The consequences of the effects of the chemotherapeutic drug (vincristine) in organs and the influence on the bioavailability of two radio-biocomplexes used for bone evaluations in balb/c female mice

The development of animal model to evaluate the toxicological action of compounds used as pharmaceutical drugs is desired. The model described in this work is based on the capability of drugs to alter the bioavailability of radiopharmaceuticals (radiobiocomplexes) labeled with technetium-99 m(99mTc). There are evidences that the bioavailability or the pharmacokinetic of radiobiocomplexes can be modified by some factors, as drugs, due to their toxicological action in specific organs. Vincristine is anatural product that has been utilized in oncology. The vincristine effect on the bioavailability of the radiobiocomplexes 99mTc- ethylenediphosphonic acid (99mTc-MDP) and 99mTc-pyrophosphate (99mTc- PYP) in Balb/c female mice was evaluated. The fragments of kidney were processed to light microscopy and transmission electron microscopy. The aim of this work was to study at structural and ultrastructural levels the alterations caused by vincristine in organs. One hour after the last dose ofvincristine, 99mTc-PYP or 99mTc-MDP was injected, the animals were sacrificed and the percentage of radioactivity (%ATI) was determined in the isolated organs. Concerning 99mTc-PYP, the %ATI (i) decreased in spleen, thymus, lymph nodes (inguinal and mesentheric), kidney, lung, liver, pancreas, stomach, heart and brain and (ii) increased in bone and thyroid. Concerning 99mTc-MDP, the %ATI (iii) decreased in spleen, thymus, lymph nodes (inguinal and mesentheric), kidney, liver, pancreas,stomach, heart, brain, bone, ovary and uterus. In conclusion, the toxic effect of vincristine in determined organs could be responsible for the alteration of the uptake of the studied radiobiocomplexes

Feasibility of large-scale deployment of multiple wearable sensors in Parkinson’s disease

Wearable devices can capture objective day-to-day data about Parkinson’s Disease (PD). This study aims to assess the feasibility of implementing wearable technology to collect data from multiple sensors during the daily lives of PD patients. The Parkinson@home study is an observational, two-cohort (North America, NAM; The Netherlands, NL) study. To recruit participants, different strategies were used between sites. Main enrolment criteria were self-reported diagnosis of PD, possession of a smartphone and age ≥18 years. Participants used the Fox Wearable Companion app on a smartwatch and smartphone for a minimum of 6 weeks (NAM) or 13 weeks (NL). Sensor-derived measures estimated information about movement. Additionally, medication intake and symptoms were collected via self-reports in the app. A total of 953 participants were included (NL: 304, NAM: 649). Enrolment rate was 88% in the NL (n = 304) and 51% (n = 649) in NAM. Overall, 84% (n = 805) of participants contributed sensor data. Participants were compliant for 68% (16.3 hours/participant/day) of the study period in NL and for 62% (14.8 hours/participant/day) in NAM. Daily accelerometer data collection decreased 23% in the NL after 13 weeks, and 27% in NAM after 6 weeks. Data contribution was not affected by demographics, clinical characteristics or attitude towards technology, but was by the platform usability score in the NL (χ2 (2) = 32.014, p<0.001), and self-reported depression in NAM (χ2(2) = 6.397, p = .04). The Parkinson@home study shows that it is feasible to collect objective data using multiple wearable sensors in PD during daily life in a large cohort

Transanal total mesorectal excision: a pure NOTES approach for selected patients

Background: The concept of natural orifice transluminal endoscopic surgery (NOTES) has stimulated the development of various “incisionless” procedures. One of the most popular is the transanal approach for rectal lesions. The aims of this study were to report how we standardized NOTES technique for transanal mesorectal excision without abdominal assistance, discuss the difficulties and surgical outcomes of this technique and report its feasibility in a small group of selected patients. Methods: Three consecutive female patients underwent transanal NOTES rectal resection without transabdominal laparoscopic assistance for rectal lesions. Functional results were assessed with the Fecal Incontinence Quality of Life scale and the Wexner score. Results: The technical steps are described in details and complemented with a video. All procedures were completed without transabdominal laparoscopic help. The mesorectal plane was entirely dissected without any disruption, and distal and circumferential margins were tumor-free. No major complications were observed. Functional results show a significant impairment after surgery with improvement at 6 months to levels near those of the preoperative period. Conclusions: The performance and publication of NOTES procedures are subject to much discussion. Despite the small number of patients, this procedure appears feasible and can be accomplished maintaining fecal continence and respecting oncologic principles

Novel Strains of Mice Deficient for the Vesicular Acetylcholine Transporter: Insights on Transcriptional Regulation and Control of Locomotor Behavior

Defining the contribution of acetylcholine to specific behaviors has been challenging, mainly because of the difficulty in generating suitable animal models of cholinergic dysfunction. We have recently shown that, by targeting the vesicular acetylcholine transporter (VAChT) gene, it is possible to generate genetically modified mice with cholinergic deficiency. Here we describe novel VAChT mutant lines. VAChT gene is embedded within the first intron of the choline acetyltransferase (ChAT) gene, which provides a unique arrangement and regulation for these two genes. We generated a VAChT allele that is flanked by loxP sequences and carries the resistance cassette placed in a ChAT intronic region (FloxNeo allele). We show that mice with the FloxNeo allele exhibit differential VAChT expression in distinct neuronal populations. These mice show relatively intact VAChT expression in somatomotor cholinergic neurons, but pronounced decrease in other cholinergic neurons in the brain. VAChT mutant mice present preserved neuromuscular function, but altered brain cholinergic function and are hyperactive. Genetic removal of the resistance cassette rescues VAChT expression and the hyperactivity phenotype. These results suggest that release of ACh in the brain is normally required to “turn down” neuronal circuits controlling locomotion

Onset of asymptotic scaling in deuteron photodisintegration

We investigate the transition from the nucleon-meson to quark-gluon description of the strong interaction using the photon energy dependence of the $d(\gamma,p)n$ differential cross section for photon energies above 0.5 GeV and center-of-mass proton angles between $30^{\circ}$ and $150^{\circ}$. A possible signature for this transition is the onset of cross section $s^{-11}$ scaling with the total energy squared, $s$, at some proton transverse momentum, $P_T$. The results show that the scaling has been reached for proton transverse momentum above about 1.1 GeV/c. This may indicate that the quark-gluon regime is reached above this momentum.Comment: Accepted by PRL; 5 pages, 2 figure