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Treatment outcome in a specialized unit for adults with severe and extreme anorexia nervosa at one-year follow up
No full textBackground:
Inpatient treatment successfully increases body weight and decreases eating disorder and associated symptoms in patients with anorexia nervosa (AN). However, relapse rates are high, particularly within the first year after discharge.
Methods:
We examined treatment outcome one year after discharge in adults with AN (N = 80, 2 males; BMI at admission: M = 13.2 kg/m2, SD = 1.79) who received treatment in a specialized inpatient unit for AN patients with severe underweight (body mass index < 15 kg/m2) and/or excessive purging or exercising.
Results:
From admission to discharge, body weight and self-reported life satisfaction significantly increased and self-reported eating disorder symptoms, depressive symptoms, and compulsive exercise significantly decreased. From discharge to follow up, life satisfaction and body weight decreased, and eating disorder symptoms, depressive symptoms, and compulsive exercise increased, although 87% of patients indicated to have received some kind of eating disorder treatment in the past six months. At follow up, the majority of patients indicated that they regularly ate three meals per day in the past week, including consumption of high-calorie, formerly forbidden foods. However, only a minority of patients indicated that they adhered to the hospital’s guidelines on portion sizes. Patients’ self-reported desired body weight at follow up was significantly higher than their current body weight.
Conclusions:
While inpatient treatment results in substantial improvements that are partially maintained after discharge, severe and extreme cases of AN require more long-lasting, alternating treatment approaches (e.g., interval treatment) to ensure long-term recovery
Temperament and personality: preliminary evidence of possible relationships with multifactorial stress reactivity in healthy adolescents
No full textObjective: It is hypothesized that personality and temperament influence the stress response. However, no study has thoroughly investigated the impact of these factors during adolescence, a critical stage of development and consolidation. In this study, we aimed to explore this relationship, both for personality and temperament aspects, in a sample of adolescents. Therefore, an experimental stress induction, combined with multifactorial stress assessment, incorporating both biological and subjective measures, was conducted.
Method: An acute psychosocial stress reaction was induced in 73 healthy adolescents (11–17 years of age, 63.0% female). Features of the stress response were recorded, including salivary cortisol, salivary alpha-amylase, heart rate, heart rate variability, and subjective stress. We investigated relationships between these factors and control variables (e.g., stress vulnerability and traumatic life experiences), specific trait facets, personality profiles according to the Big Five, and temperament dimensions according to Cloninger.
Results: In bivariate correlations, salivary cortisol response was negatively associated with Extraversion. Regarding bivariate correlations with temperament, Harm Avoidance was particularly associated with cortisol response and with the subjective stress response. Only stress vulnerability was significantly related to the subjective stress response.
Conclusion: In conclusion, the associations between personality/temperament profiles with the stress response are already evident during adolescence, highlighting the developmental aspect and the early emergence of these relationships. These findings suggest that personality and temperament profiles relate to individual differences in adolescent stress sensitivity. Identifying profiles linked to heightened or prolonged stress responses—such as high harm avoidance—may inform early interventions to support at-risk youth
Nocturnal hypoxemic burden is associated with worsening prognosis of chronic kidney disease in patients with type 2 diabetes
No full textIntroduction:
Lower estimated glomerular filtration rate (eGFR) and more severe albuminuria categories are associated with increased risk for adverse outcomes such as mortality, cardiovascular and kidney outcomes. The aim of the analysis was to evaluate whether nocturnal hypoxemic burden (NHB) is associated with worsening prognosis of CKD in a population with T2D.
Methods:
Overnight oximetry data from patients enrolled in the DIACORE (DIAbetes COhoRtE) sleep-disordered breathing sub-study, a prospective cohort study of patients with T2D, was analyzed and NHB as cumulative time spent below 90% oxygen saturation (T90) was quantified. Very-high-risk CKD was defined according to KDIGO risk classification: eGFR 30 mg albumin/g creatinine; or eGFR 300 mg/g. Logistic regression analyses adjusting for known risk factors for CKD prognosis were performed to assess the association between NHB and incident very-high-risk CKD.
Results:
The analysis population comprised 857 participants (41% female, mean age 65 years, median diabetes duration 9.0 years, median eGFR 82 ml/min/1.73 m2). During follow-up, 72 (8.4%) patients developed very-high-risk CKD, and patients with high T90 significantly more often developed very-high-risk CKD than patients with lower T90 (quartile 4 vs. quartiles 1–3: 15.0 vs. 6.2%, p < 0.001). NHB was significantly associated with an increased incidence of very-high-risk CKD. Patients in the highest quartile of T90 had a 3.0-fold higher risk compared to patients in the lowest quartile, independently of other risk factors for CKD prognosis such as age, sex, waist-hip ratio, hypertension, antihypertensive and lipid-lowering medication, HbA1c, diabetes duration, and eGFR and hemoglobin levels at baseline (OR 2.96, 95% CI (1.24; 7.07), p = 0.014; p for trend 0.013).
Conclusion:
We identified NHB as a novel risk factor for worsening CKD prognosis in patients with T2D. Further research is needed to ascertain whether T90 reduction constitutes a clinically meaningful prevention target
A New Thallide Auride Double Salt: Cs3.4K4.6[Au][Tl7] Featuring [Tl7]7– Zintl Clusters
No full textCs3.4K4.6[Au][Tl7] has been prepared from the elements (Pnma, a = 39.6898(12) Å, b = 12.0407(4) Å, c = 10.9334(3) Å, V = 5225.0(3) Å3, Z = 8, R1/wR2 = 0.0556/0.0935). Band structure calculations reveal a small bandgap at EF (0.10139 eV)
Untersuchung zur Stressantwort von E.coli nach Behandlung mit antimikrobieller photodynamischer Therapie (aPDT)
No full textAngesichts der zunehmenden globalen Problematik der Antibiotikaresistenzen ist die Entwicklung alternativer therapeutischer Strategien von hoher Relevanz. Eine vielversprechende Methode stellt die antimikrobielle photodynamische Therapie (aPDT) dar, deren Mechanismen auf die Erzeugung reaktiver Sauerstoffspezies zur Inaktivierung bakterieller Zellen abzielen. In der vorliegenden Studie wurden die Auswirkungen verschiedener Stressfaktoren – Hitzeschock, oxidativer Stress durch H₂O₂ sowie aPDT – auf die Expression spezifischer Proteine in Escherichia coli untersucht. Zur Definition subletaler Stressbedingungen wurden Toxizitätstests durchgeführt, wobei eine Reduktion der koloniebildenden Einheiten (KBE) um weniger als 3 log₁₀ - Stufen als subletal eingestuft wurde. Andere Studien verwenden teils Kriterien mit Reduktionen von ≤ 2 - log₁₀ bis 0,5 log₁₀ - Stufen. In der vorliegenden Arbeit wurde für oxidativen Stress eine subletale H₂O₂ - Konzentration von 0,5 % bei 5 - minütiger Exposition bestimmt. Der Test zeigte, dass die Katalaseaktivität bei höheren H₂O₂ - Konzentrationen niedriger war, was darauf hinweisen könnte, dass die Bedingung für einige Bakterien letal gewesen sein könnte. Beobachtet man die Aktivität im zeitlichen Verlauf, fällt auf, dass ein Anstieg nach 30 Minuten nach Behandlung mit H₂O₂ und ein anschließender Abfall nach 60 Minuten zu erkennen ist. Laut Literatur induziert E.coli die Expression von KatG solange die Bakterien oxidativem Stress, wie H₂O₂, ausgesetzt sind. Nach Bestimmung der subletalen Bedingungen, wurden diese Parameter verwendet, um dann die Proteinexpression von DnaK, RecA, KatG und GAPDH durch Western Blot - Analysen zu messen, um Veränderungen als Antwort auf die verschiedenen Stressbedingungen zu identifizieren. GAPDH sollte ursprünglich als Housekeepingprotein verwendet werden. Da es aber eine Regulation in diesen Versuchen zeigte, war es dafür nicht geeignet und wurde dafür nicht verwendet. Für die Stressproteine konnte keine homogene Regulation beobachtet werden. Die Western Blots zeigten eine stärkere Expression von DnaK und RecA nach einer H₂O₂ – Behandlung von 0,5 %. KatG wies keine relevanten Expressionsänderungen auf. Im Hitzeschockexperiment wurde eine Regulation von DnaK, RecA und KatG festgestellt. Für aPDT wurden die Photosensibilisatoren TMPyP (0,4 μM und 0,8 μM) und Methylenblau (4 μM und 8 μM) verwendet. TMPyP führte zu keiner signifikanten Regulation von DnaK. Eine erhöhte DnaK-Expression wurde in dieser Untersuchung nach Behandlung mit 4 μM Methylenblau nach 30 und 60 Minuten festgestellt. Andere Studien zeigten einerseits ebenfalls keine DnaK Regulation nach aPDT mit dem PS SAPYR, andererseits eine deutliche dnak - Hochregulation auf Genebene mit verschiedenen Photosensibilisatoren, darunter Toluidinblau (TBO) und Chlorin e6 (Ce6). In der vorliegenden Untersuchung zeigte sich eine 3 - fache Erhöhung von RecA nach 90 Minuten bei niedriger TMPyP-Konzentration (0,4 μM). Auch in der UK - Gruppe sowie bei 8 μM Methylenblau (MB) wurde eine relevante Regulation beobachtet. Die verstärkte RecA-Expression nach antimikrobieller photodynamischer Therapie (aPDT) könnte laut Literatur auf DNA- Schäden hindeuten. Andere Studien zeigten ebenfalls eine verstärkte RecA Expression nach aPDT nach Behandlung mit anderen PS. In den hier durchgeführten Untersuchungen zeigte KatG lediglich eine signifikante Erhöhung nach MB – Behandlung (4 μM) zum Zeitpunkt 0 Minuten. Mit Behandlung von TMPyP wurde in dieser Untersuchung keine Erhöhung festgestellt. In anderen Untersuchungen wurde nach aPDT mit anderen PS (SAPYR und Chl) keine erhöhte Expression von KatG auf Gen – oder Proteinebene festgestellt. Insgesamt zeigten die Ergebnisse, dass die bakterielle Stressantwort auf aPDT gegenwärtig keinem gängigen Schema folgt und somit vermutlich von mehreren Faktoren abhängt. Entscheidend könnten hierbei die Wahl des Photosensibilisators und dessen chemischer Struktur, die applizierte Lichtdosis sowie die Definition der subletalen Dosis sein. Zusätzlich wäre es sinnvoll, neben der Proteinebene auch die Genebene zu untersuchen, um ein umfassenderes Bild der bakteriellen Stressantwort zu erhalten. In dieser Untersuchung wurde die Proteinregulation anhand der Graustufenverteilung quantitativ bestimmt, während viele Studien Western Blots qualitativ auswerten
Inhibition of protein kinase C activity enables mineralization of senescent dental follicle cells with almost no osteogenic differentiation potential
No full textObjective
Dental follicle cell lines with a senescence phenotype have a poor differentiation potential into biomineralizing cells. Previous studies have shown that protein kinase C (PKC) and protein kinase B (AKT) regulate the differentiation of DFCs. This study investigates the extent to which regulation of PKC and AKT can improve the differentiation of dental follicle cells with poor osteogenic potential.
Design
Human senescence dental follicle cells with poor osteogenic differentiation potential were osteogenic differentiated with cell culture media containing dexamethasone or bone morphogenetic protein (BMP) 2 as an inducer. GÖ6976 was used as a PKC inhibitor, and MK-2206 as an AKT inhibitor. The AKT activator SC-79 was also used. Western blot analyses were performed with specific antibodies for the active form of AKT, phosphorylated substrate of PKC and collagen 1. Osteogenic differentiation was quantitatively determined by measuring alkaline phosphatase (ALP) activity and biomineralization using alizarin staining. The gene expression of sclerostin (SOST) and PTHLH was quantitatively determined using real-time RT-PCRs.
Results
The results showed that both the inhibitor MK-2206 inhibits AKT and the activator SC-79 can activate AKT in DFCs. Only inhibition of AKT slightly but significantly enhanced osteogenic differentiation. While inhibition of PKC activity apparently only occurred from day 14 of differentiation using the inhibitor GÖ6976, PKC inhibition promoted osteogenic differentiation and inhibits the expression of SOST and Parathyroid hormone-related protein (PTHLH).
Conclusion
Our results suggest that the addition of GÖ6976 is an efficient method to induce biomineralization in senescent DFCs
The role of LHEP in spontaneous closure of full-thickness macular holes
No full textPurpose
Spontaneous closure of full-thickness macular holes (SCMH) is a rare condition. However, this can sometimes be seen in patients waiting for operation. Here we present our morphologic findings in SCMH and discuss the possible pathogenesis.
Methods
Retrospective analysis. Over the period of 2014 to 2024, 20 eyes of 20 patients showed SCMH. Morphologic characteristics were evaluated by SD-OCT imaging and patients were categorized by the existence of vitreomacular traction (VMT), epiretinal membrane (ERM) and lamellar hole associated epiretinal proliferation (LHEP). A relevant amount of epiretinal material of medium and homogenous reflectivity was labeled as LHEP. The study population consisted of 13 women and 7 men, all between ages of 52 and 85 years.
Conclusions and importance
LHEP was identified in 12 of the 20 eyes (60%) with spontaneous hole closure. In 4 out of 20 eyes (20%) vitreomacular traction was found, 1 eye (5%) showed epiretinal membrane and another 3 (15%) no epiretinal pathologies at all. The frequent presence of LHEP in eyes with SCMH is in line with the recent postulations that LHEP might be the body’s attempt to counter the tangential traction on the retinal tissue around the hole and thus facilitate its closure. This understanding of the LHEP as a reparative process leads to the discussion whether a more conservative approach towards small full-thickness macular holes in association with LHEP may be justified
Zielgerichtete antiangiogenetische Therapie arteriovenöser Malformationen im Zellkulturmodell
No full textMedikamentöse Therapien arteriovenöser Malformationen sind bisher limitiert. Unter der Hypothese eines Krankheitsprogresses von AVM durch mechanische Belastung im Sinne der Blutströmungseigenschaften und interventioneller Manipulationen über einen VEGF-vermittelten Signaltransduktionsweg wurde die Wirksamkeit von Bevacizumab und Thalidomid auf AVM in einem Zellkulturmodell untersucht. Zur Simulation der mechanischen Belastung wurde eine zyklische mechanische Dehnung durchgeführt. Ermittelt wurde der Einfluss auf AVM-Zellproliferation sowie VEGF-Gen- und Proteinexpression und eine in-vitro Angiogenese simuliert durch Tube-Formation-Assays
On the Challenges of Integrating Digital Twins
No full textDigital Twins (DTs) are a key technology for smart ecosystems to provide accurate digital representation of their constituents, e.g., smart buildings, farms, transportation, and citizens, as well as synchronization between the digital and the real subject, and the exploration of what-if scenarios and tradeoff reasoning. To cope with emerging complex socio-technical ecosystems, we need to bring DTs together, which is a challenging endeavor. After giving a historical overview of system adaptation, we review the many enabling technologies that can help with DT integration. Using a smart city as an illuminating example to highlight scenarios that require integration of DTs, we discuss a model-based conceptual framework that identifies DT integration strategies and elaborate on nine key integration challenges that still need to be addressed. We call on the DT community to investigate these challenges