Comparative analysis of Bricker versus Wallace ureteroenteric anastomosis and identification of predictors for postoperative ureteroenteric stricture.

PURPOSE: Ureteroenteric anastomosis after cystectomy is usually performed using the Bricker or Wallace technique. Deterioration of renal function is the most common long-term complication of urinary diversion (UD). To improve surgical care and optimize long-term renal function, we compared the Bricker and Wallace anastomotic techniques and identified risk factors for ureteroenteric strictures (UES) in patients after cystectomy. MATERIAL AND METHODS: Retrospective, monocentric analysis of 135 patients who underwent cystectomy with urinary diversion at the University Hospital Essen between January 2015 and June 2019. Pre- and postoperative renal function, relevant comorbidities, prior chemo- or radiotherapy, pathological findings, urinary diversion, postoperative complications, and ureteroenteric strictures (UES) were analyzed. RESULTS: Of all 135 patients, 69 (51.1%) underwent Bricker anastomosis and 66 (48.9%) Wallace anastomosis. Bricker and Wallace groups included 134 and 132 renal units, respectively. At a median follow-up of 14 (6-58) months, 21 (15.5%) patients and 30 (11.27%) renal units developed UES. We observed 22 (16.6%) affected renal units in Wallace versus 8 (5.9%) in Bricker group (p < 0.001). A bilateral stricture was most common in Wallace group (69.2%) (p < 0.001). Previous chemotherapy and 90-day Clavien-Dindo grade ≥ III complications were independently associated with stricture formation, respectively (OR 9.74, 95% CI 2-46.2, p = 0.004; OR 4.01, 95% CI 1.36-11.82, p = 0.013). CONCLUSION: The results of this study show no significant difference in ureteroenteric anastomotic techniques with respect to UES development regarding individual patients but suggest a higher risk of bilateral UES formation in patients undergoing Wallace anastomosis. This is reflected in the increased UES rate under consideration of the individual renal units.

Complications and satisfaction in transwomen receiving breast augmentation: short- and long-term outcomes.

BACKGROUND: To achieve long-term improvement in health care of transgender women, it is necessary to analyze all aspects of gender-confirming surgery, especially the relation of risks and benefits occurring in these procedures. While there are many studies presenting data on the urologic part of the surgery, there are just few data about complications and satisfaction with breast augmentation. METHODS: This is a retrospective study using parts of the BREAST-Q Augmentation Questionnaire and additional questions for symptoms of capsular contracture and re-operations and analyzing archived patient records of all transwomen which were operated at University Hospital Essen from 2007 to 2020. RESULTS: 99 of these 159 patients (62%) completed the questionnaire after a median time of 4 years after surgery. Breast augmentation led to re-operations due to complications in 5%. The rate of capsular contracture (Baker Grad III-IV) in this population was 3%. Most patients (75%) rated high scores of satisfaction with outcome (more than 70 points) and denied to have restrictions due to their implants in their everyday life. All patients reported an improvement in their quality of life owing to breast augmentation. CONCLUSION: Breast augmentation by inserting silicon implants is a safe surgical procedure which takes an important part in reducing gender dysphoria.

Transrectal Ultrasound Guided Hydrodistension - A New Surgical Way in Transgender Surgery.

BACKGROUND: Creating the neovaginal canal in transwomen is one of the most delicate steps of Genital Gender Affirming Surgery (GGAS). Injury to the rectum is a rare but serious complication that can lead to further surgery and even creation of a colostomy. AIM: Implementation of a novel hydrospacing technique (HST) based on transrectal ultrasound (TRUS)-guided hydrodistension. METHODS: Between June 2018 and June 2020 54 transwomen received GGAS with HST. Immediately before GGAS transperineal hydrodistension was performed using a TSK-Supra-Needle (20 Gauge, 120 mm length), that was placed under direct TRUS-guided visual control between Denonvilliers' fascia and the anterior rectal wall. 40 - 60 ml normal saline were administered perineally to separate Denonvilliers' fascia from the anterior rectal wall to create a dissection of at least 20 mm. For better intraoperative visualization the hydrodissected space was also dyed using 2ml of methylenblue while retracting the needle. A retrospectively analysed, clinically and demographically comparable series of 84 transwomen who underwent GGAS between June 2016 and June 2018 served as control group. All 138 surgeries were performed by the same experienced surgeon. OUTCOMES: The effect of the novel hydrospacing technique on neovaginal dimensions and operating time. RESULTS: Patients in both groups did not differ in baseline patient characteristics such as age and body mass index (HST 35 vs 38 years in control group, P = .44 and body mass index 26 vs 25 kg/m2, P = .73). Vaginal depth and width were significantly larger in the HST subgroup as compared to controls (14.4 cm vs 13.5 cm, P = .01 and 4.2 cm vs 3.8 cm, P < .001). No statistically significant difference occurred in intraoperative rectal injury (n = 0 in HST group, n = 2 in control group, P = .26). Median total OR-time was comparable for GGAS including HST before vaginoplasty to standard technique (211 minutes for HST vs 218 minutes; P = 0.19). CLINICAL IMPLICATIONS: The proposed additional surgical step during GGAS is minimally invasive and safe, simplifies GGAS and potentially helps to avoid complications such as rectal injury. STRENGTH & LIMITATIONS: Single-surgeon series, limited follow-up time and no prospective randomization. CONCLUSION: HST is a safe and feasible procedure, which facilitates a safe preparation of the neovaginal canal during male to female GGAS. Panic A, Rahmani N, Kaspar C, et al. Transrectal Ultrasound Guided Hydrodistension - A New Surgical Way in Transgender Surgery. J Sex Med 2021;18:1135-1141.

M0CRPC overview of management options.

Though prostate cancer usually responds to androgen deprivation therapy (ADT) in the beginning, the majority of prostate cancers will develop castration resistance over time. The androgen receptor (AR) pathway is often found to be activated in castration resistant prostate cancer (CRPC). Thus, AR signalling remains a therapeutic target upon the development of CRPC. The term M0CRPC is used when ADT leads to castration resistance and there are no metastases detectable by means of conventional imaging. Until recently, there was no therapeutic standard for this group of patients. With the PROSPER-, SPARTAN- and ARAMIS-studies three large placebo-controlled phase III trials have been published lately that showed a significant benefit in metastasis-free survival in men with M0CRPC and short PSA doubling time (PSADT). The efficacy data are very similar in these studies, meaning that the drugs' safety profiles, final analyses of overall survival and their availability will be more important to help clinicians decide which of these three drugs they use for their patients with M0CRPC.

A systematic review of the effects of temperature and precipitation on pollen concentrations and season timing, and implications for human health.

Climate and weather directly impact plant phenology, affecting airborne pollen. The objective of this systematic review is to examine the impacts of meteorological variables on airborne pollen concentrations and pollen season timing. Using PRISMA methodology, we reviewed literature that assessed whether there was a relationship between local temperature and precipitation and measured airborne pollen. The search strategy included terms related to pollen, trends or measurements, and season timing. For inclusion, studies must have conducted a correlation analysis of at least 5 years of airborne pollen data to local meteorological data and report quantitative results. Data from peer-reviewed articles were extracted on the correlations between seven pollen indicators (main pollen season start date, end date, peak date, and length, annual pollen integral, average daily pollen concentration, and peak pollen concentration), and two meteorological variables (temperature and precipitation). Ninety-three articles were included in the analysis out of 9,679 articles screened. Overall, warmer temperatures correlated with earlier and longer pollen seasons and higher pollen concentrations. Precipitation had varying effects on pollen concentration and pollen season timing indicators. Increased precipitation may have a short-term effect causing low pollen concentrations potentially due to "wash out" effect. Long-term effects of precipitation varied for trees and weeds and had a positive correlation with grass pollen levels. With increases in temperature due to climate change, pollen seasons for some taxa in some regions may start earlier, last longer, and be more intense, which may be associated with adverse health impacts, as pollen exposure has well-known health effects in sensitized individuals.

MK-8719, a Novel and Selective O-GlcNAcase Inhibitor That Reduces the Formation of Pathological Tau and Ameliorates Neurodegeneration in a Mouse Model of Tauopathy.

Deposition of hyperphosphorylated and aggregated tau protein in the central nervous system is characteristic of Alzheimer disease and other tauopathies. Tau is subject to O-linked N-acetylglucosamine (O-GlcNAc) modification, and O-GlcNAcylation of tau has been shown to influence tau phosphorylation and aggregation. Inhibition of O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc moieties, is a novel strategy to attenuate the formation of pathologic tau. Here we described the in vitro and in vivo pharmacological properties of a novel and selective OGA inhibitor, MK-8719. In vitro, this compound is a potent inhibitor of the human OGA enzyme with comparable activity against the corresponding enzymes from mouse, rat, and dog. In vivo, oral administration of MK-8719 elevates brain and peripheral blood mononuclear cell O-GlcNAc levels in a dose-dependent manner. In addition, positron emission tomography imaging studies demonstrate robust target engagement of MK-8719 in the brains of rats and rTg4510 mice. In the rTg4510 mouse model of human tauopathy, MK-8719 significantly increases brain O-GlcNAc levels and reduces pathologic tau. The reduction in tau pathology in rTg4510 mice is accompanied by attenuation of brain atrophy, including reduction of forebrain volume loss as revealed by volumetric magnetic resonance imaging analysis. These findings suggest that OGA inhibition may reduce tau pathology in tauopathies. However, since hundreds of O-GlcNAcylated proteins may be influenced by OGA inhibition, it will be critical to understand the physiologic and toxicological consequences of chronic O-GlcNAc elevation in vivo. SIGNIFICANCE STATEMENT: MK-8719 is a novel, selective, and potent O-linked N-acetylglucosamine (O-GlcNAc)-ase (OGA) inhibitor that inhibits OGA enzyme activity across multiple species with comparable in vitro potency. In vivo, MK-8719 elevates brain O-GlcNAc levels, reduces pathological tau, and ameliorates brain atrophy in the rTg4510 mouse model of tauopathy. These findings indicate that OGA inhibition may be a promising therapeutic strategy for the treatment of Alzheimer disease and other tauopathies.

[Mutation signatures in head and neck squamous cell carcinoma : Pathogenesis and therapeutic potential]. / Mutationssignaturen beim Kopf- und Hals-Tumor : Pathogenese und Potenzial für die Therapie.

BACKGROUND: The pathogenesis of head and neck squamous cell carcinoma (HNSCC) is a complex and multistage process which results from the interaction of exogenous and endogenous cellular processes. Each of these processes leaves a characteristic pattern of mutations on the tumor genome, a so-called mutational signature. STATE OF THE ART: The subject of current studies is to decipher specific signatures of mutational processes operating during HNSCC pathogenesis and to address their prognostic value. Computational analysis of genomic sequencing data by The Cancer Genome Atlas (TCGA) revealed mutational signatures 1, 2, 4, 5, 7, and 13 as the main players in HNSCC pathogenesis. Signature 16 was first discovered in human papillomavirus (HPV)-negative oral and oropharyngeal tumors. In many studies, an association of signature 16 with alcohol and tobacco consumption as well as with an unfavorable prognosis was described.

Why is there selective subcortical vulnerability in ADHD? Clues from postmortem brain gene expression data.

Sub-cortical volumetric differences were associated with attention-deficit/hyperactivity disorder (ADHD) in a recent multi-site, mega-analysis of 1713 ADHD persons and 1529 controls. As there was a wide range of effect sizes among the sub-cortical volumes, it is possible that selective neuronal vulnerability has a role in these volumetric losses. To address this possibility, we used data from Allen Brain Atlas to investigate variability in gene expression profiles between subcortical regions of typically developing brains. We tested the hypothesis that the expression of genes in a set of curated ADHD candidate genes and five a priori selected, biological pathways would be associated with the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) findings. Across the subcortical regions studied by ENIGMA, gene expression profiles for three pathways were significantly correlated with ADHD-associated volumetric reductions: apoptosis, oxidative stress and autophagy. These correlations were strong and significant for children with ADHD, but not for adults. Although preliminary, these data suggest that variability of structural brain anomalies in ADHD can be explained, in part, by the differential vulnerability of these regions to mechanisms mediating apoptosis, oxidative stress and autophagy.

Neuregulin-1 (NRG1) polymorphisms linked with psychosis transition are associated with enlarged lateral ventricles and white matter disruption in schizophrenia.

BACKGROUND: Two single-nucleotide polymorphisms (SNPs) (rs4281084 and rs12155594) within the neuregulin-1 (NRG1) gene have been associated with psychosis transition. However, the neurobiological changes associated with these SNPs remain unclear. We aimed to determine what relationship these two SNPs have on lateral ventricular volume and white matter integrity, as abnormalities in these brain structures are some of the most consistent in schizophrenia. METHODS: Structural (n = 370) and diffusion (n = 465) magnetic resonance imaging data were obtained from affected and unaffected individuals predominantly of European descent. The SNPs rs4281084, rs12155594, and their combined allelic load were examined for their effects on lateral ventricular volume, fractional anisotropy (FA) as well as axial (AD) and radial (RD) diffusivity. Additional exploratory analyses assessed NRG1 effects on gray matter volume, cortical thickness, and surface area throughout the brain. RESULTS: Individuals with a schizophrenia age of onset ⩽25 and a combined allelic load ⩾3 NRG1 risk alleles had significantly larger right (up to 50%, p adj = 0.01) and left (up to 45%, p adj = 0.05) lateral ventricle volumes compared with those with allelic loads of less than three. Furthermore, carriers of three or more risk alleles, regardless of age of onset and case status, had significantly reduced FA and elevated RD but stable AD in the frontal cortex compared with those carrying fewer than three risk alleles. CONCLUSIONS: Our findings build on a growing body of research supporting the functional importance of genetic variation within the NRG1 gene and complement previous findings implicating the rs4281084 and rs12155594 SNPs as markers for psychosis transition.

A high plasma: red blood cell transfusion ratio during liver transplantation is associated with decreased blood utilization.

BACKGROUND: During massive transfusion, the volume ratio of administered plasma (PL Vol) to red blood cell (RBC Vol) appears to be associated with reduced blood utilization and improved survival. The aim of this study was to evaluate the optimal component ratio in the setting of liver transplantation. METHODS: This is a retrospective chart review of patients who underwent liver transplantation and received at least 500 ml of red blood cells from January 2013 through December 2015. Kernel smoothing analysis determined the proper component ratios to evaluate were a ≥0·85:1 ratio (high) to a ≤0·85:1 ratio (low). Two groups, plasma volume to RBC volume (PL Vol/RBC Vol) and plasma contained in the platelet units added to the plasma calculation [PL + PLT (platelet)] Vol/RBC Vol, were used to evaluate the component ratios. RESULTS: A total of 188 patients were included in the analysis. In the PL Vol/RBC Vol evaluation, a low ratio revealed that 1238 ml (977-1653 ml) (P < 0·0001) and 1178 ml (747-1178) (P < 0·0001) of RBC were used in excess compared to the high ratio, in the univariable and multivariable analysis, respectively. In the PL +PLT Vol/RBC Vol evaluation, a low ratio used 734 ml (193-1275) (P = 0·008) and 886 ml (431-1340) (P < 0·0001) of RBC in excess when compared to high ratio in the univariable and multivariable analysis, respectively. CONCLUSION: In patients undergoing liver transplantation, the transfusion of plasma to RBC ratio ≥0·85 was associated with decreased need of RBC transfusions.

A data-driven patient blood management strategy in liver transplantation.

BACKGROUND AND OBJECTIVES: Blood utilization during liver transplant has decreased, but remains highly variable due to many complex surgical and physiologic factors. Previous models attempted to predict utilization using preoperative variables to stratify cases into two usage groups, usually using entire blood units for measurement. We sought to develop a practical predictive model using specific transfusion volumes (in ml) to develop a data-driven patient blood management strategy. MATERIALS AND METHODS: This is a retrospective evaluation of primary liver transplants at a single institution from 2013 to 2015. Multivariable analysis of preoperative recipient and donor factors was used to develop a model predictive of intraoperative red-blood-cell (pRBC) use. RESULTS: Of 256 adult liver transplants, 207 patients had complete transfusion volume data for analysis. The median intraoperative allogeneic pRBC transfusion volume was 1250 ml, and the average was 1563 ± 1543 ml. Preoperative haemoglobin, spontaneous bacterial peritonitis, preoperative haemodialysis and preoperative international normalized ratio together yielded the strongest model predicting pRBC usage. When it predicted <1250 ml of pRBCs, all cases with 0 ml transfused were captured and only 8·6% of the time >1250 ml were used. This prediction had a sensitivity of 0·91 and a specificity of 0·89. If predicted usage was >2000 ml, 75% of the time blood loss exceeded 2000 ml. CONCLUSION: Patients likely to require low or high pRBC transfusion volumes were identified with excellent accuracy using this predictive model at our institution. This model may help predict bleeding risk for each patient and facilitate optimized blood ordering.

Correlation of Venous Blood Gas and Pulse Oximetry With Arterial Blood Gas in the Undifferentiated Critically Ill Patient.

RATIONALE: Blood gas analysis is often used to assess acid-base, ventilation, and oxygenation status in critically ill patients. Although arterial blood gas (ABG) analysis remains the gold standard, venous blood gas (VBG) analysis has been shown to correlate with ABG analysis and has been proposed as a safer less invasive alternative to ABG analysis. OBJECTIVE: The purpose of this study was to evaluate the correlation of VBG analysis plus pulse oximetry (SpO2) with ABG analysis. METHODS: We performed a prospective cohort study of patients in the emergency department (ED) and intensive care unit (ICU) at a single academic tertiary referral center. Patients were eligible for enrollment if the treating physician ordered an ABG. Statistical analysis of VBG, SpO2, and ABG data was done using paired t test, Pearson χ2, and Pearson correlation. MAIN RESULTS: There were 156 patients enrolled, and 129 patients completed the study. Of the patients completing the study, 53 (41.1%) were in the ED, 41 (31.8%) were in the medical ICU, and 35 (27.1%) were in the surgical ICU. The mean difference for pH between VBG and ABG was 0.03 (95% confidence interval: 0.03-0.04) with a Pearson correlation of 0.94. The mean difference for pCO2 between VBG and ABG was 4.8 mm Hg (95% confidence interval: 3.7-6.0 mm Hg) with a Pearson correlation of 0.93. The SpO2 correlated well with PaO2 (the partial pressure of oxygen in arterial blood) as predicted by the standard oxygen-hemoglobin dissociation curve. CONCLUSION: In this population of undifferentiated critically ill patients, pH and pCO2 on VBG analysis correlated with pH and pCO2 on ABG analysis. The SpO2 correlated well with pO2 on ABG analysis. The combination of VBG analysis plus SpO2 provided accurate information on acid-base, ventilation, and oxygenation status for undifferentiated critically ill patients in the ED and ICU.

A splicing-regulatory polymorphism in DRD2 disrupts ZRANB2 binding, impairs cognitive functioning and increases risk for schizophrenia in six Han Chinese samples.

The rs1076560 polymorphism of DRD2 (encoding dopamine receptor D2) is associated with alternative splicing and cognitive functioning; however, a mechanistic relationship to schizophrenia has not been shown. Here, we demonstrate that rs1076560(T) imparts a small but reliable risk for schizophrenia in a sample of 616 affected families and five independent replication samples totaling 4017 affected and 4704 unaffected individuals (odds ratio=1.1; P=0.004). rs1076560(T) was associated with impaired verbal fluency and comprehension in schizophrenia but improved performance among healthy comparison subjects. rs1076560(T) also associated with lower D2 short isoform expression in postmortem brain. rs1076560(T) disrupted a binding site for the splicing factor ZRANB2, diminished binding affinity between DRD2 pre-mRNA and ZRANB2 and abolished the ability of ZRANB2 to modulate short:long isoform-expression ratios of DRD2 minigenes in cell culture. Collectively, this work implicates rs1076560(T) as one possible risk factor for schizophrenia in the Han Chinese population, and suggests molecular mechanisms by which it may exert such influence.

Clinical and laboratory correlates of platelet alloimmunization and refractoriness in the PLADO trial.

BACKGROUND AND OBJECTIVES: Platelet alloimmunization and refractoriness to platelet transfusion are complications of platelet transfusion therapy. The platelet dose (PLADO) trial, as the largest prospective randomized trial of prophylactic platelet therapy to date, afforded an opportunity to analyse these two issues. MATERIALS AND METHODS: PLADO patient records were examined for evidence of platelet alloimmunization, defined as an increase in HLA Class I panel-reactive antibodies (PRA) to ≥20%, and clinical refractoriness, defined as two consecutive ≤4 h posttransfusion corrected platelet count increments (CCI) of <5000. Multivariate logistic regression, restricted to platelet-transfused subjects who received exclusively either in-process leucoreduction apheresis or whole blood-derived (WBD) leucocyte-reduced platelets, compared the frequency of these outcomes by platelet unit and patient characteristics. RESULTS: Forty of 816 evaluable platelet-transfused patients (5%) became alloimmunized during the trial. Prior pregnancy, chemotherapy only compared to progenitor cell transplant, and low platelet dose - all were associated with significantly higher rates of alloimmunization. Among 35 alloimmunized patients evaluated for refractoriness, 8 (23%) had two consecutive CCI < 5000/µl. Regardless of alloimmunization status, CCIs < 5000/µl were observed following 17% of platelet transfusions. Among 734 patients receiving at least two platelet transfusions, two consecutive CCIs of ≤5000 occurred in 102 (14%). CONCLUSIONS: The incidence of new platelet alloimmunization was low in the PLADO study, but follow-up was at most 30 days. Alloimmunization was present in only 8 of 102 (8%) of observed cases of refractoriness, suggesting that other causes of poor posttransfusion increments are frequent.

Management characteristics, lameness, and body injuries of dairy cattle housed in high-performance dairy herds in Wisconsin.

The objective of this study was to benchmark the prevalence of lameness, hock and knee injuries, and neck and back injuries among high-performance, freestall-housed dairy herds in Wisconsin. A random selection of 66 herds with 200 or more cows was derived from herds that clustered with high performance in year 2011 Dairy Herd Improvement records for milk production, udder health, reproduction, and other health parameters. Herds were surveyed to collect information about management, facilities, and well-being. Well-being measures were obtained through direct observation of the high-producing mature cow group, surveying 9,690 cows in total. Total herd size averaged (mean ± standard deviation) 851±717 cows, ranging 203 to 2,966 cows, with an energy-corrected milk production of 40.1±4.4kg/cow per day. Prevalence of clinical lameness (5-point scale, locomotion score ≥3) and severe lameness (locomotion score ≥4) averaged 13.2±7.3 and 2.5±2.7%, respectively. The prevalence of all hock and knee injuries, including hair loss, swelling, and ulceration, was similar at 50.3±28.3 and 53.0±24.0%, respectively. Severe (swelling and ulceration) hock and knee injury prevalence were 12.2±15.3 and 6.2±5.5%, respectively. The prevalence of all neck injuries (including hair loss, swelling and ulceration) was 8.6±16.3%; whereas the prevalence of swollen or abraded necks was low, averaging 2.0±4.1%. Back injuries (proportion of cows with missing or abraded spinous processes, hooks, or pins) followed a similar trend with a low mean prevalence of 3.6±3.4%. Overall, physical well-being characteristics of this selection of high-producing, freestall-housed dairy herds provide evidence that lameness and injury are not inevitable consequences of the confinement housing of large numbers of dairy cattle. In particular, lameness prevalence rivals that of lower-production grazing systems. However, hock and other injury risk remains a concern that can be addressed through a choice in stall surface type. Use of deep, loose bedding yielded significant advantages over a mat or mattress type surface in terms of lameness, hock and knee injury, and proportion of cows with dirty udders (distinct demarcated to confluent plaques of manure). The performance benchmarks achieved by these herds may be used to set standards by which similarly managed herds may be judged using welfare audit tools.

[Preclinical models in head and neck tumors : Evaluation of cellular and molecular resistance mechanisms in the tumor microenvironment]. / Präklinische Modelle für Kopf-Hals-Tumoren : Aufklärung zellulärer und molekularer Resistenzmechanismen im Gewebekontext.

Because head and neck squamous cell carcinomas (HNSCC) are characterized by a distinct intertumorigenic and intratumorigenic heterogeneity, they often show substantial differences in the response to established therapy strategies. At present, a multitude of biologics and new pharmacological compounds for targeted therapies are available that allow more efficient and less toxic treatment. There is increasing pressure to establish predictive assays not only for ex ante analysis of the individual patient response to combined chemoradiotherapy and targeted therapies but also for investigation of the efficacy of new drugs. In this respect it is essential to maintain the pathophysiological tissue composition as it is known that paracrine tumor-stroma cell interactions may influence tumor reactivity to treatment. More complex models for individualized sensitivity testing have recently been described and the results are promising to pave the way for personalized cancer therapy. This review article focuses on different systems for maintaining the tumor microenvironment and hence the individual cellular composition, such as 3D organotypic models, organotypic multicellular spheroids, patient-derived xenografts and ex vivo tissue cultures and discusses the advantages and disadvantages in terms of translation into clinical application.

[Diabetes mellitus as a prognostic marker in oropharyngeal and laryngeal squamous cell carcinoma]. / Diabetes mellitus als prognostischer Marker beim Oropharynx- und Larynxkarzinom.

Recent experimental and clinical studies have provided compelling evidence that diabetes mellitus (DM) is an important risk factor in various cancers, and may affect both pathogenesis and prognosis. Additionally, antidiabetic agents such as metformin exhibit an antitumorigenic effect. However, to date there is insufficient knowledge about the role of DM in the pathogenesis and prognosis of head and neck squamous cell carcinoma (HNSCC).In a retrospective monocentric study including 424 patients with SCC of the oropharynx (OPSCC) or larynx (LaSCC), the impact of DM on clinical and histopathologic parameters was investigated. The authors found a rising incidence of DM among LaSCC patients (<10 % until 2005 and 20 % since 2006) and a significant association between DM and clinical and histopathologic features (age, gender, tumor size, and pathologic grading), which depended on the anatomic site. Moreover, a clear trend toward unfavorable progression-free and overall survival of HNSCC patients with DM upon current treatment modalities was evident.The presented data support a relative increase in patients with DM, particularly for LaSCC. This might have a sustained influence on treatment decisions and management, and should be considered in future clinical trials. A better understanding of the cellular and molecular traits of HNSCC in DM could pave the way for innovative therapeutic strategies in terms of personalized medicine.

Survey of facility and management characteristics of large, Upper Midwest dairy herds clustered by Dairy Herd Improvement records.

A survey of management practices was conducted to investigate potential associations with groupings of herds formed by cluster analysis (CA) of Dairy Herd Improvement (DHI) data of 557 Upper Midwest herds of 200 cows or greater. Differences in herd management practices were identified between the groups, despite underlying similarities; for example, freestall housing and milking in a parlor. Group 6 comprised larger herds with a high proportion of primiparous cows and most frequently utilized practices promoting increased production [e.g., 84.4% used recombinant bovine somatotropin (rbST)], decreased lameness (e.g., 96.9% used routine hoof trimming for cows), and improved efficiency in reproduction [e.g., 93.8% synchronized the first breeding in cows (SYNCH)] and labor (e.g., mean ± SD, 67 ± 19 cows per 50-h per week full-time equivalent worker). Group 1 had the best mean DHI performances and followed most closely group 6 for the rate of adoption of intensive management practices while tending to outperform group 6 despite a generally smaller mean herd size (e.g., 42.3 ± 3.6 kg vs. 39.9 ± 3.6 kg of energy-corrected milk production; 608 ± 352 cows vs. 1,716 ± 1,405 cows). Group 2 were smaller herds with relatively high levels of performance that used less intensive management (e.g., 100% milked twice daily) and less technology (33.3 vs. 73.0% of group 1 used rbST). Group 4 were smaller but poorer-performing herds with low turnover and least frequently used intensive management practices (e.g., 39.1% SYNCH; 30.4% allowed mature, high-producing cows access to pasture). Group 5 used modern technologies and practices associated with improved production, yet had the least desirable mean DHI performance of all 6 groups. This group had the lowest proportion of deep loose-bedded stalls (only 52.2% used sand bedding) and the highest proportion (34.8%) of herds not using routine hoof trimming. The survey of group 3 herds did not reveal strong trends in management. The differences identified between herd groupings confirm significant variation in management practices linked to variation in overall herd performance measured by DHI variables. This approach provides an opportunity for consultants and outreach educators to better tailor efforts toward a certain type of dairy management philosophy, rather than taking a blanket approach to applying recommendations to farms simply because of their larger herd size.

Apparent ileal amino acid digestibility of reduced-oil distillers dried grains with solubles fed to broilers from 23 to 31 days of age.

An experiment was conducted using male Ross×Ross 708 broiler chicks to determine the effect of oil extraction from corn distillers dried grains with solubles on apparent ileal amino acid digestibility from 23 to 31 d of age. On an as-fed basis, ether extract concentrations were determined as 5.4% (L-distillers dried grains with solubles), 7.9% (M-distillers dried grains with solubles), and 10.5% (H-distillers dried grains with solubles) for the 3 experimental distillers dried grains with solubles sources. Prior to experimentation, each sample (H-distillers dried grains with solubles (control), M-distillers dried grains with solubles and L-distillers dried grains with solubles) was analyzed on an as-fed basis for crude protein (29.2, 27.6, and 27.9%), starch (4.4, 5.2, and 6.1%), neutral detergent fiber (29.5, 33.2, and 29.9%), and total dietary fiber (31.4, 36.6, and 33.6 %). Four hundred and thirty-two male chicks (12 birds per cage; 0.04 m2 per bird) were randomly assigned to 36 battery grower cages. Broilers were fed one of 3 semi-purified diets, which were comprised of 76% L-distillers dried grains with solubles, M- distillers dried grains with solubles, or H-distillers dried grains with solubles as the sole amino acid source from 23 to 31 d of age. Apparent ileal amino acid digestibility coefficients were negatively affected (P<0.05) by oil extraction for Met (0.722, 0.788, and 0.791), Lys (0.504, 0.510, and 0.552), Thr (0.563, 0.566, and 0.612), Trp (0.708, 0.733, and 0.767), and Arg (0.762, 0.776, and 0.799) for L-distillers dried grains with solubles, M-distillers dried grains with solubles, and H-distillers dried grains with solubles, respectively. Conversely, no differences in apparent amino acid coefficients were reported for Ile, Leu, and Val. These results indicated that L-distillers dried grains with solubles had lower apparent amino acid digestibility coefficients for Met, Lys, Thr, Trp, and Arg compared with H-distillers dried grains with solubles.

Opportunities and Challenges in the Design and Analysis of Biomass Supply Chains.

The biomass supply chain is one of the most critical elements of large-scale bioenergy production and in many cases a key barrier for procuring initial funding for new developments on specific energy crops. Most productions rely on complex transforming chains linked to feed and food markets. The term 'supply chain' covers various aspects from cultivation and harvesting of the biomass, to treatment, transportation, and storage. After energy conversion, the product must be delivered to final consumption, whether it is in the form of electricity, heat, or more tangible products, such as pellets and biofuels. Effective supply chains are of utmost importance for bioenergy production, as biomass tends to possess challenging seasonal production cycles and low mass, energy and bulk densities. Additionally, the demand for final products is often also dispersed, further complicating the supply chain. The goal of this paper is to introduce key components of biomass supply chains, examples of related modeling applications, and if/how they address aspects related to environmental metrics and management. The paper will introduce a concept of integrated supply systems for sustainable biomass trade and the factors influencing the bioenergy supply chain landscape, including models that can be used to investigate the factors. The paper will also cover various aspects of transportation logistics, ranging from alternative modal and multi-modal alternatives to introduction of support tools for transportation analysis. Finally gaps and challenges in supply chain research are identified and used to outline research recommendations for the future direction in this area of study.