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There is emerging but limited data assessing single-port (SP) robot-assisted surgery as an alternative to multi-port (MP) platforms. We compared perioperative outcomes between SP and MP robot-assisted approaches for excision of high and low complexity renal masses. Retrospective chart review was performed for patients undergoing robot-assisted partial or radical nephrectomy using the SP surgical system (n = 23) at our institution between November 2019 and November 2021. Renal masses were categorized as high complexity (7+) or low complexity (4–6) using the R.E.N.A.L. nephrometry scoring system. Adjusting for baseline characteristics, patients were matched using a prospectively maintained MP database in a 2:1 (MP:SP) ratio. For high complexity tumors (n = 12), SP surgery was associated with a significantly longer operative time compared to MP (248.4 vs 188.1 min, p = 0.02) but a significantly shorter length of stay (1.9 vs 2.8 days, p = 0.02). For low complexity tumors (n = 11), operative time (177.7 vs 161.4 min, p = 0.53), estimated blood loss (69.6.0 vs 142.0 mL, p = 0.62), and length of stay (1.6 vs 1.8 days, p = 0.528) were comparable between SP and MP approaches. Increasing nephrometry score was associated with a greater relative increase in operative time for SP compared to MP renal surgery (p = 0.07) using best of fit linear modeling. SP robot-assisted partial and radical nephrectomy is safe and feasible for low complexity renal masses. For high complexity renal masses, the SP system is associated with a significantly longer operative time compared to the MP technique. Careful consideration should be given when selecting patients for SP robot-assisted kidney surgery.

CO2 reduction (CO2RR) can convert CO2 into feedstock for the chemical industry. In aqueous CO2electrolysis a key challenge is how to combine the CO2 educt with a neutral or alkaline electrolyte andachieve a stable cell operation. We propose a novel cell design and operation mode based on a catalystcoated cation exchange membrane: a cationic acid (NH4+), with a volatile conjugate base (NH3), replacesthe protons usually present for ion transport. The approach avoids a high proton concentration at thecathode catalyst while still removing all products within the gas phase. In this paper different cell conceptsare investigated to identify a pathway to a stable, efficient and scalable operation mode. In a completelynovel cell design a FECO > 50% was already maintained for over 35 h at 50 mA cm−2, and at 200 mA cm−2a cell voltage of 3.6 V (FECO > 60%) was achieved. Surprisingly, ammonium oxidation at the anode was fullysupressed under the reaction conditions.

Usher syndrome (USH) is the most common form of hereditary deaf-blindness in humans. USH is a complex genetic disorder, assigned to three clinical subtypes differing in onset, course and severity, with USH1 being the most severe. Rodent USH1 models do not reflect the ocular phenotype observed in human patients to date; hence, little is known about the pathophysiology of USH1 in the human eye. One of the USH1 genes, USH1C, exhibits extensive alternative splicing and encodes numerous harmonin protein isoforms that function as scaffolds for organizing the USH interactome. RNA-seq analysis of human retinae uncovered harmonin_a1 as the most abundant transcript of USH1C. Bulk RNA-seq analysis and immunoblotting showed abundant expression of harmonin in Müller glia cells (MGCs) and retinal neurons. Furthermore, harmonin was localized in the terminal endfeet and apical microvilli of MGCs, presynaptic region (pedicle) of cones and outer segments (OS) of rods as well as at adhesive junctions between MGCs and photoreceptor cells (PRCs) in the outer limiting membrane (OLM). Our data provide evidence for the interaction of harmonin with OLM molecules in PRCs and MGCs and rhodopsin in PRCs. Subcellular expression and colocalization of harmonin correlate with the clinical phenotype observed in USH1C patients. We also demonstrate that primary cilia defects in USH1C patient-derived fibroblasts could be reverted by the delivery of harmonin_a1 transcript isoform. Our studies thus provide novel insights into PRC cell biology, USH1C pathophysiology and development of gene therapy treatment(s).

The standard discharge pathway following robotic-assisted laparoscopic prostatectomy (RALP) involves overnight hospital admission. Models for same-day discharge (SDD) have been explored for multiport RALP, however, less is known regarding SDD for single-port RALP, especially in terms of patient experience.Patient enrollment, based on preoperative determination of potential SDD eligibility, commenced March 2020 and ended March 2021. Day-of-surgery criteria were utilized to determine which enrolled patients underwent SDD. Differences in preoperative characteristics and perioperative outcomes between patients undergoing SDD and patients undergoing standard discharge were evaluated. A prospectively administered questionnaire was designed to characterize patient-centered factors informing SDD perception.Fifteen patients underwent SDD and 36 underwent standard discharge. Overall mean ± SD age and BMI were 63.6 ± 7.0 years and 29.7 ± 4.4 kg/mWith comparable outcomes to the standard discharge pathway, SDD is safe and effective in single-port RALP. Post-operative pain and perceptions of distance are implicated as patient-centered barriers to SDD; proactive pain management and patient education strategies may facilitate SDD.

Osteosarcoma (OS) is a molecularly heterogeneous, aggressive, poorly differentiated pediatric bone cancer that frequently spreads to the lung. Relatively little is known about phenotypic and epigenetic changes that promote lung metastases. To identify key drivers of metastasis, we studied human CCH-OS-D OS cells within a previously described rat acellular lung (ACL) model that preserves the native lung architecture, extracellular matrix, and capillary network. This system identified a subset of cells—termed derived circulating tumor cells (dCTCs)—that can migrate, intravasate, and spread within a bioreactor-perfused capillary network. Remarkably, dCTCs highly expressed epithelial-to-mesenchymal transition (EMT)-associated transcription factors (EMT-TFs), such as ZEB1, TWIST, and SOX9, which suggests that they undergo cellular reprogramming toward a less differentiated state by coopting the same epigenetic machinery used by carcinomas. Since YAP/TAZ and AXL tightly regulate the fate and plasticity of normal mesenchymal cells in response to microenvironmental cues, we explored whether these proteins contributed to OS metastatic potential using an isogenic pair of human OS cell lines that differ in AXL expression. We show that AXL inhibition significantly reduced the number of MG63.2 pulmonary metastases in murine models. Collectively, we present a laboratory-based method to detect and characterize a pure population of dCTCs, which provides a unique opportunity to study how OS cell fate and differentiation contributes to metastatic potential. Though the important step of clinical validation remains, our identification of AXL, ZEB1, and TWIST upregulation raises the tantalizing prospect that EMT-TF-directed therapies might expand the arsenal of therapies used to combat advanced-stage OS.

Desmoplastic small round cell tumor (DSRCT) is an aggressive, usually incurable sarcoma subtype that predominantly occurs in post-pubertal young males. Recent evidence suggests that the androgen receptor (AR) can promote tumor progression in DSRCTs. However, the mechanism of AR-induced oncogenic stimulation remains undetermined. Herein, we demonstrate that enzalutamide and AR-directed antisense oligonucleotides (AR-ASO) block 5α-dihydrotestosterone (DHT)-induced DSRCT cell proliferation and reduce xenograft tumor burden. Gene expression analysis and chromatin immunoprecipitation sequencing (ChIP-seq) were performed to elucidate how AR signaling regulates cellular epigenetic programs. Remarkably, ChIP-seq revealed novel DSRCT-specific AR DNA binding sites adjacent to key oncogenic regulators, including WT1 (the C-terminal partner of the pathognomonic fusion protein) and FOXF1. Additionally, AR occupied enhancer sites that regulate the Wnt pathway, neural differentiation, and embryonic organ development, implicating AR in dysfunctional cell lineage commitment. Our findings have direct clinical implications given the widespread availability of FDA-approved androgen-targeted agents used for prostate cancer.

Introduction The purpose of our study was to evaluate the benefit of bilateral inferior alveolar nerve block (BIANB) in managing postoperative pain, nausea and vomiting and opioid and antiemetic consumption in mandibular osteotomy. Material and methods 51 patients operated for bilateral sagittal split osteotomy (BSSO) were included in this prospective randomized controlled, double-blind, superiority trial. In the first group (n = 25), standard protocol was applied (general anesthesia and postoperative multimodal analgesia). The second group (n = 26) received bilateral inferior alveolar nerve block anesthesia at the start of surgery in addition to routine protocol. Postoperative monitoring was conducted every 4 h over the first 24 h and targeted the following criteria: postoperative nausea and vomiting (PONV), the visual analog scale (VAS) for pain, consumption of morphine (cumulative dose) and antiemetic agents, need for removal of guiding elastics. Results PONV was significantly lower in the BIANB group (15.4 % VS 40 %, p = 0.049), as were mean VAS scores for pain (1 VS 1.57, p = 0.045) and medians of morphine bolus (8 [6–16] VS 5.5 [1–8], p = 0.033). We found no significant difference in incidence of guiding elastic removal, and antiemetic consumption. Discussion The use of BIANB in BSSO improved postoperative patient comfort in terms of PONV and pain. Furthermore, it led to a decrease in opioid consumption. In conclusion, it is an additional therapeutic means of improving patients' postoperative comfort.

Numerical modeling provides an opportunity to quantify the reaction of lakes to alterations in their environment, such as changes in climate or hydrological conditions. The one-dimensional hydrodynamic General Lake Model (GLM) is an open-source software and widely used within the limnological research community. Nevertheless, no interface to process the input data and run the model and no tools for an automatic parameter calibration yet exist. Hence, we developed glmGUI, a graphical user interface (GUI) including a toolbox for an autocalibration, parameter sensitivity analysis, and several plot options. The tool is provided as a package for the freely available scientific code language R. The model parameters can be analyzed and calibrated for the simulation output variables water temperature and lake level. The glmGUI package is tested for two sites (lake Ammersee, Germany, and lake Baratz, Italy), distinguishing size, mixing regime, hydrology of the catchment area (i.e., the number of inflows and their runoff seasonality), and climatic conditions. A robust simulation of water temperature for both lakes (Ammersee: RMSE =1.17 ∘C; Baratz: RMSE =1.30 ∘C) is achieved by a quick automatic calibration. The quality of a water temperature simulation can be assessed immediately by means of a difference plot provided by glmGUI, which displays the distribution of the spatial (vertical) and temporal deviations. The calibration of the lake-level simulations of lake Ammersee for multiple hydrological inputs including also unknown inflows yielded a satisfactory model fit (RMSE =0.20 m). This shows that GLM can also be used to estimate the water balance of lakes correctly. The tools provided by glmGUI enable a less time-consuming and simplified parameter optimization within the calibration process. Due to this, i.e., the free availability and the implementation in a GUI, the presented R package expands the application of GLM to a broader field of lake modeling research and even beyond limnological experts.

Die Darmvorbereitung vor elektiven Kolonresektionen wird unterschiedlich durchgefuhrt. Ziel dieser Studie war es, den Einfluss verschiedener Darmvorbereitungen auf Wundinfektionen, Anastomoseninsuffizienzen und die postoperative Darmatonie in der elektiven Kolonchirurgie zu untersuchen. Wir fuhrten eine retrospektive Untersuchung von Patienten der eigenen Klinik mit elektiver Kolonresektion im Zeitraum 2013 bis 2019 durch. Die Patienten erhielten unterschiedliche Darmvorbereitungen und wurden in drei Gruppen eingeteilt: keine Darmspulung („MBP−“), orthograde Darmspulung ohne orale Antibiotikaprophylaxe („MBP+/OABP−“) und mit oraler Antibiotikaprophylaxe („MBP+/OABP+“). Die Gruppen wurden hinsichtlich folgender Parameter verglichen: Wundinfektionen, Anastomoseninsuffizienzen und Dauer bis zum ersten postoperativen Stuhlgang. Insgesamt 260 konsekutive Patienten („MBP−“: n = 48; „MBP+/OABP−“: n = 145; „MBP+/OABP+“: n = 67) gingen in die Analyse ein. Durch die kombinierte Darmvorbereitung konnte die Rate an SSI erheblich reduziert werden („MBP−“ vs. „MBP+/OABP+“: 16,7 % vs. 4,5 %, p = 0,05). In der multivariaten Analyse war die Darmvorbereitung der einzige Einflussfaktor auf Wundinfektionen. Dagegen hatte diese weder uni- noch multivariat Auswirkung auf die Rate an Anastomoseninsuffizienzen und die Dauer der postoperativen Darmatonie. Vor elektiven Kolonresektionen erweist sich das Vorbereitungsschema „MBP+/OABP+“ als vorteilhaft aufgrund deutlich geringerer Raten an Wundinfektionen.

Desmoplastic small round cell tumor (DSRCT) is an aggressive, usually incurable sarcoma subtype that predominantly occurs in post-pubertal young males. Recent evidence suggests that the androgen receptor (AR) can promote tumor progression in DSRCTs. However, the mechanism of AR-induced oncogenic stimulation remains undetermined. Herein, we demonstrate that enzalutamide and AR-directed antisense oligonucleotides (AR-ASO) block 5α-dihydrotestosterone (DHT)-induced DSRCT cell proliferation and reduce xenograft tumor burden. Gene expression analysis and chromatin immunoprecipitation sequencing (ChIP-seq) were performed to elucidate how AR signaling regulates cellular epigenetic programs. Remarkably, ChIP-seq revealed novel DSRCT-specific AR DNA binding sites adjacent to key oncogenic regulators, including WT1 (the C-terminal partner of the pathognomonic fusion protein) and FOXF1. Additionally, AR occupied enhancer sites that regulate the Wnt pathway, neural differentiation, and embryonic organ development, implicating AR in dysfunctional cell lineage commitment. Our findings have immediate clinical implications given the widespread availability of FDA-approved androgen-targeted agents used for prostate cancer.ONE SENTENCE SUMMARYWe demonstrate that DSRCT, an aggressive pediatric cancer, is an AR-driven malignancy capable of responding to androgen deprivation therapy.

DNA methylation age acceleration (DNAmAA, derived from an epigenetic clock) and relative leukocyte telomere length (rLTL) are widely accepted biomarkers of aging. Nevertheless, it is still unclear which aspects of aging they represent best. Here we evaluated longitudinal associations between baseline rLTL and DNAmAA (estimated with 7-CpG clock) and functional assessments covering different domains of aging. Additionally, we made use of cross-sectional data on these assessments and examined their association with DNAmAA estimated by 5 different DNAm age measures. Two-wave longitudinal data were available for 1 083 participants of the Berlin Aging Study II who were reexamined on average 7.4 years after baseline as part of the GendAge study. Functional outcomes were assessed with Fried’s frailty score, Tinetti mobility test, falls in the past 12 months (yes/no), finger-floor distance, Mini-Mental State Examination, Center for Epidemiologic Studies—Depression scale, activities of daily living, instrumented ADL, and mini nutritional assessment. Overall, we found no evidence for an association between the molecular biomarkers measured at baseline, rLTL, and DNAmAA (7-CpG clock), and functional assessments assessed at follow-up. Similarly, a cross-sectional analysis of follow-up data did also not show evidence for associations of the various DNAmAA measures (7-CpG clock, Horvath’s clock, Hannum’s clock PhenoAge, and GrimAge) with functional assessments. In conclusion, neither rLTL nor 7-CpG DNAmAA was able to predict impairment in the analyzed assessments over a ~7-year time course. Similarly, DNAmAA estimated from 5 epigenetic clocks was not a good cross-sectional marker of health deterioration either.

The ability of the body to maintain homeostasis requires constant communication between the brain and peripheral tissues. Different organs produce signals, often in the form of hormones, which are detected by the hypothalamus. In response, the hypothalamus alters its regulation of bodily processes, which is achieved through its own pathways of hormonal communication. The generation and transmission of the molecules involved in these bi-directional axes can be affected by redox balance. The essential trace element selenium is known to influence numerous physiological processes, including energy homeostasis, through its various redox functions. Selenium must be obtained through the diet and is used to synthesize selenoproteins, a family of proteins with mainly antioxidant functions. Alterations in selenium status have been correlated with homeostatic disturbances in humans and studies with animal models of selenoprotein dysfunction indicate a strong influence on energy balance. The relationship between selenium and energy metabolism is complicated, however, as selenium has been shown to participate in multiple levels of homeostatic communication. This review discusses the role of selenium in the various pathways of communication between the body and the brain that are essential for maintaining homeostasis.

Usher syndrome (USH) is the most common form of hereditary deafness-blindness in humans. USH is a complex genetic disorder, assigned to three clinical subtypes differing in onset, course, and severity, with USH1 being the most severe. Rodent USH1 models do not reflect the ocular phenotype observed in human patients to date; hence, little is known about the pathophysiology of USH1 in the human eye. One of the USH1 genes, USH1C, exhibits extensive alternative splicing and encodes numerous harmonin protein isoforms that function as scaffolds for organizing the USH interactome. RNA-seq analysis of human retinas uncovered harmonin_a1 as the most abundant transcript of USH1C. Bulk RNA-seq analysis and immunoblotting showed abundant expression of harmonin in Müller glia cells (MGCs) and retinal neurons. Furthermore, harmonin was localized in the terminal endfeet and apical microvilli of MGCs, presynaptic region (pedicle) of cones, and outer segments of rods as well as at adhesive junctions of MGCs and photoreceptors in the outer limiting membrane (OLM). Our data provide evidence for the interactions of harmonin with OLM molecules in photoreceptors (PRCs) and MGCs and rhodopsin in PRCs. Subcellular expression and colocalization of harmonin correlate with the clinical phenotype observed in USH1C patients. In addition, primary cilia defects in USH1C patient-derived fibroblasts could be reverted by the delivery of harmonin_a1 transcript isoform. Our data provide novel insights into PRC cell biology, USH1C pathophysiology, and for developing gene therapy treatment.

Background Preclinical data from a murine model of acute colitis suggest that dual blockade of interleukin(IL)-23 and TNFα more effectively prevented the development of colonic inflammation than each monotherapy. Guselkumab(GUS), an IL-23p19 subunit antagonist, is being studied in inflammatory bowel disease. Golimumab(GOL), a TNFα antagonist, is approved for ulcerative colitis(UC). The objective of this study was to evaluate the efficacy and safety of combination induction therapy with GUS+GOL vs GUS or GOL alone in adults with moderately-to-severely active UC. Methods 214 patients(pts) naïve to TNFα antagonists and refractory or intolerant to conventional therapy(ie, immunomodulators and/or corticosteroids) were randomly assigned to receive GUS 200mg intravenous(IV) at weeks(wks) 0, 4, and 8(n=71); GOL 200mg subcutaneous(SC) at wk0 then 100mg SC at wks2, 6, and 10(n=72); or combination with GUS 200mg IV+GOL 200mg SC at wk0, GOL 100mg SC at wks2, 6, and 10, and GUS 200mg IV at wks4 and 8(n=71). The primary endpoint was clinical response at wk12; the major secondary endpoint was clinical remission at wk12. Other key endpoints were clinical remission based on the modified Mayo score (mMayo), symptomatic remission, endoscopic improvement, endoscopic normalization, histologic remission, composite histologic-endoscopic endpoints, and biomarker outcomes. Results Baseline disease characteristics were similar among groups(Table 1), however a greater proportion of pts in both monotherapy groups had pancolitis vs the combination group. A greater proportion of pts who received combination therapy achieved clinical response at wk12(83.1%) vs GUS(74.6%) or GOL(61.1%)(Table 2). Similarly, the proportion of pts who achieved clinical remission in the combination group(36.6%) was greater than that of monotherapy groups(21.1% and 22.2%, respectively). Clinical remission by mMayo score, endoscopic improvement, histologic remission, both histologic remission and endoscopic improvement, and biomarker normalization (calprotectin, CRP) rates at wk12 were also greater in the combination group vs GUS or GOL. Percentages of pts with endoscopic normalization and both histologic remission and endoscopic normalization were nearly double with combination therapy vs either monotherapy. Adverse event(AE), serious AE, and infection rates were comparable among treatment groups. One pt receiving combination therapy experienced a serious infection of influenza and sepsis. No deaths, malignancies, or TB cases were reported through wk12. Conclusion Combination induction treatment with GUS+GOL more effectively induced clinical response, clinical remission, and endoscopic improvement at wk12 than either monotherapy alone. AE rates were comparable among the treatment groups.

Most diagnostic testing for West Nile virus (WNV) disease is accomplished using serologic testing, which is subject to cross-reactivity, may require cumbersome confirmatory testing, and may fail to detect infection in specimens collected early in the course of illness. The objective of this project was to determine whether a combination of molecular and serologic testing would increase detection of WNV disease cases in acute serum samples. A total of 380 serum specimens collected ≤7 days after onset of symptoms and submitted to four state public health laboratories for WNV diagnostic testing in 2014 and 2015 were tested. WNV immunoglobulin M (IgM) antibody and RT-PCR tests were performed on specimens collected ≤3 days after symptom onset. WNV IgM antibody testing was performed on specimens collected 4–7 days after onset and RT-PCR was performed on IgM-positive specimens. A patient was considered to have laboratory evidence of WNV infection if they had detectable WNV IgM antibodies or WNV RNA in the submitted serum specimen. Of specimens collected ≤3 days after symptom onset, 19/158 (12%) had laboratory evidence of WNV infection, including 16 positive for only WNV IgM antibodies, 1 positive for only WNV RNA, and 2 positive for both. Of specimens collected 4–7 days after onset, 21/222 (9%) were positive for WNV IgM antibodies; none had detectable WNV RNA. These findings suggest that routinely performing WNV RT-PCR on acute serum specimens submitted for WNV diagnostic testing is unlikely to identify a substantial number of additional cases beyond IgM antibody testing alone.

Purpose The purpose of this paper is to explore how Monte Carlo Simulation (MCS) could have enhanced understanding of the risks involved in the financial strategy for revitalization of Rio de Janeiro’s central city based on the capture of value generated by government interventions. Design/methodology/approach The study first describes the process involved in developing the financial strategy and model without MCS. Then, it shows how the MCS could have been integrated into this process and evaluates its potential impacts on the quality of risk analysis. Findings If MCS is fully integrated into the decision-making process, it can serve as a heuristic tool that helps team members to better understand risks by generating forecasts of land value and other variables as a probability distributions. By showing the variance of the forecasted variable, MCS integrates elements of modern risk analysis into financial model development in a cost-effective manner. Research limitations/implications MCS covers only the risks associated with the variables in the financial model. Events that seem extremely unlikely (i.e. “black swans”) can occur and must be assessed separately. Practical implications MCS can help analysts to understand the financial risks of large-scale development projects involving value capture, even in the prefeasibility stage. Social implications By facilitating value capture, MCS could help close the financing gap for sustainable urban development and subsidies for lower income families. Originality/value The study “retrofits” MCS on a successfully completed financial prefeasibility study to assess its usefulness as a heuristic tool.

OBJECTIVE To evaluate long-term outcomes and identify factors associated with death or the need for revision surgery in dogs with permanent tracheostomies (PTs). DESIGN Retrospective cohort study. ANIMALS 69 client-owned dogs that received a PT between January 2002 and June 2016 at 1 of 4 veterinary teaching hospitals. PROCEDURES Medical records were reviewed, and data extracted included signalment, history, clinical signs, radiographic and laryngeal examination findings, presence of esophageal abnormalities, date and reason for receiving a PT, postoperative complications, cause of death, and survival time. Dogs surviving < 2 weeks after receiving a PT were excluded. RESULTS Major complications occurred in 42 of 69 (61%) dogs, with aspiration pneumonia (13 [19%]), skinfold occlusion (13 [19%]), and stoma stenosis (12 [17%]) being most common. Revision surgery was performed in 24 of 69 (35%) dogs, most commonly because of stoma stenosis or skinfold occlusion (9/24 [38%] each). Brachycephalic dogs were more likely (OR, 3.5; 95% confidence interval, 1.2 to 10.2) to require revision surgery than were nonbrachycephalic dogs. The overall median survival time was 1,825 days, and dogs that received corticosteroids before receiving a PT, had tracheal collapse, or were older had shorter survival times. CONCLUSIONS AND CLINICAL RELEVANCE Results of the present study indicated that creation of a PT was a viable treatment option for obstructive upper airway diseases in dogs and that long-term survival after receiving a PT was possible; however, a PT may not reduce the risk of aspiration pneumonia in dogs.

The gold standard for the evaluation of liver fibrosis is histology. However, the heterogenous distribution of fibrosis limits the sensitivity of histology. The collection of two samples with a 16G needle is therefore recommended to reduce the risk of sampling error. The aim of this study was to investigate whether this standard is also applicable to patients with autoimmune hepatitis (AIH). This retrospective study included patients with AIH, who underwent mini-laparoscopic biopsy at our center between 2011 and 2020 (n = 32). Diagnosis was verified by usage of the simplified AIH score (≥ 6). Patients were categorized into three groups, based on the number of portal fields (PF) in the collected liver tissue (10 PF, 10 - 19 PF, ≥ 20 PF). We correlated the histological staging for these groups with the mini-laparoscopic fibrosis score (MLFS). Furthermore, non-invasive methods for the assessment of fibrosis were correlated with the histological staging (acoustic radiation force impulse (ARFI) and FIB-4 score). MLFS correlated well with histological staging (r = 0.649, p = 0.0001). The correlation between MLFS and histology improved with higher numbers of histologically analyzed portal fields (10 PF: r = 0.400, p = 0.378; 10 - 19 PF: r = 0.5467, p = 0.023; ≥ 20 PF: r = 0.956, p = 0.0002). The probability of collecting at least 10 or 20 portal fields was dependent on the number and diameter of the samples. For all patients with at least two 16G biopsies, 10 or more PF were available. With three 16G biopsies, at least 20 PF were obtained for all patients. ARFI correlated with MLFS and histological staging only in patients with low/moderate-grade inflammation as defined by ALT10xULN (upper limit of normal) (MLFS: r = 0.723; p = 0.004; histology: r = 0.619, p = 0.018). FIB-4 did not correlate with histological staging. The amount of liver tissue obtained by liver biopsy is crucial to minimalize the risk of sampling error and thus underestimation of fibrosis. This study was the first to investigate the amount of liver tissue required for histological staging in AIH. Our data suggest that diagnostic accuracy is likely to be higher with 20 PF compared to the generally recommended 10 PF. We therefore recommend to perform three biopsies with a 16G needle in (suspected) AIH patients. ARFI correlated well with histological staging unless inflammatory activity is high.

To determine whether androgen, estrogen, and/or progesterone signaling play a role in the pathophysiology of adherent perinephric fat (APF). We prospectively recruited patients undergoing robotic assisted partial nephrectomy during 2015-2017. The operating surgeon documented the presence or absence of APF. For those with clear cell renal cell carcinoma (ccRCC), representative sections of tumor and perinephric fat were immunohistochemically stained with monoclonal antibody to estrogen α, progesterone, and androgen receptors. Patient characteristics, operative data, and hormone receptor presence were compared between those with and without APF. Of 51 patients total, 18 (35.3%) and 33 (64.7%) patients did and did not have APF, respectively. APF was associated with history of diabetes mellitus (61.1% vs 24.2%, p = 0.009) and larger tumors (4.0 cm vs 3.0 cm, p = 0.017) but not with age, gender, BMI, Charleston comorbidity index, smoking, or preoperative estimated glomerular filtration rate. APF was not significantly associated with length of operation, positive margins, or 30-day postoperative complications but incurred higher estimated blood loss (236.5 mL vs 209.2 mL, p = 0.049). Thirty-two had ccRCC and completed hormone receptor staining. The majority of tumors and perinephric fat were negative for estrogen and progesterone while positive for androgen receptor expression. There was no difference in hormone receptor expression in either tumor or perinephric fat when classified by presence or absence of APF (p 0.05). APF is more commonly present in patients with diabetes or larger tumors but was not associated with differential sex hormone receptor expression in ccRCC.

Summary What role have batteries to play in the transition toward terawatt levels of photovoltaics? In this perspective, we attempt to answer this question by looking at technical, economic, and ecological features of PV-battery systems. We argue that the window of opportunity for batteries lies in the capacities of a few kWh/kWP, the exact amount depending on various factors including battery cost, degradation rate, location, load profile, diversification of renewable energy sources, and interconnections. Using a simple PV plus battery model, we illustrate that such storage capacities efficiently reduce fluctuations in electricity generation, enabling higher PV adoption rates at competitive costs, and with a carbon footprint that is at least five times lower than that of the current energy mixes. Using sensible capacities, batteries are a powerful companion for solar energy, yet technical, economic, and policy innovations are needed to expand adoption. We see longer battery lifetimes and low capacity degradation rates are the most impactful technological parameters. Economic efforts should aim to reduce balance of plant costs and create better market opportunities for stationary storage, whereas policies should provide a strong regulatory framework to facilitate multipurpose usage and sector coupling.

Bowel preparation is performed in different ways prior to elective colon surgery. The aim of this study was to evaluate the influence of different bowel preparations on surgical site infections, anastomotic leakage and postoperative ileus in elective colon surgery.A retrospective analysis was performed in this institution with patients who underwent elective colon surgery from 2013-2019. Patients received different types of bowel preparation and were divided into three different groups: no mechanical bowel preparation (MBP-), mechanical bowel preparation without oral antibiotics (MBP+/OABP-) and with oral antibiotics (MBP+/OABP+). These groups were compared with respect to surgical site infections, anastomotic leakage, and the duration of postoperative ileus.A total of 260 consecutive patients (MBP- n = 48, MBP+/OABP- n = 145 and MBP+/OABP+ n = 67) were analyzed. With a combined bowel preparation, the rate of surgical site infections could be considerably reduced (MBP- vs. MBP+/OABP+ 16.7% vs. 4.5%, p = 0.05). The type of bowel preparation was identified as the only factor associated with the incidence of surgical site infections; however, the type of bowel preparation did not have an influence on the rate of anastomotic leakages or duration of postoperative ileus in univariate and multivariate analyses.Bowel preparation with mechanical cleansing and oral antibiotics (MBP+/OABP+) is beneficial due to a significant reduction of surgical site infections.

Background Despite advances in the treatment of inflammatory bowel diseases (IBD), fewer than, 40% of patients reach clinical remission, suggesting that improved response rates may require targeting of multiple pathogenic pathways through combination therapy. However, the rational selection of combination therapies based on patient and pre-clinical data remains a significant challenge. Methods Here, we used Crohn’s disease (CD) patient-derived molecular networks as a platform for bridging pre-clinical animal models of combination therapy to human disease. Intestinal transcriptional signatures of anti-TNF, anti-IL-23 or combination treatments were generated from the anti-CD40 agonistic antibody murine colitis model and the murine genes mapped to their human orthologues. Humanized gene signatures were intersected with human disease networks to generate treatment subnetworks and enrichment analyses performed. Results The anti-TNF subnetwork was enriched in genes expressed in myeloid cells, chemokine signaling and NFkB signaling, while the anti-IL-23 subnetwork was enriched in genes expressed in the intestinal epithelium, IL-17 signaling, and cell adhesion. The intersection of these two therapeutic gene signature subnetworks was significantly enriched in IBD GWAS loci genes and human CD inflammatory gene signatures, suggesting that the molecular mechanisms reflected in the pre-clinical model faithfully captures aspects of the human disease. Simultaneous inhibition of these two pathways could result in enhanced efficacy through targeting shared inflammatory pathways and complementary biology in myeloid and epithelial cells to reduce colitis. To test this hypothesis, mice were treated with varying doses of anti-IL-23, anti-TNF, or the combination of both. A synergistic response to combination therapy was observed both in reduction of systemic weight loss and inhibition of local colonic tissue inflammation by histopathology. A set of genes uniquely significantly modulated by the combination therapy compared to either monotherapy was mapped to our human IBD network. Upregulated gene networks in the combination therapy enriched in stromal cells, epithelial mesenchymal transition and extracellular matrix pathways, and adhesion pathways while downregulated gene networks were enriched in IBD disease signatures, M1 macrophages, neutrophils and IFN-γ signaling. Conclusion These results provide a novel, data-driven approach to predict effective combination therapies for inflammatory diseases and suggest that anti-TNF and anti-IL-23 combination therapy may drive more patients into deep remission through impacts on both shared and unique molecular pathways involved in IBD pathogenesis.

Objective To report the outcome and owner satisfaction after planectomy for nasal planum neoplasia with cosmetic reconstruction with bilateral labial mucocutaneous rotation flaps in dogs. Study design Multi-institutional, retrospective case series. Animals Twenty-six client-owned dogs. Methods Medical records were searched for dogs that had undergone the procedure. Signalment, diagnosis, surgery, complications, requirement for revision surgery, recurrence, and survival information were recorded. Owners were contacted by telephone about their dog's quality of life after the procedure and their satisfaction with their dog's outcome. Results Twenty-five dogs underwent radical planectomy, and 1 dog underwent resection of the nasal planum. Twenty-four dogs had a diagnosis of squamous cell carcinoma, 1 had a diagnosis of atypical adenocarcinoma, and 1 had a diagnosis of a mast cell tumor. Complications occurred in 19 (73%) dogs, with 9 dogs requiring revision surgery; 1 dog not surviving to discharge. Median survival time was 1542 days (range, 3-2010). Recurrence of the primary tumor was suspected in 2 (7.7%) dogs, both with narrow or incomplete excision. Among 11 owners interviewed, 10 were satisfied with their dog's appearance, and 8 reported they would consent to the procedure again. Conclusion Dehiscence was common after this procedure, but local tumor control and survival times were excellent. Owner satisfaction was high, although preoperative client education is vital. Clinical significance This technique should be considered as a viable option for dogs with nasal planum neoplasia given the high rate of recurrence with less aggressive treatment. Complications common following surgery, but do not persist long term and survival times were excellent.

Patienten mit primar biliarer Cholangitis (PBC, vormals primar biliare Zirrhose) und unzureichendem Therapieansprechen oder Risikofaktoren haben ein deutlich erhohtes Risiko, dass die Erkrankung bis zur Leberzirrhose und deren Komplikationen fortschreitet. Ferner ist die Lebensqualitat zahlreicher Patienten aufgrund extrahepatischer Manifestationen teils deutlich reduziert. Dieser Beitrag gibt einen Uberblick uber die Standardbehandlung mit Ursodesoxycholsaure (UDCA) sowie weitergehende medikamentose Optionen bei unzureichendem Therapieansprechen. Daneben werden symptomorientierte Therapien praxisbezogen und kompakt dargestellt. Grundlage dieser Ubersichtsarbeit sind die neue europaische und deutsche Leitlinie aus dem Jahr 2017, daneben zahlreiche Grundlagenarbeiten sowie Expertenempfehlungen. Alle PBC-Patienten sollen lebenslang mit UDCA behandelt werden. Bei unzureichendem Therapieansprechen ist die Gallensaure Obeticholsaure (OCA) als Zweitlinientherapie seit 2016 zugelassen. Fibrate und Budesonid stellen Off-label-Alternativen dar. Pruritus sollte zunachst mit dem zugelassenen Colestyramin behandelt werden. Bei unzureichender Effizienz oder Unvertraglichkeit stellt Rifampicin die potenteste Off-label-Option dar. Hinsichtlich der Fatigue ist nach suffizienter Differenzialdiagnostik die Vermittlung von Coping-Strategien sinnvoll, auch regelmasige korperliche Ertuchtigung wirkt sich wahrscheinlich positiv aus. UDCA und OCA sind potente und zugelassene Therapeutika zur Behandlung der PBC. Patienten mit unzureichendem Therapieansprechen oder Risikofaktoren sollen konsequent behandelt werden. Durch die verbesserten Behandlungsoptionen bezuglich der Grunderkrankung rucken zunehmend Therapien zur Linderung von Fatigue und Pruritus in den Vordergrund.

With the increasing share of fluctuating renewables in power grids the need for, but also the value of, electrical energy storage is identified. Particularly advanced battery systems such as lithium ion offer various opportunities: they can be designed to be highly modular and are therefore flexible in usage and they offer comparably high efficiency as well as long calendar and cycle life times. Typical examples of such grid connected stationary applications are described in this chapter. These include small residential as well as commercial battery storage for increased self-consumption and self-sufficiency. The principles of system design and the integration of the key components such as inverter and energy management are described for such applications. Furthermore, test results of market available products show the achievements but also the remaining optimization potential, which has to be addressed in future developments. In particular, in the field of commercial and industrial applications, bankability and insurability are key for mass market dissemination. Therefore critical topics such as safety, reliability as well as performance are discussed in this chapter.

Microorganisms are well adapted to their habitat but are partially sensitive to toxic metabolites or abiotic compounds secreted by other organisms or chemically formed under the respective environmental conditions. Thermoacidophiles are challenged by pyroglutamate, a lactam that is spontaneously formed by cyclization of glutamate under aerobic thermoacidophilic conditions. It is known that growth of the thermoacidophilic crenarchaeon Saccharolobus solfataricus (formerly Sulfolobus solfataricus) is completely inhibited by pyroglutamate. In the present study, we investigated the effect of pyroglutamate on the growth of S. solfataricus and the closely related crenarchaeon Sulfolobus acidocaldarius. In contrast to S. solfataricus, S. acidocaldarius was successfully cultivated with pyroglutamate as a sole carbon source. Bioinformatical analyses showed that both members of the Sulfolobaceae have at least one candidate for a 5-oxoprolinase, which catalyses the ATP-dependent conversion of pyroglutamate to glutamate. In S. solfataricus, we observed the intracellular accumulation of pyroglutamate and crude cell extract assays showed a less effective degradation of pyroglutamate. Apparently, S. acidocaldarius seems to be less versatile regarding carbohydrates and prefers peptidolytic growth compared to S. solfataricus. Concludingly, S. acidocaldarius exhibits a more efficient utilization of pyroglutamate and is not inhibited by this compound, making it a better candidate for applications with glutamate-containing media at high temperatures.

To what extent could greater municipal fiscal effort on the real estate property and transfer taxes (IPTU and ITBI) and greater use of betterment levies help to close the financing gap for infrastructure and social programs? To address this question, we develop a Fiscal Effort Index (FEI) that “controls for” the effects of fiscal capacity indicators by calibrating a model with 2010 data from Brazilian municipalities with 50,000 or more inhabitants. We then simulate total potential revenue using different fiscal effort scenarios and analyze the correlations of this index with socioeconomic indicators. Finally, we discuss cases where technical assistance and financial incentives (Parana and Campo Grande, MS) have increased municipal fiscal effort. Municipalities ranking the top quartile showed FEIs 48% or more higher than the benchmarks, suggesting room for improvement for municipalities with lower fiscal effort.