Emerging magnetic resonance imaging (MRI) biomarkers of hepatic steatosis have demonstrated tremendous promise for accurate quantification of hepatic triglyceride concentration. These methods quantify the “proton density fat-fraction” (PDFF), which reflects the concentration of triglycerides in tissue. Previous in vivo studies have compared MRI-PDFF with histologic steatosis grading for assessment of hepatic steatosis. However, the correlation of MRI-PDFF with the underlying hepatic triglyceride content remained unknown. The aim of this ex vivo study was to validate the accuracy of MRI-PDFF as an imaging biomarker of hepatic steatosis. Using ex vivo human livers, we compared MRI-PDFF with magnetic resonance spectroscopy-PDFF (MRS-PDFF), biochemical triglyceride extraction and histology as three independent reference standards. A secondary aim was to compare the precision of MRI-PDFF relative to biopsy for the quantification of hepatic steatosis. MRI-PDFF was prospectively performed at 1.5T in 13 explanted human livers. We performed co-localized paired evaluation of liver fat content in all nine Couinaud segments using single-voxel MRS-PDFF (n=117), tissue wedges for biochemical triglyceride extraction (n=117), and five core biopsies performed in each segment for histologic grading (n=585). Accuracy of MRI-PDFF was assessed through linear regression with MRS-PDFF, triglyceride extraction and histology. Intra-observer agreement, inter-observer agreement and repeatability of MRI-PDFF and histologic grading were assessed through Bland-Altman analyses. MRI-PDFF showed an excellent correlation with MRS-PDFF (r=0.984; CI: 0.978–0.989) and strong correlation with histology (r=0.850; CI: 0.791–0.894) and triglyceride extraction (r=0.871; CI: 0.818–0.909). Intra-observer agreement, inter-observer agreement and repeatability showed a significantly smaller variance for MRI-PDFF than for histologic steatosis grading (all p<0.001). Conclusion MRI-PDFF is an accurate, precise and reader-independent non-invasive imaging biomarker of liver triglyceride content, capable of steatosis quantification over the entire liver.
ObjectiveUsing multidisciplinary treatment modalities the majority of children with cancer can be cured but we are increasingly faced with therapy-related toxicities. We studied brain morphology and neurocognitive functions in adolescent and young adult survivors of childhood acute, low and standard risk lymphoblastic leukemia (ALL), which was successfully treated with chemotherapy. We expected that intravenous and intrathecal chemotherapy administered in childhood will affect grey matter structures, including hippocampus and olfactory bulbs, areas where postnatal neurogenesis is ongoing.MethodsWe examined 27 ALL-survivors and 27 age-matched healthy controls, ages 15–22 years. ALL-survivors developed disease prior to their 11th birthday without central nervous system involvement, were treated with intrathecal and systemic chemotherapy and received no radiation. Volumes of grey, white matter and olfactory bulbs were measured on T1 and T2 magnetic resonance images manually, using FIRST (FMRIB’s integrated Registration and Segmentation Tool) and voxel-based morphometry (VBM). Memory, executive functions, attention, intelligence and olfaction were assessed.ResultsMean volumes of left hippocampus, amygdala, thalamus and nucleus accumbens were smaller in the ALL group. VBM analysis revealed significantly smaller volumes of the left calcarine gyrus, both lingual gyri and the left precuneus. DTI data analysis provided no evidence for white matter pathology. Lower scores in hippocampus-dependent memory were measured in ALL-subjects, while lower figural memory correlated with smaller hippocampal volumes.InterpretationFindings demonstrate that childhood ALL, treated with chemotherapy, is associated with smaller grey matter volumes of neocortical and subcortical grey matter and lower hippocampal memory performance in adolescence and adulthood.
Neural tissue engineering focuses on development of biomaterials that could support regeneration of neurons after trauma as well as injury caused by degenerative diseases. In this work we describe novel soft alginate hydrogels, which provide an adhesive matrix for rat and human neurons and facilitate neurite outgrowth. Only soft hydrogels, prepared with sub-stoichiometric concentrations of Ca²⁺, Ba²⁺, and Sr²⁺ cations by cross-linking with no >10% of all potentially available gelation sites in alginate, facilitated rapid and abundant neurite outgrowth in primary neuronal monolayer cultures, neural spheroids, and neurons derived from rat and human neural stem cells. To support neurite growth, hydrogels did not require modification by any extracellular matrix components and were prepared from high as well as low viscous alginates of different origin. In addition, neurons cultured on soft hydrogels were resistant to oxidative stress injury induced by hydrogen peroxide. These findings, which apply both to rat and human neurons, go beyond the well-described role of alginates as inert materials for cell encapsulation. Such soft alginate hydrogels may be useful for the preparation of pharmaceutical compositions for prophylaxis and treatment of neurodegenerative disorders, for promoting neuronal regeneration in the peripheral and central nervous system and for neural tissue engineering applications.
Background Visceral leishmaniasis (VL) or Kala-azar has been a major public health problem in Bihar, India, for several decades. A few VL infected districts including Vaishali have reported >600 cases annually. Hence, in 2015, the Government of India entrusted ICMR-Rajendra Memorial Research Institute of Medical Sciences, Patna, to implement an integrated control strategy for achieving the VL elimination target (<1 case per 10,000 people at the block level) in the Vaishali District of Bihar. Methodology This study was conducted between January 2015 and December 2016. An integrated control strategy including the spatio-temporal mapping of VL-case distribution, active case detection, chemical-based vector control using indoor residual spraying (IRS), community awareness campaigns, the training of IRS members, the training of medical doctors for effective treatment, daily monitoring and the supervision of IRS activities, logistic management, post-IRS quality assurance, epidemiological surveillance, and entomological monitoring was performed. An insecticide quantification test was performed for evaluating the IRS quality on sprayed walls. A modern compression pump was used to maintain spray quality on different wall surfaces. The impact of IRS was assessed through sand fly collection in human dwellings and cattle sheds in pre-and post-IRS. The insecticide susceptibility of local P. argentipes was performed before each IRS round (in February and June) during 2015-2016. Statistical analysis such as the mean, percentage, and 95% CI were used to summarize the results.
Background:Acute poisoning is a common health-care problem requiring admission in the intensive care unit (ICU) in the developing countries. The study was conducted to assess the epidemiological parameters of acute poisoning and factors affecting clinical course and outcome of the patients in ICU in the eastern part of Nepal.Methodology:This was a prospective observational study conducted at ICU of tertiary care hospital in the eastern part of Nepal for the duration of 2 years. All the acute poisoning cases admitted in the ICU were studied for epidemiological profiles, poisoning characteristics, and various clinical factors affecting the outcome of the patients.Results:Eighty-five patients with acute poisoning were included in the study. Suicidal attempt leading to acute poisoning was seen in majority of the young population. Majority of the poisoning was due to the organophosphorous compounds (43.5%). Patients with organophosphorous poisoning had a significantly longer duration of ICU stay (P = 0.020). The survival of the patients was significantly affected by age, duration of presentation to the hospital, Glasgow Coma Scale, Sequential Organ Failure Assessment score, need for mechanical ventilation, duration of ICU stay, hepatic failure, coagulopathy, and need for vasoactive drugs (P < 0.05). The independent predictors of mortality observed in the study were age, delayed presentation to the hospital, hepatic failure, and need for mechanical ventilation.Conclusion:Organophosphorous poisoning was the most common acute poisoning in young population leading to the ICU admission. Older age, delayed initiation of the resuscitative measures, need for mechanical ventilation, and hepatic failure significantly affected the mortality.
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