Articles from BioMed Central


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  • Muilu, Paula; Rantalaiho, Vappu; Kautiainen, Hannu; Virta, Lauri J; Eriksson, Johan G; Puolakka, Kari (BioMed Central, 2020)
    Abstract Background In this retrospective cohort study, we evaluated the drug therapies used for early rheumatoid (RA) and undifferentiated (UA) arthritis patients. Methods From a nationwide register maintained by the Social Insurance Institution, information on sex, date of birth, and date of special medicine reimbursement decision for all new Finnish RA and UA patients between 2011 and 14 were collected, and their DMARD (Disease Modifying Antirheumatic Drug) purchases during the first year after the diagnosis were analyzed. Results A total of 7338 patients with early RA (67.3% female, 68.1% seropositive) and 2433 with early UA (67.8% female) were identified. DMARDs were initiated during the first month after the diagnosis to 92.0% of the patients with seropositive RA, 90.3% with seronegative RA and to 87.7% with UA (p < 0.001). Respectively, 72.1, 63.4, and 42.9% of the patients (p < 0.001) purchased methotrexate; 49.8, 35.9, and 16.0% (p < 0.001) as part of a DMARD combination during the first month. By the end of the first year after the diagnosis, self-injected biologics were purchased by 2.6, 5.3 and 3.1% (p < 0.001) of them. Only 1.4, 2.6 and 3.0% (p < 0.001) of the patients were not receiving any DMARDs. During the first year, 83.4% of the seropositive RA patients had purchased methotrexate, 50.4% sulfasalazine, 72.1% hydroxychloroquine, and 72.6% prednisolone. Conclusions Currently, combination therapy including methotrexate is a common treatment strategy for early seropositive RA in Finland. Despite an easy access to biologics, these drugs are seldom needed during the first year after diagnosis.
  • Hemminki, Otto; dos Santos, João M; Hemminki, Akseli (BioMed Central, 2020)
    Abstract In this review, we discuss the use of oncolytic viruses in cancer immunotherapy treatments in general, with a particular focus on adenoviruses. These serve as a model to elucidate how versatile viruses are, and how they can be used to complement other cancer therapies to gain optimal patient benefits. Historical reports from over a hundred years suggest treatment efficacy and safety with adenovirus and other oncolytic viruses. This is confirmed in more contemporary patient series and multiple clinical trials. Yet, while the first viruses have already been granted approval from several regulatory authorities, room for improvement remains. As good safety and tolerability have been seen, the oncolytic virus field has now moved on to increase efficacy in a wide array of approaches. Adding different immunomodulatory transgenes to the viruses is one strategy gaining momentum. Immunostimulatory molecules can thus be produced at the tumor with reduced systemic side effects. On the other hand, preclinical work suggests additive or synergistic effects with conventional treatments such as radiotherapy and chemotherapy. In addition, the newly introduced checkpoint inhibitors and other immunomodulatory drugs could make perfect companions to oncolytic viruses. Especially tumors that seem not to be recognized by the immune system can be made immunogenic by oncolytic viruses. Logically, the combination with checkpoint inhibitors is being evaluated in ongoing trials. Another promising avenue is modulating the tumor microenvironment with oncolytic viruses to allow T cell therapies to work in solid tumors. Oncolytic viruses could be the next remarkable wave in cancer immunotherapy.
  • Padidela, Raja; Nilsson, Ola; Makitie, Outi; Beck-Nielsen, Signe; Ariceta, Gema; Schnabel, Dirk; Brandi, Maria L; Boot, Annemieke; Levtchenko, Elena; Smyth, Michael; Jandhyala, Ravi; Mughal, Zulf (BioMed Central, 2020)
    Abstract Background X-linked hypophosphataemia (XLH) is a rare, hereditary, progressive and lifelong phosphate wasting disorder characterised by pathological elevations in fibroblast growth factor (FGF) 23 concentration and activity; XLH has an incidence of approximately 1 in 20–25,000 individuals. Excess FGF23 activity leads to increased phosphate excretion in the kidneys – mediated by downregulation of renal tubular phosphate transporters – and reduced phosphate absorption in the intestines – due to impaired vitamin D activation. This results in impaired bone growth and mineralisation, short and disproportionate stature, leg bowing, musculoskeletal pain, spontaneous dental abscesses, rickets, and osteomalacia. The spectrum of manifestations differs between paediatric and adult patients. Those involved in the treatment of this condition face many challenges, including a lack of robust natural history and demographic data. This multicentre, international, rare-disease patient registry (XLH Registry) was established to address the paucity of data in XLH and to help inform future clinical practice. Results The XLH Registry collects standard diagnostic and monitoring practice data, including (where applicable) diagnosis and disease progression history, treatment regimens and family history; the protocol does not mandate any interventions or clinical assessments. The XLH Registry aims to recruit 1200 paediatric and adult patients with XLH over 10 years, and several data analyses and peer-reviewed publications are expected to be generated throughout this period. A post-authorisation safety study for Bburosumab, for which the registry Sponsor is the marketing authorisation holder, will be nested as a sub-study within the XLH Registry via a subsequent protocol amendment. Conclusion The data collected within this rare-disease patient registry will be utilised to synthesise real-world evidence to inform the management of XLH, to improve the quality of life and standard of care of patients living with this rare debilitating disease.
  • Tuominen, Heidi; Al-Samadi, Ahmed; Salo, Tuula; Rautava, Jaana (BioMed Central, 2020)
    Abstract Background This study was designed to investigate the invasion of human papillomavirus (HPV) positive human cervical carcinoma cell lines in human leiomyoma-based extracellular matrices in vitro, and to test the suitability of the model for studying the irradiation effects on the cancer cell invasion. Methods HPV positive cervical carcinoma cell lines SiHa and CaSki, and HPV negative squamous cell carcinoma cell line HSC-3 were used. CaSki cells contain around 600 copies of HPV 16 virus in the genome, whereas SiHa have only 1–2 copies per cell. Cells were analyzed using two different human tumor derived extracellular matrix methods (3D myoma disc model, and Myogel Transwell invasion assay). Cultures were irradiated with 4 Gy. Myoma invasion area and the depth of invasion were measured with ImageJ 1.51j8 software. Statistical analyses were performed with SPSS Statistics (IBM SPSS® Statistics 25). Results All cells invaded through Myogel coated Transwell membranes and within myoma discs. In myoma discs, a difference in the invasion depth (p = 0.0001) but not in invasion area (p = 0.310) between the HPV positive cell lines was seen, since SiHa (less HPV) invaded slightly better than CaSki (more HPV). HSC-3 cells (HPV negative) invaded deepest (p = 0.048) than either of the HPV positive cell line cells. No difference was detected in the invasion area (p = 0.892) between HPV positive and HPV negative cells. The ionized radiation significantly reduced the invasion depth of HSC-3 (p = 0.008), SiHa (p = 0.0001) and CaSki (p = 0.005). No significant effect on the invasion area was detected in any of the cell lines. However, a significant difference was observed between SiHa and CaSki in the reduction of the invasion depth after radiation (p = 0.013) as the reduction was greater with SiHa than CaSki. Conclusions Both solid and gelatinous human leiomyoma-based extracellular matrix models were suitable platforms to study the invasion of HPV positive cervical carcinoma cells in vitro. SiHa cells with less HPV copy number cells invaded slightly better and were slightly more sensitive to irradiation than CaSki cells with high HPV copy number. However, there was no drastic differences between the invasion properties of these carcinoma cells.
  • Lehmonen, Lauri; Jalanko, Mikko; Tarkiainen, Mika; Kaasalainen, Touko; Kuusisto, Johanna; Lauerma, Kirsi; Savolainen, Sauli (BioMed Central, 2020)
    Abstract Background Left ventricle rotation and torsion are fundamental components of myocardial function, and several software packages have been developed for analysis of these components. The purpose of this study was to compare the suitability of two software packages with different technical principles for analysis of rotation and torsion of the left ventricle during systole. Methods A group of hypertrophic cardiomyopathy (HCM) patients (N = 14, age 43 ± 11 years), mutation carriers without hypertrophy (N = 10, age 34 ± 13 years), and healthy relatives (N = 12, age 43 ± 17 years) underwent a cardiovascular magnetic resonance examination, including spatial modulation of magnetization tagging sequences in basal and apical planes of the left ventricle. The tagging images were analyzed offline using a harmonic phase image analysis method with Gabor filtering and a non-rigid registration-based free-form deformation technique. Left-ventricle rotation and torsion scores were obtained from end-diastole to end-systole with both software. Results Analysis was successful in all cases with both software applications. End-systolic torsion values between the study groups were not statistically different with either software. End-systolic apical rotation, end-systolic basal rotation, and end-systolic torsion were consistently higher when analyzed with non-rigid registration than with harmonic phase-based analysis (p <  0.0001). End-systolic rotation and torsion values had significant correlations between the two software (p <  0.0001), most significant in the apical plane. Conclusions When comparing absolute values of rotation and torsion between different individuals, software-specific reference values are required. Harmonic phase flow with Gabor filtering and non-rigid registration-based methods can both be used reliably in the analysis of systolic rotation and torsion patterns of the left ventricle.
  • Duru, Ilhan C; Andreevskaya, Margarita; Laine, Pia; Rode, Tone M; Ylinen, Anne; Løvdal, Trond; Bar, Nadav; Crauwels, Peter; Riedel, Christian U; Bucur, Florentina I; Nicolau, Anca I; Auvinen, Petri (BioMed Central, 2020)
    Abstract Background High pressure processing (HPP; i.e. 100–600 MPa pressure depending on product) is a non-thermal preservation technique adopted by the food industry to decrease significantly foodborne pathogens, including Listeria monocytogenes, from food. However, susceptibility towards pressure differs among diverse strains of L. monocytogenes and it is unclear if this is due to their intrinsic characteristics related to genomic content. Here, we tested the barotolerance of 10 different L. monocytogenes strains, from food and food processing environments and widely used reference strains including clinical isolate, to pressure treatments with 400 and 600 MPa. Genome sequencing and genome comparison of the tested L. monocytogenes strains were performed to investigate the relation between genomic profile and pressure tolerance. Results None of the tested strains were tolerant to 600 MPa. A reduction of more than 5 log10 was observed for all strains after 1 min 600 MPa pressure treatment. L. monocytogenes strain RO15 showed no significant reduction in viable cell counts after 400 MPa for 1 min and was therefore defined as barotolerant. Genome analysis of so far unsequenced L. monocytogenes strain RO15, 2HF33, MB5, AB199, AB120, C7, and RO4 allowed us to compare the gene content of all strains tested. This revealed that the three most pressure tolerant strains had more than one CRISPR system with self-targeting spacers. Furthermore, several anti-CRISPR genes were detected in these strains. Pan-genome analysis showed that 10 prophage genes were significantly associated with the three most barotolerant strains. Conclusions L. monocytogenes strain RO15 was the most pressure tolerant among the selected strains. Genome comparison suggests that there might be a relationship between prophages and pressure tolerance in L. monocytogenes.
  • Tolvi, Morag; Tuominen-Salo, Hanna; Paavola, Mika; Mattila, Kimmo; Aaltonen, Leena-Maija; Lehtonen, Lasse (BioMed Central, 2020)
    Abstract Background While previous studies have evaluated the effect of some patient characteristics (e.g. gender, American Society of Anesthesiologists (ASA) class and comorbidity) on outcome in orthopedic and hand day surgery, more detailed information on anesthesia related factors has previously been lacking. Our goal was to investigate the perioperative factors that affect overstay, readmission and contact after day surgery in order to find certain patient profiles more prone to problemed outcomes after day surgery. Methods We examined orthopedic and hand day surgery at an orthopedic day surgery unit of Helsinki University Hospital. Patient data of all adult orthopedic and hand day surgery patients (n = 542) over a 3-month period (January 1 – March 31, 2015) operated on at the unit were collected retrospectively using the hospital’s surgery database. These data comprised anesthesia and patient records with a follow-up period of 30 days post-operation. Patients under the age of 16 and patients not eligible for day surgery were excluded. Patient records were searched for an outcome of overstay, readmission or contact with the emergency room or policlinic. Pearson chi-square test, Fischer’s exact test and multivariable logistic regression were used to analyze the effect of various perioperative factors on postoperative outcome. Results Various patient and anesthesia related factors were examined for their significance in the outcomes of overstay, readmission or contact. Female gender (p = 0.043), total amount of fentanyl (p = 0.00), use of remifentanil (p = 0.036), other pain medication during procedure (p = 0.005) and administration of antiemetic medication (p = 0.048) emerged as statistically significant on outcome after day surgery. Conclusions Overstay and readmission in orthopedic and hand day surgery were clearly connected with female patients undergoing general anesthesia and needing larger amounts of intraoperative opioids. By favoring local and regional anesthesia, side effects of general anesthesia, as well as recovery time, will decrease.
  • Kyrklund, Kristiina; Sloots, Cornelius E J; de Blaauw, Ivo; Bjørnland, Kristin; Rolle, Udo; Cavalieri, Duccio; Francalanci, Paola; Fusaro, Fabio; Lemli, Annette; Schwarzer, Nicole; Fascetti-Leon, Francesco; Thapar, Nikhil; Johansen, Lars S; Berrebi, Dominique; Hugot, Jean-Pierre; Crétolle, Célia; Brooks, Alice S; Hofstra, Robert M; Wester, Tomas; Pakarinen, Mikko P (BioMed Central, 2020)
    Abstract Background Hirschsprung’s disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management. Aims This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders. Methods Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted. Results Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion. Conclusion In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.
  • Olafsdottir, Steinunn A; Jonsdottir, Helga; Bjartmarz, Ingibjörg; Magnusson, Charlotte; Caltenco, Héctor; Kytö, Mikko; Maye, Laura; McGookin, David; Arnadottir, Solveig A; Hjaltadottir, Ingibjörg; Hafsteinsdottir, Thora B (BioMed Central, 2020)
    Abstract Background Technical applications can promote home-based exercise and physical activity of community-dwelling stroke survivors. Caregivers are often able and willing to assist with home-based exercise and physical activity but lack the knowledge and resources to do so. ActivABLES was established to promote home-based exercise and physical activity among community-dwelling stroke survivors, with support from their caregivers. The aim of our study is to investigate the feasibility of ActivABLES in terms of acceptability, demand, implementation and practicality. Methods A convergent design of mixed methods research in which quantitative results were combined with personal experiences of a four-week use of ActivABLES by community-dwelling stroke survivors with support from their caregivers. Data collection before, during and after the four-week period included the Berg Balance Scale (BBS), Activities-Specific Balance Confidence Scale (ABC), Timed-Up-and-Go (TUG) and Five Times Sit to Stand Test (5xSST) and data from motion detectors. Semi-structured interviews were conducted with stroke survivors and caregivers after the four-week period. Descriptive statistics were used for quantitative data. Qualitative data was analysed with direct content analysis. Themes were identified related to the domains of feasibility: acceptability, demand, implementation and practicality. Data was integrated by examining any (dis)congruence in the quantitative and qualitative findings. Results Ten stroke survivors aged 55–79 years participated with their informal caregivers. Functional improvements were shown in BBS (+ 2.5), ABC (+ 0.9), TUG (− 4.2) and 5xSST (− 2.7). More physical activity was detected with motion detectors (stand up/sit down + 2, number of steps + 227, standing + 0.3 h, hours sitting/lying − 0.3 h). The qualitative interviews identified themes for each feasibility domain: (i) acceptability: appreciation, functional improvements, self-initiated activities and expressed potential for future stroke survivors; (2) demand: reported use, interest in further use and need for follow-up; (3) implementation: importance of feedback, variety of exercises and progression of exercises and (4) practicality: need for support and technical problems. The quantitative and qualitative findings converged well with each other and supported the feasibility of ActivABLES. Conclusions ActivABLES is feasible and can be a good asset for stroke survivors with slight or moderate disability to use in their homes. Further studies are needed with larger samples.
  • Paalanen, Laura; Reinikainen, Jaakko; Härkänen, Tommi; Mattila, Tiina; Laatikainen, Tiina; Jousilahti, Pekka; Tolonen, Hanna (BioMed Central, 2020)
    Abstract Background The disability-adjusted life years (DALYs) summarize the burden of years of life lost (YLL) due to premature mortality and years lost due to disability (YLD). Our aim was to estimate the burden of ischemic heart disease (IHD) and chronic obstructive pulmonary disease (COPD) in Finland in 2012, and to examine, how much the YLD are affected by the use of different data sources. Methods The YLL were calculated using mortality data for the Finnish 25–74-year-old population in 2012. The YLD were calculated using data from the FINRISK 2012 survey (3041 males, 3383 females aged 25–74 years) and then directly adjusted to the corresponding population. Different administrative registers on 1) hospital inpatient episodes and specialist outpatient visits, 2) entitlement to specially reimbursed medicines, and 3) purchases of prescribed medicines were used for estimation of the YLD in addition to self-reported data. The DALYs were calculated without age-weighting. Results The YLL for IHD were 37.5 for males and 9.1 for females per 1000 population among 25–74-year-old people in Finland in 2012. The YLD for IHD varied markedly depending on which data sources were used. All data sources combined, the YLD per 1000 were 5.3 for males and 2.5 for females resulting in estimated 42.8 and 11.6 DALYs per 1000 due to IHD among males and females, respectively. For COPD, the YLL were 4.7 for males and 2.0 for females per 1000. Also for COPD, the YLD varied markedly depending on data sources used. The YLD per 1000 based on all data sources combined were 2.0 for males and 1.6 for females. As a result, estimated 6.7 and 3.6 DALYs per 1000 were due to COPD among males and females, respectively. Conclusions Especially for COPD, all mild disease cases could probably not be identified from the included registers. Thereby, including survey data improved the coverage of the data. The YLD of IHD and COPD varied markedly between the data sources used in the calculations. However, as YLL constituted a major part of DALYs for these diseases, the variation in YLD did not lead to substantial variation in DALYs.
  • Kolosowska, Natalia; Gotkiewicz, Maria; Dhungana, Hiramani; Giudice, Luca; Giugno, Rosalba; Box, Daphne; Huuskonen, Mikko T; Korhonen, Paula; Scoyni, Flavia; Kanninen, Katja M; Ylä-Herttuala, Seppo; Turunen, Tiia A; Turunen, Mikko P; Koistinaho, Jari; Malm, Tarja (BioMed Central, 2020)
    Abstract Background Ischemic stroke is a devastating disease without a cure. The available treatments for ischemic stroke, thrombolysis by tissue plasminogen activator, and thrombectomy are suitable only to a fraction of patients and thus novel therapeutic approaches are urgently needed. The neuroinflammatory responses elicited secondary to the ischemic attack further aggravate the stroke-induced neuronal damage. It has been demonstrated that these responses are regulated at the level of non-coding RNAs, especially miRNAs. Methods We utilized lentiviral vectors to overexpress miR-669c in BV2 microglial cells in order to modulate their polarization. To detect whether the modulation of microglial activation by miR-669c provides protection in a mouse model of transient focal ischemic stroke, miR-669c overexpression was driven by a lentiviral vector injected into the striatum prior to induction of ischemic stroke. Results Here, we demonstrate that miR-669c-3p, a member of chromosome 2 miRNA cluster (C2MC), is induced upon hypoxic and excitotoxic conditions in vitro and in two different in vivo models of stroke. Rather than directly regulating the neuronal survival in vitro, miR-669c is capable of attenuating the microglial proinflammatory activation in vitro and inducing the expression of microglial alternative activation markers arginase 1 (Arg1), chitinase-like 3 (Ym1), and peroxisome proliferator-activated receptor gamma (PPAR-γ). Intracerebral overexpression of miR-669c significantly decreased the ischemia-induced cell death and ameliorated the stroke-induced neurological deficits both at 1 and 3 days post injury (dpi). Albeit miR-669c overexpression failed to alter the overall Iba1 protein immunoreactivity, it significantly elevated Arg1 levels in the ischemic brain and increased colocalization of Arg1 and Iba1. Moreover, miR-669c overexpression under cerebral ischemia influenced several morphological characteristics of Iba1 positive cells. We further demonstrate the myeloid differentiation primary response gene 88 (MyD88) transcript as a direct target for miR-669c-3p in vitro and show reduced levels of MyD88 in miR-669c overexpressing ischemic brains in vivo. Conclusions Collectively, our data provide the evidence that miR-669c-3p is protective in a mouse model of ischemic stroke through enhancement of the alternative microglial/macrophage activation and inhibition of MyD88 signaling. Our results accentuate the importance of controlling miRNA-regulated responses for the therapeutic benefit in conditions of stroke and neuroinflammation.
  • Gilchrist, James J; Uyoga, Sophie; Pirinen, Matti; Rautanen, Anna; Mwarumba, Salim; Njuguna, Patricia; Mturi, Neema; Hill, Adrian V S; Scott, J. A G; Williams, Thomas N (BioMed Central, 2020)
    Abstract Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency state in humans. The clinical phenotype is variable and includes asymptomatic individuals, episodic hemolysis induced by oxidative stress, and chronic hemolysis. G6PD deficiency is common in malaria-endemic regions, an observation hypothesized to be due to balancing selection at the G6PD locus driven by malaria. G6PD deficiency increases risk of severe malarial anemia, a key determinant of invasive bacterial disease in malaria-endemic settings. The pneumococcus is a leading cause of invasive bacterial infection and death in African children. The effect of G6PD deficiency on risk of pneumococcal disease is undefined. We hypothesized that G6PD deficiency increases pneumococcal disease risk and that this effect is dependent upon malaria. Methods We performed a genetic case-control study of pneumococcal bacteremia in Kenyan children stratified across a period of falling malaria transmission between 1998 and 2010. Results Four hundred twenty-nine Kenyan children with pneumococcal bacteremia and 2677 control children were included in the study. Among control children, G6PD deficiency, secondary to the rs1050828 G>A mutation, was common, with 11.2% (n = 301 of 2677) being hemi- or homozygotes and 33.3% (n = 442 of 1329) of girls being heterozygotes. We found that G6PD deficiency increased the risk of pneumococcal bacteremia, but only during a period of high malaria transmission (P = 0.014; OR 2.33, 95% CI 1.19–4.57). We estimate that the population attributable fraction of G6PD deficiency on risk of pneumococcal bacteremia in areas under high malaria transmission is 0.129. Conclusions Our data demonstrate that G6PD deficiency increases risk of pneumococcal bacteremia in a manner dependent on malaria. At the population level, the impact of G6PD deficiency on invasive pneumococcal disease risk in malaria-endemic regions is substantial. Our study highlights the infection-associated morbidity and mortality conferred by G6PD deficiency in malaria-endemic settings and adds to our understanding of the potential indirect health benefits of improved malaria control.
  • Unemo, Magnus; Hansen, Marit; Hadad, Ronza; Puolakkainen, Mirja; Westh, Henrik; Rantakokko-Jalava, Kaisu; Thilesen, Carina; Cole, Michelle J; Boiko, Iryna; Lan, Pham T; Golparian, Daniel; Ito, Shin; Sundqvist, Martin (BioMed Central, 2020)
    Abstract Background Four new variants of Chlamydia trachomatis (nvCTs), detected in several countries, cause false-negative or equivocal results using the Aptima Combo 2 assay (AC2; Hologic). We evaluated the clinical sensitivity and specificity, as well as the analytical inclusivity and exclusivity of the updated AC2 for the detection of CT and Neisseria gonorrhoeae (NG) on the automated Panther system (Hologic). Methods We examined 1004 clinical AC2 samples and 225 analytical samples spiked with phenotypically and/or genetically diverse NG and CT strains, and other potentially cross-reacting microbial species. The clinical AC2 samples included CT wild type (WT)-positive (n = 488), all four described AC2 diagnostic-escape nvCTs (n = 170), NG-positive (n = 214), and CT/NG-negative (n = 202) specimens. Results All nvCT-positive samples (100%) and 486 (99.6%) of the CT WT-positive samples were positive in the updated AC2. All NG-positive, CT/NG-negative, Trichomonas vaginalis (TV)-positive, bacterial vaginosis-positive, and Candida-positive AC2 specimens gave correct results. The clinical sensitivity and specificity of the updated AC2 for CT detection was 99.7 and 100%, respectively, and for NG detection was 100% for both. Examining spiked samples, the analytical inclusivity and exclusivity were 100%, i.e., in clinically relevant concentrations of spiked microbe. Conclusions The updated AC2, including two CT targets and one NG target, showed a high sensitivity, specificity, inclusivity and exclusivity for the detection of CT WT, nvCTs, and NG. The updated AC2 on the fully automated Panther system offers a simple, rapid, high-throughput, sensitive, and specific diagnosis of CT and NG, which can easily be combined with detection of Mycoplasma genitalium and TV.
  • Picazo, Félix; Vilmi, Annika; Aalto, Juha; Soininen, Janne; Casamayor, Emilio O; Liu, Yongqin; Wu, Qinglong; Ren, Lijuan; Zhou, Jizhong; Shen, Ji; Wang, Jianjun (BioMed Central, 2020)
    Abstract Background Understanding the large-scale patterns of microbial functional diversity is essential for anticipating climate change impacts on ecosystems worldwide. However, studies of functional biogeography remain scarce for microorganisms, especially in freshwater ecosystems. Here we study 15,289 functional genes of stream biofilm microbes along three elevational gradients in Norway, Spain and China. Results We find that alpha diversity declines towards high elevations and assemblage composition shows increasing turnover with greater elevational distances. These elevational patterns are highly consistent across mountains, kingdoms and functional categories and exhibit the strongest trends in China due to its largest environmental gradients. Across mountains, functional gene assemblages differ in alpha diversity and composition between the mountains in Europe and Asia. Climate, such as mean temperature of the warmest quarter or mean precipitation of the coldest quarter, is the best predictor of alpha diversity and assemblage composition at both mountain and continental scales, with local non-climatic predictors gaining more importance at mountain scale. Under future climate, we project substantial variations in alpha diversity and assemblage composition across the Eurasian river network, primarily occurring in northern and central regions, respectively. Conclusions We conclude that climate controls microbial functional gene diversity in streams at large spatial scales; therefore, the underlying ecosystem processes are highly sensitive to climate variations, especially at high latitudes. This biogeographical framework for microbial functional diversity serves as a baseline to anticipate ecosystem responses and biogeochemical feedback to ongoing climate change. Video Abstract
  • Yamaguchi, Kakuhiro; Iwamoto, Hiroshi; Mazur, Witold; Miura, Shinichiro; Sakamoto, Shinjiro; Horimasu, Yasushi; Masuda, Takeshi; Miyamoto, Shintaro; Nakashima, Taku; Ohshimo, Shinichiro; Fujitaka, Kazunori; Hamada, Hironobu; Hattori, Noboru (BioMed Central, 2020)
    Abstract Background The endogenous secretory receptor for advanced glycation end products (esRAGE) is a soluble isoform produced by alternative splicing of the RAGE gene. The isoform has anti-inflammatory properties due to its inhibition of the RAGE/ligand interaction and is reduced in the lung tissue of patients with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the association of esRAGE serum and bronchoalveolar lavage fluid (BALF) levels with progression of IPF. Methods This study included 79 IPF patients and 90 healthy controls. IPF and control serum esRAGE levels were compared, and the correlation between serum and BALF esRAGE levels was analyzed in 57 IPF patient samples. We also investigated the relationship of esRAGE serum and BALF levels with prognoses and lung function parameters in patients with IPF. Results Serum esRAGE levels in IPF patients were significantly lower than those in healthy controls (162.0 ± 102.4 ng/ml and 200.7 ± 107.3 ng/ml, p = 0.009), although the baseline characteristics of age and smoking history were not matched. Serum levels of esRAGE were correlated with BALF esRAGE levels (rs = 0.317). The BALF esRAGE levels were also correlated with diffusion capacity for carbon monoxide (rs = 0.406). A Kaplan-Meier curve analysis and univariate/multivariate Cox hazard proportion analysis revealed that lower levels of esRAGE in blood and BALF were significantly associated with poorer prognoses in patients with IPF. Conclusions Decreased esRAGE levels in BALF and blood were associated with poor prognoses in patients with IPF. These results suggest that esRAGE could be related to the pathophysiology of IPF and serum esRAGE could be a potential prognostic marker of IPF.
  • Yang, Bin; Cui, Leilei; Perez-Enciso, Miguel; Traspov, Aleksei; Crooijmans, Richard P M A; Zinovieva, Natalia; Schook, Lawrence B; Archibald, Alan; Gatphayak, Kesinee; Knorr, Christophe; Triantafyllidis, Alex; Alexandri, Panoraia; Semiadi, Gono; Hanotte, Olivier; Dias, Deodália; Dovč, Peter; Uimari, Pekka; Iacolina, Laura; Scandura, Massimo; Groenen, Martien A M; Huang, Lusheng; Megens, Hendrik-Jan (BioMed Central, 2020)
    An amendment to this paper has been published and can be accessed via the original article.
  • Eklund, Marjut; Aaltonen, Kirsi; Sironen, Tarja; Raunio-Saarnisto, Mirja; Grönthal, Thomas; Nordgren, Heli; Pitkälä, Anna; Vapalahti, Olli; Rantala, Merja (BioMed Central, 2020)
    Abstract Background Streptococcus halichoeri infections have been reported in grey seals, a European badger, a Stellar sea lion and humans, but its presence in companion and fur animals is unknown. Since 2010, S. halichoeri-like bacteria (SHL) have been isolated from fur animals and dogs in Finland. Our aim was to retrospectively investigate laboratory records for SHL from canine and fur animal infections, characterize the isolates and compare their genetic relatedness in relation to three reference strains: CCUG 48324T, originating from a grey seal, and strains 67100 and 61265, originally isolated from humans. Results A total of 138 and 36 SHLs from canine and fur animal infections, respectively, were identified in the laboratory records. SHL was commonly associated with skin infections, but rarely as the only species. A set of 49 canine and 23 fur animal SHLs were further characterized. MALDI-TOF confirmed them as being S. halichoeri. The growth characteristics were consistent with the original findings, but isolates were catalase positive. In total, 17 distinct API 20 Strep patterns were recorded among all 75 isolates tested, of which pattern 5563100 was the most common (n = 30). Antimicrobial resistance to erythromycin and clindamycin was common in canine isolates, but rare in fur animal isolates. Three clusters were observed by PFGE, and 16S rRNA sequencing revealed 98.1–100% similarities with the human strains and 98.1–99.5% with the seal strain. A phylogenetic tree of concatenated 16S rRNA and rpoB revealed closely related isolates with two clades. Fifteen canine isolates were identical to the human strains based on concatenated 16S rRNA and rpoB sequencing. Conclusions Streptococcus halichoeri appears to be quite a common bacterial species in the skin of dogs and fur animals. The clinical significance of S. halichoeri is uncertain, as it was rarely isolated as a monoculture. No apparent temporal or spatial clustering was detected, but isolates from different sources were genetically very similar. Because many canine isolates were genetically similar to the human reference strains, transmission between dogs and humans may be possible. WGS sequencing of strains from different sources is needed to further investigate the epidemiology and virulence of S. halichoeri.
  • Metso, Leena; Nyrhinen, Kirsi-Maaria; Bister, Ville; Sandelin, Jerker; Harilainen, Arsi (BioMed Central, 2020)
    Abstract Background A femoral bone tunnel in ACL reconstruction can be constructed from the outside in or from the inside out. When doing it inside out, the approach can be via the anteromedial (AM) portal or through the tibial bone tunnel. It has been suggested that better results might be expected by doing it anteromedially. Clinical results after femoral tunnel drilling via the AM or transtibial (TT) techniques in reconstruction of anterior cruciate ligament (ACL) are presented. Methods Three hundred patients with ACL injuries were chosen for this study from previously collected data on ACL reconstructions. They were divided into two groups: 150 patients treated with AM drilling and 150 treated with TT drilling. In the AM group, the reconstructions were performed using a semitendinosus graft with the Tape Locking Screw (TLS™) technique (n = 87) or Retrobutton™ femoral and BioScrew™ tibial fixation with a semitendinosus-gracilis graft (n = 63). In the TT group, the fixation method used was Rigidfix™ femoral and Intrafix tibial fixation with a semitendinosus-gracilis graft. The evaluation methods were clinical examination, knee scores (Lysholm, Tegner and IKDC) and instrumented laxity measurements (KT-2000™). Our aim was to evaluate if there was better rotational stability and therefore better clinical results when using AM drilling compared to TT drilling. Results After excluding revision ACL reconstructions, there were 132 patients in the AM group and 133 in the TT group for evaluation. At the 2-year follow-up, there were 60 patients in the AM group (45.5%) and 58 in the TT group (43.6%). There were no statistically significant differences between the groups in any of the evaluation methods used. Conclusion Both drilling techniques resulted in improved patient performance and satisfaction. We found no data supporting the hypothesis that the AM drilling technique provides better rotational stability to the knee. Trial registration ISRCTN registry with study ID ISRCTN16407730. Retrospectively registered Jan 9th 2020.
  • Li, Jing; Zhang, Xiaoyue; Xiao, Lin; Liu, Ke; Li, Yue; Zhang, Ziwei; Chen, Qiang; Ao, Xiaolin; Liao, Decong; Gu, Yunfu; Ma, Menggen; Yu, Xiumei; Xiang, Quanju; Chen, Ji; Zhang, Xiaoping; Yang, Tao; Penttinen, Petri; Zhao, Ke (BioMed Central, 2020)
    Abstract Background Earthen sites are immobile cultural relics and an important part of cultural heritage with historical, artistic and scientific values. The deterioration of features in earthen sites result in permanent loss of cultural information, causing immeasurable damage to the study of history and culture. Most research on the deterioration of earthen sites has concentrated on physicochemical factors, and information on microbial communities in earthen sites and their relationship with the earthen site deterioration is scarce. We used high-throughput sequencing to analyze bacterial and fungal communities in soils from earthen walls with different degree of deterioration at Jinsha earthen site to characterize the microbial communities and their correlation with environmental factors, and to compare microbial community structures and the relative abundances of individual taxa associated with different degree of deterioration for identifying possible marker taxa. Results The relative abundances of Proteobacteria and Firmicutes were higher and that of Actinobacteria lower with higher degree of deterioration. At the genus level, the relative abundances of Rubrobacter were highest in all sample groups except in the most deteriorated samples where that of Bacteroides was highest. The relative abundance of the yeast genus Candida was highest in the severely deteriorated sample group. The bacterial phylum Bacteroidetes and genus Bacteroides, and fungal class Saccharomycetes that includes Candida sp. were specific for the most deteriorated samples. For both bacteria and fungi, the differences in community composition were associated with differences in EC, moisture, pH, and the concentrations of NH4+, K+, Mg2+, Ca2+ and SO42−. Conclusion The microbial communities in soil with different degree of deterioration were distinctly different, and deterioration was accompanied with bigger changes in the bacterial than in the fungal community. In addition, the deteriorated soil contained higher concentrations of soluble salts. Potentially, the accumulation of Bacteroides and Candida plays an important role in the deterioration of earthen features. Further work is needed to conclude whether controlling the growth of the bacteria and fungi with high relative abundances in the deteriorated samples can be applied to alleviate deterioration.
  • Heikkala, Eveliina; Ala-Mursula, Leena; Taimela, Simo; Paananen, Markus; Vaaramo, Eeva; Auvinen, Juha; Karppinen, Jaro (BioMed Central, 2020)
    Abstract Background The relevance of health-related behaviors to exclusion from the labor market in early adulthood remains poorly studied in relation to the magnitude of the problem. We explored whether adolescents’ accumulated unhealthy behaviors and psychosocial problems are associated with later labor market exclusion, and whether multisite musculoskeletal pain (MMSP) impacts these relations. Methods We gathered questionnaire data on unhealthy behaviors and psychosocial problems and MMSP among adolescents aged 15 to 16 belonging to the Northern Finland Birth Cohort 1986. The findings were combined with registry data on unemployment, employment and permanent work disability during a five-year follow-up between the ages of 25 and 29 (n = 6692). In the statistical modeling we used education, family leave and socioeconomic status of childhood family as potential confounders, as well as latent class and logistic regression analyses. Results The Externalizing behavior cluster associated with over one year of unemployment (RR 1.64, CI 1.25–2.14) and permanent work disability (OR 2.49, CI 1.07–5.78) in the follow-up among the men. The Sedentary cluster also associated with over one year (RR 1.41, CI 1.13–1.75) and under one year of unemployment (RR 1.25, CI 1.02–1.52) and no employment days (RR 1.93, CI 1.26–2.95) among the men. Obese male participants were at risk of over one year of unemployment (RR 1.50, CI 1.08–2.09) and no employment days (RR 1.93, CI 1.07–3.50). Among the women, the Multiple risk behavior cluster related significantly to over one year of unemployment (RR 1.77, CI 1.37–2.28). MMSP had no influence on the associations. Conclusions Unhealthy behavior patterns and psychosocial problems in adolescence have long-term consequences for exclusion from the labor market in early adulthood, especially among men. Simultaneously supporting psychological well-being and healthy behaviors in adolescence may reduce labor market inclusion difficulties in the early phase of working life.

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