Albumin precursorandHsp70modulatecornealwoundhealinginanorgan culturemodel

In order to investigate the role of albumin precursor and Hsp70 in corneal wound healing, we have analyzed the distribution of these proteins in wounded and non-wounded corneas of rabbits and the effects of topical applications of anti-albumin precursor and anti-Hsp70 antibodies on wound healing. Anti-albumin precursor and anti-Hsp70 antibodies were topically applied in healing corneal epithelium of rabbit eyes in organ culture. Corneas were allowed to heal in vitro for up to 120 h in serum-free medium with 5 and 10 μg/ml or without (migrating control) anti-albumin precursor/ or anti-Hsp70 antibodies. Fibronectin (Fb) (5 μg/ml) was used as a positive control. Immunofluorescence labelling was used to detect proteins in corneal epithelium at various time intervals following an epithelial defect. Delay in wound healing (pp120 h with 10 μg/ml. Additionally, immunofluoresence showed a strong co-localization of Hsp70 and albumin precursor during the active phase of wound healing. The presence of albumin precursor and Hsp70 in the epithelial compartment of the cornea indicates a role for these proteins in modulating cell behavior such as epithelial growth, adhesion or regeneration, thus contributing to corneal epithelial wound healing

Hepatitis B virus interacts with albumin precursor in vivo

A range of proteins has been recognized as mediators/hypothetical receptors for hepatitis B virus (HBV), but the results are conflicting and inconclusive especially regarding their biological significance. This study was aimed at identifying a novel HBV-interacting protein which would provide a better understanding of its transport in blood, attachment, fusion and entry into hepatocytes. Serum samples positive for HBV confirmed by PCR were subjected to ammonium sulfate fractionations at 50, 75, 100%, saturation. PCR of each fraction demonstrated amplification of HBV in 100% fraction. Protein analysis by SDS PAGE of fractions showed one band of approximately 69 kDa protein, in 100% fraction. The 100% fraction band was excised from gel and sequence was determined by MALDI TOF which showed mass values from 705 to 3722. Mass spectrometry of trypsinized 69 kDa species revealed peptide sequences that covered 54% of the serum albumin precursor amino acid sequence, with pI of 5.9. Western blot, carried out using primary anti-albumin precursor antibody, further validated this protein. This study establishes that Hepatitis B Virus binds to albumin precursor, suggesting its role in the initiation of HBV infection and hence may offer new therapeutic strategies against HBV infection

Effect of Whitefly Transmitted Geminiviruses on the Physiology of Tomato (Lycopersicon esculentum L.) and Tobacco (Nicotiana benthamiana L.) Plants

Viruses always have profound effect on the growth and development of plants and interact with host defense mechanism and results in altering the physiology of plants. In the present study effect of different whitefly transmitted begomoviruses; (monopartite as well as bipartite) on the contents of soluble sugar and chlorophyll of Lycopersicon esculentum and Nicotiana benthamiana plants were investigated. It was found that the leaf relative water contents (RWC), total soluble sugars (TSS), fresh and dry biomass, photosynthetic pigments level were more in healthy plants as compared to virus infected plants. Plant infected both with Tomato leaf curl new dehli virus and Cotton leaf curl burewalla virus associated with betasatelite showed reduced TSS and leaf relative water contents as compared to healthy plants. Among infectious clones Cotton leaf curl burewalla virus associated with beta satellite (CLCuV+CLCuB), Tomato leaf curl new dehli virus (ToLCNDV) caused more reduction while Malvestrum yellow vein change manga virus (MYVCMV) caused less reduction as compared to above mentioned clones. CLCuV+ CLCuB showed significant effect on Chlorophyll a (9.60, 8.93mg/g), Chlorophyll b (7.2, 5.86 mg/g) and total chlorophyll contents (16.8, 14.8 mg/g) in both plants respectively. While ToLCNDV caused reduction in RWC (80% to 36%) in case of L. esculentum while RWC (75 to 30%) in N. benthamiana. Among L. esculentum TSS was reduced (8.13 to 3.33 mg/g) due to CLCuV+CLCuB infection. In case of N. benthamiana TSS was reduced (9.433 to 2.5 mg/g) due to ToLCNDV. Keywords: Geminivirus, Plant Physiology, TSS, Chlorophyll.

Cerebellar mutism syndrome after surgical resection of posterior fossa neoplastic lesions

Cerebellar Mutism Syndrome (CMS) is a well-described clinical entity that complicates surgeries for posterior fossa tumours; more so in children than adults. This review focuses on the current understanding of CMS, its incidence and risk factors. Incidence showed a variable range in retrospective studies due to variety of definitions. Risk factors can be classified as either modifiable including surgical technique, or non-modifiable which include tumour related factors. A positive correlation has been associated between tumour pathology, brain stem invasion and size of tumour at time of presentation with development of CMS

Childhood medulloblastoma

Medulloblastoma is the most common malignant brain tumour in children and is a major cause of mortality and morbidity, particularly in low- and middle-income countries. It has been risk-stratified on the basis of clinical (age, metastasis and extent of resection) and histological subtypes (classic, desmoplastic and anaplastic). However, recently medulloblastoma has been sub-grouped by using a variety of different genomic approaches, such as gene expression profiling, micro-ribonucleic acid profiling and methylation array into 4 groups, namely Wingless, Sonic hedgehog, Group 3 and Group 4. This new sub-grouping has important therapeutic and prognostic implications. After acute leukaemia, brain tumour is the second most common malignancy in the paediatric age group. The improvement in outcome of acute lymphoblastic leukaemia in low- and middle-income countries reflects the relative simplicity of diagnostic procedures and management. Unlike leukaemia, the management of brain tumours requires a complex multidisciplinary approach, including neuro-radiologists, neurosurgeons with a paediatric expertise, neuropathologists, radiation oncologists and neuro-oncologists. In addition, the equipment required for the diagnosis (magnetic resonance imaging scan, histological, molecular and genetic techniques) and the management (operating room, radiation facilities) is a limiting factor in countries with limited resources. In Pakistan, there are very few centres able to treat children with brain tumours. The current literature review was planned to provide an update on the management of this tumour

Synthesis and cytotoxic activity of some derivatives of alkyl piperidine

Abstract: Synthesis of novel phenacyl derivatives of alkyl piperidine as cytotoxic agents via simple and single step reaction procedure is going to be reported here. Twelve new compounds were successfully synthesized in moderate yield and in solid form. Their synthesis was confirmed by TLC, melting point, CHN analysis and through different spectral studies such as UV, IR, Mass and proton NMR. The advantages of this synthetic route are simple operation, mild reaction conditions and good yields. These newly synthesized derivatives were extensively explored for their cytotoxicity by brine shrimp lethality assay

Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: a report of the international immuno‐oncology biomarker working group

The clinical significance of the tumor-immune interaction in breast cancer (BC) has been well established, and tumor-infiltrating lymphocytes (TILs) have emerged as a predictive and prognostic biomarker for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) breast cancer (TNBC) and HER2-positive breast cancer. How computational assessment of TILs can complement manual TIL-assessment in trial- and daily practices is currently debated and still unclear. Recent efforts to use machine learning (ML) for the automated evaluation of TILs show promising results. We review state-of-the-art approaches and identify pitfalls and challenges by studying the root cause of ML discordances in comparison to manual TILs quantification. We categorize our findings into four main topics; (i) technical slide issues, (ii) ML and image analysis aspects, (iii) data challenges, and (iv) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns, or design choices in the computational implementation. To aid the adoption of ML in TILs assessment, we provide an in-depth discussion of ML and image analysis including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial- and routine clinical management of patients with TNBC

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

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

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

Ethnotaxonomical Approach in the Identification of Useful Medicinal Flora of Tehsil Pindigheb (District Attock) Pakistan

researchThe presented research investigated the use of folk remedies among the people of Tehsil Pindigheb, District Attock of Pakistan. During the ethnobotanical survey, we documented indigenous knowledge and collected plant specimens which included medicinal plants. Through questionnaire, ethnomedicinal data was collected from key informants and local inhabitants in randomly selected villages. One hundred plant species belonging to 44 families were recorded as medicinal flora of the area. Due to construction of new housing colonies, modern agricultural practices and cultural changes within the community, the use of traditional knowledge and medicinal plant species are threatened day by day in the area. This study will provide help in future conservation strategies