Microbial and metabolic succession on common building materials under high humidity conditions.

Despite considerable efforts to characterize the microbial ecology of the built environment, the metabolic mechanisms underpinning microbial colonization and successional dynamics remain unclear, particularly at high moisture conditions. Here, we applied bacterial/viral particle counting, qPCR, amplicon sequencing of the genes encoding 16S and ITS rRNA, and metabolomics to longitudinally characterize the ecological dynamics of four common building materials maintained at high humidity. We varied the natural inoculum provided to each material and wet half of the samples to simulate a potable water leak. Wetted materials had higher growth rates and lower alpha diversity compared to non-wetted materials, and wetting described the majority of the variance in bacterial, fungal, and metabolite structure. Inoculation location was weakly associated with bacterial and fungal beta diversity. Material type influenced bacterial and viral particle abundance and bacterial and metabolic (but not fungal) diversity. Metabolites indicative of microbial activity were identified, and they too differed by material

GRB Repetition Limits from Current BATSE Observations

Revised upper limits on gamma-ray burst repetition rates are found using the BATSE 3B and 4B catalogs. A statistical repetition model is assumed in which sources burst at a mean rate but in which BATSE observes bursts randomly from each source

Web-based patient-reported outcomes using the International Consortium for Health Outcome Measurement dataset in a major German university hospital: observational study

Background: Collecting patient-reported outcome (PRO) data systematically enables objective evaluation of treatment and its related outcomes. Using disease-specific questionnaires developed by the International Consortium for Health Outcome Measurement (ICHOM) allows for comparison between physicians, hospitals, and even different countries. Objective: This pilot project aimed to establish a digital system to measure PROs for new patients with breast cancer who attended the Charité Breast Center. This approach should serve as a blueprint to further expand the PRO measurement to other disease entities and departments. Methods: In November 2016, we implemented a Web-based system to collect PRO data at Charité Breast Center using the ICHOM dataset. All new patients at the Breast Center were enrolled and answered a predefined set of questions using a tablet computer. Once they started their treatment at Charité, automated emails were sent to the patients at predefined treatment points. Those emails contained a Web-based link through which they could access and answer questionnaires. Results: By now, 541 patients have been enrolled and 2470 questionnaires initiated. Overall, 9.4% (51/541) of the patients were under the age of 40 years, 49.7% (269/541) between 40 and 60 years, 39.6% (214/541) between 60 and 80 years, and 1.3% (7/541) over the age of 80 years. The average return rate of questionnaires was 67.0%. When asked about the preference regarding paper versus Web-based questionnaires, 6.0% (8/134) of the patients between 50 and 60 years, 6.0% (9/150) between 60 and 70 years, and 12.7% (9/71) over the age of 70 years preferred paper versions. Conclusions: Measuring PRO in patients with breast cancer in an automated electronic version is possible across all age ranges while simultaneously achieving a high return rate

Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease

Alzheimer’s disease (AD) is characterized by extracellular accumulation of amyloid-β peptide (Aβ), generated by proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. Aβ generation is inhibited when the initial ectodomain shedding is caused by α-secretase, cleaving APP within the Aβ domain. Therefore, an increase in α-secretase activity is an attractive therapeutic target for AD treatment. APP and the APP-cleaving secretases are all transmembrane proteins, thus local membrane lipid composition is proposed to influence APP processing. Although several studies have focused on γ-secretase, the effect of the membrane lipid microenvironment on α-secretase is poorly understood. In the present study, we systematically investigated the effect of fatty acid (FA) acyl chain length (10:0, 12:0, 14:0, 16:0, 18:0, 20:0, 22:0, 24:0), membrane polar lipid headgroup (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine), saturation grade and the FA double-bond position on α-secretase activity. We found that α-secretase activity is significantly elevated in the presence of FAs with short chain length and in the presence of polyunsaturated FAs, whereas variations in the phospholipid headgroups, as well as the double-bond position, have little or no effect on α-secretase activity. Overall, our study shows that local lipid membrane composition can influence α-secretase activity and might have beneficial effects for AD

Influence of interdisciplinary frailty screening on perioperative complication rates in elderly ovarian cancer patients : results of a retrospective observational study

Purpose: Frailty is a frequent and underdiagnosed multidimensional age-related syndrome, involving decreased physiological performance reserves and marked vulnerability against major stressors. To standardize the preoperative frailty assessment and identify patients at risk of adverse surgical outcomes, commonly used global health assessment tools were evaluated. We aimed to assess three interdisciplinary preoperative screening assessments to investigate the influence of frailty status with in-hospital complications irrespective of surgical complexity and radicality in older women with ovarian cancer (OC). Methods: Preoperative frailty status was examined by the G8 geriatric screening tool (G8 Score-geriatric screening), Eastern Cooperative Oncology Group performance status (ECOG PS-oncological screening), and American Society of Anesthesiologists Physical Status System (ASA PS-anesthesiologic screening). The main outcome measures were the relationship between perioperative laboratory results, intraoperative surgical parameters and the incidence of immediate postoperative in-hospital complications with the preoperative frailty status. Results: 116 consecutive women 60 years and older (BMI 24.8 ± 5.2 kg/m2) with OC, who underwent elective oncological surgery in University Medical Center Mainz between 2008 and 2019 were preoperatively classified with the selected global health assessment tools as frail or non-frail. The rate of preoperative anemia (hemoglobin ≤ 12 g/dl) and perioperative transfusions were significantly higher in the G8-frail group (65.9% vs. 34.1%; p = 0.006 and 62.7% vs. 41.8%, p = 0.031; respectively). In addition, patients preoperatively classified as G8-frail exhibited significantly more postoperative clinical in-hospital complications (27.8% vs. 12.5%, p = 0.045) independent of chronological age and BMI. In contrast, ECOG PS and ASA PS did not predict the rates of postoperative complications (all p values > 0.05). After propensity score matching, the complication rate in the G8-frail cohort was approximately 1.7 times more common than in the G8-non-frail cohort. Conclusion: Preoperative frailty assessment with the G8 Score identified elderly women with OC recording a significantly higher rate of postoperative in-hospital complications. In G8-frail patients, preoperative anemia and perioperative transfusions were significantly more recorded, regardless of chronological age, abnormal BMI and surgical complexity. Standardized preoperative frailty assessment should be added to clinical routine care to enhance risk stratification in older cancer individuals for surgical patient-centered decision-making

A novel grading approach predicts worse outcomes in stage pT1 non‐muscle‐invasive bladder cancer

Objective To develop a prognostically relevant scoring system for stage pT1 non-muscle-invasive bladder cancer (NMIBC) incorporating tumour budding, growth pattern and invasion pattern because the World Health Organisation grading system shows limited prognostic value in such patients. Patients and Methods The tissue specimens and clinical data of 113 patients with stage pT1 NMIBC who underwent transurethral resection of bladder tumour were retrospectively investigated. Tumour budding, and growth and invasion patterns were evaluated and categorised into two grade groups (GGs). GGs and other clinical and histopathological variables were investigated regarding recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS) using univariable and multivariable Cox regression analyses. Results The integration of two tumour budding groups, two growth patterns, and two invasion patterns yielded an unfavourable GG (n = 28; 24.7%) that had a high impact on oncological outcomes. The unfavourable GG was identified as an independent RFS and OS predictor (P = 0.004 and P = 0.046, respectively) and linked to worse PFS (P = 0.001) and CSS (P = 0.001), irrespective of the European Association of Urology risk group. The unfavourable GG was associated with higher rates of BCG-unresponsive tumours (P = 0.006). Study limitations include the retrospective, single-centre design, diverse therapies and small cohort. Conclusions We present a morphology-based grading system for stage pT1 NMIBC that correlates with disease aggressiveness and oncological patient outcomes. It therefore identifies a highest risk group of stage pT1 NMIBC patients, who should be followed up more intensively or receive immediate radical cystectomy. The grading incorporates objective variables assessable on haematoxylin and eosin slides and immunohistochemistry, enabling an easy-to-use low-cost approach that is applicable in daily routine. Further studies are needed to validate and confirm these results

Ureteroplasty with buccal mucosa graft without omental wrap: an effective method to treat ureteral strictures

Purpose Successful treatment options for ureteral strictures are limited. Surgical options such as ileal interposition and kidney autotransplantation are difficult and associated with morbidity and complications. Techniques such as Boari flap and psoas hitch are limited to distal strictures. Only limited case studies on the success of open buccal mucosa graft (BMG) ureteroplasty exist to this date. The purpose of this study was to evaluate the success of open BMG ureteroplasty without omental wrap. Methods In this single-center retrospective study between July 2020 and January 2023, we included 14 consecutive patients with ureteric strictures who were treated with open BMG ureteroplasty without omental wrap. The primary outcome was the success of open BMG ureteroplasty. Further endpoints were complications and hospital readmission. Outcome variables were assessed by clinical examination, kidney sonography, and patient anamnesis. Results Out of 14 patients, 13 were stricture and ectasia-free without a double-J stent at a median follow-up of 15 months (success rate 93%). No complications were observed at the donor site, and the complication rate overall was low with 3 out of 14 patients (21%) having mild-to-medium complications. Conclusions Open BMG ureteroplasty without omental wrap is a successful and feasible technique for ureteric stricture repair

Peripheral Nerve Regeneration–Adipose-Tissue-Derived Stem Cells Differentiated by a Three-Step Protocol Promote Neurite Elongation via NGF Secretion

The lack of supportive Schwann cells in segmental nerve lesions seems to be one cornerstone for the problem of insufficient nerve regeneration. Lately, adipose-tissue-derived stem cells (ASCs) differentiated towards SC (Schwann cell)-like cells seem to fulfill some of the needs for ameliorated nerve recovery. In this study, three differentiation protocols were investigated for their ability to differentiate ASCs from rats into specialized SC phenotypes. The differentiated ASCs (dASCs) were compared for their expressions of neurotrophins (NGF, GDNF, BDNF), myelin markers (MBP, P0), as well as glial-marker proteins (S100, GFAP) by RT-PCR, ELISA, and Western blot. Additionally, the influence of the medium conditioned by dASCs on a neuron-like cell line was evaluated. The dASCs were highly diverse in their expression profiles. One protocol yielded relatively high expression rates of neurotrophins, whereas another protocol induced myelin-marker expression. These results were reproducible when the ASCs were differentiated on surfaces potentially used for nerve guidance conduits. The NGF secretion affected the neurite outgrowth significantly. It remains uncertain what features of these SC-like cells contribute the most to adequate functional recovery during the different phases of nerve recovery. Nevertheless, therapeutic applications should consider these diverse phenotypes as a potential approach for stem-cell-based nerve-injury treatment

Body Composition as a Comorbidity-Independent Predictor of Survival following Nephroureterectomy for Urothelial Cancer of the Upper Urinary Tract

Radical nephroureterectomy (NUE) is the gold standard treatment for high-risk urothelial cancer of the upper urinary tract (UTUC). Besides sarcopenia and frailty, fat distribution is moving increasingly into focus. Components of body composition were assessed in patients undergoing NUE due to UTUC. The study cohort included 142 patients. By using CT-based measurements, the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured at the height of the third lumbar vertebra. Overall survival (OS) and cancer-specific survival (CSS) were estimated using univariable und multivariable Cox regression models. The prevalence of sarcopenia in the study population (n = 142) was 37%. OS and CSS were significantly reduced in sarcopenic patients. In the multivariable cox regression analysis, including age, ACE-27, T-stage, R-stage, LVI and necrosis, sarcopenia remained a significant risk factor of OS (HR, 1.77; 95% CI 1.02–3.07; p = 0.042) and CSS (HR, 2.17; 95% CI 1.18–3.99; p = 0.012). High visceral adipose tissue seems to be protective, although not statistically significant. Sarcopenia is a comorbidity-independent risk factor in patients who underwent NUE due to UTUC. Visceral fat represents a potentially protective factor. These results suggest that specific factors of body composition can be used for better risk stratification