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Background: Subarachnoid block is the most commonly used anesthetic technique for lower limb surgeries. Fentanyl is very often combined with hyperbaric bupivacaine as an adjuvant. This study was conducted to compare the block characteristics by administrating bupivacaine and fentanyl in a sequential and premixed manner. Aims and Objectives: The primary objective was to compare the effects of hyperbaric bupivacaine and fentanyl administered either as a premixed solution or sequentially on block characteristics-onset of sensory and motor blockade, regression of block and duration of analgesia. The secondary objective was to study the hemodynamic changes and adverse effects. Materials and Methods: A total of 72 patients scheduled to undergo lower limb surgery were allocated to three groups. Patients in Group A received 15 mg of 0.5 % bupivacaine heavy (H), followed by 25 mcg of fentanyl intrathecally using different syringes. Group B received 25 mcg of fentanyl, followed by 15 mg of 0.5% bupivacaine H in a separate syringe. Group C received premixed 0.5 % bupivacaine H 15 mg and fentanyl 25 mcg in single syringe. The block characteristics-onset and regression of sensory and motor blockade, duration of analgesia, and adverse effects were studied. Results: The mean time (minutes) taken for onset of sensory block was 2.40±0.51 in group A, 4.80±0.53 in Group B and 6.70±0.50 in Group C. Mean time (minutes) taken for onset of motor block was 4.35±0.43 in Group A, while it was 5.64±0.65 and 7.32±0.64 in Groups B and C, respectively. Two segment regression and duration of motor blockade were found to be longer in Group A. Conclusion: Sequential intrathecal administration of bupivacaine followed by fentanyl has a faster onset and prolonged duration of block when compared to the premixed group.

Effective bladder-preserving therapeutic options are needed for patients with bacillus Calmette-Guérin unresponsive non–muscle-invasive bladder cancer. Nadofaragene firadenovec-vncg (Adstiladrin®) was approved by the US Food and Drug Administration as the first gene therapy in urology and the first intravesical gene therapy indicated for the treatment of adult patients with high-risk bacillus Calmette-Guérin–unresponsive non–muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors. The proposed mechanism of action underlying nadofaragene firadenovec efficacy is likely due to the pleiotropic nature of interferon-α and its direct and indirect antitumor activities. Direct activities include cell death and the mediation of an antiangiogenic effect, and indirect activities are those initiated through immunomodulation of the innate and adaptive immune responses. The sustained expression of interferon-α that results from this treatment modality contributes to a durable response. This review provides insight into potential mechanisms of action underlying nadofaragene firadenovec efficacy.

Machinability is a generalized framework that attempts to quantify the response of a workpiece material to mechanical cutting, which has been developed as one of the key factors that drive the final selection of cutting parameters, tools, and coolant applications. Over the years, there are many attempts have been made to develop a standard evaluation method of machinability. However, due to the complexity of the influence factors, i.e., from work material and cutting tool to machine tool, that can affect the materials machinability, currently there is no uniquely defined quantification of machinability. As one of the outcomes from the CIRP's Collaborative Working Group on "Integrated Machining Performance for Assessment of Cutting Tools (IMPACT)", this paper conducts an extensive study to learn interacting machinability parameters to evaluate the overall machining performance. Specifically, attention is focused on recent advances made towards the determination of the machinability through tool wear, cutting force and temperature, chip form and breakability, as well as the surface integrity. Furthermore, the advanced methods that have been developed over the years to enable the improvement of machinability have been reviewed. [ABSTRACT FROM AUTHOR]