A sensor for needle puncture force measurement during interventional radiological procedures

Computer-based simulation for interventional radiology training has attracted increasing attention in recent years because of its potential to train remotely from patients and to provide objective assessment of proficiency. Yet developing a high fidelity simulator with realistic tactile feedback requires accurate knowledge of forces exerted on medical devices during interventional radiology procedures. This paper presents the development and validation of a force sensor for the measurement of axial forces generated during needle, and combined cannula/trocar, puncture procedures in patients. In order to assess the performance of this sensor, in vitro measurements were obtained using needle penetration of porcine liver, kidney and muscle. The results were compared with forces measured by means of a tensile tester.Calibration results showed that the force sensor has high sensitivity and linearity. Comparison of the force profiles obtained from the sensor and the tensile tester shows that good agreement was achieved in the in vitro studies for all the tissues tested.Preliminary clinical force measurements during arterial puncture and liver biopsy procedures have been performed in patients. An example of force recording for each procedure type is presented.     

Oxidant-free,three-component synthesis of 7-amino-6H-benzo[c]chromen-6-ones under green conditions

An oxidant-free three-component synthesis of biologically significant 7-amino-6H-benzo[c]chromen-6-ones was established involving a Sc(OTf)₃ catalyzed three-component reaction between primary amines, β-ketoesters and 2-hydroxychalcones under green conditions. In this strategy, both the B and C rings of 6H-benzo[c]chromen-6-ones were constructed simultaneously starting from acyclic precursors by generating four new bonds including two C–C, one C–N and one C–O in a single synthetic operation. The mechanism of this sequential cascade process involves the initial formation of a β-enaminone intermediate followed by Michael addition with 2-hydroxychalcone, intramolecular cyclization, dehydration, lactonization and aromatization steps. Unlike the related literature approaches, this reaction delivered the products without the addition of any external oxidants to achieve the key aromatization step.

Three-component synthesis of 7-amino-6H-benzo[c]chromen-6-ones was achieved under oxidant-free green conditions.     

Therapeutic Potential of Semaglutide,a Newer GLP-1 Receptor Agonist,in Abating Obesity,Non-Alcoholic Steatohepatitis and Neurodegenerative diseases: A Narrative Review

Pharmaceutical Research - Semaglutide, a peptidic GLP-1 receptor agonist, has been clinically approved for treatment of type 2 diabetes mellitus and is available in subcutaneous and oral dosage...     

Evaluation of wound healing and antimicrobial potentials of Ixora coccinea root extract

ObjectiveTo evaluate the wound healing and antimicrobial activity of root extracts of Ixora coccinea (I. coccinea).MethodsTo investigate the wound healing efficacy of root extract of I. coccinea Linn, five groups of animals were divided each containing six animals. Two wound models including incision and excision wound models were used in this study. The parameters studied were tensile strength on incision wound model and in terms of wound contraction for excision wound model were compared with standard Nitrofurazone (NFZ) ointment (0.2% w/w). Six extracts (ethanol, aqueous, petroleum ether, benzene, chloroform and ethyl acetate) of I. coccinea were screened for in vitro growth inhibiting activity against different bacterial strains viz, Staphylococcus aureus, Bacillus pumilius, Enterococcus faecalis, Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa and fungi Candida albicans and Aspergillus niger were compared with the standard drugs ciprofloxacin and chloramphenicol for antibacterial and griseofulvin for antifungal screening. The serial dilution and cup (or) well plate methods were used for the antimicrobial study and MIC was determined.ResultsThe ethanolic extract showed significant (P<0.001) wound healing activity when compared to standard drug NFZ with respect to normal control group. Amongst all, ethanolic extract showed highly significant antibacterial activity against all bacterial strains used in this study when compared to standard. The aqueous extract showed moderate significant inhibition against all bacterial strains when compared to standard. All the extracts were shown negligible activity against the fungal strains used in this study.ConclusionsThe ethanolic root extract of I. coccinea showed pronounced wound healing and antibacterial activity. The probable reason to heal the wound was that the external application of the extract prevented the microbes to invade through the wound thus the protection of wound occurs against the infection of the various organisms.     

Ribosome–SRP–FtsY cotranslational targeting complex in the closed state

The signal recognition particle (SRP)-dependent pathway is essential for correct targeting of proteins to the membrane and subsequent insertion in the membrane or secretion. In Escherichia coli, the SRP and its receptor FtsY bind to ribosome–nascent chain complexes with signal sequences and undergo a series of distinct conformational changes, which ensures accurate timing and fidelity of protein targeting. Initial recruitment of the SRP receptor FtsY to the SRP–RNC complex results in GTP-independent binding of the SRP–FtsY GTPases at the SRP RNA tetraloop. In the presence of GTP, a closed state is adopted by the SRP–FtsY complex. The cryo-EM structure of the closed state reveals an ordered SRP RNA and SRP M domain with a signal sequence-bound. Van der Waals interactions between the finger loop and ribosomal protein L24 lead to a constricted signal sequence-binding pocket possibly preventing premature release of the signal sequence. Conserved M-domain residues contact ribosomal RNA helices 24 and 59. The SRP–FtsY GTPases are detached from the RNA tetraloop and flexible, thus liberating the ribosomal exit site for binding of the translocation machinery.The Escherichia coli signal recognition particle (SRP) is a complex consisting of the universally conserved protein Ffh and 4.5S RNA, which adopts a hairpin structure (1). Ffh is composed of the N-terminal domain, the G domain that harbors GTPase activity, and the C-terminal methionine-rich M domain that interacts with 4.5S RNA (2, 3) and with the signal sequence (4, 5). The N and G domains form a compact structural and functional unit termed “the NG domain.” Targeting of ribosome-nascent chain complexes (RNC) containing a signal sequence depends on the interaction of the RNC–SRP complex with the SRP receptor FtsY, which is membrane associated (6–9). FtsY and Ffh interact via their homologous NG domains and form a composite GTPase active site (10, 11). Crystal structures of the M domain reveal a hydrophobic groove used to capture signal sequences (4, 5, 12).Protein targeting is driven by highly regulated conformational rearrangements of SRP and FtsY as well as GTP hydrolysis. SRP recognizes and tightly binds to RNCs displaying a signal sequence (cargo). Next, RNC-bound SRP efficiently recruits FtsY to form a nucleotide-independent, transient early state that rearranges to a GTP-stabilized closed state (13). Ultimately, in the activated state, handover of the RNC to the Sec translocon takes place, followed by GTP hydrolysis and disassembly of the SRP–FtsY complex (14–16). These distinct conformational transitions are regulated by the ribosome and translocon in the membrane, leading to a switch from cargo recognition by SRP to cargo release (17, 18).Cryo-EM structures of bacterial SRP-bound RNCs revealed a tight cargo-recognition complex (19, 20). In the SRP–FtsY early complex an overall detachment of SRP from the ribosome was observed (21). In this state, the G domain of FtsY contacts the conserved SRP RNA tetraloop, and Ffh and FtsY interact via their N domains (21) forming a pseudosymmetric V-shaped complex positioned above the ribosomal tunnel exit. The active sites of the GTPase domains are apart from each other, explaining why the early state is inactive in GTP hydrolysis (13, 21, 22).GTP is required for SRP and FtsY to rearrange into the closed state. FRET experiments indicate that, in this state, the Ffh–FtsY NG domains adopt a conformation that resembles the intimate heterodimeric architecture observed in crystal structures (10, 11, 13). The complete SRP was crystallized in complex with the FtsY NG domain in the closed/activated state showing the NG domains docked at the distal end of the RNA hairpin (23, 24). Single-molecule total internal reflection fluorescence microscopy directly demonstrated that the Ffh–FtsY NG domains need to relocate from the tetraloop to the RNA distal end to become activated for GTP hydrolysis and to progress further in the targeting reaction (24).Although the early, closed, and activated SRP–FtsY targeting complexes have been well-characterized biochemically, the generation of distinct, conformationally homogenous closed and activated ribosome–SRP–FtsY complexes for structural studies proved to be exceedingly difficult, because the ribosome stabilizes the early state (13). We overcame this challenge by developing a robust complex preparation strategy, and describe here the cryo-EM structure of the closed state of the RNC–SRP–FtsY complex at a resolution of 5.7 Å.     

A novel system for the irrigation of open fractures

It is accepted that a good washout of contaminated wounds with copious fluids reduces the rate of infection. We describe a simple method of rapidly irrigating wounds with high volumes of fluid.