% of these patients experienced improvement. Altogether, 31 (34.4%) patients discontinued the therapy due to inadequate treatment response. No anti-vedolizumab antibodies were detected. Conclusions During the maintenance of VDZ therapy, the majority of VDZ TCs were within the suggested range. Measurement of VDZ TC did not lead to any treatment changes in two-thirds of patients. Dose optimization occurred in a quarter of patients and a third of them benefited from it.
  • Nowak, Jessika; Visnovsky, Sandra B.; Pitman, Andrew R.; Cruz, Cristina D.; Palmer, Jon; Fletcher, Graham C.; Flint, Steve (2021)
    Listeria monocytogenes is a ubiquitous foodborne pathogen that results in a high rate of mortality in sensitive and immunocompromised people. Contamination of food with L. monocytogenes is thought to occur during food processing, most often as a result of the pathogen producing a biofilm that persists in the environment and acting as the source for subsequent dispersal of cells onto food. A survey of seafoodprocessing plants in New Zealand identified the persistent strain 15G01, which has a high capacity to form biofilms. In this study, a transposon library of L. monocytogenes 15G01 was screened for mutants with altered biofilm formation, assessed by a crystal violet assay, to identify genes involved in biofilm formation. This screen identified 36 transposants that showed a significant change in biofilm formation compared to the wild type. The insertion sites were in 27 genes, 20 of which led to decreased biofilm formation and seven to an increase. Two insertions were in intergenic regions. Annotation of the genes suggested that they are involved in diverse cellular processes, including stress response, autolysis, transporter systems, and cell wall/membrane synthesis. Analysis of the biofilms produced by the transposants using scanning electron microscopy and fluorescence microscopy showed notable differences in the structure of the biofilms compared to the wild type. In particular, inactivation of uvrB and mltD produced coccoid-shaped cells and elongated cells in long chains, respectively, and the mgtB mutant produced a unique biofilm with a sandwich structure which was reversed to the wild-type level upon magnesium addition. The mltD transposant was successfully complemented with the wild-type gene, whereas the phenotypes were not or only partially restored for the remaining mutants. IMPORTANCE The major source of contamination of food with Listeria monocytogenes is thought to be due to biofilm formation and/or persistence in food-processing plants. By establishing as a biofilm, L. monocytogenes cells become harder to eradicate due to their increased resistance to environmental threats. Understanding the genes involved in biofilm formation and their influence on biofilm structure will help identify new ways to eliminate harmful biofilms in food processing environments. To date, multiple genes have been identified as being involved in biofilm formation by L. monocytogenes; however, the exact mechanism remains unclear. This study identified four genes associated with biofilm formation by a persistent strain. Extensive microscopic analysis illustrated the effect of the disruption of mgtB, clsA, uvrB, and mltD and the influence of magnesium on the biofilm structure. The results strongly suggest an involvement in biofilm formation for the four genes and provide a basis for further studies to analyze gene regulation to assess the specific role of these biofilm-associated genes.
  • Vered, Marilena; Lehtonen, Meri; Hotakainen, Lari; Pirila, Emma; Teppo, Susanna; Nyberg, Pia; Sormunen, Raija; Zlotogorski-Hurvitz, Ayelet; Salo, Tuula; Dayan, Dan (2015)
  • Sioofy-Khojine, Amir-Babak; Lehtonen, Jussi; Nurminen, Noora; Laitinen, Olli H.; Oikarinen, Sami; Huhtala, Heini; Pakkanen, Outi; Ruokoranta, Tanja; Hankaniemi, Minna M.; Toppari, Jorma; Vähä-Mäkilä, Mari; Ilonen, Jorma; Veijola, Riitta; Knip, Mikael; Hyöty, Heikki (2018)
    Aims/hypothesis Islet autoimmunity usually starts with the appearance of autoantibodies against either insulin (IAA) or GAD65 (GADA). This categorises children with preclinical type 1 diabetes into two immune phenotypes, which differ in their genetic background and may have different aetiology. The aim was to study whether Coxsackievirus group B (CVB) infections, which have been linked to the initiation of islet autoimmunity, are associated with either of these two phenotypes in children with HLA-conferred susceptibility to type 1 diabetes. Methods All samples were from children in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study. Individuals are recruited to the DIPP study from the general population of new-born infants who carry defined HLA genotypes associated with susceptibility to type 1 diabetes. Our study cohort included 91 children who developed IAA and 78 children who developed GADA as their first appearing single autoantibody and remained persistently seropositive for islet autoantibodies, along with 181 and 151 individually matched autoantibody negative control children, respectively. Seroconversion to positivity for neutralising antibodies was detected as the surrogate marker of CVB infections in serial follow-up serum samples collected before and at the appearance of islet autoantibodies in each individual. Results CVB1 infections were associated with the appearance of IAA as the first autoantibody (OR 2.4 [95% CI 1.4, 4.2], corrected p = 0.018). CVB5 infection also tended to be associated with the appearance of IAA, however, this did not reach statistical significance (OR 2.3, [0.7, 7.5], p = 0.163); no other CVB types were associated with increased risk of IAA. Children who had signs of a CVB1 infection either alone or prior to infections by other CVBs were at the highest risk for developing IAA (OR 5.3 [95% CI 2.4, 11.7], p <0.001). None of the CVBs were associated with the appearance of GADA. Conclusions/interpretation CVB1 infections may contribute to the initiation of islet autoimmunity being particularly important in the insulin-driven autoimmune process.
  • Booksmythe, Isobel; Gerber, Nina; Ebert, Dieter; Kokko, Hanna (2018)
    Cyclical parthenogenesis presents an interesting challenge for the study of sex allocation, as individuals' allocation decisions involve both the choice between sexual and asexual reproduction, and the choice between sons and daughters. Male production is therefore expected to depend on ecological and evolutionary drivers of overall investment in sex, and those influencing male reproductive value during sexual periods. We manipulated experimental populations, and made repeated observations of natural populations over their growing season, to disentangle effects of population density and the timing of sex from effects of adult sex ratio on sex allocation in cyclically parthenogenetic Daphnia magna. Male production increased with population density, the major ecological driver of sexual reproduction; however, this response was dampened when the population sex ratio was more male-biased. Thus, in line with sex ratio theory, we show that D.magna adjust offspring sex allocation in response to the current population sex ratio.
  • Gerber, Nina; Kokko, Hanna; Ebert, Dieter; Booksmythe, Isobel (2018)
    The timing of sex in facultatively sexual organisms is critical to fitness, due to the differing demographic consequences of sexual versus asexual reproduction. In addition to the costs of sex itself, an association of sex with the production of dormant life stages also influences the optimal use of sex, especially in environments where resting eggs are essential to survive unfavourable conditions. Here we document population dynamics and the occurrence of sexual reproduction in natural populations of Daphnia magna across their growing season. The frequency of sexually reproducing females and males increased with population density and with decreasing asexual clutch sizes. The frequency of sexually reproducing females additionally increased as population growth rates decreased. Consistent with population dynamic models showing that the opportunity cost of sexual reproduction (foregoing contribution to current population growth) diminishes as populations approach carrying capacity, we found that investment in sexual reproduction was highest when asexual population growth was low or negative. Our results support the idea that the timing of sex is linked with periods when the relative cost of sex is reduced due to low potential asexual growth at high population densities. Thus, a combination of ecological and demographic factors affect the optimal timing of sexual reproduction, allowing D. magna to balance the necessity of sex against its costs.
  • Palonen, Pauliina; Lettojarvi, Iiris; Luoranen, Jaana; Ruhanen, Hanna; Rantanen, Marja; Haikonen, Tuuli; Finni, Sanna (2021)
    In the future climate scenario the transient warm spells during winter are predicted to become more frequent and potentially increase the risk of frost damage in perennial horticultural crops. The aim of our study was to examine, whether apple (Males x domestica Borkh.), blackcurrant (Ribes nigrum L.), and raspberry (Rubus idaeus L.) cultivars differing in winter hardiness have a different susceptibility to deacclimation during a warm spell and the ability to reacclimate in response to a subsequent cold period. Shoot samples were collected from commercial orchards in Finland on Feb. 6, 2019. Samples were subjected to a deacclimation treatment (+5 degrees C, 4 d) followed by a reacclimation treatment (-7 degrees C, 7 d). Controlled freezing tests were conducted immediately after sampling, and at the end of deacclimation and reacclimation treatments to determine frost hardiness (FH). FH was most stable in those cultivars that are known to be hardy in the Finnish climate conditions, i.e. 'Pirja' apple, 'Mikael' and `Ojebyn' blackcurrants, and 'Maurin Makea' raspberry. Buds were consistently less hardy than shoots, the difference being largest in blackcurrant, 25 degrees C . The buds of all cultivars, except 'Pirja' apple, deacclimated during four days at +5 degrees C, but only 'Ben Tron' blackcurrant buds were able to reacclimate. The depth of dormancy was determined by forcing the shoot samples in a greenhouse to examine the relationship of the FH stability to the dormancy status in the cultivars. Sixty to 95 % of apple, 98 to 100 % of blackcurrant, and 55 to 67 % of raspberry buds broke during five weeks in forcing. Only the apple cultivars exhibited cultivar differences in the dormancy status in the beginning of February. `Pirja' despite having the most stable FH of the apple cultivars, showed the most complete and fastest bud break in forcing. Consequently, the susceptibility to deacclimation during a warm spell and the ability to reacclimate at subsequent low temperatures were not related to the status of dormancy in these cultivars.
  • Luchkina, Natalia V.; Huupponen, Johanna; Clarke, Vernon R. J.; Coleman, Sarah K.; Keinanen, Kari; Taira, Tomi; Lauri, Sari E. (2014)
  • Calabro, Lorenzo; Bougouin, Wulfran; Cariou, Alain; De Fazio, Chiara; Skrifvars, Markus; Soreide, Eldar; Creteur, Jacques; Kirkegaard, Hans; Legriel, Stephane; Lascarrou, Jean-Baptiste; Megarbane, Bruno; Deye, Nicolas; Taccone, Fabio Silvio (2019)
    Background Although targeted temperature management (TTM) is recommended in comatose survivors after cardiac arrest (CA), the optimal method to deliver TTM remains unknown. We performed a meta-analysis to evaluate the effects of different TTM methods on survival and neurological outcome after adult CA. Methods We searched on the MEDLINE/PubMed database until 22 February 2019 for comparative studies that evaluated at least two different TTM methods in CA patients. Data were extracted independently by two authors. We used the Newcastle-Ottawa Scale and a modified Cochrane ROB tools for assessing the risk of bias of each study. The primary outcome was the occurrence of unfavorable neurological outcome (UO); secondary outcomes included overall mortality. Results Our search identified 6886 studies; 22 studies (n = 8027 patients) were included in the final analysis. When compared to surface cooling, core methods showed a lower probability of UO (OR 0.85 [95% CIs 0.75-0.96]; p = 0.008) but not mortality (OR 0.88 [95% CIs 0.62-1.25]; p = 0.21). No significant heterogeneity was observed among studies. However, these effects were observed in the analyses of non-RCTs. A significant lower probability of both UO and mortality were observed when invasive TTM methods were compared to non-invasive TTM methods and when temperature feedback devices (TFD) were compared to non-TFD methods. These results were significant particularly in non-RCTs. Conclusions Although existing literature is mostly based on retrospective or prospective studies, specific TTM methods (i.e., core, invasive, and with TFD) were associated with a lower probability of poor neurological outcome when compared to other methods in adult CA survivors (CRD42019111021).
  • Rodionov, Andrei; Savolainen, Sarianna; Kirveskari, Erika; Mäkelä, Jyrki P.; Shulga, Anastasia (2020)
    Recovery of lower-limb function after spinal cord injury (SCI) is dependent on the extent of remaining neural transmission in the corticospinal pathway. The aim of this proof-of-concept pilot study was to explore the effects of long-term paired associative stimulation (PAS) on leg muscle strength and walking in people with SCI. Five individuals with traumatic incomplete chronic tetraplegia (>34 months post-injury, motor incomplete, 3 females, mean age 60 years) with no contraindications to transcranial magnetic stimulation (TMS) received PAS to one or both legs for 2 months (28 sessions in total, 5 times a week for the first 2 weeks and 3 times a week thereafter). The participants were evaluated with the Manual Muscle Test (MMT), AIS motor and sensory examination, Modified Asworth Scale (MAS), and the Spinal Cord Independence Measure (SCIM) prior to the intervention, after 1 and 2 months of PAS, and after a 1-month follow-up. The study was registered at (NCT03459885). During the intervention, MMT scores and AIS motor scores increased significantly (p = 0.014 and p = 0.033, respectively). Improvements were stable in follow-up. AIS sensory scores, MAS, and SCIM were not modified significantly. MMT score prior to intervention was a good predictor of changes in walking speed (Radj2 = 0.962). The results of this proof-of-concept pilot study justify a larger trial on the effect of long-term PAS on leg muscle strength and walking in people with chronic incomplete SCI.
  • Sane, Famara; Bertin, Antoine; Sioofy-Khojine, Amir-Babak; Oikarinen, Sami; Alidjinou, Enagnon K.; Veijola, Riitta; Toppari, Jorma; Ilonen, Jorma; Knip, Mikael; Engelmann, Ilka; Hyöty, Heikki; Hober, Didier (2020)
    Abstract Studies in prospective cohorts have suggested that enterovirus infections are associated with the appearance of islet autoantibodies that precede later appearance of type 1 diabetes (T1D). It was shown that in addition to an antibody-mediated anti-coxsackievirus (CV)-B neutralizing activity of serum from patients with T1D, there was also enhancing anti-CV-B activity in vitro. In this study the patterns of enhancing and neutralizing anti-CV activities were analyzed from consecutive serum samples collected from children who were followed from birth until they developed T1D in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study and compared to those in non-diabetic control children. The titers of serum neutralizing activity were analyzed against those CVs which were detected in the stools in these children (CV-B3, CV-B5 or CV-A4) using plaque assay. The enhancing activity of these serum samples was analysed by measuring interferon-alpha (INF-α) production in cultures of peripheral blood mononuclear cells (PBMC) inoculated with a mixture of these viruses and diluted serum. A sustained anti-CV enhancing activity was observed in consecutive serum samples in patients with T1D. The pattern of responses differed between children who developed T1D and control children. In patients, the anti-CV enhancing activity was predominant or even exclusive over the neutralizing activity, whereas in controls the enhancing and neutralizing activities were more balanced or the neutralizing activity was largely predominant. In conclusion, evaluating the anti-enterovirus neutralizing and enhancing activity of serum samples can be useful to investigate further the relationship between enteroviruses and the development of T1D. This article is protected by copyright. All rights reserved.