Die Rolle Kalzium-abhängiger Kaliumkanäle bei UUO-induzierter Nierenfibrose

Das terminale Nierenversagen mit der Nierenfibrose als pathologischem Korrelat zwingt in Deutschland jährlich zahlreiche Menschen zu einer lebenseinschränkenden Therapie und geht einher mit einer erhöhten Mortalität. In der vorliegenden Arbeit konnte anhand einer in vivo-Studie gezeigt werden, dass Kalzium-abhängige Kaliumkanäle, im Speziellen KCa3.1, die Krankheitsprogression beeinflussen. Eine pharmakologische Blockade des Kanals könnte ein wichtiger Ansatzpunkt für die Zukunft sein

Design of a randomized superiority trial of a brief couple treatment for PTSD.

Interpersonal difficulties are common among veterans with posttraumatic stress disorder (PTSD) and are associated with poorer treatment response. Treatment outcomes for PTSD, including relationship functioning, improve when partners are included and engaged in the therapy process. Cognitive-behavioral conjoint therapy for PTSD (CBCT) is a manualized 15-session intervention designed for couples in which one partner has PTSD. CBCT was developed specifically to treat PTSD, engage a partner in treatment, and improve interpersonal functioning. However, recent research suggests that an abbreviated CBCT protocol may lead to sufficient gains in PTSD and relationship functioning, and yield lower dropout rates. Likewise, many veterans report a preference for receiving psychological treatments through clinical videoteleconferencing (CVT) rather than traditional face-to-face modalities that require travel to VA clinics. This manuscript describes the development and implementation of a novel randomized controlled trial (RCT) that examines the efficacy of an abbreviated 8-session version of CBCT ("brief CBCT," or B-CBCT), and compares the efficacy of this intervention delivered via CVT to traditional in-person platforms. Veterans and their partners were randomized to receive B-CBCT in a traditional Veterans Affairs office-based setting (B-CBCT-Office), CBCT through CVT with the veteran and partner at home (B-CBCT-Home), or an in office-delivered, couple-based psychoeducation control condition (PTSD Family Education). This study is the first RCT designed to investigate the delivery of B-CBCT specifically to veterans with PTSD and their partners, as well as to examine the delivery of B-CBCT over a CVT modality; findings could increase access to care to veterans with PTSD and their partners

Enhancement of the Functional Properties of Mead Aged with Oak (Quercus) Chips at Different Toasting Levels

Consumers increasingly prefer and seek functional beverages, which, given their characteristics, provide important bioactive compounds that help prevent and treat chronic diseases. Mead is a traditional fermented alcoholic beverage made from honey solution. The aging process of mead with oak chips is innovative and bestows functional characteristics to this beverage. Thus, in this study, we sought to develop and characterize a novel functional beverage by combining the health benefits of honey with the traditional aging process of alcoholic beverages in wood. Phenolic compounds, flavonoids, and antioxidant capacity were analyzed in mead using oak chips at different toasting levels and aged for 360 days. LC-ESI-QTOF-MS/MS was used to analyze the chemical profile of different meads. Over time, the aging process with oak chips showed a higher total phenolic and flavonoid content and antioxidant capacity. Eighteen compounds belonging to the classes of organic acids, phenolic acids, flavonoids, and tannins were identified in meads after 360 days. Our findings revealed that the addition of oak chips during aging contributed to p-coumaric, ellagic, abscisic, and chlorogenic acids, and naringenin, vanillin, and tiliroside significantly impacted the functional quality of mead

Total exhumation across the Beichuan fault in the Longmen Shan (eastern Tibetan plateau, China): Constraints from petrology and thermobarometry

The deep structure and deformation mechanisms of the Longmen Shan thrust belt (Sichuan, China), at the eastern border of the Tibetan plateau, were largely debated after the devastating Mw 7.9 Wenchuan earthquake (2008). Recent geophysical studies and field investigations have been focused on the active motion of the major Beichuan fault, which ruptured during the earthquake. However, the total exhumation across the fault still remains unclear. In the hanging wall of the Beichuan fault, the South China block is exhumed in the Pengguan massif. Close to the Beichuan fault, the rocks of the Pengguan massif underwent greenschist facies metamorphism associated with brittle-ductile deformation. No metamorphism is observed in the footwall of the fault. In this study, we characterize and date the metamorphic history recorded in the hanging wall of the Beichuan fault in order to constrain the depth and timing of exhumation of the rocks of the Pengguan massif along the fault. A high-resolution petrological approach involving chemical analyses and X-ray maps was used to analyze the micrometric metamorphic minerals. The P-T conditions of the greenschist facies metamorphic event were estimated by an inverse multi-equilibrium thermodynamic approach. The results, 280 ± 30 °C and 7 ± 1 kbar, suggest that the rocks of the Pengguan massif were exhumed from ca. 20 km depth. Our results underline the importance of the thrusting component in the long-term behavior of the Beichuan fault and provide a minimal depth at which the fault is rooted. In situ laser ablation 40Ar/39Ar dating of metamorphic white mica revealed that the greenschist overprint occurred at 135–140 Ma. The Pengguan massif was therefore partially thrusted along the Beichuan fault during the Lower Cretaceous, long before the Eocene-Miocene exhumation phase which is well-constrained by low-temperature thermochronology. Our results provide the first independent depth information for the exhumation history of the Pengguan massif and reveal a previously undocumented Lower Cretaceous tectonic event that marks the onset of the thick-skinned deformation in the external domain of the Longmen Shan (East of the Wenchuan Fault)

The incorporation of emotion-regulation skills into couple- and family-based treatments for post-traumatic stress disorder

Abstract Post-traumatic stress disorder (PTSD) is a disabling, potentially chronic disorder that is characterized by re-experience and hyperarousal symptoms as well as the avoidance of trauma-related stimuli. The distress experienced by many veterans of the Vietnam War and their partners prompted a strong interest in developing conjoint interventions that could both alleviate the core symptoms of PTSD and strengthen family bonds. We review the evolution of and evidence base for conjoint PTSD treatments from the Vietnam era through the post-911 era. Our review is particularly focused on the use of treatment strategies that are designed to address the emotions that are generated by the core symptoms of the disorder to reduce their adverse impact on veterans, their partners and the relationship. We present a rationale and evidence to support the direct incorporation of emotion-regulation skills training into conjoint interventions for PTSD. We begin by reviewing emerging evidence suggesting that high levels of emotion dysregulation are characteristic of and predict the severity of both PTSD symptoms and the level of interpersonal/marital difficulties reported by veterans with PTSD and their family members. In doing so, we present a compelling rationale for the inclusion of formal skills training in emotional regulation in couple−/family-based PTSD treatments. We further argue that increased exposure to trauma-related memories and emotions in treatments based on learning theory requires veterans and their partners to learn to manage the uncomfortable emotions that they previously avoided. Conjoint treatments that were developed in the last 30 years all acknowledge the importance of emotions in PTSD but vary widely in their relative emphasis on helping participants to acquire strategies to modulate them compared to other therapeutic tasks such as learning about the disorder or disclosing the trauma to a loved one. We conclude our review by describing two recent innovative treatments for PTSD that incorporate a special emphasis on emotion-regulation skills training in the dyadic context: structured approach therapy (SAT) and multi-family group for military couples (MFG-MC). Although the incorporation of emotion-regulation skills into conjoint PTSD therapies appears promising, replication and comparison to cognitive-behavioral approaches is needed to refine our understanding of which symptoms and veterans might be more responsive to one approach versus others

Renal fibrosis is attenuated by targeted disruption of K(Ca)3.1 potassium channels

Proliferation of interstitial fibroblasts is a hallmark of progressive renal fibrosis commonly resulting in chronic kidney failure. The intermediate-conductance Ca2+-activated K+ channel (K(Ca)3.1) has been proposed to promote mitogenesis in several cell types and contribute to disease states characterized by excessive proliferation. Here, we hypothesized that K(Ca)3.1 activity is pivotal for renal fibroblast proliferation and that deficiency or pharmacological blockade of K(Ca)3.1 suppresses development of renal fibrosis. We found that mitogenic stimulation up-regulated K(Ca)3.1 in murine renal fibroblasts via a MEK-dependent mechanism and that selective blockade of K(Ca)3.1 functions potently inhibited fibroblast proliferation by G(0)/G(1) arrest. Renal fibrosis induced by unilateral ureteral obstruction (UUO) in mice was paralleled by a robust up-regulation of K(Ca)3.1 in affected kidneys. Mice lacking K(Ca)3.1 (K(Ca)3.1(-/-)) showed a significant reduction in fibrotic marker expression, chronic tubulointerstitial damage, collagen deposition and alpha SMA(+) cells in kidneys after UUO, whereas functional renal parenchyma was better preserved. Pharmacological treatment with the selective K(Ca)3.1 blocker TRAM-34 similarly attenuated progression of UUO-induced renal fibrosis in wild-type mice and rats. In conclusion, our data demonstrate that K(Ca)3.1 is involved in renal fibroblast proliferation and fibrogenesis and suggest that K(Ca)3.1 may represent a therapeutic target for the treatment of fibrotic kidney disease

Askival: An altered feldspathic cumulate sample in Gale crater

Askival is a light‐toned, coarsely crystalline float rock, which was identified near the base of Vera Rubin Ridge in Gale crater. We have studied Askival, principally with the ChemCam instrument but also using APXS compositional data and MAHLI images. Askival and an earlier identified sample, Bindi, represent two rare examples of feldspathic cumulate float rocks in Gale crater with >65% relict plagioclase. Bindi appears unaltered whereas Askival shows textural and compositional signatures of silicification, along with alkali remobilization and hydration. Askival likely experienced multiple stages of alteration, occurring first through acidic hydrolysis of metal cations, followed by deposition of silica and possible phyllosilicates at low T and neutral‐alkaline pH. Through laser‐induced breakdown spectroscopy compositional analyses and normative calculations, we suggest that an assemblage of Fe‐Mg silicates including amphibole and pyroxene, Fe phases, and possibly Mg‐rich phyllosilicate are present. Thermodynamic modeling of the more pristine Bindi composition predicts that amphibole and feldspar are stable within an upper crustal setting. This is consistent with the presence of amphibole in the parent igneous rocks of Askival and suggests that the paucity of amphiboles in other known Martian samples reflects the lack of representative samples of the Martian crust rather than their absence on Mars

Malnutrition Is Highly Prevalent in Patients With Chronic Pancreatitis and Characterized by Loss of Skeletal Muscle Mass but Absence of Impaired Physical Function

Background/Aims Patients with chronic pancreatitis (CP) have an increased risk of malnutrition, a condition linked to reduced muscle mass and physical performance. We have investigated the risk factors, phenotypic presentation, and health implications associated with malnutrition in CP. Materials and Methods In a multicenter cross-sectional study we recruited patients with confirmed CP and healthy volunteers as a control group. Malnutrition was diagnosed according to the criteria proposed by the Global Leadership Initiative on Malnutrition. We performed detailed examinations of body composition and physical function as well as testing of routine blood parameters and markers of inflammation. Results We included 66 patients [mean (±SD) age: 56.0 (±14.5) years; 51 males] and an equal number of age- and sex-matched controls. Moderate malnutrition was diagnosed in 21% (n = 14) and severe malnutrition in 42% (n = 28) of patients. Besides weight loss malnourished patients showed lower fat and skeletal muscle mass compared to both non-malnourished subjects and healthy controls. Only in severe malnutrition, blood parameters reflected elevated inflammation and reduced muscle reserves. Handgrip strength in patients did not differ by nutritional status but there was a significant correlation (rho = 0.705, p < 0.001) with skeletal muscle mass. Although 20 patients (30%) had pathologically reduced skeletal muscle mass, only two individuals (3%) had sarcopenia with concomitantly reduced handgrip strength. Conclusion Malnutrition is a frequent complication of CP characterized by loss of skeletal muscle mass. As this condition becomes evident only at an advanced stage, regular testing for altered body composition is recommended. Suitable biomarkers and the link between loss of muscle mass and physical function require further investigation. Clinical Trial Registration [https://clinicaltrials.gov/ct2/show/NCT04474743], identifier [NCT04474743]