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Surgery is indeed one of the most fascinating medical professions. However, it is also a stressful field of work with a high workload, and often leaves little time for personal and family needs. Within the last decade, a noticeable decline occurred in the willingness of medical students to enter a surgical residency. In fact, Generation Y is highly interested in a medical career with a respectful working atmosphere and balanced work and private life, as published in several recent papers. Therefore, surgery must evolve with the times to retain its attractiveness as a career choice for medical students and to compete for the best talents from Generation Y. However, little is known about what senior surgeons really expect from young surgical residents. On the basis of a recent survey by the Professional Association of German Surgeons, this paper tries to give some insights in this very relevant topic and a perspective on how to increase the attractiveness of our fascinating specialty. In fact, in this survey, senior surgeons defined a very clear requirement profile for surgical residency applicants. While the colleagues defined accurate applicant documents, a previous internship, self-motivation, and impressions from the job interview as the most important factors for a successful application for a surgical residency, a standard period of study or a dissertation was deemed of lower importance.

Distance education courses have become popular due to the increased number of commuter students as well as people already in the workforce who need further education for advancement within their careers. A graduate-level Web-based course entitled Special Topics—Poultry Food Safety Microbiology was developed from an existing senior undergraduate advanced food microbiology course in the Poultry Science Department at Texas A&M University. Conversion of standard lecture material into a distance education course can provide unique challenges to maintain comparable course content in an asynchronous manner. The overall objective for this course was to examine bacterial activities including ecology in food, animals, raw and processed meat, eggs, and human pathogenesis. Students were surveyed at the end of the class and the majority agreed that they would be willing to take the course as an online course, although they were not willing to pay an extra fee for an online course. The majority of students used the online version of the course as a supplement to the classroom rather than as a substitute. [ABSTRACT FROM AUTHOR]

Reticuloendotheliosis virus (REV) and lymphoproliferative disease virus (LPDV) are avian retroviruses that can cause neoplastic disease and present with similar pathologies. Lymphoproliferative disease virus has been reported in the Eastern US and states bordering Texas, USA, but has not been previously detected within the state. In a prior study, we detected REV in native Rio Grande Wild Turkeys (Meleagris gallopavo intermedia) and an Eastern Wild Turkey (Meleagris gallopavo silvestris) originating from West Virginia. Given LPDV detection in states bordering Texas and our finding of an REV-positive Eastern Wild Turkey imported from a LPDV endemic region, we sought to determine LPDV prevalence in Texas and continue surveillance for REV. During 2018-20, dried blood spots from 373 individual Rio Grande Wild Turkeys from 20 different counties were tested for the presence of proviral REV or LPDV DNA. In affected counties, approximately 4% of individuals were infected with REV (7/197) or LPDV (10/273) and one bird was coinfected with both viruses. Phylogenetic analysis indicated a close relationship of the LPDV isolates to variants from other Southern and Central states. This study provides molecular evidence of LPDV in Texas, and continued surveillance is necessary to determine the potential effects of the virus on reproductive success, coinfections, and overall health of Wild Turkey populations., (© Wildlife Disease Association 2022.)

We report the genome sequence of a nearly intact reticuloendotheliosis virus (REV) insertion within a field strain of fowlpox virus from a Rio Grande wild turkey in Gillespie County, TX. The proviral REV genome comprises 7,943 bp and contains partial long terminal repeats.

Chronic wasting disease (CWD) is a prevalent prion disease affecting cervids. CWD is thought to be transmitted through direct animal contact or by indirect exposure to contaminated environmental fomites. Other mechanisms of propagation such as vertical and maternal transmissions have also been suggested using naturally and experimentally infected animals. Here, we describe the detection of CWD prions in naturally-infected, farmed white-tailed deer (WTD) fetal tissues using the Protein Misfolding Cyclic Amplification (PMCA) technique. Prion seeding activity was identified in a variety of gestational and fetal tissues. Future studies should demonstrate if prions present in fetuses are at sufficient quantities to cause CWD after birth. This data confirms previous findings in other animal species and furthers vertical transmission as a relevant mechanism of CWD dissemination., (© 2021. The Author(s).)

No proper treatment option for peri-implantitis exists yet. Based on previous studies showing the in vitro effectiveness of electrochemical disinfection using boron-doped diamond electrodes, novel double diamond electrodes (DDE) were tested here. Using a ceramic carrier and a laser structuring process, a clinically applicable electrode array was manufactured. Roughened metal discs ( n = 24) made from Ti-Zr alloy were exposed to the oral cavities of six volunteers for 24 h in order to generate biofilm. Then, biofilm removal was carried out either using plastic curettes and chlorhexidine digluconate or electrochemical disinfection. In addition, dental implants were contaminated with ex vivo multispecies biofilm and disinfected using DDE treatment. Bacterial growth and the formation of biofilm polymer were determined as outcome measures. Chemo-mechanical treatment could not eliminate bacteria from roughened surfaces, while in most cases, a massive reduction of bacteria and biofilm polymer was observed following DDE treatment. Electrochemical disinfection was charge- and time-dependent and could also not reach complete disinfection in all instances. Implant threads had no negative effect on DDE treatment. Bacteria exhibit varying resistance to electrochemical disinfection with Bacillus subtilis , Neisseria sp., Rothia mucilaginosa , Staphylococcus haemolyticus , and Streptococcus mitis surviving 5 min of DDE application at 6 V. Electrochemical disinfection is promising but requires further optimization with respect to charge quantity and application time in order to achieve disinfection without harming host tissue.

Reticuloendotheliosis virus (REV) is an immunosuppressive and sometimes oncogenic avian retrovirus that establishes lifelong infection in a wide range of avian species. REV-infected wild birds roaming near at-risk captive flocks, such as is the case for the highly endangered Attwater's Prairie Chicken (APC; Tympanuchus cupido attwateri ), could act as a reservoir for viral transmission. In wild birds, prevalence rates of REV are low and appearance of associated disease is uncommon. During 2016-17, nearly half of all captive adult APC mortality at Fossil Rim Wildlife Center captive breeding facility in Glen Rose, Texas, US was attributed to REV infection. The unusually high REV prevalence rate prompted us to survey for this virus in wild galliforms throughout the region. From 2016-17, 393 blood samples collected from two subspecies of Wild Turkeys ( Meleagris gallopavo ) were tested for REV proviral DNA through amplification of the viral 3' long terminal repeat and segments of the viral pol gene. In REV-affected counties, 5% (5/98) of native Rio Grande Wild Turkeys ( Meleagris gallopavo intermedia ) were identified as REV-positive. In addition, we detected REV in one of 62 Eastern Wild Turkeys ( Meleagris gallopavo silvestris ) that had been imported during conservation efforts. To better determine protective measures, continued surveillance, including collection and genetic analysis of REV-infected samples, is necessary to identify sources of REV outbreaks in captive APC flocks.

Study Design: Collagen fiber orientation analysis in moderately degenerated human cadaveric annulus fibrosus (AF) tissue samples., Objective: Little is known about the changes in tissue architecture during early degeneration of intervertebral disks (IVDs). As collagen organization strongly affects the disk function, the objective of this study was to quantify the AF collagen orientation and its spatial distribution in moderately degenerated IVDs (Pfirrmann grade III)., Methods: AF tissue samples were dissected from four circumferential (anterior, left and right lateral, and posterior) and two radial (outer and inner) locations. Cryosections were imaged using Second Harmonic Generation microscopy, and the collagen fiber orientations per location were determined utilizing a fiber-tracking image analysis algorithm. Also, the proportionality between the fibers aligned in the primary direction versus other oriented fibers was determined., Results: Mean collagen fiber angles ranged between 21 and 31 degrees for outer and 15 to 19 degrees for inner AF samples. Mean collagen orientations at circumferential locations were only significantly different from each other at inner anterior and lateral location. Similarly, fiber angles between the outer and inner AF were not significantly different except at the posterior location. Fiber orientation proportionality did not show large variations. Except for a significant difference in outer AF proportionality between posterior and lateral positions, no other differences were observed., Conclusion: The results of this study provide the first quantitative evidence that the collagen fiber orientation of moderately degenerated disks exhibits a spatial rather than homogeneous distribution and typical collagen orientation gradients characterizing healthy IVDs are only partially retained.

Genetic profiling of urine cell free DNA (cfDNA) has not been evaluated in advanced prostate cancer. We performed whole genome sequencing of urine cfDNAs to identify tumor-associated copy number variations in urine before and after initiating androgen deprivation therapy in HSPC stage and docetaxel chemotherapy in CRPC stage. A log2 ratio-based copy number analysis detected common genomic abnormalities in prostate cancer including AR amplification in 5/10 CRPC patients. Other abnormalities identified included TMPRSS2-ERG fusion, PTEN gene deletion, NOTCH1 locus amplification along with genomic amplifications at 8q24.3, 9q34.3, 11p15.5 and 14q11.2, and deletions at 4q35.2, 5q31.3, 7q36.3, 12q24.33, and 16p11.2. By comparing copy number between pre- and post-treatment, we found significant copy number changes in 34 genomic loci. To estimate the somatic tumor DNA fraction in urine cfDNAs, we developed a Urine Genomic Abnormality (UGA) score algorithm that summed the top ten most significant segments with copy number changes. The UGA scores correlated with tumor burden and the change in UGA score after stage-specific therapies reflected disease progression status and overall survival. The study demonstrates the potential clinical utility of urine cfDNAs in predicting treatment response and monitoring disease progression., Competing Interests: The authors declare that there is no conflict of interests.

Extracellular vesicles are selectively enriched in RNA that has potential as disease biomarkers. To systemically characterize circulating extracellular RNA (exRNA) profiles, we performed RNA sequencing analysis on plasma extracellular vesicles derived from 50 healthy individuals and 142 cancer patients. Of ~12.6 million raw reads for each individual, the number of mappable reads aligned to RNA references was ~5.4 million including miRNAs (~40.4%), piwiRNAs (~40.0%), pseudo-genes (~3.7%), lncRNAs (~2.4%), tRNAs (~2.1%), and mRNAs (~2.1%). By expression stability testing, we identified a set of miRNAs showing relatively consistent expression, which may serve as reference control for exRNA quantification. By performing multivariate analysis of covariance, we identified significant associations of these exRNAs with age, sex and different types of cancers. In particular, down-regulation of miR-125a-5p and miR-1343-3p showed an association with all cancer types tested (false discovery rate <0.05). We developed multivariate statistical models to predict cancer status with an area under the curve from 0.68 to 0.92 depending cancer type and staging. This is the largest RNA-seq study to date for profiling exRNA species, which has not only provided a baseline reference profile for circulating exRNA, but also revealed a set of RNA candidates for reference controls and disease biomarkers.

Objectives: Cell free tumor DNA (cfDNA) circulating in blood has a great potential as biomarker for cancer clinical management. The objective of this study is to evaluate if cfDNA in blood plasma is detectable in early stage lung cancer patients., Materials and Methods: We extracted cfDNAs and tumor tissue DNAs from 8 lung adenocarcinoma patients. We also extracted cfDNAs from 8 normal controls. To evaluate copy number variations (CNV) and identify potential mutations, we performed low pass whole genome sequencing and targeted sequencing of 50 cancer genes. To accurately reflect the tumor-associated genomic abnormality burden in plasma, we developed a new scoring algorithm, plasma genomic abnormality (PGA) score, by summarizing absolute log2 ratios in most variable genomic regions. We performed digital PCR and allele-specific PCR to validate mutations detected by targeted sequencing., Results and Conclusions: The median yield of cfDNA in 400 ul plasma was 4.9 ng (range 2.25-26.98 ng) in patients and 2.32 ng (range 1.30-2.81 ng) in controls (p=0.003). The whole genome sequencing generated approximately 20 million mappable sequence reads per subject and 5303 read counts per 1Mb genomic region. Log2 ratio-based CNV analysis showed significant chromosomal abnormality in cancer tissue DNAs and subtle but detectable differences in cfDNAs between patients and controls. Genomic abnormality analysis showed that median PGA score was 9.28 (7.38-11.08) in the 8 controls and 19.50 (5.89-64.47) in the 8 patients (p=0.01). Targeted deep sequencing in tumor tissues derived from the 8 patients identified 14 mutations in 12 different genes. The PCR-based assay confirmed 3 of 6 selected mutations in cfDNAs. These results demonstrated that the PGA score and cfDNA mutational analysis could be useful tool for the early detection of lung cancer. These blood-based genomic and genetic assays are noninvasive and may sensitively distinguish early stage disease when combined with other existing screening strategies including low-dose CT scanning., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Evidence that home telemonitoring for patients with chronic heart failure (CHF) offers clinical benefit over usual care is controversial as is evidence of a health economic advantage., Methods: Between January 2010 and June 2013, patients with a confirmed diagnosis of CHF were enrolled and randomly assigned to 2 study groups comprising usual care with and without an interactive bi-directional remote monitoring system (Motiva®). The primary endpoint in CardioBBEAT is the Incremental Cost-Effectiveness Ratio (ICER) established by the groups' difference in total cost and in the combined clinical endpoint "days alive and not in hospital nor inpatient care per potential days in study" within the follow-up of 12 months., Results: A total of 621 predominantly male patients were enrolled, whereof 302 patients were assigned to the intervention group and 319 to the control group. Ischemic cardiomyopathy was the leading cause of heart failure. Despite randomization, subjects of the control group were more often in NYHA functional class III-IV, and exhibited peripheral edema and renal dysfunction more often. Additionally, the control and intervention groups differed in heart rhythm disorders. No differences existed regarding risk factor profile, comorbidities, echocardiographic parameters, especially left ventricular and diastolic diameter and ejection fraction, as well as functional test results, medication and quality of life. While the observed baseline differences may well be a play of chance, they are of clinical relevance. Therefore, the statistical analysis plan was extended to include adjusted analyses with respect to the baseline imbalances., Conclusions: CardioBBEAT provides prospective outcome data on both, clinical and health economic impact of home telemonitoring in CHF. The study differs by the use of a high evidence level randomized controlled trial (RCT) design along with actual cost data obtained from health insurance companies. Its results are conducive to informed political and economic decision-making with regard to home telemonitoring solutions as an option for health care. Overall, it contributes to developing advanced health economic evaluation instruments to be deployed within the specific context of the German Health Care System., Trial Registration: ClinicalTrials.gov NCT02293252 ; date of registration: 10 November 2014.

Background: Extracellular microRNAs (miRNAs) embedded in circulating exosomes may serves as prognostic biomarkers in cancer., Objective: To identify and evaluate plasma exosomal miRNAs for prognosis in castration-resistant prostate cancer (CRPC)., Design, Setting, and Participants: RNA sequencing was performed to identify candidate exosomal miRNAs associated with overall survival in a screening cohort of 23 CRPC patients. Candidate miRNAs were further evaluated for prognosis using quantitative real-time polymerase chain reaction in a follow-up cohort of 100 CRPC patients., Outcome Measurements and Statistical Analysis: Cox regression and Kaplan-Meier survival analyses were used to evaluate survival association using candidate miRNAs along with clinical prognostic factors., Results and Limitations: RNA sequencing in screening cohort generated approximately 6.80 million mappable reads per patient. Of those with normalized read counts ≥ 5, 43% were mapped to miRNAs for a total of 375 known and 57 novel miRNAs. Cox regression analysis identified an association of miR-1290, -1246, and -375 with overall survival (false discover rate < 0.05). Of those, higher levels of miR-1290 and -375 were significantly associated with poor overall survival (p < 0.004) in the follow-up cohort. Incorporation of miR-1290/-375 into putative clinical prognostic factors-based models in CRPC stage significantly improved predictive performance with a time-dependent area under the curve increase from 0.66 to 0.73 (p = 6.57 × 10(-6))., Conclusions: Plasma exosomal miR-1290 and miR-375 are promising prognostic biomarkers for CRPC patients. Prospective validation is needed for further evaluation of these candidate miRNAs., Patient Summary: In this study, we evaluated whether small RNAs circulating in blood could be used to predict clinical outcomes in late-stage prostate cancer patients. We identified two blood-based small RNAs whose levels showed significant association with survival. Our results warrant further investigation because the noninvasive blood-based test has great potential in the management of late-stage prostate cancer., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Regenerative medicine approaches aiming at treating degenerating intervertebral discs, a major cause of back pain, are increasingly tested in ex-vivo disc explant models mimicking in-vivo conditions. For assessing the efficacy of regenerative therapies, cell viability is commonly measured requiring specific labels to stain cells. Here, we demonstrate and evaluate how cellular auto-fluorescence can be utilized to non-invasively assess viability in disc tissue in-situ using label-free two-photon microscopy. Live and dead bovine disc cells (0% and 100% cell viability) from the nucleus pulposus were seeded into collagen gels and auto-fluorescence was characterized. Subsequently, nucleus pulposus explants were cultured for 6 days in media with different glucose supplementation (0, 0.25, 0.5, and 1 g/L) to induce different degrees of cell death. Then, samples were split and viability was assessed using label-free two-photon microscopy and conventional staining. Results show that live and dead nucleus pulposus cells systematically emit auto-fluorescent light with distinct characteristics. Cell viability values obtained with label-free microscopy did not significantly differ from those acquired with staining. In summary, monitoring auto-fluorescence facilitates accurate cell viability assessment in nucleus tissue requiring no additional dyes. Thus, this technique may be suitable for pre-clinical testing of regenerative therapies in nucleus pulposus cultures. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:545-550, 2014., (© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Small noncoding RNAs that are 19-23 nucleotides long, known as microRNAs (miRNAs), are involved in almost all biological mechanisms during carcinogenesis. Recent studies show that miRNAs released from live cells are detectable in body fluids and may be taken up by other cells to confer cell-cell communication. These released miRNAs (here referred to as extracellular miRNAs) are often protected by RNA-binding proteins or embedded inside circulating microvesicles. Due to their relative stability, extracellular miRNAs are believed to be promising candidates as biomarkers for diagnosis and prognosis of disease, or even as therapeutic agents for targeted treatment. In this review, we first describe biogenesis and characteristics of these miRNAs. We then summarize recent publications involving extracellular miRNA profiling studies in three representative urologic cancers, including: prostate cancer, bladder cancer, and renal cell carcinoma. We focus on the diagnostic, prognostic, and therapeutic potential of these miRNAs in biological fluids, such as serum, plasma, and urine. Finally, we discuss advantages and challenges of these miRNAs in clinical applications.

After assessing cell viability (CV), tissue-engineered constructs are often discarded, as current CV assays commonly require specific (fluorescent) dyes to stain cells and may need scaffold/tissue digestion before quantifying the live and dead cells. Here, we demonstrate and evaluate how cellular auto-fluorescence can be exploited to facilitate a noninvasive CV estimation in three-dimensional scaffolds using two advanced microscopy methods. Mixtures of live and dead C2C12 myoblasts (0%, 25%, 50%, 75%, and 100% live cells) were prepared, and CV was determined before seeding cells into collagen carriers using the trypan blue (TB) assay. Cell-seeded collagen gels ([CSCGs], n=5/cell mixture) were produced by mixing collagen solution with the live/dead cell mixtures (7×10(6) cells/mL). After polymerization, two-photon microscopy (TPM) and confocal microscopy images of the CSCG were acquired (n=30 images/CSCG). It was found that live and dead cells systematically emit auto-fluorescent light with different spectral characteristics. Viable cells showed predominantly blue fluorescence with a peak emission around 470 nm, whereas dead cells appeared to mainly emit green fluorescent light with a peak intensity around 560 nm. For TPM, live and dead cells were distinguished spectrally. For confocal images, the intensity ratio of images taken with band-pass filters was used to distinguish live from dead cells. CV values obtained with both TPM and confocal imaging did not significantly differ from those acquired with the established TB method. In comparison to TPM, confocal microscopy was found to be less accurate in assessing the exact CV in constructs containing mostly live or dead cells. In summary, monitoring cellular auto-fluorescence using advanced microscopy techniques allows CV assessment requiring no additional dyes and/or scaffold digestion and, thus, may be especially suitable for tissue-engineering studies where CV is measured at multiple time points.