Bethesda University

Abstract Anxiety disorders are accompanied by changes in brain plasticity, stress vulnerability and heightened risk of depression. Here, we found that serum LPA16:0 abundance increased with trait anxiety in both human and mice and was sufficient to reduce the proliferation of adult hippocampal neural stem/progenitor cells. In humans, the main LPA receptor, LPA1, bears single nucleotide polymorphism variants associated with anxiety. In mice, LPA16:0 decreased hippocampal neurogenesis and stress resilience, whereas LPA1antagonism or the reduction of platelets, the main source of circulating LPA16:0, increased adult neurogenesis and resilience to acute stress. Finally, the inhibition of adult neurogenesis abolished the beneficial effect of LPA1antagonism on resilience against both acute and chronic stress.Together, these findings identify LPA16:0-LPA1signaling as a regulation mechanism of adult neurogenesis and a potential therapeutic target for mood disorders.

PurposeThis study aims to compare the outcomes of repair/redo ileal pouch-anal anastomosis (repair/redo-IPAA) with the conversion of IPAA to continent ileostomy (CI) in an effort to prevent the need for a permanent ileostomy (IS) following IPAA failure.MethodsThis research involved a retrospective analysis of surgical records, employing descriptive statistics and Kaplan-Meier survival analysis.ResultsAmong 57 patients with an IPAA, up to three revisions were necessary due to complications or complete failure. Ultimately, repair/redo-IPAA preserved the IPAA in 14 patients (24.6%), conversion to CI salvaged the pouch in 21 patients (36.8%), and IS was unavoidable in 22 patients (38.6%). The cumulative probability of requiring conversion surgery was calculated to be 54.0% at 20 years, thereby reducing the cumulative risk of IS to 32.3%. The 20-year cumulative probability of pouch salvage by repair/redo IPAA was only 21.9%. However, this rate increased to 67.7% when conversion procedures were considered. Following repair/redo-IPAA, only 8.3% of patients reported evacuation frequencies of ≤ 4 during the day, and 16.7% were evacuation-free at night. In contrast, after conversion to CI, 98.0% of patients reported a maximum of four evacuations in a 24-h period. After undergoing repair/redo IPAA, between half and two-thirds of patients reported experiencing incontinence or soiling, while complete continence was achieved in all patients following conversion to CI. Notably, the majority of patients expressed overall satisfaction with their respective procedures. A positive correlation was identified between very high subjective satisfaction and positive objective surgical outcomes exclusively in patients who underwent conversion to CI. ConclusionWhen complications or failure of IPAA occur, conversion to CI emerges as a highly viable alternative to repair/redo IPAA. This conclusion is supported by the observation that patient satisfaction appears to be closely tied to stable surgical outcomes. To reinforce these findings, further prospective studies are warranted.

Der folgende Artikel ist im Jahr 2003 unter dem Titel „Clinical Pragmatism: A Method of Moral Problem Solving“ in dem Sammelband „Pragmatic bioethics“ erschienen, welcher sich mit der Bedeutung der pragmatistischen Philosophie fur die Praxis befasst. In dem vom Internisten und Bioethiker Joseph J. Fins (New York Presbyterian Hospital und Weill Cornell Medical College in New York, USA), dem Thoraxchirurgen Matthew D. Bacchetta (Medical Center der Vanderbilt University in Nashville, USA) und dem Philosophen und Medizinethiker Franklin G. Miller (Department of Bioethics des National Institutes of Health in Bethesda, USA) verfassten Beitrag wird der pragmatistische Ansatz in der klinischen Ethik anhand eines Fallbeispiels gleichzeitig beschrieben, begrundet und demonstriert. Obgleich die Denkrichtung der pragmatistischen Philosophie sowohl wissenschaftstheoretisch wie praktisch hoch bedeutsam ist – ohne diese ist weder die heutige sozialwissenschaftliche Forschung noch die angewandte, insbesondere die klinische Ethik denkbar –, werden pragmatistische Ansatze im deutschsprachigen Raum bis heute eher rudimentar rezipiert.

Space environment and related matters as they apply to spacecraft hardware design will be discussed in this chapter.

Anisotropic gold nanostructures with unique plasmonic properties, specifically the strong absorption of light in the near-infrared region (650-900 nm) due to the excitation of plasmon oscillations, have been widely employed as photothermal conversion agents (PTCAs) for cancer photothermal therapy (PTT). However, the reported PTCAs show suboptimal photothermal conversion efficiency (η), even gold nanocages (η = 63%), which limits their biomedical applications. Herein, we fabricated gold bellflowers (GBFs) with an ultrahigh photothermal conversion efficiency (η = 74%) via a novel liquid/liquid/gas triphasic interface system, using chloroauric acid as a gold source, and o-phenetidine as a reducing agent. The well-defined GBFs with multiple-branched petals show adjustable localized surface plasmon resonance (LSPR) from 760 to 1100 nm by tuning the petal length and circular bottom diameter. Originating from the monophasic and biphasic systems used in the creation of gold nanourchins (GNUs) and gold microspheres (GMPs) respectively, the triphasic interface system successfully produced GBFs. The possible formation mechanisms of GNUs, GMPs, and GBFs in the different systems were also investigated and discussed. We found that the formation mechanism of GNUs and GBFs followed classical crystallization, while the formation of GMPs followed non-classical crystallization.

A new type of photothermally responsive nanoprobe based on Edman degradation has been synthesized and characterized. Under irradiation by an 808 nm laser, the heat generated by the gold nanorod core breaks the thiocarbamide structure and releases the fluorescent dye Cy5.5 with increased near-infrared (NIR) fluorescence under mild acidic conditions. This RGD modified nanoprobe is capable of fluorescence imaging of ανβ3 over-expressing U87MG cells in vitro and in vivo. This Edman degradation-based nanoprobe provides a novel strategy to design activatable probes for biomedical imaging and drug/gene delivery.

Photoacoustic tomography (PAT) can offer structural, functional and molecular contrasts at scalable observation level. By ultrasonically overcoming the strong optical scattering, this imaging technology can reach centimeters penetration depth while retaining high spatial resolution in biological tissue. Recent extensive research has been focused on developing new contrast agents to improve the imaging sensitivity, specificity and efficiency. These emerging materials have substantially accelerated PAT applications in signal sensing, functional imaging, biomarker labeling and therapy monitoring etc. Here, the potentials of different optical probes as PAT contrast agents were elucidated. We first describe the instrumental embodiments and the measured functional parameters, then focus on emerging contrast agent-based PAT applications, and finally discuss the challenges and prospects.