The Alcatraz-Strategy: a roadmap to break the connectivity barrier in malignant brain tumours.

In recent years, the discovery of functional and communicative cellular tumour networks has led to a new understanding of malignant primary brain tumours. In this review, the authors shed light on the diverse nature of cell-to-cell connections in brain tumours and propose an innovative treatment approach to address the detrimental connectivity of these networks. The proposed therapeutic outlook revolves around three main strategies: (a) supramarginal resection removing a substantial portion of the communicating tumour cell front far beyond the gadolinium-enhancing tumour mass, (b) morphological isolation at the single cell level disrupting structural cell-to-cell contacts facilitated by elongated cellular membrane protrusions known as tumour microtubes (TMs), and (c) functional isolation at the single cell level blocking TM-mediated intercellular cytosolic exchange and inhibiting neuronal excitatory input into the malignant network. We draw an analogy between the proposed therapeutic outlook and the Alcatraz Federal Penitentiary, where inmates faced an impassable sea barrier and experienced both spatial and functional isolation within individual cells. Based on current translational efforts and ongoing clinical trials, we propose the Alcatraz-Strategy as a promising framework to tackle the harmful effects of cellular brain tumour networks.

Synchronous versus metachronous spinal metastasis: a comparative study of survival outcomes following neurosurgical treatment.

PURPOSE: Patients with spinal metastases (SM) from solid neoplasms typically exhibit progression to an advanced cancer stage. Such metastases can either develop concurrently with an existing cancer diagnosis (termed metachronous SM) or emerge as the initial indication of an undiagnosed malignancy (referred to as synchronous SM). The present study investigates the prognostic implications of synchronous compared to metachronous SM following surgical resection. METHODS: From 2015 to 2020, a total of 211 individuals underwent surgical intervention for SM at our neuro-oncology facility. We conducted a survival analysis starting from the date of the neurosurgical procedure, comparing those diagnosed with synchronous SM against those with metachronous SM. RESULTS: The predominant primary tumor types included lung cancer (23%), prostate cancer (21%), and breast cancer (11.3%). Of the participants, 97 (46%) had synchronous SM, while 114 (54%) had metachronous SM. The median overall survival post-surgery for those with synchronous SM was 13.5 months (95% confidence interval (CI) 6.1-15.8) compared to 13 months (95% CI 7.7-14.2) for those with metachronous SM (p = 0.74). CONCLUSIONS: Our findings suggest that the timing of SM diagnosis (synchronous versus metachronous) does not significantly affect survival outcomes following neurosurgical treatment for SM. These results support the consideration of neurosurgical procedures regardless of the temporal pattern of SM manifestation.

[ViaCogScreen: An Efficient, Valid, and Repeatable Screening Tool for Cognitive Performance Assessment of the Elderly]. / ViaCogScreen: ein zeitökonomisches, valides und wiederholbares Screeningverfahren zum Leistungsmonitoring älterer Menschen.

Given the demographic change with an aging society in Germany, cognitive performance assessment of the elderly is of great importance. The Viacogscreen developed by us is a computer- and web-based brain performance screening for older adults that not only meets the criteria of a measurement instrument, but is also economical and repeatable. The test captures interlocking word list learning with delayed free recall and recognition, semantic word selection and fluidity, phonemic word fluidity and inverted number range, as well as incidental memory, resulting in a total of 17 performance parameters that provide a quick orientation (approximate test duration: 10-12 minutes) regarding the cognitive performance of a test subject. Three performance areas are depicted: executive functions, episodic and semantic memory. The test was standardized for 200 healthy test subjects in 6 different age groups (range: 50-85 years). For the first clinical validation, the test was used in the memory clinics in Bonn and Ulm, where 33 patients with MCI (mild cognitive impairment) and 42 patients with suspected Alzheimer's disease (VAD) were tested. A control group of 42 healthy people of approximately the same age served as the control group. With regard to the cognitive test procedure, all three groups showed significantly different results regarding the overall score (ANOVA F=73.9, p<0.001), executive functions (F=27.6 p<0.001) and semantic memory (F=54.4 p<0.001). Regarding episodic memory, both clinical groups differed significantly from the control group, but not from each other (F=48.7, p<0.001). The Viacogscreen thus produced very good results in its first validation in two memory clinics with regard to differentiation of VAD, and good results with regard to MCI. In addition to use in neurodegenerative diseases, the Viacogscreen is also suitable for other neurological and neuro-oncological diseases, as well as for use in large clinical studies since it enables electronic data collection.

Design of amyloidogenic peptide traps.

Segments of proteins with high ß-strand propensity can self-associate to form amyloid fibrils implicated in many diseases. We describe a general approach to bind such segments in ß-strand and ß-hairpin conformations using de novo designed scaffolds that contain deep peptide-binding clefts. The designs bind their cognate peptides in vitro with nanomolar affinities. The crystal structure of a designed protein-peptide complex is close to the design model, and NMR characterization reveals how the peptide-binding cleft is protected in the apo state. We use the approach to design binders to the amyloid-forming proteins transthyretin, tau, serum amyloid A1 and amyloid ß1-42 (Aß42). The Aß binders block the assembly of Aß fibrils as effectively as the most potent of the clinically tested antibodies to date and protect cells from toxic Aß42 species.

Functional outcome after late cranioplasty after decompressive craniectomy: a single-center retrospective study.

OBJECTIVE: The best time for cranioplasty (CP) after decompressive craniectomy (DC) is controversial, and there are no authoritative guidelines yet. Both complications as well as outcome may depend on the timing of CP. The aim of this single-center study was to evaluate the impact of late CP on procedural safety as well as on patient outcome. METHODS: All patients receiving CP at a tertiary university medical center between 01/2015 and 12/2022 were included retrospectively. Patients' conditions were assessed according to the modified Rankin Scale (mRS) prior to CP and 6 months after. Baseline characteristics, indication for DC, time from DC to CP, and postoperative complications according to the Landriel Ibañez Classification were analyzed. RESULTS: CP was performed in 271 patients who previously underwent DC due to traumatic brain injury (25.5%), ischemic stroke (29.5%), aneurysmal subarachnoid hemorrhage (26.9%), or intracerebral hemorrhage (18.1%). The median interval between DC and CP was 143 days (interquartile range 112-184 days). Receiver operating characteristic analysis revealed a cut-off of 149 days, where CP performed within 149 days after DC led to an improvement on mRS after CP (p = 0.001). In multivariate analysis, additional rehabilitation after and better mRS before CP were independently associated with improvement of outcome. The rate of complications was similar between early and late CP (24.8% and 25.4%, respectively, p = 0.562). CONCLUSIONS: Late cranioplasty is a safe procedure. The outcome was improved when additional rehabilitation was performed after cranioplasty and was not associated with the timing of cranioplasty.

Specific Regulation of Enzymatic Activity by Interface Pulses.

The thermodynamic state of the interface in which an enzyme is embedded can regulate the enzymatic activity. Indeed, it has been demonstrated by others and us that close to the maximum in compressibility, the activity of the enzyme is at a maximum as well. Pulses propagating along the interface can modulate the interface state and were demonstrated to be able to modulate the activity of interface-associated acetylcholinesterase (AChE). Here, we demonstrate that enzyme activity modulation by interface pulses depends specifically on the pulse type. Using membrane-embedded enzyme phospholipase A2 (PLA2), enzyme activity can be monitored by detecting the lateral pressure without an additional assay required. We show that pulses that shift the state toward higher pressure and higher lateral density increase the enzymatic activity, while pulses that reduce the pressure induce the opposite effect. These results further support a physical mechanism for enzyme-enzyme communication where compressibility, lateral density, and pressure (thermodynamic state) and not specific molecular modifications regulate enzymatic activity.

Structural Analysis of Breast-Milk αS1-Casein: An α-Helical Conformation Is Required for TLR4-Stimulation.

Breast-milk αS1-casein is a Toll-like receptor 4 (TLR4) agonist, whereas phosphorylated αS1-casein does not bind TLR4. The objective of this study was to analyse the structural requirements for these effects. In silico analysis of αS1-casein indicated high α-helical content with coiled-coil characteristics. This was confirmed by CD-spectroscopy, showing the α-helical conformation to be stable between pH 2 and 7.4. After in vitro phosphorylation, the α-helical content was significantly reduced, similar to what it was after incubation at 80 °C. This conformation showed no in vitro induction of IL-8 secretion via TLR4. A synthetic peptide corresponding to V77-E92 of αS1-casein induced an IL-8 secretion of 0.95 ng/mL via TLR4. Our results indicate that αS1-casein appears in two distinct conformations, an α-helical TLR4-agonistic and a less α-helical TLR4 non-agonistic conformation induced by phosphorylation. This is to indicate that the immunomodulatory role of αS1-casein, as described before, could be regulated by conformational changes induced by phosphorylation.

Multicentric Assessment of Safety and Efficacy of Combinatorial Adjuvant Brain Metastasis Treatment by Intraoperative Radiation Therapy and Immunotherapy.

PURPOSE: After surgical resection of brain metastases (BMs), intraoperative radiation therapy (IORT) provides a promising alternative to adjuvant external beam radiation therapy by enabling superior organ-at-risk preservation, reduction of in-hospital times, and timely admission to subsequent systemic treatments, which increasingly comprise novel targeted immunotherapeutic approaches. We sought to assess the safety and efficacy of IORT in combination with immune checkpoint inhibitors (ICIs) and other targeted therapies (TTs). METHODS AND MATERIALS: In a multicentric approach incorporating individual patient data from 6 international IORT centers, all patients with BMs undergoing IORT were retrospectively assessed for combinatorial treatment with ICIs/TTs and evaluated for toxicity and cumulative rates, including wound dehiscence, radiation necrosis, leptomeningeal spread, local control, distant brain progression (DBP), and estimated overall survival. RESULTS: In total, 103 lesions with a median diameter of 34 mm receiving IORT combined with immunomodulatory systemic treatment or other TTs were included. The median follow-up was 13.2 (range, 1.2-102.4) months, and the median IORT dose was 25 (range, 18-30) Gy prescribed to the applicator surface. There was 1 grade 3 adverse event related to IORT recorded (2.2%). A 4.9% cumulative radiation necrosis rate was observed. The 1-year local control rate was 98.0%, and the 1-year DBP-free survival rate was 60.0%. Median time to DBP was 5.5 (range, 1.0-18.5) months in the subgroup of patients experiencing DBP, and the cumulative leptomeningeal spread rate was 4.9%. The median estimated overall survival was 26 (range, 1.2 to not reached) months with a 1-year survival rate of 74.0%. Early initiation of immunotherapy/TTs was associated with a nonsignificant trend toward improved DBP rate and overall survival. CONCLUSIONS: The combination of ICIs/TTs with IORT for resected BMs does not seem to increase toxicity and yields encouraging local control outcomes in the difficult-to-treat subgroup of larger BMs. Time gaps between surgery and systemic treatment could be shortened or avoided. The definitive role of IORT in local control after BM resection will be defined in a prospective trial.

Finding navigation cues near fishways.

Many fish species depend on migration for various parts of their life cycle. Well-known examples include diadromous fish such as salmon and eels that need both fresh water and salt water to complete their life cycle. Migration also occurs within species that depend only on fresh water. In recent decades, anthropogenic pressures on freshwater systems have increased greatly, and have resulted, among other effects, in drastic habitat fragmentation. Fishways have been developed to mitigate the resulting habitat fragmentation, but these are not always effective. To improve fishway efficiency, the variety of navigation cues used by fish must be better understood: fish use a multitude of sensory inputs ranging from flow variables to olfactory cues. The reaction of a fish is highly dependent on the intensity of the cue, the fish species involved, and individual traits. Recently developed monitoring technologies allow us to gain insights into different combinations of environmental and physiological conditions. By combining fish behavioural models with environmental models, interactions among these components can be investigated. Several methods can be used to analyse fish migration, with state-space models, hidden Markov models, and individual-based models potentially being the most relevant since they can use individual data and can tie them to explicit spatial locations within the considered system. The aim of this review is to analyse the navigational cues used by fish and the models that can be applied to gather knowledge on these processes. Such knowledge could greatly improve the design and operation of fishways for a wider range of fish species and conditions.

EULAR recommendations for the management of systemic lupus erythematosus: 2023 update.

OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence. METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item. RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease. CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.

The proneural subtype is not associated with survival benefit from bevacizumab in newly diagnosed glioblastoma: a secondary analysis of the GLARIUS trial.

PURPOSE: The AVAglio trial reported a significant survival benefit for first line bevacizumab treatment in patients with IDH wildtype glioblastoma of the proneural gene expression subtype. We here aim to replicate these findings in an independent trial cohort. METHODS: We evaluate the treatment benefit of bevacizumab according to gene expression subtypes of pretreatment tumor samples (n = 123) in the GLARIUS trial (NCT00967330) for MGMT unmethylated glioblastoma patients with Kaplan-Meier analyses, log-rank tests and Cox regression models. RESULTS: Employing the Phillips classifier, bevacizumab conferred a significant PFS advantage in patients with proneural IDH wild-type tumors (10.4 vs. 6.0 months, p = 0.002), but no OS advantage (16.4 vs. 17.4 months, p = 0.6). Multivariable analysis adjusting for prognostic covariates confirmed the absence of a significant OS advantage from bevacizumab (hazard ratio, 1.05, 95% CI, 0.42 to 2.64; p = 0.14). Further, there was no interaction between the proneural subtype and treatment arm (p = 0.15). These results were confirmed in analyses of tumor subgroups according to the Verhaak classifier. CONCLUSION: In contrast to AVAglio, glioblastoma gene expression subgroups were not associated with a differential OS benefit from first-line bevacizumab in the GLARIUS trial.

Intraoperative or postoperative stereotactic radiotherapy for brain metastases: time to systemic treatment onset and other patient-relevant outcomes.

PURPOSE: Intraoperative radiotherapy (IORT) has become a viable treatment option for resectable brain metastases (BMs). As data on local control and radiation necrosis rates are maturing, we focus on meaningful secondary endpoints such as time to next treatment (TTNT), duration of postoperative corticosteroid treatment, and in-hospital time. METHODS: Patients prospectively recruited within an IORT study registry between November 2020 and June 2023 were compared with consecutive patients receiving adjuvant stereotactic radiotherapy (SRT) of the resection cavity within the same time frame. TTNT was defined as the number of days between BM resection and start of the next extracranial oncological therapy (systemic treatment, surgery, or radiotherapy) for each of the groups. RESULTS: Of 95 BM patients screened, IORT was feasible in 84 cases (88%) and ultimately performed in 64 (67%). The control collective consisted of 53 SRT patients. There were no relevant differences in clinical baseline features. Mean TTNT (range) was 36 (9 - 94) days for IORT patients versus 52 (11 - 126) days for SRT patients (p = 0.01). Mean duration of postoperative corticosteroid treatment was similar (8 days; p = 0.83), as was mean postoperative in-hospital time (11 versus 12 days; p = 0.97). Mean total in-hospital time for BM treatment (in- and out-patient days) was 11 days for IORT versus 19 days for SRT patients (p < 0.001). CONCLUSION: IORT for BMs results in faster completion of interdisciplinary treatment when compared to adjuvant SRT, without increasing corticosteroid intake or prolonging in-hospital times. A randomised phase III trial will determine the clinical effects of shorter TTNT.

Defining the physician global assessment threshold equivalent to remission in patients with systemic lupus erythematosus.

OBJECTIVES: The optimal threshold of the physician global assessment (PGA) for remission in SLE has never been evaluated systematically. The aim of this study was to assess the ideal PGA threshold associated with physician remission and to investigate its impact on remission rates in our Lupus cohort. METHODS: In this monocentric cross-sectional study, patients with SLE were evaluated for physician remission by asking the treating physicians if they considered their patient in remission regardless of objective remission criteria. Further, two objective remission definitions were applied: 1) DORIS remission using a PGA of < 2 (0-10) (corresponding to < 0.5 on a VAS 0-3 used in DORIS); 2) DORIS remission with omission of PGA (modDORIS). A receiver operating characteristic analysis and regression analyses were performed to assess the ideal PGA threshold and factors influencing PGA. RESULTS: Of the 233 patients included, 126 patients (54.0%) were in physician remission, 42.5% in DORIS remission and 67.0% in modDORIS remission. A PGA of < 2 NRS 0-10) had the highest sensitivity (79%) and specificity (81%) for physician remission and modDORIS (AUC 0.85 and 0.69). PGA of patients fulfilling any of the remission definitions was associated with pain and hypocomplementemia. Damage was numerically higher in patients in modDORIS only; no association between PGA and damage was found in regression analysis. CONCLUSION: Using a PGA threshold of < 2 (0-10), corresponding to < 0.6 (0-3) resulted in best prediction of physician remission. PGA levels seem to be influenced by pain and complement levels but not disease damage.

Undetected pseudoprogressions in the CeTeG/NOA-09 trial: hints from postprogression survival and MRI analyses.

PURPOSE: In the randomized CeTeG/NOA-09 trial, lomustine/temozolomide (CCNU/TMZ) was superior to TMZ therapy regarding overall survival (OS) in MGMT promotor-methylated glioblastoma. Progression-free survival (PFS) and pseudoprogression rates (about 10%) were similar in both arms. Further evaluating this discrepancy, we analyzed patterns of postprogression survival (PPS) and MRI features at first progression according to modified RANO criteria (mRANO). METHODS: We classified the patients of the CeTeG/NOA-09 trial according to long vs. short PPS employing a cut-off of 18 months and compared baseline characteristics and survival times. In patients with available MRIs and confirmed progression, the increase in T1-enhancing, FLAIR hyperintense lesion volume and the change in ADC mean value of contrast-enhancing tumor upon progression were determined. RESULTS: Patients with long PPS in the CCNU/TMZ arm had a particularly short PFS (5.6 months). PFS in this subgroup was shorter than in the long PPS subgroup of the TMZ arm (11.1 months, p = 0.01). At mRANO-defined progression, patients of the CCNU/TMZ long PPS subgroup had a significantly higher increase of mean ADC values (p = 0.015) and a tendency to a stronger volumetric increase in T1-enhancement (p = 0.22) as compared to long PPS patients of the TMZ arm. CONCLUSION: The combination of survival and MRI analyses identified a subgroup of CCNU/TMZ-treated patients with features that sets them apart from other patients in the trial: short first PFS despite long PPS and significant increase in mean ADC values upon mRANO-defined progression. The observed pattern is compatible with the features commonly observed in pseudoprogression suggesting mRANO-undetected pseudoprogressions in the CCNU/TMZ arm of CeTeG/NOA-09.

High Frequency of Osteophytes Detected by High-Resolution Ultrasound at the Finger Joints of Asymptomatic Factory Workers.

Hand Osteoarthritis (HOA) is a frequently occurring musculoskeletal disease that impacts health. Diagnostic criteria often incorporate osteophytes documented through imaging procedures. Radiographic imaging is considered the gold standard; however, more sensitive and safer methods like ultrasound imaging are becoming increasingly important. We conducted a population-based cross-sectional study to examine the prevalence, grade, and pattern of osteophytes using high-resolution ultrasound investigation. Factory workers were recruited on-site for the study. Each participant had 26 finger joints examined using ultrasonography to grade the occurrence of osteophytes on a semi-quantitative scale ranging from 0-3, where higher scores indicate larger osteophytes. A total of 427 participants (mean age 53.5 years, range 20-79 years) were included, resulting in 11,000 joints scored. At least one osteophyte was found in 4546 out of 11,000 (41.3%) joints or in 426 out of 427 (99.8%) participants, but only 5.0% (553) of the joints showed grade 2 or 3 osteophytes. The total osteophyte sum score increased by 0.18 per year as age increased (p < 0.001). The distal interphalangeal joints were the most commonly affected, with 61%, followed by the proximal interphalangeal joints with 48%, carpometacarpal joint 1 with 39%, and metacarpophalangeal joints with 16%. There was no observed impact of gender or workload. In conclusion, ultrasound imaging proves to be a practical screening tool for osteophytes and HOA. Grade 1 osteophytes are often detected in the working population through ultrasound assessments and their incidence increases with age. The occurrence of grade 2 or 3 osteophytes is less frequent and indicates the clinical presence of HOA. Subsequent evaluations are imperative to ascertain the predictive significance of early osteophytes.

Downregulation of MGMT expression by targeted editing of DNA methylation enhances temozolomide sensitivity in glioblastoma.

Glioblastoma is the most common and aggressive primary tumor of the central nervous system with poor outcome. Current gold standard treatment is surgical resection followed by a combination of radio- and chemotherapy. Efficacy of temozolomide (TMZ), the primary chemotherapeutic agent, depends on the DNA methylation status of the O6-methylguanine DNA methyltransferase (MGMT), which has been identified as a prognostic biomarker in glioblastoma patients. Clinical studies revealed that glioblastoma patients with hypermethylated MGMT promoter have a better response to TMZ treatment and a significantly improved overall survival. In this study, we thus used the CRISPRoff genome editing tool to mediate targeted DNA methylation within the MGMT promoter region. The system carrying a CRISPR-deactivated Cas9 (dCas9) fused with a methyltransferase (Dnmt3A/3L) domain downregulated MGMT expression in TMZ-resistant human glioblastoma cell lines through targeted DNA methylation. The reduction of MGMT expression levels reversed TMZ resistance in TMZ-resistant glioblastoma cell lines resulting in TMZ induced dose-dependent cell death rates. In conclusion, we demonstrate targeted RNA-guided methylation of the MGMT promoter as a promising tool to overcome chemoresistance and improve the cytotoxic effect of TMZ in glioblastoma.

A population-based projection of psoriatic arthritis in Germany until 2050: analysis of national statutory health insurance data of 65 million German population.

The population-based prevalence of psoriatic arthritis (PsA) is still unclear and not well described globally. The aim of this study was to conduct a population-based prevalence projection and provide long-term future estimations of PsA patients in Germany until 2050, using the illness-death model and based on historical data. We analyzed the national statutory health insurance data of 65 million population in the German Institute for Medical Documentation and Information between January 2009 and December 2012. We constructed an estimation of the PsA burden among the German population using the relevant epidemiological parameters to project the numbers of patients with PsA in Germany until 2050 under five possible scenarios by varying the incidence and mortality. The overall conservatively estimated prevalence of PsA in Germany in 2019 was 0.31% (95% CI 0.28-0.36%). Women contribute a higher prevalence than men in all five scenarios. In the assumed scenarios with increased incidence, the prevalence of PsA at 60 years of age could rise from 1% in 2019 to more than 3% in 2050 for both genders, with the increase particularly pronounced for women, reaching around 3.5%. However, in the assumed scenarios with decreasing incidence, the prevalence curve may flatten and begin a decreasing trend from 2035 to 2050 for both genders, achieving a prevalence of less than 1% in 2050. Our research is to generate assumed population-based data on PsA in Germany that can serve as a reference for public health stakeholders to prepare an optional intervention. We would expect worryingly high numbers in the coming decades if preventive strategies are not implemented. In the long term, it will be necessary to implement preventive strategies to identify predictors and treat psoriasis symptoms early in order to delay or even prevent the transition of psoriasis to PsA.

Characterizing stenosis severity of coronary heart disease by myocardial work measurement in patients with preserved ejection fraction.

Background: The novel echocardiographic parameter of myocardial work incorporates left ventricular pressure into the assessment of left ventricular systolic function and thereby corrects for afterload. We sought to investigate the diagnostic value of myocardial work to identify different grades of stenosis severity in coronary heart disease (CHD) patients with preserved left ventricular ejection fraction and without regional wall motion abnormalities. Methods: One hundred and seventeen consecutive subjects with preserved ejection fraction referred for coronary angiography were randomized and prospectively included in this study. Forty-six in the control group, and 25, 24, and 22 in each of the grade-1, grade-2, and grade-3 CHD groups as classified by the Gensini score. The following indices of myocardial work were assessed with a Vivid E95 Version 203 instrument: global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE). Results: Both GWI (P<0.001) and GCW (P<0.001) decreased significantly in CHD grade-1, increased slightly in CHD grade-2 compared with CHD grade-1, and decreased significantly in CHD grade-3. GWW (P<0.001) increased significantly from CHD grade-1 to CHD grade-3, while GWE (P<0.001) decreased significantly from CHD grade-1 to CHD grade-3. Receiver operating characteristic curves analysis revealed good discrimination between the control group and CHD grade-3 for GWI [area under the curve (AUC): 0.810; 95% confidence interval (CI): 0.691-0.930], GCW (AUC: 0.758; 95% CI: 0.631-0.885), GWW (AUC: 0.754; 95% CI: 0.624-0.885) and GWE (AUC: 0.817; 95% CI: 0.709-0.926). The assessment of intraobserver and interobserver variability in the MW echocardiographic data documented good interclass correlation coefficients (all >0.85). Conclusions: Myocardial work incorporates left ventricular pressure into the assessment of left ventricular systolic function and thereby corrects for afterload. It identifies patients with incipient left ventricular dysfunction caused by chronic ischemia due to CHD. A gradual worsening of myocardial work parameters was observed when comparing patients with higher degrees of stenosis severity. Therefore, adding myocardial work when evaluating patients with suspected CHD may help increase diagnostic accuracy.

Modification of 3D-Printed PLA Structures Using Photo-Iniferter Polymerization: Toward On-Demand Antimicrobial Water Filters.

Water filtration is an important application to ensure the accessibility of clean drinking water. As requirements and contaminants vary on a local level, adjustable filter devices and their evaluation with contaminants are required. Within this work, modular filter devices are designed featuring an adjustable surface functionalization. For this purpose, 3D-printed structures are created consisting of bio-based poly(lactic acid) (PLA) that are manufactured by extrusion printing. The surface of PLA is activated with amino groups that are used to install xanthates as chain transfer agents. Subsequently, photo-iniferter (PI) polymerization is used to create cationic polymer brushes on the surface of PLA substrates. Multiple surface characterization techniques are employed to prove successful growth of polymer brushes on PLA. After initial optimization studies on flat surfaces, filter devices are printed, functionalized, and used to remove bacteria from contaminated water. Significant reduction of the number of microorganisms is detected after filtration (single filtration or cycling) and contaminating organism can also be removed from freshwater samples by simple incubation with a 3D-printed filter. The herein developed setup for producing functional filter devices and probing their performance in affinity filtration is a useful platform technology, enabling the rapid testing of polymer brushes for such applications.