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Physiotherapists increasingly deliver treatment informed by cognitive-behavioural therapy, including Acceptance and Commitment Therapy (ACT), for persistent pain. This study explored patients' experiences of ACT-informed physiotherapy to better understand therapeutic processes and outcomes.A qualitative descriptive study was conducted. Focus groups explored participants' experience of ACT-informed physiotherapy in the context of a pain management programme. Responses were audio recorded, transcribed verbatim, and analysed using a hybrid inductive-deductive reflexive thematic analysis.A single tertiary care pain management service.The sample consisted of fifteen patients from two treatment groups who completed an intensive multidisciplinary ACT-based pain management programme. Participants were included irrespective of their treatment response.One overarching theme (living more and struggling less) and four interconnected themes were generated from the data: 1) awareness and openness help to approach physical activities flexibly; 2) from battling against to working with the body compassionately; 3) from narrow focus to curiosity, freedom, and expansion; and 4) social connection is a catalyst for openness and engagement.Participants experienced ACT-informed physiotherapy as helping them to live more and struggle less with pain; this occurred in the context of a psychologically flexible relationship with the physiotherapist and was catalysed by social connection. These findings should be seen as preliminary given the small number and relatively brief duration of focus groups conducted. Further research is needed to explore how principles within ACT-informed physiotherapy may support patients and clinicians to respond effectively to the challenges that persistent pain can bring.

Data concerning the comparison between transcatheter aortic valve implantation and surgical aortic valve replacement in a real-world setting are scarce and in Central and Eastern Europe no such data exist. In this study, we aimed at analyzing retrospectively the characteristics and outcome of patients with aortic stenosis treated either with surgical aortic valve replacement or transcatheter aortic valve implantation between 2006 and 2016 in the Silesian Province, Poland in a representative real-world cohort.In the Silesian Cardiovascular Database we retrospectively identified 5186 patients who received either transcatheter aortic valve implantation or surgical aortic valve replacement in 1 of 3 tertiary cardiovascular centers. Baseline characteristics, including relevant clinical history, and outcomes were compared before and after propensity-score matching of both groups, with 348 pairs of patients constituting the propensity-matched study cohort. The primary end-point was 24-month all-cause mortality.Preoperative characteristics of propensity-matched groups were similar. There was no difference between transcatheter aortic valve implantation and surgical aortic valve replacement groups with respect to the death rate at 2 years (19.9% vs. 15.6%; P =.479). In the transcatheter aortic valve implantation group, cardiac resynchronization therapy devices were more frequently implanted after the procedure (3.7% vs. 0.0, P.001). The groups had similar rates of myocardial infarction, stroke, and re-hospitalization. Hospital stay in the matched groups was shorter after transcatheter aortic valve implantation: 14.1 versus 15.7 days (P.001).At 24 months, transcatheter aortic valve implantation patients had similar outcomes as surgical aortic valve replacement except for a higher rate of cardiac resynchronization therapy device implantation and shorter hospital stay.

OBJECTIVE To assess how bone morphology and mineralization changes with age, in women by digital X-ray radiogrammetry (DXR). DXR has potential as a screening tool for osteoporosis, as it can evaluate bone mineralization similarly to dual-energy X-ray absorptiometry. METHODS The nondominant hand was analyzed with DXR in 13,285 women ages 40-74 years undergoing mammography. 1,556 women attended two consecutive examinations with 18 to 24 months interval. Changes in bone parameters were calculated and compared in 5-year age groups. Regression analysis and ANOVA tests were performed. RESULTS Univariate linear regression showed no significant difference in age or bone size between the groups with single or consecutive measurements. In the group with consecutive measurements, the average inner diameter (DXR-ID) of the metacarpals significantly increased with age from 0.38 cm in the 40-45 years age span to 0.47 cm in the 65+ age group (P

AIMS: Sepsis-induced cardiomyopathy is a major complication of septic shock and contributes to its high mortality. This pilot study investigated myocardial tissue differentiation in critically ill, sedated, and ventilated patients with septic shock using cardiovascular magnetic resonance (MR). METHODS AND RESULTS: Fifteen patients with septic shock were prospectively recruited from the intensive care unit. Individuals received a cardiac MR scan (1.5 T) within 48 h after initial catecholamine peak and a transthoracic echocardiography at 48 and 96 h after cardiac MR. Left ventricular ejection fraction was assessed using both imaging modalities. During cardiac MR imaging, balanced steady-state free precession imaging was performed for evaluation of cardiac anatomy and function in long-axis and short-axis views. Native T1 maps (modified Look-Locker inversion recovery 5 s(3 s)3 s), T2 maps, and extracellular volume maps were acquired in mid-ventricular short axis and assessed for average plane values. Patients were given 0.2 mmol/kg of gadoteridol for extracellular volume quantification and late gadolinium enhancement imaging. Critical care physicians monitored sedated and ventilated patients during the scan with continuous invasive monitoring and realized breathholds through manual ventilation breaks. Laboratory analysis included high-sensitive troponine T and N terminal pro brain natriuretic peptide levels. Twelve individuals with complete datasets were available for analysis (age 59.5 ± 16.9 years; 6 female). Nine patients had impaired systolic function with left ventricular ejection fraction (LVEF)

Sepsis can affect various organs as well as the hematologic system. Systemic dysregulation, present in sepsis, affects particularly red blood cells (RBCs). One of the widely available RBC indices is RBC distribution width (RDW). Sepsis may also affect hemostasis, with septic patients presenting with coagulopathy or disseminated intravascular coagulation. The aim of our study was to analyze the impact of sepsis on RBC indices and coagulation parameters on admission to the intensive care unit (ICU) and their association with presence of sepsis and sepsis outcomes in anemic critically ill patients. We performed a retrospective observational study covering consecutive patients admitted to a 10-bed mixed ICU in the years 2020–2021. We found significant differences between septic and non-septic patients for the following parameters: RDW (p = 0.02), INR (p < 0.01), aPTT (p < 0.01), D-dimers (p < 0.01), fibrinogen (p = 0.02), platelets (p = 0.04). International normalized ratio was the only parameter with adequate sepsis predictive value (AUROC = 0.70; 95% CI 0.63–0.76; p < 0.01), with an optimal cut-off value of >1.21. Combination of INR with fibrinogen and a severity of disease score improved INR’s predictive value (AUROC 0.74–0.77). Combination of INR with a severity of disease score was an adequate ICU mortality predictor in septic patients (AUROC 0.70–0.75). Sepsis significantly affects RDW and most coagulation parameters. Increased INR can be used for sepsis screening, whereas combination of INR with a severity of disease score can be a predictor of short-term mortality in septic patients.

The pathophysiological changes underlying stress-related mental disorders remain unclear. However, research suggests that alterations in astrocytes and neurons may be involved. This study examined potential peripheral markers of such alterations, including S100B and neurofilament light chain (NF-L). We compared plasma levels of S100B and NF-L in patients with chronic stress-induced exhaustion disorder (SED), patients with major depressive disorder (MDD), and healthy controls. We also investigated whether levels of S100B and NF-L correlated with levels of astrocyte-derived extracellular vesicles (EVs that indicate astrocyte activation or apoptosis) and with symptom severity. Only women had measurable levels of S100B. Women with SED had higher plasma levels of S100B than women with MDD (P P s = 0.434, P = 0.005) as were depressive symptoms (rs = 0.319, P s = 0.464, P

Cel pracyCelem niniejszego badania była ocena roli różnego rodzaju strategii radzenia sobie jako czynnika pośredniczącego pomiędzy wsparciem społecznym a symptomami depresji wśród pacjentów po przeszczepieniu sercaMetodaW badaniu udział wzięło 123 pacjentów po przeszczepieniu serca. Wszyscy uczestnicy badania wypełnili kwestionariusze samooceny z użyciem następujących standaryzowanych narzędzi: skróconej wersji Skali Depresji Becka (Beck Depression Inventory Short Form, BDI SF), Berlińskich Skali Wsparcia Społecznego (Berlin Social Support Scales, BSSS) oraz Wielowymiarowego Inwentarza do Pomiaru Radzenia Sobie ze Stresem (Coping Orientation to Problems Experienced, skrócona wersja COPE).WynikiWyniki pokazały, że w odniesieniu do obecności symptomów depresji, aktualnie otrzymywane wsparcie społeczne oraz spostrzegane dostępne wsparcie społeczne (zarówno emocjonalne, jak i instrumentalne) okazały się mieć istotny bezpośredni wpływ. Strategie radzenia sobie miały pośredniczący efekt w korelacji między aktualnie otrzymywanym wsparciem społecznym, spostrzeganym dostępnym wsparciem społecznym a symptomami depresji. Osoby z niskim spostrzeganym dostępnym wsparciem społecznym oraz aktualnie otrzymywanym wsparciem społecznym (zarówno emocjonalnym, jak i instrumentalnym), jak również osoby stosujące strategie radzenia sobie polegające na unikaniu i wyparciu okazały się być podatne na doświadczanie symptomów depresji. Istotny efekt pośredniczący wobec symptomów depresji określono dla związku między aktywnym radzeniem sobie, planowaniem, pozytywnym przewartościowaniem, obwinianiem siebie oraz rzeczywiście otrzymywanym wsparciemWnioskiWszystkie rodzaje wsparcia społecznego okazały się bezpośrednio skorelowane z symptomami depresji. Strategie radzenia sobie okazały się mieć pośredniczący efekt w korelacji między postrzeganym wsparciem społecznym a depresją.

Disease relapse is the greatest cause of treatment failure in paediatric B-cell acute lymphoblastic leukaemia (B-ALL). Current risk stratifications fail to capture all patients at risk of relapse. Herein, we used a machine-learning approach to identify B-ALL blast-secreted factors that are associated with poor survival outcomes. Using this approach, we identified a two-gene expression signature (CKLF and IL1B) that allowed identification of high-risk patients at diagnosis. This two-gene expression signature enhances the predictive value of current at diagnosis or end-of-induction risk stratification suggesting the model can be applied continuously to help guide implementation of risk-adapted therapies.

JC polyomavirus (JCPyV) is the causative agent of the fatal, incurable, neurological disease, progressive multifocal leukoencephalopathy (PML). The virus is present in most of the adult population as a persistent, asymptotic infection in the kidneys. During immunosuppression, JCPyV reactivates and invades the central nervous system. A main predictor of disease outcome is determined by mutations within the hypervariable region of the viral genome. In patients with PML, JCPyV undergoes genetic rearrangements in the noncoding control region (NCCR). The outcome of these rearrangements influences transcription factor binding to the NCCR, orchestrating viral gene transcription. This study examines 989 NCCR sequences from patient isolates deposited in GenBank to determine the frequency of mutations based on patient isolation site and disease status. The transcription factor binding sites (TFBS) were also analyzed to understand how these rearrangements could influence viral transcription. It was determined that the number of TFBS was significantly higher in PML samples compared to non-PML samples. Additionally, TFBS that could promote JCPyV infection were more prevalent in samples isolated from the cerebrospinal fluid compared to other locations. Collectively, this research describes the extent of mutations in the NCCR that alter TFBS and how they correlate with disease outcome.

Introduction Neurotoxicity, including optic nerve injury, is one of the most common adverse effects of tacrolimus, the principal calcineurin inhibitor used after kidney transplantation (KTx). The electrophysiologic measurements of both pattern visual evoked potentials (PVEP) and flash visual evoked potentials (FVEP) are valuable when drug-induced optic neuropathy is suspected. Objectives To determine whether VEP measurement is a sensitive and repeatable method for monitoring tacrolimus neurotoxicity. Material and methods This prospective study focused on 35 patients (20 M, 15F, 69 eyes, mean age 43 ± 11 years) who were at a median of 3.0 (IQR, 2.2–3.7) months after KTx at the time of the initial VEP evaluation and were treated with tacrolimus since KTx. The follow-up VEP examination was done after a median of 24 (22–27) months (both VEP measurements followed the ISCEV standards). The P100 wave latency and amplitude for the 1° and 15’ PVEP simulations, and the P2 wave latency and amplitude for the FVEP were analyzed. Results For the 1° checks, the P100 wave latency and amplitude values were significantly worse in the follow-up examination compared to the early post-transplant time-point. Independent associations between FVEP parameters and the tacrolimus blood trough level were observed in the follow-up examination but not at the early post-transplant period. The P2 wave latency correlated with the tacrolimus trough level only in patients treated with the twice-daily, but not the once-daily, tacrolimus formulation. The brain derived neurotrophic factor (BDNF) level correlated with the P100 (15’) latency (R = 0.499; p = 0.005) and the P2 latency (R = 0.409; p = 0.025) only in patients treated with the once-daily, but not the twice-daily, tacrolimus formulation. Conclusion The observations in this study may support the rationale for the use of VEP measurements as non-invasive monitoring of subclinical tacrolimus neurotoxicity.

Aim This study aimed to assess the factors influencing decision making about living donation among medical students. Method Three standardized survey questionnaires (the Altruism Questionnaire A-N, the Individual Questionnaire for studying approaches to transplantology, the Interpersonal Reactivity Index) were used among 316 students of nursing and paramedics. Results Nearly all the respondents (98%) approve cell transplantation, tissue transplantation, and organ transplantation if obtained from living donors. Of the respondents, 66% would consent to donate bone marrow, and 26% would give their consent only in specific situations. Most respondents reported to be encouraged to donate organs by the ability to help other people (56%), while their refusal would be because of the fear of undergoing medical procedures (13%). Older age and a higher score in the personal distress subscale are correlated with a lack of consent to donate bone marrow for transplantation. In the case of living organ donation, the increase in the scores in the fantasy scale caused a higher chance for consent to living donation, whereas older age was the predictor of lack of consent. Higher scores in the perspective taking subscale were found to be significantly correlated with fear of surgical treatment as the reason for refusing to give one’s consent to living donation. The belief that willingness to become a donor shows a person who has a sense of prosocial behavior was influenced by the fantasy and the empathic concern subscales. Conclusions The study group approves cell transplantation, tissue transplantation, and organ transplantation from living donors. These attitudes are determined by empathic behavior.

Aims The aim of this study was to determine the relationship between electrical and mechanical activation in heart failure (HF) patients and whether electromechanical coupling is affected by scar. Methods and results Seventy HF patients referred for cardiac resynchronization therapy or biological therapy underwent endocardial anatomo-electromechanical mapping (AEMM) and delayed-enhancement magnetic resonance (CMR) scans. Area strain and activation times were derived from AEMM data, allowing to correlate mechanical and electrical activation in time and space with unprecedented accuracy. Special attention was paid to the effect of presence of CMR-evidenced scar. Patients were divided into a scar (n = 43) and a non-scar group (n–27). Correlation between time of electrical and mechanical activation was stronger in the non-scar compared to the scar group [R = 0.84 (0.72–0.89) vs. 0.74 (0.52–0.88), respectively; P = 0.01]. The overlap between latest electrical and mechanical activation areas was larger in the absence than in presence of scar [72% (54–81) vs. 56% (36–73), respectively; P = 0.02], with smaller distance between the centroids of the two regions [10.7 (4.9–17.4) vs. 20.3 (6.9–29.4) % of left ventricular radius, P = 0.02]. Conclusion Scar decreases the association between electrical and mechanical activation, even when scar is remote from late activated regions.

BACKGROUND Permanent right ventricular pacing (RVP) results in cardiac dyssynchrony that may lead to heart failure and may be an indication for the use of cardiac resynchronization therapy (CRT). The study aimed to evaluate predictors of outcomes in patients with pacing-induced cardiomyopathy (PICM) if upgraded to CRT. METHODS One hundred fifteen patients, 75.0 years old (IQR 67.0-80.0), were upgraded to CRT due to the decline in left ventricle ejection fraction (LVEF) caused by the long-term RVP. A retrospective analysis was performed using data from hospital and outpatient clinic records and survival data from the National Health System. RESULTS The prior percentage of RVP was 100.0% (IQR 97.0-100.0), with a QRS duration of 180.0 ms (IQR 160.0-200.0). LVEF at the time of the upgrade procedure was 27.0% (IQR 21.0-32.75). The mean follow-up was 980 ± 522 days. The primary endpoint, death from any cause, was met by 26 (22%) patients. Age > 82 years (HR 5.96; 95% CI 2.24-15.89; P = .0004) and pre-CRT implantation LVEF

Women live longer than men but experience greater disability and a longer period of illness as they age. Despite clear sex differences in aging, the impact of pregnancy and its complications, such as preeclampsia, on aging is an underexplored area of geroscience. This review summarizes our current knowledge about the complex links between pregnancy and age-related diseases, including evidence from epidemiology, clinical research, and genetics. We discuss the relationship between normal and pathological pregnancy and maternal aging, using preeclampsia as a primary example. We review the results of human genetics studies of preeclampsia, including genome wide association studies (GWAS), and attempted to catalogue genes involved in preeclampsia as a gateway to mechanisms underlying an increased risk of later life cardio- and neuro- vascular events. Lastly, we discuss challenges in interpreting the GWAS of preeclampsia and provide a functional genomics framework for future research needed to fully realize the promise of GWAS in identifying targets for geroprotective prevention and therapeutics against preeclampsia.

INTRODUCTION Transcatheter aortic valve-in-valve implantation (ViV-TAVI) emerged recently as an alternative to re-do surgery for patients with failed surgical aortic valve (SAV). OBJECTIVES To evaluate the safety and efficacy of transcatheter aortic valves (TAV) in failed SAV in Poland. PATIENTS AND METHODS Data was acquired using a nationwide, multicenter (n=14) Polish Transcatheter Aortic Valve-in-Valve Implantation (ViV-TAVI) Registry (ClinicalTrials.gov Identifier, NCT03361046) with online form collection and 1-year follow-up. RESULTS ViV-TAVI procedures (n=130) constituted 1.9% of all TAVI in Poland with increasing numbers since 2018 (n=59, 45% of all). Hancock II® (21%), Freestyle® (13%), and homograft (11.5%) were identified as the most frequently treated SAV's with self-expanding, supra-annular Corevalve/Evolut® TAV used in the majority of cases (76%). Average post-procedural pressure gradient (average PG) >20 mmHg was found in 21% and 1-year all-cause mortality was 10.8%. SAV stenosis compared to regurgitation/mixed disease was associated with higher average (16, IQR 13.5 - 22.5 vs 14.5, IQR 10-19 mmHg, p=0.004) whereas implantation of supra-annular TAV resulted in lower average PG (14, IQR 10.5-20 vs. intra-annular 19, IQR 16-26 mmHg, P=0.004). After introduction of 2nd generation TAV, shorter procedure time (120, IQR 80-165 min. vs. 135, IQR 108-200 min., P=0.04), less frequent need for additional TAV (2% vs. 10%, P=0.04) and better 1-year freedrom from cardiovascular deaths (95% vs. 82.8%, hazard ratio 0.25, 95% confidence intervals 0.17-0.88, P=0.03) was observed vs. 1st generation. CONCLUSIONS Transcatheter treatment of failed SAV is becoming more frequent, showing the best hemodynamic effect with the use of supra-annular TAV and improved procedural as well as clinical results with the introduction of 2nd generation TAV.

Astrocytes are a main target of JC polyomavirus (JCPyV) in the central nervous system (CNS), where the destruction of these cells, along with oligodendrocytes, leads to the fatal disease progressive multifocal leukoencephalopathy (PML). There is no cure currently available for PML, so it is essential to discover antivirals for this aggressive disease. Additionally, the lack of a tractable in vivo models for studying JCPyV infection makes primary cells an accurate alternative for elucidating mechanisms of viral infection in the CNS. This research to better understand the signaling pathways activated in response to JCPyV infection reveals and establishes the importance of the PI3K/AKT/mTOR signaling pathway in JCPyV infection in primary human astrocytes compared to transformed cell lines. Using RNA sequencing and chemical inhibitors to target PI3K, AKT, and mTOR, we have demonstrated the importance of this signaling pathway in JCPyV infection of primary astrocytes not observed in transformed cells. Collectively, these findings illuminate the potential for repurposing drugs that are involved with inhibition of the PI3K/AKT/mTOR signaling pathway and cancer treatment as potential therapeutics for PML, caused by this neuroinvasive virus.

Objectives: No standardized algorithm exists to identify patients at risk of bleeding after transcatheter aortic valve replacement (TAVR). The aim of this study was to generate and validate a useful predictive model. Background: Bleeding events after TAVR influence prognosis and quality of life and may be preventable. Methods: Using machine learning and multivariate regression, more than 100 clinical variables from 5,185 consecutive patients undergoing TAVR in the prospective multicenter RISPEVA (Registro Italiano GISE sull'Impianto di Valvola Aortica Percutanea; NCT02713932) registry were analyzed in relation to Valve Academic Research Consortium-2 bleeding episodes at 1 month. The model's performance was externally validated in 5,043 TAVR patients from the prospective multicenter POL-TAVI (Polish Registry of Transcatheter Aortic Valve Implantation) database. Results: Derivation analyses generated a 6-item score (PREDICT-TAVR) comprising blood hemoglobin and serum iron concentrations, oral anticoagulation and dual antiplatelet therapy, common femoral artery diameter, and creatinine clearance. The 30-day area under the receiver-operating characteristic curve (AUC) was 0.80 (95% confidence interval [CI]: 0.75–0.83). Internal validation by optimism bootstrap-corrected AUC was 0.79 (95% CI: 0.75–0.83). Score quartiles were in graded relation to 30-day events (0.8%, 1.1%, 2.5%, and 8.5%; overall p

Background The adverse health effects of stress induced exhaustion disorder (SED) cause increasing concern in Western societies. This disorder is characterized by severe fatigue, decreased tolerance to further stress, and attention and memory lapses. Despite subjective complaints, individual cognitive deficits are not always detected in a clinical setting, which calls for the validation of more sensitive instruments. Aim The objective of this study was to investigate if a short, tablet-based serial naming task, MapCog Spectra (MCS) could be used as a marker for cognitive problems in SED. Participants The study comprised of 39 subjects (35 females, four males) with SED. Their mean age was 46,8 years (SD 10.1; range 30–60 yrs.). All participants were healthcare professionals, with a college or university degree, doctors, registered nurses, and psychologists. Methods The MCS was used to assess the number of aberrant pauses during serial naming of coloured geometrical shapes. The Coding, Matrix Reasoning, Digit Span, Symbol Search of the WAIS-IV, and RUFF 2&7 tests, were administered together with a short interview. Results Mean values were within normal reference limits for all tests, except for the MCS, which showed a significantly higher number of aberrant pauses (p Conclusion Here we report that subjects with SED have performance deficits on the MCS, in terms of aberrant pause times, despite average performance on WAIS-IV tests measuring inductive reasoning, processing speed, working memory, and attention. We also demonstrate that subjects use different strategies to overcome their problems. These findings add to the growing evidence of cognitive deficits in SED and that the MCS might aid neuropsychologists in disentangling cognitive markers, important to substantiate the subjective complaints of affected individuals.

JC polyomavirus (JCPyV) is a neuroinvasive pathogen causing a fatal, demyelinating disease of the central nervous system (CNS) known as progressive multifocal leukoencephalopathy (PML). Within the CNS, JCPyV predominately targets two cell types: oligodendrocytes and astrocytes. The underlying mechanisms of astrocytic infection are poorly understood, yet recent findings suggest critical differences in JCPyV infection of primary astrocytes compared to a widely studied immortalized cell model. RNA sequencing was performed in primary normal human astrocytes (NHAs) to analyze the transcriptomic profile that emerges during JCPyV infection. Through a comparative analysis, it was validated that JCPyV requires the mitogen-activated protein kinase, extracellular signal-regulated kinase (MAPK/ERK) pathway, and additionally requires the expression of dual-specificity phosphatases (DUSPs). Specifically, the expression of DUSP1 is needed to establish a successful infection in NHAs, yet this was not observed in an immortalized cell model of JCPyV infection. Additional analyses demonstrated immune activation uniquely observed in NHAs. These results support the hypothesis that DUSPs within the MAPK/ERK pathway impact viral infection and influence potential downstream targets and cellular pathways. Collectively, this research implicates DUSP1 in JCPyV infection of primary human astrocytes, and most importantly, further resolves the signaling events that lead to successful JCPyV infection in the CNS.

The aim of this study was to minimize the risk of life-threatening thromboembolism in the ventricle through the use of a new biomimetic heart valve based on metal–polymer composites. Finite volume element simulations of blood adhesion to the material were carried out, encompassing radial flow and the cone and plane test together with determination of the effect of boundary conditions. Both tilt-disc and bicuspid valves do not have optimized blood flow due to their design based on rigid valve materials (leaflet made of pyrolytic carbon). The main objective was the development of materials with specific properties dedicated to contact with blood. Materials were evaluated by dynamic tests using blood, concentrates, and whole human blood. Hemostability tests under hydrodynamic conditions were related to the mechanical properties of thin-film materials obtained from tribological tests. The quality of the coatings was high enough to avoid damage to the coating even as they were exposed up to maximum loading. Analysis towards blood concentrates of the hydrogenated carbon sample and the nitrogen-doped hydrogenated carbon sample revealed that the interaction of the coating with erythrocytes was the strongest. Hemocompatibility evaluation under hydrodynamic conditions confirmed very good properties of the developed coatings.

For many years, immunonutrition was believed to reduce postoperative complications in patients undergoing major abdominal surgery. However, recent studies questioned that belief. Moreover, the perioperative intake of proteins has gained more and more attention and has shown clinical value. Therefore, the aim of this study was to compare the clinical effect of immunomodulating (IM) plus high-protein (HP) and pure HP supplements during the preoperative period.Between January 2011 and December 2020, 299 well-nourished patients (130 female and 169 male; mean age: 60.8 y) undergoing major abdominal surgery at two surgical centers were randomized to receive either preoperative IM or HP oral supplements for 7 d after surgery. In all patients, an enhanced recovery after surgery protocol was applied. Outcome measures of the intend-to-treat analysis were number and type of complications, length of hospitalization, and mortality.Both groups were comparable in terms of age, sex, and type of surgery. The median length of postoperative hospital stay was 8 d (range, 6-12 d) in the IM group and 7 d (range, 6-10 d) in the HP group (P = 0.153). Postoperative complications were observed in 29 patients (21.3%) in the IM group and 28 (17.8%) in the HP group (P = 0.442) The risk of readmission was comparable (5.1% vs 4.9%; P = 0.924) for IM and HP supplements, respectively. Postoperative nausea and vomiting occurred in 21 patients in the IM group (15.4%) and 17 patients in the HP group (10.4%; P = 0.195). No difference in gastrointestinal function evaluated with time to first flatus was observed (P = 0.272) CONCLUSIONS: The study demonstrated no difference between preoperative IM + HP and HP supplements in surgical patients. Therefore, the routine preoperative use of IM supplements in all surgical patients cannot be recommended.

Background The failure of reperfusion therapy in patients with ST-segment elevation myocardial infarction (STEMI) is more frequent than considered previously. Aim To evaluate sex-related differences in long-term outcomes in patients with STEMI and incomplete infarct-related artery reperfusion after a primary percutaneous coronary intervention. Patients and methods Of consecutive 42 752 patients with STEMI hospitalized between 2009 and 2011 in Poland, we analyzed a group of 766 (35%) women and 1453 (65%) men with less than thrombolysis in myocardial infarction (TIMI) flow grade 3 following a primary percutaneous coronary intervention. Results In the 2-year follow-up, the mortality rate among women was significantly higher compared with men: 39.8 versus 30.9% (P = 0.0009) in the TIMI 0 or 1 group, and 31.6 versus 20% (P < 0.0001) in the TIMI 2 group. In women, the risk of rehospitalization because of heart failure was significantly higher irrespective of the final TIMI flow grade. In the multivariate analysis, female sex did not influence both in-hospital (odds ratio: 1.09; 95% confidence interval: 0.82–1.44; P = 0.54) and long-term (hazard ratio: 1.14; 95% confidence interval: 0.97–1.34; P = 0.11) mortality. Peripheral artery disease, anterior myocardial infarction, and previous stroke were associated with increased mortality only in men. Postprocedural TIMI flow grade 2 (vs. TIMI grade 0 or 1) was the strongest factor impacting mortality irrespective of sex. Conclusion Women with STEMI and postprocedural suboptimal epicardial blood flow have higher mortality than men and are at high risk of developing heart failure, with frequent in-patient visits. However, these differences may be attributed to the advanced age and worse clinical presentation of women compared with men

Background Despite an increase in the number of pancreas transplants in the Scandiatransplant region in the last decade, there continues to be a gap between demand and supply of transplantable organs. This imbalance has encouraged the transplant community to consider new sources of grafts, such as the reintroduction of donors after circulatory death (DCD) who were the standard donors in our center before 1988. Material and Methods In this long-term follow-up study, we compare 44 consecutive, simultaneous pancreas kidney transplants performed at Karolinska University Hospital between 1986 and 1991: 21 patients received DCD grafts and 23 received grafts from donors after brain death. Results Both groups had similar donor and recipient characteristics, but cold ischemia times were significantly shorter in the DCD group. Warm ischemia times were very short compared with other studies on DCDs. Patient and graft survival rates were similar in both groups. Conclusion This study suggests that controlled DCD pancreas and kidney grafts transplanted simultaneously can be a feasible option for reducing organ shortage without any negative impact on the long-term results.

Background and Aim: According to several guidelines, both invasive and non-invasive tests can be used to detect Helicobacter pylori (H. pylori). Invasive methods include H. pylori culture, histological staining, rapid urease tests (RUTs) and PCR. Non-invasive methods include urease breath test, stool antigen and serum IgG testing. The aim of our study was to compare all commercially available RUTs and histology in Germany. Material and Methods: One hundred fifty patients were enrolled in our study, irrespective of proton pump inhibitors (PPIs) or antibiotic use. If the results of RUTs and histology were diverging, real-time PCR to detect H. pylori DNA was undertaken. Results: We detected no differences in the sensitivity or specificity between the different RUTs. In PPI and/or antibiotic-treated patients, RUTs seemed to be more sensitive for the detection of H. pylori infection compared to histology. In addition to the cheaper price of RUTs, they are also quicker to process. We show that histological staining in patients with signs of gastritis is expensive and not necessary, if there are no additional histological questions besides H. pylori status. Conclusions: In conclusion, we consider RUTs to be cheap and fast alternatives to histology in patients with endoscopic signs of gastritis, independently of whether PPIs or antibiotic are used. Histological evaluation is expensive, time consuming and may be unnecessary in some cases.

Multimodal therapies are used to treat advanced cancers including castration-resistant prostate cancer to manage the biological characteristics of the tumors like inflammation, bone metastases, and participation of metabolically altered cancer stem cells (CSCs) that have integral roles in disease dissemination and progression. We developed a multifunctional polymer-based self-assembled technology to deliver a predefined stoichiometric combination of a chemotherapy and an anti-inflammatory agent in a stimuli responsive manner, to complement and improve the currently established treatment methods of prostate cancer. We combined clinically applicable fractionated radiation therapy (XRT) to further sensitize the activity of this targeted multifunctional platform towards prostate-specific membrane antigen (PSMA) expressing advanced prostate cancer. After irradiation, our PSMA-targeted self-assembly system could modulate the mitochondrial metabolism, cellular respiration and the overall radiation-induced DNA damage process. We report the synthesis of this advanced multifunctional platform and describe its unique properties that allow the ability to load multiple FDA approved drugs with a predefined stoichiometric ratio for targeted co-delivery of chemotherapeutics and anti-inflammatory agents. The efficacy of this platform was demonstrated using several in vitro and in vivo studies, in a unique bilateral PSMA expressing prostate cancer tumor model, and in patient derived CSCs.

Aim To compare flash visual evoked potentials (FVEP) elicited using a Ganzfeld bowl (G), Mini Ganzfeld (MG) and Flash Goggles (GG) with eyes open and closed. Patients and method The study group comprised 17 volunteers with mean age of 30 years; all of them were examined with the Roland Consult electrophysiological diagnostic system. Active electrodes were placed at O1 and O2. With the G and MG stimulators, the flash generated by white-light-emitting diodes (LEDs) presented standard flash of 3 cd s m−2. The GG used red LED flash of 3 cd s m−2. Stimulus frequency of 1.0 Hz, low-pass filter of 1.0 Hz and high-pass filters of 100 Hz (G); 50 Hz (MG); 30 Hz (GG) were used. P2 amplitude and latency were compared by the means of the Wilcoxon matched-pairs signed-rank test. Results After right eye stimulation (from O1; n = 17), the mean amplitudes of P2, elicited with the G, MG and GG, were 13, 7 and 10 µV, respectively. The respective latencies were 129, 114 and 110 ms. Hence, the difference between the results obtained with these stimulators was statistically significant (p

Patients with stress-induced exhaustion disorder (SED) demonstrate cognitive dysfunction similar to patients with minor traumatic brain injury (TBI). We have previously detected elevated concentrations of astrocyte-derived extracellular vesicles (EVs) in patients with TBI. As such, we hypothesized that astrocyte-derived EVs could be higher in patients with SED than in patients with major depressive disorder (MDD) and healthy controls. Patients with SED (n = 31), MDD (n = 31), and healthy matched controls (n = 61) were included. Astrocyte-derived EVs (previously known as microparticles) were measured in plasma with flow cytometry and labeled against glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4). In addition, platelet EVs and their CD40 ligand expression were measured. Patients with SED had significantly higher concentrations of AQP4 and GFAP-positive EVs and EVs co-expressing AQP4/GFAP than patients with MDD and healthy controls. Patients with MDD had significantly higher concentrations of GFAP-positive EVs and EVs co-expressing AQP4/GFAP than healthy controls. Platelet EVs did not differ between groups. CD40 ligand expression was significantly higher in patients with SED and MDD than in controls. In conclusion, the present study suggests that patients with SED, and to some extent, patients with MDD, have increased leakage of astrocyte-derived EVs through the blood–brain barrier.

Vascular endothelial growth factor (VEGF) has been implicated in the pathophysiology of stress-related mental disorders. However, VEGF levels have seldom been compared across mental disorders and never by isoforms. Pathophysiological processes involving leakage of astrocyte-derived extracellular vesicles (EVs) across the blood–brain barrier could be associated with VEGF levels in patients with stress-related mental disorders. This cross-sectional study compared plasma levels of VEGF121, VEGF165, and VEGF121 + VEGF165 (VEGFtotal) in patients with stress-induced exhaustion disorder (SED) (n = 31), patients with major depressive disorder (MDD) (n = 31), and healthy controls (n = 61). It also analyzed the correlation between VEGF and astrocyte-derived EVs in plasma. An enzyme-linked immunosorbent assay (ELISA) was used to measure VEGF121 and VEGF165 in citrate plasma, and flow cytometry was used to measure astrocyte-derived EVs in plasma. The mean concentration of soluble VEGF121 (sVEGF121) was significantly higher in patients with SED than healthy controls (P = 0.043). Mean sVEGF165 was significantly lower in patients with MDD than patients with SED (P = 0.004) or healthy controls (P = 0.037). Mean sVEGFtotal was significantly higher in patients with SED than in patients with MDD (P = 0.021) and also higher in patients with SED than healthy controls (P = 0.040). Levels of sVEGF121 were positively correlated with levels of astrocyte-derived EVs only in patients with SED (P = 0.0128). The same was true of levels of sVEGFtotal and astrocyte-derived EVs (P = 0.0046). Differing levels of VEGF isoforms may reflect different pathophysiological mechanisms in SED and MDD. Further research is needed to better understand the potential roles of VEGF isoforms and astrocyte-derived EVs in mental disorders.

Polyomaviruses are mostly non-pathogenic, yet some can cause human disease especially under conditions of immunosuppression, including JC, BK, and Merkel cell polyomaviruses. Direct interactions between viruses and the host early during infection dictate the outcome of disease, many of which remain enigmatic. However, significant work in recent years has contributed to our understanding of how this virus family establishes an infection, largely due to advances made for animal polyomaviruses murine and SV40. Here we summarize the major findings that have contributed to our understanding of polyomavirus entry, trafficking, disassembly, signaling, and immune evasion during the infectious process and highlight major unknowns in these processes that are open areas of study.

Currently available chemotherapeutic treatments for blood cancers (leukemia) usually have strong side effects. More selective, efficient and less toxic anticancer agents are needed. We synthesized seven, new, optically pure (12aS)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12-(2H,11H)-dione derivatives and examined their cytotoxicity towards eight cancer cell lines, including urinary bladder (TCC-SUP, UM-UC-3, KU-19-9), colon (LoVo), and breast (MCF-7, MDA-MB-231) cancer representatives, as well as two leukemic cell lines (MV-4-11, CCRF-CEM) and normal murine fibroblasts (Balb/3T3) as a reference cell line. Three of the seven newly-obtained compounds ((12aS)-8-bromo-2-(3-phenylbenzoyl)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12(2H,11H)-dione, (12aS)-8,9-dimethoxy-2-(4-phenylbenzoyl)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12(2H,11H)-dione and (12aS)-8-nitro-2-(4-phenylbenzoyl)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12(2H,11H)-dione, showed enhanced activity and selectivity toward the leukemic MV-4-11 cell line when compared to our previously reported compounds, with IC50 values in the range of 2.9-5.6 µM. Additionally, (12aS)-9-nitro-2-(4-phenylbenzoyl)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12(2H,11H)-dione exhibited a strong cytotoxic effect against the leukemic CCRF-CEM (IC50 = 6.1 µM) and MV-4-11 (IC50 = 11.0 µM) cell lines, a moderate cytotoxic effect toward other tumor lines (IC50 = 31.8-55.0 µM) and very weak cytotoxic effect toward the Balb/3T3 reference cell line. Selected compounds were further evaluated for their potential to induce apoptotic cell death in MV-4-11 cells by measuring caspase-3 activity. We also obtained the crystal structure of three products and investigated the effect of 22 derivatives of 1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12-(2H,11H)-dione on the activity of the cancer-associated enzyme autotaxin. All compounds proved to be weak inhibitors of autotaxin, although some (R) and (S) enantiomers had Ki values of 10-19 µM. The obtained results showed that the tested compounds exhibited a selective anti-leukemic effect, which appeared not to be related directly to autotaxin. Molecular targets responsible for this effect remain to be identified. The newly obtained compounds can be used in the search for new, selective anticancer therapies.

Background: Non-ST-segment elevation myocardial infarction (NSTEMI) has become the most frequently encountered type of myocardial infarction. The patient clinical profile and management has evolved over the past decade. As there is still a scarcity of data on the latest trends in NSTEMI, changes herein were observed and assessed in the treatment and outcomes in Poland between 2005 and 2014. Methods: A total of 197,192 patients with NSTEMI who enrolled in the Polish Registry of Acute Coronary Syndromes (PL-ACS) between 2005 and 2014 were analyzed. In-hospital and 12-month mortality were assessed. Results: Coronary angiography use increased from 35.8% in 2005–2007 to 90.7% in 2012–2014 (p < 0.05), whereas percutaneous coronary intervention increased from 25.7% in 2005–2007 to 63.6% in 2012–2014 (p < 0.05). There was a 50% reduction in in-hospital mortality (from 5.6% in 2005–2007 to 2.8% in 2012–2014; p < 0.05) and a 30% reduction in 1-year mortality (from 19.4% in 2005–2007 to 13.7% in 2012–2014; p < 0.05). A multivariate analysis confirmed an immense impact of invasive strategy on patient prognosis during in-hospital observation with an odds ratio (OR) of 0.31 (95% confidence interval [CI] 0.29–0.33; p < 0.05) as well as during the 12-month observation with an OR of 0.51 (95% CI 0.49–0.52; p < 0.05). Conclusions: Over the past 10 years, an important advance in the management of NSTEMI has taken place in Poland. Routine invasive strategy resulted in a significant decrease in mortality rates in all groups of NSTEMI patients.

There is a paucity of real‑world registries concerning patients with chronic coronary syndromes (CCS).We aimed to assess the long‑term outcomes of patients with CCS and after coronary angiography performed in accordance with the treatment strategy.The analysis involved 11 021 patients treated in a single center between 2006 and 2016 who were enrolled into the ongoing PRESAGE registry. Based on the results of coronary angiography and the treatment strategy adopted, patients were classified into 4 groups: with nonsignificant lesions (n = 3637), undergoing percutaneous coronary intervention (n = 4678), undergoing coronary artery bypass grafting (CABG; n = 997), and receiving conservative treatment (notwithstanding significant lesions on an angiogram; n = 1709). All‑cause death, assessed in every study group at 1-, 3-, and 5‑year follow‑up, was regarded as the primary outcome measure.The mean (SD) age of the study patients was 64.6 (9.5) years, and women constituted 35% of the cohort. Patients treated conservatively were the oldest (mean [SD] age, 64.9 [9.3] years) in the group and showed the highest prevalence of previous myocardial infarction (50.5%), CABG (31.8%), diabetes (40.3%), chronic total occlusion (65.5%), and left ventricular ejection fraction below 35% (24.4%). Death from any cause in patients with nonsignificant lesions, undergoing percutaneous coronary intervention, undergoing CABG, and receiving conservative treatment occurred 5 years following the index hospitalization in 11.2%, 16.2%, 9.7%, and 21% of those patients, respectively.The PRESAGE registry provides valuable information about the clinical characteristics and long‑term outcomes of patients with CCS. The population of CCS patients is heterogeneous, and long‑term prognosis is also varied. The poorest characteristics and outcomes were reported in patients with significant lesions and ineligible for revascularization procedures.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) accounts for 0.05–2% of all RCCs. The majority of patients have germline mutations, most frequently in the SDHB gene. People with these mutations are predisposed to developing paragangliomas, phaeochromocytomas and gastrointestinal stromal tumours. Patients should be referred to genetic services for further workup and close surveillance imaging due to the risk of development of further tumours. We present a woman with SDH-deficient RCC and review the literature associated with this uncommon entity.

A series of fourteen novel, eight-membered lactam- and dilactam-based analogues of tricyclic drugs were obtained in a simple one-pot procedure. Crystal structures of two compounds were determined by single-crystal X-ray diffraction analysis and their selected structural features were discussed and compared with those of imipramine and dibenzepine. Affinity of developed molecules for histamine receptor H1, serotonin receptors 5-HT1A, 5-HT2A, 5-HT6, 5-HT7, serotonin transporter (SERT) and dopamine receptor D2 was determined. The commercial drug dibenzepine was also checked on these molecular targets, as its mechanism of action is largely unknown. Two derivatives of 11,12-dihydrodibenzo[b,f]azocin-6(5H)-one (7,8) and two of dibenzo[b,f]azocin-6(5H)-one (9,10) were found to be active toward the H1 receptor in sub-micromolar concentrations.

Objective To provide an update on the literature regarding the management of complications secondary to synthetic mesh placed to treat stress urinary incontinence (SUI). Methods We performed a systematic review of the literature using a multi-database structured search within OVID, the Medical Literature Analysis and Retrieval System Online (MEDLINE), the Excerpta Medica dataBASE (EMBASE) and Cochrane library databases; using the keywords: urology, incontinence, mesh and surgery. Results Several million synthetic polypropylene meshes have been inserted into women worldwide to manage SUI. Unfortunately, a significant number of women have now reported life-changing complications. We found a paucity of studies, heterogeneity of cohorts, poor long-term follow-up, and lack of evidence on the effective management of mesh-related complications. Conclusions The contemporary evidence is low-level and often contradictory, which prevents robust recommendations regarding treatment. A prospective registry will be required to generate meaningful outcome data and help in the complex management of patients who have mesh-related complications.

Left ventricle, LV wringing wall motion relies on physiological muscle fiber orientation, fibrotic status, and electromechanics (EM). The loss of proper EM activation can lead to rigid-body-type (RBT) LV rotation, which is associated with advanced heart failure (HF) and challenges in resynchronization. To describe the EM coupling and scar tissue burden with respect to rotational patterns observed on the LV in patients with ischemic heart failure with reduced ejection fraction (HFrEF) left bundle branch block (LBBB). Thirty patients with HFrEF/LBBB underwent EM analysis of the left ventricle using an invasive electro-mechanical catheter mapping system (NOGA XP, Biosense Webster). The following parameters were evaluated: rotation angle; rotation velocity; unipolar/bipolar voltage; local activation time, LAT; local electro-mechanical delay, LEMD; total electro-mechanical delay, TEMD. Patients underwent late-gadolinium enhancement cMRI when possible. The different LV rotation pattern served as sole parameter for patients’ grouping into two categories: wringing rotation (Group A, n = 6) and RBT rotation (Group B, n = 24). All parameters were aggregated into a nine segment, three sector and whole LV models, and compared at multiple scales. Segmental statistical analysis in Group B revealed significant inhomogeneities, across the LV, regarding voltage level, scar burdening, and LEMD changes: correlation analysis showed correspondently a loss of synchronization between electrical (LAT) and mechanical activation (TEMD). On contrary, Group A (relatively low number of patients) did not present significant differences in LEMD across LV segments, therefore electrical (LAT) and mechanical (TEMD) activation were well synchronized. Fibrosis burden was in general associated with areas of low voltage. The rotational behavior of LV in HF/LBBB patients is determined by the local alteration of EM coupling. These findings serve as a strong basic groundwork for a hypothesis that EM analysis may predict CRT response.Clinical trial registration: SUM No. KNW/0022/KB1/17/15.

Objective To evaluate the predictive ability of digital X-ray radiogrammetry (DXR) for fracture in women attending general mammography screening. Study design In a nested case-control study, women aged between 40 and 75 years, who attended the regional mammography screening program, had their bone mass assessed with DXR and provided information regarding clinical risk factors for osteoporosis. Follow-up was done through cross-referencing with National Patient Registers. Associations between DXR, clinical risk factors and fracture risk were examined. Receiver operating characteristics curves for DXR T-score and different fracture types were plotted, and their respective AUC calculated. Main outcome measures Fractures (hip, major osteoporotic and any clinical facture). Fracture diagnoses were retrieved from National Patient Registers. Results 14,841 women had their bone mass examined in conjunction with mammography. Of these women, 10,967 returned fully completed questionnaires regarding clinical risk factors. In total 605 fractures (including 355 major osteoporotic fractures and 18 hip fractures) occurred during the follow-up period (median follow-up time was 3.3 years). Women with fractures were older and had lower DXR T-score compared with those without. DXR T-score correlated with fracture risk. HR/SD T-score decrease was 2.15 (CI 1.55–3.00) for hip, 1.47 (CI 1.36–1.59) for major osteoporotic and 1.33 (CI 1.26–1.42) for any clinical fracture. The AUCs for the different fracture types were 0.79 (hip), 0.69 (major osteoporotic) and 0.65 (any clinical). Conclusions DXR T-score is negatively correlated with risk of fracture in a general female population. This indicates a potential use of DXR in population-based screening for osteoporosis.

Keeping the lid on infection spread From February to April 2020, many countries introduced variations on social distancing measures to slow the ravages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Publicly available data show that Germany has been particularly successful in minimizing death rates. Dehning et al. quantified three governmental interventions introduced to control the outbreak. The authors predicted that the third governmental intervention—a strict contact ban since 22 March—switched incidence from growth to decay. They emphasize that relaxation of controls must be done carefully, not only because there is a 2-week lag between a measure being enacted and the effect on case reports but also because the three measures used in Germany only just kept virus spread below the growth threshold. Science , this issue p. eabb9789

JC polyomavirus (JCPyV) infects 50 to 80% of the population and is the causative agent of a fatal demyelinating disease of the central nervous system (CNS). JCPyV presents initially as a persistent infection in the kidneys of healthy people, but during immunosuppression, the virus can reactivate and cause progressive multifocal leukoencephalopathy (PML). Within the CNS, JCPyV predominately targets two cell types, oligodendrocytes and astrocytes. Until recently, the role of astrocytes has been masked by the pathology in the myelin-producing oligodendrocytes, which are lytically destroyed by the virus. To better understand how astrocytes are impacted during JCPyV infection, the temporal regulation and infectious cycle of JCPyV were analyzed in primary normal human astrocytes (NHAs). Previous research to define the molecular mechanisms underlying JCPyV infection has mostly relied on the use of cell culture models, such as SVG-A cells (SVGAs), an immortalized, mixed population of glial cells transformed with simian virus 40 (SV40) T antigen. However, SVGAs present several limitations due to their immortalized characteristics, and NHAs represent an innovative approach to study JCPyV infection in vitro Using infectivity assays, quantitative PCR, and immunofluorescence assay approaches, we have further characterized JCPyV infectivity in NHAs. The JCPyV infectious cycle is significantly delayed in NHAs, and the expression of SV40 T antigen alters the cellular environment, which impacts viral infection in immortalized cells. This research establishes a foundation for the use of primary NHAs in future studies and will help unravel the role of astrocytes in PML pathogenesis.IMPORTANCE Animal models are crucial in advancing biomedical research and defining the pathogenesis of human disease. Unfortunately, not all diseases can be easily modeled in a nonhuman host or such models are cost prohibitive to generate, including models for the human-specific virus JC polyomavirus (JCPyV). JCPyV infects most of the population but can cause a rare, fatal disease, progressive multifocal leukoencephalopathy (PML). There have been considerable advancements in understanding the molecular mechanisms of JCPyV infection, but this has mostly been limited to immortalized cell culture models. In contrast, PML pathogenesis research has been greatly hindered because of the lack of an animal model. We have further characterized JCPyV infection in primary human astrocytes to better define the infectious process in a primary cell type. Albeit a cell culture model, primary astrocytes may better recapitulate human disease, are easier to maintain than other primary cells, and are less expensive than using an animal model.

Objective The main objective of the researchers was to determine the level of life quality among heart and kidney transplant recipients depending on the time and type of the transplant. Methods The study was conducted using standardized questionnaires: the 36-Item Short-Form Health Survey, Life Orientation Test–Revised, and Hospital Anxiety and Depression Scale. The study included 146 recipients (109 heart transplant recipients and 37 kidney transplant recipients) from 1 to 26 years after the transplantation surgery (mean 9 years). Results The mean age of the study group was 52 years. The mean time since organ transplantation was 10 years for heart transplantation and 4.3 years for kidney transplantation. The study group obtained a slightly lower score for quality of life compared to the general population. In the Physical Component Summary (PCS), the study participants obtained the highest mean for the domain bodily pain (47.6), while the lowest score was in the domain role physical (41.82). As for the Mental Component Summary (MCS), the highest mean was obtained for the domain vitality (50.57), whereas the lowest one was for the domain role emotional (43.38). In 33% of the participants, risk of depression was identified. Statistically significant differences were observed depending on the type of the transplanted organ in the PCS for the domains general health, physical functioning, and bodily pain and the MCS for role emotional and social functioning. The statistically significant predictors for the PCS domain were the type of transplanted organ, recipients’ age, and occurrence of anxiety. In turn, the predictor for the MCS was the occurrence of depression. Conclusions The quality of life (QOL) assessment varies between kidney and heart transplant recipients. The QOL is determined by the recipients’ age and the occurrence of anxiety and depression. The obtained QOL assessment results are slightly lower than those in the general population.

SIGNIFICANCE This case highlights the importance of using ultrasonography to evaluate an eye that has no clear view of the fundus. PURPOSE Uveal melanoma stems from melanocytes found in the iris, ciliary body, and choroid, and it is the most common primary intraocular malignancy found in adults. The lesion is identified predominantly via fundus biomicroscopy and binocular indirect ophthalmoscopy. The authors present a unique case where visual evaluation of the fundus was not possible, and ultrasonography was used to assess the retina and choroid. CASE REPORT A 38-year-old Hispanic man with prior ocular trauma presented with an eye that could not be clinically examined owing to complete pupil occlusion. The diagnosis of presumed uveal melanoma was made exclusively based on the outcome of ocular ultrasonography. Further histologic, antibody, and genetic testing was completed once the patient had undergone treatment of the affected eye and uveal melanoma was confirmed. CONCLUSIONS In this rare instance, B-scan ultrasonography provided a finding that required the patient to undergo enucleation in an eye without visual potential. Genetic testing was then used to appropriately categorize the tumor as a class 1B melanoma, indicating that there is a risk of metastasis. Consequently, the patient is being monitored by a medical oncologist.

Clinical phenotypes of familial hypobetalipoproteinemia (FHBL) are related to a number of defective apolipoprotein B (APOB) alleles. Fatty liver disease is a typical manifestation, but serious neurological symptoms can appear. In this study, genetic analysis of the APOB gene and ophthalmological diagnostics were performed for family members with FHBL. Five relatives with FHBL, including a proband who developed neurological disorders, were examined. A sequencing analysis of the whole coding region of the APOB gene, including flanking intronic regions, was performed using the next-generation sequencing (NGS) method. Electrophysiological ophthalmological examinations were also done. In the proband and his affected relatives, NGS identified the presence of the pathogenic, rare heterozygous splicing variant c.3696+1G>T. Two known heterozygous missense variants—c.2188G>A, p.(Val730Ile) and c.8353A>C, p.(Asn2785His)—in the APOB gene were also detected. In all patients, many ophthalmologic abnormalities in electrophysiological tests were also found. The identified splicing variant c.3696+1G>T can be associated with observed autosomal, dominant FHBL with coexisting neurological symptoms, and both identified missense variants could be excluded as the main cause of observed clinical signs, according to mutation databases and the literature. Electroretinography examination is a sensitive method for the detection of early neuropathy and should therefore be recommended for the care of patients with FHBL.

OBJECTIVE To compare the safety and efficacy of transcathether aortic valve-in-valve implantation (ViV-TAVI) in degenerated stentless bioprostheses with failed stented valves and degenerated native aortic valves. INTRODUCTION Little is known about ViV-TAVI in degenerated stentless valves. METHODS Out of 45 ViV-TAVI procedures reported in the POL-TAVI registry, 20 failed stentless valves were compared with 25 stented prostheses and propensity-matched with 45 native TAVI cases. The mean follow-up was 633 (95% confidence interval [CI], 471-795) days and Valve Academic Research Consortium-2 (VARC-2) definitions were applied. RESULTS Patients with degenerated stentless valves were younger (65.6, CI 58-73.1 years vs 75.6, CI 72.2-78 [stented] vs 80.1, CI 78.7-81.6 y. [native], P

Decellularized porcine heart valves offer promising potential as biocompatible prostheses. However, this procedure alter matrix fibres and glycans, leading to lower biomechanical resistance and increased their thrombotic potential. Therefore, their durability is limited due to calcification and weak regeneration in vivo. Surface modifications are highly requested to improve the scaffolds re-endothelialization required to restore functional and haemocompatible heart valve. Fucoidan, a natural sulphated polysaccharide, carries antithrombotic and anti-inflammatory properties and is known to enhance endothelial adhesion and proliferation when associated with vascular endothelial growth factor (VEGF). Based on these features, we constructed fucoidan/VEGF polyelectrolyte multilayer film (PEM) coated valve scaffold in an attempt to develop functional heart valve bioprosthesis. We investigated the haemocompatibility of the PEM coated valve scaffolds, the adhesion and growth potential of endothelial cells (HUVECs) in flow, as well as long term culture with stem cells. Fucoidan/VEGF PEM coated scaffolds demonstrated antithrombotic and non-calcifying properties. The PEM application increased HUVECs adhesion in flow (6 h) and HUVECs viability over time (72 h). HUVECs were well spread and aligned in flow direction. Interestingly, stem cells infiltration was improved by the PEM coating at 21 days. Thus, the fucoidan/VEGF PEM is a promising surface modification to obtain valve bioprostheses for clinical applications with increased antithrombotic and re-endothelialization potential.

Background This study aims to determine the validity of the Karolinska Interpersonal Violence Scale (KIVS), as a screening tool for PTSD, among women with borderline personality disorder (BPD) and severe suicidal behavior. Method 106 women with BPD and at least two suicide attempts were assessed with the KIVS for exposure to interpersonal violence as a child and as an adult. The screening ability of the KIVS for the diagnosis of PTSD was analyzed using receiver operating characteristic curve analysis. Results PTSD diagnosis was valid for 61 (58%) women with BPD. The KIVS – exposure of lifetime interpersonal violence, displayed fair accuracy of predicting diagnosis of PTSD (area under the curve 0.79, confidence interval [0.71, 0.88]) and performed well (sensitivity 0.90 and specificity 0.62), with a cut-off score of 4 (range 0–10). Poly-traumatization was not significantly related to PTSD diagnosis as compared to single traumatization, whereas sexual victimization was significantly more prevalent in women with PTSD diagnosis, as compared to other types of traumatic events. Conclusion A score of 4 or more on the KIVS – exposure to interpersonal lifetime violence presents well as a screening instrument for risk of PTSD, among women with BPD.

Cancer remains one of the most serious long-term complications after liver transplantation (LT). Data for all adult LT patients between 1982 and 2013 was extracted from the Nordic Liver Transplant Registry. Through linkage with respective national cancer-registry data, we calculated standardized incidence ratios (SIRs) based on country, sex, calendar time, and age-specific incidence rates. Altogether 461 cancers were observed in 424 individuals out the 4246 LT patients during a mean 6.6-year follow-up. The overall SIR was 2.22 (95%CI 2.02-2.43). SIRs were especially increased for colorectal cancer in recipients with PSC (4.04) and for lung cancer in recipients with alcoholic liver disease (4.96). A decrease in the SIR for cancers occurring within 10 years post-LT was observed from the 1980s: 4.53 (95%CI 2.47-7.60), the 1990s: 3.17 (95%CI 2.70-3.71), to the 2000s: 1.76 (95%CI 1.51-2.05). This was observed across age- and indication-groups. The sequential decrease for the SIR of non-Hodgkin lymphoma was 25.0 - 12.9 - 7.53, and for non-melanoma skin cancer 80.0 - 29.7 - 10.4. Cancer risk after LT was found to be decreasing over time, especially for those cancers that are strongly associated with immunosuppression. Whether immunosuppression minimization contributed to this decrease merits further study. This article is protected by copyright. All rights reserved.

Background Heart transplantation (HTx) is the standard treatment for end-stage cardiomyopathy and coronary artery disease. Although major improvements have been made in the prevention and treatment of acute graft rejection, comorbidities still limit the long-term survival of heart transplant recipients. The risk of poor outcome, such us major health status aggravation and death, can stimulate the occurrence of depression and stress in this population. The aim of this study was to determine the impact of comorbidities on depressive symptoms and distress among heart transplant recipients. Material/methods The sample included 131 HTx recipients from one site. Data were collected during a follow-up in-hospital appointment, using the questionnaires assessing depression (Beck Depression Inventory Short Form) and stress (Perceived Stress Scale-10). Statistical analyses included descriptive statistics, Pearson correlations, t-tests, and generalized linear models. Results Study patients were 75.6% (n = 97) male, 100% (n = 131) Caucasian, 74% (n = 89) married, with the mean age of 54 years at time of heart transplantation. Nearly half of the participants (40.5%) presented depression symptoms at the time of evaluation. Severe stress was observed in 30% of individuals. Depression symptoms and severe distress were more commonly observed in patients with many comorbidities, requiring multiple drug therapy, and high NYHA score. Moreover, in a multivariate logistic regression, depression and high distress level occurrence were predicted by the following independent factors: cardiac allograft vasculopathy, cancer, diabetes, higher NYHA score, and comorbidities. Conclusions The prevalence of depression and severe distress is common among heart transplant recipients. Patients with many comorbidities are at higher risk of psychological indisposition.

Background and Aims: An enterocutaneous fistula (ECF) poses a major surgical problem. The definitive surgical repair of persistent fistulas remains a surgical challenge with a high rate of re-fistulation and mortality, and the reasons for that is not the surgical technique alone. Enhanced Recovery after Surgery (ERAS®) is an evidence-based multimodal perioperative protocol proven to reduce postoperative complications. The aim of the study was to assess the clinical value of the ERAS protocol in surgical patients with ECF. Methods: ERAS protocol was used in all patients scheduled for surgery for ECF at the Stanley Dudrick’s Memorial Hospital in Skawina between 2011 and 2020. A multidisciplinary team (MDT) was in charge of the program and performed annual audits. A consecutive series of 100 ECF patients (44 females, 56 males, mean age 54.1 years) were evaluated. Postoperative complications rate, readmission rate, length of hospital stay, prevalence of postoperative nausea and vomiting were assessed. Registered under ClinicalTrials.gov Identifier no. NCT04771832. Results: ERAS protocol was successfully introduced for ECF surgeries, however, eight modifications to the ERAS program was performed in 2015. They led to improvement of surgical outcomes: reduction of postoperative nausea and vomiting (15 vs. 17% patients, p = 0.025), overall complication rate (11 vs. 10, p = 0.021), median length of hospital stay (overall and after surgery, p = 0.022 and 0.002, respectively). Conclusions: ERAS protocol can be successfully used for ECF patients. Prescheduled audits can contribute to the improvement of care.