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Zusammenfassung Hintergrund Die aktinische Keratose (AK) ist ein epitheliales Carcinoma in situ der Haut. Aufgrund des Risikos einer malignen Transformation besteht ein frühzeitiger Behandlungsbedarf. Gerade die initiale Therapie sollte neben der Wirksamkeit eine gute Verträglichkeit und Anwenderfreundlichkeit aufweisen. Kaliumhydroxid (KOH)-Lösung ist als keratolytische Behandlungsoption bei hyperkeratotischen Hauterkrankungen, wie z. B. Mollusca contagiosa, bereits etabliert. Methodik Wirksamkeit und Verträglichkeit von KOH-5 %-Lösung zur Behandlung der leichten bis moderaten AK wurden in einer prospektiven, einarmigen, multizentrischen Medizinproduktestudie (Treatment of AK with KOH [TAKKOH]) untersucht. Die KOH-Lösung wurde 2‑mal täglich über 14 Tage aufgetragen mit anschließender Behandlungspause von 14 Tagen (≙ 1 Behandlungszyklus) für maximal 3 Behandlungszyklen oder mindestens bis zum Behandlungserfolg. Das primäre Zielkriterium „Behandlungserfolg“ wurde als komplette Remission (CR) aller AK-Läsionen eines Patienten definiert. Sekundäre Zielkriterien beinhalteten die Beurteilung der partiellen Remission (PR), der Anzahl an AK-Läsionen in Remission, die Wirksamkeitsbeurteilung anhand von Schulnoten durch Prüfärzte und Patienten sowie sicherheitsrelevante Endpunkte. Ergebnisse Es wurden 73 Patienten in die Studie eingeschlossen. Eine CR wurde von 54,9 % der Patienten erreicht, eine PR von 64,8 % bei einer Reduktion der Gesamtzahl an Läsionen um 69,9 %. Bei 46,6 % der Patienten wurden unerwünschte Ereignisse beobachtet. Diese überwiegend unerwünschten Wirkungen (82,6 %) stellten ausnahmslos transiente und milde lokale Hautreaktionen dar. Schlussfolgerung Die Studie liefert Hinweise auf die Wirksamkeit und Sicherheit von KOH-5 %-Lösung zur läsionsgerichteten topischen Therapie der AK.

BACKGROUND Laparoscopic removal of cryptorchid testes has been routinely reported through enlarged parainguinal incisions in dorsally recumbent horses. Outcomes following removal through an extended umbilical incision have not been previously reported. OBJECTIVE To describe the surgical technique of removing cryptorchid testes in dorsally recumbent horses through an enlarged umbilical portal after laparoscopic intra-abdominal castration. STUDY DESIGN Retrospective case series. METHODS Medical records were reviewed for horses that underwent laparoscopic removal of unilateral or bilateral cryptorchid testes from January 2006 to December 2016. Horses were placed under general anaesthesia, positioned in dorsal recumbency and then tilted into Trendelenburg position. Cryptorchid testes were castrated by ligating loop application and/or electrosurgery. The umbilical portal incision was extended along the linea alba for testes removal. All descended testes were removed by routine closed castration with the scrotal incision left to heal by second intention. Perianaesthetic laboratory values, surgical procedure descriptions, surgery and anaesthesia times, and in-hospital perioperative complications were recorded. RESULTS A total of 79 horses, aged 1-14 years, with unilateral or bilateral cryptorchidism were included: 90 cryptorchid testes were successfully removed through an enlarged umbilical portal incision. Sixty-eight horses were unilaterally cryptorchid and 11 were bilaterally cryptorchid. Two horses had minor post-operative complications related to the extended umbilical portal incision. MAIN LIMITATIONS Retrospective nature of the study, no control population for comparison and no follow-up after hospital discharge. CONCLUSION An extended umbilical portal incision is a successful alternative to extending a parainguinal incision for testis removal after laparoscopic castration.

Background The lipid-lowering and positive cardiovascular effect of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors was shown in several studies, hence, they are more widely used in the lipid-lowering management of individuals with high cardiovascular risk. As real-world data are still scarce, specifically in patients with type 2 diabetes (T2D), the aim of this retrospective analysis was to investigate the efficacy of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol (LDL-C) in an outpatient clinic of a tertiary care center in routine care. Methods A retrospective analysis of data extracted from the electronic patient record was performed. Patients who were routinely prescribed with PCSK9 inhibitor therapy (alirocumab or evolocumab) during the years 2016 and 2019 were included in the analysis. Characteristics of the patient population, the effects on LDL-C and HbA1c levels as well as subsequent cardiovascular events were assessed over an observation period of 18 months. Results We identified 237 patients treated with PCSK9 inhibitors between January 2016 and September 2019. Almost all patients (97.5%) received PCSK9 inhibitors for secondary prevention. 26.2% of the population had a concomitant diabetes diagnosis. Intolerance to statins (83.1%), ezetimibe (44.7%) or both agents (42.6%) was reported frequently. Three months after initiation of PCSK9 inhibitor therapy, 61.2% of the patients achieved LDL-C levels 54 mmol/mol) had a higher reduction in LDL-C but still were more likely to subsequent cardiovascular events. Conclusions Significant reductions in LDL-C and a high percentage of patients achieving recommended treatment targets were observed. The percentage of patients with T2D meeting recommended LDL-C targets was higher than in those without T2D. Still some patients did not achieve LDL-C levels as recommended in current guidelines. Special attention to the characteristics of these patients is required in the future to enable achievement of treatment goals and avoid adverse cardiovascular outcomes.

Traumatic brain injury (TBI) produces microstructural damage to white matter pathways connecting neural structures in pre-frontal and striatal regions involved in self-regulation (SR). Dorsal and ventral frontostriatal pathways have been linked to cognitive (“cool”) and emotional (“hot”) SR, respectively. We evaluated the relation of frontostriatal pathway fractional anisotropy (FA) 2 months post-TBI on cool and hot SR assessed 7 months post-TBI. Participants were 8–15 years of age, including children with uncomplicated mild TBI (mTBI; n = 24), more severe TBI (complicated-mild, moderate, severe [cms]TBI; n = 60), and typically developing (TD) children (n = 55). Diffusion tensor tractography was used to map frontostriatal pathways. Cool SR included focused and sustained attention performance, and parent-reported attention, whereas hot SR included risk-taking performance and parent-reported emotional control. Multivariate general linear models showed that children with cmsTBI had greater parent-reported cool and hot SR difficulties and lower dorsal and ventral FA than TD children. Focused attention, risk taking, and emotional control correlated with FA of specific dorsal and ventral pathways; however, only the effect of TBI on focused attention was mediated by integrity of dorsal pathways. Results suggest that frontostriatal FA may serve as a biomarker of risk for SR difficulties or to assess response to interventions targeting SR in pediatric TBI and in broader neurodevelopmental populations.

Probiotic bacteria, such as different lactobacilli strains, have successfully been used to treat gingivitis and periodontitis or caries. By formulating probiotics as orodispersible tablet (ODT), the benefits of this dosage form could be utilized. Without any further measures, the probiotic bacteria will be eliminated too fast from the intended site of action, the oral mucosa. The use of mucoadhesive granules, composed of mucoadhesive polymer and probiotics, is a promising strategy to prolong the contact time between lactobacilli and oral mucosa without delaying disintegration. Three common mucoadhesive polymers, anionic Carbopol 971P NF, nonionic Metolose 65SH50 and cationic chitosan were included into tablets either by direct compression (DC) or after granulation with the probiotics. Disintegration, mucoadhesion of the tablets, and storage stability of the probiotics were characterized. By incorporating a sufficient amount of polymer superior probiotic mucoadhesion could be achieved. All formulations based on granulated probiotics and mucoadhesive polymer fulfilled the Food and Drug Administration (FDA) acceptance level for disintegration of orodispersible tablets. These formulations exhibited excellent storage stability under refrigerated conditions over 30 months. Interestingly, ODTs including Carbopol 971P NF still proved superior mucoadhesion after long-term storage, whereas the mucoadhesive effect of Metolose 65SH50 and chitosan declined markedly. The results of this study suggest that Carbopol 971P NF was the most appropriate polymer for a probiotic mucoadhesive ODT.

Neben akuten Wunden durch Traumen oder chirurgische Eingriffe stellen chronische Wunden eine relativ grose, heterogene Erkrankungsgruppe dar. Dazu zahlen Beinulzera, bei denen die venose Genese die der arteriellen Genese deutlich ubertrifft, aber auch das diabetische Fussyndrom und Druckulzera. Aufgrund der Therapieresistenz v. a. chronischer Wunden werden dringend weitere, additiv wirksame Therapieoptionen benotigt. Die zusatzliche Behandlung mit kaltem Atmospharendruckplasma (KAP) stellt eine derartige innovative Option dar. Betrachtet wird die Wirkung von Kaltplasma auf die Heilung akuter und chronischer Wunden, und es wird der aktuelle Stand der Forschung aufgezeigt. Literatur zur Anwendung von KAP zur Wundbehandlung wurde gesichtet und als Ubersichtsarbeit zusammengefasst. Mit einer KAP-Behandlung konnen mehrere wundheilungsfordernde Effekte in einer Anwendung erzielt werden. Zum einen besitzt KAP eine starke und breite antimikrobielle Aktivitat auch gegen Biofilm. Zum anderen mediiert der Plasmacocktail, der aus reaktiven Stickstoff- und Sauerstoffspezies, UV und geladenen Teilchen (Stromfluss) besteht, gewebestimulierende und durchblutungsfordernde sowie antiinflammatorische Effekte. Eine deutliche Reduktion der Keimbesiedelung und eine schnellere Wundheilung konnten in kontrollierten Studien bereits klar nachgewiesen werden. Die mittlerweile umfassende Studienlandschaft mit strukturierten Fallberichten und randomisierten Fall-Kontroll-Studien lasst den Schluss zu, dass KAP zur Wundbehandlung sicher, effektiv und einfach einsetzbar ist. Die Anwendung von KAP zur Wundbehandlung hat vereinzelt bereits den Einzug in die klinische Routine gefunden.

Background As a result of the Fontan procedure, the prognosis of congenital single-ventricle heart disease has improved, with many affected children surviving into adulthood. However, the unanticipated consequences of chronic exposure to Fontan hemodynamics has revealed a new set of secondary noncardiac complications. Fontan-associated liver disease (FALD) is characterized by progressive hepatic fibrosis in nearly all patients post-Fontan, with the potential to develop cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. A lack of data regarding FALD-related prognosis makes consideration of indications for and timing of heart alone versus combined heart-liver transplantation challenging. Methods A multidisciplinary group within the American Society for Transplantation analyzed several administrative datasets in order to study the epidemiology of FALD. Results This approach presented several obstacles, and efforts to characterize FALD were limited by a lack of Fontan- and FALD-specific diagnostic codes and an inability to follow individual patients through multiple health systems. Several ongoing Fontan registries were also reviewed but these do not adequately capture FALD-related variables. Such barriers highlight the need for large-scale data collection in patients post-Fontan to better understand and care for this complex population. Conclusions This study emphasizes the challenges of studying emerging transplant-related diagnoses in existing datasets and the need for mechanisms to adapt registries to appropriately identify patients with rare or emerging conditions.

Plasmamedizin hat sich zu einem innovativen Forschungsgebiet mit diversen Anwendungsmoglichkeiten insbesondere in der Dermatologie entwickelt. Kaltes Atmospharendruckplasma (KAP) kann sowohl gewebeschonend als auch zur Destruktion von malignem Gewebe eingesetzt werden. KAP besteht aus einer komplexen Mixtur aus verschiedenen biologisch aktiven Agenzien, die zum Teil synergistisch auf das zu behandelnde Material oder Gewebe wirken. Dargestellt werden die Anwendungsgebiete fur KAP in der Dermatologie sowie der aktuelle Stand der Forschung. Literatur zur Anwendung von KAP in der Dermatologie wurde gesichtet und als Ubersichtsarbeit zusammengefasst. Mit einer KAP-Behandlung konnen beispielsweise antimikrobielle, gewebestimulierende, durchblutungsfordernde, aber auch proapoptotische Effekte erreicht werden. Unter Ausnutzung dieser Effekte kommt KAP in der Dermatologie erfolgreich zur Desinfektion und Wundbehandlung zum Einsatz. Des Weiteren zeigen Untersuchungen zur Anwendung von KAP bei der Behandlung von Tumoren, aktinischen Keratosen, Narben, Ichthyose, atopischen Ekzemen sowie zur Linderung von Schmerz und Juckreiz positive Effekte. Wahrend die Anwendung von KAP zur Desinfektion und zur Wundbehandlung vereinzelt bereits den Einzug in die klinische Praxis gefunden hat, befindet sich die Anwendung in weiteren Bereichen, beispielsweise zur Tumortherapie, noch im Forschungskontext.

Prophylactic endoscopy is routine in adults with portal hypertension (PHTN), but there is limited data in pediatrics. We sought to describe our experience with prophylactic endoscopy in pediatric PHTN. This is a retrospective study of 87 children who began surveillance endoscopy prior to gastrointestinal bleeding (primary prophylaxis) and 52 who began after an episode of bleeding (secondary prophylaxis) from 01/01/1994 to 07/01/2019. Patients who underwent primary prophylaxis had a lower mean number of endoscopies (3.897 vs 6.269, p = 0.001). The primary prophylaxis group was less likely to require a portosystemic shunt (6% vs 15%, p

The automated analysis of digital human communication data often focuses on specific aspects such as content or network structure in isolation. This can provide limited perspectives while making cross-methodological analyses, occurring in domains like investigative journalism, difficult. Communication research in psychology and the digital humanities instead stresses the importance of a holistic approach to overcome these limiting factors. In this work, we conduct an extensive survey on the properties of over forty semi-automated communication analysis systems and investigate how they cover concepts described in theoretical communication research. From these investigations, we derive a design space and contribute a conceptual framework based on communication research, technical considerations, and the surveyed approaches. The framework describes the systems' properties, capabilities, and composition through a wide range of criteria organized in the dimensions (1) Data, (2) Processing and Models, (3) Visual Interface, and (4) Knowledge Generation. These criteria enable a formalization of digital communication analysis through visual analytics, which, we argue, is uniquely suited for this task by tackling automation complexity while leveraging domain knowledge. With our framework, we identify shortcomings and research challenges, such as group communication dynamics, trust and privacy considerations, and holistic approaches. Simultaneously, our framework supports the evaluation of systems and promotes the mutual exchange between researchers through a structured common language, laying the foundations for future research on communication analysis., Comment: 11 pages, 2 tables, 1 figure

We report on the visible LGS-AO experimental facility which we are building to be installed at the 1m ESA Optical Ground Station at Observatorio del Teide, Tenerife, Canary Islands. We focus on the system aspects related to optics. The instrument will be a novel facility to perform strategic LGS-AO technology R&D in future years, demonstrating a 50+ W CW 589nm laser, uplink laser beam pre-compensation on sodium LGS in pulsed laser operation. The rationale for the LGS-AO facility is to have a synergy between astronomical and space awareness adaptive optics, to technologies for astrophysics and optical communication with satellites (Optical Feeder Links), including daytime LGS-AO, for future OGS systems.

Pre-frontal limbic circuitry is vulnerable to effects of stress and injury. We examined microstructure of pre-frontal limbic circuitry after traumatic brain injury (TBI) or extracranial injury (EI) and its relation to post-traumatic stress symptoms (PTSS). Participants aged 8 to 15 years who sustained mild to severe TBI (n = 53) or EI (n = 26) in motor vehicle incidents were compared with healthy children (n = 38) in a prospective longitudinal study. At the seven-week follow-up, diffusion tensor imaging was obtained in all groups; injured children completed PTSS ratings using a validated scale. Using probabilistic diffusion tensor tractography, pathways were seeded from bilateral amygdalae and hippocampi to estimate the trajectory of white matter connecting them to each other and to targeted pre-frontal cortical (PFC) regions. Microstructure was estimated using fractional anisotropy (FA) in white matter and mean diffusivity (MD) in gray matter. Pre-frontal limbic microstructure was similar across groups, except for reduced FA in the right hippocampus to orbital PFC pathway in the injured versus healthy group. We examined microstructure of components of pre-frontal limbic circuitry with concurrently obtained PTSS cluster scores in the injured children. Neither microstructure nor PTSS scores differed significantly in the TBI and EI groups. Across PTSS factors, specific symptom clusters were related positively to higher FA and MD. Higher hyperarousal, avoidance, and re-experiencing symptoms were associated with higher FA in amygdala to pre-frontal and hippocampus to amygdala pathways. Higher hippocampal MD had a central role in hyperarousal and emotional numbing symptoms. Age moderated the relation of white and gray matter microstructure with hyperarousal scores. Our findings are consistent with models of traumatic stress that implicate disrupted top-down PFC and hippocampal moderation of overreactive subcortical threat arousal systems. Alterations in limbic pre-frontal circuitry and PTSS place children with either brain or body injuries at elevated risk for both current and future psychological health problems.

Background Animal attacks pose a significant public health problem in the United States. Non-venomous animals are the leading cause of mortality in these attacks, and extremity injuries leading to hemorrhage are a common pattern. The Stop the Bleed campaign advocates for public training in bleeding control tactics and public access to bleeding control kits. Controlling life-threatening bleeding, as promoted by the Stop the Bleed campaign, may be a method to reduce preventable death in these attacks. Methodology We searched the Nexus Uni database, which compiles international news media articles, to collect newspaper articles in the United States between 2010 and 2019 that referenced animal attacks on humans in which a tourniquet was applied. We screened articles to assess for inclusion criteria and isolated a single report for each attack. Results A total of 50 individual attacks met the inclusion criteria and were included for data collection. Overall, 92% (n = 46) of the victims survived the attacks, and the average victim age was 33. California was the most common location of the attacks (n = 12, 24%), sharks caused the most attacks (n = 26, 52%), and victims most often sustained isolated extremity injuries (n = 24, 48% for arm and n = 24, 48% for leg). Laypeople applied the most tourniquets (n = 29, 58%), and appliers most frequently used improvised tourniquets (n = 30, 60%). Conclusions While mortality in this series was low, there are hundreds of fatalities from non-venomous animal attacks each year. Equipping and training the at-risk public to stop bleeding may save additional lives. Future Stop the Bleed efforts should improve access to public hemorrhage control equipment and expand educational outreach to people engaged in high-risk activities with animals.

BackgroundThe lipid-lowering and positive cardiovascular effect of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors was shown in several studies, hence, they are more widely used in the lipid-lowering management of patients with high cardiovascular risk. As real-world data are still scarce, the aim of this retrospective analysis was to investigate the efficacy of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol (LDL-C) in an outpatient clinic of a tertiary care center in routine care.MethodsA retrospective analysis of data extracted from the electronic patient record was performed. Patients who were routinely prescribed with PCSK9 inhibitor therapy (Alirocumab or Evolocumab) during the years 2016 and 2019 were included in the analysis. Characteristics of the patient population, the effects on LDL-C and HbA1c levels were assessed over the course of treatment.ResultsWe identified 237 patients treated with PCSK9 inhibitors between January 2016 and September 2019. Almost all patients (97.5%) received PCSK9 inhibitors for secondary prevention. Comorbidities at baseline included: arterial hypertension (68.8%), diabetes mellitus (25.3%), smoking (5.9%). Vascular disease at baseline was present as follows: coronary heart disease (74.7%), history of stroke or transient ischemic attack (13.5%), carotid artery disease (30.8%), peripheral artery disease (18.1%), chronic kidney disease (9.7%), history of percutaneous coronary intervention (46.4%), history of coronary artery bypass surgery (16.0%).Intolerance to statins (83.1%), ezetimibe (44.7%), and both agents was reported frequently (42.6%).Six to nine months after initiation of PCSK9 inhibitor therapy, 61.7% of the patients achieved LDL-C levels ≤70 mg/dl, and 44.3% achieved LDL-C levels ≤55 mg/dl. The median LDL-C was lowered from 141 (IQR 117 - 188) mg/dl at baseline, to 60 (43 - 91) mg/dl (6 to 9 months) and 67 (44 - 89) mg/dl (12 to 18 months) indicating a reduction of LDL-C as follows: -54.9% (interquartile range (IQR) 44.4 – 57.3) after 6 to 9 months, -53.2% (IQR 42.6 – 67.1) after 12 to 18 months from baseline. ConclusionsSignificant reductions in LDL-C and a high percentage of patients achieving recommended treatment targets were observed. Still some patients did not achieve LDL-C levels recommended in current guidelines. Special attention to the characteristics of these patients is required in the future to enable achievement of treatment goals and avoid adverse cardiovascular outcomes.

Leveraging hypergraph structures to model advanced processes has gained much attention over the last few years in many areas, ranging from protein-interaction in computational biology to image retrieval using machine learning. Hypergraph models can provide a more accurate representation of the underlying processes while reducing the overall number of links compared to regular representations. However, interactive visualization methods for hypergraphs and hypergraph-based models have rarely been explored or systematically analyzed. This paper reviews the existing research landscape for hypergraph and hypergraph model visualizations and assesses the currently employed techniques. We provide an overview and a categorization of proposed approaches, focusing on performance, scalability, interaction support, successful evaluation, and the ability to represent different underlying data structures, including a recent demand for a temporal representation of interaction networks and their improvements beyond graph-based methods. Lastly, we discuss the strengths and weaknesses of the approaches and give an insight into the future challenges arising in this emerging research field., Comment: 2021 IEEE Visualization Conference (VIS)

BACKGROUND The objectives of this retrospective cohort study are to describe rates of adherence to laboratory testing 6 months to 3 years post-liver transplantation and to examine demographic and clinical factors related to lab non-adherence and the association with medication adherence and clinical outcomes. METHODS Medical chart review was conducted for 54 youth (mean age = 5.0 years) transplanted between 2003 and 2014. Lab adherence (≥80%) was measured as the proportion of completed labs out of the number expected. Immunosuppressant drug-level variability was used as a proxy for medication adherence. Clinical outcomes included LAR, viral infection, hospitalization, and non-routine clinic visit ≥12 months after transplant. RESULTS Lab adherence decreased substantially over time. Single-parent household (aOR 5.86; 95% CI: 1.38-24.93) and no history of early rejection (aOR 3.96; 95% CI: 1.04-15.24) were independently associated with non-adherence. Lab non-adherence was significantly associated with medication non-adherence (P

Surgical innovation and multidisciplinary management have allowed children born with univentricular physiology congenital heart disease to survive into adulthood. An estimated global population of 70 000 patients have undergone the Fontan procedure and are alive today, most of whom are

Wolfram syndrome (WS) is a rare, progressive disorder characterized by childhood-onset diabetes mellitus, optic nerve atrophy, hearing loss, diabetes insipidus, and neurodegeneration. Currently, there is no effective treatment for WS, and patients typically die between 30 and 40 years of age. WS is primarily caused by autosomal recessive mutations in the Wolfram syndrome 1 (WFS1) gene (OMIM 222300), which encodes for wolframin (WFS1). This disorder is therefore a valuable monogenic model for prevalent diseases, particularly diabetes mellitus and neurodegeneration. Whereas reduced survival and secretion are known cellular impairments causing WS, the underlying molecular pathways and the physiological function of WFS1 remain incompletely described. Here, we characterize WFS1 as a regulator of intracellular calcium homeostasis, review our current understanding of the disease mechanism of WS, and discuss candidate treatment approaches. These insights will facilitate identification of new therapeutic strategies not only for WS but also for diabetes mellitus and neurodegeneration.

Background After chemotherapy, many cancer survivors suffer from long-lasting cognitive impairment, colloquially known as “chemobrain.” However, the trajectories of cognitive changes and the underlying mechanisms remain unclear. We previously established paclitaxel-induced inositol trisphosphate receptor (InsP3R)-dependent calcium oscillations as a mechanism for peripheral neuropathy, which was prevented by lithium pretreatment. Here, we investigated if a similar mechanism also underlay paclitaxel-induced chemobrain. Method Mice were injected with 4 doses of 20 mg/kg paclitaxel every other day to induced cognitive impairment. Memory acquisition was assessed with the displaced object recognition test. The morphology of neurons in the prefrontal cortex and the hippocampus was analyzed using Golgi-Cox staining, followed by Sholl analyses. Changes in protein expression were measured by Western blot. Results Mice receiving paclitaxel showed impaired short-term spatial memory acquisition both acutely 5 days post injection and chronically 23 days post injection. Dendritic length and complexity were reduced in the hippocampus and the prefrontal cortex after paclitaxel injection. Concurrently, the expression of protein kinase C α (PKCα), an effector in the InsP3R pathway, was increased. Treatment with lithium before or shortly after paclitaxel injection rescued the behavioral, cellular, and molecular deficits observed. Similarly, memory and morphological deficits could be rescued by pretreatment with chelerythrine, a PKC inhibitor. Conclusion We establish the InsP3R calcium pathway and impaired neuronal morphology as mechanisms for paclitaxel-induced cognitive impairment. Our findings suggest lithium and PKC inhibitors as candidate agents for preventing chemotherapy-induced cognitive impairment.

Wolfram syndrome is a rare multisystem disease characterized by childhood-onset diabetes mellitus and progressive neurodegeneration. Most cases are attributed to pathogenic variants in a single gene, Wolfram syndrome 1 (WFS1). There currently is no disease-modifying treatment for Wolfram syndrome, as the molecular consequences of the loss of WFS1 remain elusive. Because diabetes mellitus is the first diagnosed symptom of Wolfram syndrome, we aimed to further examine the functions of WFS1 in pancreatic β cells in the context of hyperglycemia. Knockout (KO) of WFS1 in rat insulinoma (INS1) cells impaired calcium homeostasis and protein kinase B/Akt signaling and, subsequently, decreased cell viability and glucose-stimulated insulin secretion. Targeting calcium homeostasis with reexpression of WFS1, overexpression of WFS1's interacting partner neuronal calcium sensor-1 (NCS1), or treatment with calpain inhibitor and ibudilast reversed deficits observed in WFS1-KO cells. Collectively, our findings provide insight into the disease mechanism of Wolfram syndrome and highlight new targets and drug candidates to facilitate the development of a treatment for this disorder and similar diseases.

Torsion of an accessory spleen is an exceedingly rare cause of abdominal pain in pediatric patients. The diagnosis is frequently challenging as presentation is variable and diagnostic imaging can be aspecific. The current case describes an unusual presentation of a torted accessory spleen in a 5-year-old girl with biliary atresia splenic malformation syndrome who initially presented with non-specific abdominal symptoms and fever. The diagnosis was made following fine-needle aspiration of a suspected intraabdominal abscess. The case highlights the diagnostic challenge of accessory splenic torsion and stresses the importance of its inclusion on the differential diagnosis of pediatric patients, especially those with known splenic or laterality abnormalities, presenting with both acute and sub-acute abdominal symptoms.

In their recent study addressing efficacy of oral vancomycin (OVT) and ursodeoxycholic acid (UDCA) compared to no therapy in pediatric primary sclerosing cholangitis (PSC), Deneau et al. state: "OVT and UDCA are not effective treatments for PSC in children" [1]. Their study shows that the null hypothesis of no effect has not been rejected; a real effect might have been present but missed. Complications take up to 10 years to develop, but their median follow-up was just 4.2 years. The subsequent editorial [2] noted the limitations of a retrospective, propensity-matched study and argues cogently for the need to replace empiric practice with data from well-planned randomized controlled trials (RCTs).

Formation of crystals in saturated and undersaturated solutions is studied as a result of intense sound, or shock waves, produced by high intensity focused laser pulses. Many tiny crystals are created immediately throughout the solution by the laser-generated sound waves. The compression waves can be created by focusing within the liquid or onto the walls of a container. This new method allows for the instantaneous formation of many “seed” crystals, which are then available for further impurity-free crystal growth. More importantly, the tiny “baby” crystals can be harvested before complete growth into “adult” crystals can occur. This method is shown to produce enough “baby” crystals to provide a glimpse into the initial stages of crystal growth using modern microscopy techniques such as SEM. By employing this new method, simple salts such as sodium bromate, sodium chloride, sodium chlorate, and tartaric acid were successfully crystallized. This method of crystal growth may also allow for the generation of...

Background Cryptosporidium enteritis can be devastating in the immunocompromised host. In pediatric liver transplant recipients, infection may be complicated by prolonged carriage of the parasite, rejection, and biliary tree damage and fibrosis. Herein, we report on six patients and their long-term outcomes following cryptosporidiosis. Methods We reviewed all cases of cryptosporidiosis in a pediatric liver transplant population over a 17-year period at a single center. Six patients with infection were identified, and their outcomes were analyzed. Results Infection was associated with significant diarrhea and dehydration in all cases, and led to hospitalization in one-half of patients. Four of the six patients developed biopsy-proven rejection following infection, with three of those patients developing rejection that was recalcitrant to intravenous steroid treatment. Additionally, three patients developed biliary tree abnormalities with similarity to sclerosing cholangitis. In one patient, those biliary changes led to repeated need for biliary drain placement and advancing fibrotic liver allograft changes. Conclusions Cryptosporidiosis in pediatric liver transplant recipients may lead to significant complications, including recalcitrant episodes of rejection and detrimental biliary tree changes. We advocate for increased awareness of this cause of diarrheal disease and the allograft injuries that may accompany infection.

Long-term survival for children who undergo LT is now the rule rather than the exception. However, a focus on the outcome of patient or graft survival rates alone provides an incomplete and limited view of life for patients who undergo LT as an infant, child, or teen. The paradigm has now appropriately shifted to opportunities focused on our overarching goals of "surviving and thriving" with long-term allograft health, freedom of complications from long-term immunosuppression, self-reported well-being, and global functional health. Experts within the liver transplant community highlight clinical gaps and potential barriers at each of the pretransplant, intra-operative, early-, medium-, and long-term post-transplant stages toward these broader mandates. Strategies including clinical research, innovation, and quality improvement targeting both traditional as well as PRO are outlined and, if successfully leveraged and conducted, would improve outcomes for recipients of pediatric LT.

Elevated serum soluble (s) suppressor of tumorigenicity-2 is observed during cardiovascular and inflammatory bowel diseases. To ascertain whether modulated ST2 levels signify heart (HTx) or small bowel transplant (SBTx) rejection, we quantified sST2 in serially obtained pediatric HTx (n = 41) and SBTx recipient (n = 18) sera. At times of biopsy-diagnosed HTx rejection (cellular and/or antibody-mediated), serum sST2 was elevated compared to rejection-free time points (1714 ± 329 vs. 546.5 ± 141.6 pg/mL; p = 0.0002). SBTx recipients also displayed increased serum sST2 during incidences of rejection (7536 ± 1561 vs. 2662 ± 543.8 pg/mL; p = 0.0347). Receiver operator characteristic (ROC) analysis showed that serum sST2 > 600 pg/mL could discriminate time points of HTx rejection and nonrejection (area under the curve [AUC] = 0.724 ± 0.053; p = 0.0003). ROC analysis of SBTx measures revealed a similar discriminative capacity (AUC = 0.6921 ± 0.0820; p = 0.0349). Quantitative evaluation of both HTx and SBTx biopsies revealed that rejection significantly increased allograft ST2 expression. Pathway and Network Analysis of biopsy data pinpointed ST2 in the dominant pathway modulated by rejection and predicted tumor necrosis factor-α and IL-1β as upstream activators. In total, our data indicate that alloimmune-associated pro-inflammatory cytokines increase ST2 during rejection. They also demonstrate that routine serum sST2 quantification, potentially combined with other biomarkers, should be investigated further to aid in the noninvasive diagnosis of rejection.

Korrektur zu 10.1038/s41375-020-0826-9

Utilization of geothermal energy in low enthalpy regions is made possible with the use of EGS (Enhanced Geothermal Systems), which utilize a system of two boreholes connected by artificially fractured rock volume providing permeability for heating the cold water injected in one of the boreholes and produced in the other one. We focus on the area of Litoměřice in the NW part of Bohemian Massif, where a pilot 2.1 km deep geothermal borehole was drilled in 2007. We combine existing geological knowledge with newly acquired data to build a conceptual geological model of the area. Temperature logging and thermal characteristics of the collected rock samples provided data for thermal modelling. The lower part of the borehole samples relatively homogeneous mica-schists, which are overlain by rhyolite ignimbrites, upper-Carboniferous continental siliciclastic sediments and sedimentary cover of Bohemian Cretaceous Basin on the top. Several sets of brittle structures of various ages were identified in the area, however only some of them are prone for reactivation in the present stress field corresponding to NNW-SSE compression. The prevailing orientation of metamorphic foliation and missing signs for contact metamorphism appear to preclude the possible occurrence of granites in the deeper horizons. Equilibrium temperature in 1.8 km is 57.5 °C, which combined with the thermal characteristics of the rocks gives the heat flux of 78 mW/m2 and temperature prediction of about 140 °C in 5 km depth, which ranks the area to typical geothermal provinces of the NW part of the Bohemian Massif. Further research will be focused on seismic surveys and stress measurements to assess the seismicity potential of the formation.

Although TEG directs effective resuscitation in adult surgical patients, pediatric data are lacking. We performed a retrospective comparative review of the effect of TEG on blood product utilization and outcomes following pediatric liver transplantation in 38 patients between 2008 and 2014. Diagnoses, laboratory values, fluid and blood product use, and outcomes were examined. Nineteen patients underwent liver transplantation prior to the implementation of TEG, and 19 had perioperative TEG. The most common indications for transplant were BA (n = 14), HB (n = 7), and metabolic disorders (n = 7). Intraoperative blood loss, urine output, fluid and blood product use were similar between groups. However, the use of fresh frozen plasma decreased significantly in TEG patients within the first 24 hours (29 vs 0 mL/kg, P

SRL-based immunosuppressive strategies in pediatric liver transplantation are not clearly defined, especially within the first year after liver transplant. TAC is the more common, traditional immunosuppressant used. However, SRL may modulate TAC-associated kidney injury and may also have antiproliferative properties that are valuable in the management of patients following liver transplantation for HB. We sought to determine whether early conversion from TAC to SRL was safe, effective, and beneficial in a subset of liver transplant recipients with unresectable HB exposed to CDDP-based chemotherapy. Between 2008 and 2013, six patients were transplanted for unresectable HB. All patients received at least one cycle of CDDP-based chemotherapy prior to transplant. All patients were switched from TAC- to SRL-based immunosuppression within 1 year of transplant. Five patients had improvement in their mGFR, while one patient had a slight decline. The improvement in mGFR was statistically significant. No adverse events were identified. Three patients had BPAR that responded to pulsed steroids. Historical controls showed similar rates of BPAR within the first year after transplant. There were no identified HB recurrences in the follow-up time period. Conversion from TAC to SRL appears to be safe and effective in this selected group of pediatric liver transplant recipients without adverse reaction or HB recurrences.

Background: Probiotic bacteria with anti-inflammatory properties have the potential to be of therapeutic benefit in gingivitis. Objective: To evaluate the effects of potential probiotic strains on inflammatory mediators involved in early gingivitis using an ex vivo inflammation model. Methods: Strains were screened in viable and attenuated forms for effects on bacterial lipopolysaccharide (LPS)-stimulated release of interleukins (IL)-1β, -6 and -8, tumor necrosis factor-α, prostaglandin E2 and 8-isoprostane from human primary monocytes, and then, if anti-inflammatory effects were shown, on IL-1β-stimulated release of inflammatory mediators from primary gingival fibroblasts. Lead strains were evaluated for optimal dosing, batch-to-batch variation and functional consistency in toothpaste. Results: Twenty-one of 73 strains showed anti-inflammatory effects in monocytes; of which, seven showed effects in both viable and attenuated forms. Seven of 14 strains showed effects in fibroblasts. Strains Lactobacillus paracasei LPc-G110(SYBIO-15) and Lactobacillus plantarum GOS42(SYBIO-41) induced statistically significant dose-dependent reductions in the release of multiple inflammatory mediators from monocytes, which were consistent across batches. Viable L. paracasei LPc-G110 tooth paste significantly reduced IL-6, IL-8 and prostaglandin E2 release from monocytes versus placebo. Conclusion: Strains L. paracasei LPc-G110 and L. plantarum GOS42 have potential for use as probiotics in oral care products to reduce gingival inflammation.

BACKGROUND There is a lack of large database research relating to the epidemiology and health resource utilization associated with short bowel syndrome (SBS) in the United States. METHODS We analyzed the Kids' Inpatient Database for the year 2012 and utilized International Classification of Diseases, Ninth Revision, and Clinical Modification ( ICD-9-CM) diagnosis codes to identify patients 0-3 years of age with SBS, who were matched by age and sex to children without SBS. The study variables included patient and hospital demographics, All Patient Refined Diagnosis Related Groups, in-hospital mortality, hospital length of stay, and hospitalization costs. We also determined the most frequent ICD-9-CM diagnostic and procedural codes associated with SBS. RESULTS Children with SBS demonstrated a higher rate of mortality than that of children without SBS (1.6% vs 0.7%; P < .001). Children with SBS also experienced a longer length of stay (median days [interquartile range]: 8 [15] vs 2 [3]; P < .001) and higher hospital costs ($17,000 [$34,000] vs $3000 [$5000]; P < .001). The most frequent medical diagnoses associated with SBS were infection (62%), anemia (29%), and liver disease (17%). Children with SBS also demonstrated more severe illness as assessed by an All Patient Refined Diagnosis Related Group score of 3 or 4 (94.30% vs 16.20%; P < .001). CONCLUSIONS Children hospitalized with SBS have a high severity of illness and experience complicated inpatient courses related to their disease. Our study represents the first use of national U.S. data to study the epidemiology and health resource utilization associated with SBS.

Purpose To investigate the incidence and risk factors for the occurrence of cystoid macular edema (CME) after secondary posterior chamber intraocular lens (PC IOL) fixation. Setting Eye Clinic Herzog Carl Theodor, Munich, Germany. Design Retrospective case series. Methods Eyes with secondary PC IOL implantation were included. Eyes in Group 1 were treated because of preexisting aphakia; eyes in Group 2 had reimplantation or refixation of a failed primary PC IOL (Group 2). Patients were followed for at least 12 months with measurement of corrected distance visual acuity (CDVA) and central retinal thickness with optical coherence tomography (OCT). Risk factors for CME occurrence were evaluated with standard statistical procedures. Cutoff points of sensitivity and specificity were calculated for the prediction of CME with the receiver operating characteristic (ROC) method. Results Forty-two eyes of 40 patients (16 men, 24 women; mean age 75.4 years ± 13.7 [SD]) were included. There were 28 eyes in Group 1 and 14 eyes in Group 2. Seven eyes (16.7%) developed CME with significant impairment of CDVA and an increase in central retinal thickness on OCT. Five eyes in Group 1 and 2 eyes in Group 2 were affected, without a significant difference between groups. The CDVA after surgery had a significant influence, and there was a trend toward patient age as a risk factor. The ROC analysis yielded 83.9 years of age and a CDVA of 0.35 logMAR, respectively, as meaningful cutoff points. Conclusions Secondary PC IOL fixation was performed with good results despite the inherent CME risk from the procedure. Advanced age and poor CDVA after surgery might predict CME occurrence. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

A 10-yr-old female okapi (Okapia johnstoni) at the San Diego Zoo Safari Park was evaluated for intermittent malaise, inappetence, occasional cough, abdominal splinting, and licking at both flanks. Physical examination revealed tachypnea, tachycardia, and fluid sounds on thoracic auscultation. Transthoracic ultrasound showed multiple uniform, anechoic filled structures in the right and left pleural space. Surgical exploration of the thoracic cavity revealed bilateral, mature, fibrous, compartmentalizing adhesions between the visceral and parietal pleura, confirming a diagnosis of chronic, infectious, fibrinous pleuritis. The suspected etiology was occult aspiration pneumonia secondary to historical episodes of regurgitation associated with general anesthesia. Culture of the pleural fluid and fibrous adhesions grew Trueperella (Arcanobacterium) pyogenes, Arcanobacterium haemolyticum, and few Fusobacterium species. Treatment consisted of chest-tube placement to establish drainage, thoracic lavage, unilateral surgical debridement, and long-term antibiotics. The animal made a complete clinical recovery over 7 mo.

BACKGROUND Whereas disease surveillance for infectious diseases such as rubella is important, it is critical to identify pregnant women at risk of passing rubella to their offspring, which can be fatal and can result in congenital rubella syndrome (CRS). The traditional centralized model for diagnosing rubella is cost-prohibitive in resource-limited settings, representing a major obstacle to the prevention of CRS. As a step toward decentralized diagnostic systems, we developed a proof-of-concept digital microfluidic (DMF) diagnostic platform that possesses the flexibility and performance of automated immunoassay platforms used in central facilities, but with a form factor the size of a shoebox. METHODS DMF immunoassays were developed with integrated sample preparation for the detection of rubella virus (RV) IgG and IgM. The performance (sensitivity and specificity) of the assays was evaluated with serum and plasma samples from a commercial antirubella mixed-titer performance panel. RESULTS The new platform performed the essential processing steps, including sample aliquoting for 4 parallel assays, sample dilution, and IgG blocking. Testing of performance panel samples yielded diagnostic sensitivity and specificity of 100% and 100% for both RV IgG and RV IgM. With 1.8 μL sample per assay, 4 parallel assays were performed in approximately 30 min with CONCLUSIONS This proof of concept establishes DMF-powered immunoassays as being potentially useful for the diagnosis of infectious disease.

The guidelines published by Scientific Medical Societies in Germany are aids which have been systematically developed to assist physicians when making decisions in specific situations. The guidelines are based on current scientific knowledge and on established methods which have been proven in practice; the aim is to improve safety in medicine but also to take economic aspects into account. The guidelines are not legally binding for physicians and therefore the guidelines neither create liability nor do they constitute a release from liability. AWMF takes the greatest care when registering and publishing the guidelines of different scientific societies; nevertheless, AWMF cannot be held responsible for the accuracy of their contents. Please administer doses in accordance with manufacturerʼs instructions! © Deutsche Gesellschaft fur Gynakologie und Geburtshilfe Approved for electronic publication: AWMF online Date of compilation 02/2010 Revised 02/2014 Next planned revision 01/2017 Long version Vorgehen bei Terminuberschreitung und Ubertragung; AWMF Registry No. 015/065; classification: S1; effective: 28.02.2014, valid until January 31, 2017; www.awmf.org/ Guideline report Guideline report on the S1-Guideline 015/065: Vorgehen bei Terminuberschreitung und Ubertragung, effective: 02/2 014; http://www.awmf.org/ Statement of conflict of interest All members of the commission signed a statement on potential conflicts of interest. Potential CoI were assessed with regard to their relevance for the contents of the guidelines. The members reported having no contact to persons who might be relevant for the guideline. The CoI table can be viewed at http://www.awmf.org/. Slide show version Vorgehen bei Terminuberschreitung und Ubertragung. www.awmf.org/ Contributing professional societies and organizations Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften [Association of Scientific Medical Societies in Germany] Deutsche Gesellschaft fur Gynakologie und Geburtshilfe [German Society for Gynecology and Obstetrics] Arbeitsgemeinschaft Materno-fetale Medizin [Maternal Fetal Medicine Study Group] Deutsche Gesellschaft fur Perinatale Medizin [German Society for Perinatal Medicine] Osterreichische Gesellschaft fur Gynakologie und Geburtshilfe [Austrian Society for Gynecology and Obstetrics] Schweizerische Gesellschaft fur Gynakologie und Geburtshilfe [Swiss Society for Gynecology and Obstetrics] Authors of the last revised version PD Dr. Harald Abele, Tubingen, Germany Dr. Clemens Bartz, Saarbrucken, Germany Prof. Dr. Thorsten Fischer, Salzburg, Austria Dr. Maximilian Franz, Vienna, Austria Prof. Dr. Ulrich Gembruch, Bonn, Germany PD Dr. Markus Gonser, Wiesbaden, Germany Prof. Dr. Kurt Heim, Kirchdorf, Austria Prof. Dr. Franz Kainer, Nuremberg, Germany Dr. Annegret Kiefer, Heiligenstadt, Germany Dr. Klaus Konig, Steinbach, Germany Dr. Babette Ramsauer, Berlin, Germany PD Dr. Frank Reister, Ulm, Germany Prof. Dr. K. T. M. Schneider, Munich, Germany Prof. Dr. Daniel Surbek, Bern, Switzerland Prof. Dr. Klaus Vetter, Berlin, Germany Prof. Friedrich Wolff, Cologne, Germany PD Dr. Erich Weiss, Boblingen, Germany View it in a separate window