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Abstract Background Informing individuals about their risk of cancer can sometimes have negative consequences, such as inflicting unnecessary worry and fostering stigma. This study aims to explore how patients diagnosed with breast or colorectal cancer perceive and experience risk communication, particularly concerning the increased focus on lifestyle behaviors as the cause of cancer. Methods Semi-structured interviews were conducted during autumn 2023, with 23 Swedish individuals, aged 34 to 79 years, diagnosed with breast or colorectal cancer. The collected data were analyzed using inductive thematic analysis described by Braun & Clark. The study adopted an experiential orientation grounded in critical realism. Results Five themes with ten sub-themes were identified: Thoughts and feelings about the causes of cancer, Moralizing messages and negative encounters, The need to take action, Balancing uncertain risks and a fulfilling life, and Societal benefits of risk communication. The participants expressed that knowledge of the the cause of cancer is closely related to the possibility of taking preventive action against relapses. Ability to take action was also perceived important for their well-being. Therefore, risk information entails both feelings of self-blame and hope for the future. Participants asked for both information and lifestyle support from healthcare professionals. Lifestyle interventions and patient support groups were solicited and perceived as an important aspect of cancer survivals’ well-being, and may help to reduce the cancer-related stigma. Conclusion Individuals that have or have had breast or colorectal cancer, including those leading healthy lifestyles, found moralistic risk information offensive, leading to feelings of shame when thinking about other peoples thoughts. Balancing information involves providing transparent, evidence-based information while considering individual and social contexts, avoiding stigmatization and blame, and supplementing information with support.

Background: Dermal fillers containing copolyamide are used for breast augmentation and are marketed under different labels, such as Aquafilling, Los Deline, Aqualift, and Activegel. In recent years, the number of publications reporting complications after use of these fillers has increased. Methods: Through a computerized search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of published studies on complications, treatment options, and radiological findings related to breast augmentation with dermal fillers containing copolyamide was performed. Publications between January 1, 2007, and January 23, 2023, were included. Retrieved studies were screened for inclusion and quality assessment. The Joanna Briggs checklist for case reports and the Strengthening the Reporting of Observational Studies in Epidemiology checklist for cross-sectional studies were used. Results: Sixteen studies met the inclusion criteria: 14 case reports and 2 retrospective cohort studies, including 196 women and 333 complications. Long-term complications (≥30 days after surgery) were described in 15 studies. The most commonly reported complications were nodules in the breast (130 patients), pain (92 patients), inflammation and/or infection (43 patients), breast deformities (35 patients), and migration of the filler to the pectoralis muscle, abdominal wall, thoracic wall, pubic area, back, or upper extremity (27 patients). The median time between injection of the dermal filler and any complication was 18 months, and the majority of patients with complications required surgical intervention. Conclusion: Given the reports of severe complications months to years after injection of dermal fillers containing copolyamide and the lack of studies evaluating long-term safety, our interpretation is that dermal fillers containing copolyamide should not be used for breast augmentation.

Multi-physics thermo-fluid modeling has been extensively used as an approach to understand melt pool dynamics and defect formation as well as optimizing the process-related parameters of laser powder-bed fusion (L-PBF). However, its capabilities for being implemented as a reliable tool for material design, where minor changes in material-related parameters must be accurately captured, is still in question. In the present research, first, a thermo-fluid computational fluid dynamics (CFD) model is developed and validated against experimental data. Considering the predicted material properties of the pure Mg and commercial ZK60 and WE43 Mg alloys, parametric studies are done attempting to elucidate how the difference in some of the material properties, i.e., saturated vapor pressure, viscosity, and solidification range, can influence the melt pool dynamics. It is found that a higher saturated vapor pressure, associated with the ZK60 alloy, leads to a deeper unstable keyhole, increasing the keyhole-induced porosity and evaporation mass loss. Higher viscosity and wider solidification range can increase the non-uniformity of temperature and velocity distribution on the keyhole walls, resulting in increased keyhole instability and formation of defects. Finally, the WE43 alloy showed the best behavior in terms of defect formation and evaporation mass loss, providing theoretical support to the extensive use of this alloy in L-PBF. In summary, this study suggests an approach to investigate the effect of materials-related parameters on L-PBF melting and solidification, which can be extremely helpful for future design of new alloys suitable for L-PBF.

Abstract Background The ongoing global migration has led to multicultural societies, with many migrants who do not speak the official language in the host country. This could contribute to communication problems with staff in healthcare and a risk to patient safety. Research on patient safety in medication use in migrants is an under-researched area. The aim was to explore diverse foreign-born people’s experiences and perceptions of self-management of medication and determine if home-based practice patterns have implications on medication safety, and what factors may support safe medication use. Methods A qualitative explorative study, with individual semi-structured interviews and participant observations in the patients’ home. Qualitative content analysis was applied. Results A purposeful sample of 15 foreign-born persons identified by healthcare staff as having language difficulties in Swedish that may pose a safety risk in connection with medication use at home, was selected. Three categories were identified. The first category showed respondents being dependent on another person, having experiences of not receiving information about their medications due to language barriers, having difficulties getting access to the healthcare centre and feeling distrusted/misunderstood. The second category showed respondents being independent and self-motivated Although they struggled, they managed to get access/contact with the healthcare centre themselves and felt understood/listened to by the staff. The last category concerned factors that facilitating medication use; such as having a medication list in the respondents’ own language and offering a choice of language on the answering machine at the healthcare centre. Although they knew it was impossible to get an interpreter at the pharmacy, they felt safe knowing there was always a solution for receiving understandable information. Conclusion The findings highlighted that language barriers can complicate the communication between migrants and the healthcare, which can affect the medication safety. Understanding of this group is essential to improve the cooperation between patients and staff, leading to culturally congruent care. This knowledge should be used in healthcare to understand the gap in communication to increase patient safety. Further research from other angles, e.g. pharmacy/healthcare staff and relatives is needed to identify and evaluate facilitation to improve the outcome of the intended medication treatment.

We investigate the microstructural degradation during rolling contact fatigue (RCF) in a martensitic dual-hardening bearing steel. The dual-hardening steel makes use of both carbide precipitation and intermetallic precipitation hardening. The microstructural degradation leading to fatigue failure is studied using electron microscopy, atom probe tomography, and synchrotron X-ray diffraction (SXRD). The initial microstructure of the steel consists of tempered martensite with a fine dispersion of secondary M7C3, and NiAl precipitates. During RCF testing at 2.2 GPa contact pressure, ferrite microbands develop and the partial dissolution of NiAl and M7C3 precipitates occur within the ferrite microbands. For the RCF testing at higher contact pressure of 2.8 GPa, nanosized ferrite grains develop in the ferrite microbands. The SXRD analysis reveals a decrease in dislocation density in the sub-surface region experiencing microstructural degradation. This is believed to be associated with the rearrangement of dislocations into low energy configuration cells. We conclude this manuscript by proposing a microstructure decay mechanism for martensitic dual-hardening bearing steel that provides insights in the fatigue initiation process.

Objective: The aim of this research was to investigate whether sublingual varices (SV) are associated with new events of ischaemic heart disease (IHD) and new events of cerebrovascular disease. Methods: A prospective observational study was conducted amongst 1139 dental patients aged between 48 and 84 years across 2 cohorts (201 enrolled from 2010–2013 and 938 from 2018–2020). Participants provided baseline data on demographics, risk factors, and medical diagnoses, followed by an assessment of their tongue's ventral surface to classify veins as either having no sublingual varices (nSV) or having sublingual varices (SV). Information regarding medical diagnoses was gathered during the follow-up period from both participants and their medical records. The primary outcome variables were the onset of new IHD and new cerebrovascular disease events. Comparisons were made between participants with SV and nSV. Results: The study population comprised 54% women with an average age of 66 years. SV were present in 33% of participants. Those with SV predominantly were male, older, and smokers; had a higher body mass index, and exhibited more instances of hypertension, diabetes, and dyslipidaemia than those with nSV. New occurrences of IHD (4.5% vs 1.8%, P = .009) and cerebrovascular disease (4.2% vs 2.0%, P = .026) were more prevalent in the SV group compared with the nSV group. The link between SV and new IHD events persisted even after adjustments for sex, age, and smoking habits (OR, 2.26; 95% CI, 1.074.76), but not for new cerebrovascular disease events (OR, 1.77; 95% CI, 0.843.71). Conclusions: Our study identifies a correlation between SV and new events of IHD, but not new events of cerebrovascular disease. The detection of SV occurred prior to the IHD events, suggesting a temporal relationship. This novel finding proposes a potential shared pathophysiology between IHD and SV.

Material decay in bearing steels under rolling contact fatigue (RCF) leads to fatigue initiation and failure. This study examines the local structure-property relationship in decayed material through in-situ compression testing of micropillars prepared from a dual-hardening martensitic bearing steel (Hybrid 60) before and after RCF testing. The results demonstrate a pronounced enhancement in local yield strength for decayed regions (2200–2340 MPa) as compared to non-decayed regions (1755–1780 MPa). The higher initial stress for dislocations glide in the decayed regions and their discontinuous yield behavior are attributed to the presence of ferrite microbands. Crystal plasticity simulations corroborated these findings, showingincreased critical resolved shear stress (CRSS) and reduced strain hardening in decayed samples.

Abstract We assessed the repeatability and agreement of ganglion cell complex (GCC) in the macular area and the peripapillary retinal nerve fiber layer (ppRNFL) with individual and combined macula and disc scans. The macular GCC and ppRNFL thicknesses from 34 control eyes and 43 eyes with glaucoma were measured with the Canon Optical Coherence Tomography (OCT) HS-100. Two repeated measurements were performed with both scan modes. The repeatability limit (Rlim) and agreement analysis were performed. The individual scan showed better repeatability than the combined scan in both groups. However, the differences in the Rlim for the GCC in most sectors were lower than 3 μm (axial resolution of the OCT), and this was larger than 3 μm for most of the ppRNFL sectors. The mean differences in the thickness between both scan modes for the GCC and ppRNFL measurements were less than 3 and 6 μm, respectively. The interval of the limits of agreement was about 10 μm in some sectors for the GCC, and about 40 and 60 μm in some sectors in controls and glaucoma eyes, respectively. Both scan modes showed good repeatability in both groups. The agreement results suggest that the scan modes cannot be used interchangeably.

Background The geometrical relationship between atrial and ventricular short‐axis cross‐sectional area determines the hydraulic forces acting on intracardiac blood. This is important for diastolic filling. In patients undergoing heart transplantation (HTx), the left atrium is often enlarged as a result of the standard surgical technique. We hypothesized that diastolic filling in HTx patients is affected by the surgery altering the geometrical relationship between atrium and ventricle. Methods and Results This retrospective, cross‐sectional study included 25 HTx patients (median age, 52 [range, 25–70] years), 15 patients with heart failure with reduced ejection fraction (median age, 63 [range, 52–75] years), 15 patients with heart failure with preserved ejection fraction (median age, 74 [range, 56–82] years), and 15 healthy controls (median age, 64 [range, 58–67] years) who underwent cardiac magnetic resonance imaging. Left ventricular, atrial, and total heart volumes (THV) were obtained. Atrioventricular area difference at end diastole and end systole was calculated as the largest ventricular short‐axis area minus the largest atrial short‐axis area. Left atrial minimum volume normalized for THV (LAmin/THV) was larger in HTx patients (median, 0.13 [range, 0.07–0.19]) compared with controls (median, 0.05 [range, 0.03–0.08], P

Background and purpose: Losing independence is a main concern for hip fracture patients, and particularly not being able to return home. Given the large impact on quality of life by loss of independence and the high risk for institutionalization after hip fracture, it is of importance to identify modifiable risk factors for such negative outcomes. This study aimed to investigate the association between two such factors, that is, lean body mass and 4 months post-discharge walking capacity, and the risk of institutionalization in previously independent living older people who suffer a hip fracture. Patients and methods: A retrospective cohort study was conducted using Swedish national-based population registers. Patients ⩾60 years with a hip fracture during 2008–2017 were included from the Swedish National Registry for Hip Fractures. Risk of institutionalization over the 1-year period following a hip fracture was analyzed using logistic regression analyses adjusted for potential predictors and characteristics. Results: In total, 11,265 patients were included. Over the first year, 8% (95% CI: 8–9) of the patients with a hip fracture had lost independence, increasing to 15% (95% CI: 14–16) after 5 years. Poor recovery of post-discharge walking ability was associated with a higher odds ratio of losing independence compared with good recovery (OR 12.0; 95% CI: 7.8–18.4; p

Abstract Aim To describe what registered nurses' experience to be important to job satisfaction in nursing home settings. Design This is a qualitative study based on data from individual interviews. Methods Sixteen registered nurses working in nursing homes were interviewed, and their responses were analysed with systematic text condensation. Results A total of six categories were developed to describe various aspects of job satisfaction among registered nurses at nursing homes: meaningfulness is essential, to possess control and manageability is central, a possibility to balance daily challenges with professional development, supportive leadership is imperative, the nursing team's competence and companionship, and being confident in one's own profession. Conclusion In the present study, meaningfulness was essential to job satisfaction, and work was experienced to be meaningful and engaging when the demands were manageable, the workload controllable, and when the registered nurses felt supported by management and co‐workers. Conversely, if the demands were too high, the workload was beyond their control and the nurses felt unsupported, then the work felt meaningless and thus unsatisfactory.

The effect of chemical cleaning and regular backwashing on the efficiency of an ultrafiltration membrane fouled during stormwater treatment was studied. Increasing backwash time from 30 to 60 s resulted in an increase in productivity by 20%. However, the productivity was highest when a backwash time of 45 s was used (3% higher than using 60 s). Chemical cleaning was carried out using an alkaline solution (NaOH with or without NaOCl) followed by acid washing with HCl. The addition of NaOCl to the cleaning chemical did not significantly increase the efficiency of chemical cleaning, and the average pure water permeability increase was 97 ± 13 LMH bar−1 after chemical cleaning with NaOH followed by HCl and 117 ± 15 LMH bar−1 after chemical cleaning with NaOH + NaOCl followed by HCl, on average. In addition, reversibility after chemical cleaning was 96 ± 67%, on average. The result from scanning electron microscopy showed that at the end of the experiments, inorganic foulants existed in both the inner layer (feed side) and the outer layer (permeate side) of the membrane. HIGHLIGHTS Longer backwash time resulted in higher permeability and backwash efficiency.; Chemical cleaning using NaOH with/without NaOCl followed by acidic cleaning by HCl could recover pure water permeability and reversibility of the ultrafiltration membrane.; A significant amount of inorganic material was found on the fouling layer.;

Abstract Background Hospital length of stay (LoS) after a hip fracture likely mirrors health status; however, a too short hospitalization might increase the risk of readmission. In this national register-based study, we investigated the association between LoS after a hip fracture and the risk of readmissions. Methods 73,551 patients with a first hip fracture between 2012 and 2019 were followed for 4 months after discharge. LoS was categorized by cubic splines and the association with readmissions was analyzed with Cox regression models. Results The mean LoS was 11 ± 6 days and 25% of the study population had at least one readmission. Compared to the mean LoS of 9–12 days, there was a 18% decreased risk of readmission for LoS of 2–4 days (HR 0.82 [95% CI 0.77–0.87]) and 13% decrease for 5–8 days (HR 0.87 [95% CI 0.83–0.91]), when adjusting for sex, age, walking ability, ASA score, CCI, complications during hospitalization and living arrangements. For longer LoS, risk of readmission increased (13–23 days: HR 1.09 [95% CI 1.05–1.13] and 24 + days: HR 1.19 [95% CI 1.11–1.28]). The results were robust across sex, age, and living arrangements. The most common specific reasons for readmission were trauma/injury, cardiovascular and complications, and the proportions did not differ considerably between short and long LoS-categories. Conclusions While a long LoS can be explained by the care need of the patient, a short LoS - compared to the average stay - does not increase the risk of readmission regardless of health status and hospital complications in a Swedish setting.

Abstract In Fontan patients, a lung deprived of hepatic blood may develop pulmonary arterio-venous malformations (PAVMs) resulting in shunting, reduced pulmonary vascular resistance (PVR) and decreased oxygenation. To provide guidance for corrective invasive interventions, we aimed to non-invasively determine how the hepatic to pulmonary blood flow balance correlates with pulmonary flow, PVR, and with oxygen saturation. Magnetic resonance imaging (MRI) data from eighteen Fontan patients (eight females, age 3–14 years) was used to construct patient-specific computational fluid dynamics (CFD) models to calculate the hepatic to pulmonary blood flow. This was correlated with pulmonary vein flow, simulated PVR and oxygen saturation. Clinical applicability of the findings was demonstrated with an interventional patient case. The hepatic to pulmonary blood flow balance correlated with right/left pulmonary vein flow (R2 = 0.50), left/right simulated PVR (R2 = 0.47), and oxygen saturation at rest (R2 = 0.56). In the interventional patient, CFD predictions agreed with post-interventional MRI measurements and with regressions in the cohort. The balance of hepatic blood to the lungs has a continuous effect on PVR and oxygen saturation, even without PAVM diagnosis. MRI combined with CFD may help in planning of surgical and interventional designs affecting the hepatic to pulmonary blood flow balance in Fontan patients.

Abstract Background A significant proportion of individuals with suspicious onset of multiple sclerosis (MS) does not fulfill the diagnostic criteria. Although some receive other diagnoses, many remain undiagnosed and lack healthcare follow‐up. This study aimed to characterize persons with undetermined diagnosis (PwUD) through a questionnaire. Methods Incident cases with suspected MS were consecutively admitted to a tertiary neurological healthcare center in a prospective cohort study. Those who remained undiagnosed after 40 months (mean, range 31–52) were considered PwUD. They completed a modified questionnaire, previously used in a population‐based case‐control study of incident MS cases. Their responses were compared with two control cohorts, persons with MS (PwMS) and healthy controls, randomly selected from national registries, matched by age, gender, and area of residence. Results Out of 271 patients with suspected MS onset, 72 (20.3%) were PwUD with a female majority (79%). The response rate was 83% and 39% reported persisting MS‐like symptoms. Compared to controls (n = 548) and PwMS (n = 277), fewer PwUD were currently smoking (p = .4 and p = .03), consumed less alcohol (p = .04 and p = .01), and had children (p = .02 and p = .002). PwUD reported occurrence of other autoimmune disease in 29%, higher compared to PwMS and controls (p

Oluf Andersen,1 Ingemar Ernberg,2 Anna Karin Hedström3 1Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2Department of Microbiology, Tumor and Cell Biology, Biomedicum Q8C, Karolinska Institutet, Stockholm, 171 77, Sweden; 3Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, SwedenCorrespondence: Anna Karin Hedström, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, 171 76, Sweden, Tel +46762736426, Email anna.hedstrom@ki.seAbstract: Epstein-Barr virus (EBV), a causative agent for several types of lymphomas and mucosal cancers, is a human lymphotropic herpesvirus with the capacity to establish lifelong latent infection. More than 90% of the human population worldwide is infected. The primary infection is usually asymptomatic in childhood, whereas infectious mononucleosis (IM) is common when the infection occurs in adolescence. Primary EBV infection, with or without IM, or reactivation of latent infection in immunocompromised individuals have been associated with a wide range of neurologic conditions, such as encephalitis, meningitis, acute disseminated encephalomyelitis, and cerebellitis. EBV is also involved in malignant lymphomas in the brain. An increasing number of reports on EBV-related disorders of the central nervous system (CNS) including the convincing association with multiple sclerosis (MS) have put in focus EBV-related conditions beyond its established link to malignancies. In this review, we present the clinical manifestations of EBV-related CNS-disorders, put them in the context of known EBV biology and focus on available treatment options and future therapeutic approaches.Keywords: Epstein-Barr virus, infectious mononucleosis, central nervous system disease, multiple sclerosis, treatment, vaccination

Abstract Background There is increasing evidence of crosstalk between organs. The neuromuscular junction (NMJ) is a peripheral chemical synapse whose function and morphology are sensitive to acetylcholine (ACh) release and muscle depolarization. In an attempt to improve our understanding of NMJ plasticity and muscle crosstalk, the effects of unilateral direct electrical stimulation of a hindlimb muscle on the NMJ were investigated in rats exposed long‐term post‐synaptic neuromuscular blockade. Methods Sprague Dawley rats were subjected to post‐synaptic blockade of neuromuscular transmission by systemic administration of α‐cobrotoxin and mechanically ventilated for up to 8 days and compared with untreated sham operated controls and animals exposed to unilateral chronic electrical stimulation 12 h/day for 5 or 8 days. Results NMJs produced axonal and glial sprouts (growth of processes that extend beyond the confines of the synapse defined by high‐density aggregates of acetylcholine receptors [AChRs]) in response to post‐synaptic neuromuscular blockade, but less than reported after peripheral denervation or pre‐synaptic blockade. Direct electrical soleus muscle stimulation reduced the terminal Schwann cell (tSC) and axonal sprouting in both stimulated and non‐stimulated contralateral soleus. Eight days chronic stimulation reduced (P

BackgroundA new app, Sukaribit, was designed to enable contact between the caregiver and the patient with the intent to improve self-care and glycemic control (hemoglobin A1c [HbA1c]). ObjectiveThis study investigated the feasibility of the study methodology and the intervention in preparation for a larger effectiveness study. MethodsAdults with type 2 diabetes were recruited in this randomized controlled feasibility study with a mixed methods design. The intervention group (n=28) tried Sukaribit for 2 months. They were encouraged to report blood glucose levels and medications, and they received feedback from a physician. The control group (n=31) received standard care. Both groups were evaluated with pre and postmeasurements of glycemic control (HbA1c), diabetes distress, physical activity, and self-care. Feasibility was evaluated against 5 progression criteria regarding recruitment, study methods, and active participation. ResultsOf the 5 progression criteria, only 2 were met or partially met. The recruitment process exceeded expectations, and data collection worked well for self-reported data but not for HbA1c measured with a home testing kit. The participants were less active than anticipated, and the effect sizes were small. Only the number of blood glucose tests per day was positively affected by the intervention, with 0.6 more tests per day in the intervention group. ConclusionsRecruitment of participants to a future fully powered study may work with minor adjustments. The collection of HbA1c using home testing constituted a major problem, and an alternative strategy is warranted. Finally, the app was not used as intended. In order to proceed with a larger study, the app and study procedures need improvement.

BackgroundParkinson disease (PD) is a complex, noncurable, and progressive neurological disease affecting different areas of the human nervous system. PD is associated with both motor and nonmotor symptoms, which negatively affect patients’ quality of life and may cause changes in socialization such as intentional social withdrawal. This may further lead to social isolation and loneliness. The use of information and communication technology (ICT) plays an important role in managing social isolation and loneliness. Currently, there is a lack of research focusing on designing and developing ICT solutions that specifically address social isolation and loneliness among people living with PD. ObjectiveThis study addresses this gap by investigating barriers and social needs in the context of social isolation, loneliness, and technology use among people living with PD. The insights gained can inform the development of effective ICT solutions, which can address social isolation and loneliness and improve the quality of life for people living with PD. MethodsA qualitative study with 2 phases of data collection were conducted. During the first phase, 9 health care professionals and 16 people living with PD were interviewed to understand how PD affects social life and technology use. During the second phase, 2 focus groups were conducted with 4 people living with PD in each group to gather insights into their needs and identify ways to manage social isolation and loneliness. Thematic analysis was used to analyze both data sets and identify key themes. ResultsThe results showed that the barriers experienced by people living with PD due to PD such as “fatigue,” “psychological conditions,” “social stigma,” and “medication side effects” affect their social life. People living with PD also experience difficulties using a keyboard and mouse, remembering passwords, and navigating complex applications due to their PD-related physical and cognitive limitations. To manage their social isolation and loneliness, people living with PD suggested having a simple and easy-to-use solution, allowing them to participate in a digital community based on their interests, communicate with others, and receive recommendations for social events. ConclusionsThe new ICT solutions focusing on social isolation and loneliness among people living with PD should consider the barriers restricting user’s social activities and technology use. Given the wide range of needs and barriers experienced by people living with PD, it is more suitable to adopt user-centered design approaches that emphasize the active participation of end users in the design process. Importantly, any ICT solution designed for people living with PD should not encourage internet addiction, which will further contribute to the person’s withdrawal from society.

BackgroundSevere left-sided cardiac obstructions are associated with high morbidity and mortality if not detected in time. The correct prenatal diagnosis of coarctation of the aorta (CoA) is difficult. Fetal cardiac magnetic resonance imaging (CMR) may improve the prenatal diagnosis of complex congenital heart defects. Flow measurements in the ascending aorta could aid in predicting postnatal CoA, but its accurate visualization is challenging.ObjectivesTo compare the flow in the descending aorta (DAo) and umbilical vein (UV) in fetuses with suspected left-sided cardiac obstructions with and without the need for postnatal intervention and healthy controls by fetal phase-contrast CMR flow. A second objective was to determine if adding fetal CMR to echocardiography (echo) improves the fetal CoA diagnosis.MethodsProspective fetal CMR phase-contrast flow in the DAo and UV and echo studies were conducted between 2017 and 2022.ResultsA total of 46 fetuses with suspected left-sided cardiac obstructions [11 hypoplastic left heart syndrome (HLHS), five critical aortic stenosis (cAS), and 30 CoA] and five controls were included. Neonatal interventions for left-sided cardiac obstructions (n = 23) or comfort care (n = 1 with HLHS) were pursued in all 16 fetuses with suspected HLHS or cAS and in eight (27%) fetuses with true CoA. DAo or UV flow was not different in fetuses with and without need of intervention. However, DAo and UV flows were lower in fetuses with either retrograde isthmic systolic flow [DAo flow 253 (72) vs. 261 (97) ml/kg/min, p = 0.035; UV flow 113 (75) vs. 161 (81) ml/kg/min, p = 0.04] or with suspected CoA and restrictive atrial septum [DAo flow 200 (71) vs. 268 (94) ml/kg/min, p = 0.04; UV flow 89 vs. 159 (76) ml/kg/min, p = 0.04] as well as in those without these changes. Adding fetal CMR to fetal echo predictors for postnatal CoA did not improve the diagnosis of CoA.ConclusionFetal CMR-derived DAo and UV flow measurements do not improve the prenatal diagnosis of left-sided cardiac obstructions, but they could be important in identifying fetuses with a more severe decrease in blood flow across the left side of the heart. The physiological explanation may be a markedly decreased left ventricular cardiac output with subsequent retrograde systolic isthmic flow and decreased total DAo flow.

BackgroundReliable and valid assessment of paranoia is important in forensic psychiatry for providing adequate care. VR technology may add to current assessment procedures, as it enables observation within realistic (social) situations resembling the complexity of everyday life. VR constitutes a promising tool within forensics, due to the restricted nature of forensic psychiatric hospitals and ethical challenges arising from observing potentially dangerous behaviors in real life.ObjectiveTo investigate the feasibility of VR assessment for paranoid ideation in forensic psychiatric inpatients qualitatively by assessing the experiences of patients and a clinician, and to explore how the VR measures relate to established clinical measures.MethodsOne clinician (experienced psychiatrist) and 10 forensic psychiatric inpatients with a history or suspicion of paranoid ideation were included. Patients participated in two immersive VR scenarios (bus and supermarket) during which paranoia was assessed by the clinician. Qualitative interviews were performed with patients and the clinician performing the assessment to investigate experiences and feasibility. Further, measures of paranoia, social anxiety, and positive symptoms were obtained.ResultsNine out of 10 participants with varying levels of paranoid ideation completed the assessment. Manifest inductive content analyses of the interviews revealed general experiences, advantages such as enabling observing participants from a different perspective, and challenges of the VR assessment, such as a lack of objectivity and the laboriousness of the assessment for the clinician. Although more paranoia was experienced during the supermarket scenario, correlates with classical measures were only significant for the bus scenario.DiscussionThe VR assessment was appreciated by most patients and the clinician. Based on our results short, standardized VR assessment scenarios are feasible, however, they do not appear reliable or objective for assessing paranoia. The clinical usefulness is most likely as a collaborative tool and add-on measure to existing methods.

Objective: To investigate cognitive functioning in patients with higher education having post COVID-19 condition. Design: Prospective cohort study. Setting: Outpatient rehabilitation clinic. Participants: Patients (N=38; mean age, 48.5y; 71% women) at the Cognitive Post COVID-19 Clinic at Danderyd University Hospital in Stockholm, Sweden, who sought health care because of self-experienced cognitive problems. All had at least 4 years of university education and an initially mild infection (ie, most were not hospital admitted, none were admitted to intensive care). Interventions: Not applicable. Main Outcome Measures: Cognitive test performance assessed with a comprehensive neuropsychological test battery including Information, Matrix Reasoning, Coding, and Digit Span from Wechsler's Adult Intelligence Scale-IV, Buschke Selective Reminding Test, Rey Complex Figure Test, Ruff 2&7, Color-Word Interference Test, Verbal Fluency, and Trail Making Test. The mean time between the infection and the assessment was 18 months. Results: Cognitive deficits were evident on tests of verbal learning and memory (Buschke Selective Reminding Test) and selective attention (Ruff 2&7). Approximately 50% of the participants had scores lower than 1 SD below the mean in the norm group on the measures of verbal learning and memory. When estimated premorbid cognitive functioning was accounted for, deficits were suggested in most cognitive domains. Conclusions: Post COVID-19 condition seems to be associated with cognitive deficits, even in patients with high education and an initially mild infection.

It is well established that women’s sexual and reproductive health (SRHR) is negatively affected by war. While global health research often emphasises infrastructure and systematic factors as key impediments to women’s SRHR in war and postwar contexts, reports from different armed conflicts indicate that women’s reproduction may be controlled both by state and other armed actors, limiting women’s choices and access to maternal and reproductive health care even when these are available. In addition, it is important to examine and trace disparities in sexual reproductive health access and uptake within different types of wars, recognising gendered differences in war and postwar contexts. Adding feminist perspectives on war to global health research explanations of how war affects women's sexual and reproductive health might then contribute to further understanding the complexity of the different gendered effects war and armed conflicts have on women’s sexual and reproductive health.

Abstract Background Critical illness myopathy (CIM) is a consequence of modern critical care resulting in general muscle wasting and paralyses of all limb and trunk muscles, resulting in prolonged weaning from the ventilator, intensive care unit (ICU) treatment and rehabilitation. CIM is associated with severe morbidity/mortality and significant negative socioeconomic consequences, which has become increasingly evident during the current COVID‐19 pandemic, but underlying mechanisms remain elusive. Methods Ten neuro‐ICU patients exposed to long‐term controlled mechanical ventilation were followed with repeated muscle biopsies, electrophysiology and plasma collection three times per week for up to 12 days. Single muscle fibre contractile recordings were conducted on the first and final biopsy, and a multiomics approach was taken to analyse gene and protein expression in muscle and plasma at all collection time points. Results (i) A progressive preferential myosin loss, the hallmark of CIM, was observed in all neuro‐ICU patients during the observation period (myosin:actin ratio decreased from 2.0 in the first to 0.9 in the final biopsy, P 2) and activation of protein degradation pathways (false discovery rate [FDR] 65% during the 12 day observation period (muscle fibre cross‐sectional area [CSA] and maximum single muscle fibre force normalized to CSA [specific force] declined 30% [P

Abstract Objective To investigate whether sublingual varices are constant or inconstant over time and whether this is connected to background variables, cardiovascular risk factors or disease. Design This longitudinal observational study was performed between 2010 and 2020 at the Public Dental Services Västra Vall, Varberg, Sweden. The study was based on 431 patients included in a previous study in which the relationship between sublingual varices and hypertension was examined. In connection to the annual dental examination, 281 patients were included in the follow-up study. They completed a questionnaire about background and health factors and diseases. Length and weight were measured. Two intraoral photos were taken with a digital camera. Two dentists independent of each other graded all photographs as none/few visible sublingual varices (nSV) or medium/severe sublingual varices (SV). Results The prevalence of SV was 25.6% at baseline and 30.6% at follow-up. At the follow up, a total of 76.5% had maintained their sublingual vascular status. Of those with nSV at baseline (n209), 80.9% still had nSV, and 19.1% had developed SV during the 8-year follow-up period. Of those 72 participants who had SV at baseline, 46 (63.9%) were unchanged at follow-up, and 26 (36.1%) were classified as nSV. Those who had developed SV at follow-up had a higher mean age (p = 0.003) and a higher prevalence of cardiovascular disease (CVD), 13.2% versus 3.0% (p = 0.021). This association with CVD did not persist after an adjustment for sex and age (OR 3.2, 95% CI 0.81–12.46). They exhibited more hypertension (35.0% vs. 22.5%) and diabetes type 2 (7.5% vs. 3.0%), but with no significant difference. Conclusions This study revealed that 76.5% of the participants had an unchanged status regarding sublingual varices during an 8-year period and that the development from nSV to SV was associated with advanced age.

Abstract Objectives To investigate the association between psychosocial vulnerability, defined as either low social support or low decision latitude at work, and disease remission at 3, 12, and 60 months in patients with rheumatoid arthritis (RA). Methods This cohort study included all patients enrolled in both the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) 1996–2015 and the Swedish Rheumatology Quality Register (SRQ, n = 2820). Information on social support and decision latitude at work at RA diagnosis were identified from the EIRA questionnaire. Indexes for levels of social support and decision latitude at work, respectively, were calculated based on the questionnaire. Low social support and low decision latitude at work, respectively, were identified by a score in the lowest quartile and compared with the three other quartiles (not low). Disease-activity parameters were retrieved from SRQ at 3, 12, and 60 months. The associations between social support or decision latitude at work, respectively, and Disease Activity Score 28 joint count with C-reactive protein (DAS28-CRP) remission were analysed using logistic regression models adjusted for age, sex, smoking habits, alcohol habits, symptom duration, and educational level. Results Having low social support (n = 591) was not associated with DAS28-CRP remission at 3 (OR 0.93, 95% CI 0.74–1.16), 12 (OR 0.96, 95%CI 0.75–1.23), or 60 (OR 0.89, 95%CI 0.72–1.10) months compared to not low social support (n = 2209). No association was observed for low (n = 212) versus not low (n = 635) decision latitude at work and DAS28-CRP remission at 3 (OR 0.84, 95%CI 0.54–1.31), 12 (OR 0.81, 95%CI 0.56–1.16), or 60 (OR 1.37, 95%CI 0.94–2.01) months. Conclusion In a country with general access to healthcare, psychosocial vulnerability does not influence the likelihood of achieving remission in early RA.

Abstract Background Critical illness myopathy (CIM) is a debilitating condition characterized by the preferential loss of the motor protein myosin. CIM is a by‐product of critical care, attributed to impaired recovery, long‐term complications, and mortality. CIM pathophysiology is complex, heterogeneous and remains incompletely understood; however, loss of mechanical stimuli contributes to critical illness‐associated muscle atrophy and weakness. Passive mechanical loading and electrical stimulation (ES) therapies augment muscle mass and function. While having beneficial outcomes, the mechanistic underpinning of these therapies is less known. Therefore, here we aimed to assess the mechanism by which chronic supramaximal ES ameliorates CIM in a unique experimental rat model of critical care. Methods Rats were subjected to 8 days of critical care conditions entailing deep sedation, controlled mechanical ventilation, and immobilization with and without direct soleus ES. Muscle size and function were assessed at the single cell level. RNAseq and western blotting were employed to understand the mechanisms driving ES muscle outcomes in CIM. Results Following 8 days of controlled mechanical ventilation and immobilization, soleus muscle mass, myosin : actin ratio, and single muscle fibre maximum force normalized to cross‐sectional area (CSA; specific force) were reduced by 40–50% (P

Compelling evidence indicates that Epstein Barr virus (EBV) infection is a prerequisite for multiple sclerosis (MS). The disease may arise from a complex interplay between latent EBV infection, genetic predisposition, and various environmental and lifestyle factors that negatively affect immune control of the infection. Evidence of gene-environment interactions and epigenetic modifications triggered by environmental factors in genetically susceptible individuals supports this view. This review gives a short introduction to EBV and host immunity and discusses evidence indicating EBV as a prerequisite for MS. The role of genetic and environmental risk factors, and their interactions, in MS pathogenesis is reviewed and put in the context of EBV infection. Finally, possible preventive measures are discussed based on the findings presented.

Infiltration and inflow (I/I) into sanitary sewers causes numerous negative effects on the whole wastewater management system and ultimately, on the receiving waters. Consequently, a number of methods have been developed to analyse the performance of sewer systems with respect to I/I, including: distributed temperature sensing (DTS), closed-circuit television (CCTV) inspections, flow and conductivity measurements, automatic or grab sampling of ammonium, smoke testing, and visual inspection of manholes. Such methods were compared in an application to sanitary sewers in a small community and assessed with respect to their accuracy and ability to identify locations of sources of I/I, as well as temporal and spatial resolutions of the obtained results. Furthermore, different approaches to ammonium sampling during I/I monitoring campaigns were discussed. It was concluded that among the methods tested in this study, DTS had the highest temporal and spatial resolution, while ammonium grab sampling showed promise for initial screening of large catchments. HIGHLIGHTS Number of methods to analyse I/I in sewer system were compared.; CCTV and visual inspection provided many locations with a potential risk of I/I but were not confirmed by other methods.; Advantages and practical limitations of different ammonium sampling strategies were discussed.; Combination of two to three methods is recommended depending on the main focus of an I/I monitoring programme.;

Abstract Background Previous studies have found an increase in cardiac troponins (cTns) and echocardiographic abnormalities in patients with COVID-19 and reported their association with poor clinical outcomes. Whether acute injury occurs during the course of critical care and if it is associated with cardiac function is unknown. The purpose of this study was to document the incidence of acute myocardial injury (AMInj) and echocardiographically defined left ventricular (LV) and right ventricular (RV) systolic dysfunction in consecutive patients admitted to an intensive care unit (ICU) for COVID-19. The relationship between AMInj and echocardiographic abnormalities during the first 14 days of ICU admission was studied. Finally, the association between echocardiographic findings, AMInj and clinical outcome was evaluated. Methods Seventy-four consecutive patients (≥18 years) admitted to the ICU at Linköping University Hospital between 19 Mar 2020 and 31 Dec 2020 for COVID-19 were included. High-sensitivity troponin-T (hsTnT) was measured daily for up to 14 days. Transthoracic echocardiography was conducted within 72 h of ICU admission. Acute myocardial injury was defined as an increased hsTnT > 14ng/l and a > 20% absolute change with or without ischaemic symptoms. LV and RV systolic dysfunction was defined as at least 2 abnormal indicators of systolic function specified by consensus guidelines. Results Increased hsTnT was observed in 59% of patients at ICU admission, and 82% developed AMInj with peak levels at 8 (3–13) days after ICU admission. AMInj was not statistically significantly associated with 30-day mortality but was associated with an increased duration of invasive mechanical ventilation (10 (3–13) vs. 5 days (0–9), p=0.001) as well as ICU length of stay (LOS) (19.5 (11–28) vs. 7 days (5–13), p=0.015). After adjustment for SAPS-3 and admission SOFA score, the effect of AMInj was significant only for the duration of mechanical ventilation (p=0.030). The incidence of LV and RV dysfunction was 28% and 22%, respectively. Only indices of LV and RV longitudinal contractility (mitral and tricuspid annular plane systolic excursion) were associated with AMInj. Echocardiographic parameters were not associated with clinical outcome. Conclusions Myocardial injury is common in critically ill patients with COVID-19, with AMInj developing in more than 80% after ICU admission. In contrast, LV and RV dysfunction occurred in approximately one-quarter of patients. AMInj was associated with an increased need for mechanical ventilation and ICU LOS but neither AMInj nor ventricular dysfunction was significantly associated with mortality.

Håkan Bergh,1,2 Margit Albrektson,3 Clovis Kastberg,4 Amir Baigi,1,2 Lennart Hedström3 1School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; 2Department of Research & Development Unit, Hospital Varberg, Region Halland, Sweden; 3Public Dental Services, Västra Vall, Varberg, Sweden; 4Tre Tandläkare, Varberg, SwedenCorrespondence: Håkan Bergh, School of Public Health and Community Medicine, Institute of Medicine, P.O. Box 463, Gothenburg, 405 30, Sweden, Email hakan.e.bergh@gmail.com Lennart Hedström, Public Dental Service, Västra Vallgatan 14, Varberg, S-43244, Region Halland, Sweden, Email h.lennart.hedstrom@gmail.comObjective: To study the association between sublingual varices (SV) and cardiovascular (CVD) risk factors.Methods: A total of 989 consecutive dental patients aged 55– 84 years participated in the study, which applied a survey about risk factors, diseases and medications. Digital photos of the lateral borders of the tongue, height, weight, waist, hip and blood pressure were registered, and blood samples were analyzed. Those with SV were compared with those without SV (nSV).Results: Those with SV had more hypertension 41.8% vs 27.0% (p< 0.0001), a higher systolic blood pressure (BP) 139.5 (SD 18.6) mmHg vs 134.3 (SD 18.8) mmHg (95% CI − 7.73 &boxh; − 2.72), more diabetes type 2 (DM-2) 7.4% vs 3.8% (p=0.014), a higher fasting plasma glucose 5.9 (SD 1.5) mmol/L vs 5.7 (SD 1.0) mmol/L (95% CI − 0.42 &boxh; − 0.05), more dyslipidemia 24.1% vs 17.7% (p=0.018), lower HDL 1.6 vs 1.7 (p=0.003), a greater waist circumference 97.0 cm vs 93.9 cm (95% CI − 4.66 &boxh; − 1.46), a greater waist/hip ratio 0.92 cm/cm vs 0.90 cm/cm (95% CI − 0.03 &boxh; − 0.01), and a higher BMI 26.6 kg/m2 vs 26.0 kg/m2 (95% CI − 1.11 &boxh; − 0.03). The following associations with SV were found in multivariate analysis: hypertension OR=1.6 (95% CI 1.19 &boxh;2.13), a high systolic BP OR =1.5 (95% CI 1.11 &boxh;2.13), a high fP-glucose OR= 1.8 (95% CI 1.03 &boxh;3.21), a low HDL OR= 1.8 (95% CI 1.15 &boxh;2.92), a greater waist circumference OR= 1.68 (95% CI 1.10 &boxh;2.58), a greater waist/hip ratio OR=2.21 (95% CI 1.36 &boxh;3.58), and a higher BMI OR=1.05 (95% CI 1.02 &boxh;1.09).Conclusion: This study shows an association between SV and a high BP, a high fP-glucose, hypertension, diabetes mellitus type 2, dyslipidemia, abdominal obesity, older age and smoking.Keywords: sublingual varices, cardiovascular riskfactors

A “body activism” movement, with roots in fat activism and body positivity, has developed in Sweden during the last decade. As new forms of activism emerge, boundaries and approaches are being negotiated. Who is the movement for? Who can engage in it, and how? Through semi-structured interviews, we seek to understand how young Swedes who follow and engage in “body activism” on social media experience and reflect on the activism, belonging and entitlement, and their own participation. The informants discussed activism in terms of inclusiveness and political potential, where the most accessible activism is also the one ascribed with the least political potential. Entitlement is linked to collective identity, where an active participation requires belonging to the marginalised group. This article highlights the significance of boundary work in movements, where too narrowly drawn boundaries can lead to decreased participation and result in an unexploited potential for social change.

Background and purpose: Waiting time to surgery is a modifiable risk factor in hip fracture surgery. However, there is no consensus regarding the acceptable duration of waiting time. We used the Swedish Hip Fracture Register RIKSHÖFT and 3 administrative registers to explore the association between time to surgery and adverse outcomes after discharge. Patients and methods: 63,998 patients ≥ 65 years, admitted to a hospital between January 1, 2012, and August 31, 2017 were included. Time to surgery was divided into < 12, 12–24, and > 24 hours. Diagnoses investigated were atrial fibrillation/flutter (AF), congestive heart failure (CHF), pneumonia, and “acute ischemia” (a combination of stroke/intracranial bleeding, myocardial infarction, and acute kidney injury). Crude and adjusted survival analyses were performed. Time spent in hospital following the initial hospitalization was described for the 3 groups. Results: Waiting > 24 hours was associated with an increased risk of AF (HR 1.4, 95%CI 1.2–1.6), CHF (HR 1.3, CI 1.1–1.4) and “acute ischemia” (HR 1.2, CI 1.01–1.3). However, stratifying for ASA grade revealed that these associations were present only in patients with ASA 3–4. There was no association between waiting time and pneumonia after the initial hospitalization (HR 1.1, CI 0.97–1.2), but one was found with pneumonia during hospital stay OR 1.2 (CI 1.1–1.4). Time in hospital after the initial hospitalization was similar over the waiting time groups. Conclusion: The associations between waiting > 24 hours for hip fracture surgery and AF, CHF, and acute ischemia suggest that shorter waiting time may reduce adverse outcomes for the sicker patients.

Abstract Background Quantitative bacterial culture (QBC) is the gold standard for diagnosing canine urinary tract infection. Current guidelines recommend QBC within 24 h of urine collection and that unpreserved urine is refrigerated until culture. However, temperature-controlled transport is rarely feasible, indicating a need for alternative storage during transport of urine from primary veterinary practices to the microbiology laboratory. The objective was to investigate the effect of storage temperature and boric acid sponge-preservation on quantitative bacterial culture of canine urine. Results Significant bacteriuria was detected in 72 out of 179 samples (40%) collected from 141 dogs. Overall accuracy was 94–98% for both storage conditions and time points. Non-inferiority (15% margin) to reference quantitative bacterial culture was evident for sensitivity, specificity and predictive values for both storage methods and time points, except for the negative predictive value for 48 h boric acid preservation (NPV: 89, 95% CI [79;95]). There was no significant difference between the sensitivity and specificity for either of the time-points (p-value = 0.07–1). Conclusions Boric acid sponge-preservation using Uriswab™ is a useful alternative to refrigeration of urine samples during transport. Reliable quantitative bacterial culture results can be obtained from canine urine up to 48 h after collection if urine is refrigerated, and for at least 24 h if urine is stored using a boric acid-containing urine transport system.

Background: Gallstones intervention during pregnancy might be a stressful event for both mother and fetus and stress might affect outcome. The aim of this study was to identify factors that might improve the care of pregnant patients in need of intervention for gallstone disease. Methods: By crossmatching the Swedish Registry of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks) and the Swedish Medical Birth Registry, we identified patients with gallstone intervention during pregnancy. A questionnaire covering patient experience before, during and after surgery and the Beck Depression Inventory II (BDI-II) were distributed. Results: In total, 275 patients subjected to cholecystectomy, endoscopic retrograde cholangiopancreatography (ERCP) or both were identified, and 146 (54%) patients responded. Surgery was in median performed in pregnancy week 16 (12–20), and 62 (42%) patients had symptoms of gallstone disease before pregnancy, with 17 of these patients scheduled for surgery before pregnancy. Thirty-four (24%) patients felt that the information regarding the upcoming surgery was inadequate, with differences comparing patients with overall favorable versus overall non-favorable experiences (103 (89%) vs. 8 (27%) p < 0.001) and similar differences regarding information on disease/symptoms (95 (84%) vs. 12 (43%), p < 0.001). A majority (57%) were very worried about their expected child, and 51% thought that no measures were taken to relieve their worries. Recurring as suggested improvements was more information about the disease and the surgical procedure. Conclusion: Intervention due to gallstone disease during pregnancy is a stressful event that impacts many patients negatively, both before and after surgery. Patient education might positively affect patient experience.

Melatonin is a hormone that regulates sleep–wake cycles and is mainly synthesized in the pineal gland from tryptophan after its conversion into serotonin. Under normal conditions, less than 5% of tryptophan is reserved for the synthesis of serotonin and melatonin. The remaining 95% is metabolized in the liver through the kynurenine pathway. Increased levels of proinflammatory cytokines and cortisol increase the metabolism of tryptophan through the kynurenine pathway and reduce its availability for the synthesis of melatonin and serotonin, which may cause alterations in mood and sleep. The standardized saffron extract (affron®) has shown beneficial effects on mood and sleep disorders in humans, but the underlying mechanisms are not well understood. Thus, the aim of this work was to study the effects of affron® supplementation on the kynurenine pathway and the synthesis of melatonin in rats. For this purpose, adult male Wistar rats were supplemented for 7 days with 150 mg/kg of affron® or vehicle (2 mL/kg water) administered by gavage one hour before sleep. Affron® supplementation reduced body weight gain and increased the circulating levels of melatonin, testosterone, and c-HDL. Moreover, animals supplemented with affron® showed decreased serum levels of kynurenine, ET-1, and c-LDL. In the pineal gland, affron® reduced Il-6 expression and increased the expression of Aanat, the key enzyme for melatonin synthesis. In the liver, affron® administration decreased the mRNA levels of the enzymes of the kynurenine pathway Ido-2, Tod-2, and Aadat, as well as the gene expression of Il-1β and Tnf-α. Finally, rats treated with affron® showed increased mRNA levels of the antioxidant enzymes Ho-1, Sod-1, Gsr, and Gpx-3, both in the liver and in the pineal gland. In conclusion, affron® supplementation reduces kynurenine levels and promotes melatonin synthesis in rats, possibly through its antioxidant and anti-inflammatory effects, making this extract a possible alternative for the treatment and/or prevention of mood and sleep disorders.

Analytical tools used in infrastructure asset management of urban water pipe networks are reliant on asset data. Traditionally, data required by analytical tools has not been collected by most water utilities because it has not been needed. The data that is collected might be characterised by low availability, integrity and consistency. A process is required to support water utilities in assessing the accuracy and completeness of their current data management approach and defining improvement pathways in relation to their objectives. This study proposes a framework to enable increased data-driven asset management in pipe networks. The theoretical basis of the framework was a literature review of data management for pipe network asset management and its link to the coherence of set objectives. A survey to identify the current state of data management practice and challenges of asset management implementation in five Swedish water utilities and three focus group workshops with the same utilities was carried out. The main findings of this research were that the quality of pipe network datasets and lack of interoperability between asset management tools are drivers for creating data silos between asset management levels, which may hinder the implementation of data-driven asset management. Furthermore, these findings formed the basis for the proposed conceptual framework. The suggested framework aims to support the selection, development and adoption of improvement pathways to enable increased data-driven asset management in municipal pipe networks. Results from a preliminary application of the proposed framework are also presented. HIGHLIGHTS A link between data quality and interoperability relative to the data management approach and data silos between IAM levels was established.; A conceptual framework is proposed to assess the state of data management relative to data-driven IAM.; A preliminary application of the framework to sewer blockage data and IAM tools in one municipality showed low interoperability with medium data quality, i.e. intuitive IAM.;

Additive Manufacturing (AM) is becoming an important technology for manufacturing of metallic materials. Laser-Powder Bed Fusion (L-PBF), Electron beam-Powder Bed Fusion (E-PBF) and Directed Energy Deposition (DED) have attracted significant interest from both the scientific community and the industry since these technologies offer great manufacturing opportunities for niche applications and complex geometries. Understanding the physics behind the complex and dynamic phenomena occurring during these processes is essential for overcoming the barriers that constrain the metal AM development. In-situ synchrotron X-ray characterization is suitable for investigating the microstructure evolution during processing and provides new profound insights. Here, we provide an overview of the research on metal PBF and DED using in-situ synchrotron X-ray imaging, diffraction and small-angle scattering, highlighting the state of the art, the instrumentation, the challenges and the gaps in knowledge that need to be filled. We aim at presenting a scientific roadmap for in-situ synchrotron analysis of metal PBF and DED where future challenges in instrumentation such as the development of experimental stations, sample environments and detectors as well as the need for further application oriented research are included.

Background and purpose: Internal fixation (IF) has been the standard procedure for undisplaced femoral neck fractures (FNFs). However, there is a changing trend towards hip replacement (HR). Yet there is a knowledge gap regarding the benefits of this surgical method. We investigated functional outcomes in patients ≥ 70 years following HR compared to IF for undisplaced FNFs. Patients and methods: Patients ≥ 70 years with undisplaced FNF registered in the Swedish National Hip Fracture Registry (SHR) who underwent either IF or HR (hemiarthroplasty [HA)] or total hip arthroplasty [THA]) were investigated in terms of 1-year survival and proportion of reoperation. In a subsample with 4-month follow-up data (n = 3,623), pain, changes in living status, and physical function were additionally analyzed. Results: 7,758 patients were included with a mean age of 85 years. 93% of the patients were operated on with IF, 5% with HA, and 2% with THA. Patients with THA more often lived independently and were able to walk outdoors, both before and after the hip fracture. The IF and HA groups were similar in baseline characteristics, and in functional and survival outcomes. The THA group had a 54% lower adjusted risk of 1-year mortality. The proportion of reoperations within 1 year was 9.5% for IF, 5.3% for HA, and 7% for THA. Interpretation: The pre-fracture difference in health and function between patients operated on with IF, HA, and THA maked it difficult to compare outcomes of the 2 methods. Decision on surgical method must be taken on an individual level, considering patients’ well-being and allocation of resources.

Restoration of the p53 tumor suppressor for personalised cancer therapy is a promising treatment strategy. However, several high-affinity MDM2 inhibitors have shown substantial side effects in clinical trials. Thus, elucidation of the molecular mechanisms of action of p53 reactivating molecules with alternative functional principle is of the utmost importance. Here, we report a discovery of a novel allosteric mechanism of p53 reactivation through targeting the p53 N-terminus which promotes inhibition of both p53/MDM2 (murine double minute 2) and p53/MDM4 interactions. Using biochemical assays and molecular docking, we identified the binding site of two p53 reactivating molecules, RITA (reactivation of p53 and induction of tumor cell apoptosis) and protoporphyrin IX (PpIX). Ion mobility-mass spectrometry revealed that the binding of RITA to serine 33 and serine 37 is responsible for inducing the allosteric shift in p53, which shields the MDM2 binding residues of p53 and prevents its interactions with MDM2 and MDM4. Our results point to an alternative mechanism of blocking p53 interaction with MDM2 and MDM4 and may pave the way for the development of novel allosteric inhibitors of p53/MDM2 and p53/MDM4 interactions.

Nutraceuticals are products of natural origin widely used for the treatment and/or prevention of some chronic diseases that are highly prevalent in Western countries, such as obesity or type II diabetes, among others. However, its possible use in the prevention of acute diseases that can put life at risk has been poorly studied. Sepsis is an acute condition that causes cardiovascular and skeletal muscle damage due to a systemic inflammatory state. The aim of this work was to evaluate the possible beneficial effect of a new nutraceutical based on a mixture of algae oil (AO) and extra virgin olive oil (EVOO) supplemented with an olive leaf extract (OLE) in the prevention of cardiovascular alterations and skeletal muscle disorders induced by sepsis in rats. For this purpose, male Wistar rats were treated with the nutraceutical or with water p.o. for 3 weeks and after the treatment they were injected with 1mg/kg LPS twice (12 and 4 h before sacrifice). Pretreatment with the nutraceutical prevented the LPS-induced decrease in cardiac contractility before and after the hearts were subjected to ischemia-reperfusion. At the vascular level, supplementation with the nutraceutical did not prevent hypotension in septic animals, but it attenuated endothelial dysfunction and the increased response of aortic rings to the vasoconstrictors norepinephrine and angiotensin-II induced by LPS. The beneficial effects on cardiovascular function were associated with an increased expression of the antioxidant enzymes SOD-1 and GSR in cardiac tissue and SOD-1 and Alox-5 in arterial tissue. In skeletal muscle, nutraceutical pretreatment prevented LPS-induced muscle proteolysis and autophagy and significantly increased protein synthesis as demonstrated by decreased expression of MURF-1, atrogin-1, LC3b and increased MCH-I and MCH -IIa in gastrocnemius muscle. These effects were associated with a decrease in the expression of TNFα, HDAC4 and myogenin. In conclusion, treatment with a new nutraceutical based on a mixture of AO and EVOO supplemented with OLE is useful to prevent cardiovascular and muscular changes induced by sepsis in rats. Thus, supplementation with this nutraceutical may constitute an interesting strategy to reduce the severity and mortality risk in septic patients.

The low oxidative stability of polyunsaturated fatty acids (PUFA) in omega-3 supplements may cause the formation of compounds that may have negative healthy effects. Extra virgin olive oil (EVOO) contains high content of monounsaturated fatty acids (MUFA) and polyphenols, which might improve PUFA oxidative stability when combined with vegetable oils enriched in them. In order to prevent the formation of oxidized compounds and improve the shelf-life of PUFA, different proportions of EVOO (enriched in oleic acid and polyphenols) and algae oil (AO) were studied. For this purpose, both pure oils combined in different proportions were stored under accelerated degradation conditions (40 and 55 °C) for 70 days. Correlations and significant changes in levels of fatty acids composition, phenolic components and oxidation rates during storage time were studied. Throughout storage, higher EVOO quantity at the final mixture was related with less PUFA degradation, where a 27.53% decrease in PUFA of AO passed to less than 12% in a resulting oil of at least 75% of EVOO. PUFA concentration correlated with the formation of secondary peroxides, while MUFA content from EVOO produced a reduction in PUFA degradation. In addition, high secoiridoid levels in mixtures decreased the hydrolysis of triglycerides over the time.

Abstract It is unclear whether smoking interacts with different aspects of Epstein–Barr virus (EBV) infection with regard to multiple sclerosis (MS) risk. We aimed to investigate whether smoking acts synergistically with elevated EBNA-1 antibody levels or infectious mononucleosis (IM) history regarding MS risk. Two Swedish population-based case–control studies were used (6,340 cases and 6,219 matched controls). Subjects with different smoking, EBNA-1 and IM status were compared regarding MS risk, by calculating odds ratios (OR) with 95% confidence intervals (CI) employing logistic regression. Potential interaction on the additive scale was evaluated by calculating the attributable proportion due to interaction (AP). Current and past smokers had higher EBNA-1 antibody levels than never smokers (p

An analytical flow stress model, based on isotropic strain gradient plasticity theory, for precipitation hardened materials, is proposed and evaluated against tensile data on a 15 wt% Cr - 5 wt% Ni (15-5) PH stainless steel. The 15-5 PH material was aged at 500 °C for 1 h, 2 h, 5 h and 50 h to obtain a wide range of precipitate sizes. Detailed characterisation of precipitates was obtained using atom probe tomography (APT). A second material, a 15-5 stainless steel without added Cu was heat treated to obtain a similar matrix microstructure as in the 15-5 PH, but without Cu precipitates. Tensile testing revealed that the heat treated 15-5 PH material covered the full range from under- to overaged conditions. The analytical model, which accounts for stress reducing effects of plastic relaxation around particles, manages to capture the experimental data in a very satisfying manner using only a total of three tunable parameters. It is believed that the proposed model can offer an alternative to the much more commonly used work hardening models based on the internal variable approach.

BackgroundAdvancements in science and various technologies have resulted in people having access to better health care, a good quality of life, and better economic situations, enabling humans to live longer than ever before. Research shows that the problems of loneliness and social isolation are common among older adults, affecting psychological and physical health. Information and communication technology (ICT) plays an important role in alleviating social isolation and loneliness. ObjectiveThe aim of this review is to explore ICT solutions for reducing social isolation or loneliness among older adults, the purpose of ICT solutions, and the evaluation focus of these solutions. This study particularly focuses on customized ICT solutions that either are designed from scratch or are modifications of existing off-the-shelf products that cater to the needs of older adults. MethodsA scoping literature review was conducted. A search across 7 databases, including ScienceDirect, Association for Computing Machinery, PubMed, IEEE Xplore, PsycINFO, Scopus, and Web of Science, was performed, targeting ICT solutions for reducing and managing social isolation and loneliness among older adults. Articles published in English from 2010 to 2020 were extracted and analyzed. ResultsFrom the review of 39 articles, we identified 5 different purposes of customized ICT solutions focusing on reducing social isolation and loneliness. These were social communication, social participation, a sense of belonging, companionship, and feelings of being seen. The mapping of purposes of ICT solutions with problems found among older adults indicates that increasing social communication and social participation can help reduce social isolation problems, whereas fulfilling emotional relationships and feeling valued can reduce feelings of loneliness. In terms of customized ICT solution types, we found the following seven different categories: social network, messaging services, video chat, virtual spaces or classrooms with messaging capabilities, robotics, games, and content creation and management. Most of the included studies (30/39, 77%) evaluated the usability and acceptance aspects, and few studies (11/39, 28%) focused on loneliness or social isolation outcomes. ConclusionsThis review highlights the importance of discussing and managing social isolation and loneliness as different but related concepts and emphasizes the need for future research to use suitable outcome measures for evaluating ICT solutions based on the problem. Even though a wide range of customized ICT solutions have been developed, future studies need to explore the recent emerging technologies, such as the Internet of Things and augmented or virtual reality, to tackle social isolation and loneliness among older adults. Furthermore, future studies should consider evaluating social isolation or loneliness while developing customized ICT solutions to provide more robust data on the effectiveness of the solutions.

The most common gene regulation mechanism is when a transcription factor (TF) protein binds to a regulatory sequence to increase or decrease RNA transcription. However, TFs face two main challenges when searching for these sequences. First, the sequences are vanishingly short relative to the genome length. Second, there are many nearly identical sequences scattered across the genome, causing proteins to suspend the search. But as pointed out in a computational study of LacI regulation in Escherichia coli , such almost-targets may lower search times if considering DNA looping. In this paper, we explore if this also occurs over chromosome-wide distances. To this end, we developed a cross-scale computational framework that combines established facilitated-diffusion models for basepair-level search and a network model capturing chromosome-wide leaps. To make our model realistic, we used Hi-C data sets as a proxy for 3D proximity between long-ranged DNA segments and binding profiles for more than 100 TFs. Using our cross-scale model, we found that median search times to individual targets critically depend on a network metric combining node strength (sum of link weights) and local dissociation rates. Also, by randomizing these rates, we found that some actual 3D target configurations stand out as considerably faster or slower than their random counterparts. This finding hints that chromosomes’ 3D structure funnels essential TFs to relevant DNA regions.

The impact of cooling rate during high-pressure gas quenching on the fatigue performance of low-pressure carburized spur gears was studied for steel grades 20MnCr5 and 17NiCrMo6-4. The results show an increased fatigue limit by 10 to 11% when applying a slower cooling rate for both steel grades. Moreover, for 20MnCr5 the slower cooled gears show an increase in compressive residual stresses by 130 MPa compared to the faster cooling, although no significant difference was observed for 17NiCrMo6-4. It is also seen that the cooling rate affects the core hardness for both steel grades, while other properties like surface hardness, case-hardness depth and martensite variant pairing were unaffected. The results for the retained austenite content and average martensite unit size show no clear effect of the cooling rate. The possible influence of different carbon distributions after quenching for the two used cooling rates on the carbide precipitation and fatigue limit is discussed.