Photoimmunotherapy of Prostate Cancer With Antibody and Fab Fragments Targeting the Prostate Specific Membrane Antigen.

BACKGROUND/AIM: The standard treatment for localized prostate cancer involves surgical removal of the prostate with curative intent. However, when tumor cells persist in the operation site, there is high risk of local recurrence and tumor spread, leading to stressful follow-up treatments, impaired quality of life, and reduced overall survival. This study examined photoimmunotherapy (PIT) as a new treatment option for prostate cancer cells. MATERIALS AND METHODS: We generated conjugates consisting of either a humanized antibody or Fab fragments thereof targeting the prostate specific membrane antigen (PSMA), along with our silicon phthalocyanine photosensitizer dye WB692-CB1. PSMA-expressing prostate cancer cells were incubated with the antibody dye or Fab dye conjugates and cell binding was measured using flow cytometry. Cells were irradiated with varying doses of red light for dye activation, and cytotoxicity was determined by erythrosin B staining and subsequent analysis using a Neubauer counting chamber. RESULTS: Specific cytotoxicity was induced with the antibody dye conjugate in the prostate cancer cells in a light dose-dependent manner. Treatment of the cells with the Fab dye conjugate resulted in lower cytotoxicity, which could be attributed to a reduced binding affinity and a reduced dye uptake of the Fab fragment. CONCLUSION: Our new antibody dye and Fab dye conjugates offer potential for future intraoperative PIT in patients with localized prostate cancer, with the aim to ensure complete removal of tumor cells from the surgical area, to avoid local recurrence, and to improve clinical outcome.

"PNP slows down" - linearly-reduced whole body joint velocities and altered gait patterns in polyneuropathy.

Introduction: Gait disturbances are a common consequence of polyneuropathy (PNP) and a major factor in patients' reduced quality of life. Less is known about the underlying mechanisms of PNP-related altered motor behavior and its distribution across the body. We aimed to capture whole body movements in PNP during a clinically relevant mobility test, i.e., the Timed Up and Go (TUG). We hypothesize that joint velocity profiles across the entire body would enable a deeper understanding of PNP-related movement alterations. This may yield insights into motor control mechanisms responsible for altered gait in PNP. Methods: 20 PNP patients (61 ± 14 years) and a matched healthy control group (CG, 60 ± 15 years) performed TUG at (i) preferred and (ii) fast movement speed, and (iii) while counting backward (dual-task). We recorded TUG duration (s) and extracted gait-related parameters [step time (s), step length (cm), and width (cm)] during the walking sequences of TUG and calculated center of mass (COM) velocity [represents gait speed (cm/s)] and joint velocities (cm/s) (ankles, knees, hips, shoulders, elbows, wrists) with respect to body coordinates during walking; we then derived mean joint velocities and ratios between groups. Results: Across all TUG conditions, PNP patients moved significantly slower (TUG time, gait speed) with prolonged step time and shorter steps compared to CG. Velocity profiles depend significantly on group designation, TUG condition, and joint. Correlation analysis revealed that joint velocities and gait speed are closely interrelated in individual subjects, with a 0.87 mean velocity ratio between groups. Discussion: We confirmed a PNP-related slowed gait pattern. Interestingly, joint velocities in the rest of the body measured in body coordinates were in a linear relationship to each other and to COM velocity in space coordinates, despite PNP. Across the whole body, PNP patients reduce, on average, their joint velocities with a factor of 0.87 compared to CG and thus maintain movement patterns in terms of velocity distributions across joints similarly to healthy individuals. This down-scaling of mean absolute joint velocities may be the main source for the altered motor behavior of PNP patients during gait and is due to the poorer quality of their somatosensory information. Clinical Trial Registration: https://drks.de/search/de, identifier DRKS00016999.

Age-related changes in mobility assessments correlate with repetitive goal-directed arm-movement performance.

BACKGROUND: There is ample evidence that mobility abilities between healthy young and elderly people differ. However, we do not know whether these differences are based on different lower leg motor capacity or instead reveal a general motor condition that could be detected by monitoring upper-limb motor behavior. We therefore captured body movements during a standard mobility task, namely the Timed Up and Go test (TUG) with subjects following different instructions while performing a rapid, repetitive goal-directed arm-movement test (arm-movement test). We hypothesized that we would be able to predict gait-related parameters from arm motor behavior, even regardless of age. METHODS: Sixty healthy individuals were assigned to three groups (young: mean 26 ± 3 years, middle-aged 48 ± 9, old 68 ± 7). They performed the arm-movement and TUG test under three conditions: preferred (at preferred movement speed), dual-task (while counting backwards), and fast (at fast movement speed). We recorded the number of contacts within 20 s and the TUG duration. We also extracted TUG walking sequences to analyze spatiotemporal gait parameters and evaluated the correlation between arm-movement and TUG results. RESULTS: The TUG condition at preferred speed revealed differences in gait speed and step length only between young and old, while dual-task and fast execution increased performance differences significantly among all 3 groups. Our old group's gait speed decreased the most doing the dual-task, while the young group's gait speed increased the most during the fast condition. As in our TUG results, arm-movements were significant faster in young than in middle-aged and old. We observed significant correlations between arm movements and the fast TUG condition, and that the number of contacts closely predicts TUG timefast and gait speedfast. This prediction is more accurate when including age. CONCLUSION: We found that the age-related decline in mobility performance that TUG reveals strongly depends on the test instruction: the dual-task and fast condition clearly strengthened group contrasts. Interestingly, a fast TUG performance was predictable by the performance in a fast repetitive goal-directed arm-movements test, even beyond the age effect. We assume that arm movements and the fast TUG condition reflect similarly reduced motor function. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) number: DRKS00016999, prospectively registered on March, 26, 2019.

Type of exercise may influence postural adaptations in chemotherapy-induced peripheral neuropathy.

OBJECTIVE: Traditional posturography measurements characterize postural instability in patients with chemotherapy-induced peripheral neuropathy (CIPN), while underlying postural control mechanisms remain unclear. Taking a model-based approach can yield insights into these mechanisms. This study's aim was to characterize the modifications in postural control of CIPN patients associated with exercise in relation to the postural behavior of healthy control participants (hCON) via an exploratory approach. METHODS: Thirty-one CIPN patients were randomly assigned to two interventions (balance plus moderate endurance training vs. moderate endurance training only) and exercised twice per week over 12 weeks. Baseline data were compared to 36 matched hCONs. We recorded spontaneous sway and postural reactions to platform tilts using Optotrak and a Kistler force platform pre- and post-intervention. Data interpretation relied on a model-based parameter identification procedure. RESULTS: Spontaneous sway amplitudes were larger and postural reactions smaller, with a relative phase advance, in our pre-intervention patients than the hCONs. Post-intervention, spontaneous sway, and postural reactions were reduced and the sensory-motor ratio larger in both groups, while the postural reaction timing differed between groups. INTERPRETATION: The abnormally small postural reactions in CIPN patients before the intervention can be interpreted as the consequence of abnormally strong velocity control-a strategy modification that may serve as a prediction mechanism to compensate for the lack of timely and accurate proprioceptive signals. While both groups reduced postural sway and showed an adapted sensory-motor ratio post-intervention, the interventions seemed to trigger different velocity control strategies. This study emphasizes the need for taking a more differentiated perspective on intervention effects. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) number: DRKS00005419, prospectively registered on November 19, 2013.

Power Output and Efficiency During Supine, Recumbent, and Upright Cycle Ergometry.

Recumbent and supine cycling are common exercise modes in rehabilitation and clinical settings but the influence of postures on work efficiency is unclear. Therefore, the aim of this study was to compare metabolic and ventilatory efficiency during upright, recumbent, and supine postures. Potential differences should be assessed for suitable diagnostics and for prescriptions of training that probably is performed in alternative postures. Eighteen healthy subjects (age: 47.2 ± 18.4 years; 10 female, 8 male) participated in the study and each completed three incremental cycle ergometer tests until exhaustion in upright, recumbent (40°), and supine positions. Gas exchange, heart rate (HR), and lactate concentrations were analyzed and efficiency was calculated subsequently. Testing sessions were performed in random order within a 2-week period. Upright cycling resulted in significantly higher peak values [power output, oxygen uptake (Vo2), HR] as well as performance at lactate and ventilatory thresholds in comparison to recumbent or supine positions. Vco2/Vo2 slope and ventilatory efficiency (VE/Vco2 slope) were not affected by posture. Aerobic work efficiency (Vo2/P slope) and gross efficiency (GE) differed significantly between postures. Hereby, GE was lowest in supine cycling, particularly obvious in a mainly aerobic condition at 70 Watt [Median 11.6 (IQR 10.9-13.3) vs. recumbent: 15.9 (IQR 15.6-18.3) and upright: 17.4 (IQR 15.1-18.3)]. Peak power as well as GE and work efficiency values are influenced by cycling position, reinforcing the importance of adjusting test results for training prescriptions. Surprisingly, ventilatory efficiency was not affected in this study and therefore does not seem to falsify test results for pulmonary diagnostics.

Cardiopulmonary performance in allogeneic hematopoietic cell transplantation recipients-evaluation of pre-transplant risk assessments.

Cardiopulmonary performance reflects how well different organ systems interact. It is inter alia influenced by body composition, determines patients' quality of life and can also predict mortality. However, it is not yet used for risk prediction prior to allogeneic hematopoietic cell transplantations (alloHCT). Thus, we aimed to examine the predictive power of peak oxygen consumption (VO2peak) as a representative of cardiopulmonary performance and that of body composition before alloHCT to determine overall survival (OS) and non-relapse mortality (NRM) 2 years after transplantation. We also compared it with the predictive power of four commonly-used risk scores: revised Pretransplant Assessment of Mortality (rPAM), Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), revised Disease Risk Index (rDRI), European Society for Blood and Marrow Transplantation (EBMT). Fifty-nine patients performed a cardiopulmonary exercise test and body composition assessments before alloHCT and were observed for 2 years. Sixteen patients died. VO2peak and most risk scores assessed pre-transplant revealed no association with OS or NRM. Body composition parameters only within univariable analyses. But higher rDRI and the male sex, were associated with shorter OS and higher NRM. We thus propose that the current risk assessments be reconsidered. The predictive value of VO2peak and body composition need further clarification, however.

Accuracy of Two Point-of-Care Tests for Rapid Diagnosis of Bovine Tuberculosis at Animal Level using Non-Invasive Specimens.

Bovine tuberculosis (BTB) testing in cattle requires a significant investment of time, equipment, and labor. Novel, rapid, cheaper and accurate methods are needed. The Alere Determine TB lipoarabinomannan antigen (LAM-test) is a World Health Organization-endorsed point-of-care urine test designed to detect active TB disease in humans. The Lionex Animal TB Rapid Test (Lionex-test) is a novel animal specific TB diagnostic blood test. An animal level analysis was performed using urine (n = 141) and milk (n = 63) samples from depopulated BTB-suspected cattle to test the accuracy of the LAM-test when compared to results of positive TB detection by any routine BTB tests (BOVIGAM, necropsy, histology, culture, PCR) that are regularly performed by the United States Department of Agriculture (USDA). The agreement between the urine LAM-test and USDA standard tests were poor at varying testing time points. The same milk samples did not elicit statistically significant agreement with the Lionex-test, although positive trends were present. Hence, we cannot recommend the LAM-test as a valid BTB diagnostic test in cattle using either urine or milk. The Lionex-test's production of positive trends using milk samples suggests larger sample sizes may validate the Lionex-test in accurately diagnosing BTB in cattle using milk samples, potentially providing a quick and reliable field test for BTB.