Effectiveness of electronic patient reporting outcomes, by a digital telemonitoring platform, for prostate cancer care: the Protecty study.

Research aim and purpose: The benefits of Electronic Patient -Reported Outcomes (e-PRO) for telemonitoring are well established, allowing early detection of illnesses and continuous monitoring of patients. The primary objective of the PROTECTY study was to assess the compliance with patient use of the telemonitoring platform Cureety. An exploratory objective was to assess if the first-month health status is a prognostic factor of progression free-survival (PFS) and overall survival (OS) for prostate cancer patient. Methods: This prospective study was conducted at the Military Hospital Bégin on prostate cancer patients. Patients were allowed to respond to a symptomatology questionnaire based on CTCAE v.5.0, personalized to their pathology and treatment. An algorithm evaluates the health status of the patient based on the reported adverse events, with a classification into 2 different states: Good Health Status (GHS) and Poor Health status (PHS). Results: Sixty-one patients were enrolled between July 1st, 2020 and September 30th, 2021. The median age was 74.0 (range 58.0-94.0). 78% presented a metastatic stage, and the most represented cancer was mHSPC. Overall, 2,457 questionnaires were completed by the patients, 4.0% resulted in a health classification in to monitor or critical state. 87% of patients were classified in the GHS group. The compliance was 72% in the overall population during the first month, 71% in GHS group and 75% in PHS group. The median follow-up was 8 months. PFS at 6 months was 84% in GHS group vs. 57% in PHS group, p = 0.19. OS at 6 months was 98% in GHS group vs. 83% in PHS group, p = 0.31. Conclusions: Our study showed that compliance was satisfactory. The feasibility of remote monitoring for prostate cancer patients means that they should benefit from its implementation. Our study is also the first to assess the correlation between treatment tolerance and survival. The initial results suggest that e-PRO assessment could help identify in the early stages the patients that require further health assessment and potential therapeutic changes. While further follow-up of more patients will be required, our study highlights the importance of e-PRO in cancer patient care.

A new agarose-based microsystem to investigate cell response to prolonged confinement.

Emerging evidence suggests the importance of mechanical stimuli in normal and pathological situations for the control of many critical cellular functions. While the effect of matrix stiffness has been and is still extensively studied, few studies have focused on the role of mechanical stresses. The main limitation of such analyses is the lack of standard in vitro assays enabling extended mechanical stimulation compatible with dynamic biological and biophysical cell characterization. We have developed an agarose-based microsystem, the soft cell confiner, which enables the precise control of confinement for single or mixed cell populations. The rigidity of the confiner matches physiological conditions and its porosity enables passive medium renewal. It is compatible with time-lapse microscopy, in situ immunostaining, and standard molecular analyses, and can be used with both adherent and non-adherent cell lines. Cell proliferation of various cell lines (hematopoietic cells, MCF10A epithelial breast cells and HS27A stromal cells) was followed for several days up to confluence using video-microscopy and further documented by Western blot and immunostaining. Interestingly, even though the nuclear projected area was much larger upon confinement, with many highly deformed nuclei (non-circular shape), cell viability, assessed by live and dead cell staining, was unaffected for up to 8 days in the confiner. However, there was a decrease in cell proliferation upon confinement for all cell lines tested. The soft cell confiner is thus a valuable tool to decipher the effects of long-term confinement and deformation on the biology of cell populations. This tool will be instrumental in deciphering the impact of nuclear and cytoskeletal mechanosensitivity in normal and pathological conditions involving highly confined situations, such as those reported upon aging with fibrosis or during cancer.

Differences in trochlear parameters between native and prosthetic kinematically or mechanically aligned knees.

INTRODUCTION: Kinematic (KA) and mechanical (MA) alignment techniques are two different philosophies of implant positioning that use the same TKA implants. This might generate differences in the resulting prosthetic trochleae parameters between the two techniques of alignment. Our study aim was to test the following hypotheses : (1) mechanically or kinematically aligned femoral implant understuffs the native trochlear articular surface and poorly restores the native groove orientation, and (2) the orientation of the prosthetic trochlear groove and trochlear fill are different between MA and KA. METHODS: Three-dimensional models of the femur were made from segmentation of preoperative Magnetic Resonance Imaging scans (MRIs) of ten subjects with isolated medial tibiofemoral osteoarthritis. In-house planning and analysis software kinematically and mechanically aligned a modern cruciate retaining femoral component and determined differences in parameters of the trochlear fit between native and prosthetic trochleae, and between KA and MA prosthetic trochleae. RESULTS: The MA prosthetic trochleae did not fill (understuffed) the entire length of the native medial facet and the proximal 70% of the native groove and lateral facet, and oriented the trochleae groove 8° more valgus than native. The KA prosthetic trochleae understuffed the proximal 70% of the native trochleae, and had a groove 6° more valgus than native. The KA trochleae understuffed the medial facet distally and oriented the groove 2° less valgus and 3° more internally rotated than the MA trochleae. CONCLUSION: MA and KA prosthetic trochleae substantially understuff and create a prosthetic groove more valgus compared to native trochlear anatomy, and they also differed between each other regarding trochleae stuffing and groove alignment. Although randomized trials have not shown differences in patellofemoral complications between KA and MA, a femoral component designed specifically for KA that more closely restores the native trochlear anatomy might improve patient reported satisfaction and function. LEVEL OF EVIDENCE: Level 2 controlled laboratory study.

Modified first or second cervical nerve transplantation technique for the treatment of recurrent laryngeal neuropathy in horses.

BACKGROUND: In horses, the only established method for reinnervation of the larynx is the nerve-muscle pedicle implantation, whereas in human medicine, direct nerve implantation is a standard surgical technique for selective laryngeal reinnervation in human patients suffering from bilateral vocal fold paralysis. OBJECTIVES: (1) To describe a modified first or second cervical nerve transplantation technique for the treatment of recurrent laryngeal neuropathy (RLN) in horses and (2) evaluate the outcomes of reinnervation using direct nerve needle-stimulation of the first cervical nerve and exercising endoscopy before and after surgery. STUDY DESIGN: Case series. METHODS: Nerve transplantation surgery, in which the first or second cervical nerve is tunnelled through the atrophied left cricoarytenoideus dorsalis muscle, was performed in combination with ipsilateral laser ventriculocordectomy. Ultrasound-guided stimulation of the first cervical nerve at the level of the alar foramen was used to confirm successful reinnervation post-operatively. Exercising endoscopy was performed before and after surgery. The exercising RLN grade of the left arytenoid was blindly determined at the highest stride frequency for each examination. RESULTS: Surgery was performed in 17 client-owned animals with RLN. Reinnervation was confirmed by nerve stimulation and subsequent arytenoid abduction observed in 11 out of 12 cases between 4 and 12 months post-operatively. Fourteen horses had exercising endoscopy before and after surgery. Nine horses had an improved exercising RLN grade, four horses had the same exercising grade and one horse had a worse exercising grade after surgery. MAIN LIMITATIONS: A sham-operated control group was not included and follow-up beyond 12 months and objective performance data were not obtained. CONCLUSIONS: The modified first or second cervical nerve transplantation technique, using tunnelling and direct implantation of the donor nerve into the cricoarytenoideus dorsalis muscle, resulted in reinnervation in 11 out of 12 cases and improved exercising grade in 9 out of 14 horses within 12 months after surgery.

Mechanical alignment technique for TKA: Are there intrinsic technical limitations?

BACKGROUND: Mechanically aligned (MA) total knee arthroplasty (TKA) is affected by disappointing functional outcomes in spite of the recent improvements in surgical precision and implant designs. This might suggest the existence of intrinsic technical limitations. Our study aims to compare the prosthetic and native trochlear articular surfaces and to estimate the extent of collateral ligament imbalance, which is technically uncorrectable by collateral ligament release when TKA implants are mechanically aligned. STUDY HYPOTHESIS: Conventional MA technique generates a high rate of prosthetic overstuffing of the distal groove, distal lateral trochlear facet and distal lateral femoral condyle (Hypothesis 1), and technically uncorrectable collateral ligament imbalance (hypothesis 2)? Disregarding the distal femoral joint line obliquity (DFJLO) when performing femoral cuts explains distal lateral femoral prosthetic stuffing and uncorrectable imbalance (hypothesis 3)? METHODS: Twenty patients underwent a conventional MA TKA. Pre-operative MRI-based 3D knee models were generated and MA TKA was simulated. Native and prosthetic trochlear articular surfaces were compared using in-house analysis software. Following the automatic determination by the planning software of the size of the extension and flexion gaps, an algorithm was applied to balance the gaps and the frequency and amplitude of technically uncorrectable knee imbalance were estimated. RESULTS: The conventional MA technique generates a significant slight distal lateral femoral prosthetic overstuffing (mean 0.6mm, 0.8mm, 1.25mm for the most distal lateral facet point, groove, and at the most distal point of lateral femoral condyle, respectively) and a high rate of type 1 and 2 uncorrectable knee imbalance (30% and 40%, respectively). The incidence of distal lateral prosthetic overstuffing (trochlea and condyle) and uncorrectable knee imbalance were strongly to very strongly correlated with the DFJLO (r=0.53 to 0.89). CONCLUSION: Conventional MA technique for TKA generates frequent lateral distal femoral prosthetic overstuffing and technically uncorrectable knee imbalance secondary to disregarding the DFJLO when adjusting the femoral component frontal and axial rotations, respectively. LEVEL OF EVIDENCE: level 4.

The kinematic alignment technique for TKA reliably aligns the femoral component with the cylindrical axis.

INTRODUCTION: Kinematic alignment (KA) technique is an alternative technique for positioning a TKA, which aims a patient-specific implant positioning in order to reproduce the pre-arthritic knee anatomy. Because reliability in implant positioning is of interest to obtain reproducible good functional results, our study tests the hypothesis that the medial and lateral distal and posterior positions of the planned and surgically implanted kinematically aligned femoral component are similar. METHODS: Preoperative knee magnetic resonance imaging (MRI) and postoperative knee computed tomography (CT) of 13 patients implanted with a KA Persona® TKA (Zimmer, Warsaw, USA) using manual instrumentation (kinematically-aligned TKA procedure pack®, Zimmer Biomet, Warsaw, USA) were segmented to create 3D femoral models. The kinematic alignment position of the femoral component was planned on the 3D model created from the preoperative MRI. Differences in the positions of the planned and surgically implanted kinematically-aligned femoral component were determined with in-house analysis software. RESULTS: The average differences between the medial and lateral distal and posterior positions of the planned and surgically implanted kinematically-aligned femoral component were inferior to 1mm and no statistically significant. In terms of variability, 62% (8/13) of performed implants matched all four positions within 1.5mm, and the maximum difference was 3mm. CONCLUSION: In this small series, intraoperative kinematic positioning of the femoral component with the specific manual instrumentation closely matched the planned position, which suggests that this technique reliably aligned the flexion-extension axis of the femoral component to the cylindrical axis. LEVEL OF EVIDENCE: Level 3.

Alignment options for total knee arthroplasty: A systematic review.

In spite of improvements in implant designs and surgical precision, functional outcomes of mechanically aligned total knee arthroplasty (MA TKA) have plateaued. This suggests probable technical intrinsic limitations that few alternate more anatomical recently promoted surgical techniques are trying to solve. This review aims at (1) classifying the different options to frontally align TKA implants, (2) at comparing their safety and efficacy with the one from MA TKAs, therefore answering the following questions: does alternative techniques to position TKA improve functional outcomes of TKA (question 1)? Is there any pathoanatomy not suitable for kinematic implantation of a TKA (question 2)? A systematic review of the existing literature utilizing PubMed and Google Scholar search engines was performed in February 2017. Only studies published in peer-reviewed journals over the last ten years in either English or French were reviewed. We identified 569 reports, of which 13 met our eligibility criteria. Four alternative techniques to position a TKA are challenging the traditional MA technique: anatomic (AA), adjusted mechanical (aMA), kinematic (KA), and restricted kinematic (rKA) alignment techniques. Regarding osteoarthritic patients with slight to mid constitutional knee frontal deformity, the KA technique enables a faster recovery and generally generates higher functional TKA outcomes than the MA technique. Kinematic alignment for TKA is a new attractive technique for TKA at early to mid-term, but need longer follow-up in order to assess its true value. It is probable that some forms of pathoanatomy might affect longer-term clinical outcomes of KA TKA and make the rKA technique or additional surgical corrections (realignment osteotomy, retinacular ligament reconstruction etc.) relevant for this sub-group of patients. Longer follow-up is needed to define the best indication of each alternative surgical technique for TKA. Level I for question 1 (systematic review of Level I studies), level 4 for question 2.

The influence of spine-hip relations on total hip replacement: A systematic review.

Sagittal pelvic kinematics along with spino-pelvic angular parameters have recently been studied by numerous investigators for their effect on total hip replacement (THR) clinical outcomes, but many issue of spine-hip relations (SHR) are currently unexplored. Therefore, our review aims at clarifying the following questions: is there any evidence of a relationship between articular impingement/dislocation risk in primary THR and (1) certain sagittal pelvic kinematics patterns, (2) pelvic incidence, and (3) types of SHRs? A systematic review of the existing literature utilising PubMed and Google search engines was performed in January 2017. Only clinical or computational studies published in peer-reviewed journals over the last five years in either English or French were reviewed. We identified 769 reports, of which 12 met our eligibility criteria. A review of literature shows that sagittal pelvic kinematics, but not the pelvic incidence, influences the risk of prosthetic impingement/dislocation. We found no study having assessed the relationship between this risk and the types of SHRs. Sagittal pelvic kinematics is highly variable among individuals and certain kinematic patterns substantially influences the risk of prosthetic impingement/dislocation. Recommendations for cup positioning are therefore switching from a systematic to a patient-specific approach, with the standing cup orientation Lewinneck safe zone progressively giving way to a new parameter of interest: the functional orientation of the cup. Based on a recently published classification for SHRs, We propose a new concept of "kinematically aligned THR" for the purposes of THR planning. Further studies are needed to investigate the relevance of such a classification towards the assumptions and hypothesis we have made. Level of evidence,- Level IV, systematic review of level III and IV studies.

Spine-hip relations add understandings to the pathophysiology of femoro-acetabular impingement: A systematic review.

Relationship between hip pathoanatomy and symptomatic FAI has been reported to be weak. This is explained by the reciprocal interaction between proximal femur and acetabular anatomies, but potentially also by the individual spine-hip relations (SHR). The key-answer for a complete understanding of the pathophysiology of FAI might lie in the comprehension of the SHRs, which have not yet been fully addressed. Therefore we conducted a systematic review to answer the subsequent questions: Is there any evidence of a relationship between FAI and (1) sagittal pelvic kinematics, (2) pelvic incidence, and (3) types of SHRs? A systematic review of the existing literature utilizing PubMed and Google search engines was performed in December 2016. Only studies published in peer-reviewed journals over the last ten years in either English or French were reviewed. We identified 90 reports, of which 9 met our eligibility criteria. Review of literature shows Caucasian FAI patients have a pelvis with higher anterior tilt, lesser sagittal mobility, and lower pelvic incidence compared to healthy patients. We found no study having assessed the relationship between SHR and FAI. In order to help further investigations at answering questions 3 and 4, we have developed a classification for SHRs. The classification according spino-pelvic parameters allows identifying patient at risk regarding FAI occurrence. Higher anterior pelvic tilt in standing, sitting and squatting positions and lower pelvic incidence have been found to correlate with symptomatic FAI. Because defining the individual SHR might increase the understanding of the pathophysiology of hip impingement, we have developed a classification for SHRs. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and IV studies.

[Genital lymphedema associated with Crohn's disease]. / Lymphœdème génital associé à une maladie de Crohn.

INTRODUCTION: Crohn's disease is a chronic inflammatory intestinal pathology which can be associated to different extra-digestive manifestations. We reported a case of recurrent genital lymphedema leading to Crohn's disease diagnosis. CASE REPORT: A 49-year-old man was referred for increased penis and scrotal volume, associated with recurrent febrile flare during the 10 previous years. Clinically, we noted an inflammatory penis and scrotum lymphedema. Clinical urological examination, and biological, bacteriological, computer-tomography examinations were negative. Metastatic Crohn's disease was diagnosed in association with concomitant severe terminal ileitis. Treatment with corticosteroids and azathioprine resulted in significant decrease of inflammatory genital lymphedema. CONCLUSION: Genital inflammatory lymphedema occurs during inflammatory, infectious, and tumor diseases. Some cases of metastatic genital lymphedema related to Crohn's disease are described, most often in children. Inflammatory genital lymphedema associated with gastrointestinal symptoms may suggest Crohn's disease.

Metal-on-metal hip resurfacing compared with 28-mm diameter metal-on-metal total hip replacement: a randomised study with six to nine years' follow-up.

A total of 219 hips in 192 patients aged between 18 and 65 years were randomised to 28-mm metal-on-metal uncemented total hip replacements (THRs, 107 hips) or hybrid hip resurfacing (HR, 112 hips). At a mean follow-up of eight years (6.6 to 9.3) there was no significant difference between the THR and HR groups regarding rate of revision (4.0% (4 of 99) vs 5.8% (6 of 104), p = 0.569) or re-operation rates without revision (5.1% (5 of 99) vs 2.9% (3 of 104), p = 0.428). In the THR group one recurrent dislocation, two late deep infections and one peri-prosthetic fracture required revision, whereas in the HR group five patients underwent revision for femoral head loosening and one for adverse reaction to metal debris. The mean University of California, Los Angeles activity scores were significantly higher in HR (7.5 (sd 1.7) vs 6.9 (sd 1.7), p = 0.035), but similar mean Western Ontario and McMaster Universities Osteoarthritis Index scores were obtained (5.8 (sd 9.5) in HR vs 5.1 (sd 8.9) in THR, p = 0.615) at the last follow-up. Osteolysis was found in 30 of 81 THR patients (37.4%), mostly in the proximal femur, compared with two of 83 HR patients (2.4%) (p < 0.001). At five years the mean metal ion levels were < 2.5 µg/l for cobalt and chromium in both groups; only titanium was significantly higher in the HR group (p = 0.001). Although revision rates and functional scores were similar in both groups at mid-term, long-term survival analysis is necessary to determine whether one procedure is more advantageous than the other.

Multivariate data analysis to evaluate the fingerprint peaks responsible for the cytotoxic activity of Mallotus species.

The Mallotus genus comprises numerous species used as traditional medicines in oriental countries and provides scientists a broad basis in the search for pharmacologically active constituents. In this paper, the cytotoxicity of 39 Mallotus extracts, different in species, part of the plant used, origin, and harvest season, is evaluated combining cytotoxicity assays with fingerprint technology and data handling tools. At first, the antiproliferative activity of the plant extracts is analyzed both on a non-cancerous cell line (WI-38--human lung fibroblast) and on a cancerous cell line (HeLa human cervix carcinoma). The results are linked to a data set of high-performance liquid chromatographic fingerprint profiles of the samples using multivariate calibration techniques. The regression coefficients of the multivariate model are then evaluated to indicate those peaks potentially responsible for the cytotoxic activity of the Mallotus extracts. In a final step, the cytotoxic extracts are analyzed by HPLC-MS and the indicated peaks identified.

A Study Ex Vivo of the Effect of Epicardial Fat on the HeartLander Robotic Crawler.

A tethered epicardial crawling robot known as HeartLander has been developed for minimally-invasive surgery on the beating heart. The crawler has been tested in vivo many times in a porcine model, a model which provides generally authentic conditions in many ways; however, the pigs tested generally have little epicardial fat, whereas the epicardial fat in human patients will be considerable. As a result, it is necessary to determine the effect of such fat on the performance of the crawler. In one experiment, using fresh ovine hearts ex vivo, clogging of the suction chambers of the crawler during sliding over tissue with active suction was investigated for a variety of thicknesses of epicardial fat. In a second experiment, the maximum traction force during each step was measured when sliding with active suction repeatedly over the same location for a variety of fat thicknesses. The clogging experiment showed accumulation of fat in the suction chamber, with the amount dependent on the state of the epicardial membrane, but the suction line did not clog. The traction experiment showed that traction was maintained in all cases except when the epicardial membrane was excised completely.

Multi-luminescent hybrid gadolinium oxide nanoparticles as potential cell labeling.

This manuscript analyses the use of newly developed hybrid gadolinium oxide nanoparticles as cell-labeling tracers. The nanoparticles are core-shell particles composed of a core of gadolinium oxide of [2-4] nm and a protecting shell of polysiloxane [1-3 nm] where different organic dyes (fluoresceine isothiocyanate (FITC) or rhodamine B isothiocyanate (RBITC)) are embedded. They are functionalized with poly(ethylene glycol)bis(carboxymethyl) to ensure their colloidal stability in biological buffers. These particles are potential multi-labeling tracers (magnetic and optical). In this paper, we show by optical imaging that they can be efficiently internalized in cells without cell alteration. The in-vitro uptake of the nanoparticles was followed in two cell lines (human fibroblasts and a human adenocarnima cell lines MCF7 cells). Nanoparticles distribution within cells was analysed by confocal analysis, and gadolinium concentration within cells was quantified by mass spectrometry (ICP-MS analysis). Nanoparticles uptake is found to be fast and efficient for both cell lines, with fluorescent labeling visible after 10 min of incubation whatever the nature of the fluorophore. The fluorescent intensity is mainly found as concentrated dots in the perinuclear region of the cells and decreases with the number of days in culture, but is still easily detectable after 3 days in culture. No significant effect on cell growth was detected. Finally, we show in this study the protective effect of the polysiloxane layer: encapsulation of RBITC within the polysiloxane shell, leads to a better photostability of this low cost dye than Cy3 and even reach a level comparable to Alexa 595. With their high photostability and long-lasting contrast properties, these hybrid luminescent nanoparticles appears thus as a versatile solution to assess multiple cell fate both in in-vitro cell model as well as in-vivo.

Development of HPLC fingerprints for Mallotus species extracts and evaluation of the peaks responsible for their antioxidant activity.

Some Mallotus species are used in traditional medicine in Vietnam. To use certain species in Western medicines or as food supplements, they should be identified and quality control should be more strict, for instance, to avoid the erroneous switching of species. In species with interesting activities, the compounds responsible for them should be identified. For these identifications, HPLC fingerprint methodology can be used. In this paper, HPLC fingerprints of different lengths were developed for a number of Mallotus species. Secondly, a multivariate regression model was constructed to model the antioxidant activity of the Mallotus samples from the HPLC fingerprints with the aim to indicate peaks possibly responsible for this activity. For this purpose, after data pretreatment, the calibration technique partial least squares (PLS) was applied.

Changes in the magnitude and distribution of forces at different Dictyostelium developmental stages.

The distribution of forces exerted by migrating Dictyostelium amebae at different developmental stages was measured using traction force microscopy. By using very soft polyacrylamide substrates with a high fluorescent bead density, we could measure stresses as small as 30 Pa. Remarkable differences exist both in term of the magnitude and distribution of forces in the course of development. In the vegetative state, cells present cyclic changes in term of speed and shape between an elongated form and a more rounded one. The forces are larger in this first state, especially when they are symmetrically distributed at the front and rear edge of the cell. Elongated vegetative cells can also present a front-rear asymmetric force distribution with the largest forces in the crescent-shaped rear of the cell (uropod). Pre-aggregating cells, once polarized, only present this last kind of asymmetric distribution with the largest forces in the uropod. Except for speed, no cycle is observed. Neither the force distribution of pre-aggregating cells nor their overall magnitude are modified during chemotaxis, the later being similar to the one of vegetative cells (F(0) approximately 6 nN). On the contrary, both the force distribution and overall magnitude is modified for the fast moving aggregating cells. In particular, these highly elongated cells exert lower forces (F(0) approximately 3 nN). The location of the largest forces in the various stages of the development is consistent with the myosin II localization described in the literature for Dictyostelium (Yumura et al.,1984. J Cell Biol 99:894-899) and is confirmed by preliminary experiments using a GFP-myosin Dictyostelium strain.

Magnetic control of Dictyostelium aggregation.

We report the control of cell migration by external magnetic forces during the early stage of Dictysostelium discoideum morphogenesis. Magnetically labeled aggregating cells respond to the presence of a magnetic field created by a thin magnetic tip: forces as low as 30 pN are sufficient to elicit the aggregation of the cells at the extremity of the tip. This induced magnetotaxis is competitive to classical chemotaxis. We therefore underline the interplay between external mechanical forces and morphogenesis. This magnetic assay will open new possibilities in the study of morphogenesis in Dictyostelium.

Antiproliferative effects of isopentenylated coumarins isolated from Phellolophium madagascariense Baker.

From the leaves of Phellolophium madagascariense Baker (Apiaceae), an endemic herb to Madagascar, three known coumarins (osthol, murraol and meranzin hydrate) have been isolated and identified. This is the first report of these compounds in this species. The structural elucidations were based on the analysis of physical and spectroscopic data. The anticancer activity of the three isolated compounds and of a synthetic sample of osthol was evaluated on L1210 mouse leukemia and on human prostatic cancer hormonosensitive LNCaP and hormonoindependent PC3 and DU145 cell lines.

Long-term expression and repeated administration of AAV type 1, 2 and 5 vectors in skeletal muscle of immunocompetent adult mice.

Adeno-associated viral (AAV) vectors promote long-term gene transfer into muscle in many animal species. Increased expression levels may be obtained by using alternative serotypes in combination with repeated administrations. Here we compared AAV vectors based on serotypes 1, 2 and 5 in immunocompetent mice and assessed the feasibility of multiple administrations of either identical (readministration) or different (cross-administration) serotype-based vectors. A 1-year-long dose-response study confirmed the superiority of recombinant (r)AAV1, achieving transduction levels 5 to 10-fold higher than rAAV2 and rAAV5 in mouse skeletal muscle, respectively. Repeated administration demonstrated that increased gene transfer level was achieved with a second injection of rAAV1 following the first administration of rAAV2 or rAAV5. A readministration study with a vector encoding a different gene allowed the evaluation of gene expression from the second vector only. All three rAAVs were inhibited when the animals were previously exposed to the same serotype. In contrast, no significant change in gene expression from the second vector was observed in cross-administration. A humoral immune response was elicited against the viral capsid for all three serotypes following the initial exposure. Neutralizing antibody (NAB) levels correlated with the vector dose injected. No significant cross-reactivity of NAB from a given serotype toward another was observed in vitro. These data provide the first direct comparative evaluation of re- and cross-administration of rAAV1, rAAV2 and rAAV5 in muscle, and further indicate that rAAV1 is capable of transducing muscle tissue when cross-administered.

Improved traction for a mobile robot traveling on the heart.

This document describes the effects of several design parameters on the traction generated by the suction pads of a mobile robot that walks on the surface of the heart. HeartLander is a miniature mobile robot that adheres to the epicardial surface of the heart using suction, and can travel to any desired location on the heart to administer therapeutic applications. To maximize the effectiveness of locomotion, the gripper pads must provide sufficient traction to avoid slipping. Our testing setup measured the force applied to the gripper pad adhering to ovine epicardial tissue, and recorded overhead video for tracking of the pad and tissue during an extension. By synchronizing the force and video data, we were able to determine the point at which the pad lost traction and slipped during the extension. Of the pads tested, the pad with no suction grate achieved maximum traction. Increasing the extension speed up to 20 mm/s resulted in a corresponding increase in traction. Increasing the vacuum pressure also improved the traction, but the magnitude of the effect was less than the improvement gained from increasing extension speed.