Microarray analysis reveals distinct immune signatures in BCR?ABL positive and negative myeloproliferative neoplasms

Background: BCR?ABL mutation on the Philadelphia chromosome is the key driver of chronic myeloid leukemia (CML) pathogenesis. However, there are certain cases of myeloproliferative neoplasms (MPN) wherein no inherent driver mutation is detected resulting in clinical phenotype. It is important to identify key genes and pathways in driving the disease. The aim of the study was to use a gene-based omics approach to molecularly characterize these mutation-positive and negative cases to further strengthen diagnostics and precision medicine. Methods: A microarray profiling was done on CD34 positive cells isolated from two BCR?ABL positive and five BCR?ABL negative samples. JAK2V617F mutation testing was also done to rule out the presence of any other mutation in the latter group. The fold change cut-off was taken as �5 with p?0.5 for significant genes. The gene network and pathway analysis were done using DAVID and STRING software. Results: The genes upregulated in BCR?ABL negative samples were shown to be involved in immune regulation, signal transduction and T- and B-cell signalling. The protein-protein interaction network of upregulated genes in these samples were enriched for various immunomodulatory genes such as HLADP, HLADQ , IL7R, CCR7, CD3 subtypes. These genes further formed a network with signal transduction genes such as LCK, FYN, RAG1, DOCK1, AKT3, SMAD3, LEF1. Conclusion: The results suggested a modulation of immune response genes and its subsequent effect on oncogenic signalling in BCR?ABL negative samples as compared to BCR?ABL positive samples. The protein network analysis was enriched for genes involved in Src, TGF-beta and PI3K-AKT pathway contributing to the proliferation of neoplastic clone.

Target-Oriented Clinical Skill Enhancement (TOCSE) builds up confidence of fourth-year medical students during first-time patient encounter: An effective bridging tool after online didactic undergraduate classes during the COVID-19 pandemic

@#<jats:p>Background and Objective: Teaching clinical skills to undergraduate medical students has brought significant challenges during the COVID-19 pandemic. Patient discussion utilized hypothetical cases from history taking to diagnosis and management. Further, everything was delivered online. Target-Oriented Clinical Skill Enhancement (TOCSE) is a teaching and learning tool that integrates the basic medical sciences, such as anatomy, physiology, pathology, microbiology, and pharmacology, at the clinical level. TOCSE has been proven to improve the clinical performance of fourth-year medical students. However, clinical confidence remains an issue, especially for medical students on pure online mode of learning during the pandemic. Therefore, this study was undertaken to determine if TOCSE also facilitates the development of confidence in the clinical performance of 4th-year medical students during the first-time patient encounter after online undergraduate classes. Methods: Eight-item Clinical Performance Confidence Scale survey was performed at three (3) time points of fourth-year medical student’s rotation in the Department of Medicine: (1) prior to the deployment to the outpatient department (Pre-OPD), (2) after the first-time patient encounter without TOCSE workshop (Post-OPD no TOCSE), and (3) after the patient encounter with TOCSE workshop (Post-OPD with TOCSE). Mean and standard deviations were used to summarize the confidence level of the 4th-year medical students, based on the 10-point differential scale being 0 as not confident at all and 10 as very confident. Wilcoxon Signed Rank assessed improvements of confidence level from Pre-OPD to Post-OPD. Effect sizes were also calculated to compare the improvement in the items. All statistical tests were performed in SPSS version 26.0. P-values less than 0.05 indicate a significant increase in the confidence level of 4th-year medical students. Results: There is a significant increase in the clinical confidence of 4th-year medical students from Pre-OPD to Post-OPD no TOCSE (mean ± SD: 6.32 ± 1.02 to 7.06 ± 0.95, p<0.001). Comparing the eight items between Pre-OPD and Post-OPD with no TOCSE, performing a complete physical examination has the most remarkable improvement. Further, there is a significant increase in the clinical confidence of 4th-year medical students from Post-OPD no TOCSE to Post-OPD with TOCSE (mean ± SD: 7.06 ± 0.95 to 7.51 ± 0.89, p<0.001). The performance of a complete history-taking has the most considerable improvement (7.29 + 1.03 to 7.89 + 1.01, p<0.001). Correspondingly, the most significant increase in the clinical confidence of 4th-year medical students was seen among the Post-OPD with TOCSE compared to their Pre- OPD confidence scores (mean ± SD: 6.32 ± 1.02 to 7.51 ± 0.89, p<0.001). Among the eight items between Pre-OPD and Post-OPD with TOCSE confidence scores, the item on performing a complete physical examination has the most remarkable improvement (5.67 ± 1.37 to 7.20 ± 1.22, p<0.001), closely followed by performing a complete history-taking (6.53 ± 1.19 to 7.89 ± 1.01, p<0.001). The most significant improvements in clinical confidence were seen in all the items in the Post-OPD with TOCSE than in the Post-OPD with no TOCSE versus Pre-OPD confidence scores. In addition, with TOCSE, the number of medical students who scored 7.50 and above was amplified more than 3 times (17.4% to 58.7%, p<0.001, Pre-OPD vs. Post-OPD with TOCSE, respectively). Conclusion: Target-Oriented Clinical Skill Enhancement (TOCSE) effectively builds up confidence during first-time patient encounters among fourth-year medical students taught online with hypothetical cases during their undergraduate classes. Key words: Target-Oriented Clinical Skill Enhancement, clinical confidence, clinical skill, fourth-year medical students, medical undergraduate challenge, online teaching in COVID-19 pandemic</jats:p>

Serological Detection of Antibodies against Anaplasma spp. in Cattle Reared in the Gyeongsangbuk-do, Korea

Anaplasmosis is a tick-borne, non-contagious, zoonotic disease caused by Anaplasma spp., which include Anaplasma marginale, A. centrale, A. phagocytophilum, A. platys, A. ovis, and A. bovis. Recently, in Korea, the prevalence of Anaplasma spp. has been investigated in some animals, such as dogs, horses, goats, cats, and Korean water deer. In cattle, A. marginale is the most virulent species and regarded as the typical type of species. However, data on the seroprevalence of Anaplasma spp. in cattle in Korea during the last decade is limited. This study was designed to investigate the seroprevalence of bovine anaplasmosis in Korea. From 2010 to 2013, blood samples were collected from 568 cattle. Forty animals (7.0%) tested seropositive for Anaplasma spp. by cELISA. Despite that current bovine anaplasmosis seropositivity rate in the Gyeongsangbuk-do is lower than those in tropical countries, anaplasmosis needs to be regarded as a concerning disease. The identification of the specific Anaplasma species infecting cattle in this province requires additional molecular studies. Moreover, further monitoring and control programs for bovine anaplasmosis is required, and the information from this study will be beneficial to develop these programs.

Quantitative Analysis of Dammarane-type Ginsenosides in Different Ginseng Products

Ginseng products available in different forms and preparations are reported to have varied bioactivities and chemical compositions. In our previous study, four new dammarane-type ginsenosides were isolated from Panax ginseng, which are ginsenoside Rg18 (1), 6-acetyl ginsenoside Rg3 (2), ginsenoside Rs11 (3), and ginsenoside Re7 (4). Accordingly, the goal of this study was to determine the distribution and content of these newly characterized ginsenosides in different ginseng products. The content of compounds 1 – 4 in different ginseng products was determined via HPLC-UV. The samples included ginseng roots from different ginseng species, roots harvested from different localities in Korea, and samples harvested at different cultivation ages and processed under different manufacturing methods. The four ginsenosides were present at varying concentrations in the different ginseng samples examined. The variations in their content could be attributed to species variation, and differences in cultivation conditions and manufacturing methods. The total concentration of compounds 1 – 4 were highest in ginseng obtained from Geumsan (185 µg/g), white-6 yr ginseng (150 µg/g), and P. quinquefolius (186 µg/g). The results of this study provide a basis for the optimization of cultivation conditions and manufacturing methods to maximize the yield of the four new ginsenosides in ginseng.

Is the global rise of asthma an early impact of anthropogenic climate change? / Será o crescimento mundial de incidência da asma um impacto antecipado de mudanças climáticas antropogênicas?

The increase in asthma incidence, prevalence, and morbidity over recent decades presents a significant challenge to public health. Pollen is an important trigger of some types of asthma, and both pollen quantity and season depend on climatic and meteorological variables. Over the same period as the global rise in asthma, there have been considerable increases in atmospheric carbon dioxide concentration and global average surface temperature. We hypothesize anthropogenic climate change as a plausible contributor to the rise in asthma. Greater concentrations of carbon dioxide and higher temperatures may increase pollen quantity and induce longer pollen seasons. Pollen allergenicity can also increase as a result of these changes in climate. Exposure in early life to a more allergenic environment may also provoke the development of other atopic conditions, such as eczema and allergic rhinitis. Although the etiology of asthma is complex, the recent global rise in asthma could be an early health effect of anthropogenic climate change.

O crescimento na incidência, prevalência e morbidade da asma durante as recentes décadas representa importante desafio para a saúde pública. Pólen é um importante desencadeador de alguns tipos de asma e tanto a sua quantidade como as especificidades das estações em que eles mais se disseminam dependem de variáveis climáticas e meteorológicas. No mesmo período em que se observa o incremento na incidência da asma houve considerável crescimento de concentração de dióxido de carbono na atmosfera e aumento da média de temperatura da superfície da terra. Nossa hipótese é a de que as mudanças antropogênicas do clima constituem um fator plausível para o incremento da incidência da asma. Maiores concentrações de dióxido de carbono e elevadas temperaturas podem aumentar a quantidade de pólen e induzir o aumento de variações climáticas que facilitam sua dispersão. Alergias a pólen podem aumentar como resultado de mudanças climáticas. Exposição precoce a ambientes que predisponham a alergias também podem provocar o desenvolvimento de condições atópicas, como eczema e rinite alérgica. Embora a etiologia da asma seja complexa, o recente incremento de sintomas de asma em nível global pode significar um dos antecipados efeitos sobre a saúde, de mudanças climáticas antropogênicas.