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Sedentarism is a risk factor for depression and anxiety. People living with the human immunodeficiency virus (PLWH) have a higher prevalence of anxiety and depression compared to HIV-negative individuals. This cross-sectional study (n = 450, median age 44 (19-75), 7.3% females) evaluates the prevalence rates and prevalence ratio (PR) of anxiety and/or depression in PLWH associated with recreational exercise. A decreased likelihood of having anxiety (PR=0.57; 0.36-0.91; p = 0.01), depression (PR=0.41; 0.36-0.94; p=0.01), and comorbid anxiety and depression (PR = 0,43; 0.24-0.75; p=0.002) was found in exercising compared to non-exercising PLWH. Recreational exercise is associated with a lower risk for anxiety and/or depression. Further prospective studies are needed to provide insights on the direction of this association.
The PNPLA3 reference single-nucleotide polymorphism rs738409 has been identified as a predisposing factor for nonalcoholic fatty liver disease. A simple method based on PCR and restriction fragment length polymorphism (RFLP) analysis had been published to detect the nonpathogenic allele PNPLA3 rs738409 variant. The presence of the pathogenic variant was deduced by the indigestibility of the corresponding PCR product with BtsCI recognizing the nonpathogenic allele. However, one cannot exclude that an enzymatic reaction does not occur for other, more trivial, reasons. For safe and secure detection of the pathogenic PNPLA3 rs738409, we have further developed the PCR-restriction fragment length polymorphism method by adding a second restriction enzyme digest, clearly identifying the correct PNPLA3 alleles and in particular the pathogenic variant. <br /> METHOD SUMMARY <br /> The method presented here represents an improved genetic diagnosis of the PNPLA3 rs738409 alleles based on conventional and inexpensive molecular biological methods. We used methodology based on PCR and restriction fragment length polymorphisms and clearly identified both described alleles by the use of two restriction enzymes. Digestion of individuals' specific PNPLA3 PCR fragments with both enzymes in independent reactions clearly showed the PNPLA3 rs738409 genotype.
Angesichts der Alterung der Gesellschaft und der hohen Kosten für die Unterstützung und Pflege in privaten Haushalten stellt sich die Frage, welche Rolle assistive Roboter spielen können. Dieser Beitrag richtet sich auf die Frage, inwieweit Roboter in der Pflege heute von der erwachsenen Bevölkerung in Deutschland akzeptiert werden. Und inwieweit beeinflussen Geschlecht, Alter und Erfahrung (beruflich, persönlich) das Ausmaß dieser Akzeptanz? Die durchgeführten Auswertungen beruhen auf drei repräsentativen Erhebungen mit insgesamt über 7000 Befragten. Zwei Erhebungen fanden in der 2. Jahreshälfte 2017 im Auftrag der Deutschen Akademie der Technikwissenschaften (acatech) und des Lebensversicherers ERGO statt, die dritte Erhebung im Auftrag des Sachverständigenrats für Verbraucherfragen (SVRV) im Frühjahr 2018. Eine vertiefte und kumulative Auswertung dieser Erhebungen und Datensätze, die von den Autoren mitkonzipiert wurden, im Hinblick auf assistive Robotik ist bislang noch nicht veröffentlicht. Trotz unterschiedlicher erfragter Einsatzszenarien für Roboter in der Pflege stimmen die Ergebnisse aller 3 Erhebungen erstaunlich überein: In Deutschland gibt es eine signifikante Minderheit von Menschen, die bereits jetzt eine funktionierende Betreuung von Robotern akzeptieren würden – sofern dadurch menschliche Pflege nicht ersetzt, sondern nur unterstützt würde. Ein gutes Drittel, das nach Alter und Geschlecht differenziert ist, lehnt die Assistenz durch Roboter grundsätzlich ab.
Jenseits der Klinik
(2021)
Unser Beitrag stellt ein interaktives Ethik-Konzept vor, das in Zusammenarbeit der BruderhausDiakonie Reutlingen und der Universität Tübingen entwickelt wurde, um den Eigenheiten und Bedarfen einer komplexen Organisationsstruktur gerecht zu werden, die mehrere Geschäftsfelder und Standorte unter sich vereint. Wir skizzieren die Grundzüge des interaktiven Nijmegener Modells, in dem die Kooperation eines auf Leitungsebene angesiedelten Komitees und situationsbezogener Fallbesprechungen ein fruchtbares Zusammenspiel zweier unverzichtbarer Reflexionsweisen bewirken soll („Top-Down“/„Bottom-Up“). Wir zeigen auf, welche Herausforderungen sich bei der Implementierung dieses Modells in die konkrete Aufbauorganisation der BruderhausDiakonie ergaben, und mit welchen konzeptionellen oder „implementationstechnischen“ Mitteln ihnen begegnet wurde. Im Zentrum steht dabei die Erweiterung des Nijmegener Modells um ein Verbindungselement, welches die Zusammenarbeit zwischen zentralem Ausschuss und dezentralen Fallbesprechungen koordiniert und das interaktive Moment des Modells erst ermöglicht.
Background and Study
Aims Recurrent laryngeal nerve palsy (RLNP) is a potential complication of anterior discectomy and fusion (ACDF). There still is substantial disagreement on the actual prevalence of RLNP after ACDF as well as on risk factors for postoperative RLNP. The aim of this study was to describe the prevalence of postoperative RLNP in a cohort of consecutive cases of ACDF and to examine potential risk factors.
Materials and Methods
This retrospective study included patients who underwent ACDF between 2005 and 2019 at a single neurosurgical center. As part of clinical routine, RLNP was examined prior to and after surgery by independent otorhinolaryngologists using endoscopic laryngoscopy. As potential risk factors for postoperative RLNP, we examined patient's age, sex, body mass index, multilevel surgery, and the duration of surgery.
Results
214 consecutive cases were included. The prevalence of preoperative RLNP was 1.4% (3/214) and the prevalence of postoperative RLNP was 9% (19/211). The number of operated levels was 1 in 73.5% (155/211), 2 in 24.2% (51/211), and 3 or more in 2.4% (5/211) of cases. Of all cases, 4.7% (10/211) were repeat surgeries. There was no difference in the prevalence of RLNP between the primary surgery group (9.0%, 18/183) versus the repeat surgery group (10.0%, 1/10;p = 0.91). Also, there was no difference in any characteristics between subjects with postoperative RLNP compared with those without postoperative RLNP. We found no association between postoperative RLNP and patient's age, sex, body mass index, duration of surgery, or number of levels (odds ratios between 0.24 and 1.05; p values between 0.20 and 0.97).
Conclusions
In our cohort, the prevalence of postoperative RLNP after ACDF was 9.0%. The fact that none of the examined variables was associated with the occurrence of RLNP supports the view that postoperative RLNP may depend more on direct mechanical manipulation during surgery than on specific patient or surgical characteristics.
Background
Anticancer compound 3-bromopyruvate (3-BrPA) suppresses cancer cell growth via targeting glycolytic and mitochondrial metabolism. The malignant peripheral nerve sheath tumor (MPNST), a very aggressive, therapy resistant, and Neurofibromatosis type 1 associated neoplasia, shows a high metabolic activity and affected patients may therefore benefit from 3-BrPA treatment. To elucidate the specific mode of action, we used a controlled cell model overexpressing proteasome activator (PA) 28, subsequently leading to p53 inactivation and oncogenic transformation and therefore reproducing an important pathway in MPNST and overall tumor pathogenesis.
Methods
Viability of MPNST cell lines S462, NSF1, and T265 in response to increasing doses (0-120 mu M) of 3-BrPA was analyzed by CellTiter-Blue (R) assay. Additionally, we investigated viability, reactive oxygen species (ROS) production (dihydroethidium assay), nicotinamide adenine dinucleotide dehydrogenase activity (NADH-TR assay) and lactate production (lactate assay) in mouse B8 fibroblasts overexpressing PA28 in response to 3-BrPA application. For all experiments normal and nutrient deficient conditions were tested. MPNST cell lines were furthermore characterized immunohistochemically for Ki67, p53, bcl2, bcl6, cyclin D1, and p21.
Results
MPNST significantly responded dose dependent to 3-BrPA application, whereby S462 cells were most responsive. Human control cells showed a reduced sensitivity. In PA28 overexpressing cancer cell model 3-BrPA application harmed mitochondrial NADH dehydrogenase activity mildly and significantly failed to inhibit lactate production. PA28 overexpression was associated with a functional glycolysis as well as a partial resistance to stress provoked by nutrient deprivation. 3-BrPA treatment was not associated with an increase of ROS. Starvation sensitized MPNST to treatment.
Conclusions
Aggressive MPNST cells are sensitive to 3-BrPA therapy in-vitro with and without starvation. In a PA28 overexpression cancer cell model leading to p53 inactivation, thereby reflecting a key molecular feature in human NF1 associated MPNST, known functions of 3-BrPA to block mitochondrial activity and glycolysis were reproduced, however oncogenic cells displayed a partial resistance. To conclude, 3-BrPA was sufficient to reduce NF1 associated MPNST viability potentially due inhibition of glycolysis which should lead to the initiation of further studies and promises a potential benefit for NF1 patients.
Background
Generalized weakness and fatigue are underexplored symptoms in emergency medicine. Triage tools often underestimate patients presenting to the emergency department (ED) with these nonspecific symptoms (Nemec et al., 2010). At the same time, physicians' disease severity rating (DSR) on a scale from 0 (not sick at all) to 10 (extremely sick) predicts key outcomes in ED patients (Beglinger et al., 2015; Rohacek et al., 2015). Our goals were (1) to characterize ED patients with weakness and/or fatigue (W|F); to explore (2) to what extent physicians' DSR at triage can predict five key outcomes in ED patients with W|F; (3) how well DSR performs relative to two commonly used benchmark methods, the Emergency Severity Index (ESI) and the Charlson Comorbidity Index (CCI); (4) to what extent DSR provides predictive information beyond ESI, CCI, or their linear combination, i.e., whether ESI and CCI should be used alone or in combination with DSR; and (5) to what extent ESI, CCI, or their linear combination provide predictive information beyond DSR alone, i.e., whether DSR should be used alone or in combination with ESI and / or CCI.
Methods
Prospective observational study between 2013-2015 (analysis in 2018-2020, study team blinded to hypothesis) conducted at a single center. We study an all-comer cohort of 3,960 patients (48% female patients, median age = 51 years, 94% completed 1-year follow-up). We looked at two primary outcomes (acute morbidity (Bingisser et al., 2017; Weigel et al., 2017) and all-cause 1- year mortality) and three secondary outcomes (in-hospital mortality, hospitalization and transfer to ICU). We assessed the predictive power (i.e., resolution, measured as the Area under the ROC Curve, AUC) of the scores and, using logistic regression, their linear combinations.
Findings
Compared to patients without W|F (n = 3,227), patients with W|F (n = 733) showed higher prevalences for all five outcomes, reported more symptoms across both genders, and received higher DSRs (median = 4; interquartile range (IQR) = 3-6 vs. median = 3; IQR = 2-5). DSR predicted all five outcomes well above chance (i.e., AUCs > similar to 0.70), similarly well for both patients with and without W|F, and as good as or better than ESI and CCI in patients with and without W|F (except for 1-year mortality where CCI performs better). For acute morbidity, hospitalization, and transfer to ICU there is clear evidence that adding DSR to ESI and/or CCI improves predictions for both patient groups; for 1-year mortality and in-hospital mortality this holds for most, but not all comparisons. Adding ESI and/or CCI to DSR generally did not improve performance or even decreased it.
Conclusions
The use of physicians' disease severity rating has never been investigated in patients with generalized weakness and fatigue. We show that physicians' prediction of acute morbidity, mortality, hospitalization, and transfer to ICU through their DSR is also accurate in these patients. Across all patients, DSR is less predictive of acute morbidity for female than male patients, however. Future research should investigate how emergency physicians judge their patients' clinical state at triage and how this can be improved and used in simple decision aids.
Secretory Wnt trafficking can be studied in the polarized epithelial monolayer of Drosophila wing imaginal discs (WID). In this tissue, Wg (Drosophila Wnt-I) is presented on the apical surface of its source cells before being internalized into the endosomal pathway. Long-range Wg secretion and spread depend on secondary secretion from endosomal compartments, but the exact post-endocytic fate of Wg is poorly understood. Here, we summarize and present three protocols for the immunofluorescencebased visualization and quantitation of different pools of intracellular and extracellular Wg in WID: (1) steady-state extracellular Wg; (2) dynamic Wg trafficking inside endosomal compartments; and (3) dynamic Wg release to the cell surface. Using a genetic driver system for gene manipulation specifically at the posterior part of the WID (EnGal4) provides a robust internal control that allows for direct comparison of signal intensities of control and manipulated compartments of the same WID. Therefore, it also circumvents the high degree of staining variability usually associated with whole-tissue samples. In combination with the genetic manipulation of Wg pathway components that is easily feasible in Drosophila, these methods provide a tool-set for the dissection of secretory Wg trafficking and can help us to understand how Wnt proteins travel along endosomal compartments for short-and long-range signal secretion.