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Objective To define the current proportion of underrepresented minority (URM) academic urologists in leadership positions. Methods A cross-sectional observational study of leadership positions in active United States Urology Residency Programs in 2020 was conducted. Academic urologists in leadership positions were electronically mailed a survey asking about personal and professional demographics. Self-reported variables including administrative position, race, and ethnicity were collected and analyzed. Results Over the study period, 133 urologists completed the survey out of a possible 320 academic urologists for a response rate of 41.6%. Overall, African-Americans represented 9.0%, Hispanics represented 3.8%, and American Indians/Alaska Natives made up 0.8% of leadership roles in the study sample. African-Americans comprised 8.5% (4 of 47) and Hispanics comprised 2.1% (1 of 47) of department chairs. African-Americans made up 7.4% (4 of 54) and Hispanics made up 1.9% (1 of 54) of program directors. The highest proportion of African-Americans in leadership positions was seen in oncology (18.2%), minimally invasive surgery (18.2%), and general urology (10%). The only subspecialties with Hispanics in leadership positions were in andrology/sexual medicine (16.7%) and female urology (15.4%). There were no reported URMs in leadership positions in endourology, neurourology, pediatrics, and reconstructive urology. Conclusions To our knowledge, this study is the first to quantify the representation of URM urologists in academic leadership. There are multiple subspecialties without URMs in leadership positions. This information is vital to understanding the presence and lack of racial representation of the leadership of our field.

Zusammenfassung Hintergrund Die roboterassistierte Prostataadenomenukleation (RAPAE) ist ein minimal-invasives Verfahren zur operativen Behandlung der Prostatahyperplasie mit Volumina >80 cm3. An der vorliegenden Analyse wurde retrospektiv die postoperative (postop.) Morbidität der RAPAE gegenüber der offenen Prostataadenomenukleation (PAE) anhand der Clavien-Dindo-Klassifikation sowie hämatologischer Parameter untersucht. Patienten und Methoden In die retrospektive Analyse wurden 78 Patienten multizentrisch eingeschlossen, wovon jeweils die Hälfte eine RAPAE und eine PAE erhielten. Folgende Parameter wurden zwischen beiden Gruppen untersucht: Alter, PSA-Wert, Prostatavolumen, ASA-Score, Krankenhausaufenthaltsdauer, Operationsdauer, Hb-Wert Abfall am 1. Tag und innerhalb der ersten 5 postop. Tage, CRP-Peak innerhalb der ersten 5 postop. Tage und die Transfusionsrate. Ergebnisse Im Vergleich der RAPAE zur PAE zeigten sich keine Unterschiede im Alter, PSA-Wert, ASA-Score und Volumina. Die RAPAE-Gruppe hatte eine erhöhte Operationsdauer (178 vs. 110 min.; p =p =p =p =0,01) und Blutkonservenmenge pro Patient (0,1 vs. 1,3; p =0,01), einen niedrigeren Clavien-Dindo Score (0,44 vs. 1,23; p =0,003) und niedrigere CRP-Werte (52 vs. 104 mg/l; p =p = Schlussfolgerung Aufgrund der minimal-invasiven Operationstechnik ist die RAPAE ein sicheres Verfahren mit weniger Blutverlust, Transfusionsrate und geringeren Komplikationen im Vergleich zur PAE. Im PAE-Kollektiv traten häufiger Komplikationen aufgrund von Blutungen auf. Dies hatte eine verlängerte Liegezeit und einen deutlich erhöhten Transfusionsbedarf zur Folge.

Brief Abstract Scrotal lymphangioma circumscriptum (LC) is an uncommon, benign skin disorder with multiple treatment modalities. We present staged treatment of extensive LC of the scrotum using staged carbon dioxide (CO2) laser ablation. We achieved near complete resolution of lesions with excellent cosmesis in the span of four months, from presentation to treatment. Therefore, the use of staged CO2 laser ablation should be strongly considered when LC presents in the genitourinary (GU) system, as it can lead to good cosmetic outcomes and prompt symptomatic relief in a short period of time.

We report about the rare occurrence of symptomatic testicular metastasis of an acinar adenocarcinoma of the prostate. Testicular metastases are usually incidentally detected in patients treated with bilateral orchiectomy or more often during autopsy. In the literature, there are only a few clinical cases describing symptomatic testicular metastases. However, the possibility of such metastases should be considered in patients diagnosed with advanced prostate cancer. Testicular examination should be performed regularly, even in patients with low prostate-specific antigen levels.Wir berichten über den äußerst seltenen Fall einer symptomatischen testikulären Metastasierung durch ein azinäres Adenokarzinom der Prostata. Bislang wurden Hodenmetastasen von Prostatakarzinomen (PCa) meist nur zufällig im Rahmen von therapeutischen Orchiektomien oder Autopsien entdeckt. Insgesamt wurden in der Literatur nur wenige klinische und v. a. symptomatische Fälle beschrieben. Trotz des raren Auftretens von Hodenmetastasen sollte bei fortgeschrittenen PCa differentialdiagnostisch an die Möglichkeit einer solchen Metastasierung gedacht werden.

The prostatic urethral lift procedure is a minimally invasive treatment option for lower urinary tract symptoms due to benign prostatic hyperplasia, with reported benefit of less adverse effects than traditional treatments. While complications are usually minimal, our patient developed a large pelvic hematoma and the first case of organ failure after prostatic urethral lift. He required temporary dialysis during his extended postoperative admission, and his chronic kidney disease permanently progressed from stage III to stage IV. This case highlights the need for research into the safest preoperative and operative approach for prostatic urethral lift procedures in patients with comorbidities.

The kinase mTOR complex 1 (mTORC1) promotes cellular growth and is frequently dysregulated in cancers. In response to nutrients, mTORC1 is activated on lysosomes by Rag and Rheb guanosine triphosphatases (GTPases) and drives biosynthetic processes. How limitations in nutrients suppress mTORC1 activity remains poorly understood. We find that when amino acids are limited, the Rap1-GTPases confine lysosomes to the perinuclear region and reduce lysosome abundance, which suppresses mTORC1 signaling. Rap1 activation, which is independent of known amino acid signaling factors, limits the lysosomal surface available for mTORC1 activation. Conversely, Rap1 depletion expands the lysosome population, which markedly increases association between mTORC1 and its lysosome-borne activators, leading to mTORC1 hyperactivity. Taken together, we establish Rap1 as a critical coordinator of the lysosomal system, and propose that aberrant changes in lysosomal surface availability can impact mTORC1 signaling output., mTORC1 regulates cellular growth from the lysosome, but how changes in the organisation of the lysosomal system affect mTORC1 signalling is poorly understood. Here the authors show that amino acid-dependent Rap1-mediated changes in lysosomal abundance determine overall signalling output of mTORC1.

Robot-assisted simple prostatectomy (RASP) is a relatively new minimally invasive procedure for surgical treatment to manage symptomatic, therapy-refractory benign prostate hyperplasia (BPH) in prostate volumes80 cmWe retrospectively reviewed a total of 78 patients: 39 patients underwent RAPS and 39 OSP. The following parameters were statistically evaluated and compared: age, PSA value, prostate volume, ASA score, duration of hospital stay, operative time, Hb decrease on postoperative (po) day 1 and in the 5 five po days, CRP peak in the first 5 po days and transfusion rate.The comparison between RASP and standard OSP showed no significant differences regarding the mean patient age (73 vs. 74 years; p =0.54), PSA values (7.7 vs. 10.7 ng/ml; p =0.17), ASA score (2.2 vs. 2.3; p =0.26) and prostate volume (130 vs. 113 cmRASP is a safe procedure that offers the advantage of reduced blood loss and blood bag consumption and rare complications due to the minimally invasive surgical method. The OSP group showed an increased occurrence of complications due to bleeding, leading to prolonged hospitalization and significantly increased need for blood transfusion. The lesser increase of CRP in RASP group is a result of the lower invasiveness of the robot-assisted procedure.

For cancer cells to survive during extracellular matrix (ECM) detachment, they must inhibit anoikis and rectify metabolic deficiencies that cause non-apoptotic cell death. Previous studies in ECM-detached cells have linked non-apoptotic cell death to reactive oxygen species (ROS) generation, although the mechanistic underpinnings of this link remain poorly defined. Here, we uncover a role for receptor-interacting protein kinase 1 (RIPK1) in the modulation of ROS and cell viability during ECM detachment. We find that RIPK1 activation during ECM detachment results in mitophagy induction through a mechanism dependent on the mitochondrial phosphatase PGAM5. As a consequence of mitophagy, ECM-detached cells experience diminished NADPH production in the mitochondria, and the subsequent elevation in ROS levels leads to non-apoptotic death. Furthermore, we find that antagonizing RIPK1/PGAM5 enhances tumour formation in vivo. Thus, RIPK1-mediated induction of mitophagy may be an efficacious target for therapeutics aimed at eliminating ECM-detached cancer cells.

Trauma is the leading cause of death in pediatric patients over 1 y of age. Controversy exists regarding prehospital airway management for these patients, with some studies suggesting that endotracheal intubation in the field or at a referring hospital is associated with increased mortality and complication rate. These studies were largely performed at urban centers, and it is unclear whether the results apply to suburban/rural networks with longer transport times and more stops at referring hospitals. The purpose of this study is to evaluate differential outcomes in pediatric trauma patients who underwent endotracheal intubation at the scene of injury, referring hospital, or pediatric trauma center in a predominantly rural/suburban setting.A retrospective review was performed evaluating trauma patients age 18 y or younger at a single institution over 10 y (2004-2014). Patients were selected who underwent endotracheal intubation and were classified based on location of intubation (scene, referring hospital, or trauma center). Fischer's exact test and t-tests were performed for comparison. Univariate and multivariate regression analyses were performed.288 patients were identified. 155 (53.8%) were intubated at the scene of injury, 55 (19.1%) at a referring hospital, and 72 (25%) at the trauma center. Overall mortality was 21.9%, which was highest in the scene intubation group (29.7%) compared with the referring hospital (20%) and trauma center (5.6%) groups (P 0.01). Patients intubated at the scene had higher Injury Severity Scores and lower Glasgow Coma Scale scores (P 0.01). Duration of intubation was lowest in the trauma center group (P 0.01). Complication rate was highest in the referring hospital group (P 0.05). Multivariate analysis revealed that age, injury severity, and neurologic status were the key drivers of mortality rather than location of intubation.Mortality and duration of intubation were lowest in trauma patients intubated at a pediatric trauma center. However, location of intubation was not a significant independent predictor of mortality or complications on multivariate analysis, suggesting that age, injury severity, and neurologic status are the main indicators of prognosis in severe pediatric trauma.

SUMMARY Metazoan cell death mechanisms are diverse and include numerous non-apoptotic programs. One program called entosis involves the invasion of live cells into their neighbors and is known to occur in cancers. Here, we identify a developmental function for entosis: to clear the male-specific linker cell in C. elegans. The linker cell leads migration to shape the gonad and is removed to facilitate fusion of the gonad to the cloaca. We find that the linker cell is cleared in a manner involving cell-cell adhesions and cell-autonomous control of uptake through linker cell actin. Linker cell entosis generates a lobe structure that is deposited at the site of gonad-to-cloaca fusion and is removed during mating. Inhibition of lobe scission inhibits linker cell death, demonstrating that the linker cell invades its host while alive. Our findings demonstrate a developmental function for entosis: to eliminate a migrating cell and facilitate gonad-to-cloaca fusion, which is required for fertility., Graphical Abstract, In Brief Entosis is a cell death mechanism, previously observed in cancer cell populations, that involves the invasion of live cells into their neighbors. Lee et al. now show that entosis has a developmental function in C. elegans, clearing the linker cell during gonad formation.

Entosis is a mechanism of cell competition occurring in cancers that involves the engulfment and killing of neighboring cells. The death of ingested cells, called entotic cell death, usually occurs in a non-apoptotic, autophagy protein-dependent manner, where microtubule-associated protein light chain 3 (LC3) is lipidated onto entotic vacuoles. Here we present methods to quantify entotic cell death and its associated LC3 lipidation.

Entosis is a mechanism of cell competition occurring in cancers that involves the engulfment and killing of neighboring cells. The death of ingested cells, called entotic cell death, usually occurs in a non-apoptotic, autophagy protein-dependent manner, where microtubule-associated protein light chain 3 (LC3) is lipidated onto entotic vacuoles. Here we present methods to quantify entotic cell death and its associated LC3 lipidation.

Moderne bildgebende Verfahren erweitern das diagnostische Spektrum und die Aussagekraft der Prostatadiagnostik. Mit dem Ziel einer verbesserten Karzinomdetektion wurde der Stellenwert der perinealen HistoScanning™- (HS-)gestutzten Templateprostatabiopsie ermittelt. Bei insgesamt 104 konsekutiven Mannern (Alter 69 Jahre, PSA 9,9 ng/ml) wurde vor einer erweiterten Prostatabiopsie eine HS-Untersuchung durchgefuhrt. Die Patienten erhielten eine gezielte templategestutzte transperineale und transrektale Biopsie der HS positiven Areale, sowie eine systematische transrektale 14-fach-Biopsie (Bx) der Prostata. Die Detektionsrate wurde hinsichtlich Lokalisation, Sensitivitat (Sens), Spezifitat (Spez), pradiktiver Genauigkeit, negativ-pradiktivem Wert (NPV) and positiv-pradiktivem Wert (PPV) analysiert. Ein Karzinom der Prostata zeigten 44 von 104 (42 %) Patienten. Histologisch waren ferner ASAP („atypical small acinar proliferations“) in 3 (2,9 %), HG-PIN („high-grade prostatic intraepithelial neoplasia“) in 16 (15,4 %) und chronische Prostatitis in 74 (71,1 %) Fallen nachweisbar. Die Detektionsrate in HS-positiven Arealen war im Vergleich zur systematischen Bx signifikant erhoht. Die jeweiligen Detektionsraten im Kollektiv waren trotz der entsprechend reduzierten Anzahl von Biopsien untereinander vergleichbar. Sens., Spez., pradiktiver Genauigkeit, NPV und PPV betrugen 37,2, 85,6, 78,6, 88,7 und 30,8 %. HS fuhrt in Kombination mit einer perinealen templategestutzen Biopsie zu einer verbesserten Detektionsrate im Vergleich zur transrektal gesteuerten Biopsie. HS erweitert den Informationsgehalt herkommlicher TRUS-Bildgebung (transrektaler Ultraschall) und verbessert den diagnostischen Stellenwert gezielter Prostatabiospien.

SUMMARY Entosis is a mechanism of cell death that involves neighbor cell ingestion. This process occurs in cancers and promotes a form of cell competition, where winner cells engulf and kill losers. Entosis is driven by a mechanical differential that allows softer cells to eliminate stiffer cells. While this process can be induced by matrix detachment, whether other stressors can activate entosis is unknown. Here, we find that entosis is induced in adherent cells by glucose withdrawal. Glucose withdrawal leads to a bimodal distribution of cells based on their deformability, where stiffer cells appear in a manner requiring the energy-sensing AMP-activated protein kinase (AMPK). We show that loser cells with high levels of AMPK activity are eliminated by winners through entosis, which supports winner cell proliferation under nutrient-deprived conditions. Our findings demonstrate that entosis serves as a cellular response to metabolic stress that enables nutrient recovery through neighbor cell ingestion., Graphical Abstract Entosis has been shown to occur in human cancers and promotes cell competition. Hamann et al. now show that nutrient deprivation, in the form of glucose withdrawal, induces entosis to support the outgrowth of winner cells that feed off of losers.

Entosis is a form of epithelial cell cannibalism that is prevalent in human cancer, typically triggered by loss of matrix adhesion. Here, we report an alternative mechanism for entosis in human epithelial cells, driven by mitosis. Mitotic entosis is regulated by Cdc42, which controls mitotic morphology. Cdc42 depletion enhances mitotic deadhesion and rounding, and these biophysical changes, which depend on RhoA activation and are phenocopied by Rap1 inhibition, permit subsequent entosis. Mitotic entosis occurs constitutively in some human cancer cell lines and mitotic index correlates with cell cannibalism in primary human breast tumours. Adherent, wild-type cells can act efficiently as entotic hosts, suggesting that normal epithelia may engulf and kill aberrantly dividing neighbours. Finally, we report that Paclitaxel/taxol promotes mitotic rounding and subsequent entosis, revealing an unconventional activity of this drug. Together, our data uncover an intriguing link between cell division and cannibalism, of significance to both cancer and chemotherapy. DOI: http://dx.doi.org/10.7554/eLife.27134.001, eLife digest For over a century, scientists looking down microscopes at samples from human cancers have noticed cells eating other cells – in other words, cell cannibalism. The causes and mechanisms involved in this unusual process, which is also known as entosis, are not well understood and its relationship to cancer is complex. On one hand, cell cannibalism may promote cancer by providing nutrients for growing tumours and making it more likely that genetic errors will occur. On the other hand, this process may resist cancer by eliminating damaged cells. In the laboratory, cell cannibalism has only been seen in cells that are detached from their surroundings. Cells in the body are typically surrounded and supported by a mesh of proteins called the extracellular matrix. However, within a tumour, cancer cells can often begin to grow without being attached to the matrix, which means that cell cannibalism can occur. A protein called Cdc42 plays a part in how cells attach to each other and to the extracellular matrix, but the role of Cdc42 in controlling entosis had not been previously explored. Durgan et al. initially set out to ask whether Cdc42 was involved in the established process of cell cannibalism, as seen in detached cells. However, the experiments showed that removing Cdc42 from human cells grown in the laboratory had little effect on this method of entosis. Unexpectedly, though, the loss of Cdc42 did enable a different form of cell cannibalism in cells that remained attached to the extracellular matrix, which had not been seen before. This new cannibalism process is linked to cell division, with cells that are dividing or that have recently divided being consumed by neighbours. This form of cell cannibalism is more commonly seen in cancers where the cells divide a lot, and some chemotherapy drugs that interfere with cell division also increase the rate of cell cannibalism. During cell division a group of proteins – including RhoA and myosin – cause cells to become rounder and stiffer. Durgan et al. suggest this allows the dividing cells to force their way inside other cells, the key first stage of entosis. Since cancer cells divide often, this form of cell cannibalism may lead to the cancer cells being destroyed by their healthy neighbours, in a form of “assisted suicide”. This reveals an unexpected link between cell division and cell cannibalism, which is relevant to both cancer and chemotherapy. Future work will explore whether entosis can be used to predict how a cancer will progress in a patient, or how they will respond to a given treatment. DOI: http://dx.doi.org/10.7554/eLife.27134.002

Entosis is a mechanism of cell death that involves neighbor cell ingestion. This process occurs in cancers and promotes a form of cell competition, where winner cells engulf and kill losers. Entosis is driven by a mechanical differential that allows softer cells to eliminate stiffer cells. While this process can be induced by matrix detachment, whether other stressors can activate entosis is unknown. Here, we find that entosis is induced in adherent cells by glucose withdrawal. Glucose withdrawal leads to a bimodal distribution of cells based on their deformability, where stiffer cells appear in a manner requiring the energy-sensing AMP-activated protein kinase (AMPK). We show that loser cells with high levels of AMPK activity are eliminated by winners through entosis, which supports winner cell proliferation under nutrient-deprived conditions. Our findings demonstrate that entosis serves as a cellular response to metabolic stress that enables nutrient recovery through neighbor cell ingestion.

Background The role of sentinel lymph node biopsy (SLNB) in soft tissue sarcoma patients has yet to be determined. We sought to evaluate the role of SLNB in the treatment of patients with clear cell sarcoma (CCS), synovial sarcoma (SS), epithelioid sarcoma (ES) and rhabdomyosarcoma (RMS). Patients and methods Sixty-two consecutive patients without history of regional lymphatic spread or evidence of distant metastases underwent SLNB. Results Positive sentinel nodes were identified in 2 out of 42 patients with SS and in 6 out of 12 patients with CCS. Only two CCS patients had further metastatic nodes in regional dissection. Both of these patients, along with another CCS patient, developed distant metastases and ultimately died of disease. The remaining three CCS patients are disease-free in follow-up. One patient with SS and another with ES developed regional lymph node metastases following a negative SLNB, while a further patient with RMS developed distant metastases followed by a local recurrence with regional metastases shortly after. Conclusions SLNB is an important diagnostic tool for patients with CCS, who appear to have a high rate of clinically occult regional lymph node metastases at diagnosis. For SS patients, SLNB appears to be of very little relevance.

SummaryIn 2013, electronic documentation of clinical care stands at a crossroads. The benefits of creating digital notes are at risk of being overwhelmed by the inclusion of easily importable detail. Providers are the primary authors of encounters with patients. We must document clearly our understanding of patients and our communication with them and our colleagues. We want to document efficiently to meet without exceeding documentation guidelines. We copy and paste documentation, because it not only simplifies the documentation process generally, but also supports meeting coding and regulatory requirements specifically. Since the primary goal of our profession is to spend as much time as possible listening to, understanding and helping patients, clinicians need information technology to make electronic documentation easier, not harder. At the same time, there should be reasonable restrictions on the use of copy and paste to limit the growing challenge of ‘note bloat’. We must find the right balance between ease of use and thoughtless documentation. The guiding principles in this document may be used to launch an interdisciplinary dialogue that promotes useful and necessary documentation that best facilitates efficient information capture and effective display. Citation: Shoolin J, Ozeran L, Hamann C, Bria W. II. Association of Medical Directors of Information Systems Consensus on Inpatient Electronic Health Record Documentation. Appl Clin Inf 2013; 4: 293–303http://dx.doi.org/10.4338/ACI-2013-02-R-0012

The purpose of this study was to present results of single-stage revision anterior cruciate ligament (ACL) reconstruction using an allograft bone dowel for isolated femoral bony deficiency.Sixteen patients underwent single-stage revision ACL reconstruction using an allograft bone dowel for isolated femoral bony deficiency between 2007 and 2012. Twelve patients (75%) completed study visits, which included CT scans as well as completion of validated outcomes measures.The average KT-1000 side-to-side difference was 1.0 mm ± 2.9 mm. The average International Knee Documentation Committee score was 70.2 ± 17.8, the Tegner score was 4.8 ± 2.8, and the visual analog scale pain score was 2.8 ± 2.4. An analysis of CT scans showed that all 12 dowels had excellent (75%) incorporation.A single-stage approach for revision ACL reconstruction using allograft dowels for isolated femoral bony deficiency yields objective and subjective outcomes comparable to those reported in the literature for two-stage and other single-stage techniques, with good incorporation of the dowels.Retrospective case series, level IV.

Auch wenn unterschiedliche Implantatmodelle, Gleitpaarungen und Verankerungstechniken in der Huftgelenkendoprothetik verfugbar sind, erfolgt die Versorgung in zunehmend standardisierter Form. Im voranstehenden Beitrag (s. S. 275) waren die Grundlagen und die Diagnostik vorgestellt worden. Dieser Beitrag nun hat als Ziel die Darstellung zementfreier, zementierter sowie kombinierter Behandlungstechniken, die im Sinne eines „Standards“ haufig Anwendung finden. Daruber hinaus wird das postoperative Management und der Umgang mit Komplikationen beschrieben. Die Beurteilung der Ergebnisqualitat schliest den Themenkomplex ab.

Die Versorgung mit kunstlichen Huftgelenken ist ein sehr verbreitetes und auserordentlich effektives medizinisches Behandlungsverfahren, mit dem betroffene Patienten nach unterschiedlichen Erkrankungen und huftnahen Frakturen haufig wieder Schmerzfreiheit, Mobilitat und eine verbesserte Lebensqualitat erreichen. Unabhangig von der Implantatwahl haben eine differenzierte Indikationsstellung, die sorgfaltige Planung und Durchfuhrung des Eingriffes und eine korrekte peri- bzw. postoperative Behandlung des Patienten sehr grose Bedeutung. Die Festschreibung eines standardisierten Vorgehens im Rahmen sogenannter „klinischer Pfade“ tragt mit zum Erfolg bei. Unter Beachtung der genannten Kriterien sind mit den allermeisten Implantaten heute Uberlebensraten von mindestens 90 % nach 10 Jahren erreichbar. Ziel dieses Beitrags ist die Vermittlung In einem weiteren Beitrag (s. S. 291) werden die Operationstechniken sowie die Nachbehandlung dargestellt.

Die Implantation einer Huftendoprothese bei fortgeschrittener Arthrose stellt eine sehr erfolgreiche und zuverlassige Operation dar. Mit der Endoprothesenplanung werden die biomechanische Situation des Huftgelenks und die zu verwendenden Komponenten sowie die Verankerungstechnik festgelegt. An einer Kohorte von 114 Patienten wurden die Gute der digitalen Rontgenbilder und der Versorgung bestimmt. Durchschnittlich wurde fur die biomechanische Situation eine geringe Beinverlangerung bei guter Offsetrekonstruktion erreicht. In der Gruppe von Patienten mit Versorgung der zweiten Seite war der Beinlangenunterschied geringer. Die verwendeten Komponentenstellungen lagen fur die Pfanneninklination durchschnittlich mit 43° bzw. 44° (Gruppe 1 und 2) im publizierten Zielbereich. Die Vorhersagegenauigkeit fur die zu verwendenden Komponentengrosen lag fur die exakte Grose der Pfanne bei 40% und fur den Schaft bei 29%. Durch eine Variabilitat bei der Skalierung wurde eine abnehmende Vorhersagegenauigkeit fur die geplanten Komponentengrosen bei digitaler Rontgentechnik gefunden. Die biomechanische Situation und Komponentenstellung zeigt eine gute Versorgungsqualitat als Ausdruck eines kontinuierlichen Qualitatsmanagement an. Die Endoprothesenplanung und Ergebnisuberprufung kann fur eine sichere Patientenversorgung empfohlen werden.

The microsegmented flow principle was applied for the preparation of polymer minirods. A microfluidic assembly was used to form monomer segments separated by an immiscible perfluorinated aliphatic solvent. These segments were transformed into polymer rods by thermal polymerization. Uniform-sized polystyrene rods with various diameters and lengths were prepared in this way. The microfluidic geometry and polymerization conditions were tuned to obtain polymer rods of various lengths and diameters. Metal nanoparticle doped polystyrene polymer rods were obtained by thermal polymerization of appropriate nanoparticle/monomer mixtures. After polymerization, the polystyrene rods were colored by an azo coupling reaction.

Background Development of treatments for obsessive-compulsive disorder (OCD) is hampered by a lack of mechanistic understanding about this prevalent neuropsychiatric condition. Although circuit changes such as elevated frontostriatal activity are linked to OCD, the underlying molecular signaling that drives OCD-related behaviors remains largely unknown. Here, we examine the significance of type 5 metabotropic glutamate receptors (mGluR5s) for behavioral and circuit abnormalities relevant to OCD. Methods Sapap3 knockout (KO) mice treated acutely with an mGluR5 antagonist were evaluated for OCD-relevant phenotypes of self-grooming, anxiety-like behaviors, and increased striatal activity. The role of mGluR5 in the striatal circuit abnormalities of Sapap3 KO mice was further explored using two-photon calcium imaging to monitor striatal output from the direct and indirect pathways. A contribution of constitutive signaling to increased striatal mGluR5 activity in Sapap3 KO mice was investigated using pharmacologic and biochemical approaches. Finally, sufficiency of mGluR5 to drive OCD-like behavior in wild-type mice was tested by potentiating mGluR5 with a positive allosteric modulator. Results Excessive mGluR5 signaling underlies OCD-like behaviors and striatal circuit abnormalities in Sapap3 KO mice. Accordingly, enhancing mGluR5 activity acutely recapitulates these behavioral phenotypes in wild-type mice. In Sapap3 KO mice, elevated mGluR5 signaling is associated with constitutively active receptors and increased and imbalanced striatal output that is acutely corrected by antagonizing striatal mGluR5. Conclusions These findings demonstrate a causal role for increased mGluR5 signaling in driving striatal output abnormalities and behaviors with relevance to OCD and show the tractability of acute mGluR5 inhibition to remedy circuit and behavioral abnormalities.