Motor Control Insights on Walking Planner and its Stability

The application of biomechanic and motor control models in the control of bidedal robots (humanoids, and exoskeletons) has revealed limitations of our understanding of human locomotion. A recently proposed model uses the potential energy for bipedal structures to model the bipedal dynamics, and it allows to predict the system dynamics from its kinematics. This work proposes a task-space planner for human-like straight locomotion that target application of in rehabilitation robotics and computational neuroscience. The proposed architecture is based on the potential energy model and employs locomotor strategies from human data as a reference for human behaviour. The model generates Centre of Mass (CoM) trajectories, foot swing trajectories and the Base of Support (BoS) over time. The data show that the proposed architecture can generate behaviour in line with human walking strategies for both the CoM and the foot swing. Despite the CoM vertical trajectory being not as smooth as a human trajectory, yet the proposed model significantly reduces the error in the estimation of the CoM vertical trajectory compared to the inverted pendulum models. The proposed model is also able to asses the stability based on the body kinematics embedding in currently used in the clinical practice. However, the model also implies a shift in the interpretation of the spatiotemporal parameters of the gait, which are now determined by the conditions for the equilibrium and not \textit{vice versa}. In other words, locomotion is a dynamic reaching where the motor primitives are also determined by gravity

Hype or hope – Can combination therapies with third-generation EGFR-TKIs help overcome acquired resistance and improve outcomes in EGFR-mutant advanced/metastatic NSCLC?

Three generations of epidermal growth factor receptor - tyrosine kinase inhibitors (EGFR-TKIs) have been developed for treating advanced/metastatic non-small cell lung cancer (NSCLC) patients harboring EGFR-activating mutations, while a fourth generation is undergoing preclinical assessment. Although initially effective, acquired resistance to EGFR-TKIs usually arises within a year due to the emergence of clones harboring multiple resistance mechanisms. Therefore, the combination of EGFR-TKIs with other therapeutic agents has emerged as a potential strategy to overcome resistance and improve clinical outcomes. However, results obtained so far are ambiguous and ideal therapies for patients who experience disease progression during treatment with EGFR-TKIs remain elusive. This review provides an updated landscape of EGFR-TKIs, along with a description of the mechanisms causing resistance to these drugs. Moreover, it discusses the current knowledge, limitations, and future perspective regarding the use of EGFR-TKIs in combination with other anticancer agents, supporting the need for bench-to-bedside approaches in selected populations

Risk factors for recurrence in patients with Clostridium difficile infection due to 027 and non-027 ribotypes

Objectives: Our objective was to evaluate factors associated with recurrence in patients with 027+ and 027– Clostridium difficile infection (CDI). Methods: Patients with CDI observed between January and December 2014 in six hospitals were consecutively included in the study. The 027 ribotype was deduced by the presence of tcdB, tcdB, cdt genes and the deletion Δ117 in tcdC (Xpert® C. difficile/Epi). Recurrence was defined as a positive laboratory test result for C. difficile more than 14 days but within 8 weeks after the initial diagnosis date with reappearance of symptoms. To identify factors associated with recurrence in 027+ and 027– CDI, a multivariate analysis was performed in each patient group. Subdistributional hazard ratios (sHRs) and 95% confidence intervals (95%CIs) were calculated. Results: Overall, 238 patients with 027+ CDI and 267 with 027– CDI were analysed. On multivariate analysis metronidazole monotherapy (sHR 2.380, 95%CI 1.549–3.60, p <0.001) and immunosuppressive treatment (sHR 3.116, 95%CI 1.906–5.090, p <0.001) were factors associated with recurrence in patients with 027+ CDI. In this patient group, metronidazole monotherapy was independently associated with recurrence in both mild/moderate (sHR 1.894, 95%CI 1.051–3.410, p 0.033) and severe CDI (sHR 2.476, 95%CI 1.281–4.790, p 0.007). Conversely, non-severe disease (sHR 3.704, 95%CI 1.437–9.524, p 0.007) and absence of chronic renal failure (sHR 16.129, 95%CI 2.155–125.000, p 0.007) were associated with recurrence in 027– CDI. Conclusions: Compared to vancomycin, metronidazole monotherapy appears less effective in curing CDI without relapse in the 027+ patient group, independently of disease severity

Meropenem-Vaborbactam as Salvage Therapy for Ceftazidime-Avibactam-, Cefiderocol-Resistant ST-512 Klebsiella pneumoniae-Producing KPC-31, a D179Y Variant of KPC-3

A 68-year-old man had recurrent bacteremia by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae resistant to ceftazidime-avibactam and cefiderocol. The sequencing of a target region showed that it harbored a KPC-3 variant enzyme (D179Y; KPC-31), which confers resistance to ceftazidime-avibactam and restores meropenem susceptibility. The patient was successfully treated with meropenem-vaborbactam

Estudo experimental da ação dos anti-inflamatórios não hormonais inibidores seletivos da ciclooxigenase 2 (COX-2) e anti-inflamatórios tradicionais na regeneração óssea

OBJECTIVE: The aim of this study is to compare the effects of traditional nonsteroidal anti-inflammatory drugs with nonsteroidal anti-inflammatory drugs that are selective cyclooxygenase-2 (COX-2) inhibitors in the process of bone regeneration in a rat model. MATERIALS AND METHODS: Forty-four Wistar strain rats were subjected to osteotomy of the right femur and randomly divided into 3 groups according to the drug to be given (diclofenac, rofecoxib, or placebo). Each group was divided into 2 subgroups according to the time to euthanasia after the surgery. The animals of Subgroup 1 were submitted to euthanasia 2 weeks after surgery, and those of Subgroup 2, underwent euthanasia 4 weeks after surgery. Radiographic examinations and bone callus histomorphometry were analyzed. RESULTS: No intergroup statistical difference was found in the bone callus area or in bone formation area 2 and 4 weeks after surgery. Intra-group analysis concerning the bone neoformation area inside the callus showed a significant difference within the diclofenac group, which presented less tissue. CONCLUSIONS: Fracture consolidation in Wistar rats occurs within less than 2 weeks, and the use of nonsteroidal anti-inflammatory drugs does not significantly influence this process.OBJETIVO: Comparar os efeitos do uso de antiinflamatórios não-esteróides tradicionais (AINES) e AINES que são inibidores seletivos da ciclooxigenase-2 (COX-2), no processo de regeneração óssea em ratos. MATERIAL E MÉTODO: Quarenta e quatro ratos da linhagem Wistar submetidos a osteotomia do femur direito e divididos em três grupos, conforme o medicamento que receberam (diclofenaco, rofecoxib e placebo). Cada grupo foi dividido em dois subgrupos, conforme o tempo até o sacrifício, após a cirurgia. Os animais do subgrupo 1 foram sacrificados duas semanas após a cirurgia e os do subgrupo 2, quatro semanas após a cirurgia. Foram analisados exames radiográficos e a histomorfometria do calo ósseo. RESULTADOS: Não foram encontradas diferenças estatísticas na área do calo ósseo 2 e 4 semanas após a cirurgia. No que se refere à área de neoformação óssea dentro do calo, observou-se diferença estatisticamente significante apenas dentro do grupo do diclofenaco, que apresentou menos tecido. CONCLUSÕES: A consolidação da fratura em ratos Wistar ocorre dentro de 2 semanas e o uso de antiinflamatórios não-esteróides não influi de forma significante neste processo