Reports of deaths are an exaggeration: all-cause and NAA-test-conditional mortality in Germany during the SARS-CoV-2 era.

Counts of SARS-CoV-2-related deaths have been key numbers for justifying severe political, social and economical measures imposed by authorities world-wide. A particular focus thereby was the concomitant excess mortality (EM), i.e. fatalities above the expected all-cause mortality (AM). Recent studies, inter alia by the WHO, estimated the SARS-CoV-2-related EM in Germany between 2020 and 2021 as high as 200 000. In this study, we attempt to scrutinize these numbers by putting them into the context of German AM since the year 2000. We propose two straightforward, age-cohort-dependent models to estimate German AM for the 'Corona pandemic' years, as well as the corresponding flu seasons, out of historic data. For Germany, we find overall negative EM of about -18 500 persons for the year 2020, and a minor positive EM of about 7000 for 2021, unveiling that officially reported EM counts are an exaggeration. In 2022, the EM count is about 41 200. Further, based on NAA-test-positive related death counts, we are able to estimate how many Germans have died due to rather than with CoViD-19; an analysis not provided by the appropriate authority, the RKI. Through 2020 and 2021 combined, our due estimate is at no more than 59 500. Varying NAA test strategies heavily obscured SARS-CoV-2-related EM, particularly within the second year of the proclaimed pandemic. We compensated changes in test strategies by assuming that age-cohort-specific NAA-conditional mortality rates during the first pandemic year reflected SARS-CoV-2-characteristic constants.

Interaction of beta-blockers with the renal uptake transporter OCT2.

AIM: The uptake of drugs from the blood into the renal tubular cells is a key determinant for renal secretion and may influence their systemic plasma concentrations and extrarenal effects. Metformin, used for treatment of type 2 diabetes, is taken up into renal tubular cells by the organic cation transporter 2 (OCT2). Because many patients with type 2 diabetes receiving metformin are concomitantly treated with beta-blockers, we tested whether beta-blockers can inhibit OCT2-mediated drug transport. METHOD: Using Madin-Darby canine kidney II cells stably expressing the uptake transporter OCT2, we analysed whether the beta-blockers bisoprolol, carvedilol, metoprolol and propranolol inhibit the transport of OCT2 substrates 1-methyl-4-phenylpyridinium (MPP(+)) and metformin. RESULTS: Neither bisoprolol nor metoprolol significantly inhibited the uptake of MPP(+), whereas a significant inhibition was observed for carvedilol und propranolol (half maximal inhibitory concentration IC(50): 26.3 and 67.5 microM) respectively. Moreover, all beta-blockers significantly inhibited OCT2-mediated metformin uptake (IC(50) for bisoprolol: 2.4 microM, IC(50) for carvedilol: 2.3 microM, IC(50) for metoprolol: 50.2 microM and IC(50) for propranolol: 8.3 microM). CONCLUSION: These in vitro results demonstrate that alterations of uptake transporter function by beta-blockers have to be considered as potential mechanisms underlying drug-drug interactions in the kidney.

Back muscle activation pattern and spectrum in defined load situations.

For the prevention and rehabilitation of low back pain the understanding muscle function in the low back region is essential. Important aspects of function include the muscle activation patterns and muscle fatigue. In the low back region m. erector spinae plays a critical role. The different parts of this muscle complex differ considerably in function. Following the concept of Bergmark [A. Bergmark, Stability of the lumbar spine, Acta Orthop. Scand. 60 (1989) 1-54] trunk muscles can be divided in two subsystems, the global-mobilizing-system and the local-stabilizing-system. At present the multifidus muscles are assigned to the local whereas the longissimus and iliocostalis muscles are assigned to the global system. From results of the four parts of our investigation, it can be shown that essential information about muscle function can be obtained by spectral and intra- as well as inter-muscular surface EMG parameters. Obtained data demonstrated functional transitions between the local and global system of trunk muscles for the multifidus muscle.

Musculoskeletal support of lumbar spine stability.

Using a biomechanical model and experimental data the self-stabilising behaviour of antagonistic trunk muscles was analyzed. The biomechanical model is constituted of a pair of antagonistic Hill-type muscles, their geometric arrangement with respect to the spine, and the instantaneous centre of rotation in frontal plane. Using Ljapunov's theory, the stability of certain motion and loading situations was analyzed. Applying a sensitivity analysis, the influence of different muscle properties and the geometric arrangement on stability was investigated. The simulations revealed that the stability of spinal movements depended primarily on the geometrical arrangement of muscles and the position of the centre of rotation of the spine, the latter was affected in turn by the activities of the profound muscles. To stabilize the situations simulated oblique muscle arrangements were necessary. In order to define an instantaneous centre of rotation in the lower region of the spine negative attachment angles (medio-lateral decline) of muscles were necessary, corresponding to the real anatomy of obliquus externus muscles. More cranially located instantaneous centres of rotation required positive attachment angles for stability, corresponding to obliquus internus or multifidus muscles. Furthermore, the fibre-type distribution of muscles influenced the stability of the system, i.e. a high percentage of fast-twitch-fibres supported the stabilisation. Conclusions drawn from the simulations were supported by experimental data. Sudden loads and quick-release perturbations with two different amplitudes were applied to the upper body of ten male subjects. In comparison to sudden load situations preactivation of muscles due to an external load, i.e. quick-release perturbation, led to significantly less dependency of the amplitude of deflection on the amplitude of the perturbation. This observation relates to the self-stabilising properties of the musculoskeletal system. In conclusion, training seems to be advantageous if directed towards not only enhancing the endurance capacity of the muscles, but also increasing the cross-sectional area of oblique fast-twitch-fibres. Training should also improve the co-ordination of deep and superficial trunk muscles. These findings may influence physiotherapy and training programs for low back pain patients.

Stimulation of GABAB receptors increases the expression of the proenkephalin gene in slice cultures of rat neocortex.

In rat neocortex the proenkephalin gene is expressed in GABAergic interneurons. Immunocytochemistry and in situ hybridisation show only a small number of cells in layers II to VI which express the gene. In organotypic slices of rat neocortex, the GABAA receptor inhibitor bicuculline methiodide enhances the expression of the gene in numerous cells. In the present study, we have investigated how GABA regulates the expression of the proenkephalin gene. The GABAA receptor antagonist bicuculline methiodide and the inhibitor of ligand-gated Cl- channels picrotoxin strongly enhanced the expression of the gene in numerous cells which were arranged in neocortical layers II/III and V/VI. Since bicuculline methiodide can also block Ca(++)-activated K+ channels, the possible involvement of such channels was tested. However, apamin which blocks only Ca(++)-activated K+ channels had no effect on the expression of the proenkephalin gene indicating that the effect of bicuculline methiodide was due to inhibition of GABAA receptors. In addition, the GABAB receptor agonist baclofen increased the neocortical expression of the proenkephalin gene mainly in cells located in layers V/VI of the neocortex. The effect of baclofen was inhibited by the GABAB receptor antagonists CGP35348 and CGP52432. Also muscimol, an agonist at GABAA receptors, enhanced the expression of the proenkephalin gene. This effect was blocked by CGP52432 confirming previous observations that muscimol can also stimulate GABAB receptors. Our results indicate that GABA can regulate the expression of the opioid peptide in neocortical neurons in a bidirectional manner. The expression is suppressed via GABAA and enhanced via GABAB receptors.

Evidence for cell specific regulation by PACAP38 of the proenkephalin gene expression in neocortical cells.

During the first postnatal week, glial cell production for the neocortex continues in the neocortical subventricular zone. During this time, the proenkephalin gene (PEnk) is expressed in numerous cells of the subventricular zone and of the adjacent neocortex. When neocortical astroglial cells are brought into dissociation culture, they also produce PEnk mRNA. We have investigated the effect of pituitary adenylate cyclase activating peptide-38 (PACAP38) on PEnk gene expression in dissociation cultures as well as in slice cultures, which contained the subventricular zone and the adjacent neocortex. PACAP38 enhanced the levels of PEnk mRNA in both culture systems. In dissociated astroglial cells, inhibition of protein kinase A, of p44,42 mitogen-activated protein kinase as well as of the EGF-receptor tyrosine kinase by H89, PD98059 and AG1478, respectively, reduced the PACAP38-induced expression in a synergistic manner. In the neocortical part of the slice cultures, the effect of PACAP38 on PEnk gene expression was inhibited only by H89 and PD98059. Here, protein kinase A and p44,42 MAP kinases shared a mechanism which increased the gene expression. Surprisingly, the expression of the PEnk gene in the glial progenitors of the subventricular zone as induced by PACAP38 was not affected by any of the three protein kinase inhibitors, but was blocked by the unspecific kinase inhibitor H7. It is concluded that PACAP38 induced the PEnk gene expression in both culture systems in a cell-type specific manner.

[Abdominal complications after heart surgery interventions]. / Abdominelle Komplikationen nach kardiochirurgischen Eingriffen.

OBJECTIVE: Risk factors of abdominal complications after cardiac surgery are largely unknown. We undertook this study to determine different types of abdominal complications after cardiac surgery and to identify patients at risk. PATIENTS AND METHODS: 3312 adult patients were operated between Jan. 91 and Oct. 95 (2352 males, 960 females, 62.6 +/- 0.18y). We included all patients who suffered from abdominal complications within 30 days postoperatively. RESULTS: Abdominal complications are rare after cardiac surgery using cardiopulmonary bypass (CPB) (1.4%), but they are associated with high mortality (14.5%) in our department. Abdominal complications like paralytic ileus (43.8%), erosive gastritis (22.9%) and gastrointestinal bleeding (18.8%) are more often, compared with acute cholecystitis (14.5%), acute pancreatitis (8.3%) and intestinal ischemia (19.5%). Patients with intestinal ischemia are at high risk and do have a high mortality (83%). Abdominal complications can be found more often in connection with prolonged myocardial ischemia and valve replacement or combined operations. Prediction of complications on the basis of anamnestic data alone was not possible. CONCLUSION: Abdominal complications after cardiac surgery, especially intestinal ischaemia, are life-threatening. Prediction of abdominal complications is impossible. We have to concentrate on an early diagnosis and therapeutic intervention to lower mortality. A close cooperation between cardiac and general surgeons is mandatory for a successful treatment of life-threatening abdominal complications such as intestinal ischemia.

[Spontaneous liver rupture in eclampsia]. / Die spontane Leberruptur bei Eklampsie.

We report on a case of a 34-year old nullipara who suffered from rupture of the liver during eclampsia and survived despite most serious complications. Most cases of rupture of a non-traumatic subcapsular haematoma of the liver during pregnancy are associated with symptoms of pre-eclampsia. The pathogenesis of this severe complication as well as diagnostic imaging and surgical treatment are discussed. The classical trias of pre-eclampsia, epigastric pain and sudden circulary collapse may vary considerably. Since early diagnosis is crucial for maternal and foetal outcome, a subcapsular haematoma of the liver should be considered in women during pregnancy and childbed presenting with pre-eclampsia and upper abdominal pain. Here ultrasonographic imaging is a valuable and readily available diagnostic tool for the obstetrician.