[Urogenital tumors following kidney transplantation-monocentric analysis of incidences and overview of urological preventive measures]. / Urogenitale Tumoren nach Nierentransplantation ­ monozentrische Aufarbeitung der Inzidenzen und Überblick urologischer Vorsorgemaßnahmen.

BACKGROUND: Urogenital tumors are among the most common solid malignancies after kidney transplantation (TX). OBJECTIVE: We analyzed the incidence and mortality of urogenital tumors after kidney TX in our own patient population as well as answered the question of recommended follow-up necessity and frequency in this cohort. MATERIALS AND METHODS: Retrospective monocentric data collection of tumor diseases and the most common urogenital tumors after kidney TX at the Transplant Center Dresden between 2010 and 2020 was done. From this, we derived recommendations for a useful follow-up concept. RESULTS: A total of 13% (93/710) of kidney TX patients developed a neoplasm. Older patients (60.1 ± 10.6 vs. 53.8 ± 12.5; p < 0.001), with higher Charlson scores (≥ 4: 68% vs. 46%; p < 0.001) and a previous tumor history (18% vs. 8%; p < 0.001) were more likely to develop a neoplasm after transplantation. In the multivariate analysis, previous tumor history was found to be an independent predictor of tumor development after renal transplantation (OR 2.2; 95%-KI [1.2-4.1]; p = 0.01). Urogenital tumors accounted for 30% (28/93) of all malignancies. Renal cell carcinoma of the native kidney was the most common (n = 12) neoplasm, followed by prostate cancer (n = 9). CONCLUSION: Most solid malignancies after kidney TX arise from the urinary tract. Due to their frequency, there is an urgent need for specialized urological therapy and long-term follow-up care. Even before listing for TX, risk factors can be recognized and individual concepts for follow-up care can be developed.

[Organ donation in Germany under the new legislation]. / Organspende in Deutschland im Zeichen der neuen Gesetzgebung.

The political debate concerning organ donations reached increased public awareness from 2012, despite the multiple scandals around organ allocation. The process of organ donation has been restructured since financing improved by the GZSO (Gesetz für bessere Zusammenarbeit und bessere Strukturen bei der Organspende). The focus should be reduction of deficits in donor identification and notification within hospitals. Hence, it is time to introduce an "opt-out" solution, a system already standard in other European countries. Finally, to increase in the much-needed organ donations within Germany a multistructured concept should be established: improving hospital pathways, staff recognition, public awareness and political support.

The Early Psychosis Screener (EPS): Item development and qualitative validation.

A panel of experts assembled and analyzed a comprehensive item bank from which a highly sensitive and specific early psychosis screener could be developed. Twenty well-established assessments relating to the prodromal stage, early psychosis, and psychosis were identified. Using DSM-5 criteria, we identified the core concepts represented by each of the items in each of the assessments. These granular core concepts were converted into a uniform set of 490 self-report items using a Likert scale and a 'past 30days' time frame. Partial redundancy was allowed to assure adequate concept coverage. A panel of experts and TeleSage staff rated these items and eliminated 189 items, resulting in 301 items. The items were subjected to five rounds of cognitive interviewing with 16 individuals at clinically high risk for psychosis and 26 community mental health center patients. After each round, the expert panel iteratively reviewed, rated, revised, added, or deleted items to maximize clarity and centrality to the concept. As a result of the interviews, 36 items were revised, 52 items were added, and 205 items were deleted. By the last round of cognitive interviewing, all of the items were clearly understood by all participants. In future work, responses to the final set of 148 items and machine learning techniques will be used to quantitatively identify the subset of items that will best predict clinical high-risk status and conversion.

[Management of urological complications after renal transplantation]. / Behandlung urologischer Komplikationen nach Nierentransplantation.

Urological complications after kidney transplantation can cause a major reduction in renal function. Surgical complications like urinary leakage and ureteral obstruction need to be solved by a specialist in the field of endourological procedures and open surgical interventions. The article summarizes this and other common urological problems after kidney transplantation.

Comparative evaluation of the Bio-Rad Geenius HIV-1/2 Confirmatory Assay and the Bio-Rad Multispot HIV-1/2 Rapid Test as an alternative differentiation assay for CLSI M53 algorithm-I.

INTRODUCTION: The CLSI-M53-A, Criteria for Laboratory Testing and Diagnosis of Human Immunodeficiency Virus (HIV) Infection; Approved Guideline includes an algorithm in which samples that are reactive on a 4th generation EIA screen proceed to a supplemental assay that is able to confirm and differentiate between antibodies to HIV-1 and HIV-2. The recently CE-marked Bio-Rad Geenius HIV-1/2 Confirmatory Assay was evaluated as an alternative to the FDA-approved Bio-Rad Multispot HIV-1/HIV-2 Rapid Test which has been previously validated for use in this new algorithm. METHODS: This study used reference samples submitted to the Canadian - NLHRS and samples from commercial sources. Data was tabulated in 2×2 tables for statistical analysis; sensitivity, specificity, predictive values, kappa and likelihood ratios. RESULTS: The overall performance of the Geenius and Multispot was very high; sensitivity (100%, 100%), specificity (96.3%, 99.1%), positive (45.3, 181) and negative (0, 0) likelihood ratios respectively, high kappa (0.96) and low bias index (0.0068). The ability to differentiate HIV-1 (99.2%, 100%) and HIV-2 (98.1%, 98.1%) Ab was also very high. CONCLUSION: The Bio-Rad Geenius HIV-1/2 Confirmatory Assay is a suitable alternative to the validated Multispot for use in the second stage of CLSI M53 algorithm-I. The Geenius has additional features including traceability and sample and cassette barcoding that improve the quality management/assurance of HIV testing. It is anticipated that the CLSI M53 guideline and assays such as the Geenius will reduce the number of indeterminate test results previously associated with the HIV-1 WB and improve the ability to differentiate HIV-2 infections.

Human mitochondrial tRNAs in health and disease.

The human mitochondrial genome encodes 13 proteins, all subunits of the respiratory chain complexes and thus involved in energy metabolism. These genes are translated by 22 transfer RNAs (tRNAs), also encoded by the mitochondrial genome, which form the minimal set required for reading all codons. Human mitochondrial tRNAs gained interest with the rapid discovery of correlations between point mutations in their genes and various neuromuscular and neurodegenerative disorders. In this review, emerging fundamental knowledge on the structure/function relationships of these particular tRNAs and an overview of the large variety of mechanisms within translation, affected by mutations, are summarized. Also, initial results on wide-ranging molecular consequences of mutations outside the frame of mitochondrial translation are highlighted. While knowledge of mitochondrial tRNAs in both health and disease increases, deciphering the intricate network of events leading different genotypes to the variety of phenotypes requires further investigation using adapted model systems.

Manipulation of tRNA properties by structure-based and combinatorial in vitro approaches.

The wide knowledge accumulated over the years on the structure and function of transfer RNAs (tRNAs) has allowed molecular biologists to decipher the rules underlying the function and the architecture of these molecules. These rules will be discussed and the implications for manipulating tRNA properties by structure-based and combinatorial in vitro approaches reviewed. Since most of the signals conferring function to tRNAs are located on the two distal extremities of their three-dimensional L shape, this implies that the structure of the RNA domain connecting these two extremities can be of different architecture and/or can be modified without disturbing individual functions. This concept is first supported by the existence in nature of RNAs of peculiar structures having tRNA properties, as well as by engineering experiments on natural tRNAs. The concept is further illustrated by examples of RNAs designed by combinatorial methods. The different procedures used to select RNAs or tRNA-mimics interacting with aminoacyl-tRNA synthetases or with elongation factors and to select tRNA-mimics aminoacylated by synthetases are presented, as well as the functional and structural characteristics of the selected molecules. Production and characteristics of aptameric RNAs fulfilling aminoacyl-tRNA synthetase functions and of RNAs selected to have affinities for amino acids are also described. Finally, properties of RNAs obtained by either the structure-based or the combinatorial methods are discussed in the light of the origin and evolution of the translation machinery, but also with a view to obtain new inhibitors targeting specific steps in translation.

[Coronary intervention and occupational rehabilitation--a prospective, randomized intervention study]. / Koronarintervention und berufliche Reintegration--Eine prospektive, randomisierte Interventionsstudie (KIRL).

Coronary catheter revascularisation is less costly than bypass surgery due to lower direct (medical) and indirect costs (loss of work). Many studies show that the time patients stay out of work following coronary intervention is much longer than necessary. This leads to a considerable increase of indirect costs, which can far exceed the medical costs of the treatment. This prospective randomised study was done to determine whether specific information to patient and family doctor results in an earlier return to work. After catheter revascularisation 100 working patients (mean age 52.4 years) were randomised either to the intervention group (information to patient and family doctor) or to the control group (no specific information about return to work). Four months later 81 patients had returned to their previous jobs (mean sick leave 18.9 +/- 24.8 days) while 19 were still out of work. In the control group, the rate was 79% and the mean sick leave was 16.4 +/- 22.0 days (median 7); in the intervention group 83% had returned to work after a mean of 21.5 +/- 27.4 days (median 10). There was no significant difference between the two groups, neither according to the rate of returned workers nor to the duration of sick leave. In the subgroup of patients with a private insurance (23% of all) 96% started to work again (mean sick leave 5.7 +/- 5.1 days median 3.5), while the rate was 77% in the group of panel patients (mean sick leave 23.7 +/- 27.4 days, median 11). The difference in sick leave between these two groups was highly significant (p = 0.0003). Specific information to the patient and family doctor has no effect on the time patients stay out of work following catheter revascularisation. It seems that the observed delay depends on social and psychological factors that cannot be influenced directly.

Selection of viral RNA-derived tRNA-like structures with improved valylation activities.

The tRNA-like structure (TLS) of turnip yellow mosaic virus (TYMV) RNA was previously shown to be efficiently charged by yeast valyl-tRNA synthetase (ValRS). This RNA has a noncanonical structure at its 3'-terminus but mimics a tRNA L-shaped fold, including an anticodon loop containing the major identity nucleotides for valylation, and a pseudoknotted amino acid accepting domain. Here we describe an in vitro selection experiment aimed (i) to verify the completeness of the valine identity set, (ii) to elucidate the impact of the pseudoknot on valylation, and (iii) to investigate whether functional communication exists between the two distal anticodon and amino acid accepting domains. Valylatable variants were selected from a pool of 2 x 10(13) RNA molecules derived from the TYMV TLS randomized in the anticodon loop nucleotides and in the length (1-6 nucleotides) and sequence of the pseudoknot loop L1. After nine rounds of selection by aminoacylation, 42 have been isolated. Among them, 17 RNAs could be efficiently charged by yeast ValRS. Their sequence revealed strong conservation of the second and the third anticodon triplet positions (A(56), C(55)) and the very 3'-end loop nucleotide C(53). A large variability of the other nucleotides of the loop was observed and no wild-type sequence was recovered. The selected molecules presented pseudoknot domains with loop L1 varying in size from 3-6 nucleotides and some sequence conservation, but did neither reveal the wild-type combination. All selected variants are 5-50 times more efficiently valylated than the wild-type TLS, suggesting that the natural viral sequence has emerged from a combination of evolutionary pressures among which aminoacylation was not predominant. This is in line with the role of the TLS in viral replication.

Rapid selection of aminoacyl-tRNAs based on biotinylation of alpha-NH2 group of charged amino acids.

A rapid selection procedure to separate low amounts of aminoacylated tRNAs from large pools of inactive variants is described. The procedure involves a three-step protocol. After initial aminoacylation of a tRNA pool, N-hydroxysuccinimide ester chemistry is applied to biotinylate the alpha-NH2 group of the amino acid bound to the 3'-end of a tRNA. The biotin tag is used to capture the derivatized tRNAs on streptavidin-conjugated magnetic beads. Variants bound to the solid phase can be amplified by RT-PCR and transcription, providing tRNAs for subsequent selection rounds.

Contact lens use after corneal trauma.

BACKGROUND: This study was performed to explore the epidemiology and visual outcomes of major anterior segment trauma cases referred to the Contact Lens Service (CLS) in a large, urban, eye trauma center at a university hospital. METHODS: All eye trauma patients seen on the CLS at The University of Illinois in Chicago for a 2-year period were identified (n = 122). A search of all eye trauma cases seen at UIC (n = 2279) during the same period yielded 757 cases with the same diagnostic codes. RESULTS: CLS cases represent 16.1% of cases with similar diagnoses and 5.35% of all cases seen during the period of study. Cases were predominantly young men (mean age, 28 years). The mean age for CLS cases (mean age, 17 years) was significantly younger. Best-corrected visual acuity was 20/100 or better in 75% of cases with a contact lens and in 68% of cases with a spectacle lens; 82% of CLS cases had iris damage versus 14.5% of non-CLS cases; 73% of CLS cases were aphakic; 105 CLS cases were given contact lenses. Mean follow-up time was 24 months. Mean wearing time was 11 hours/day. On interview, 35 of 79 cases (44%) continued to wear lenses. CONCLUSIONS: Cases referred to the CLS tended to be young men with unilateral injuries-predominantly open globes-with resultant aphakia and iris damage. Good visual acuity was achieved in most cases. Long-term success wearing contact lenses for this population was poor, suggesting that alternatives to contact lens wear should be more actively considered.

Additive, cooperative and anti-cooperative effects between identity nucleotides of a tRNA.

We have investigated the functional relationship between nucleotides in yeast tRNAAsp that are important for aspartylation by yeast aspartyl-tRNA synthetase. Transcripts of tRNAAsp with two or more mutations at identity positions G73, G34, U35, C36 and base pair G10-U25 have been prepared and the steady-state kinetics of their aspartylation were measured. Multiple mutations affect the catalytic activities of the synthetase mainly at the level of the catalytic constant, kcat. Kinetic data were expressed as free energy variation at transition state of these multiple mutants and comparison of experimental values with those calculated from results on single mutants defined three types of relationships between the identity nucleotides of this tRNA. Nucleotides located far apart in the three-dimensional structure of the tRNA act cooperatively whereas nucleotides of the anticodon triplet act either additively or anti-cooperatively. These results are related to the specific interactions of functional groups on identity nucleotides with amino acids in the protein as revealed by the crystal structure of the tRNAAsp/aspartyl-tRNA synthetase complex. These relationships between identity nucleotides may play an important role in the biological function of tRNAs.