Edistyksellisen tiedeliiton kunniajäsen, ministeri Jaakko Numminen 1928–2022

Ministeri, opetusministeriön pitkäaikainen kansliapäällikkö ja koulutus- ja kulttuuripoliittinen vaikuttaja Jaakko Numminen kuoli 19.9. 2022 Helsingissä

Hubungan Kadar Laktat dengan Kejadian Mortalitas Pasien Sepsis di Intensive Care Unit RSUP DR. M. Djamil Padang Tahun 2017-2018

Sepsis is the leading cause of death for critically ill patients admitted to the ICU. The cause of death in sepsis is multiple organ dysfunction due to tissue hypoperfusion caused by excessive inflammatory response in sepsis which causes inadequate tissue oxygen resulting in hypoxia. This can increase lactate levels because glycolysis mostly occurs anaerobically. The aims of this study is to determine the relationship of lactate levels with the incidence of mortality in septic patients. This study is an analytical study with cross-sectional design of 23 patients with sepsis who have been treated at the ICU Hospital Dr. M. Djamil Padang from 2017-2018. The lactate levels obtained are presented in the form of mean ± standard deviation (SD). Data were analyzed by independent T test. The value of p <0.05 indicates that there is a significant relationship between the two variables. The results showed male sepsis patients were 60.9% more than female patients 39.1%. The mean age of patients is 58 years. Most sepsis patients experience hyperlactatemia (91.3%). The mean lactate level of sepsis patients was 5.1 mmol / L. The mortality rate of sepsis patients in the ICU Dr. M. Djamil Padang is still high (82.6%). The results of the analysis showed a significant difference between the mean lactate levels of sepsis patients who died and those who did not die with a p value of 0.021 (p <0.05) This study shows there is relationship between lactate levels and the incidence of mortality in septic patients

Analysis of BMP4 and BMP7 signaling in breast cancer cells unveils time-dependent transcription patterns and highlights a common synexpression group of genes

<p>Abstract</p> <p>Background</p> <p>Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily of growth factors. They are known for their roles in regulation of osteogenesis and developmental processes and, in recent years, evidence has accumulated of their crucial functions in tumor biology. BMP4 and BMP7, in particular, have been implicated in breast cancer. However, little is known about BMP target genes in the context of tumor. We explored the effects of BMP4 and BMP7 treatment on global gene transcription in seven breast cancer cell lines during a 6-point time series, using a whole-genome oligo microarray. Data analysis included hierarchical clustering of differentially expressed genes, gene ontology enrichment analyses and model based clustering of temporal data.</p> <p>Results</p> <p>Both ligands had a strong effect on gene expression, although the response to BMP4 treatment was more pronounced. The cellular functions most strongly affected by BMP signaling were regulation of transcription and development. The observed transcriptional response, as well as its functional outcome, followed a temporal sequence, with regulation of gene expression and signal transduction leading to changes in metabolism and cell proliferation. Hierarchical clustering revealed distinct differences in the response of individual cell lines to BMPs, but also highlighted a synexpression group of genes for both ligands. Interestingly, the majority of the genes within these synexpression groups were shared by the two ligands, probably representing the core molecular responses common to BMP4 and BMP7 signaling pathways.</p> <p>Conclusions</p> <p>All in all, we show that BMP signaling has a remarkable effect on gene transcription in breast cancer cells and that the functions affected follow a logical temporal pattern. Our results also uncover components of the common cellular transcriptional response to BMP4 and BMP7. Most importantly, this study provides a list of potential novel BMP target genes relevant in breast cancer.</p

Antibacterial Activity of Electrodeposited Copper and Zinc on Metal Injection Molded (MIM) Micropatterned WC-CO Hard Metals

Antibacterial activity of electrodeposited copper and zinc both on flat and micropatterned hard metal tungsten carbide-cobalt (WC-Co) specimens was studied. Tribological wear was applied on electrodeposited specimens: coatings were completely removed from flat surfaces whereas only top of the micropillars was exposed to wear for the micropatterned specimens protecting the functional metal coating in between the micropillars. The growth of Staphylococcus aureus (S. aureus) Gram-positive bacterial species was studied on the specimens using a touch test mimicking bacterial transfer from the surfaces. Copper coated specimens prevented bacterial growth completely independent of wear or surface structure, i.e., even residual traces of copper were sufficient to prevent bacterial growth. Zinc significantly suppressed the bacterial growth both on flat and micropatterned specimens. However, adhesion of zinc was low resulting in an easy removal from the surface by wear. The micropatterned zinc specimens showed antibacterial activity as electrodeposited zinc remained intact on the sample surface between the micropillars. This was sufficient to suppress the growth of S. aureus. On the contrary, the flat zinc coated surfaces did not show any antibacterial activity after wear. Our results show that micropatterned hard metal specimens can be used to preserve antibacterial activity under tribological wear

Expected impact of MRI-related interreader variability on ProScreen prostate cancer screening trial: a pre-trial validation study

Background: The aim of this study is to investigate the potential impact of prostate magnetic resonance imaging (MRI) -related interreader variability on a population-based randomized prostate cancer screening trial (ProScreen). Methods: From January 2014 to January 2018, 100 men aged 50-63 years with clinical suspicion of prostate cancer (PCa) in Helsinki University Hospital underwent MRI. Nine radiologists individually reviewed the pseudonymized MRI scans of all 100 men in two ProScreen trial centers. All 100 men were biopsied according to a histological composite variable comprising radical prostatectomy histology (N = 38) or biopsy result within 1 year from the imaging (N = 62). Fleiss' kappa (kappa) was used to estimate the combined agreement between all individual radiologists. Sample data were subsequently extrapolated to 1000-men subgroups of the ProScreen cohort. Results: Altogether 89% men of the 100-men sample were diagnosed with PCa within a median of 2.4 years of follow-up. Clinically significant PCa (csPCa) was identified in 76% men. For all PCa, mean sensitivity was 79% (SD +/- 10%, range 62-96%), and mean specificity 60% (SD +/- 22%, range 27-82%). For csPCa (Gleason Grade 2-5) MRI was equally sensitive (mean 82%, SD +/- 9%, range 67-97%) but less specific (mean 47%, SD +/- 20%, range 21-75%). Interreader agreement for any lesion was fair (kappa 0.40) and for PI-RADS 4-5 lesions it was moderate (kappa 0.60). Upon extrapolating these data, the average sensitivity and specificity to a screening positive subgroup of 1000 men from ProScreen with a 30% prevalence of csPCa, 639 would be biopsied. Of these, 244 men would be true positive, and 395 false positive. Moreover, 361 men would not be referred to biopsy and among these, 56 csPCas would be missed. The variation among the radiologists was broad as the least sensitive radiologist would have twice as many men biopsied and almost three times more men would undergo unnecessary biopsies. Although the most sensitive radiologist would miss only 2.6% of csPCa (false negatives), the least sensitive radiologist would miss every third. Conclusions: Interreader agreement was fair to moderate. The role of MRI in the ongoing ProScreen trial is crucial and has a substantial impact on the screening process.Peer reviewe

Expected impact of MRI-related interreader variability on ProScreen prostate cancer screening trial: a pre-trial validation study

Background: The aim of this study is to investigate the potential impact of prostate magnetic resonance imaging (MRI) -related interreader variability on a population-based randomized prostate cancer screening trial (ProScreen). Methods: From January 2014 to January 2018, 100 men aged 50-63 years with clinical suspicion of prostate cancer (PCa) in Helsinki University Hospital underwent MRI. Nine radiologists individually reviewed the pseudonymized MRI scans of all 100 men in two ProScreen trial centers. All 100 men were biopsied according to a histological composite variable comprising radical prostatectomy histology (N = 38) or biopsy result within 1 year from the imaging (N = 62). Fleiss' kappa (kappa) was used to estimate the combined agreement between all individual radiologists. Sample data were subsequently extrapolated to 1000-men subgroups of the ProScreen cohort. Results: Altogether 89% men of the 100-men sample were diagnosed with PCa within a median of 2.4 years of follow-up. Clinically significant PCa (csPCa) was identified in 76% men. For all PCa, mean sensitivity was 79% (SD +/- 10%, range 62-96%), and mean specificity 60% (SD +/- 22%, range 27-82%). For csPCa (Gleason Grade 2-5) MRI was equally sensitive (mean 82%, SD +/- 9%, range 67-97%) but less specific (mean 47%, SD +/- 20%, range 21-75%). Interreader agreement for any lesion was fair (kappa 0.40) and for PI-RADS 4-5 lesions it was moderate (kappa 0.60). Upon extrapolating these data, the average sensitivity and specificity to a screening positive subgroup of 1000 men from ProScreen with a 30% prevalence of csPCa, 639 would be biopsied. Of these, 244 men would be true positive, and 395 false positive. Moreover, 361 men would not be referred to biopsy and among these, 56 csPCas would be missed. The variation among the radiologists was broad as the least sensitive radiologist would have twice as many men biopsied and almost three times more men would undergo unnecessary biopsies. Although the most sensitive radiologist would miss only 2.6% of csPCa (false negatives), the least sensitive radiologist would miss every third. Conclusions: Interreader agreement was fair to moderate. The role of MRI in the ongoing ProScreen trial is crucial and has a substantial impact on the screening process.Peer reviewe

Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans

Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.Peer reviewe