The TLK-ASF1 histone chaperone pathway plays a critical role in IL-1b-mediated AML progression.

Identifying and targeting microenvironment-driven pathways that are active across acute myeloid leukemia (AML) genetic subtypes should allow the development of more broadly effective therapies. The pro-inflammatory cytokine IL-1 is abundant in the AML microenvironment and promotes leukemic growth. Through RNA-sequencing analysis, we identify that IL-1 upregulated ASF1B (anti-silencing function-1B), a histone chaperone, in AML progenitors compared to healthy progenitors. ASF1B, along with its paralogous protein ASF1A recruits H3-H4 histones onto the replication fork during S-phase, a process regulated by tousled-like kinase 1 and 2 (TLKs). While ASF1s and TLKs are known to be overexpressed in multiple solid tumors and associated with poor prognosis, their functional roles in hematopoiesis and inflammation-driven leukemia remain unexplored. In this study, we identify that ASF1s and TLKs are over-expressed in multiple genetic subtypes of AML. We demonstrate that depletion of ASF1s significantly reduces leukemic cell growth in both in vitro and in vivo models using human cells. Using a murine model we show that overexpression of ASF1B accelerates leukemia progression. Moreover, Asf1b or Tlk2 deletion delayed leukemia progression while these proteins are dispensable for normal hematopoiesis. Through proteomics and phosphoproteomics analyses, we uncover that the TLK-ASF1 pathway promotes leukemogenesis by impacting the cell cycle and DNA damage pathways. Collectively, our findings identify the TLK1-ASF1 pathway as a novel mediator of inflammatory signaling and a promising therapeutic target for AML treatment across diverse genetic subtypes. Selective inhibition of this pathway offers potential opportunities to intervene effectively, address intratumoral heterogeneity, and ultimately improve clinical outcomes in AML.

Family language policy in retrospect: Narratives of success and failure in an Indian-Iranian transnational family.

In this study, we investigate family language policy in a transnational family through a collaborative autoethnography. Following the theoretical underpinnings of family language policy (Spolsky in J Multiling Multicult Dev 31:3-11, 2012), we present parental language beliefs, management, and practices in retrospect to shine a light on the long-term impact of the family's language policy on their daughter's linguistic development in heritage languages (i.e., Persian and Hindi) and English. The components of the family language policy in this cross-cultural transnational family are sketched in the second author's narratives of her experiences of multilingual childrearing and heritage language maintenance. We engage with, and critique, recent family language scholarship that apply postmodernist lens to examine families' translingual use of languages at home to get by their daily life, showing how having failed to set boundaries between the home/heritage languages and English over the past nine years has resulted in their child's predominant proficiency in English. We argue that such failure has its roots in parents' own past lived, and future imagined, experiences, as well as language ideologies that are polycentric and scaled, the consequences of which concern emotional, linguistic, cultural and social frictions across generations. Drawing on the narratives of success and failure in the family, we call for critical adoption of translingual frameworks in examining family language policy paying careful attention to the long-term impact of such practices at home on children's linguistic development.

Quantification of human adenovirus in irrigation water-soil-crop continuum: are consumers of wastewater-irrigated vegetables at risk?

Because of health concerns regarding the presence of enteric viruses in wastewater effluents, this study was designed to investigate the occurrence of human adenovirus (HAdV) in the irrigation water-soil-crop continuum. Viral particles were extracted from wastewater and wastewater- or water-irrigated soil and crop samples and analyzed using real-time PCR. Concentration of fecal indicator bacteria (FIB) were also determined. Quantitative microbial risk assessment was performed to determine the HAdV illness risk associated with the consumption of wastewater-irrigated vegetables. HAdV-F was detected in 74% of wastewater effluent samples with a mean concentration of 38 Genomic Copy (GC)/mL. HAdV was also detected in wastewater-irrigated soil (2 × 102 GC/g) and crop (< 10 GC/g) samples, with no statistically significant difference in concentrations between wastewater- and freshwater-irrigated samples. The results showed no correlation between concentrations of FIB and HAdV in the analyzed samples. Mean probability of illness risk from consumption of wastewater-irrigated vegetables was 4 × 10-1 per person per year (pppy) which was about two orders of magnitude higher than the proposed value by WHO (10-3 pppy) for safe reuse of wastewater. This finding suggests that the wastewater reuse for irrigation of vegetables eaten raw could pose a threat to human health with respect to the risk of viral illness, signifying stricter management of wastewater reuse. However, because of uncertainties in the QMRA model, particularly the ratio of infectious to non-infectious virus particles, more data is required to validate the predicted risk. This information is especially important in arid and semi-arid regions where high temperatures, UV radiation intensity, and desiccation can efficiently inactivate microorganisms in the environment.

The global status and genetic characterization of hydatidosis in camels (Camelus dromedarius): a systematic literature review with meta-analysis based on published papers.

Hydatidosis is a potential zoonotic helminthic disease affecting a broad spectrum of mammals, including humans, worldwide. The current review was conducted to investigate the genotypic status and prevalence of hydatid disease in camels across the world. For the purpose of the study, the articles addressing the worldwide prevalence of hydatidosis in camels were searched in several English language databases. The search process resulted in the inclusion of 122 papers. Based on the data presented in the reviewed articles, the pooled prevalence of hydatid disease in camels across the world was measured at 23.75% (95% CI 20.15-27.55). Moreover, the subgroup analysis demonstrated significant differences in the overall prevalence of hydatidosis among camels based on year, geographic area, climate parameters, camel population, gender, infected organ, fertility rate of the cyst and laboratory diagnostic technique. Furthermore, the Echinococcus granulosus genotypes identified in camels with hydatidosis included G1, G2, G3, G1-G3, G5, G6, G7, G6-G7 and G6-G10, with G6 being the most common genotype throughout the world. The data obtained from the current study are central to the better conceptualization of the biological and epidemiological characteristics of E. granulosus s.l. genotypes around the world, which can be helpful in the planning and adoption of more comprehensive control strategies.

Sarcocystosis in Ruminants of Iran, as Neglected Food-Borne Disease: A Systematic Review and Meta-analysis.

PURPOSE: Sarcocystis is a zoonotic parasitic pathogen which endangers the safety of meat and meat products. This systematic review and meta-analysis aimed to evaluate the prevalence rate and status of Sarcocystis spp. in ruminants as important food sources in Iran. METHODS: Data were collected from papers indexed in five English language electronic databases (PubMed, Scopus, Web of Science, Science Direct, and Google Scholar) and four Persian electronic databases (IranMedex, SID, IranDoc, and Magiran) from January to April 2019. Papers were selected based on inclusion criteria. Data analysis was performed in StatsDirect statistical software, version 2.7.2. RESULTS: The searching process resulted in the identification of 73 studies. Data analyses revealed that the total prevalence (95% confidence intervals) of Sarcocystis spp. in Iranian ruminants was 74.40% (64.01-83.56). In addition, a significant association was also observed between sarcocystosis infection in Iranian ruminants and year, host, location, and diagnostic technique (P < 0.001). CONCLUSIONS: According to our data, the prevalence of Sarcocystis infection in ruminants is relatively high. High pathogenicity of some Sarcocystis spp. and the negative impact that the spread of some parasites among ruminants can have on human and animal health necessitate the direction of more attention toward monitoring, controlling, and preventing sarcocystosis.

Evaluation of safety standards accomplishment in educational hospitals of Neyshabur University of Medical Sciences-Iran.

Patient's safety and staff in hospital is one issue that has always been considered as an important principle by experts in health systems. Therefore, for increase safety, standards and safety regulations must be considered. This study aims to evaluation of safety standards accomplishment in educational hospitals of Neyshabur University of medical Sciences. This cross-sectional descriptive study, safety standard status of all wards including 17 various wards from 22 Bahman hospital and 14 various wards from hakim Hospital in Neyshabur city (2016) was investigated. Data were collected using a questionnaire safety standard status hospitals (264 questions). Also data analyzed by SPSS16 software, using descriptive (Mean ± SD) and inferential statistics (T-Test). The results revealed that Safety standard status in 22bahman and hakim hospital were weak (2.42 ± 0.14) and moderate (3.04 ± 0.18) respectively. Also result showed in Hakim hospital, the highest and lowest safety standard status in Internal and Administrative-financial unit was (3.42 ± 0.19) (1.36 ± 0.58) respectively. In addition in hakim hospital, the highest and lowest safety standard status in operation room and administrative-financial unit (3.53 ± 0.28), 1.36 ± 0.58) respectively. According to the result, the safety condition in hospitals of Neyshabur city is moderate and poor status. However, imperfect implementation of safety protocols can endanger safety conditions in hospital. Therefore, it is necessary to take the required correcting measures to ensure full safety in hospitals. •Safety is defined by development of systems for preventing incidents, injuries, and other unpleasant events in organizations.•This article showed the safety status is not appropriate in most units of hospitals, which can lead to dangers for patients and personnel.•It is suggested for future studies to compare the safety status of different provinces.

Microbial contamination of keyboards and electronic equipment of ICU (Intensive Care Units) in Kashan University of medical sciences and health service hospitals.

Microbial contamination of computer keyboards and inanimate surfaces of electronic equipment in ICU (Intensive Care Units) can have a significant role for ICU-acquired colonization and a spectrum of nosocomial infections. The aim of this study was to survey the incidence of bacterial contamination and the distribution of species of computer keyboards and inanimate surfaces of bed side equipment in ICUs in Kashan University of medical sciences and health service hospitals. This descriptive, cross-sectional study was done on 75 computer keyboards and inanimate surfaces electronic equipment in 5 ICUs during 2016-2017. Samples were collected from computer keyboards and electronic equipment with normal saline rinsed swabs. Samples were Cultivated on Blood Agar (BA), and MacConkey Agar (MAC) and growing bacteria were identified based on their morphology and biochemical properties. Seventy six (76%) out of 75 computer Keyboards and electronic equipment were contaminated with bacteria and fungi. The most contamination pertained to gram positive bacteria (70.7%) and the most isolated bacteria were coagulase-negative staphylococci. The highest contamination rates were found on computer keyboards and electronic equipment of which were nurses. •This study demonstrates that monitoring inanimate surfaces and considering these surfaces as source of nosocomial infections is necessary.•In total, Seventy six (76%) out of 75 computer keyboards and electronic equipment in ICUs had positive culture.•It can be concluded that it is necessary for ICUs of Kashan university of medical sciences and Health service hospitals to have practical and regular program to reduce nosocomial infections.

Community health assessment: Knowledge, attitude and practice of women regarding water-pipe smoking in Bandar Abbas.

Based on the results of seventh round of community health assessment (CHA) in suburban areas of Bandar Abbas, "water-pipe smoking in women" was one of the major concerns of community members. Therefore, the present study designed to assess the knowledge, attitude and practice of women towards water-pipe smoking and related factors. High consumption of water-pipe among women was ranked as a prioritized health problem. To diagnose the problem, for creating action plan, the present cross - sectional study was conducted on 205 women aged over 18 randomly selected from Green-Tree region in suburb of Bandar Abbas city. All statistical analyses were performed using SPSS 24 software with 5% as the significant level. 205 women with a mean age of 36.9 (standard deviation:12.86) years, and a water-pipe prevalence of 15.1% were analyzed. The significant predictors of knowledge were educational level (ß = 0.182, p-value = 0.037), and being water-pipe smoker (ß = -0.251, p-value < 0.001); while for attitude they were educational level (ß = 0.221, p-value = 0.002), family size(ß = 0.152, p-value = 0.023), and subjective social status(ß = 0.149; p-value = 0.035); and for practice they was smoking waterpipe in parents (ß = -0.276, p-value < 0.001).The development action plans based on "CHA" could improve public health and enhance the performance of the community through improved education, policies and health interventions.

Microbiological dataset of rural drinking water supplies in Zahedan, Iran.

The residual chlorine and microbial quality of drinking water in the Zahedan villages by a number of1221 samples from all 168 villages were collected between 2014-2015. Then the samples were evaluated using 9-tube fermentation methods and portable chlorine method test. Based on the microbial coliform and fecal coliform indices, the data indicated that the maximum and minimum controlling of the bacteria in the distribution network were in the winter (90.62%) and autumn (85.56%), respectively. Also in the reservoirs, the maximum and minimum controlling of the bacteria were in winter (93.49%) and autumn (87.35%), respectively. The residual chlorine was prepared in almost all of seasons.

Data on drinking water quality using water quality index (WQI) and assessment of groundwater quality for irrigation purposes in Qorveh&Dehgolan, Kurdistan, Iran.

This data article aimed to investigate the quality of drinking water of Qorveh and Dehgolan Counties in Kurdistan province based on the water quality index (WQI) and agricultural quality index based on RSC, PI, KR, MH, Na, SAR and SSP indices. Also, Piper diagram was used to determine hydro chemical features of the groundwater area. The calculation of WQI for groundwater samples indicated that 36% of the samples could be considered as excellent water and 64% of the samples were classified as good water category. The results of the calculated indices for agricultural water quality indicate that water quality in all collected samples are in a good and excellent category. The Piper classification showed that dominant type of groundwater hydro chemical faces of region was calcium bicarbonate (Ca-HCO3-).

Inhibition of interleukin-1 receptor-associated kinase-1 is a therapeutic strategy for acute myeloid leukemia subtypes.

Interleukin-1 receptor-associated kinase 1 (IRAK1), an essential mediator of innate immunity and inflammatory responses, is constitutively active in multiple cancers. We evaluated the role of IRAK1 in acute myeloid leukemia (AML) and assessed the inhibitory activity of multikinase inhibitor pacritinib on IRAK1 in AML. We demonstrated that IRAK1 is overexpressed in AML and provides a survival signal to AML cells. Genetic knockdown of IRAK1 in primary AML samples and xenograft model showed a significant reduction in leukemia burden. Kinase profiling indicated pacritinib has potent inhibitory activity against IRAK1. Computational modeling combined with site-directed mutagenesis demonstrated high-affinity binding of pacritinib to the IRAK1 kinase domain. Pacritinib exposure reduced IRAK1 phosphorylation in AML cells. A higher percentage of primary AML samples showed robust sensitivity to pacritinib, which inhibits FLT3, JAK2, and IRAK1, relative to FLT3 inhibitor quizartinib or JAK1/2 inhibitor ruxolitinib, demonstrating the importance of IRAK1 inhibition. Pacritinib inhibited the growth of AML cells harboring a variety of genetic abnormalities not limited to FLT3 and JAK2. Pacritinib treatment reduced AML progenitors in vitro and the leukemia burden in AML xenograft model. Overall, IRAK1 contributes to the survival of leukemic cells, and the suppression of IRAK1 may be beneficial among heterogeneous AML subtypes.

Causes and consequences of chromatin variation between inbred mice.

Variation at regulatory elements, identified through hypersensitivity to digestion by DNase I, is believed to contribute to variation in complex traits, but the extent and consequences of this variation are poorly characterized. Analysis of terminally differentiated erythroblasts in eight inbred strains of mice identified reproducible variation at approximately 6% of DNase I hypersensitive sites (DHS). Only 30% of such variable DHS contain a sequence variant predictive of site variation. Nevertheless, sequence variants within variable DHS are more likely to be associated with complex traits than those in non-variant DHS, and variants associated with complex traits preferentially occur in variable DHS. Changes at a small proportion (less than 10%) of variable DHS are associated with changes in nearby transcriptional activity. Our results show that whilst DNA sequence variation is not the major determinant of variation in open chromatin, where such variants exist they are likely to be causal for complex traits.

Intragenic enhancers act as alternative promoters.

A substantial amount of organismal complexity is thought to be encoded by enhancers which specify the location, timing, and levels of gene expression. In mammals there are more enhancers than promoters which are distributed both between and within genes. Here we show that activated, intragenic enhancers frequently act as alternative tissue-specific promoters producing a class of abundant, spliced, multiexonic poly(A)(+) RNAs (meRNAs) which reflect the host gene's structure. meRNAs make a substantial and unanticipated contribution to the complexity of the transcriptome, appearing as alternative isoforms of the host gene. The low protein-coding potential of meRNAs suggests that many meRNAs may be byproducts of enhancer activation or underlie as-yet-unidentified RNA-encoded functions. Distinguishing between meRNAs and mRNAs will transform our interpretation of dynamic changes in transcription both at the level of individual genes and of the genome as a whole.

Comparison of the effects of canola oil versus sunflower oil on the biochemical markers of bone metabolism in osteoporosis.

BACKGROUND: Recently, omega-3 fatty acids are in the center of attention for their potent anti-inflammatory effects. Osteoporosis as a chronic senile disease is associated with inflammation, and the role of inflammatory mediators has been demonstrated in the recent years. The beneficial effects of n-3 fatty acids on bone were proven in many animal studies, while to date, no conclusive data is available in human. The aim of this study was to evaluate the impact of n-3 fatty acids on bone biomarkers in osteoporotic women. MATERIAL AND METHODS: Forty osteoporotic post-menopausal women were recruited in the study and randomized in receiving either 40 g canola oil or the same amount sunflower oil per day as their dietary oil for 3 months. Serum levels of osteocalcin, bone alkaline phosphatase (BALP), N telo peptide collagen (NTX) and 25- hydroxy vitamin D3 were measured at baseline and at the end of the third month in both groups. RESULTS: In the canola oil group, BALP and NTX were increased after 3 months while Osteocalcin decreased in both groups slightly; however,none of these changes were significant. In both groups, serum vitamin D3 was increased significantly; however, this change between groups was not significant. CONCLUSION: Canola oil did not affect bone formation and resorption significantly after 3 months consumption. Further investigations with longer follow up are recommended.

Work-related eye injury: the main cause of ocular trauma in Iran.

PURPOSE: Occupational eye injuries are among the major causes of ocular trauma and can cause severe visual impairment, with even minor injuries incurring considerable financial costs due to work absenteeism. This study was designed to evaluate the epidemiology of eye trauma and the role of occupational injuries at Farabi Eye Hospital, which is the largest eye hospital in Iran. METHODS: In this prospective, cross-sectional study, 822 eyes from 768 trauma patients presenting to Farabi Eye Hospital were enrolled in the study. The Birmingham Eye Trauma Terminology System and the United States Eye Injury Registry model were adopted as the basis for the study questionnaire. The questionnaires were completed through in-person interviews and comprehensive ocular examinations. RESULTS: The mean age of ocular trauma patients was 31.11 years, and 685 (89.2%) patients were male. Of all eye injuries, 73.7% were work-related. Only 2.2% of the patients were wearing safety goggles at the time of injury. History of previous eye trauma was positive in 44.3% of cases. An Ocular Trauma Score 3 or more was present in 4% of patients. CONCLUSIONS: Work-related eye trauma is the major cause of eye injury in Iran and most often occurs as a result of the lack of proper eye protection. Most work-related eye injury patients are young men.