Summary
Intravenous lidocaine is used widely for its effect on postoperative pain and recovery but it can be, and has been, fatal when used inappropriately and incorrectly. The risk‐benefit ratio of ...i.v. lidocaine varies with type of surgery and with patient factors such as comorbidity (including pre‐existing chronic pain). This consensus statement aims to address three questions. First, does i.v. lidocaine effectively reduce postoperative pain and facilitate recovery? Second, is i.v. lidocaine safe? Third, does the fact that i.v. lidocaine is not licensed for this indication affect its use? We suggest that i.v. lidocaine should be regarded as a ‘high‐risk’ medicine. Individual anaesthetists may feel that, in selected patients, i.v. lidocaine may be beneficial as part of a multimodal peri‐operative pain management strategy. This approach should be approved by hospital medication governance systems, and the individual clinical decision should be made with properly informed consent from the patient concerned. If i.v. lidocaine is used, we recommend an initial dose of no more than 1.5 mg.kg‐1, calculated using the patient’s ideal body weight and given as an infusion over 10 min. Thereafter, an infusion of no more than 1.5 mg.kg‐1.h‐1 for no longer than 24 h is recommended, subject to review and re‐assessment. Intravenous lidocaine should not be used at the same time as, or within the period of action of, other local anaesthetic interventions. This includes not starting i.v. lidocaine within 4 h after any nerve block, and not performing any nerve block until 4 h after discontinuing an i.v. lidocaine infusion.
The Himalayas are highly susceptible to various natural disasters, such as the tectonically induced land deformation, earthquakes, landslides, and extreme climatic events. Recently, the Joshimath ...town witnessed a significantly large land subsidence activity. The phenomenon resulted in the development of large cracks in roads and in over 868 civil structures, posing a significant risk to inhabitants and infrastructure of the area. This study uses a time-series synthetic aperture radar (SAR) interferometry-based PSInSAR approach to monitor land deformation utilizing multi-temporal Sentinel-1 datasets. The line of sight (LOS) land deformation velocity for the Joshimath region, calculated for the year 2022-2023 using a PSInSAR-based approach, varies from - 89.326 to + 94.46 mm/year. The + ve sign indicates the LOS velocity/displacement away from the SAR sensor, whereas - ve sign signifies the earth's movement towards the SAR sensor in the direction of LOS. In addition, the study investigates feature tracking land displacement analysis using multi-temporal high-resolution Planet datasets. The result of this analysis is consistent with the PSInSAR results. The study also estimated the land deformation for the periods 2016-2017, 2018-2019, and 2020-2021 separately. Our results show that the Joshimath region experienced the highest land deformation during the year 2022-2023. During this period, the maximum land subsidence was observed in the north-western part of the town. The maximum LOS land deformation velocity + 60.45 mm/year to + 94.46 mm/year (2022-2023), occurred around Singhdwar, whereas the north and central region of the Joshimath town experienced moderate to high subsidence of the order of + 10.45 mm/year to + 60.45 mm/year (2022-2023), whereas the south-west part experienced an expansion of the order of 84.65 mm/year to - 13.13 mm/year (2022-2023). Towards the south-east, the town experienced rapid land subsidence, - 13.13 mm/year to - 5 mm/year (2022-2023). The study analyzes the causative factors of the observed land deformation in the region. Furthermore, this work assesses the ground conditions of the Joshimath region using UAV datasets acquired in the most critically affected areas such as Singhdhaar, Hotel Mountain View, Malhari Hotel, and Manoharbagh. Finally, the study provides recommendations and future prospects for the development policies that need to be adopted in the critical Himalayan regions susceptible to land deformation. The study suggests that land deformation in the region is primarily attributed to uncontrolled anthropogenic activities, infrastructural development, along with inadequate drainage systems.
The synchondrosis in the cranial base is an important growth center for the craniofacial region. Abnormalities in the synchondroses affect the development of adjacent regions, including the ...craniofacial skeleton. Here, we report that the transcription factor TBX1, the candidate gene for DiGeorge syndrome, is expressed in mesoderm-derived chondrocytes and plays an essential and specific role in spheno-occipital synchondrosis development by inhibiting the expression of genes involved in chondrocyte hypertrophy and osteogenesis. In Tbx1-deficient mice, the spheno-occipital synchondrosis was completely mineralized at birth. TBX1 interacts with RUNX2, a master molecule of osteoblastogenesis and a regulator of chondrocyte maturation, and suppresses its transcriptional activity. Indeed, deleting Tbx1 triggers accelerated mineralization due to accelerated chondrocyte differentiation, which is associated with ectopic expression of downstream targets of RUNX2 in the spheno-occipital synchondrosis. These findings reveal that TBX1 acts as a regulator of chondrocyte maturation and osteogenesis during the spheno-occipital synchondrosis development. Thus, the tight regulation of endochondral ossification by TBX1 is crucial for the normal progression of chondrocyte differentiation in the spheno-occipital synchondrosis.
In this paper, a rectangular triple-band microstrip antenna has been designed for Bluetooth application by successively loading notches and slots of different dimension in radiating patch. The ...conventional microstrip antenna suffers with narrow impedance bandwidth. The current work affords an alternate option to enhance the bandwidth of antenna that resonates in triple-band operation. Initially, the antenna is resonating in single-band but after loading slots, the bandwidth of microstrip antenna has been obtained 1.97% (lower band), 10.35% (middle band) and 33.16% (upper band) resonating in triple-band with three resonant frequency at 1.422 GHz (lower resonant frequency), 1.791 GHz (middle resonant frequency) and 2.467 GHz (higher resonant frequency). The suggested antenna has upper frequency band in the range of 2.045–2.858 GHz resonating at 2.467 GHz frequency and it is appropriate for Bluetooth applications (2.40–2.48 GHz) and both lower band useful for other wireless (L-band) applications. The return loss of upper band is − 34.52 dB at 2.467 GHz. The suggested microstrip antenna is directly fed by 50 ohm microstrip line feed. The suggested antenna has been designed, simulated and analyzed by IE3D simulation software.
Some new kind of azetidinone derivatives of benzotriazole 5a–i synthesized from N-(benzylidene hydrazino)-propyl-benzotriazole 4a–i. The reaction was carried out by both conventional and microwave ...methods. Some azetidinone derivatives of benzotriazole displayed better antitubercular and antimicrobial activity.
We report herein the synthesis and biological activity of a new kind of azetidinone derivatives of benzotriazole. The reaction was carried out by both conventional and microwave methods. The chemical structures of all the synthesized compounds were deduced according to FTIR, 1H NMR, 13C NMR and FAB-mass spectral along with microanalytical data. All the synthesized compounds of series 5a–i were evaluated for their antitubercular activity against Mycobacterium tuberculosis H37RV and antimicrobial activity against some selected microorganism. Unexpectedly, some azetidinone derivatives of benzotriazole displayed better activities.
Bacteria sense and respond to environmental cues to control important developmental processes. Two widely conserved and important strategies that bacteria employ to sense changes in population ...density and local environmental conditions are quorum sensing (QS) and cyclic di-GMP (c-di-GMP) signaling, respectively. The importance of these pathways in controlling a broad variety of functions, including virulence, biofilm formation, and motility, has been recognized in many species. Recent research has shown that these pathways are intricately intertwined. Here we review the regulatory connections between QS and c-di-GMP signaling. We propose that the integration of QS with c-di-GMP allows bacteria to assimilate information about the local bacterial population density with other physicochemical environmental signals within the broader c-di-GMP signaling network.
This study investigated longitudinal patterns of psychological distress in adult survivors of childhood cancer.
Participants included 4569 adult survivors in the Childhood Cancer Survivor Study ...Cohort (CCSS) who completed the Brief Symptom Inventory-18 on three occasions between 1994 and 2010. Longitudinal latent class analysis was used to identify discrete classes of psychological distress. Predictors of class membership were examined through logistic regression modelling with odds ratios (ORs) and 95% confidence intervals (CIs) reported.
Survivors were a median of 39 years of age and 30 years from diagnosis at the most recent follow-up. Most survivors reported few or no symptoms of distress over time, although subsets of survivors reported persistently elevated (depression: 8.9%; anxiety: 4.8%; somatisation: 7.2%) or significant increases in distress symptoms over the follow-up period (depression: 10.2%; anxiety: 11.8%; somatisation: 13.0%). Increasing distress symptoms were predicted by survivor perception of worsening physical health over time (depression: OR=3.3; 95% CI=2.4-4.5; anxiety: OR=3.0; 95% CI=2.2-4.0; somatisation: OR=5.3; 95% CI=3.9-7.4). Persistent distress symptoms were also predicted by survivor perception of worsening physical health over time, as well as by worsening pain and ending analgesic use.
Subgroups of adult survivors are at-risk for chronic distress or significant increases in distress decades following their original cancer diagnosis. Routine screening of psychological distress in adult survivors of childhood cancer is warranted, especially for survivors who experience physical health morbidities.
Sirtuins are emerging as the key regulators of metabolism and aging, and their potential activators and inhibitors are being explored as therapeutics for improving health and treating associated ...diseases. Despite the global structural similarity among all seven isoforms of sirtuins (of which most of them catalyze the deacetylation reaction), SIRT5 is the only isoform that catalyzes the cleavage of negatively charged acylated substrates, and the latter feature appears to be encoded by the presence of Tyr102 and Arg105 residues at the active site pocket of the enzyme. To determine the contributions of the above residues in SIRT5 (vis a vis the corresponding residues of SIRT1) on substrate selectivity, inhibition by EX527 and nicotinamide, secondary structural features and thermal stability of the enzymes, we created single and double mutations (viz. Y102A, R105l, and Y102A/R105I) in SIRT5. The kinetic data revealed that while Y102A mutant enzyme catalyzed both deacetylation and desuccinylation reactions with comparable efficiencies, R105I and Y102A/R105I mutant enzymes favored the deacetylase reaction. Like SIRT1, the nicotinamide inhibition of SIRT5 double mutant (Y102A/R105I) exhibited the mixed non-competitive behavior. On the other hand, the desuccinylation reaction of both wild-type and Y102A mutant enzymes conformed to the competitive inhibition model. The inhibitory potency of EX527 progressively increased from Y102A, R105I, to Y102A/R105 mutant enzymes in SIRT5, but it did not reach to the level obtained with SIRT1. The CD spectroscopic data for the wild-type and mutant enzymes revealed changes in the secondary structural features of the enzymes, and such changes were more pronounced on examining their thermal denaturation patterns. A cumulative account of our experimental data reveal mutual cooperation between Y102 and R105 residues in promoting the desuccinylation versus deacetylation reaction in SIRT5, and the overall catalytic feature of the enzyme is manifested via the mutation induced modulation in the protein structure.
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