SUMMARY1. Mechanical properties of permeabilized single fibres from rabbit psoas and soleus muscle were determined by measuring the length responses due to abrupt changes in load and the force responses due to isovelocity length changes at different phosphate and Ca21 concentrations.2. The length responses due to abrupt increases in load from psoas fibres showed a rapid lengthening during the change in load followed by a phase of lengthening during which the velocity gradually decreased. In soleus fibres an abrupt lengthening during the change in load was followed by a phase of lengthening during which the velocity remained constant or decreased slightly for increases in load to less than 1-45 of the isometric force (FO). For larger increases in load the velocity during this later phase first increased and thereafter decreased.3. The initial force-velocity curve, derived from the early part of the isotonic responses after the change in load, as well as the late force-velocity curve derived from the force level attained during isovelocity length changes, were sensitive to phosphate. Phosphate caused a shift of the absolute force-velocity curves of both psoas and soleus fibres towards lower values of force. In psoas fibres, the relative force-velocity curves derived by normalization of the force level to the force developed isometrically was shifted by phosphate to smaller velocities. In soleus fibres, the initial velocity at low and intermediate relative loads (< 1-75 FO) was increased by phosphate but at higher loads it decreased, while the late force-velocity curve showed an overall decrease in velocity.4. The force responses during isovelocity lengthening of psoas fibres showed an early rapid increase in force followed by a slow rise in force. The position of this break point in force was sensitive to the phosphate concentration. In soleus fibres, the force responses without phosphate showed an overshoot followed by a slow rise in force. The overshoot diminished with increasing phosphate concentration.5. Phosphate and Ca2+ affected the force responses in psoas and soleus fibres in different ways. When the isometric starting levels were the same, force during and after the length change at submaximal activation was always less than at maximal activation in the presence of 15 mM-phosphate.MS 8477 17 PHY 451 5. J. M. STIENEN AND OTHERS 6. The changes in the mechanical performance during lengthening caused by phosphate in psoas as well as in soleus fibres, are in agreement with a decrease in the average force per attached crossbridge. The results are compatible with a crossbridge model in which phosphate causes a shift of attached crossbridges from a high-forceproducing state to a low-or non-force-producing state. However, a decrease in the number of attached crossbridges might contribute to the kinetics of the phosphate effects.

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Titin is a multifunctional filamentous protein anchored in the M-band, a hexagonally organized supramolecular lattice in the middle of the muscle sarcomere. Functionally, the M-band is a framework that cross-links myosin thick filaments, organizes associated proteins, and maintains sarcomeric symmetry via its structural and putative mechanical properties. Part of the M-band appears at the C-terminal end of isolated titin molecules in the form of a globular head, named here the “M-complex”, which also serves as the point of head-to-head attachment of titin. We used high-resolution atomic force microscopy and nanosurgical manipulation to investigate the topographical and internal structure and local mechanical properties of the M-complex and its associated titin molecules. We find that the M-complex is a stable structure that corresponds to the transverse unit of the M-band organized around the myosin thick filament. M-complexes may be interlinked into an M-complex array that reflects the local structural and mechanical status of the transversal M-band lattice. Local segments of titin and the M-complex could be nanosurgically manipulated to achieve extension and domain unfolding. Long threads could be pulled out of the M-complex, suggesting that it is a compact supramolecular reservoir of extensible filaments. Nanosurgery evoked an unexpected volume increment in the M-complex, which may be related to its function as a mechanical spacer. The M-complex thus displays both elastic and plastic properties which support the idea that the M-band may be involved in mechanical functions within the muscle sarcomere.

Titin is a giant protein spanning between the Z-and M-lines of the sarcomere. In the M-line the C-terminal region of titin overlaps with that of oppositely oriented titin from the other half of the sarcomere. Furthermore, titin-binding proteins such as myomesin and M-protein localize in the M-line so as to form a complex. The M-line complex appears as a globular head-like structure in titin preparations. The exact structure and the molecular arrangement within this M-line complex is unknown. We analyzed the structure and stability of the M-line complex by using atomic force microscopy (AFM). We mechanically

HÁTTÉR – A nagy értékű orvosi képalkotó diagnosztikai eljárások kulcsfontosságú elemei az onkológiai betegség gyanújával rendelkező betegek klinikai vizsgálatának és a megkezdett terápia hatékonysága megállapításának. Magyarországon a magas diagnosztikai igények következtében a komputertomográfia (CT) vagy mágneses rezonanciás képalkotás (MR) diagnosztikai várólistái általában hosszúak és kevésbé átlátható leletezési időt eredményeznek, még a potenciálisan daganatgyanús egyéneknél vagy a diagnosztizált daganatos beteg terápiájának követése esetén is. A JELEN TANULMÁNY CÉLJA – Az Egészséges Budapest Program (EBP) keretén belül megvalósuló budapesti onkodiagnosztikai program félidős elemzése, a tapasztalatok leszűrése és a háttérben meghúzódó egészségpolitikai folyamatok bemutatása. EREDMÉNYEK – A Program keretében a Fővárosi Önkormányzat 2020 novemberétől 2022. december 31-ig 5437 kontrasztanyagos CT és 2948 MR, C-s vagy D-s iránydiagnózissal, az úgynevezett „ BP” térítési kategóriában beutalt eset vizsgálatát finanszírozta szektorsemleges módon köz- és magánegészségügyi képalkotó szolgáltatók felé. A Semmelweis Egyetem tanulmánya szerint az EBP-s betegek esetében a radiológiai vizsgálatok átlagosan 15,2 nappal gyorsabban megtörténtek (16,1 kontra 31,3 nap), mint a NEAK-finanszírozott esetekben, az átlagos várakozási idő a CT vagy MR-vizsgálatokra 13 nappal rövidült (4,2 nap, szemben a 17,2 nappal). Az esetek 86%-ában a betegek egyszer, 14%-ában kétszer vagy még többször vették igénybe a Programot. A Programon belüli igénybevétel ugyanakkor fővárosi kerületenként jelentős különbséget mutat: az eredetileg kerületi bontású – demográfiai, prevalencia- és incidenciaadatok alapján tervezett – esetszámkereteket az egyes kerületek CT esetében 3–45%, MR esetében pedig 8–37% közötti mértékben aknázták ki a kerületi lakosoknak, döntően a kerületi szakrendelői intézeti szakorvosok BP Programba való beutalása révén, a 2020. november és 2022. augusztus közötti időszakban. KONKLÚZIÓ – Az eredetileg a Covid-járvány előtt tervezett esetszámokhoz képest a Program kisebb mértékben került felhasználásra. A tervezett szakmai célkitűzéseket tekintve a CT és MR diagnosztikai előjegyzési idők és várólisták csökkenése révén a Program elérte hatását, illetve közvetve hatással van a budapesti képalkotó diagnosztikai várólisták csökkenésére, ugyanakkor ez önmagában nem elegendő a teljes onkológiai vizsgálati sor gyorsításához és rendezetté tételéhez. Emiatt a Programot további diagnosztikai elemekkel és beteg - útszervezési modulok irányába kívánjuk továbbfejleszteni.

Background and Objectives: Medical imaging is a key element in the clinical workup of patients with suspected oncological disease. In Hungary, due to the high number of patients, waiting lists for Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) were created some years ago. The Municipality of Budapest and Semmelweis University signed a cooperation agreement with an extra budget in 2020 (HBP: Healthy Budapest Program) to reduce the waiting lists for these patients. The aim of our study was to analyze the impact of the first experiences with the HBP. Material and Methods: The study database included all the CT/MRI examinations conducted at Semmelweis University with a referral diagnosis of suspected oncological disease within the first 13 months of the HBP (6804 cases). In our retrospective, two-armed, comparative clinical study, different components of the waiting times in the oncology diagnostics pathway were analyzed. Using propensity score matching, we compared the data of the HBP-funded patients (n = 450) to those of the patients with regular care provided by the National Health Insurance Fund (NHIF) (n = 450). Results: In the HBP-funded vs. the NHIF-funded patients, the time interval from the first suspicion of oncological disease to the request for imaging examinations was on average 15.2 days shorter (16.1 vs. 31.3 days), and the mean waiting time for the CT/MRI examination was reduced by 13.0 days (4.2 vs. 17.2 days, respectively). In addition, the imaging medical records were prepared on average 1.7 days faster for the HBP-funded patients than for the NHIF-funded patients (3.4 vs. 5.1 days, respectively). No further shortening of the different time intervals during the subsequent oncology diagnostic pathway (histological investigation and multidisciplinary team decision) or in the starting of specific oncological therapy (surgery, irradiation, and chemotherapy) was observed in the HBP-funded vs. the NHIF-funded patients. We identified a moderately strong negative correlation (r = −0.5736, p = 0.0350) between the CT/MR scans requested and the active COVID-19 case rates during the pandemic waves. Conclusion: The waiting lists for diagnostic CT/MR imaging can be effectively shortened with a targeted project, but a more comprehensive intervention is needed to shorten the time from the radiological diagnosis, through the decisions of the oncoteam, to the start of the oncological treatment.

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