We investigated the associations of the measures of arterial health with cognition in adolescents and whether physical activity (PA) or sedentary time (ST) confounds these associations. One hundred sixteen adolescents (71 boys) aged 15.9 ± 0.4 participated in the study. PA and ST were assessed using a combined accelerometer/heart rate monitor. Overall cognition was computed from the results of psychomotor function, attention, working memory, and paired-associate learning tests. Pulse wave velocity was measured by impedance cardiography, carotid intima-media thickness, and carotid artery distensibility by carotid ultrasonography. Systolic and diastolic blood pressure (SBP and DBP) were measured using an aneroid sphygmomanometer. SBP was inversely associated with overall cognition (standardized regression coefficient [β] = -0.216, 95% confidence interval (CI) -0.406 to -0.027, p = 0.025). Pulse wave velocity (β = -0.199, 95% CI -0.382 to -0.017, p = 0.033) was inversely associated with working memory task accuracy. SBP was directly associated with reaction time in the attention (β = 0.256, 95% CI 0.069 to 0.443, p = 0.008) and errors in the paired-associate learning tasks (β = 0.308, 95% CI 0.126 to 0.489, p = 0.001). Blood pressure was inversely associated with overall cognition. PA or ST did not confound the associations. Results suggest that preventing high blood pressure is important for promoting cognition in adolescents.

Cells use glycolytic intermediates for anabolism, e.g., via the serine synthesis and pentose phosphate pathways. However, we still understand poorly how these metabolic pathways contribute to skeletal muscle cell biomass generation. The first aim of this study was therefore to identify enzymes that limit protein synthesis, myotube size, and proliferation in skeletal muscle cells. We inhibited key enzymes of glycolysis, the pentose phosphate pathway, and the serine synthesis pathway to evaluate their importance in C2C12 myotube protein synthesis. Based on the results of this first screen, we then focused on the serine synthesis pathway enzyme phosphoglycerate dehydrogenase (PHGDH). We used two different PHGDH inhibitors and mouse C2C12 and human primary muscle cells to study the importance and function of PHGDH. Both myoblasts and myotubes incorporated glucose-derived carbon into proteins, RNA, and lipids, and we showed that PHGDH is essential in these processes. PHGDH inhibition decreased protein synthesis, myotube size, and myoblast proliferation without cytotoxic effects. The decreased protein synthesis in response to PHGDH inhibition appears to occur mainly mechanistic target of rapamycin complex 1 (mTORC1)-dependently, as was evident from experiments with insulin-like growth factor 1 and rapamycin. Further metabolomics analyses revealed that PHGDH inhibition accelerated glycolysis and altered amino acid, nucleotide, and lipid metabolism. Finally, we found that supplementing an antioxidant and redox modulator, N-acetylcysteine, partially rescued the decreased protein synthesis and mTORC1 signaling during PHGDH inhibition. The data suggest that PHGDH activity is critical for skeletal muscle cell biomass generation from glucose and that it regulates protein synthesis and mTORC1 signaling.NEW & NOTEWORTHY The use of glycolytic intermediates for anabolism was demonstrated in both myoblasts and myotubes, which incorporate glucose-derived carbon into proteins, RNA, and lipids. We identify phosphoglycerate dehydrogenase (PHGDH) as a critical enzyme in those processes and also for muscle cell hypertrophy, proliferation, protein synthesis, and mTORC1 signaling. Our results thus suggest that PHGDH in skeletal muscle is more than just a serine-synthesizing enzyme.

The rate of incisional hernia after closure of a temporary loop ileostomy is significant. Synthetic meshes are still commonly avoided in contaminated wounds. The Preloop trial was a multicentre RCT designed to evaluate the benefits of synthetic mesh in incisional hernia prevention, and its safety for use in a contaminated surgical site compared with biological mesh. Study patients who underwent closure of a loop ileostomy after anterior resection for rectal cancer were assigned to receive either retrorectus synthetic or biological mesh to prevent incisional hernia. The primary outcomes were surgical-site infections within 30 days, and clinical or radiological incisional hernia incidence at 10 months. Secondary outcomes were reoperation rate, operating time, duration of hospital stay, other complications within 30 days of surgery, 5-year quality of life measured by RAND-36, and incisional hernia incidence within 5 years of follow-up. Between November 2018 and September 2021, 102 patients were randomised, of whom 97 received the intended allocation. At 10-month follow-up, 90 patients had undergone clinical evaluation and 88 radiological evaluation. One patient in each group (2 per cent) had a clinical diagnosis of incisional hernia (P = 0.950) and one further patient in each group had a CT-confirmed incisional hernia (P = 0.949). The number of other complications, reoperation rate, operating time, and duration of hospital stay did not differ between the study groups. Synthetic mesh appeared comparable to biological mesh in efficacy and safety for incisional hernia prevention at the time of loop ileostomy closure. NCT03445936 (http://www.clinicaltrials.gov).

A better understanding of the earliest stages of Alzheimer's disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among Finnish biobank donors according to TWINGEN study criteria. A multi-center study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behavior and sleep. A sub-cohort are being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. TWINGEN data will be transferred to Finnish Institute of Health and Welfare (THL) biobank and we aim to further to transfer it to the FinnGen study where it will be combined with health registry data for prediction of AD. This recall study consists of FTC/THL/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.

ABSTRACT Purpose A prerequisite for successful rehabilitation is that the rehabilitees are in central role of the rehabilitation process. However, the rehabilitees and rehabilitation professionals may both lack knowledge and understanding of how to implement rehabilitee-centered participation in practice. This study aimed to explore the qualitatively different ways of understanding rehabilitee participation as conceptualized by the rehabilitees. Methods We generated data from individual interviews with 20 rehabilitees after a six-month rehabilitation process. These interviews were analyzed based on phenomenographic methodology. Results We identified three understandings of rehabilitee participation as conceptualized by the participants: 1) Dependent participation; 2) Progressive participation; and 3) Committed participation. These categories varied according to four themes: 1) Rehabilitation process; 2) Rehabilitation in everyday life; 3) Interaction in rehabilitation; and 4) Rehabilitation support network. We also identified critical aspects highlighting differences between the qualitatively distinct categories. Conclusion This study generated new insights into understanding the phenomenon of rehabilitee participation, as conceptualized by rehabilitees themselves. The findings in terms of three descriptive categories and critical aspects between the categories, reflect the ascending and shifting complexity from dependent to progressive and committed participation. These findings as such can be utilized in the design, development, and implementation of rehabilitee participation and rehabilitee-centered practice.

Projection radiography is the most common radiological modality, and radiation safety of it concerns both radiation workers and the public. We measured and generated a series of scattered radiation maps for projection radiography and estimated effective doses of the supporting person during exposure. Measured adult patient protocols included chest posterior-anterior, chest lateral, pelvis anterior-posterior (AP), abdomen AP and bedside chest AP. Maps concretise spatial distribution and the scattered radiation dose rates in different imaging protocols. Highest and lowest rates were measured in abdomen AP and bedside chest AP protocols, respectively. The effective dose of supporting person in abdomen AP examination at distance of 0.5m was 300nSv and in bedside supine chest AP examination at distance of 0.7m was 0.5nSv. The estimated annual effective dose of emergency unit radiographer was 0.11mSv. The obtained effective dose values are small compared to annual dose limits of radiation workers and the public.

The incidence of tibial plateau fractures (TPF) is 1% of all fractures and increases with age. Whether non-operatively or operatively treated, complications (infection, malalignment, loss of reduction and delayed union or nonunion) and post-traumatic osteoarthritis are not uncommon, and the risk for complications has generally been assumed to rise with age. This study investigated all post-TPF complications and secondary surgery after non-operative and operative treatment. Secondary aims were to determine the incidence and epidemiology of TPF in the population of the Central Finland region. All patients over age 18years with a TPF, including incidence, etiology, fracture type, and possible complications and reoperations, sustained during the period 1998-2019 were retrospectively identified from hospital records. The annual mean incidence of TPF was 14.4/100,000, with older women at highest risk. The proportions of non-operative and operatively treated patients who had undergone at least one additional surgical operation were 6% and 26%, respectively. Age and female gender were identified as risk factors for complications and secondary operations. The risk peaked in patients aged 60-65years, decreasing thereafter. Non-operative treatment showed low risk for both non-union and loss of reduction. Older women were at the highest risk for TPF and for subsequent complications and secondary operations after TPF. Secondary operations after operatively treated TPF were not uncommon and patients aged 60-65years were at highest risk. Given the low rates of complications and re-operations, non-operative treatment may be a safe option in cases of all minimally displaced TPF.

To examine how pediatric traumatic brain injury (pTBI) correlated with incidence of epilepsy at later ages in Finland. A nationwide retrospective register-based cohort study from 1998 to 2018. The study group consisted of 71 969 pediatric (<18 years) patients hospitalized with TBI and a control group consisting of 64 856 pediatric patients with distal extremity fracture. Epilepsy diagnoses were gathered from the Finnish Social Insurance Institution. Kaplan-Meier (KM) and multivariable Cox regression models were conducted to analyze the probability of epilepsy with 95% confidence intervals (CI). Cumulative incidence rates (CIR) for the first 2 years were 0.5% in the pTBI group and 0.1% in the control group. The corresponding rates after 15 years of follow-up were 1.5% in the pTBI group and 0.7% in the control group. Due to proportional hazard (PH) violations, the study population was split to the first 2 years and in subgroup analysis 4 years. During the first 2 years of surveillance, the hazard ratio (HR) for the pTBI group was 4.38 (CI: 3.39-5.66). However, between years 2 and 20, the HR for the pTBI group was 2.02 (CI: 1.71-2.38). A total of 337 patients (0.47%) underwent neurosurgery and 36 (10.7%) patients subsequently developed epilepsy. The CIR for the first year after TBI were 4.5% (CI: 2.3-6.7%) in operatively managed patients and 0.3% (CI: 0.3-0.4%) in non-operatively managed patients. Corresponding figures after 15 years were 12.0% (CI: 8.2-15.8%) and 1.5% (CI: 1.4-1.6%). During the first 4 years of surveillance, the HR for the operative pTBI group was 14.37 (CI: 9.29-20.80) and 3.67 (CI: 1.63-8.22) between years 4 and 20. pTBI exposes patients to a higher risk for posttraumatic epilepsy (PTE) for many years after initial trauma. Children who undergo operative management for TBI have a high risk for epilepsy, and this risk was highest during the first 4 years after injury.

BackgroundAmong the working population, a transient loss of working ability due to distal radius fracture (DRF) has a societal impact in terms of sick leave. Non-operative cast immobilization is the most common treatment option for DRF. However, these fractures are increasingly treated operatively. This retrospective cohort study of patients aged 20–64 with DRF compares the effects of different treatment strategies on sick leave length and overall cost of treatment.MethodsMultivariable regression analysis was used with treatment modality as an exposure and sick leave length as an outcome. Sick leave data were obtained from a national register. Costs were evaluated by adding the direct cost of the treatment modality to the mean cost of sick leave per patient in different treatment groups.ResultsOf 614 working-age patients with a DRF who were treated at a tertiary hospital in Finland between January 2013 and December 2014, 521 were primarily treated non-operatively with cast immobilization and 93 were primarily operated. Of the primarily non-operatively treated patients, 48 were operated during follow-up. The mean follow-up was 5 years. The median time lost from work after DRF was 55 days (7.9 weeks), and the separated medians by treatment modality were 49 (7 weeks) and 70 days (10 weeks) for conservative and operative treatment, respectively. Multivariable linear regression analyses were performed for those patients who had sick leave (n = 292). Regression analysis also showed that operative treatment correlates with longer sick leave.ConclusionsOperative treatment of distal radius fracture led more often to longer time lost from work than conservative treatment. Moreover, due to longer sick leave and the costs of the operation itself, operative treatment is over two times more expensive than conservative treatment.Trial registrationretrospectively registered.

This study aimed to provide procedure-specific estimates of the risk of symptomatic venous thromboembolism and major bleeding in the absence of thromboprophylaxis, following gynecologic cancer surgery. We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice. Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least 1 of the following were included: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding requiring reintervention (including reexploration and angioembolization), bleeding leading to transfusion, or postoperative hemoglobin <70 g/L. Two reviewers independently assessed eligibility, performed data extraction, and evaluated risk of bias of eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors. The GRADE approach was applied to rate evidence certainty. We included 188 studies (398,167 patients) reporting on 37 gynecologic cancer surgery procedures. The evidence certainty was generally low to very low. Median symptomatic venous thromboembolism risk (in the absence of prophylaxis) was <1% in 13 of 37 (35%) procedures, 1% to 2% in 11 of 37 (30%), and >2.0% in 13 of 37 (35%). The risks of venous thromboembolism varied from 0.1% in low venous thromboembolism risk patients undergoing cervical conization to 33.5% in high venous thromboembolism risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1% to 1.3%. Median risks of bleeding requiring reintervention were <1% in 22 of 29 (76%) and 1% to 2% in 7 of 29 (24%) procedures. Venous thromboembolism reduction with thromboprophylaxis likely outweighs the increase in bleeding requiring reintervention in many gynecologic cancer procedures (eg, open surgery for ovarian cancer and pelvic exenteration). In some procedures (eg, laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding venous thromboembolism and bleeding.