Efficient methods for enol phosphate synthesis using carbon-centred magnesium bases

Efficient conversion of ketones into kinetic enol phosphates under mild and accessible conditions has been realised using the developed methods with di-tert-butylmagnesium and bismesitylmagnesium. Optimisation of the quench protocol resulted in high yields of enol phosphates from a range of cyclohexanones and aryl methyl ketones, with tolerance of a range of additional functional units

LAVH or TAH – choosing it wise and making it safe

Background: Hysterectomy is the most commonly performed surgery in our gynaecological practice, abdominal route being the most common. Here we compare the various features and outcomes of laparoscopically assisted vaginal hysterectomy (LAVH) with total abdominal hysterectomy (TAH).Methods: The study design is a retrospective observational study. Outcome measures were indication, duration, complications of surgery, post op recovery and cost following TAH and LAVH.Results: A total of 116 cases underwent hysterectomy. Of these 98 underwent TAH and 18 underwent LAVH. Commonest indication for TAH in our study was fibroid followed by abnormal uterine bleeding (AUB); whereas in LAVH it was AUB followed by fibroid. Mean operating time in TAH was 118 minutes whereas in LAVH it was 166 minutes. One patient who underwent LAVH had ureteric injury and another had vault abscess. There were no major complications among TAH cases. A few patients had minor complications like fever, wound infection and urinary tract infection following TAH whereas fever was the only minor complication seen in a minority of the LAVH patients. Mean fall in haemoglobin in TAH was 1.05 gm% whereas in LAVH it was 0.95 gm%. None of the patients required postoperative blood transfusion. A few patients following TAH required additional analgesics apart from routine whereas in LAVH none required it. Mean duration of hospital stay following TAH was 6.84 days where as in LAVH it was 3.1 days. Mean hospital expenses in TAH were INR 28480, while for LAVH it was 44360.Conclusions: Undoubtedly expertise is the decisive factor behind the success of hysterectomy. LAVH though advantageous in many aspects like less post operative pain and cosmetic benefits, it could be technically demanding with availability only in well-equipped centres and cost factors. Surgeons need to be trained in all modalities of hysterectomy

PHYTOCHEMICAL SCREENING AND ANTIMICROBIAL ACTIVITY OF BLUMEA MOLLIS (D.DON) MERRILL

Objective: The objective of this research was to carry out the preliminary phytochemical screening and to evaluate the antimicrobial activity of the methanolic extract of the Blumea mollis. Methods: In the present work, the phytochemicals of the whole plant were extracted using petroleum ether, chloroform, methanol, ethanol, and distilled water. These were then screened for triterpenes/steroids, alkaloids, anthraquinones, coumarins, flavonoids, saponins, tannins, and phenolic acids using standard methods. Further, the antimicrobial activity of the methanolic extract was determined using Gram-positive and negative bacteria. Agar well diffusion method was employed for antimicrobial activity study, and the zone of inhibition was found out. Results: The intensity of the color produced or the precipitate formed was used as the analytical response to these tests. Flavonoids, tannins, and phenolic acids showed positive results for phytochemical screening. The concentration of total phenols and flavonoids of the decoction was 45.5±0.2000 μg/ml gallic acid equivalent and 42.3±0.3606 μg/ml quercetin equivalent, respectively. Staphylococcus aureus, Escherichia coli, and Candida albicans were inhibited by the methanolic extract of B. mollis in agar well diffusion test. Conclusion: The results of the present study showed that the methanolic extract of B. mollis contains glycosides, phenolics, tannins, and flavonoids. Plant possesses significant antibacterial and antifungal property; the potent antimicrobial activity of the plant could be attributed to the presence of flavonoids and phenolic compounds in it

Withania somnifera Root Extract Enhances Chemotherapy through ‘Priming’

Withania somnifera extracts are known for their anti-cancerous, anti-inflammatory and antioxidative properties. One of their mechanisms of actions is to modulate mitochondrial function through increasing oxidative stress. Recently ‘priming’ has been suggested as a potential mechanism for enhancing cancer cell death. In this study we demonstrate that ‘priming’, in HT-29 colon cells, with W. somnifera root extract increased the potency of the chemotherapeutic agent cisplatin. We have also showed the W. somnifera root extract enhanced mitochondrial dysfunction and that the underlying mechanism of ‘priming’ was selectively through increased ROS. Moreover, we showed that this effect was not seen in non-cancerous cells

Variation in the provision and practice of implant-based breast reconstruction in the UK: Results from the iBRA national practice questionnaire

Introduction The introduction of biological and synthetic meshes has revolutionised the practice of implant-based breast reconstruction (IBBR) but evidence for effectiveness is lacking. The iBRA (implant Breast Reconstruction evAluation) study is a national trainee-led project that aims to explore the practice and outcomes of IBBR to inform the design of a future trial. We report the results of the iBRA National Practice Questionnaire (NPQ) which aimed to comprehensively describe the provision and practice of IBBR across the UK. Methods A questionnaire investigating local practice and service provision of IBBR developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Summary data for each survey item were calculated and variation between centres and overall provision of care examined. Results 81 units within 79 NHS-hospitals completed the questionnaire. Units offered a range of reconstructive techniques, with IBBR accounting for 70% (IQR:50–80%) of participating units' immediate procedures. Units on average were staffed by 2.5 breast surgeons (IQR:2.0–3.0) and 2.0 plastic surgeons (IQR:1.0–3.0) performing 35 IBBR cases per year (IQR:20-50). Variation was demonstrated in the provision of novel different techniques for IBBR especially the use of biological (n = 62) and synthetic (n = 25) meshes and in patient selection for these procedures. Conclusions The iBRA-NPQ has demonstrated marked variation in the provision and practice of IBBR in the UK. The prospective audit phase of the iBRA study will determine the safety and effectiveness of different approaches to IBBR and allow evidence-based best practice to be explored

Selective Cholinergic Depletion in Medial Septum Leads to Impaired Long Term Potentiation and Glutamatergic Synaptic Currents in the Hippocampus

Cholinergic depletion in the medial septum (MS) is associated with impaired hippocampal-dependent learning and memory. Here we investigated whether long term potentiation (LTP) and synaptic currents, mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the CA1 hippocampal region, are affected following cholinergic lesions of the MS. Stereotaxic intra-medioseptal infusions of a selective immunotoxin, 192-saporin, against cholinergic neurons or sterile saline were made in adult rats. Four days after infusions, hippocampal slices were made and LTP, whole cell, and single channel (AMPA or NMDA receptor) currents were recorded. Results demonstrated impairment in the induction and expression of LTP in lesioned rats. Lesioned rats also showed decreases in synaptic currents from CA1 pyramidal cells and synaptosomal single channels of AMPA and NMDA receptors. Our results suggest that MS cholinergic afferents modulate LTP and glutamatergic currents in the CA1 region of the hippocampus, providing a potential synaptic mechanism for the learning and memory deficits observed in the rodent model of selective MS cholinergic lesioning

A retrospective comparison of venetoclax alone or in combination with an anti-CD20 monoclonal antibody in R/R CLL

Venetoclax (VEN) is approved for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as monotherapy (VENmono) or in combination with rituximab. Whether VEN plus anti-CD20 (VENcombo) is superior to VENmono is unknown. We conducted a multicenter, retrospective cohort analysis comparing 321 CLL patients treated with VENmono vs VENcombo across the United States and the United Kingdom. We examined demographics, baseline characteristics, dosing, adverse events, response rates, and outcomes. The primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated by Kaplan-Meier method, in patients treated with VENmono vs VENcombo. Univariate and bivariate analyses were performed with COX regression. Three hundred twenty-one CLL patients were included (3 median prior treatments, 78% prior ibrutinib). The overall response rates (ORRs) were similar (VENmono, 81% ORR, 34% complete remission [CR] vs VENcombo, 84% ORR, 32% CR). With a median follow-up of 13.4 months, no differences in PFS and OS were observed between the groups. In unadjusted analyses, the hazard ratios (HRs) for PFS and OS for VENmono vs VENcombo were HR 1.0 (95% confidence interval [CI], 0.6-1.8; P = .7) and HR 1.2 (95% CI, 0.6-2.3; P = .5), respectively. When adjusting for differences between the cohorts, the addition of an anti-CD20 antibody in combination with VEN did not impact PFS (HR, 1.0; 95% CI, 0.5-2.0; P = .9) or OS (HR, 1.1; 95% CI, 0.4-2.6; P = .8). We demonstrate comparable efficacy between VENmono and VENcombo in a heavily pretreated, high-risk, retrospective cohort, in terms of both response data and survival outcomes. Prospective studies are needed to validate these findings

Neuroprotection by Bromocriptine Against 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine-induced Neurotoxicity in Micel

Mice were treated with 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg i.p. twice, 16 h apart). This resulted in changes in motor performance and toxic insult of nigral neurons as evidenced by dopamine depletion in nucleus caudatus putamen. In vitro and in vivo treatment of MPTP caused the generation of hydroxyl radicals (•OH) as measured by a sensitive salicylate hydroxylation procedure. A dopamine agonist, bromocriptine (10 mM and 10 mg/kg i.p.), blocked •OH formation caused by MPTP in vitro (20 mM) and in vivo (30 mg/kg i.p.). An MPTP-induced increase in the activity of catalase and superoxide dismutase in substantia nigra on the seventh day was reduced by bromocriptine pretreatment. Bromocriptine blocked MPTP-induced behavioral dysfunction as well as glutathione and dopamine depletion, indicating its potent neuroprotective action. This study suggests that bromocriptine stimulates antioxidant mechanisms in the brain and acts as a free radical scavenger in addition to its action at dopamine receptors, thus indicating its strength as a valuable neuroprotectant. —Muralikrishnan, D., Mohanakumar, K. P. Neuroprotection by bromocriptine against 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice