The MIR-17-92 Cluster Contributes to MLL Leukemia Development Through the Repression of the Meis1 Competitor Pknox1

Mixed lineage leukemias have a relatively poor prognosis and arise as a result of translocations between the MLL gene and one of multiple partner genes. Downstream targets of MLL are aberrantly upregulated and include the developmentally important HOX genes and MEIS1, as well as multiple miRNAs, including the miR-17-92 cluster and miR-196b. Here I utilize custom anti-miRNA oligonucleotides to examine the contribution of specific miRNAs to MLL leukemias both as individual miRNAs and in cooperation with other miRNAs. Combinatorial treatment with antagomirs against miR-17 and miR-19a of the miR-17-92 cluster dramatically reduces colony forming ability of MLL-fusion containing cell lines but not non-MLL AML controls. Further, I validated PKNOX1 as a target of both miR-17 and miR-19a. MEIS1 and PKNOX1 are TALE domain proteins that participate in ternary complexes with HOX and PBX proteins. Here I examine the competitive relationship between PKNOX1 and MEIS1 in PBX-containing complex formation and determine the antagonistic role of PKNOX1 to leukemia in a murine MLL-AF9 model. Collectively, these data implicate the miR-17-92 cluster as part of a regulatory mechanism necessary to maintain MEIS1/HOXA9 -mediated transformation in MLL leukemia. This approach represents a paradigm where targeting multiple non-homologous miRNAs may be utilized as a novel therapeutic regimen

Adenoma detection rate as a quality indicator for colonoscopy: A descriptive cross-sectional study from a tertiary care hospital in Pakistan

Background and study aims: Adenoma detection rate (ADR) is validated for measuring quality of colonoscopy, however there is lack of colorectal cancer (CRC) screening program in South Asia. The purpose of this study is to analyze and review the polyp detection rate (PDR) and ADR and provide insight into the factors that influence them in Pakistan. Patients and methods: This retrospective, cross-sectional study was performed at the Aga Khan University Hospital, Karachi, Pakistan, on patients ≥ 18 years, who underwent colonoscopy between January 1, 2017 and June 30, 2018. Results: Of 1985 patients, 59 % were male and 41 % female, with mean age of 47.8 ± 16.2 years. The most common indication for colonoscopy was bleeding-per-rectum (28.0 %) and overall PDR and ADR were 17.9 % and 9.9 %, respectively. There was no significant difference between genders for either PDR ( P = 0.378) or ADR ( P = 0.574). Significantly higher PDR and ADR were found for patients ≥ 50 years ( P \u3c 0.001), as well as for suboptimal bowel preparation [PDR (25.7 %; P = 0.007) and ADR (18.6 %; P = 0.014)]. Interestingly, endoscopists with \u3c 500 colonoscopy-procedural-experience reported a higher PDR (21.6 %; P = 0.020) and ADR (14.4 %; P = 0.049), corresponding to a significantly higher PDR (20.6 %; P = 0.005) and ADR (11.7 %; P = 0.02) for endoscopists in practice for ≤ 10 years. Conclusions: We have noticed low PDR and ADR, which require further investigation and research. In addition, we believe there should be a different baseline ADR and PDR as a quality indicator for colonoscopy in our region, where no internationally recommended colonoscopic screening programs have been implemented

Neurological involvement associated with plasmodium vivax malaria from Pakistan

Plasmodium vivax is the most common specie causing malaria outside Africa with approximately 13.8 million reported cases worldwide. We report case of P. vivax infection with cerebral involvement. A nine year old boy presented with high grade fever accompanied by projectile vomiting and abnormal behavior later he developed seizures, shock, and unconsciousness. P. vivax monoinfection was diagnosed based on peripheral smears and PCR. After antimalarial therapy, patient made full recovery. Current case highlights increasing trend of cerebral complications caused by P. vivax

Mammalian alteration/deficiency in activation 3 (Ada3) is essential for embryonic development and cell cycle progression.

Ada3 protein is an essential component of histone acetyl transferase containing coactivator complexes conserved from yeast to human. We show here that germline deletion of Ada3 in mouse is embryonic lethal, and adenovirus-Cre mediated conditional deletion of Ada3 in Ada3(FL/FL) mouse embryonic fibroblasts leads to a severe proliferation defect which was rescued by ectopic expression of human Ada3. A delay in G(1) to S phase of cell cycle was also seen that was due to accumulation of Cdk inhibitor p27 which was an indirect effect of c-myc gene transcription control by Ada3. We further showed that this defect could be partially reverted by knocking down p27. Additionally, drastic changes in global histone acetylation and changes in global gene expression were observed in microarray analyses upon loss of Ada3. Lastly, formation of abnormal nuclei, mitotic defects and delay in G(2)/M to G(1) transition was seen in Ada3 deleted cells. Taken together, we provide evidence for a critical role of Ada3 in embryogenesis and cell cycle progression as an essential component of HAT complex

Rosai-Dorfman\u27s disease, an uncommon cause of common clinical presentation

Sinus histiocytosis with massive lymphadenopathy also known as Rosai-Dorfman disease is a rare benign disease that typically manifests as lymphadenopathy with or without systemic manifestations whose etiology remains poorly understood. Most common clinical presentation is painless bilateral cervical lymphadenopathy. However, it also can present in various extranodal sites and can easily be missed because of its rarity if not considered in the differential diagnosis. It commonly occurs in children and young adults with a slightly male predominance. Clinically patients may be mistaken for lymphoma and other infectious disorders like tuberculosis especially in developing countries like in Pakistan where tuberculosis is more prevalent. Here we report a case of a 38-years-old gentleman with bilateral cervical lymphadenopathy and worsening ascites. His symptoms initially mimicking tuberculosis and lymphoma, was finally diagnosed as having Rosai-Dorfman\u27s Disease on intra abdominal lymph node biopsy

A common presentation of uncommon disease - biliary fasciola hepatica

Hepatobiliary fascioliasis is one of the rare but important parasitic infection in endemic areas such as Pakistan. Clinical manifestations overlap with common clinical conditions such as hepatitis and biliary stones causing common bile duct obstruction. Fascioliasis is a zoonotic infection caused by a leaf-shaped organism known as Fasciola Hepatica. Humans are accidentally infected by consuming contaminated water or food, especially undercooked cattle and sheep liver or raw green vegetables. We report three cases with similar clinical manifestations presenting in two different cities in Pakistan. After detailed clinical evaluation and laboratory investigations, the diagnosis was established by abdominal ultrasound and diagnostic and therapeutic cholangiography. Patients were followed till complete resolution of their symptoms and normalisation of liver function test

Enhanced removal of hexavalent chromium from aqueous media using a highly stable and magnetically separable rosin-biochar-coated TiO2@C nanocomposite

Recently, nanosized metal-oxides have been extensively investigated for their ability to remove metal ions from aqueous media. However, the activity and capacity of these nanosized metal-oxides for removing metal ions decrease owing to their agglomeration in aqueous media. Herein, we synthesized a highly stable and magnetically separable rosin-biochar-coated (RBC) TiO2@C nanocomposite through a facile and environment-friendly wet chemical coating process, followed by a one-step heating route (pyrolysis) for efficient removal of Cr(VI) from aqueous solution. An array of techniques, namely, TEM, HRTEM, TEM-EDS, XRD, FTIR, VSM, BET and TGA, were used to characterize the prepared nanocomposite. The pyrolysis of rosin into biochar and the fabrication of Fe onto the RBC-TiO2@C nanocomposite were confirmed by FTIR and XRD examination, respectively. Moreover, TEM and HRTEM images and elemental mapping using TEM-EDS showed good dispersion of iron and carbon on the surface of the RBC-TiO2@C nanocomposite. Sorption of Cr(VI) ions on the surface of the RBC-TiO2@C nanocomposite was very fast and efficient, having a removal efficiency of similar to 95% within the 1st minute of reaction. Furthermore, thermodynamic analysis showed negative values of Gibb's free energy at all five temperatures, indicating that the adsorption of Cr(VI) ions on the RBC-TiO2@C nanocomposite was favorable and spontaneous. Conclusively, our results indicate that the RBC-TiO2@C nanocomposite can be used for efficient removal of Cr(VI) from aqueous media due to its novel synthesis and extraordinary adsorption efficacy during a short time period

Knowledge and perception attributes about halitosis and its treatment modalities among undergraduate students of dentistry and medicine: An analytical cross-sectional study

Background: A worldwide halitosis frequency of 10% - 30% is a common oral health complaint. Bad breath is described as a persistent condition in which a person's oral emissions are unpleasant or disagreeable. It not only hinders the person's ability to go about their routine activities, but also causes them shame and lowers their self-esteem, which in turn lowers their overall quality of life. Objective: The purpose of this study is to investigate how students majoring in dentistry and medicine see their own halitosis. Methodology: The students inducted in Bachelors in Medicine & Bachelors in Surgery (MBBS), and Bachelors in Dental Surgery (BDS) programs at various Teaching Institutes in Rawalpindi participated in this descriptive cross-sectional analytical epidemiological study. Around 500 undergraduates were given a self-administered questionnaire. Results: In our study, 96 (22.54%) were male students and 330 (77.46%) were female students respectively.  62 (64.6%) male and 255 (77.3%) female students from a variety of disciplines were familiar with the term ‘Halitosis’. 29 students (6.8%) said that halitosis had a mild impact, 189 students (44.36%) said that it had a moderate effect whereas 206 students (48.35%) rendered it as a major severe significant factor affecting their social life deleteriously

Developmental selenium exposure and health risk in daily foodstuffs: A systematic review and meta-analysis

Selenium (Se) is a trace mineral and an essential nutrient of vital importance to human health in trace amounts. It acts as an antioxidant in both humans and animals, immunomodulator and also involved in the control of specific endocrine pathways. The aim of this work is to provide a brief knowledge on selenium content in daily used various foodstuffs, nutritional requirement and its various health consequences. In general, fruits and vegetables contain low content of selenium, with some exceptions. Selenium level in meat, eggs, poultry and seafood is usually high. For most countries, cereals, legumes, and derivatives are the major donors to the dietary selenium intake. Low level of selenium has been related with higher mortality risk, dysfunction of an immune system, and mental failure. Selenium supplementation or higher selenium content has antiviral outcomes and is necessary for effective reproduction of male and female, also decreases the threat of chronic disease (auto immune thyroid). Generally, some advantages of higher content of selenium have been shown in various potential studies regarding lung, colorectal, prostate and bladder cancers risk, nevertheless results depicted from different trials have been diverse, which perhaps indicates the evidence that supplementation will merely grant advantage if the intakes of a nutrient is deficient. In conclusion, the over-all people should be advised against the usage of Se supplements for prevention of cardiovascular, hepatopathies, or cancer diseases, as advantages of Se supplements are still ambiguous, and their haphazard usage could result in an increased Se toxicity risk. The associations among Se intake/status and health, or disease risk, are complicated and need exposition to notify medical practice, to improve dietary recommendations, and to develop adequate communal health guidelines

One-step synthesis of N-doped metal/biochar composite using NH3-ambiance pyrolysis for efficient degradation and mineralization of Methylene Blue

A series of new biochar-supported composite based on the combination of biochar and metallic nanoparticles (NPs) were produced through single-step pyrolysis of FeCl3-Ti(OBu)(4) laden agar biomass under NH3 environment. The physiochemical properties of composites were characterized thoroughly. It has found that heating temperature and N-doping through NH3-ambiance pyrolysis significantly influence the visible-light sensitivity and bandgap energy of composites. The catalytic activities of composites were measured by degradation of Methylene Blue (MB) in the presence or absence of H2O2 and visible-light irradiation. Our best catalyst (N-TiO2-Fe3O4-biochar) exhibits rapid and high MB removal competency (99.99%) via synergism of adsorption, photodegradation, and Fenton-like reaction. Continuous production of O-2 center dot(-) and center dot OH radicles performs MB degradation and mineralization, confirmed by scavenging experiments and degradation product analysis. The local trap state Ti3+, Fe3O4, and N-carbon of the catalyst acted as active sites. It has suggested that the Ti3+ and N-doped dense carbon layer improve charge separation and shuttle that prolonged photo-Fenton like reaction. Moreover, the catalyst is highly stable, collectible, and recyclable up to 5 cycles with high MB degradation efficiency. This work provides a new insight into the synthesis of highly visible-light sensitized biochar-supported photocatalyst through NH3-ambiance pyrolysis of NPs-laden biomass. (c) 2018 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V