Itaconate is a metabolic regulator of bone formation in homeostasis and arthritis.

OBJECTIVES: Bone remodelling is a highly dynamic process dependent on the precise coordination of osteoblasts and haematopoietic-cell derived osteoclasts. Changes in core metabolic pathways during osteoclastogenesis, however, are largely unexplored and it is unknown whether and how these processes are involved in bone homeostasis. METHODS: We metabolically and transcriptionally profiled cells during osteoclast and osteoblast generation. Individual gene expression was characterised by quantitative PCR and western blot. Osteoblast function was assessed by Alizarin red staining. immunoresponsive gene 1 (Irg1)-deficient mice were used in various inflammatory or non-inflammatory models of bone loss. Tissue gene expression was analysed by RNA in situ hybridisation. RESULTS: We show that during differentiation preosteoclasts rearrange their tricarboxylic acid cycle, a process crucially depending on both glucose and glutamine. This rearrangement is characterised by the induction of Irg1 and production of itaconate, which accumulates intracellularly and extracellularly. While the IRG1-itaconate axis is dispensable for osteoclast generation in vitro and in vivo, we demonstrate that itaconate stimulates osteoblasts by accelerating osteogenic differentiation in both human and murine cells. This enhanced osteogenic differentiation is accompanied by reduced proliferation and altered metabolism. Additionally, supplementation of itaconate increases bone formation by boosting osteoblast activity in mice. Conversely, Irg1-deficient mice exhibit decreased bone mass and have reduced osteoproliferative lesions in experimental arthritis. CONCLUSION: In summary, we identify itaconate, generated as a result of the metabolic rewiring during osteoclast differentiation, as a previously unrecognised regulator of osteoblasts.

"For the first time I am seriously fighting burnout": clinician experiences with a challenging electronic health record transition.

Objectives: The Department of Veterans Affairs (VA) is transitioning from its legacy electronic health record (EHR) to a new commercial EHR in a nationwide, rolling-wave transition. We evaluated clinician and staff experiences to identify strategies to improve future EHR rollouts. Materials and Methods: We completed a convergent mixed-methods formative evaluation collecting survey and interview data to measure and describe clinician and staff experiences. Survey responses were analyzed using descriptive statistics; interview transcripts were coded using a combination of a priori and emergent codes followed by qualitative content analysis. Qualitative and quantitative findings were compared to provide a more comprehensive understanding of participant experience. Employees of specialty and primary care teams at the first nationwide EHR transition site agreed to participate in our study. We distributed surveys at 1-month pre-transition, 2 months post-transition, and 10 months post-transition to each of the 68 identified team members and completed longitudinal interviews with 30 of these individuals totaling 122 semi-structured interviews. Results: Interview participants reported profoundly disruptive experiences during the EHR transition that persisted at 1-year post implementation. Survey responses indicated training difficulties throughout the transition, and sharp declines (P ≤ .05) between pre- and post-go-live measures of EHR usability and increase in EHR burden that were perceived to be due in part to system inefficiencies, discordant positive messaging that initially ignored user challenges, and inadequate support for and attention to ongoing EHR issues. Participants described persistent high levels of stress associated with these disruptions. Discussion: Our findings highlight strategies to improve employee experiences during EHR transitions: (1) working with Oracle Cerner to resolve known issues and improve usability; (2) role-based training with opportunities for self-directed learning; (3) peer-led support systems and timely feedback on issues; (4) messaging that responds to challenges and successes; and (5) continuous efforts to support staff with issues and address clinician and staff stress and burnout. Conclusion: Our findings provide relevant strategies to navigate future EHR transitions while supporting clinical teams.

High Rates of Organ Preservation in Rectal Cancer with Papillon Contact X-ray Radiotherapy: Results from a Swiss Cohort.

Rectal cancer typically necessitates a combination of radiotherapy (RT), chemotherapy, and surgery. The associated functional disorders and reduction in quality of life have led to an increasing interest in organ preservation strategies. Response strongly correlates with RT dose, but dose escalation with external beam remains limited even with modern external beam RT techniques because of toxicity of the surrounding tissues. This study reports on the use of Papillon, an endocavitary Radiotherapy device, in the treatment of rectal cancer. The device delivers low energy X-rays, allowing for safe dose escalation and better complete response rate. Between January 2015 and February 2024, 24 rectal cancer patients were treated with the addition of a boost delivered by Papillon to standard RT, with or without chemotherapy, in an upfront organ preservation strategy. After a median follow-up (FU) of 43 months, the organ preservation rate was 96% (23/24), and the local relapse rate was 8% (2/24). None of our patients developed grade 3 or more toxicities. Our results demonstrate that the addition of Papillon contact RT provides a high rate of local remission with sustained long-term organ preservation, offering a promising alternative to traditional surgical approaches in patients with rectal cancer.

The impact of elevated C-reactive protein levels on long-term outcomes of patients undergoing transcatheter aortic valve replacement.

BACKGROUND: In patients undergoing transcatheter aortic valve replacement (TAVR), elevated pre-procedural C-reactive protein (CRP) levels are frequently observed. Its impact on long-term results of TAVR is unclear. The aim of the study was to investigate the long-term (up to six years) clinical outcomes of TAVR patients with normal compared to elevated CRP levels before TAVR. METHODS: Consecutive patients undergoing TAVR between August 2012 and January 2023 at a tertiary cardiology facility were included. Patients were divided into two cohorts based on the baseline CRP levels: normal CRP (≤ 5 mg/l) and elevated CRP (>5 mg/l). The cohorts were followed clinically for up to six years after TAVR. RESULTS: From a total of 1000 TAVR patients (mean age 81 ± 6 years), 268 patients (27 %) were found to have elevated baseline CRP (>5 mg/l). Such patients had significantly more co-morbidities (e.g. chronic obstructive pulmonary disease, atrial fibrillation, heart failure, concomitant valvopathies). They also developed periprocedural infections more frequently (3 % vs. 1 %, p = 0.007) and required more commonly repeat hospitalizations for infections during follow-up (HR 1.97, CI 1.47-2.64, p < 0.001). All-cause mortality and development of valve dysfunction did not significantly differ between patients with elevated and normal baseline CRP levels. CONCLUSION: Albeit long-term results of TAVR patients with elevated pre-procedural CRP levels seem favorable in terms of survival and development of valve dysfunction, they have an increased risk for periprocedural infections and re-admissions due to infections of any type during the follow-up period.

Voltage-Gated Ion Channels Are Transcriptional Targets of Sox10 during Oligodendrocyte Development.

The transcription factor Sox10 is an important determinant of oligodendroglial identity and influences oligodendroglial development and characteristics at various stages. Starting from RNA-seq data, we here show that the expression of several voltage-gated ion channels with known expression and important function in oligodendroglial cells depends upon Sox10. These include the Nav1.1, Cav2.2, Kv1.1, and Kir4.1 channels. For each of the four encoding genes, we found at least one regulatory region that is activated by Sox10 in vitro and at the same time bound by Sox10 in vivo. Cell-specific deletion of Sox10 in oligodendroglial cells furthermore led to a strong downregulation of all four ion channels in a mouse model and thus in vivo. Our study provides a clear functional link between voltage-gated ion channels and the transcriptional regulatory network in oligodendroglial cells. Furthermore, our study argues that Sox10 exerts at least some of its functions in oligodendrocyte progenitor cells, in myelinating oligodendrocytes, or throughout lineage development via these ion channels. By doing so, we present one way in which oligodendroglial development and properties can be linked to neuronal activity to ensure crosstalk between cell types during the development and function of the central nervous system.

A collective agenda: A qualitative study on Exercise is Medicine® On Campus gold-level institutions.

Objective: The Exercise is Medicine® On Campus (EIM-OC) international campaign leverages university resources (e.g., health centers, recreation, and kinesiology departments) to encourage students, faculty, and staff to integrate physical activity into campus culture. This involves evaluating student physical activity levels during health visits and establishing referral systems for exercise prescriptions. EIM-OC allows universities to earn tiered recognition (Gold, Silver, or Bronze) based on their on-campus physical activity promotion and integration. For Gold recognition, schools must incorporate routine physical activity assessments into their health system, ultimately connecting healthcare providers with health/fitness professionals (HFPs, e.g., campus recreation professionals, kinesiology professors). This research worked to uncover pivotal factors driving EIM-OC on-campus collaborations through HFPs' perspectives. Methods: HFPs (n = 11) working full-time at a Gold-level institution (n = 10 in United States) participated. Semi-structured, Zoom-recorded interviews with a generic qualitative research design were completed between June and September 2022. Results: Major thematic findings included the importance of tangible support (e.g., personnel), encounters with both trust and tension cross-campus, positive student development opportunities, and variations in outcome reporting and program evaluation. Faculty and staff emphasized the need for methods to obtain and sustain program funding. Participants also expressed the importance of interdisciplinary collaboration to increase the collective impact of EIM-OC on student health and overall collegiate success. Conclusion: HFPs expanded on their EIM-OC experiences and program sustainment or growth requirements. With increased interdisciplinary collaboration, rigor in outcome reporting, and tangible resources, the collective impact of EIM-OC on student health outcomes and overall collegiate success could be greatly perpetuated.

Alexithymia as a mediator between adverse childhood events and the development of psychopathology: a meta-analysis.

Introduction: Victims of child abuse have an elevated risk of developing mental health issues later in life. Several variables have been suggested as mediators of this correlation, but little is known about the possible influence of alexithymia. Alexithymia is a sub-clinical personality trait that manifests as difficulties recognizing and verbalizing emotions. Methods: In this study, two separate meta-analyses were conducted using questionnaire data, and Pearson correlations for overall effects were estimated. Results: The correlation between child abuse and alexithymia showed to be significant (r = .26), as did the correlation between alexithymia and general psychopathology (r = .44). Further analyses revealed no indication for possible publication bias. When investigating differences between various subtypes of child maltreatment, each subtype significantly correlated with alexithymia. Emotional abuse, emotional neglect, and physical neglect had stronger correlations than physical and sexual abuse. Discussion: These results suggest that alexithymia plays a mediating role, at least in part, in the relationship between experiences of child abuse and general psychopathology in adulthood. Therefore, alexithymia may be relevant to further research and deserves attention in the prevention of and therapy for mental health issues in victims of child abuse.

Spinal cord injury disrupts plasma extracellular vesicles cargoes leading to neuroinflammation in the brain and neurological dysfunction in aged male mice.

Aged individuals with spinal cord injury (SCI) are prevalent with increased mortality and worse outcomes. SCI can cause secondary brain neuroinflammation and neurodegeneration. However, the mechanisms contributing to SCI-induced brain dysfunction are poorly understood. Cell-to-cell signaling through extracellular vesicles (EVs) has emerged as a critical mediator of neuroinflammation, including at a distance through circulation. We have previously shown that SCI in young adult (YA) male mice leads to robust changes in plasma EV count and microRNAs (miRs) content. Here, our goal was to investigate the impact of old age on EVs and brain after SCI. At 24 h post-injury, there was no difference in particle count or size distribution between YA and aged mice. However, aged animals increased expression of EV marker CD63 with SCI. Using the Fireplex® miRs assay, Proteomics, and mass spectrometry-based Lipidomics, circulating EVs analysis identified distinct profiles of miRs, proteins, and lipid components in old and injury animals. In vitro, plasma EVs from aged SCI mice, at a lower concentration comparable to those of YA SCI mice, induced the secretion of pro-inflammatory cytokines and neuronal apoptosis. Systemic administration of plasma EVs from SCI animals was sufficient to impair general physical function and neurological function in intact animals, which is associated with pro-inflammatory changes in the brain. Furthermore, plasma EVs from young animals had rejuvenating effects on naïve aged mice. Collectively, these studies identify the critical changes in circulating EVs cargoes after SCI and in aged animals and support a potential EV-mediated mechanism for SCI-induced brain changes.

Epithelial Remodeling and Epithelial Wavefront Aberrometry after Spherical vs. Cylindrical Myopic Small Incision Lenticule Extraction (SMILE).

Background/Objectives: To compare the epithelial thickness changes and the changes in epithelial wavefront aberrometry following spherical versus astigmatic myopic small incision lenticule extraction (SMILE). Methods: Eighty-six eyes of 86 patients who underwent SMILE were included in this retrospective study. A total of 43 eyes underwent myopic spherical correction (spherical group) and 43 eyes underwent myopic cylindrical correction (cylindrical group). The groups were matched according to the spherical equivalent of surgically corrected refraction. Subjective manifest refraction as well as high-resolution anterior segment optical coherence tomography (MS-39; CSO; Florence, Italy) were obtained preoperatively as well as 3 months postoperatively. The latter was utilized for computing epithelial wavefront aberrometry in addition to epithelial thickness mapping. Results: Epithelial thickness increased significantly in both groups after SMILE (p < 0.01). In the cylindrical group, epithelial thickening was more pronounced on the flat meridian compared to the steep meridian (p = 0.04). In both groups, epithelial wavefront aberrometry showed a significant postoperative increase in the epithelium's spherical refractive power, causing a myopization of -0.24 ± 0.42 diopters (D) in the spherical group (p < 0.01) and -0.41 ± 0.52 D in the cylindrical group (p < 0.0001). While no significant changes in epithelial cylindrical refractive power were observed in the spherical group, a significant increase was noted in the cylindrical group from -0.21 ± 0.24 D to -0.37 ± 0.31 D (p = 0.01). In both groups, epithelial higher-order aberrations increased significantly (p < 0.001). Conclusions: Postoperative epithelial remodeling after SMILE alters lower-order (sphere and cylinder) and higher-order aberrations of the corneal epithelial wavefront and might contribute to refractive undercorrection, especially in astigmatic corrections. Epithelial wavefront aberrometry can be used to quantify the refractive effect of epithelial remodeling processes after keratorefractive surgery.

In the I of the beholder: an attempt to capture the implicit self-concept regarding psychopathy.

This article explores the implicit self-concept pertaining to psychopathy. Two online studies showed inconsistent results, with Study 1 (n = 243) suggesting that psychopathy is linked to an implicit self-concept marked by low empathy and Study 2 (n = 230) implying no such relationship. In a sample of offenders and community controls (Study 3a, n = 166), higher scores on the Psychopathy Checklist-Revised (PCL-R) were related to an implicit self-concept of being less rather than more antisocial, and the implicit self-concept showed incremental validity compared to the explicit self-concept. The retesting of an offender subsample (Study 3b, n = 47) yielded no evidence for temporal stability or convergent validity. The implicit self-concept of highly psychopathic individuals thus appears to vary, depending on the social context. Future studies should replicate these results in different samples, using additional external correlates.

Impact of Lipoprotein(a) Level on Low-Density Lipoprotein Cholesterol- or Apolipoprotein B-Related Risk of Coronary Heart Disease.

BACKGROUND: Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities. OBJECTIVES: The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDLLp(a)corr) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events. METHODS: Among 68,748 CHD-free subjects at baseline LDLLp(a)corr was calculated as "LDL-C-Lp(a)-C," where Lp(a)-C was 30% or 17.3% of total Lp(a) mass. Fine and Gray competing risk-adjusted models were applied for the association between the outcome incident CHD and: 1) LDL-C and LDLLp(a)corr in the total sample; and 2) LDL-C and apoB after stratification by Lp(a) mass (≥/<90th percentile). RESULTS: Similar risk estimates for incident CHD were found for LDL-C and LDL-CLp(a)corr30 or LDL-CLp(a)corr17.3 (subdistribution HR with 95% CI) were 2.73 (95% CI: 2.34-3.20) vs 2.51 (95% CI: 2.15-2.93) vs 2.64 (95% CI: 2.26-3.10), respectively (top vs bottom fifth; fully adjusted models). Categorization by Lp(a) mass resulted in higher subdistribution HRs for uncorrected LDL-C and incident CHD at Lp(a) ≥90th percentile (4.38 [95% CI: 2.08-9.22]) vs 2.60 [95% CI: 2.21-3.07]) at Lp(a) <90th percentile (top vs bottom fifth; Pinteraction0.39). In contrast, apoB risk estimates were lower in subjects with higher Lp(a) mass (2.43 [95% CI: 1.34-4.40]) than in Lp(a) <90th percentile (3.34 [95% CI: 2.78-4.01]) (Pinteraction0.49). CONCLUSIONS: Correction of LDL-C for its Lp(a)-C content provided no meaningful information on CHD-risk estimation at the population level. Simple categorization of Lp(a) mass (≥/<90th percentile) influenced the association between LDL-C or apoB with future CHD mostly at higher Lp(a) levels.

Neurosteroids and translocator protein 18 kDa (TSPO) ligands as novel treatment options in depression.

Recently, the gamma-aminobutyric acid (GABA) system has come into focus for the treatment of anxiety, postpartum depression, and major depressive disorder. Endogenous 3α-reduced steroids such as allopregnanolone are potent positive allosteric modulators of GABAA receptors and have been known for decades. Current industry developments and first approvals by the U.S. food and drug administration (FDA) for the treatment of postpartum depression with exogenous analogues of these steroids represent a major step forward in the field. 3α-reduced steroids target both synaptic and extrasynaptic GABAA receptors, unlike benzodiazepines, which bind to synaptic receptors. The first FDA-approved 3α-reduced steroid for postpartum depression is brexanolone, an intravenous formulation of allopregnanolone. It has been shown to provide rapid relief of depressive symptoms. An orally available 3α-reduced steroid is zuranolone, which also received FDA approval in 2023 for the treatment of postpartum depression. Although a number of studies have been conducted, the efficacy data were not sufficient to achieve approval of zuranolone in major depressive disorder by the FDA in 2023. The most prominent side effects of these 3α-reduced steroids are somnolence, dizziness and headache. In addition to the issue of efficacy, it should be noted that current data limit the use of these compounds to two weeks. An alternative to exogenous 3α-reduced steroids may be the use of substances that induce endogenous neurosteroidogenesis, such as the translocator protein 18 kDa (TSPO) ligand etifoxine. TSPO has been extensively studied for its role in steroidogenesis, in addition to other functions such as anti-inflammatory and neuroregenerative properties. Currently, etifoxine is the only clinically available TSPO ligand in France for the treatment of anxiety disorders. Studies are underway to evaluate its antidepressant potential. Hopefully, neurosteroid research will lead to the development of fast-acting antidepressants.

Charge Trapping and Defect Dynamics as Origin of Memory Effects in Metal Halide Perovskite Memlumors.

Large language models for artificial intelligence applications require energy-efficient computing. Neuromorphic photonics has the potential to reach significantly lower energy consumption in comparison with classical electronics. A recently proposed memlumor device uses photoluminescence output that carries information about its excitation history via the excited state dynamics of the material. Solution-processed metal halide perovskites can be used as efficient memlumors. We show that trapping of photogenerated charge carriers modulated by photoinduced dynamics of the trapping states themselves explains the memory response of perovskite memlumors on time scales from nanoseconds to minutes. The memlumor concept shifts the paradigm of the detrimental role of charge traps and their dynamics in metal halide perovskite semiconductors by enabling new applications based on these trap states. The appropriate control of defect dynamics in perovskites allows these materials to enter the field of energy-efficient photonic neuromorphic computing, which we illustrate by proposing several possible realizations of such systems.

Quantitative imaging of loop extruders rebuilding interphase genome architecture after mitosis.

How cells establish the interphase genome organization after mitosis is incompletely understood. Using quantitative and super-resolution microscopy, we show that the transition from a Condensin to a Cohesin-based genome organization occurs dynamically over two hours. While a significant fraction of Condensins remains chromatin-bound until early G1, Cohesin-STAG1 and its boundary factor CTCF are rapidly imported into daughter nuclei in telophase, immediately bind chromosomes as individual complexes and are sufficient to build the first interphase TAD structures. By contrast, the more abundant Cohesin-STAG2 accumulates on chromosomes only gradually later in G1, is responsible for compaction inside TAD structures and forms paired complexes upon completed nuclear import. Our quantitative time-resolved mapping of mitotic and interphase loop extruders in single cells reveals that the nested loop architecture formed by sequential action of two Condensins in mitosis is seamlessly replaced by a less compact, but conceptually similar hierarchically nested loop architecture driven by sequential action of two Cohesins.

Implementation of and Systems-Level Barriers to Guideline-Driven Germline Genetic Evaluation in the Care of Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia.

PURPOSE: Knowledge of an inherited predisposition to myelodysplastic syndrome (MDS) and AML has important clinical implications for treatment decisions, surveillance, and care of at-risk relatives. National Comprehensive Cancer Network (NCCN) guidelines recently incorporated recommendations for germline genetic evaluation of patients with MDS/AML on the basis of personal and family history features, but the practicality of implementing these recommendations has not been studied. METHODS: A hereditary hematology quality improvement (QI) committee was formed to implement these guidelines in a prospective cohort of patients diagnosed with MDS/AML. Referral for germline genetic testing was recommended for patients meeting NCCN guideline criteria. Referral patterns and genetic evaluation outcomes were compared with a historical cohort of patients with MDS/AML. Barriers to evaluation were identified. RESULTS: Of the 90 patients with MDS/AML evaluated by the QI committee, 59 (66%) met criteria for germline evaluation. Implementation of the QI committee led to more referrals for germline evaluation in accordance with NCCN guidelines (31% v 14%, P = .03). However, the majority of those meeting criteria were never referred due to high medical acuity or being deceased or in hospice at the time of QI committee recommendations. Despite this, two (17%) of the 12 patients undergoing genetic testing were diagnosed with a hereditary myeloid malignancy syndrome. CONCLUSION: Current NCCN guidelines resulted in two thirds of patients with MDS/AML meeting criteria for germline evaluation. A hereditary hematology-focused QI committee aided initial implementation and modestly improved NCCN guideline adherence. However, the high morbidity and mortality and prolonged inpatient stays associated with MDS/AML challenged traditional outpatient genetic counseling models. Further improvements in guideline adherence require innovating new models of genetic counseling and testing for this patient population.

Safety and efficacy of tofacitinib for the treatment of patients with juvenile idiopathic arthritis: preliminary results of an open-label, long-term extension study.

OBJECTIVES: We report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study. METHODS: Patients (2-<18 years) with JIA who completed phase 1/3 index studies or discontinued for reasons excluding treatment-related serious adverse events (AEs) entered the LTE study and received tofacitinib 5 mg two times per day or equivalent weight-based doses. Safety outcomes included AEs, serious AEs and AEs of special interest. Efficacy outcomes included improvement since tofacitinib initiation per the JIA-American College of Rheumatology (ACR)70/90 criteria, JIA flare rate and disease activity measured by Juvenile Arthritis Disease Activity Score (JADAS)27, with inactive disease corresponding to JADAS ≤1.0. RESULTS: Of 225 patients with JIA (median (range) duration of treatment, 41.6 (1-103) months), 201 (89.3%) had AEs; 34 (15.1%) had serious AEs. 10 patients developed serious infections; three had herpes zoster. Two patients newly developed uveitis. Among patients with polyarticular course JIA, JIA-ACR70/90 response rates were 60.0% (78 of 130) and 33.6% (47 of 140), respectively, at month 1, and generally improved over time. JIA flare events generally occurred in <5% of patients through to month 48. Observed mean (SE) JADAS27 was 22.0 (0.6) at baseline, 6.2 (0.7) at month 1 and 2.8 (0.5) at month 48, with inactive disease in 28.8% (36 of 125) of patients at month 1 and 46.8% (29 of 82) at month 48. CONCLUSIONS: In this interim analysis of LTE study data in patients with JIA, safety findings were consistent with the known profile of tofacitinib, and efficacy was maintained up to month 48. TRIAL REGISTRATION NUMBER: NCT01500551.

Serial cardiac biomarkers, pulmonary artery pressures and traditional parameters of fluid status in relation to prognosis in patients with chronic heart failure: Design and rationale of the BioMEMS study.

AIMS: Heart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF-related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early-stage intervention, since haemodynamic congestion precedes clinical symptoms. METHODS: The BioMEMS study, a substudy of the MONITOR-HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR-HF trial were collected at baseline, 3-, 6-, and 12-month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS-HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death. CONCLUSION: Since the prognostic value of single baseline measurements of biomarkers like N-terminal pro-B-type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively.

Advanced linear axial wavelength spreading through cascaded double hyperchromats.

This study explores the design and optimization of cascaded double-hyperchromatic optical systems (i.e., 2×2 lenses), focusing on achieving an extremely linear axial spectral decomposition characterized by an exceptionally low equivalent Abbe number. The investigation involves two double hyperchromats, considering both purely refractive systems and hybrid configurations that combine refractive and diffractive elements. For purely refractive systems, alternating focal length signs of divergent and collective lenses are crucial to achieve significant axial chromatic dispersion. In hybrid systems, the position of the diffractive optical element (DOE) and the selection of focal lengths play key roles in obtaining extremely low equivalent Abbe numbers. The optimized systems demonstrate absolute equivalent Abbe numbers of 0.983 for purely refractive and 0.65 for hybrid systems-more than four times lower than the absolute Abbe number of a single diffractive element. Notably, even systems using standard materials exhibit significantly low equivalent Abbe numbers of 2.5 and 1.4 for pure refractive and hybrid configurations, respectively. These results offer promising opportunities for improving optical applications based on axial spectral decomposition, overcoming previous limitations of axial chromatic spreading.

Antibiotic treatment after appendectomy for acute complicated appendicitis to prevent intrabdominal abscess and wound infections.

INTRODUCTION: The purpose of this analysis was to investigate the most appropriate duration of postoperative antibiotic treatment to minimize the incidence of intraabdominal abscesses and wound infections in patients with complicated appendicitis. MATERIALS AND METHODS: In this retrospective study, which included 396 adult patients who underwent appendectomy for complicated appendicitis between January 2010 and December 2020 at the University Hospital Erlangen, patients were classified into two groups based on the duration of their postoperative antibiotic intake: ≤ 3 postoperative days (group 1) vs. ≥ 4 postoperative days (group 2). The incidence of postoperative intraabdominal abscesses and wound infections were compared between the groups. Additionally, multivariate risk factor analysis for the occurrence of intraabdominal abscesses and wound infections was performed. RESULTS: The two groups contained 226 and 170 patients, respectively. The incidence of postoperative intraabdominal abscesses (2% vs. 3%, p = 0.507) and wound infections (3% vs. 6%, p = 0.080) did not differ significantly between the groups. Multivariate analysis revealed that an additional cecum resection (OR 5.5 (95% CI 1.4-21.5), p = 0.014) was an independent risk factor for intraabdominal abscesses. A higher BMI (OR 5.9 (95% CI 1.2-29.2), p = 0.030) and conversion to an open procedure (OR 5.2 (95% CI 1.4-20.0), p = 0.016) were identified as independent risk factors for wound infections. CONCLUSION: The duration of postoperative antibiotic therapy does not appear to influence the incidence of postoperative intraabdominal abscesses and wound infections. Therefore, short-term postoperative antibiotic treatment should be preferred.

Testing the effectiveness of the culturally adapted skills training START NOW to reduce mental health problems in adolescent refugees: study protocol for a randomized controlled trial.

Background: Adolescent refugees are particularly vulnerable to mental health problems, as they experience many risk factors associated with their resettlement at crucial stages of their physical and emotional development. However, despite having a greater healthcare needs than others, they face significant barriers to accessing healthcare services. Therefore, this study aims to test the effectiveness of a low-threshold, culturally adapted version of the skills training START NOW - START NOW Adapted - in reducing mental health problems among adolescent refugees. Methods: We will recruit 80 adolescent refugees (15-18 years) with symptoms of anxiety and depression or high perceived stress in Northwestern Switzerland. They will be randomly assigned to one of two study groups: an intervention group, receiving START NOW Adapted, and a control group, receiving treatment as usual (TAU). The intervention will last 10 weeks and will consist of one-hour sessions per week provided by a trained facilitator with the same cultural background, in the respective language. Assessments to collect depressive and anxious symptoms, perceived stress, social-ecological resilience, and emotion recognition abilities will be conducted pre-intervention, post-intervention (11 weeks later) and at the 3-month follow-up. Multilevel models will be computed with primary and secondary outcome measures as dependent variables. An effect of at least moderate size will be considered clinically relevant. Discussion: This randomized controlled trial aims to investigate the effectiveness of a culturally adapted version of START NOW, providing valuable insights to improve current health promotion for adolescent refugees in Switzerland (or rather lack thereof). Ultimately, the effects of START NOW may facilitate integration and promote healthy development while decreasing costs associated with treating migration- or conflict-related trauma.Clinical trial registration: ClinicalTrials.gov, identifier: NCT06324864.