Structure, Genetics and Worldwide Spread of New Delhi Metallo-β-lactamase (NDM): a threat to public health

Background: The emergence of carbapenemase producing bacteria, especially New Delhi metallo-β-lactamase (NDM-1) and its variants, worldwide, has raised amajor public health concern. NDM-1 hydrolyzes a wide range of β-lactam antibiotics, including carbapenems, which are the last resort of antibiotics for the treatment of infections caused by resistant strain of bacteria. Main body: In this review, we have discussed blaNDM-1variants, its genetic analysis including type of specific mutation, origin of country and spread among several type of bacterial species. Wide members of enterobacteriaceae, most commonly Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and gram-negative non-fermenters Pseudomonas spp. and Acinetobacter baumannii were found to carry these markers. Moreover, at least seventeen variants of blaNDM-type gene differing into one or two residues of amino acids at distinct positions have been reported so far among different species of bacteria from different countries. The genetic and structural studies of these variants are important to understand the mechanism of antibiotic hydrolysis as well as to design new molecules with inhibitory activity against antibiotics. Conclusion: This review provides a comprehensive view of structural differences among NDM-1 variants, which are a driving force behind their spread across the globe

Risk of transmission of COVID-19 virus infection from asymptomatic COVID-19 positive pregnant patients to Obs/Gynae surgical team

ABSTRACT Background: Covid 19 is highly contagious disease and Health care workers are always at risk because they are involved in care of suspected, asymptomatic and confirmed cases. It is worthwhile to adopt all practices for prevention of the disease, so they will be able to continue their duties without fear and stress of carrying infection. OBJECTIVE: To determine the number of health care workers who became Covid positive after performing caesarian sections or normal vaginal deliveries of Covid positive asymptomatic cases. Material and Methods: This study was conducted in Gynae/Obs department Of Shalamar Hospital Lahore from March 2020 to September 2020.All the health workers involved in surgeries and deliveries of Covid positive patients were included and they were asked to fill the proforma related to their exposure and development of any signs and symptoms of COVID-19 during the period of fourteen days after exposure. Findings were summarized and analyzed by using SPSS VERSION 22. Results: Total twenty patients who were Covid positive were delivered during this period. Sixty health care workers were involved in their care. During study period three health care workers one doctor and two staff nurses became Covid positive. These infected health care workers were not involved in surgery or delivery of these 20 Covid positive patients. Conclusion: If all the health care workers takes all corona precautionary measures while performing deliveries and C-sections of Covid positive patients risk of transmission to the surgical team can be reduced. Keywords: Covid-19, Health care worker

Neurological care and training in the times of covid-19: a tertiary care center experience

Resilience in these challenging times of COVID-19 at a professional and personal level is cardinal. Trainees and faculty have had to adapt to this adversity with striking limitations on formal neurological, neurovascular and neurophysiological residencies and fellowships. The revision of schedules and reallocation of assignments to cope with the practical aspects in a teaching tertiary care hospital have been overbearing. Novel structural innovation, testing, communications and supervision to assure a modified yet impactful training educational programme is mandatory and the need of the hour. Healthcare service providers remain at the highest risk of acquiring COVID-19 worldwide. Urgent measures to educate them about personal protective equipment (PPE), disease course, infectivity and complications were initialized at the first impact of COVID-19. Foreseeing the pandemic in months to come, here we describe the elemental changes made at the Aga Khan University Hospital (AKUH) Karachi, Pakistan a leading academic institute in health sciences and one of the largest tertiary care hospitals in the country and all the modifications contrived in the section of neurology to deal with the brunt of the pandemic. The neurology section devised a strategy balancing clinical work, research and academic activities.Tele health clinics were encouraged and set up across all specialties to minimize in hospital encounters whilst answering concerns of patients and their caregivers. Collaborative efforts, nationally and globally are the requirement as we continue to learn through clinical experience, trials and research on all the potential complications of COVID-19 in these dismal times

The Effect of Energy Drink on Histomorphological Changes in Skeletal Muscles of Wistar Albino Rats

Objective: To observe the histomorphological alterations induced by consumption of energy drinks on skeletal muscles of Albino rats. Study Design:An experimental study. Place and Duration of Study: The study was conducted by the Department of Anatomy in collaboration with the animal house of Liaquat national hospital and medical college (LNH&MC), Karachi from November 2 to December 1 2020. Materials and Methods: For the study, 30 adult male Wistar Albino rats weighing between 140 and 200 grammes were allocated evenly into 3 groups. Group A served as control, kept on a regular laboratory diet. Group B served as a low dose treated group receiving energy drink at a dose of 7.5ml/day while group C received a high dose of drink i-e 15ml/day via gastric tube. All the animals were sacrificed following completion of the experimental period and were subjected to microscopic examination for histo-morphological study. Data was analyzed by using SPSS version 25. Results: The Hematoxylin and Eosin (H&E) stained sections revealed significant structural and parenchymal damage in skeletal muscle tissue. The regular parallel arrangement of skeletal muscle fibers was lost with the disappearance of nuclei. Dilated and congested blood vessels were observed in the treated tissues. Infiltration of mononuclear cells was also observed suggesting the inflammatory changes in the tissues of animals treated with caffeinated beverages in the present study. Conclusion: The consumption of energy drinks produces a significant histo-morphological alteration in the skeletal muscles of Wistar Albino rat

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Synergistic Effect of Doripenem and Cefotaxime to Inhibit CTX-M-15 Type β-Lactamases: Biophysical and Microbiological Views

CTX-M-15 type β-lactamase has the ability to hydrolyse cefotaxime, a third generation cephalosporin. The infections caused by multidrug resistant strains, especially CTX-M-15 producing strains are being treated with carbapenem group of β-lactam antibiotics. The objective of the study was to know if cefotaxime in combination with doripenem (carbapemen antibiotic) at very low concentration, inhibits the CTX-M-15 producing bacterial strains. blaCTX−M−15 gene was cloned to express CTX-M-15 enzyme and construct CTX-M-15 producing strain. The clone carrying CTX-M-15 was found susceptible to doripenem. Doripenem and CTX-M-15 binding was an endothermic and spontaneous process leading to change in polarity in the micro-environment and conformational changes of enzyme as shown by fluorescence, UV and CD spectroscopic study. The catalytic efficiency of CTX-M-15 enzyme was reduced to about 15.86% when it was treated with doripenem along with cefotaxime (in 5 times molar ratio each of doripenem and cefotaxime w.r.t CTX-M-15), as compared to the studies where enzyme's efficiency was increased by 33% when treated with cefotaxime alone. Hence, doripenem in combination with cefotaxime reduces enzyme's efficiency to hydrolyse cefotaxime by about 48%. FIC study showed that doripenem paired with cefotaxime showed synergistic effect against CTX-M-15 producing bacterial strain. The study concludes that doripenem at very low concentration (25 nM), induces such a structural changes in CTX-M-15 which reduced enzyme's activity to hydrolyse cefotaxime. Hence, the synergistic use of doripenem and cefotaxime plays a significant role in inhibiting the efficiency of CTX-M-15 type β-lactamase, and may provide an alternative approach to reduce the resistance against the cephalosporin type antibiotics

Activation of Human Salivary Aldehyde Dehydrogenase by Sulforaphane: Mechanism and Significance.

Cruciferous vegetables contain the bio-active compound sulforaphane (SF) which has been reported to protect individuals against various diseases by a number of mechanisms, including activation of the phase II detoxification enzymes. In this study, we show that the extracts of five cruciferous vegetables that we commonly consume and SF activate human salivary aldehyde dehydrogenase (hsALDH), which is a very important detoxifying enzyme in the mouth. Maximum activation was observed at 1 μg/ml of cabbage extract with 2.6 fold increase in the activity. There was a ~1.9 fold increase in the activity of hsALDH at SF concentration of ≥ 100 nM. The concentration of SF at half the maximum response (EC50 value) was determined to be 52 ± 2 nM. There was an increase in the Vmax and a decrease in the Km of the enzyme in the presence of SF. Hence, SF interacts with the enzyme and increases its affinity for the substrate. UV absorbance, fluorescence and CD studies revealed that SF binds to hsALDH and does not disrupt its native structure. SF binds with the enzyme with a binding constant of 1.23 x 107 M-1. There is one binding site on hsALDH for SF, and the thermodynamic parameters indicate the formation of a spontaneous strong complex between the two. Molecular docking analysis depicted that SF fits into the active site of ALDH3A1, and facilitates the catalytic mechanism of the enzyme. SF being an antioxidant, is very likely to protect the catalytic Cys 243 residue from oxidation, which leads to the increase in the catalytic efficiency and hence the activation of the enzyme. Further, hsALDH which is virtually inactive towards acetaldehyde exhibited significant activity towards it in the presence of SF. It is therefore very likely that consumption of large quantities of cruciferous vegetables or SF supplements, through their activating effect on hsALDH can protect individuals who are alcohol intolerant against acetaldehyde toxicity and also lower the risk of oral cancer development

Clinicopathological features and survival outcomes of metaplastic breast carcinoma - an observational multi-centric study

Purpose: To describe the clinicopathological features, and subtypes of metaplastic breast cancer (MpBC) in Pakistan and further to understand its response to treatment, including region-specific survival outcomes. Patients and methods: This retrospective cohort study was conducted at two private tertiary care hospitals in Karachi, Pakistan. Our selection criteria included a total of 215 patients who were diagnosed with MpBC at an age older than 18 years from 1994 to 2021. Data regarding clinicopathological features, staging, receptor status, treatment modalities, recurrence, and survival was obtained. Death was scored as an event, and patients who were alive were censored at the time of the last follow-up. Results: The incidence of MpBC at our study centers is 3.21%. The median age of diagnosis was 50 years (range 22 to 80 years) and most patients presented at Stages II (45.1%) and III (44.2%). Among patients who received neoadjuvant chemotherapy, 31.7% achieved complete pathological response. The 3-year survival of those who received neoadjuvant chemotherapy was 96%. During our study, 19.1% of patients died and the median survival duration was 9 years 7 months 9 days. Survival of patients was significantly lower in patients who had metastasis (p-value = 0.042) and those who had tumor recurrence (p-value = 0.001). Conclusion: Metaplastic breast cancer is an extremely rare variant of breast cancer with features that exist as a spectrum. Our study demonstrated considerable success with the use of neoadjuvant chemotherapy. The pathological complete response achieved in our study is one of the highest ever reported. Our success, though limited, warrants further research in the use of neoadjuvant chemotherapy in MpB