Comparision of safety and efficacy of unilateral paravertebral block with subarachnoid block for inguinal hernia repair

INTRODUCTION: Inguinal herniorrhaphy (IH) is a common day care procedure. It can be performed under generalanaesthesia (GA) peripheral nerve blockade, subarachnoid block (SAB) or paravertebral block (PVB). PVB is providing long‑lasting unilateral anaesthesia, haemodynamic stability, early ambulation and prolonged pain relief. PVB produces ipsilateral segmental analgesia through injection of local anaesthetic onto the spinal nerve roots alongside the vertebral column. It is advocated predominantly for unilateral procedures such as thoracotomy, breast surgery, chest wall trauma, hernia or renal surgery This study was undertaken to compare safety and efficacy between unilateral PVBs and SAB in patients undergoing IH. AIM OF THE STUDY: 1. Duration of post operative analgesia (Post operative Visual Analogue Scale pain score), 2. Time to reach the discharge citeria (Modified post- anaesthetic discharge scoring), 3. Intra operative and post operativehaemodynamics, 4. Total rescue analgesic consumption. METHODOLOGY: This study was done at the Institute of Anaesthesiology and critical care, Madras Medical College between April to September 2017. The aim of this study is to Compare the safety and efficacy of Unilateral paravertebral block with Subarachnoid block for Inguinal hernia repair Patients were excluded if they had a history of sensitivity to local anesthetic, bleeding disorders or receiving anticoagulant, spine or chest wall deformity orpregnancy. Before surgery patients were randomly allocated according to thecomputer generated sequence into two equal groups. Group P (PVB = 30 patients) received ipsilatera Paravertebral block from T10 to L2 with 5ml of bupivacaine (0.5%) with 1: 400,000 epinephrine at each segment. while the group S (SAB=30 patients)received Sub arachnoid block with 12.5ml of hyperbaric bupivacaine (0.5%). PVB was performed with thepatient in sitting position from T10 to L2 thoracic vertebra under completeaseptic precaution with low resistant technique with saline using an 25- G Quincke needle seeking contact with the transverse process of the thoracicvertebra then sliding the needle caudally for 1–1.5 cm into the paravertebral space and 5 ml of bupivacaine 0.5% with 1:400,000 epinephrine at each segment was injected. SAB block wasperformed while the patient in sitting position infiltration of the skin at puncture site with 2 ml of xylocaine 2%, 25- G Quincke the needle was inserted in L3 L4 space injected 12.5mg ( 2.5ml) of hyperbaric bupivacaine (0.5%) in subarachnoid space. Hypotension was defined as a decrease of more than20% of the base line MBP and was treated with increments of 6 mg bolus doses of ephedrine iv and 250 ml fluid bolus. Intra operative haemodynamics was monitored. After the surgery patients was shifted to ward. VAS Score and Modified post anesthesia discharge scoring observed. Postoperative analgesia was provided with tramadol. Pain intensity was measured using VAS pain score. Nausea lasting more than 10 min or vomiting was treated with ondansetron 4 mg. Complications related to local anesthetic drug and PVB technique likepneumothorax or epidural spread of local anesthetic as evidenced by test for sensory deficit on contralateral side were also recorded. Chest X-ray was requested for any patient in PVB group if had any difficulty of breath, desaturated or had diminished air entry at any time after the block. Primaryoutcome was the time to first analgesia in minutes to first registration of VAS pain score >6. Secondary outcome measures were mean VAS scores,intraandpost operative hemodynamic variables and postoperative nausea and vomiting (PONV). CONCLUSION: It is concluded that paravertebral block might be an alternative to spinal anaesthesia method in inguinal hernia surgery as it provides adequate anaesthesia during perioperative period and high quality analgesia during the postoperative period

Trapping and Characterization of a Reaction Intermediate in Carbapenem Hydrolysis by \u3cem\u3eB. cereus\u3c/em\u3e Metallo-β-lactamase

Metallo-β-lactamases hydrolyze most β-lactam antibiotics. The lack of a successful inhibitor for them is related to the previous failure to characterize a reaction intermediate with a clinically useful substrate. Stopped-flow experiments together with rapid freeze−quench EPR and Raman spectroscopies were used to characterize the reaction of Co(II)−BcII with imipenem. These studies show that Co(II)−BcII is able to hydrolyze imipenem in both the mono- and dinuclear forms. In contrast to the situation met for penicillin, the species that accumulates during turnover is an enzyme−intermediate adduct in which the β-lactam bond has already been cleaved. This intermediate is a metal-bound anionic species with a novel resonant structure that is stabilized by the metal ion at the DCH or Zn2 site. This species has been characterized based on its spectroscopic features. This represents a novel, previously unforeseen intermediate that is related to the chemical nature of carbapenems, as confirmed by the finding of a similar intermediate for meropenem. Since carbapenems are the only substrates cleaved by B1, B2, and B3 lactamases, identification of this intermediate could be exploited as a first step toward the design of transition-state-based inhibitors for all three classes of metallo-β-lactamases

Rapid cloning of disease-resistance genes in plants using mutagenesis and sequence capture

Wild relatives of domesticated crop species harbor multiple, diverse, disease resistance (R) genes that could be used to engineer sustainable disease control. However, breeding R genes into crop lines often requires long breeding timelines of 5–15 years to break linkage between R genes and deleterious alleles (linkage drag). Further, when R genes are bred one at a time into crop lines, the protection that they confer is often overcome within a few seasons by pathogen evolution1. If several cloned R genes were available, it would be possible to pyramid R genes2 in a crop, which might provide more durable resistance1. We describe a three-step method (MutRenSeq)-that combines chemical mutagenesis with exome capture and sequencing for rapid R gene cloning. We applied MutRenSeq to clone stem rust resistance genes Sr22 and Sr45 from hexaploid bread wheat. MutRenSeq can be applied to other commercially relevant crops and their relatives, including, for example, pea, bean, barley, oat, rye, rice and maize

Spectroscopic and Mechanistic Studies of Heterodimetallic Forms of Metallo-β-lactamase NDM-1

In an effort to characterize the roles of each metal ion in metallo-β-lactamase NDM-1, heterodimetallic analogues (CoCo-, ZnCo-, and CoCd-) of the enzyme were generated and characterized. UV–vis, 1H NMR, EPR, and EXAFS spectroscopies were used to confirm the fidelity of the metal substitutions, including the presence of a homogeneous, heterodimetallic cluster, with a single-atom bridge. This marks the first preparation of a metallo-β-lactamase selectively substituted with a paramagnetic metal ion, Co(II), either in the Zn1 (CoCd-NDM-1) or in the Zn2 site (ZnCo-NDM-1), as well as both (CoCo-NDM-1). We then used these metal-substituted forms of the enzyme to probe the reaction mechanism, using steady-state and stopped-flow kinetics, stopped-flow fluorescence, and rapid-freeze-quench EPR. Both metal sites show significant effects on the kinetic constants, and both paramagnetic variants (CoCd- and ZnCo-NDM-1) showed significant structural changes on reaction with substrate. These changes are discussed in terms of a minimal kinetic mechanism that incorporates all of the data

Discovery and characterization of two new stem rust resistance genes in Aegilops sharonensis

Stem rust is one of the most important diseases of wheat in the world. When single stem rust resistance (Sr) genes are deployed in wheat, they are often rapidly overcome by the pathogen. To this end, we initiated a search for novel sources of resistance in diverse wheat relatives and identified the wild goat grass species Aegilops sharonesis (Sharon goatgrass) as a substantial reservoir of resistance to wheat stem rust. The objectives of this study were to discover and map novel Sr genes in Ae. sharonensis and to explore the possibility of identifying new Sr genes by genome-wide association study (GWAS). We developed two biparental populations between resistant and susceptible accessions of Ae. sharonensis and performed QTL and linkage analysis. In an F6 recombinant inbred line and an F2 population, two genes were identified that mapped to the short arm of chromosome 1Ssh, designated as Sr-1644-1Sh, and the long arm of chromosome 5Ssh, designated as Sr-1644-5Sh. The gene Sr-1644-1Sh confers a high level of resistance to race TTKSK (one of the Ug99 lineage races), while the gene Sr-1644-5Sh conditions strong resistance to TRTTF, another widely virulent race found in Yemen. Additionally, GWAS was conducted on 125 diverse Ae. sharonensis accessions for stem rust resistance. The gene Sr-1644-1Sh was detected by GWAS, while Sr-1644-5Sh was not detected, indicating that the effectiveness of GWAS might be affected by marker density, population structure, low allele frequency and other factors

Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase

Carbapenems, 'last-resort' β-lactam antibiotics, are inactivated by zinc-dependent metallo-β-lactamases (MBLs). The host innate immune response withholds nutrient metal ions from microbial pathogens by releasing metal-chelating proteins such as calprotectin. We show that metal sequestration is detrimental for the accumulation of MBLs in the bacterial periplasm, because those enzymes are readily degraded in their nonmetallated form. However, the New Delhi metallo-β-lactamase (NDM-1) can persist under conditions of metal depletion. NDM-1 is a lipidated protein that anchors to the outer membrane of Gram-negative bacteria. Membrane anchoring contributes to the unusual stability of NDM-1 and favors secretion of this enzyme in outer-membrane vesicles (OMVs). OMVs containing NDM-1 can protect nearby populations of bacteria from otherwise lethal antibiotic levels, and OMVs from clinical pathogens expressing NDM-1 can carry this MBL and the bla[subscript NDM] gene. We show that protein export into OMVs can be targeted, providing possibilities of new antibacterial therapeutic strategies.Kinship Foundation. Searle Scholars ProgramMassachusetts Institute of Technology. Department of Chemistr

Resistance gene cloning from a wild crop relative by sequence capture and association genetics

Disease resistance (R) genes from wild relatives could be used to engineer broad-spectrum resistance in domesticated crops. We combined association genetics with R gene enrichment sequencing (AgRenSeq) to exploit pan-genome variation in wild diploid wheat and rapidly clone four stem rust resistance genes. AgRenSeq enables R gene cloning in any crop that has a diverse germplasm panel