The Structure and Content Analysis of ‘Al-Qanon al-Saghir’: A Descriptive Analysis

Among the historical traditional medical texts, there are several hand-written manuscripts with the same structure and format on one topic. Two versions of these hand written manuscripts are under the titles of Al-Kafi Fi Al-Teb and Al-Kefaye Fi Elm Al-Teb, or briefly Al-Kefayeh which in the early sources is also referred to as Al-Qanon al-Saghir, attributed to Ibn Mandevaih. On the other hand, other versions of the Al-Qanon al- Saghir were attributed to Avicenna. Since it seems unlikely that these quite similar versions belong to two authors, it is necessary to figure out the actual writer of the work. This paper is a descriptive analysis of the existing evidence about Al-Qanon al-Saghirh and written scripts,  comparing their structure and contents to similar works of Ibn Mandevaih, and Avicenna, to determine whether the author is the former or the latter, or both. After investigating historical documents, the investigators found that Al-Qanon al-Saghir was attributed to Ibn Mandevaih in early works and to Ibn-Sina in later works. The he similarities found in the structure and content of the two versions make it difficult to convince the researchers to consider each text as a separate book written by different authors. Moreover, contradictory findings presented in Al-Qanon al-Saghir to Avicenna’s famous works indicated that this book belongs to Ibn Mandevaih. The brief and comprehensive al-Qanon al-Saghir is not the summary of the extensive al-Qanon Fi Teb medical textbook by Avicenna but rather an entirely different book written by  Ibn Mandevaih

9-cis-Retinoic Acid and 1,25-dihydroxy Vitamin D3Improve the Differentiation of Neural Stem Cells into Oligodendrocytes through the Inhibition of the Notch and Wnt Signaling Pathways

Background: Differentiating oligodendrocyte precursor cells (OPCs) into oligodendrocytes could be improved by inhibiting signaling pathways such as Wnt and Notch. 9-cis-retinoic acid (9-cis-RA) and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) can ameliorate oligodendrogenesis. We investigated whether they could increase oligodendrogenesis by inhibiting the Wnt and Notch signaling pathways. Methods: Cortical neural stem cells were isolated from 14-day-old rat embryos and cultured using the neurosphere assay. The cells were treated in 4 different conditions for 1 week: the negative control group received only the basic fibroblast growth factor, the positive control group received only T3 without growth factors, the RA group was treated with 9-cis-RA, and the Vit D3 group was treated with 1,25(OH)2D3. The effects of 9-cis-RA and 1,25(OH)2D3 on the level of the myelin basic protein (MBP) and the gene expression of the SOX10, MBP gene, HES5, and LRP6 were studied using flow cytometry and real-time PCR. The data were analyzed using one-way ANOVA with GraphPad Prism. A P value less than 0.05 was considered significant. Results: The mRNA expressions of the SOX10, MBP, and MBP gene were significantly increased in the treated groups compared with the negative control group; the increase was similar in the 9-cis-RA group and the positive control group. Furthermore, 9-cis-RA significantly decreased the expression of the HES5 gene, a Notch signaling pathway transcription factor, and 1,25(OH)2D3 significantly reduced the expression of the LRP6 gene, a Wnt signaling pathway co-receptor. Conclusion: It seems that 9-cis-RA and 1,25(OH)2D3 are good candidates to improve the differentiation of OPCs into oligodendrocytes

Coexistence of multiple arterial variations in the genitourinary system

Variations in the renal, adrenal and testicular arteries are of clinical significance as well as anatomical and embryological interest. The present case report describes the incidental finding of unilateral multiple renal arteries on the right side with bilateral variant testicular arteries, which had not been reported so far. These variations were observed during routine dissection of the abdominal region in an Iranian cadaver. The upper supplementary renal artery branched from the abdominal aorta and sent superior suprarenal artery to the adrenal gland. The lower supplementary renal artery arose from the main renal artery. Both additional arteries entered the kidney proximal to its hilum. The right testicular artery supplied the right suprarenal gland by an unusual branch. Double testicular arteries were seen on the left side with a relatively high origin from abdominal aorta. The objective of this report is to supplement the knowledge of vascular variations in the renal, suprarenal and testicular arteries that could be quite useful from a clinical point of view

Purification of Immature Neuronal Cells from Neural Stem Cell Progeny

Large-scale proliferation and multi-lineage differentiation capabilities make neural stem cells (NSCs) a promising renewable source of cells for therapeutic applications. However, the practical application for neuronal cell replacement is limited by heterogeneity of NSC progeny, relatively low yield of neurons, predominance of astrocytes, poor survival of donor cells following transplantation and the potential for uncontrolled proliferation of precursor cells. To address these impediments, we have developed a method for the generation of highly enriched immature neurons from murine NSC progeny. Adaptation of the standard differentiation procedure in concert with flow cytometry selection, using scattered light and positive fluorescent light selection based on cell surface antibody binding, provided a near pure (97%) immature neuron population. Using the purified neurons, we screened a panel of growth factors and found that bone morphogenetic protein-4 (BMP-4) demonstrated a strong survival effect on the cells in vitro, and enhanced their functional maturity. This effect was maintained following transplantation into the adult mouse striatum where we observed a 2-fold increase in the survival of the implanted cells and a 3-fold increase in NeuN expression. Additionally, based on the neural-colony forming cell assay (N-CFCA), we noted a 64 fold reduction of the bona fide NSC frequency in neuronal cell population and that implanted donor cells showed no signs of excessive or uncontrolled proliferation. The ability to provide defined neural cell populations from renewable sources such as NSC may find application for cell replacement therapies in the central nervous system

Oridonin Could Inhibit Inflammation and T-cell Immunoglobulin and Mucin-3/Galectin-9 (TIM-3/Gal-9) Autocrine Loop in the Acute Myeloid Leukemia Cell Line (U937) as Compared to Doxorubicin

The T-cell immunoglobulin and mucin-3 (TIM-3)/galectin-9 (Gal-9) autocrine loop is an indispensable signaling in acute myeloid leukemia (AML) cells, which induces their self-renewal through activation of nuclear factor-kappa b (NF-kB) and β-catenin pathways. In this study, we evaluated the effects of oridonin and doxorubicin on the TIM-3/Gal-9 autocrine loop. We also evaluated oridonin anti-inflammatory and anti-cancer properties on U937 cells, as an AML cell line in comparison to doxorubicin as a common anthracycline drug for AML treatment. Cell counting kit-8 (CCK-8) was applied to evaluate the cytotoxicity of oridonin and doxorubicin on U937 cells and also to determine the impact of galectin-9 (Gal-9) on their proliferation. The effects of oridonin and doxorubicin on Gal-9, TIM-3, and interleukin-1β (IL-1β) gene expression were determined by real-time polymerase chain reaction (RT-PCR). The Gal-9 secretion level was measured by enzyme-linked immunosorbent assay (ELISA) and activation of NF-kB pathway was assessed by western blotting. In a dose-dependent manner, oridonin and doxorubicin were capable to eradicate U937 cells while Gal-9 expanded them. Following the treatment of U937 cells with oridonin, the expression of Gal-9, TIM-3, and IL-1β genes was down-regulated, and the Gal-9 secretion and NF-kB phosphorylation were diminished, whereas doxorubicin increased all of these factors. Doxorubicin is a common treatment agent in AML, but it may induce inflammation and up-regulate the TIM3/Gal-9 autocrine loop, consequently can enhance the possibility of disease relapse. Meanwhile, oridonin is capable to inhibit the essential signaling pathways in AML cells and reduce the inflammation and expansion of tumor cells and postpone AML recurrence

Comparative Analysis of the Frequency and Distribution of Stem and Progenitor Cells in the Adult Mouse Brain

cells (NSCs) and progenitor cells, but it cannot discriminate between these two populations. Given two assays have purported to overcome this shortfall, we performed a comparative analysis of the distribution and frequency of NSCs and progenitor cells detected in 400 m coronal segments along the ventricular neuraxis of the adult mouse brain using the neurosphere assay, the neural colony forming cell assay (N-CFCA), and label-retaining cell (LRC) approach. We observed a large variation in the number of progenitor/stem cells detected in serial sections along the neuraxis, with the number of neurosphereforming cells detected in individual 400 m sections varying from a minimum of eight to a maximum of 891 depending upon the rostral-caudal coordinate assayed. Moreover, the greatest variability occurred in the rostral portion of the lateral ventricles, thereby explaining the large variation in neurosphere frequency previously reported. Whereas the overall number of neurospheres (3730 276) or colonies (4275 124) we detected along the neuraxis did not differ significantly, LRC numbers were significantly reduced (1186 188, 7 month chase) in comparison to both total colonies and neurospheres. Moreover, approximately two orders of magnitude fewer NSC-derived colonies (50 10) were detected using the N-CFCA as compared to LRCs. Given only 5% of the LRCs are cycling (BrdU/Ki-67) or competent to divide (BrdU/Mcm-2), and proliferate upon transfer to culture, it is unclear whether this technique selectively detects endogenous NSCs. Overall, caution should be taken with the interpretation and employment of all these techniques

Determination of oil pollutant (water, sediment and fish) in the southern part of Caspian Sea

This study was conducted to determine 16 Polyaromatic Hydrocarbons (16 PAHs) concentrations in water (during four seasons) and surface sediments (during summer and winter) at eight transects (Astara, Anzali, Sefidroud, Tonekabon, Nowshahr, Babolsar, Amirabad and Turkman) in the southern of Caspian Sea in 20102011. 94 samples of water and 45 samples of surface sediments were collected at 10, 50 and 100 meters depths. In addition, 28 samples of fish (Cyprinus Carpio) were collected during winter and spring. All samples were prepared by Soxhlet and extracting processes and then determined using High Performance Liquid Chromatography (HPLC) instrument. Results of current study showed that mean concentration and standard error (±SE) of 16PAHs water were observed 232 (±77), 1268 (±808), 538 (±190) and 151 (±53) µg/l in spring, summer, fall and winter, respectively. In addition, annual mean contents and standard error (±SE) of 16PAHs water were registered 24.10 (±8.12) µg/l. The Hazard Quotation (HQs) were calculated more than unit and belong to Benzo(a)pyrene and Dibenzo(a,h)anthracene compounds. Mean concentration and standard error (±SE) of 16PAHs sediment were observed 0.77 (±0.23) and 1.21 (±0.64) µg/g.dw in summer and winter, respectively. Also, the annual mean contents and standard error (±SE) of surface sediments were observed 0.93 (±0.33) µg/g.dw. The Hazard Quotation (HQs) were calculated more than unit and belong to Fluoranthene, Benzo(a)anthracene, Chryseneand Benzo(a)pyrene. The annual mean contents and standard error (±SE) of edible tissue of Cyprinus Carpio mussels were observed 2.21 (±0.42) µg/g.dw. Annually, pattern of 16PAH compounds were obtained 10, 70, 12 and 8% for 3,4,5, and 6 rings, respectively. Four ring compounds had high content and percentage and 2 ring was not observed in all samples of water. Also, pattern of 16PAH in surface sediments were obtained 31, 56 and 14% for 3, 4, and 5 rings, respectively. Four ring compounds had high content and percentage and 2 and 6 rings were not observed in all samples of surface sediments during two seasons. Result of Diagnostic Ratios analysis (DRs) of sediments showed that the source of oil compounds were petrogenic and pyrogenic in summer and winter, respectively. Based on DRs in water and sediments were observed oil compounds were either petrogenic or pyrogenic with different percentage in the southern Caspian Sea. In conclusion, the results revealed that in the some transects the 16PAHs concentrations of water were above the threshold levels and more petrogenic (85%) sources which represented polluted condition in this area. 16PAHs concentrations of sediments were below the threshold levels and conditions for this region were showed unpolluted. Also, the Caspian Sea sediments were classified in Class 2 (Fair). According to results of the evaluation’s risks to human health associated with consumption of the mussels containing 16PAHs suggest that there is risk for humans

Flap-enabled next-generation capture (FENGC): precision targeted single-molecule profiling of epigenetic heterogeneity, chromatin dynamics, and genetic variation

Targeted sequencing is an increasingly sought technology. Available methods, however, are often costly and yield high proportions of off-target reads. Here, we present FENGC, a scalable, multiplexed method in which target sequences are assembled into 5′ flaps for precise excision by flap endonuclease. Recovery of length-matched sequences, amplification with universal primers, and exonucleolytic removal of non-targeted genomic regions mitigate amplification biases and consistently yield ≥80% on-target sequencing. Furthermore, optimized sequential reagent addition and purifications minimize sample loss and facilitate rapid processing of sub-microgram quantities of DNA for detection of genetic variants and DNA methylation. Treatment of cultured human glioblastoma cells and primary murine monocytes with GC methyltransferase followed by FENGC and high-coverage enzymatic methyl sequencing provides single-molecule, long-read detection of differential endogenous CG methylation, dynamic nucleosome repositioning, and transcription factor binding. FENGC provides a versatile and cost-effective platform for targeted sequence enrichment for analysis of genetic and/or epigenetic heterogeneity.This work was supported by grants HDTRA1-16-1-0048 awarded by the Defense Threat Reduction Agency to P.C. and R01 CA155390 awarded by The National Institutes of Health to M.P.K.N

Adolescent transport and unintentional injuries: a systematic analysis using the Global Burden of Disease Study 2019

Background: Globally, transport and unintentional injuries persist as leading preventable causes of mortality and morbidity for adolescents. We sought to report comprehensive trends in injury-related mortality and morbidity for adolescents aged 10–24 years during the past three decades. Methods: Using the Global Burden of Disease, Injuries, and Risk Factors 2019 Study, we analysed mortality and disability-adjusted life-years (DALYs) attributed to transport and unintentional injuries for adolescents in 204 countries. Burden is reported in absolute numbers and age-standardised rates per 100 000 population by sex, age group (10–14, 15–19, and 20–24 years), and sociodemographic index (SDI) with 95% uncertainty intervals (UIs). We report percentage changes in deaths and DALYs between 1990 and 2019. Findings: In 2019, 369 061 deaths (of which 214 337 [58%] were transport related) and 31·1 million DALYs (of which 16·2 million [52%] were transport related) among adolescents aged 10–24 years were caused by transport and unintentional injuries combined. If compared with other causes, transport and unintentional injuries combined accounted for 25% of deaths and 14% of DALYs in 2019, and showed little improvement from 1990 when such injuries accounted for 26% of adolescent deaths and 17% of adolescent DALYs. Throughout adolescence, transport and unintentional injury fatality rates increased by age group. The unintentional injury burden was higher among males than females for all injury types, except for injuries related to fire, heat, and hot substances, or to adverse effects of medical treatment. From 1990 to 2019, global mortality rates declined by 34·4% (from 17·5 to 11·5 per 100 000) for transport injuries, and by 47·7% (from 15·9 to 8·3 per 100 000) for unintentional injuries. However, in low-SDI nations the absolute number of deaths increased (by 80·5% to 42 774 for transport injuries and by 39·4% to 31 961 for unintentional injuries). In the high-SDI quintile in 2010–19, the rate per 100 000 of transport injury DALYs was reduced by 16·7%, from 838 in 2010 to 699 in 2019. This was a substantially slower pace of reduction compared with the 48·5% reduction between 1990 and 2010, from 1626 per 100 000 in 1990 to 838 per 100 000 in 2010. Between 2010 and 2019, the rate of unintentional injury DALYs per 100 000 also remained largely unchanged in high-SDI countries (555 in 2010 vs 554 in 2019; 0·2% reduction). The number and rate of adolescent deaths and DALYs owing to environmental heat and cold exposure increased for the high-SDI quintile during 2010–19. Interpretation: As other causes of mortality are addressed, inadequate progress in reducing transport and unintentional injury mortality as a proportion of adolescent deaths becomes apparent. The relative shift in the burden of injury from high-SDI countries to low and low–middle-SDI countries necessitates focused action, including global donor, government, and industry investment in injury prevention. The persisting burden of DALYs related to transport and unintentional injuries indicates a need to prioritise innovative measures for the primary prevention of adolescent injury. Funding: Bill & Melinda Gates Foundation