Browsing by Subject "screening"

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  • Lähteenmäki, Hanna; Umeizudike, Kehinde A.; Heikkinen, Anna Maria; Räisänen, Ismo T.; Rathnayake, Nilminie; Johannsen, Gunnar; Tervahartiala, Taina; Nwhator, Solomon O.; Sorsa, Timo (2020)
    This communication article addresses currently available rapid non-invasive methods to screen and detect periodontitis and dental peri-implantitis. In this regard, oral fluid biomarkers have been researched extensively but self-reported oral health (SROH)-questionnaires have also been developed. Both alternatives may offer a quick and easy way to screen and detect diseased patients. Active matrix metalloproteinase (aMMP-8) is one of the most validated biomarkers for screening and detecting periodontal breakdown related to periodontitis and peri-implantitis and monitoring their treatment effects revealing successful, less- and non-successful treatment results. Currently available aMMP-8 lateral-flow technologies allow this kind of analysis, as demonstrated here, to be conducted quantitatively online and real-time as point-of-care/chairside testing in dental and even medical care settings. In this study, an aMMP-8 peri-implant sulcular fluid point-of-care-test diagnosed peri-implantitis and healthy implants far more accurately than bleeding-on-probing or the other biomarkers, such as polymorphonuclear (PMN)/neutrophil elastase, myeloperoxidase and MMP-9. Although, SROH-questionnaires allow screening in similar settings but they lack the information about the current disease activity of periodontitis and peri-implantitis, which is of essential value in periodontal diagnostics and treatment monitoring. Thus, both methods can be considered as adjunct methods for periodontitis and peri-implant diagnostics, but the value of oral fluid biomarkers analysis does not seem to be substitutable.
  • Louvanto, Karolina; Eriksson, Tiina; Gray, Penelope; Apter, Dan; Baussano, Iacopo; Bly, Anne; Harjula, Katja; Heikkila, Kaisa; Hokkanen, Mari; Huhtinen, Leila; Ikonen, Marja; Karttunen, Heidi; Nummela, Mervi; Soderlund-Strand, Anna; Veivo, Ulla; Dillner, Joakim; Elfstöm, Miriam; Nieminen, Pekka; Lehtinen, Matti (2020)
    Less frequent cervical cancer screening in human papillomavirus (HPV) vaccinated birth cohorts could produce considerable savings without increasing cervical cancer incidence and loss of life-years. We report here the baseline findings and interim results of safety and accuracy of infrequent screening among HPV16/18 vaccinated females. The entire 1992-1994 birth-cohorts (30,139 females) were invited to a community-randomized HPV16/18-vaccination trial. A total of 9,482 female trial participants received HPV16/18-vaccination in 2007-2009 at age of 13-15. At age 22, 4,273 (45%) of these females consented to attend a randomized trial on frequent (ages 22/25/28; Arm 1: 2,073 females) vs. infrequent screening (age 28; Arm 2: 2,200 females) in 2014-2017. Females (1,329), who had got HPV16/18 vaccination at age 18 comprised the safety Arm 3. Baseline prevalence and incidence of HPV16/18 and other high-risk HPV types were: 0.5% (53/1,000 follow-up years, 10(4)) and 25% (2,530/10(4)) in the frequently screened Arm 1; 0.2% (23/10(4)) and 24% (2,413/10(4)) in the infrequently screened Arm 2; and 3.1% (304/10(4)) and 23% (2,284/10(4)) in the safety Arm 3. Corresponding prevalence of HSIL/ASC-H and of any abnormal cytological findings were: 0.3 and 4.2% (Arm 1), 0.4 and 5.3% (Arm 2) and 0.3 and 4.7% (Arm 3). Equally rare HSIL/CIN3 findings in the infrequently screened safety Arm A3 (0.4%) and in the frequently screened Arm 1 (0.4%) indicate no safety concerns on infrequent screening despite the up to 10 times higher HPV16/18 baseline prevalence and incidence in the former.
  • Backman, Nina (Helsingfors universitet, 2011)
    Screening of drugs of abuse has to combine sensitivity, selectivity and repeatability. The conventional screening methods include immunoassay screening followed by a more sensitive confirmation method. The aim of the study was to develop a simple, yet sensitive sample preparation method for screening of benzodiazepines and amphetamine derivatives in urine samples with silicon micropillar array electrospray ionization chip (µPESI) coupled to mass spectrometric analysis. Another aim was to evaluate the suitability of µPESI in biological sample analysis. Ideally, the developed method would provide an alternative to immunoassay screening method in forensic urine analysis. The sample preparation methods were separately optimized for benzodiazepines and amphetamine derivatives. Methods used included solid- phase extraction with Oasis HLB cartridge and C18-phase containing ZipTip®-pipette tip, liquid-liquid extraction, and dilution and filtering without prior extraction. Optimization focused, however, on ZipTip®-extraction. The compounds were spiked in blank urine to their cut-off levels, 200 ng/ml for benzodiazepines and 300 ng/ml for amphetamine derivatives. For benzodiazepines, every extraction phase was optimized. The sample pH was adjusted to 5, the ZipTip® phase was conditioned with acetonitrile and washed with a mixture of water (pH 5) and acetonitrile (10 % v/v) and the sample was eluted with a mixture of acetonitrile, formic acid and water (95:1:4 v/v/v). For amphetamine derivatives, pH values of sample and solvents were optimized. The sample pH was adjusted to 10, the ZipTip® phase was conditioned with a mixture of water and ammoniumbicarbonate (pH 10, 1:1 v/v), washed with a mixture of water and acetonitrile (1:5 v/v) and the sample was eluted with methanol. The optimized methods were tested with authentic urine samples obtained from Yhtyneet Medix Laboratories and compared to the results of quantitative GC/MS analysis. Benzodiazepine samples were hydrolyzed prior to extraction to improve recovery. All samples were measured with Q-TOF Micro apparatus and hydrolyzed benzodiazepine samples additionally with microTOF apparatus in Yhtyneet Medix Laboratories. Based on the results the developed method needs more optimization to function properly. The main problems were lack of reproducibility and poor sample ionization. Manual sample preparation and adding to the chip sample introduction spot increased variation. Authentic benzodiazepine samples gave false negative and authentic amphetamine derivative samples false positive results. False negatives may be due to the lack of sensitivity and false positives due to the contamination of sample cone, chips or solvents.
  • Leppänen, Mari; Parkkari, Jari; Vasankari, Tommi; Äyrämo, Sami; Kulmala, Juha-Pekka; Krosshaug, Tron; Kannus, Pekka; Pasanen, Kati (2021)
    Background: Studies investigating biomechanical risk factors for knee injuries in sport-specific tasks are needed. Purpose: To investigate the association between change of direction (COD) biomechanics in a 180-degree pivot turn and knee injury risk among youth team sport players. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 258 female and male basketball and floorball players (age range, 12-21 years) participated in the baseline COD test and follow-up. Complete data were obtained from 489 player-legs. Injuries, practice, and game exposure were registered for 12 months. The COD test consisted of a quick ball pass before and after a high-speed 180-degree pivot turn on the force plates. The following variables were analyzed: peak vertical ground-reaction force (N/kg); peak trunk lateral flexion angle (degree); peak knee flexion angle (degree); peak knee valgus angle (degree); peak knee flexion moment (N.m/kg); peak knee abduction moment (N.m/kg); and peak knee internal and external rotation moments (N.m/kg). Legs were analyzed separately and the mean of 3 trials was used in the analysis. Main outcome measure was a new acute noncontact knee injury. Results: A total of 18 new noncontact knee injuries were registered (0.3 injuries/1000 hours of exposure). Female players sustained 14 knee injuries and male players 4. A higher rate of knee injuries was observed in female players compared with male players (incidence rate ratio, 6.2; 95% CI, 2.1-21.7). Of all knee injuries, 8 were anterior cruciate ligament (ACL) injuries, all in female players. Female players displayed significantly larger peak knee valgus angles compared with male players (mean for female and male players, respectively: 13.9 degrees +/- 9.4 degrees and 2.0 degrees +/- 8.5 degrees). No significant associations between biomechanical variables and knee injury risk were found. Conclusion: Female players were at increased risk of knee and ACL injury compared with male players. Female players performed the 180-degree pivot turn with significantly larger knee valgus compared with male players. However, none of the investigated variables was associated with knee injury risk in youth basketball and floorball players.
  • Kiviniemi, Eero A. (Helsingin yliopisto, 2018)
    Microbial cellulases, e.g. cellobiohydrolases, are able to degrade cellulose and lignocellulosic biomass to smaller glucose-containing monomers and oligomers. Cellulases are often multi-domain enzymes comprised of different protein domains (i.e. modules), which have different functions. The main two components, which often appear in cellulases, are the cellulose-binding module (CBM) and the catalytic domain. The CBMs bind to cellulose, bringing the catalytic domains close to their substrate and increasing the amount of enzymes on the substrate surface. The catalytic domain performs the cleavage of the substrate, e.g. in the case of cellobiohydrolases hydrolyses or “cuts” the crystalline cellulose chain into smaller soluble saccharides, mainly cellobiose. Unlike aerobic fungi, which utilize free extracellular enzymes to break down cellulose, anaerobic microbes often use a different kind of strategy. Their cellulases are organized and bound to the cell surface in a macromolecular protein complex, the cellulosome. The core of the cellulosome is formed of a scaffolding protein (the scaffoldin) consisting mainly of multiple consecutive cohesin domains, into which the catalytic subunits of enzymes attach via a dockerin domain. This creates a protein complex with multiple different catalytic domains and activities arranged in close proximity to each other. Dockerins and cohesins are known to bind each other with one of the strongest receptor-ligand -pair forces known to nature. Dockerin containing fusion proteins have also been successfully combined in vitro with proteins containing their natural counterparts, cohesins, to create functional multiprotein complexes. In this Master’s thesis work the goal was to 1) produce fusion proteins in which different CBMs were connected to dockerin domains, 2) combine these fusions with cohesin-catalytic domain fusion proteins to create stable CBM and catalytic domain containing enzyme complexes, 3) to characterize these enzyme complexes in respect of their thermostability and cellulose hydrolysis capacity and 4) to ultimately create a robust and fast domain shuffling method for multi-domain cellobiohydrolases (CBH) to facilitate their faster screening. The hypothesis of the experiments was that different CBMs fused with a dockerin domain and the cellobiohydrolase catalytic domain fused with a cohesin domain could be produced separately and then be combined to produce a functional two-domain enzyme with a dockerin-cohesin “linker” in between. In this way time and work could be saved because not every different CBM- catalytic domain -pair would have to be cloned and produced separately. Several CBM-dockerin fusion proteins (in which the CBM were of fungal or bacterial origin) were tested for expression in heterologous hosts, either in Saccharomyces cerevisiae or Escherichia coli. The purified proteins were combined with a fungal glycoside hydrolase family 7 (GH7) cellobiohydrolase-cohesin fusion protein produced in S. cerevisiae. The characterization of the catalytic domain-CBM -complexes formed through cohesin-dockerin interaction included thermostability measurements using circular dichroism and activity assays using soluble and insoluble cellulosic substrate. The results were compared to enzyme controls comprising of the same CBM and catalytic domain connected by a simple peptide linker. The results showed that the cohesin-dockerin –linked cellobiohydrolase complex performed in the cellulose hydrolysis studies in a similar manner as the directly linked enzyme controls at temperature of 50˚C and 60 ˚C. At temperatures of 70 ˚C the complex did not perform as well as the control enzymes, apparently due to the instability of the dockerin-cohesin interaction. The thermostability measurements of the enzymes, together with the previously published data supported the hydrolysis results and this hypothesis. The future work should be aimed at enhancing the thermostability of the cohesin-dockerin interaction as well as on verifying the results on different cellulase fusion complexes.
  • Vesala, Timo (2002)
    Our study examines implications of banking sector competition on economic development in an endogenous growth model, where the role of business creation is emphasised as a driving force. Production of information on potential investment projects by exerting screening is identified as a key function of viable banking sector. Assuming perfect screening technology, we derive the anticipated result that intensity of screening is adversely affected by increasing competition in banking sector. As a novelty, we also discuss a case where the assumption of perfect screening is relaxed, and introduce an option to liquidate unprofitable projects in an interim stage of financing relationship. It will be shown that screening activity may actually rise along with intensified competition, because banks start to substitute imperfect screening for liquidation as selection mechanism. Regarding the linkage to real sector, monopolistic competition tends to cause inefficiencies dampening the fraction of 'productive finance' in financial intermediation, which results from monopoly banks' tendency to lend 'too little with too high price', and possibly from excessive investment in entrepreneurial selection. Under plausible assumptions, liquidation option will amplify the distortions caused by market power. Increasing competition in banking in turn may hurt Financial efficiency by inducing too 'slack' screening, which unambiguously impairs the average quality of financing projects in the economy. In addition, since intensifying competition narrows the intermediation margin, the fixed start-up costs become harder to bear causing 'over-investment' in single projects with diminishing returns. Consequently, the relationship between banking sector competition and growth is likely to be non-monotonic. Under plausible assumptions, we derive an 'inverted U-shape' as a general pattern to describe competition-growth relationship, implying that a growth-maximizing market structure would be an oligopoly.
  • Kolho, Kaija-Leena; Alfthan, Henrik (2020)
    Objectives Fecal calprotectin is a valued surrogate marker for intestinal inflammation. It has been argued that calprotectin levels are higher in early age than in later life hampering the use of calprotectin in young children. Subjects and methods To study age-related variation, we used data from our laboratory information system on consecutive, unselected fecal calprotectin measurements from 2014 to 2017 in all children aged 0 to 18 years. From each individual, the first measurement was included and repeated measurements were excluded. Fecal calprotectin was quantitated in the major clinical laboratory in southern Finland, HUSLAB with an ELISA kit from Calpro AS (Calpro/Calprolab, Oslo, Norway). Currently, the assay is performed on two automatic pipetting analysers (Dynex DS2, Chantilly, USA) according to the instructions of the manufacturer. Results There were altogether 11,255 fecal calprotectin results from as many children. The median level of fecal calprotectin was 51 mg/kg in infants <1 year of age (95(th)percentile 648 mg/kg;n = 239). This was 3-4-fold higher when compared to yearly age groups from 1 to 10 years (total number of children included 5,691). Across yearly age groups from 11 to 18, the median values varied from 11 to 19 mg/kg (total number of included children 5,325). The proportion of samples above the routine cut-off for an elevated concentration >100 mg/kg increased with increasing age. Conclusions Fecal calprotectin values in children beyond the first year of life are in general low and comparable in children and adolescents.
  • Väliaho, Eemu-Samuli; Lipponen, Jukka A.; Kuoppa, Pekka; Martikainen, Tero J.; Jäntti, Helena; Rissanen, Tuomas T.; Castren, Maaret; Halonen, Jari; Tarvainen, Mika P.; Laitinen, Tiina M.; Laitinen, Tomi P.; Santala, Onni E.; Rantula, Olli; Naukkarinen, Noora S.; Hartikainen, Juha E. K. (2022)
    Aim: Atrial fibrillation (AF) detection is challenging because it is often asymptomatic and paroxysmal. We evaluated continuous photoplethysmogram (PPG) for signal quality and detection of AF.Methods: PPGs were recorded using a wrist-band device in 173 patients (76 AF, 97 sinus rhythm, SR) for 24 h. Simultaneously recorded 3-lead ambulatory ECG served as control. The recordings were split into 10-, 20-, 30-, and 60-min time-frames. The sensitivity, specificity, and F1-score of AF detection were evaluated for each time-frame. AF alarms were generated to simulate continuous AF monitoring. Sensitivities, specificities, and positive predictive values (PPVs) of the alarms were evaluated. User experiences of PPG and ECG recordings were assessed. The study was registered in the Clinical Trials database (NCT03507335).Results: The quality of PPG signal was better during night-time than in daytime (67.3 +/- 22.4% vs. 30.5 +/- 19.4%, p < 0.001). The 30-min time-frame yielded the highest F1-score (0.9536), identifying AF correctly in 72/76 AF patients (sensitivity 94.7%), only 3/97 SR patients receiving a false AF diagnosis (specificity 96.9%). The sensitivity and PPV of the simulated AF alarms were 78.2 and 97.2% at night, and 49.3 and 97.0% during the daytime. 82% of patients were willing to use the device at home.Conclusion: PPG wrist-band provided reliable AF identification both during daytime and night-time. The PPG data's quality was better at night. The positive user experience suggests that wearable PPG devices could be feasible for continuous rhythm monitoring.
  • Mukminov, Rinat (Svenska handelshögskolan, 2015)
    Economics and Society – 286
    In the period from 2007 to 2009 the world experienced the deepest financial crisis since the Great Depression. The world economy was in the most severe recession since the Second World War. The financial crisis was followed by a debt crisis in the euro area, which is still far from being resolved. The world economy is yet to recover from the crisis. The financial crises are recurring phenomena. The financial crisis of 2007-2009 is in many ways similar to the previous crises. It has been argued that banks’ poor screening incentives at the peak of the business cycle are one of the main causes of the recurring crises. Bank screening literature argues that in boom times, when the majority of loan applications are good, the price competition between the banks intensifies, leading to lower returns from screening loan applicants. As a consequence, screening standards decline and many bad loans end up on the bank balance sheets. Defaults of the bad loans lead to a deterioration of the banks’ loan portfolios, which causes credit crunches and bank crises. There is also an emerging finance literature arguing that a lower cost of funds, such as a lower cost of deposits, cheaper credit in the interbank market, a lower discount rate, encourages the banks to take excessive risks. Excessive risk-taking by the banks can also lead to a bank crisis. These two approaches explain excessive bank risk-taking from two different points of view: the former one from the point of view of bank revenues, while the latter approach explains excessive risk-taking from the point of view of bank costs. The aim of this dissertation is to build a bridge between these two approaches. This dissertation contributes to the screening literature by explicitly introducing the cost of funds into a bank screening model. This is novel, as most previous bank screening literature has assumed the deposit market to be fully competitive with zero interest rate, thus ignoring the impact of the deposit interest rate on bank screening incentives. This dissertation also extends the literature, which explores the effects of costs of funds on the bank risk-taking, by explicitly modelling the banks’ investment in screening of potential loan applicants.
  • Soronen, Veera; Talala, Kirsi; Raitanen, Jani; Taari, Kimmo; Tammela, Teuvo; Auvinen, Anssi (2021)
    Objective To evaluate digital rectal examination (DRE) as a predictor of prostate cancer (PC) at serum PSA level 3.0-3.9 ng/ml. We compared the PC incidence rates of men with different screening test results in this PSA range and analyzed DRE in comparison with free/total PSA ratio as an additional screening test. Materials and methods Using data from the FinRSPC trial, PC incidence rate ratios (IRR) for groups defined by the secondary screening test results (DRE vs. free/total PSA) were calculated for 17-year follow-up, using adjustment for age, family history of PC and place of residence. Screening test performance was evaluated by calculating sensitivity, specificity, positive and negative predictive value, and likelihood ratio. Results The IRR for men with a positive DRE compared to those with a negative result was 1.40 (95% confidence interval (CI) 1.00-1.96), while the IRR for men with a positive free/total PSA result compared to those with a negative one was 1.62 (95% CI 1.08-2.43). The estimated sensitivity was 0.15 (95% CI 0.11-0.20, 40/270) for DRE and 0.32 (95% CI 0.23-0.41, 36/113) for free/total PSA, and the specificity 0.91 (95% CI 0.88-0.93, 419/461) for DRE and 0.85 (95% CI 0.78-0.90, 134/158) for free/total PSA. Conclusions Our results do not support utility of DRE as a screening test for PC at serum PSA level 3.0-3.9 ng/ml, while the results regarding free/total PSA determination were more encouraging and reconfirm the decision to switch from DRE to free/total PSA.
  • Saari, Antti; Pokka, Jari; Mäkitie, Outi; Saha, Marja-Terttu; Dunkel, Leo; Sankilampi, Ulla (2021)
    Context Development of the typical growth phenotype in juvenile acquired hypothyroidism (JHT), the faltering linear growth with increasing weight, has not been thoroughly characterized. Objective To describe longitudinal growth pattern in children developing JHT and investigate how their growth differs from the general population in systematic growth monitoring. Design Retrospective case-control study. Setting JHT cases from 3 Finnish University Hospitals and healthy matched controls from primary health care. Patients A total of 109 JHT patients aged 1.2 to 15.6 years (born 1983-2010) with 554 height and weight measurements obtained for 5 years preceding JHT diagnosis. Each patient was paired with 100 healthy controls (born 1983-2008) by sex and age. Longitudinal growth pattern was evaluated in mixed linear models. Growth monitoring parameters were evaluated using receiver operating characteristics analysis. Results At diagnosis, JHT patients were heavier (mean adjusted body mass index-for-age [BMISDS] difference, 0.65 [95% CI, 0.46-0.84]) and shorter (mean adjusted height-for-age deviation from the target height [(THSDS)-S-DEV] difference, -0.34 [95% CI, -0.57 to -0.10]) than healthy controls. However, 5 years before diagnosis, patients were heavier (mean BMISDS difference, 0.33 [95% CI, 0.12-0.54]) and taller (mean (THSDS)-S-DEV difference, 0.29 [95% CI, 0.06-0.52]) than controls. JHT could be detected with good accuracy when several growth parameters were used simultaneously in screening (area under the curve, 0.83 [95% CI, 0.78-0.89]). Conclusions Abnormal growth pattern of patients with JHT evolves years before diagnosis. Systematic growth monitoring would detect abnormal growth at an early phase of JHT and facilitate timely diagnosis of JHT.
  • Skogman, Malena E.; Kanerva, Sonja; Manner, Suvi; Vuorela, Pia M.; Fallarero, Adyary (2016)
    Quorum sensing (QS) is the process by which bacteria produce and detect signal molecules to coordinate their collective behavior. This intercellular communication is a relevant target for anti-biofilm therapies. Here we have optimized a screening-applicable assay to search for new quorum sensing inhibitors from natural compound libraries. In this system, QS is correlated with the production of violacein, which is directly controlled by the LuxI/LuxR system in Chromobacterium violaceum ATCC 31532. The parallel use of C. violaceum Tn5-mutant CV026, which depends on auto-inducer addition, allows simultaneous discrimination of compounds that act as quenchers of the AHL signal (quorum quenchers). The incorporation of a redox stain into the platform allowed further distinction between QS inhibitors, quorum quenchers and antibacterial compounds. A pilot screening was performed with 465 natural and synthetic flavonoids. All the most active compounds were flavones and they displayed potencies (IC50) in the range of 3.69 to 23.35 M. These leads were particularly promising as they inhibited the transition from microcolonies into mature biofilms from Escherichia coli and Pseudomonas aeruginosa strains. This approach can be very effective in identifying new antimicrobials posing lesser risks of resistance.
  • Mohanraj, Ushanandini (Helsingin yliopisto, 2016)
    The rapid emergence of antibiotic resistance among many pathogenic bacteria has created a profound need to discover new alternatives to antibiotics. Bacteriophages are viruses which infect bacteria and are able to produce special proteins involved in bacterial lysis. However, for many bacteriophage-encoded gene products, the function is not known, i.e., hypothetical proteins of unknown function (HPUFs). Screening these proteins likely identifies a rich source of leads that will help in the development of novel antibacterial compounds. The current study presents two phage genomics-based screening approaches to identify phage HPUFs with antibacterial activity. Both screening assays are based on inhibition of bacterial growth when a toxic gene is expression cloned into a plasmid vector. The first approach was a luxAB/luxCDE -based luminescence screening assay. The luxCDE genes encoding the luciferase substrate producing enzymes were integrated into an Escherichia coli strain genome as a transcriptional fusion. Also, a vector carrying the luxAB genes, encoding the luciferase enzyme, and a cloning site for the phage HPUF genes, was constructed. Ligation of a toxic gene into the vector would result in few or rare transformants after electroporation while ligation of a non-toxic gene would result in large number of transformants, and the difference in number of transformants will be reflected in the amount of bioluminescence after electroporation. The proof of concept of the approach was verified using the control genes g150 (a structural, thus a non-toxic gene of phage R1-RT) and regB (a known toxic gene of phage T4). The results demonstrated a significant difference in Relative Luminescence Units (RLU) between the g150 and regB electroporation mixtures. The second screening approach was an optimized plating assay producing a significant difference in the number of transformants after ligation of the toxic and non-toxic genes into a cloning vector. This assay was tested and optimized with several known control toxic and non-toxic genes. Using the plating assay approach, in the current study, ninety-four R1-RT HPUFs were screened and ten of them showed toxicity in E. coli. In future, the identified toxic HPUFs of R1-RT could be purified and characterized to identify their bacterial targets. Further, both of these screening assays can be used to screen among HPUFs of other phages, and this should allow the discovery of a wide variety of putative inhibitors for the control of current and emerging bacterial pathogens.
  • Kanclerz, Piotr; Tuuminen, Raimo; Khoramnia, Ramin (2021)
    Introduction: Urbanization has caused dramatic changes in lifestyle, and these rapid transitions have led to an increased risk of noncommunicable diseases, such as type 2 diabetes. In terms of cost-effectiveness, screening for diabetic retinopathy is a critical aspect in diabetes management. The aim of this study was to review the imaging modalities employed for retinal examination in diabetic retinopathy screening. Methods: The PubMed and Web of Science databases were the main sources used to investigate the medical literature. An extensive search was performed to identify relevant articles concerning "imaging ", "diabetic retinopathy " and "screening " up to 1 June 2021. Imaging techniques were divided into the following: (i) mydriatic fundus photography, (ii) non-mydriatic fundus photography, (iii) smartphone-based imaging, and (iv) ultrawide-field imaging. A meta-analysis was performed to analyze the performance and technical failure rate of each method. Results: The technical failure rates for mydriatic and non-mydriatic digital fundus photography, smartphone-based and ultrawide-field imaging were 3.4% (95% CI: 2.3-4.6%), 12.1% (95% CI: 5.4-18.7%), 5.3% (95% CI: 1.5-9.0%) and 2.2% (95% CI: 0.3-4.0%), respectively. The rate was significantly different between all analyzed techniques (p < 0.001), and the overall failure rate was 6.6% (4.9-8.3%; I-2 = 97.2%). The publication bias factor for smartphone-based imaging was significantly higher than for mydriatic digital fundus photography and non-mydriatic digital fundus photography (b = -8.61, b = -2.59 and b = -7.03, respectively; p < 0.001). Ultrawide-field imaging studies were excluded from the final sensitivity/specificity analysis, as the total number of patients included was too small. Conclusions: Regardless of the type of the device used, retinal photographs should be taken on eyes with dilated pupils, unless contraindicated, as this setting decreases the rate of ungradable images. Smartphone-based and ultrawide-field imaging may become potential alternative methods for optimized DR screening; however, there is not yet enough evidence for these techniques to displace mydriatic fundus photography.
  • Talala, Kirsi; Heinävaara, Sirpa; Taari, Kimmo; Tammela, Teuvo L. J.; Kujala, Paula; Stenman, Ulf-Håkan; Malila, Nea; Auvinen, Anssi (2020)
    Background The long-term health-related quality of life (HRQOL) impacts of PCa screening have not been adequately evaluated. We aimed to compare the generic and disease-specific health-related quality of life (HRQOL) among men with prostate cancer in the screening arm with the control arm of the PSA-based prostate cancer screening trial in up to 15 years of follow-up. Materials and methods This study was conducted within population-based Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). During 1996-1999 80,458 men were randomized to the serum prostate-specific antigen (PSA) screening arm (SA, N = 32 000) and the control arm (CA, N = 48 458). Men in the screening arm were screened at 4-year intervals until 2007. HRQOL questionnaires were delivered to newly diagnosed prostate cancer patients in the screening and control arm 1996-2006 (N = 5128) at the time of diagnosis (baseline), at 3-month, 12-month and 5, 10, and 15-year follow-up. Validated UCLA Prostate Cancer Index (UCLA-PCI) and RAND 36-Item Health Survey were used for HRQOL assessment. The data were analyzed with a random effects model for repeated measures. Results At baseline, men with prostate cancer in the screening arm reported better Sexual Function, as well as less Sexual and Urinary Bother. Long-term follow-up revealed slightly higher HRQOL scores in the screening arm in prostate cancer specific measures at 10-year post diagnosis, but the differences were statistically significant only in Urinary Bother (UCLA-PCI score 77.9; 95% CI 75.2 to 80.5 vs. 70.9; 95% CI 66.8 to 74.9 P = .005).The generic HRQOL scores were comparable between the trial arms. The overall differences in disease-specific or generic HRQOL scores by trial arm did not vary during the follow-up. Conclusion No major differences were observed in HRQOL in men with prostate cancer between the prostate cancer screening and control arms during five to 15-year follow-up.
  • Kenttä, Laura (Helsingfors universitet, 2015)
    Susceptibility to antibiotics is constantly developing in bacteria due to selection pressure caused by use of antibiotics. For this reason, finding new antimicrobial substances is imperative. High-throughput screening (HTS) is an important tool to find new active substances. The need to analyse as many substances in as small time as possible is emphasised in modern drug development. Robust methods, suitable for fast throughput of substances, miniaturisation and automation, are particularly useful. In the context of antimicrobial screening, methods utilising bioluminescence can correspond this need, and genetic engineering can help in developing bacterial strains with beneficial features for screening. In this work, two screening methods were developed and optimised using genetically engineered Escherichia coli strains. The screening methods make use of the bioluminescent properties of the strains, and the methods can be used to screen compound libraries for antimicrobials rapidly enough to approach HTS. The strain E. coli WZM120/pCGLS 11 is constitutively luminescent, so weakening of luminescence means the cell viability weakens. The strain E. coli K12/pCSS305, where luminescence is produced by a heat-inducible runaway plasmid, can be used to especially detect compounds inhibiting DNA replication. In developing the method, workflow was optimised and conditions were validated so as to enable possible HTS campaigns. The target was to create as simple, fast and reproducible a method as possible. The Z' values calculated in assessing the performance are excellent for a cell-based method. The signal is readily distinguishable, the bacterial strains are in a stable manner, and the method is well reproducible. It is possible to continue assay development from 96-well format to 384-well format.
  • Hellinen, Laura; Bahrpeyma, Sina; Rimpela, Anna-Kaisa; Hagstrom, Marja; Reinisalo, Mika; Urtti, Arto (2020)
    Interactions between drugs and melanin pigment may have major impacts on pharmacokinetics. Therefore, melanin binding can modify the efficacy and toxicity of medications in ophthalmic and other disease of pigmented tissues, such as melanoma. As melanin is present in many pigmented tissues in the human body, investigation of pigment binding is relevant in drug discovery and development. Conventionally, melanin binding assays have been performed using an equilibrium binding study followed by chemical analytics, such as LC/MS. This approach is laborious, relatively slow, and limited to facilities with high performance quantitation instrumentation. We present here a screening of melanin binding with label-free microscale thermophoresis (MST) that utilizes the natural autofluorescence of melanin. We determined equilibrium dissociation constants (K-d) of 11 model compounds with melanin nanoparticles. MST categorized the compounds into extreme (chloroquine, penicillin G), high (papaverine, levofloxacin, terazosin), intermediate (timolol, nadolol, quinidine, propranolol), and low melanin binders (atropine, methotrexate, diclofenac) and displayed good correlation with binding parameter values obtained with the conventional binding study and LC/MS analytics. Further, correlation was seen between predicted melanin binding in human retinal pigment epithelium and choroid (RPE-choroid) and K(d)values obtained with MST. This method represents a useful and fast approach for classification of compounds regarding melanin binding. Thus, the method can be utilized in various fields, including drug discovery, pharmacokinetics, and toxicology.
  • Vepsäläinen, Teemu; Heliö, Tiina; Vasilescu, Catalina; Martelius, Laura; Weckström, Sini; Koskenvuo, Juha; Hiippala, Anita; Ojala, Tiina (2022)
    Cardiomyopathies (CMPs) are a heterogeneous group of diseases, frequently genetic, affecting the heart muscle. The symptoms range from asymptomatic to dyspnea, arrhythmias, syncope, and sudden cardiac death. This study is focused on MYH7 (beta-myosin heavy chain), as this gene is commonly mutated in cardiomyopathy patients. Due to the high combined prevalence of MYH7 variants and severe health outcomes, it is one of the most frequently tested genes in clinical settings. We analyzed the clinical presentation and natural history of 48 patients with MYH7-related cardiomyopathy belonging to a cohort from a tertiary center at Helsinki University Hospital, Finland. We made special reference to three age subgroups (0-1, 1-12, and >12 years). Our results characterize a clinically significant MYH7 cohort, emphasizing the high variability of the CMP phenotype depending on age. We observed a subgroup of infants (0-1 years) with MYH7 associated severe DCM phenotype. We further demonstrate that patients under the age of 12 years have a similar symptom burden compared to older patients.
  • Ylonen, Venla; Lindfors, Katri; Repo, Marleena; Huhtala, Heini; Fuchs, Valma; Saavalainen, Päivi; Musikka, Alex; Laurila, Kaija; Kaukinen, Katri; Kurppa, Kalle (2020)
    Non-biopsy diagnosis of celiac disease is possible in children with anti-transglutaminase 2 antibodies (TGA) > 10x the upper limit of normal (ULN) and positive anti-endomysial antibodies (EMA). Similar criteria have been suggested for adults, but evidence with different TGA assays is scarce. We compared the performance of four TGA tests in the diagnosis of celiac disease in cohorts with diverse pre-test probabilities. Serum samples from 836 adults with either clinical suspicion or family risk of celiac disease were tested with four commercial TGA assays, EmA and celiac disease-associated genetics. The diagnosis was set based on duodenal lesion or, in some cases, using special methods. 137 (57%) patients with clinical suspicion and 85 (14%) of those with family risk had celiac disease. Positive predictive value (PPV) for 10xULN was 100% in each TGA test. The first non-diagnostic investigations were encountered with ULN 1.0x-5.1x in the clinical cohort and 1.3x-4.9x in the family cohort, respectively. Using the assays' own cut-offs (1xULN) the PPVs ranged 84-100%. Serology-based diagnosis of celiac disease was accurate in adults using different commercial kits and pre-test probabilities using 10xULN. The results also suggest that the ULN threshold for biopsy-omitting approach could be lower.
  • Fallarero , Adyary; Batista-González, Ana; Hiltunen, Anna K.; Liimatainen, Jaana; Karonen, Maarit; Vuorela, Pia M. (2015)
    Natural products are complex matrices of compounds that are prone to interfere with the label-dependent methods that are typically used for cytotoxicity screenings. Here, we developed a label-free Electric Cell-substrate Impedance Sensing (ECIS)-based cytotoxicity assay that can be applied in the assessment of the cytotoxicity of natural extracts. The conditions to measure the impedance using ECIS were first optimized in mice immortalized hypothalamic neurons GT1-7 cells. The performance of four natural extracts when tested using three conventional cytotoxicity assays in GT1-7 cells, was studied. Betula pendula (silver birch tree) was found to interfere with all of the cytotoxicity assays in which labels were applied. The silver birch extract was also proven to be cytotoxic and, thus, served as a proof-of-concept for the use of ECIS. The extract was fractionated and the ECIS method permitted the distinction of specific kinetic patterns of cytotoxicity on the fractions as well as the extract's pure constituents. This study offers evidence that ECIS is an excellent tool for real-time monitoring of the cytotoxicity of complex extracts that are difficult to work with using conventional (label-based) assays. Altogether, it offers a very suitable cytotoxicity-screening assay making the work with natural products less challenging within the drug discovery workflow.