[Liability for chronic working time violations in medicine: when does the risk of fines and imprisonment loom?] / Haftung für chronische Arbeitszeitverstöße in der Medizin ­ wann drohen Bußgelder und Freiheitsstrafen?

Against the background of the changes in the collective bargaining agreement-for municipal hospitals in the version of January 1, 2021, and for university hospitals in the version of March 7, 2020-this article deals with the legal consequences of chronic violations of the German Working Hours Act in medicine, but especially in surgical specialties such as urology. It includes an overview of current law and sanctions for violations and highlights responsibilities as well as exceptions. It is important to clarify the distribution of responsibilities with regard to working hours in the institution concerned in order to avoid fines and, in the worst case, imprisonment. It should also be clear who is liable in specific cases for persistent working time violations. When changing duty models, it is important to bear in mind that this can lead to a considerable deterioration in the opportunities for further training and education of physicians, meaning that in the long term the compatibility of further training in line with working hours can only be achieved with sufficient staffing of the hospitals. In some cases, this is diametrically opposed to economic interests in the health care system and thus presents an almost insoluble dilemma. In the view of the working group, structural changes in the diagnosis-related group (DRG)-based inpatient sector are needed in the near future.

[Implementation of the new collective agreement in 2021 in urological clinics : Expectations and reality]. / Umsetzung des neuen Tarifvertrags ab 2021 in urologischen Kliniken : Wunsch und Wirklichkeit.

The amendment to the collective agreement is intended to significantly improve the working conditions of physicians and includes longer-term duty scheduling, work on a maximum of two weekends per month, less overtime. Smaller hospitals often have problems implementing these requirements and have to make compromises. At least the overtime is now better paid-overall, an improvement in working conditions can only be achieved by increasing the number of staff, then better and more intensive training is also possible.

[The working time load of specialists and senior physicians in German urology-a critical assessment]. / Die Arbeitszeitbelastung von Fach- und Oberärzten in der deutschen Urologie ­ eine Bestandsaufnahme.

BACKGROUND: The working and continued training conditions of assistant physicians in urology in Germany have already been analyzed. But what about senior urologists in Germany? Under which conditions do they have to work? As far as we know no published data currently exist which illuminate the conditions of this special urological professional group, therefore, the results of this survey are presented. OBJECTIVE: To survey and evaluate the current working conditions of certified and senior urologists in Germany as comprehensively as possible. MATERIAL AND METHODS: The working group of employed physicians of the Professional Association of German Urologists (BvDU) carried out a survey within the framework of the urological senior physician forum 2016 and on-line via the e­mail distributor of the German Society for Urology (DGU). The questions involved the workload, working conditions and satisfaction, overtime performed, working hours and opt out regulations. RESULTS: A total of 176 senior physicians participated in the survey of which 88% were male and 12% female. In Germany there are 1125 senior physicians. The average age of the responders was 44.9 years. In more than 80% of the participants the average weekly working hours were over 50 h and 70% signed an opt out regulation. An association between an increasing job dissatisfaction above a working week over 55 h and an average attendance in on-call service over 4 h could be established. The number of on-call services had no influence on job satisfaction. A total of 43% (70 out of 162) of the participants stated that overtime hours were regularly forfeited and 12% (20 out of 162) that all overtime hours were forfeited. Approximately 30% of senior physicians in German urology were dissatisfied with the current working conditions in the present form. CONCLUSION: Based on the acquired data, adaptation and improvements in the working conditions of senior urologists are necessary in order to maintain the attractiveness of the occupational image and leading positions in German urology.

[Workload, job satisfaction, Work Time Act-what is urology doing?] / Arbeitsbelastung, Arbeitszufriedenheit, Arbeitszeitgesetz ­ was macht die Urologie?

Due to demographic changes, the proportion of people requiring urological treatment will continue to rise. In order to better address this development, we need a well-trained and motivated urological medical community. Not only is continued education in urology an integral part of this, but it must also be embedded into future-oriented, flexible work-hour models, taking into account the German Work Time Act. Thus, in order to obtain a better assessment of the current situation of urological physicians undergoing specialist training, work -hour models currently used in urological clinics must be evaluated. This should allow conclusions to be drawn to find future-oriented solutions in order to do justice to the Future Offensive-Urology in 2025. Transparency, openness, and cooperation should be top priority between the DGU (German Association for Urology) working groups active in this field and the working groups of the BvDU (German Professional Association for Urologists).

[Regional Deprivation in Germany: Nation-wide Analysis of its Association with Mortality Using the German Index of Multiple Deprivation (GIMD)]. / Regionale Deprivation in Deutschland: Bundesweite Analyse des Zusammenhangs mit Mortalität unter Verwendung des 'German Index of Multiple Deprivation (GIMD)'.

BACKGROUND: Deprivation indices are increasingly being used to assess the effects of contextual factors on health. In Germany, the recently developed 'German Index of Multiple Deprivation (GIMD)' integrates various dimensions of regional deprivation. We aim to assess the validity of the GIMD through a recalculation using more recent rural and urban district level data and by analysing its association with mortality at the national level. METHODS: We calculated a new version of the GIMD based on data from 2007 to 2010 for all 412 rural and urban districts in Germany. Mortality was quantified using indirectly standardised mortality ratios (SMRs). Correlation analyses and Poisson regression analyses were used to assess the association between the GIMD scores and total mortality, as well as premature mortality (< 65 years). RESULTS: Correlation analyses showed a positive association between the GIMD and both total mortality (p<0.001) and premature mortality (p<0.001). In the Poisson regression analyses, rural and urban districts in the quintile with the highest deprivation showed a significantly elevated risk of total mortality (RR: 1.29; 95% CI: 1.28-1.30) as well as premature mortality (RR: 1.50; 95% CI: 1.47-1.53), compared to the districts in the lowest quintile. CONCLUSION: The association between regional deprivation and mortality has already been shown for the federal state of Bavaria. Using more recent data, this relationship could be confirmed here for Germany as a whole. The GIMD has been shown to be able to effectively assess regional deprivation. Concerning public health policy, the significant, positive and stable association between regional deprivation and mortality indicates an increased need for health care provision particularly in the most deprived districts. Further studies should examine, for example, whether and how the allocation of districts to quintiles of regional deprivation changes over time, and how this affects mortality.

Preservation of cocoa antioxidant activity, total polyphenols, flavan-3-ols, and procyanidin content in foods prepared with cocoa powder.

Little is known about the effects of common cooking processes on cocoa flavanols. Antioxidant activity, total polyphenols (TP), flavanol monomers, and procyanidin oligomers were determined in chocolate frosting, a hot cocoa drink, chocolate cookies, and chocolate cake made with natural cocoa powder. Recoveries of antioxidant activity, TP, flavanol monomers, and procyanidins ranged from 86% to over 100% in the chocolate frosting, hot cocoa drink, and chocolate cookies. Losses were greatest in the chocolate cake with recoveries ranging from 5% for epicatechin to 54% for antioxidant activity. The causes of losses in baked chocolate cakes were investigated by exchanging baking soda with baking powder or combinations of the 2 leavening agents. Use of baking soda as a leavening agent was associated with increased pH and darkening color of cakes. Losses of antioxidant activity, TP, flavanol monomers, and procyanidins were associated with an increased extractable pH of the baked cakes. Chocolate cakes made with baking powder for leavening resulted in an average extractable pH of 6.2 with essentially complete retention of antioxidant activity and flavanol content, but with reduced cake heights and lighter cake color. Commercially available chocolate cake mixes had final pHs above 8.3 and contained no detectable monomeric flavanols after baking. These results suggest that baking soda causes an increase in pH and subsequent destruction of flavanol compounds and antioxidant activity. Use of an appropriate leavening agent to moderate the final cake pH to approximately 7.25 or less results in both good leavening and preservation of cocoa flavanols and procyanidins.

The carboxy-terminus of VirE2 from Agrobacterium tumefaciens is required for its transport to host cells by the virB-encoded type IV transport system.

Agrobacterium tumefaciens transfers DNA from the resident 'tumour-inducing' (Ti) plasmid into plant cells, where it can be stably integrated into the plant genome, ultimately resulting in crown gall tumour formation. The mobilized DNA molecule is a single-stranded intermediate with VirD2 covalently bound to its 5' end. Successful transport of the transferred DNA (T-DNA) and integration of the DNA into the genome requires that additional proteins be transported to the plant as well, including the single-stranded (ss)DNA-binding protein, VirE2. The transport of these two different substrates occurs as a result of the activities of a type IV secretion system encoded by the virB operon. Although the substrates have been identified, the mechanism of their transport remains unknown. In the experiments described here, a region in one of these substrates, VirE2, necessary for transport is identified. The addition of a C-terminal FLAG epitope tag to VirE2, or the deletion of its C-terminal 18 amino acids, renders it non-functional in A. tumefaciens. However, transgenic plants expressing either of these virE2 genes respond to virE2 mutants of A. tumefaciens by forming wild-type tumours. These results indicate that this region of VirE2 is necessary for the protein to be transported into the plant cells, but is not necessary for its function within the plant. Additionally, these studies demonstrate that mutant forms of VirE2 lacking this region do not disrupt the activities of the VirB transporter and support the hypothesis that VirE2 and the VirD2 T-strand are transported independently, even when they co-exist in the same cell.

Mono- and di-nickellaazaphosphiranes of mono- and bis-(amido)cyclodiphosph(III)azanes.

The syntheses and solid-state structures of the first three-membered nickel-phosphorus-nitrogen ring compounds, having anionic four-electron P=N moieties are reported.

Syntheses and structures of heterobicyclic bis(tert-butylamido)cyclodiphosph(III)azane compounds having phosphorus(III) and arsenic(III) centers.

Syntheses and single-crystal X-ray diffraction studies of heterobicyclic cyclodiphosphazanes having central phosphorus(III) and arsenic(III) atoms are described. Interaction of PCl3 or AsCl3 with cis-[(tBuNP)2(tBuNLixTHF)2] produced the isomorphous ([(tBuNP)2(tBuN)2]ECl); E = P(1), As(4), respectively. These Cs-symmetric molecules crystallize with two molecules in the monoclinic space group P2(1)/m. Unit cell dimensions of 1 are (293 K) a = 9.777(1) A, b = 11.745(1) A, c = 9.986(2) A, and beta = 97.44(1) degrees; those of 4 are (213 K) a = 9.688(3) A, b = 11.873(3) A, c = 9.975(3) A, and beta = 97.80(3) degrees. When ([(tBuNP)2(tBuN)2]PCl) was treated with NaN3 or LiN(SiMe3)2, ([(tBuNP)2(tBuN)2]PN3)(2) and ([(tBuNP)2(tBuN)2]PN(SiMe3)2)(3), respectively, were obtained. Compound 2 crystallizes in the monoclinic space group P2(1)/m and has until-cell dimensions (213 K) of a = 9496(7) A, b = 12455(7) A, c = 10043(6) A, and beta = 9723(4) degrees, Z = 2.

The conjugal intermediate of plasmid RSF1010 inhibits Agrobacterium tumefaciens virulence and VirB-dependent export of VirE2.

Agrobacterium tumefaciens causes crown gall disease by transferring oncogenic, single-stranded DNA (T strand), covalently attached to the VirD2 protein, across the bacterial envelope into plant cells where its expression results in tumor formation. The single-stranded DNA binding protein VirE2 is also transferred into the plant cell, though the location at which VirE2 interacts with the T strand is still under investigation. The movement of the transferred DNA and VirE2 from A. tumefaciens to the plant cell depends on the membrane-localized VirB and VirD4 proteins. Further, the movement of the IncQ broad-host-range plasmid RSF1010 between Agrobacterium strains or from Agrobacterium to plants also requires the virB-encoded transfer system. Our earlier studies showed that the presence of the RSF1010 plasmid in wild-type strains of Agrobacterium inhibits both their virulence and their capacity to transport VirE2, as assayed by coinfection with virE mutants. Here we demonstrate that the capacity to form a conjugal intermediate of RSF1010 is necessary for this inhibition, suggesting that the transferred form of the plasmid competes with the VirD2-T strand and/or VirE2 for a common export site.

Infections with nonthoracotomy implantable cardioverter defibrillators: can these be prevented? Endotak Lead Clinical Investigators.

Nonthoracotomy ICDs are believed to be the best therapeutic modality for treatment of life-threatening ventricular arrhythmias. Little is known about the risk of infection with initial implantation of these devices. We studied the incidence, clinical characteristics, and risk factors associated with infections in 1,831 patients with nonthoracotomy ICD from the Endotak-C nonthoracotomy lead registry of Cardiac Pacemakers, Inc. A transvenous lead was implanted in 950 patients (51.9%) and a combination transvenous plus subcutaneous patch was used in 881 patients (48.1%). Nine preselected data variables were studied, and all investigators identified as having patients with infections were personally contacted. Infections occurred in 22 (1.2%) of 1,831 patients receiving this nonthoracotomy ICD system. The mean time to infection was 5.7 +/- 6.5 months (range 1-25 months). Staphylococci were isolated in 58% of patients with reported infection. The presence of a subcutaneous defibrillator patch system was associated with the development of infection. Six of 950 patients (0.63%) with a totally transvenous lead system developed infection versus 16 of 838 (1.9%) patients with a transvenous lead plus subcutaneous patch system configuration (P = 0.015, Chi-square test), with an unadjusted estimated odds ratio of 3.06 (CI 1.19-7.86). The risk of infection encountered with the nonthoracotomy ICD is low, estimated from our data to be 1.2%. Placement of a subcutaneous defibrillator patch appears to be an independent risk factor for development of infection.

Are more complex implantable cardioverter defibrillators associated with an increased mortality? Lessons learned from clinical trials.

We compared 1-year survival in patients receiving implantable cardioverter defibrillators (ICDs) that provide only shock therapy with more advanced ICDs that provide antitachycardia pacing, bradycardia pacing, low-energy cardioversion, and advanced detection algorithms. Outcome in patients with advanced-generation ICD systems was similar or improved compared with outcome in patients receiving ICDs with only monophasic shock.

Daily exercise attenuates the sympathetic nerve response to exercise by enhancing cardiac afferents.

"Central command" may initiate the sympathoexcitatory responses at the onset of exercise by shifting the operating point of the arterial baroreflex toward higher pressures. Daily exercise (DE) attenuates the sympathoexcitatory responses to submaximal exercise. This DE-induced adaptation may be due, in part, to an enhanced inhibitory influence of cardiac afferents. This is suggested because cardiac afferents exert a tonic inhibitory influence on the arterial baroreflex which is enhanced by DE. Therefore, the influence of cardiac afferents on the regulation of renal sympathetic nerve activity (RSNA) during exercise was examined in a group of sedentary and age-matched DE rabbits. The rabbits were instrumented with a Silastic catheter inserted into the pericardial sac, electrodes around the renal sympathetic nerves, and catheters in the femoral artery and vein. In the sedentary rabbits, treadmill exercise (12 m/min, 20% grade) significantly increased mean arterial pressure (delta 18 +/- 3 mmHg), heart rate (delta 36 +/- 3 beats/min), and RSNA (delta 295 +/- 23%). More importantly, cardiac afferent blockade (2% intrapericardial procainamide) did not significantly alter the RSNA response to exercise in the sedentary rabbits. DE did not alter the mean arterial pressure (delta 15 +/- 1 mmHg) or heart rate (delta 55 +/- 8 beats/min) response to exercise; however, RSNA (delta 252 +/- 9%) was significantly reduced. In contrast to the sedentary rabbits, cardiac afferent blockade in the DE rabbits significantly increased the RSNA response to exercise (delta 417 +/- 30%). These results suggest that DE attenuates the RSNA response to dynamic exercise due, in part, to an enhanced inhibitory influence of cardiac afferents.

Sympathoexcitatory response to cyclosporin A and baroreflex resetting.

We postulate that the sympathoexcitatory response associated with the immunosuppressive agent cyclosporin A is due to an upward resetting of the arterial baroreflex. We performed studies in conscious intact and sinoaortic-denervated rabbits instrumented with catheters and renal nerve electrodes. In intact rabbits, cyclosporin A (20 mg/kg i.v., 30 minutes) produced significant increases in renal sympathetic nerve activity (100% to 269 +/- 74%, P < .05) but did not increase mean arterial pressure. In intact rabbits, we determined arterial baroreflex curves relating renal sympathetic nerve activity and heart rate to mean arterial pressure by producing ramp increases (intravenous phenylephrine) and decreases (intravenous nitroprusside) in mean arterial pressure. Cyclosporin A treatment produced a shift of the midrange of the baroreflex control of heart rate (78.0 +/- 4.1 to 84.6 +/- 4.7 mm Hg, P < .05) and renal sympathetic nerve activity (74.6 +/- 3.9 to 87.0 +/- 4.8 mm Hg, P < .05). Vehicle administration produced no effects on arterial baroreflex curves relating renal sympathetic nerve activity and heart rate to mean arterial pressure. Compared with vehicle treatment, cyclosporin A reduced the maximum gain of heart rate (-5.6 +/- 0.6 versus -3.1 +/- 0.8 beats per minute per millimeter of mercury, P < .05) but had no effect on the maximum gain of renal sympathetic nerve activity. In conscious sinoaortic-denervated rabbits, cyclosporin A had no effect on mean arterial pressure (95.7 +/- 7.3 to 91.8 +/- 10.8 mm Hg), renal sympathetic nerve activity (100% to 110 +/- 6%). and heart rate (287 +/- 10 to 279 +/- 8 beats per minute). However, when the same sinoaortic-denervated rabbits were anesthetized with sodium pentobarbital, cyclosporin A (20 mg/kg i.v.) produced increases in renal sympathetic nerve activity (100% to 189 +/- 27%). These data indicate (1) that the sympathoexcitatory response to cyclosporin A depends on baroreceptor afferent input in the conscious state and (2) that this response involves an upward resetting of the arterial baroreflex.

A prospective, randomized evaluation of a nonthoracotomy implantable cardioverter defibrillator lead system. Endotak/PRX Investigator Group.

Nonthoractomy lead systems for ICDs have been developed that obviate the need for a thoracotomy and reduce the morbidity and mortality associated with implantation. However, an adequate DFT cannot be achieved in some patients using transvenous electrodes alone. Thus, a new subcutaneous "array" electrode was designed and tested in a prospective, randomized trial that compared the DFT obtained using monophasic shock waveforms with a single transvenous lead alone that has two defibrillating electrodes, the transvenous lead linked to a subcutaneous/submuscular patch electrode, and the transvenous lead linked to the investigational array electrode. There were 267 patients randomized to one of the three nonthoracotomy ICD lead systems. All had DFTs that met the implantation criterion of < or = 25 J. The resultant study population was 82% male and 18% female, mean age of 63 +/- 11 years. The indication for ICD implantation was monomorphic VT in 70%, VF in 19%, monomorphic VT/VF in 6%, and polymorphic VT in 4% of the patients, respectively. The mean LVEF was 0.33 +/- 0.13. The mean DFT obtained with the transvenous lead alone was 17.5 +/- 4.9 J as compared to 16.9 +/- 5.5 J with the lead linked to a patch electrode (P = NS), and 14.9 +/- 5.6 with the lead linked to the array electrode (array versus lead alone, P = 0.0001; array versus lead/patch, P = 0.007). The results of this investigation suggest that the subcutaneous array may be superior to the standard patch as a subcutaneous electrode to lower the DFT and increase the margin of safety for successful nonthoracotomy defibrillation.

The unique proline-rich domain of parotid proline-rich proteins functions in secretory sorting.

When expressed in pituitary AtT-20 cells, parotid proline-rich proteins enter the regulated pathway. Because the short N-terminal domain of a basic proline-rich protein is necessary for efficient export from the ER, it has not been possible to evaluate the role of this polypeptide segment as a sorting signal for regulated secretion. We now show that addition of the six-amino acid propeptide of proparathyroid hormone to the proline-rich protein, and especially to a deletion mutant lacking the N-terminal domain, dramatically accelerates intracellular transport of these polypeptides. Under these conditions the chimeric deletion mutant is stored as effectively as the full-length protein in dense core granules. The propeptide does not function as a sorting signal in AtT-20 cells as it does not reroute a constitutively secreted reporter protein to the regulated pathway. During transit, the propeptide is cleaved from the chimeric polypeptides such that the original structures of the full-length and the deletion mutant proline-rich proteins are reestablished. We have also found that the percentage stimulated secretion of the proline-rich proteins increases incrementally (almost twofold) as their level of expression is elevated. The increase reflects an enrichment of these polypeptides in the granule pool and its incremental nature suggests that sorting of proline-rich proteins involves an aggregation-based process. Because we can now rule out contributions to sorting by both N- and C-terminal segments of the proline-rich protein, we deduce that the unique proline-rich domain is responsible for storage. Thus at least some of the determinants of sorting for regulated secretion are protein-specific rather than universal.