Comparison of laparoscopic steerable instruments performed by expert surgeons and novices

As an alternative to the surgical robot, some medical companies have engineered new steerable devices that mimic the robot's capacities. This study aimed to assess how steerable instruments ameliorate the efficacy of suturing in comparison with the traditional instrument, and a combination instruments, performed by experienced and novice surgeons. The study was performed by three experienced surgeons and three novice surgeons. The instruments employed were divided into three surgical sets: two steerable dissectors; one steerable dissector and one straight needle ; two straight needle holders. The study supervisor recorded the total time for the procedure, the number of bites completed, the time for each bite, and the quality of the procedure. In our study, we found consistent data demonstrating that experienced laparoscopists completed the prescribed suture pattern with more bites in less time than novices. The use of two steerable instruments was more time consuming than standard straight instruments, but a combination of instruments was significantly less time consuming, as was the use of two straight needle holders. This result was even observed in novice surgeons. Combining a steerable instrument with a traditional straight needle holder provided more advantages in this study

CATMoS: Collaborative Acute Toxicity Modeling Suite.

BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silico models built using existing data facilitate rapid acute toxicity predictions without using animals. OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop in silico models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50≤50mg/kg)], and nontoxic chemicals (LD50>2,000mg/kg). METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495

Swine small intestine sealing performed by different vessel sealing devices: Ex-vivo test

This study aimed to evaluate the sealing quality of swine small intestine using different laparoscopic radiofrequency vessel sealing devices (two 5 mm: RFVS-1 and -2; one 10 mm: RFVS- 3) and a harmonic scalpel (HS) compared to golden standard closure technique. The study was divided into two arms. In study arm 1: n = 50 swine intestinal loops (10 per group) were transected with each instrument and the loops in which the devices provided complete sealing, at the gross inspection, were tested for maximum burst pressure (BP) and histological evaluation and compared to an automatic linear stapler. After the BP tests, the devices that achieved significantly lower BP values were excluded from the second arm. The RFVS-1 and -3 provided statistically significant results and were used in study arm 2, to obtain full-thickness biopsies along the antimesenteric border of the loop and were compared with hand-sewn intestinal closure (n = 30; 10 per group). The biopsies were histologically evaluated for thermal injury and diagnostic features, and intestinal loops tested for BP. RFVS-3 achieved comparable results (69.78 ± 4.23 mmHg, interquartile range (IQR) 5.8) to stapler closing technique (71.09 ± 4.22 mmHg, IQR 4.38; p > 0.05), while the RFVS-1 resulted in significantly (p < 0.05) lower BP (45.28 ± 15.23 mmHg, IQR 24.95) but over the physiological range, conversely to RFVS-2 (20.16 ± 7.19 mmHg, IQR 12.02) and HS (not measurable). RFVS-3 resulted not significantly different (p > 0.05) (45.09 ± 8.75 mmHg, IQR 10.48) than Suture (35.71 ± 17.51 mmHg, IQR 23.77); RFVS-1 resulted significantly lower values (23.96 ± 10.63 mmHg, IQR 9.62; p < 0.05). All biopsies were judged diagnostic. Data confirmed that RFVS-1 and -3 devices provided suitable intestinal sealing, with BP pressures over the physiological range. Conversely, the HS and RFVS-2 should not be considered for intestinal sealing. RFVS devices could be employed to obtain small intestine stump closure or full-thickness biopsies. However, further studies should be performed in live animals to assess the role of the healing process

Accelerating drug discovery by early protein drug target prediction based on a multi-fingerprint similarity search †

In this continuing work, we have updated our recently proposed Multi-fingerprint Similarity Search algorithm (MuSSel) by enabling the generation of dominant ionized species at a physiological pH and the exploration of a larger data domain, which included more than half a million high-quality small molecules extracted from the latest release of ChEMBL (version 24.1, at the time of writing). Provided with a high biological assay confidence score, these selected compounds explored up to 2822 protein drug targets. To improve the data accuracy, samples marked as prodrugs or with equivocal biological annotations were not considered. Notably, MuSSel performances were overall improved by using an object-relational database management system based on PostgreSQL. In order to challenge the real effectiveness of MuSSel in predicting relevant therapeutic drug targets, we analyzed a pool of 36 external bioactive compounds published in the Journal of Medicinal Chemistry from October to December 2018. This study demonstrates that the use of highly curated chemical and biological experimental data on one side, and a powerful multifingerprint search algorithm on the other, can be of the utmost importance in addressing the fate of newly conceived small molecules, by strongly reducing the attrition of early phases of drug discovery programs

Psychophysical health and perception of well-being between master badminton athletes and the adult italian population

Background and aim of the work: Sport participation, regular exercise and physical activity in general exert many benefits on wellness, perceived health related quality of life and social satisfaction. As the people age, physical and mental deterioration occur. Master athletes are older adults that practice different sports, such as running, swimming and badminton. This is a widespread sport practiced by over 200 million people and is one of the most exerted sport in the world. In our study we compared the health perception of Italian Badminton Master athletes and normal Italian population of same age. Methods: Thirty (22 males, 8 females) Master badminton athletes between 18 and 69 years old participating to 2018 edition of the Italian Master Badminton Championship were enrolled for the study. All athletes compiled a six questions questionnaire, about perceived quality of life, included in the 2014-2017 Italian surveillance database “PASSI” questionnaire and answers were compared to 18-69 y/o Italian population results included in the public database. Results: Statistically significative differences were not detected between genders of master athletes. There was only a significative better psychological perception of quality of life in younger class of master athletes (p<0.05). A significative better perception was detected in Master athletes compared to normal Italian population. Conclusions: Aerobic sports, such as badminton, represent positive factors for improving health, psychological wellness and social engagement. Sport has a crucial role for the positive influence on growth in youngers and on the preventive role on typical diseases of older age, such as diabetes, ischemic cardiomyopathy and mental illness. (www.actabiomedica.it)

Wound Retractor Laparoscopic Port System for Standing Laparoscopic Cryptorchidectomy in the Horse: A Case Report

Cryptorchidectomy is the most commonly performed laparoscopic procedure in horses. However, its use for the extraction of an abdominal testis has disadvantages such as loss of a resected testis from grasp and fragmentation of the specimen because of the excessive tension required for extraction through a thick body wall. The ring wound retractor laparoscopic port system was recently used in human and small animal surgery to perform laparoscopic-assisted procedures and retrieve large specimens from the abdomen. In the present case, the wound retractor was placed as the ventral port in the right flank through a minilaparotomy. Thereafter, the cap with the gas inlet and instrument port was connected. The other two ports were placed dorsally using 10-mm stainless steel cannulas. Grasping forcep was introduced through the ventral port, and the laparoscope and vessel-sealing devices were introduced through the dorsal ports. After the testis was resected, it was retrieved from the abdomen through the retractor without the grasping forceps jaw being released. This is the first case report describing the use of the wound retractor laparoscopic port system for standing cryptorchidectomy in a horse. This system can be a feasible and safe option for flank laparoscopy in horses, and it facilitates specimen retrieval from the abdominal cavity, but further studies should confirm this preliminary report

Automated identification of structurally heterogeneous and patentable antiproliferative hits as potential tubulin inhibitors

By employing a recently developed hierarchical computational platform, we identified 37 novel and structurally diverse tubulin targeting compounds. In particular, hierarchical molecular filters, based on molecular shape similarity, structure-based pharmacophore, and molecular docking, were applied on a large chemical collection of commercial compounds to identify unexplored and patentable microtubule-destabilizing candidates. The herein proposed 37 novel hits, showing new molecular scaffolds (such as 1,3,3a,4-tetraaza-1,2,3,4,5,6,7,7a-octahydroindene or dihydropyrrolidin-2-one fused to a chromen-4-one), are provided with antiproliferative activity in the m range toward MCF-7 (human breast cancer lines). Importantly, there is a likely causative relationship between cytotoxicity and the inhibition of tubulin polymerization at the colchicine binding site, assessed through fluorescence polymerization assays

De Novo Drug Design of Targeted Chemical Libraries Based on Artificial Intelligence and Pair-Based Multiobjective Optimization

Artificial intelligence and multiobjective optimization represent promising solutions to bridge chemical and biological landscapes by addressing the automated de novo design of compounds as a result of a humanlike creative process. In the present study, we conceived a novel pair-based multiobjective approach implemented in an adapted SMILES generative algorithm based on recurrent neural networks for the automated de novo design of new molecules whose overall features are optimized by finding the best trade-offs among relevant physicochemical properties (MW, logP, HBA, HBD) and additional similarity-based constraints biasing specific biological targets. In this respect, we carried out the de novo design of chemical libraries targeting neuraminidase, acetylcholinesterase, and the main protease of severe acute respiratory syndrome coronavirus 2. Several quality metrics were employed to assess drug-likeness, chemical feasibility, diversity content, and validity. Molecular docking was finally carried out to better evaluate the scoring and posing of the de novo generated molecules with respect to X-ray cognate ligands of the corresponding molecular counterparts. Our results indicate that artificial intelligence and multiobjective optimization allow us to capture the latent links joining chemical and biological aspects, thus providing easy-to-use options for customizable design strategies, which are especially effective for both lead generation and lead optimization. The algorithm is freely downloadable at https://github.com/alberdom88/moo-denovo and all of the data are available as Supporting Information

41 cases of treatment of cranial cruciate ligament rupture with porous TTA: Three years of follow up

Tibial Tuberosity Advancement (TTA) is a surgical technique based on a linear osteotomy that determines a cranial advancement of the tibial tuberosity in patients suffering from cranial cruciate ligament rupture (CCL). The aim is to neutralize the cranial tibial thrust (CTT) and to reach a 90° angle between the patellar tendon and the tibial plateau with a physiological knee extension of 135°. In our study, a Ti6AI4V ELI (Titanium Aluminium Vanadium) titanium scaffold for the Porous TTA, with excellent properties of osteointegration and osteoconduction when subjected to cyclic loading has been adopted. Based on the previous scientific work on an ovine model, the use of this type of porous scaffolds has subverted the previous models. Scaffold production technology is based on direct mechanical manufacturing called Electron Beam Melting (EBM). For this study, 41 dogs, different breeds, medium-large size, weighing between 10 and 80 kg, aged between 1 and 13 years, were enrolled. The inclusion criteria were based on clinical evaluations (different gaits), drawer test and tibial compression, LOAD score (Liverpool Osteoarthritis in Dogs questionnaire), radiographic diagnosis in sedation with a 135° positioning of the joint and baropodometric investigations (Stance Analyzer). The results show that Porous TTA is an excellent method for functional recovery of the knee joint following the partial and total rupture of the CCL