Paper Session III-C - From Motomir to Meditrain: Medical Instrumentation as Spin-Off from Space Application

The medical instrument MEDITRAIN r (patented) is a computer controlled electromechanical ergometer, which can be used in the neuro-physiological and metabolic analysis of the human motoric system and can be applied in the training, diagnostics & rehabilitation of muscles of the upper or lower extremities. The design is based on the flight hardware experiment MOTOMIR , which was developed in the context of the joint Austro-Soviet Space Mission AUSTROMIR to the MIR Space Station. MOTOMIR was launched in August 1991 and was in use aboard the space station for basic muscle research and training of the Cosmonauts up to August 1992. The functional principle of MEDITRAIN is based on the generation of precisely defined motion patterns through velocity controlled translatoric movement of two handles, to which the arms or legs of the patient are latched. These movements can be pre-defined as series of cyclic or acyclic runs of variable duration and velocity between defined start and end points. Via strain gauges in the handles, the isometric, concentric and eccentric forces exerted by the respective muscles are recorded in relation to the position & velocity of the handles (i.e. in relation to the angle and velocity of the respective extremity). In parallel, Electro-Myographic (EMG), Electro-Oculargraphic (EOG) and Electro-Cardiographic (ECG) measurements are performed and correlated to the force and machine data. MEDITRAIN currently offers up to 32 analog channels operating at a standard sampling rate of 1 kHz. All measurement data can be displayed in real-time and are stored together with the personal data of the respective patient

The Multifaceted Functions of Autophagy in Breast Cancer Development and Treatment.

Macroautophagy (herein referred to as autophagy) is a complex catabolic process characterized by the formation of double-membrane vesicles called autophagosomes. During this process, autophagosomes engulf and deliver their intracellular content to lysosomes, where they are degraded by hydrolytic enzymes. Thereby, autophagy provides energy and building blocks to maintain cellular homeostasis and represents a dynamic recycling mechanism. Importantly, the clearance of damaged organelles and aggregated molecules by autophagy in normal cells contributes to cancer prevention. Therefore, the dysfunction of autophagy has a major impact on the cell fate and can contribute to tumorigenesis. Breast cancer is the most common cancer in women and has the highest mortality rate among all cancers in women worldwide. Breast cancer patients often have a good short-term prognosis, but long-term survivors often experience aggressive recurrence. This phenomenon might be explained by the high heterogeneity of breast cancer tumors rendering mammary tumors difficult to target. This review focuses on the mechanisms of autophagy during breast carcinogenesis and sheds light on the role of autophagy in the traits of aggressive breast cancer cells such as migration, invasion, and therapeutic resistance

Diagnostic accuracy of a sequence-specific Mtb-DNA hybridization assay in urine: a case-control study including subclinical TB cases.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains one of the deadliest infectious diseases globally. Timely diagnosis is a key step in the management of TB patients and in the prevention of further transmission events. Current diagnostic tools are limited in these regards. There is an urgent need for new accurate non-sputum-based diagnostic tools for the detection of symptomatic as well as subclinical TB. In this study, we recruited 52 symptomatic TB patients (sputum Xpert MTB/RIF positive) and 58 household contacts to assess the accuracy of a sequence-specific hybridization assay that detects the presence of Mtb cell-free DNA in urine. Using sputum Xpert MTB/RIF as a reference test, the magnetic bead-capture assay could discriminate active TB from healthy household contacts with an overall sensitivity of 72.1% [confidence interval (CI) 0.59-0.86] and specificity of 95.5% (CI 0.90-1.02) with a positive predictive value of 93.9% and negative predictive value of 78.2%. The detection of Mtb-specific DNA in urine suggested four asymptomatic TB infection cases that were confirmed in all instances either by concomitant Xpert MTB/RIF sputum testing or by follow-up investigation raising the specificity of the index test to 100%. We conclude that sequence-specific hybridization assays on urine specimens hold promise as non-invasive tests for the detection of subclinical TB. There is an urgent need for a non-sputum-based diagnostic tool allowing sensitive and specific detection of all forms of tuberculosis (TB) infections. In that context, we performed a case-control study to assess the accuracy of a molecular detection method enabling the identification of cell-free DNA from Mycobacterium tuberculosis that is shed in the urine of tuberculosis patients. We present accuracy data that would fulfill the target product profile for a non-sputum test. In addition, recent epidemiological data suggested that up to 50% of individuals secreting live bacilli do not present with symptoms at the time of screening. We report, here, that the investigated index test could also detect instances of asymptomatic TB infections among household contacts

No signs of check-list fatigue - introducing the StOP? intra-operative briefing enhances the quality of an established pre-operative briefing in a pre-post intervention study.

The team timeout (TTO) is a safety checklist to be performed by the surgical team prior to incision. Exchange of critical information is, however, important not only before but also during an operation and members of surgical teams frequently feel insufficiently informed by the operating surgeon about the ongoing procedure. To improve the exchange of critical information during surgery, the StOP?-protocol was developed: At appropriate moments during the procedure, the leading surgeon briefly interrupts the operation and informs the team about the current Status (St) and next steps/objectives (O) of the operation, as well as possible Problems (P), and encourages questions of other team members (?). The StOP?-protocol draws attention to the team. Anticipating the occurrence of StOP?-protocols may support awareness of team processes and quality issues from the beginning and thus support other interventions such as the TTO; however, it also may signal an additional demand and contribute to a phenomenon akin to "checklist fatigue." We investigated if, and how, the introduction of the StOP?-protocol influenced TTO quality. This was a prospective intervention study employing a pre-post design. In the visceral surgical departments of two university hospitals and one urban hospital the quality of 356 timeouts (out of 371 included operation) was assessed by external observers before (154) and after (202) the introduction of the StOP?-briefing. Timeout quality was rated in terms of timeout completeness (number of checklist items mentioned) and timeout quality (engagement, pace, social atmosphere, noise). As compared to the baseline, after the implementation of the StOP?-protocol, observed timeouts had higher completeness ratings (F = 8.69, p = 0.003) and were rated by observers as higher in engagement (F = 13.48, p < 0.001), less rushed (F = 14.85, p < 0.001), in a better social atmosphere (F = 5.83, p < 0.016) and less noisy (F = 5.35, p < 0.022). Aspects of TTO are affected by the anticipation of StOP?-protocols. However, rather than harming the timeout goals by inducing "checklist fatigue," it increases completeness and quality of the team timeout

Preclinical investigations using [177Lu]Lu-Ibu-DAB-PSMA toward its clinical translation for radioligand therapy of prostate cancer

[$^{177}$Lu]Lu-Ibu-DAB-PSMA was previously characterized with moderate albumin-binding properties enabling high tumor accumulation but reasonably low retention in the blood. The aim of this study was to investigate [$^{177}$Lu]Lu-Ibu-DAB-PSMA in preclinical in vivo experiments and compare its therapeutic efficacy and potential undesired side effects with those of [$^{177}$Lu]Lu-PSMA-617 and the previously developed [$^{177}$Lu]Lu-PSMA-ALB-56. BALB/c nude mice without tumors were investigated on Day 10 and 28 after injection of 10 MBq radioligand. It was revealed that most plasma parameters were in the same range for all groups of mice and histopathological examinations of healthy tissue did not show any alternations in treated mice as compared to untreated controls. Based on these results, a therapy study over twelve weeks was conducted with PC-3 PIP tumor-bearing mice for comparison of the radioligands’s therapeutic efficacy up to an activity of 10 MBq (1 nmol) per mouse. In agreement with the increased mean absorbed tumor dose, [$^{177}$Lu]Lu-Ibu-DAB-PSMA (~ 6.6 Gy/MBq) was more effective to inhibit tumor growth than [$^{177}$Lu]Lu-PSMA-617 (~ 4.5 Gy/MBq) and only moderately less potent than [$^{177}$Lu]Lu-PSMA-ALB-56 (~ 8.1 Gy/MBq). As a result, the survival of mice treated with 2 MBq of an albumin-binding radioligand was significantly increased (p < 0.05) compared to that of mice injected with [$^{177}$Lu]Lu-PSMA-617 or untreated controls. The majority of mice treated with 5 MBq or 10 MBq [$^{177}$Lu]Lu-Ibu-DAB-PSMA or [$^{177}$Lu]Lu-PSMA-ALB-56 were still alive at study end. Hemograms of immunocompetent mice injected with 30 MBq [$^{177}$Lu]Lu-Ibu-DAB-PSMA or 30 MBq [$^{177}$Lu]Lu-PSMA-617 showed values in the same range as untreated controls. This was, however, not the case for mice treated with [$^{177}$Lu]Lu-PSMA-ALB-56 which revealed a drop in lymphocytes and hemoglobin at Day 10 and Day 28 after injection. The data of this study demonstrated a significant therapeutic advantage of [$^{177}$Lu]Lu-Ibu-DAB-PSMA over [$^{177}$Lu]Lu-PSMA-617 and a more favorable safety profile as compared to that of [$^{177}$Lu]Lu-PSMA-ALB-56. Based on these results, [$^{177}$Lu]Lu-Ibu-DAB-PSMA may has the potential for a clinical translation

Zinc and cobalt complexes based on tripodal ligands: synthesis, structure and reactivity toward lactide.

International audienceThe coordination chemistry of a series of pro-ligands ([L¹]-[L⁶]) with cobalt and zinc derivatives has been studied. All complexes have been characterized by multinuclear NMR, elemental analysis, and by single-crystal X-ray diffraction studies. Polymerization of rac-lactide takes place at 130 °C in the presence of cobalt and zinc complexes to yield polymers under solvent free conditions with controlled molecular masses and narrow polydispersities