Evaluation of serum procalcitonin level as a biomarker for disease severity in COVID-19 patients.

The pandemic of coronavirus disease 2019 (COVID-19) has infected millions of individuals around the globe. Forecasting the COVID-19 severity is essential, and various biomarkers could be used to evaluate it. The current study was therefore aimed to evaluate the serum pro-calcitonin (PCT) level as a biomarker for bacterial co-infection and disease severity in COVID-19 patients. A total of 430 COVID-19 positive individuals were examined, in which 332 (77.2%) were male individuals while 98 (22.8%) were female individuals. Among the examined samples, 281 were classified as moderate (PCT value 0.07 ± 0.06 ng/mL), 95 were severe (PCT value 0.5 ± 0.4 ng/mL), and 54 were classified as critical (PCT value > 1 ng/mL) individuals. The increase in the total serum level of PCT was observed with the severity of the disease (p < 0.05). The statistical analysis represented no association of PCT value with gender (p 0.9650) while revealed a significant association (p < 0.001) with the age and PCT value in COVID-19 patients. It can be concluded that the serial PCT measurement could determine the prognosis of the disease and the presence of bacterial co-infection in COVID-19 patients. Further exploration of the topic is needed to evaluate the effect of different therapies on the PCT level and to prescribe specific treatment options for coinfection.

COVID-19 outbreak: current scenario of Pakistan.

COVID-19 outbreak was first time experienced in the Wuhan City of China at the end of December 2019. Which spread rapidly in China and then worldwide in 209 countries of America, Europe, Australia and Asia including Pakistan. There are more than fifty thousand mortalities and one million plus people have been affected worldwide, while figure increases rapidly. Different steps have been taken worldwide for the control of COVID-19. Even with less resources Pakistan also taken rigorous measures like designed special hospitals, Laboratories for testing, quarantine facilities, awareness campaign and lock down to control the spread of virus. We highlighted the efforts of government to combat this deadly pneumonia.

Gamma backscattering analysis of flaw types and orientation based on Monte Carlo GEANT4 simulations.

In this study, we modeled the effects of flaws in a solid material as three different slit types (rectangular, rectilinear, and semicircular) and their orientations in a duralumin (aluminum alloy) plate in simulations based on 137Cs gamma backscattering. The simulations were performed using the Monte Carlo GEANT4 simulation toolkit. The simulation results showed that the shape of the slit had a small effect on the backscattering peak curve. Rotating the slit on the Y-axis and Z-axis of the duralumin plate influenced the 137Cs backscattering peak height in the energy range from 0.185 to 0.20 MeV, where the backscattering peak areas exhibited specific patterns due to the slit orientations.

Surgical Parathyroidectomy Services

Aims Retrospectively audit our experience with surgical parathyroidectomy over a 5 year period from the beginning of 2013 to June 2018. Methods Hospital In-patient Enquiry (HIPE) data, NIMIS radiology and theatre logs were used to identify the study cohort of a single specialist parathyroid surgeon. Demographic data plus pre and post-op calcium and parathyroid Hormone (PTH) levels were analysed. Data were coded and entered into SPSS 24 statistical software package for analysis. Results Thirty-one surgical parathyroidectomy cases were identified comprising four male and twenty seven females. Average age was 59.81 years (SD 14.75). The median pre-op and post-op calcium levels were 2.81[elevated] (Range 2.37-4.06 mmol/L) and 2.42[normal] (2.16-3.31 mmol/L) respectively and were statistically significant therapeutic reductions (p<0.05). The median pre-op and post-op PTH levels were 168.0[elevated] (Range 69-3171 pg/ml) and 41.7 [normal] (7.30-1628 pg/ml) respectively. All patients were discharged on post op day 1. Conclusion Parathyroidectomy is a safe and cost-effective treatment for PHPT in University Hospital Waterford.

Coexpression of TLR2 or TLR4 with HLA-DR potentiates the superantigenic activities of Mycoplasma arthritidis-derived mitogen.

Mycoplasma arthritidis-derived mitogen (MAM) is a member of the superantigen family that structurally differs from other members while still capable of initiating cognate APC/T cell interaction. In addition to the critical role of MHC class II molecules, it has been suggested that TLR2 and TLR4 may cooperate with MHC class II during MAM-induced responses. In this study, we investigated the direct involvement of TLR2 and TLR4 in MAM binding and presentation to T cells. Our results showed that MAM fails to bind to TLR2- and TLR4-transfected cells. However, coexpression of TLR2 or TLR4 with HLA-DR significantly increases MAM binding and the subsequent T cell activation compared with cells expressing HLA-DR alone. The upregulated MAM binding and activity in HLA-DR/TLR-transfected cells is abrogated by an anti-HLA-DR Ab. Interestingly, we also found that MAM complexed with soluble HLA-DR is capable of binding to both TLR2 and TLR4. The enhancing effect of TLR2 or TLR4 on MAM-induced T cell proliferation was not due to TLR ligand contamination in the MAM preparation. Taken together, these results strongly suggest that binding of MAM to HLA-DR leads to a conformational change in MAM structure allowing its interaction with TLR2 and TLR4 and a better recognition by T cells.

Great expectations for the World Health Organization: a Framework Convention on Global Health to achieve universal health coverage.

Establishing a reform agenda for the World Health Organization (WHO) requires understanding its role within the wider global health system and the purposes of that wider global health system. In this paper, the focus is on one particular purpose: achieving universal health coverage (UHC). The intention is to describe why achieving UHC requires something like a Framework Convention on Global Health (FCGH) that have been proposed elsewhere,(1) why WHO is in a unique position to usher in an FCGH, and what specific reforms would help enable WHO to assume this role.

RANDOMISED DOUBLE BLIND STUDY TO COMPARE EFFECTIVENESS OF HONEY, SALBUTAMOL AND PLACEBO IN TREATMENT OF COUGH IN CHILDREN WITH COMMON COLD.

BACKGROUND: Acute upper respiratory infection is the most common childhood illness and presents with cough, coryza and fever. Available evidence suggests that cough medicines may be no more effective than honey-based cough remedies. OBJECTIVE: To compare effectiveness of honey, salbutamol and placebo in the treatment of cough in children with acute onset cough. DESIGN: Randomised control trial. SETTING: Aga Khan University Hospital Paediatric Casualty. SUBJECTS: Children between ages one to twelve years presenting with a common cold between December 2010 and February 2012 were enrolled. OUTCOME MEASURES: Frequency, severity and extent to which cough bothered and disturbed child and parental sleep were assessed at baseline and over the subsequent five days through telephone interview using a validated scoring tool. RESULTS: One hundred and forty five children were enrolled in the study (45- placebo, 57 -honey, 43 -salbutamol). Of the 145 children 51% were male. Honey significantly reduced the total mean symptom score by day three (p < 0.001). Total mean difference in scores between day zero to five demonstrated a significant difference of honey's efficacy over placebo (p < 0.002) however no difference was noted when compared to salbutamol (p < 0.478). Significant differences in both total as well as each individual symptom score was detected with honey consistently scoring the best whilst placebo and salbutamol scored the worst. In paired comparisons honey was superior to placebo but not salbutamol, whilst salbutamol was not superior to placebo. CONCLUSION: Honey was most effective in symptomatic relief of symptoms associated with the common cold whilst salbutamol or placebo offered no benefit.

Generation of herpesvirus entry mediator (HVEM)-restricted herpes simplex virus type 1 mutant viruses: resistance of HVEM-expressing cells and identification of mutations that rescue nectin-1 recognition.

Both initial infection and cell-to-cell spread by herpes simplex virus type 1 (HSV-1) require the interaction of the viral glycoprotein D (gD) with an entry receptor on the cell surface. The two major HSV entry receptors, herpesvirus entry mediator (HVEM) and nectin-1, mediate infection independently but are coexpressed on a variety of cells. To determine if both receptors are active in these instances, we have established mutant viruses that are selectively impaired for recognition of one or the other receptor. In plaque assays, these viruses showed approximately 1,000-fold selectivity for the matched receptor over the mismatched receptor. Separate assays showed that each virus is impaired for both infection and spread through the mismatched receptor. We tested several human tumor cell lines for susceptibility to these viruses and observed that HT29 colon carcinoma cells are susceptible to infection by nectin-1-restricted virus but are highly resistant to HVEM-restricted virus infection, despite readily detectable HVEM expression on the cell surface. HVEM cDNA isolated from HT29 cells rendered HSV-resistant cells permissive for infection by the HVEM-restricted virus, suggesting that HT29 cells lack a cofactor for HVEM-mediated infection or express an HVEM-specific inhibitory factor. Passaging of HVEM-restricted virus on nectin-1-expressing cells yielded a set of gD missense mutations that each restored functional recognition of nectin-1. These mutations identify residues that likely play a role in shaping the nectin-1 binding site of gD. Our findings illustrate the utility of these receptor-restricted viruses in studying the early events in HSV infection.

Characterization of soluble glycoprotein D-mediated herpes simplex virus type 1 infection.

Herpes simplex virus type 1 (HSV-1) entry into permissive cells involves attachment to cell-surface glycosaminoglycans (GAGs) and fusion of the virus envelope with the cell membrane triggered by the binding of glycoprotein D (gD) to cognate receptors. In this study, we characterized the observation that soluble forms of the gD ectodomain (sgD) can mediate entry of gD-deficient HSV-1. We examined the efficiency and receptor specificity of this activity and used sequential incubation protocols to determine the order and stability of the initial interactions required for entry. Surprisingly, virus binding to GAGs did not increase the efficiency of sgD-mediated entry and gD-deficient virus was capable of attaching to GAG-deficient cells in the absence of sgD. These observations suggested a novel binding interaction that may play a role in normal HSV infection.

Role of non-raft cholesterol in lymphocytic choriomeningitis virus infection via alpha-dystroglycan.

Dystroglycan (DG) is an extracellular matrix receptor necessary for the development of metazoans from flies to humans and is also an entry route for various pathogens. Lymphocytic choriomeningitis virus (LCMV), a member of the family Arenaviridae, infects by binding to alpha-DG. Here, the role of cholesterol lipid rafts in infection by LCMV via alpha-DG was investigated. The cholesterol-sequestering drugs methyl-beta-cyclodextrin (MbetaCD), filipin and nystatin inhibited the infectivity of LCMV selectively, but did not affect infection by vesicular stomatitis virus. Cholesterol loading after depletion with MbetaCD restored infectivity to control levels. DG was not found in lipid rafts identified with the raft marker ganglioside GM1. Treatment with MbetaCD, however, enhanced the solubility of DG. This may reflect the association of DG with cholesterol outside lipid rafts and suggests that association of DG with non-raft cholesterol is critical for infection by LCMV through alpha-DG.