Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.     

A panoramic view on phytochemical,nutritional, and therapeutic attributes of Ziziphus mauritiana Lam.: A comprehensive review

Ziziphus mauritiana (Rhamnaceae), commonly known as Indian jujube, is a pharmacologically diverse medicinal plant. A plethora of active phytochemical constituents of this plant has been revealed so far, namely, berberine, quercetin, kaempferol, sitosterol, stigmasterol, lanosterol, diosgenin, and so forth. Several studies demonstrated the exploration of pharmacological potential of various parts such as fruits, leaves, and stems of the plant as antioxidant, cytotoxic, antimicrobial, anti‐diarrhoeal, antidepressant, immunomodulator, and hepatoprotective. This review gives a unique summary including phytochemistry, nutritional value, and significant pharmacological importance of Z. mauritiana. The literature search was carried out via search engine PubMed, Science Direct, and so on. The data were heterogeneous in terms of leaves, stem, roots, and fruits which were used for different experimental findings, which made the comparison a lengthy task. Study findings suggested that the extracts from this plant may possess numerous types of pharmacological activities. As the search for novel drugs from botanical sources continues, there is need for future investigations to isolate and characterize pharmacologically active agents that confer medicinal properties on Z. mauritiana, as well as to elucidate the structures of these agents by which they exert their healing properties and to scientifically validate the existing traditional practices concerning its health benefits.     

Airway management for neonates requiring ex utero intrapartum treatment (EXIT)

In utero congenital malformations in the fetus can occasionally lead to an obstructed airway at birth accompanied by hypoxic injury or peripartum demise, without intervention. Ex utero intrapartum treatment (EXIT) may help reduce morbidity and mortality associated with challenging airways by providing extra time on uteroplacental circulation to secure the airway. Meticulous preparation and planning are crucial for this procedure. Many different types of congenital malformations can result in a difficult airway, but there is no correlation between specific malformations and a required type of airway intervention. Based on our experience and literature review, an airway process flow diagram has been created to help assist teams in decision‐making for airway intervention in a neonate during the EXIT procedure. The management of the airway in this scenario involves additional unique considerations that accompany handling a partially delivered newborn in the uterine environment. Extensive preparation and team rehearsal are essential to the success of this procedure.     

Comparing computer-generated and pathologist-generated tumour segmentations for immunohistochemical scoring of breast tissue microarrays

Background:

Tissue microarrays (TMAs) have become a valuable resource for biomarker expression in translational research. Immunohistochemical (IHC) assessment of TMAs is the principal method for analysing large numbers of patient samples, but manual IHC assessment of TMAs remains a challenging and laborious task. With advances in image analysis, computer-generated analyses of TMAs have the potential to lessen the burden of expert pathologist review.

Methods:

In current commercial software computerised oestrogen receptor (ER) scoring relies on tumour localisation in the form of hand-drawn annotations. In this study, tumour localisation for ER scoring was evaluated comparing computer-generated segmentation masks with those of two specialist breast pathologists. Automatically and manually obtained segmentation masks were used to obtain IHC scores for thirty-two ER-stained invasive breast cancer TMA samples using FDA-approved IHC scoring software.

Results:

Although pixel-level comparisons showed lower agreement between automated and manual segmentation masks (κ=0.81) than between pathologists'' masks (κ=0.91), this had little impact on computed IHC scores (Allred; =0.91, Quickscore; =0.92).

Conclusions:

The proposed automated system provides consistent measurements thus ensuring standardisation, and shows promise for increasing IHC analysis of nuclear staining in TMAs from large clinical trials.     

Corticosteroid treatment exacerbates nephrotic syndrome in a zebrafish model of magi2a knockout

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HLA incompatible combined liver–kidney transplantation: Dynamics of antibody modulation revealed by a novel approach to HLA antibody characterisation

This case report confirms the utility of simultaneous liver transplantation in allowing successful kidney transplantation in the face of preformed, high levels of DSA, which would under normal circumstances be associated with hyperacute rejection and kidney graft failure. Antibody characterisation in terms of epitope specificity is more accurate and informative than antibodies described as “antigen-specific” and we suggest a method for identifying and tracking these antibodies; i.e. follow the epitope reaction not the antigen reactions. We consider that this will give a better insight into the behaviour and pathogenicity of HLA-specific sera. In the case presented here this approach has revealed some novel features of the post transplant antibody response in a sensitised recipient. These illustrate three phenomena which challenge current dogmas; an early resynthesis of DSA does not necessarily cause AMR, high levels of DSA can spontaneously modulate, and measurement of antibodies in terms of antigen specificity can give misleading results.