In Turku, Finland, we introduced a home oxygen treatment and app-based monitoring program for hospitalized COVID-19 patients to facilitate an early discharge during the Omicron wave. In this case ...series we explore the clinical parameters of patients enrolled in the program and evaluate the cost-benefit and safety issues of the program. Hospitalized COVID-19 patients with marked hypoxemia but otherwise in stable condition were screened from Turku City Hospital and Turku University Hospital by treating doctors for eligibility in the program. Peripheral oxygen saturation of > 92% and breathing frequency < 30/min in rest with oxygen supplementation were among the criteria. All patients actively participating in the program between 10.sup.th of January 2022 and 30.sup.th of September 2022 were included in this case series. Clinical data of hospitalization and monitoring were analysed, and cost-benefit evaluation was based on the number of saved hospitalization days. Nineteen COVID-19 patients were included in this case series and recruited from three different hospital departments in the Turku city region, South-West Finland. All patients were male, the median age was 59 years and the median duration of hospitalization before enrolment in the program was 6 days (range 3--20 days). The median duration of home oxygen treatment was 13 days (range 3--72 days) and the median duration of home monitoring was 18 days (range 7--41 days). A total of 210,5 hospital days were prevented, resulting in savings of euro144,490 of healthcare expenditure (on average 9 days and euro7,605 per patient). No major safety issues were reported during the program. In our case series, home oxygen treatment combined with home monitoring was safe and economically beneficial. Application based monitoring could be considered in other post-acute pulmonary conditions to reduce hospitalization and healthcare costs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Do the uterine leiomyoma driver events - mediator complex subunit 12 (
) mutations, high mobility group AT-hook (HMGA2) overexpression, and fumarate hydratase (FH) inactivation - also contribute to ...the development of uterine adenomyomas?
mutations and FH deficiency occur in a subset of uterine adenomyomas, but at lower frequencies than in leiomyomas.
Uterine adenomyomas are benign tumours with clinical features very similar to uterine leiomyomas. Mutations affecting
,
and
account for up to 80-90% of leiomyomas, but their contribution to adenomyomas is not known.
Formalin-fixed paraffin-embedded adenomyoma samples from 21 patients operated on during 2012-2014 were collected at the pathology department's archives and analysed for uterine leiomyoma driver events.
Adenomyoma diagnoses were verified by a specialized pathologist and representative areas were marked on haematoxylin-eosin slides. DNA was extracted from the tissue samples and sequenced to detect mutations in
. Expression levels of HMGA2 and 2SC, a robust indirect method to detect FH inactivation, were analysed by immunohistochemistry (IHC). The coding region of
was sequenced in one adenomyoma sample showing strong 2SC staining as well as in the same patient's normal tissue sample. All patients' medical histories were collected and reviewed.
mutation c.131G > A, p.G44D, the most common mutation in uterine leiomyomas, was identified in two samples (2/21; 9.5%). One adenomyoma displayed strong 2SC positivity and subsequent sequencing revealed a frameshift
mutation c.911delC, p.P304fs in the tumour. The mutation was also present in the patient's normal tissue sample, indicating that she has a hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. HMGA2 protein expression was normal in all adenomyomas.
Restricted sample size limits the determination of exact mutation frequencies of the studied aberrations in adenomyomas.
Uterine leiomyoma driver mutations do contribute to the development of some adenomyomas. We also report an adenomyoma in the context of hereditary HLRCC syndrome. Despite clinical similarities, the pathogenic mechanisms of adenomyomas and leiomyomas are likely different. Large-scale genomic analyses are warranted to elucidate the complete molecular background of adenomyomas.
This study was supported by The Academy of Finland, the Sigrid Jusélius Foundation, and the Cancer Society of Finland. The authors declare no conflict of interest.
Abstract
Uterine adenomyosis is a condition in which ectopic endometrial glands are present in myometrial stroma surrounded by smooth muscle cell hyperplasia. Foci of adenomyosis growing as a tumor ...like mass are called adenomyomas. Uterine adenomyomas are common tumors and they share symptoms, including pelvic pain and abnormal bleeding, with uterine leiomyomas. The two tumor types are challenging to distinguish from one another and the diagnosis is usually confirmed only after surgery by pathological evaluation. The molecular background of uterine adenomyomas is not currently well known. In uterine leiomyomas, somatic mediator complex subunit 12 (MED12) mutations, high mobility group AT-hook (HMGA2) protein overexpression, and fumarate hydratase (FH) inactivation are well established as major mutually exclusive driver events covering 80-90% of the tumors. Here, we have analyzed the presence of these changes in a set of 21 uterine adenomyomas. Representative areas of formalin-fixed paraffin embedded archival uterine adenomyoma tissue samples were used to construct a tissue microarray. The HMGA2 overexpression and the FH inactivation were assessed using immunohistochemistry with anti HMGA and 2SC antibodies, respectively. DNA was extracted from the tumor samples to determine the MED12 mutation status by direct sequencing of exons 1 and 2 of the gene. MED12 c.131GA, p.G44D mutation was found in two adenomyoma samples out of 21 (9.5%). Strong positive staining of 2SC indicating FH inactivation was present in one sample which also showed reduced FH protein expression when validated with an independent method using anti-FH immunostaining. Sequencing revealed a frameshift mutation c.911delC, p.P304fs in exon 7 leading to a premature stop codon 25 codons later. The mutation was also found in a separate uterine leiomyoma of the same patient and both tumor samples mostly presented the mutant allele indicating loss of heterozygosity of the wild type allele. This, together with the patient's medical history of previous uterine leiomyomas, indicates the germline origin of the mutation and thus a hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. No changes in HMGA2 expression were detected with all samples presenting normal expression levels. In conclusion, MED12 mutations are present in a subset of uterine adenomyomas. The mutation frequency of 9.5% that was observed here in our adenomyoma sample series is considerably lower than that of 70% in uterine leiomyomas. Our results also suggest that adenomyomas may be linked to HLRCC in which they have not been previously reported. The driver events behind uterine adenomyomas remain mostly unknown and further large-scale studies are warranted to clarify the spectrum of underlying mutations and molecular background of these common tumors.
Citation Format: Tuomas A. Heikkinen, Anna Äyräväinen, Janne Hänninen, Terhi Ahvenainen, Ralf Bützow, Annukka Pasanen, Pia Vahteristo. Uterine leiomyoma driver events in uterine adenomyomas abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4611.
Assessment of risk for a given disease and the diagnosis of diseases is often based on assays detecting biomarkers. Antibody-based biomarker-assays for diseases such as prostate cancer are often ...ambiguous and biomarker proteins are frequently also elevated for reasons that are unspecific. We have opted to use luminescence modulating phages for the analysis of known acute inflammatory response biomarker CRP (C-reactive protein) and biomarkers of prostate cancer in urine samples. Firstly, CRP was used to simulate the detection process in a controlled chemical environment. Secondly, we tried to classify more challenging lethal prostate cancer samples from control samples. Our unique method utilizes a special biopanning process in order to create special phages capable of capturing a dye necessary for detection and potential biomarkers. As the biomarker-molecules interfere with the phages, dye is repelled from the phage network resulting in an altered reporter luminescence. These changes can be observed with an absorbance reader and even with the naked eye. The simple method could present an alternative for screening of disease biomarkers. For prostate cancer urine samples, we achieved a sensitivity of 80% and specificity of 75% to detect Grade Group (GG) 4 and 5 prostate cancer.
The distribution ranges and spatio‐temporal patterns in the occurrence and activity of boreal bats are yet largely unknown due to their cryptic lifestyle and lack of suitable and efficient study ...methods. We approached the issue by establishing a permanent passive‐acoustic sampling setup spanning the area of Finland to gain an understanding on how latitude affects bat species composition and activity patterns in northern Europe. The recorded bat calls were semi‐automatically identified for three target taxa; Myotis spp., Eptesicus nilssonii or Pipistrellus nathusii and the seasonal activity patterns were modeled for each taxa across the seven sampling years (2015–2021). We found an increase in activity since 2015 for E. nilssonii and Myotis spp. For E. nilssonii and Myotis spp. we found significant latitude ‐dependent seasonal activity patterns, where seasonal variation in patterns appeared stronger in the north. Over the years, activity of P. nathusii increased during activity peak in June and late season but decreased in mid season. We found the passive‐acoustic monitoring network to be an effective and cost‐efficient method for gathering bat activity data to analyze spatio‐temporal patterns. Long‐term data on the composition and dynamics of bat communities facilitates better estimates of abundances and population trend directions for conservation purposes and predicting the effects of climate change.
The aim of this study is to assess whether articular cartilage changes in an equine model of post-traumatic osteoarthritis (PTOA), induced by surgical creation of standard (blunt) grooves, and very ...subtle sharp grooves, could be detected with ex vivo T1 relaxation time mapping utilizing three-dimensional (3D) readout sequence with zero echo time. Grooves were made on the articular surfaces of the middle carpal and radiocarpal joints of nine mature Shetland ponies and osteochondral samples were harvested at 39 weeks after being euthanized under respective ethical permissions. T1 relaxation times of the samples (n = 8 + 8 for experimental and n = 12 for contralateral controls) were measured with a variable flip angle 3D multiband-sweep imaging with Fourier transform sequence. Equilibrium and instantaneous Young's moduli and proteoglycan (PG) content from OD of Safranin-O-stained histological sections were measured and utilized as reference parameters for the T1 relaxation times. T1 relaxation time was significantly (p < 0.05) increased in both groove areas, particularly in the blunt grooves, compared with control samples, with the largest changes observed in the superficial half of the cartilage. T1 relaxation times correlated weakly (Rs ≈ 0.33) with equilibrium modulus and PG content (Rs ≈ 0.21). T1 relaxation time in the superficial articular cartilage is sensitive to changes induced by the blunt grooves but not to the much subtler sharp grooves, at the 39-week timepoint post-injury. These findings support that T1 relaxation time has potential in detection of mild PTOA, albeit the most subtle changes could not be detected.
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•Aminomethylphosphonic acid functionalized 3D-printed filters are robust scavengers for metals.•Y, Nd, and Dy can be recovered from a multimetal mining waste solution.•The ...coadsorption and desorption of Al and Ca with the rare earth elements is minimized in the developed process.
Herein we report the use of nylon-12-based 3D-printed filters incorporating α-aminomethylphosphonic acid as an active additive for the recovery of Y, Nd, and Dy from the mining waste solution containing Al, K, Ca, Sc, Fe, Co, Cu, Zn, Y, Nd, Dy, and U. Nylon-12 was chosen for the polymer matrix of the filter due to its inactivity towards the studied metals. The micrometer-level structure of the filters was studied with a scanning helium ion microscope and X-ray tomography to reveal the porosity, pore size, and active additive distribution in the filters. Furthermore, FTIR spectroscopy was used to analyze the compositional changes in the 3D-printed filters after the printing and adsorption processes. Adsorption of the metals was studied at a pH range of 1–4, and the following adsorption trend Sc > Fe > U > Y, Nd, Dy > Al, Cu, Zn > K, Ca, Co was observed in each of the studied pH values. The sequential recovery process for metals was studied at pH 2, and desorption of the metals from the filters was performed with 6 M HNO3. 100 % adsorption of REEs, Fe, and U was achieved during the recovery process, and on average, over 88 % of the adsorbed Y, Nd, and Dy were desorbed from the filters. In contrast to Y, Nd, and Dy, the desorption of Sc, Fe, and U was minimal (Fe and U) or negligible (Sc) with 6 M HNO3 due to their strong coordination to the active additive. Maximum adsorption capacities for Y, Nd, Dy, and U were determined by using linear Langmuir adsorption isotherm. The best maximum adsorption capacity was determined for Sc, Qmax = 0.51 mmol/g followed by U, Nd, Dy, and Y with capacities of 0.47, 0.24, 0.23, and 0.17 mmol/g, respectively. Overall, this study achieved a complete removal of Sc, Fe, and U from the simulated mining waste solution leaving a final eluate that mainly contained Y (320 μg), Nd (350 μg), Dy (330 μg), and Al (710 μg) demonstrating the applicability of the 3D-printed filters in the recovery of Y, Nd, and Dy from the multimetal solution.
The aim of this study is to assess whether articular cartilage changes in an equine model of post-traumatic osteoarthritis (PTOA), induced by surgical creation of standard (blunt) grooves, and very ...subtle sharp grooves, could be detected with ex vivo T
relaxation time mapping utilizing three-dimensional (3D) readout sequence with zero echo time. Grooves were made on the articular surfaces of the middle carpal and radiocarpal joints of nine mature Shetland ponies and osteochondral samples were harvested at 39 weeks after being euthanized under respective ethical permissions. T
relaxation times of the samples (n = 8 + 8 for experimental and n = 12 for contralateral controls) were measured with a variable flip angle 3D multiband-sweep imaging with Fourier transform sequence. Equilibrium and instantaneous Young's moduli and proteoglycan (PG) content from OD of Safranin-O-stained histological sections were measured and utilized as reference parameters for the T
relaxation times. T
relaxation time was significantly (p < 0.05) increased in both groove areas, particularly in the blunt grooves, compared with control samples, with the largest changes observed in the superficial half of the cartilage. T
relaxation times correlated weakly (R
≈ 0.33) with equilibrium modulus and PG content (R
≈ 0.21). T
relaxation time in the superficial articular cartilage is sensitive to changes induced by the blunt grooves but not to the much subtler sharp grooves, at the 39-week timepoint post-injury. These findings support that T
relaxation time has potential in detection of mild PTOA, albeit the most subtle changes could not be detected.
Urinary tract infections (UTIs) are a common problem worldwide. The most prevalent causative pathogen of UTI is Escherichia coli, focus of this study. The current golden standard for detecting UTI is ...bacterial culture, creating a major workload for hospital laboratories - cost-effective and rapid mass screening of patient samples is needed. Here we present an alternative approach to screen patient samples with a single-step assay utilising time-resolved luminescence and luminescence modulating biosensing phages. Filamentous phage M13 was biopanned for binding luminescence quenching metal (copper) and further E. coli. The screening assay luminescence modulation was further enhanced by selecting right chemical environment for the functioning phage clones. Semi-specific interaction between phage, target bacteria and metal was detected by modulation in the signal of a weakly chelating, easily quenchable lanthanide complex. In the presence of the target pathogen, the phages collected quenching metal from solution to the bacterial surface changing the quenching effect on the lanthanide label and thus modulating the signal. Our method was compared with the bacterial culture data obtained from 70 patient samples. The developed proof-of-principle screening assay showed sensitivity and a specificity at the 90% mark when compared to culture method although some samples had high turbidity and even blood. The detection limit of E. coli was in the range of 1000–10 000 colony forming units/mL. Untreated urine sample was screened and time-resolved luminescence signal result was achieved within 10 min in a single incubation step.
•Phage-based method to screen E. coli causing urinary tract infections.•Phage acts as a luminescence modulator as its peptides interact with bacteria and metal quencher.•Biosensing screening system, that detects E. coli in clinically relevant concentrations.
Changes in the fibril-reinforced poroelastic (FRPE) mechanical material parameters of human patellar cartilage at different stages of osteoarthritis (OA) are not known. Further, the patellofemoral ...joint loading is thought to include more sliding and shear compared to other knee joint locations, thus, the relations between structural and functional changes may differ in OA. Thus, our aim was to determine the patellar cartilage FRPE properties followed by associating them with the structure and composition. Osteochondral plugs (n = 14) were harvested from the patellae of six cadavers. Then, the FRPE material properties were determined, and those properties were associated with proteoglycan content, collagen fibril orientation angle, optical retardation (fibril parallelism), and the state of OA of the samples. The initial fibril network modulus and permeability strain-dependency factor were 72% and 63% smaller in advanced OA samples when compared to early OA samples. Further, we observed a negative association between the initial fibril network modulus and optical retardation (r = -0.537, p < 0.05). We also observed positive associations between 1) the initial permeability and optical retardation (r = 0.547, p < 0.05), and 2) the initial fibril network modulus and optical density (r = 0.670, p < 0.01).These results suggest that the reduced pretension of the collagen fibrils, as shown by the reduced initial fibril network modulus, is linked with the loss of proteoglycans and cartilage swelling in human patellofemoral OA. The characterization of these changes is important to improve the representativeness of knee joint models in tissue and cell scale.
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