Genetic risk scores: are they important for diabetes management? results from multiple cross-sectional studies.

Several genetic risk scores (GRS) for type 2 diabetes (T2DM) have been published, but not replicated. We aimed to 1) replicate previous findings on the association between GRS on prevalence of T2DM and 2) assess the association between GRS and T2DM management in a sample of community-dwelling people from Switzerland. Four waves from a prospective study conducted in Lausanne. Seven GRS related to T2DM were selected, and compared between participants with and without T2DM, and between controlled and uncontrolled participants treated for T2DM. Data from 5426, 4017, 2873 and 2170 participants from the baseline, first, second and third follow-ups, respectively, was used. In all study periods, participants with T2DM scored higher than participants without T2DM in six out of seven GRS. Data from 367, 437, 285 and 207 participants with T2DM was used. In all study periods, approximately half of participants treated for T2DM did not achieve adequate fasting blood glucose or HbA <sub>1</sub> c levels, and no difference between controlled and uncontrolled participants was found for all seven GRS. Power analyses showed that most GRS needed a sample size above 1000 to consider the difference between controlled and uncontrolled participants as statistically significant at p = 0.05. In this study, we confirmed the association between most published GRS and diabetes. Conversely, no consistent association between GRS and diabetes control was found. Use of GRS to manage patients with T2DM in clinical practice is not justified

Prevalence of functional bowel disorders and faecal incontinence: an Australian primary care survey

Accepted Article online 30 October 2014. The copyright line for this article was changed on 14 February, 2017 after original online publication.Aim: Interest in functional bowel disorders (FBDs) and faecal incontinence (FI) has increased amongst coloproctologists. The study aimed to assess the prevalence of FBDs and FI (including its severity) among Australian primary healthcare seekers using objective criteria. Method: A cross-sectional survey was conducted in a primary care setting in Sydney, Australia. A self-administered questionnaire was used to collect demographic information and diagnose FBDs (irritable bowel syndrome, constipation, functional bloating and functional diarrhoea) based on Rome III criteria. The severity of FI was determined using the Vaizey incontinence score. Associations with medical/surgical history and healthcare utilization were assessed. Results: Of 596 subjects approached, 396 (66.4%) agreed to participate. Overall, 33% had FBD and/or FI. Irritable bowel syndrome was present in 11.1% and these participants were more likely to report anxiety/depression (P 8). Participants with FI were more likely to have irritable bowel syndrome, urinary incontinence and previous anal surgery (P < 0.01). Conclusion: FBDs and FI are prevalent conditions amongst primary healthcare seekers and the needs of those affected appear to be complex given their coexisting symptoms and conditions. Currently, the majority do not reach colorectal services, although increased awareness by primary care providers could lead to sufferers being referred for specialist management.K.-S. Ng, N. Nassar, K. Hamd, A. Nagarajah and M. A. Gladma

Pengaruh internet terhadap pengetahuan dan kesedaran tentang autisme dalam kalangan dewasa awal

Autisme merupakan sejenis kecelaruan neuro tingkahlaku di mana individu autisme mempunyai masalah dalam kognisi, sosio-emosi dan interaksi sosial. Autisme boleh didiagnosis dalam seseorang individu seawal usia 3 tahun. Menurut Pusat Kawalan Penyakit (CDC), terdapat 1 daripada 68 orang kanak-kanak yang mempunyai autisme di USA. Ini bermakna hampir 9,000 kanak-kanak di Malaysia lahir dengan autisme setiap tahun. Di Malaysia, terdapat isu-isu di antara golongan autistik dengan masyarakat Malaysia kerana salah faham. Ini dapat dilihat dengan jelas melalui kes yang berlaku tahun lepas dengan lelaki autistik yang didakwa sebagai mencabul seorang wanita. Ini berlaku hanya sebab mereka tidak mengenali bahawa lelaki tersebut mempunyai autisme. Insiden ini menunjukkan bahawa ramai rakyat Malaysia sama ada mempunyai kefahaman dan pengetahuan yang kurang tentang autisme atau tidak mempunyai pengetahuan langsung tentangnya. Kajian tentang pengetahuan dan kesedaran tentang autisme dilakukan secara berleluasa dari tahun 1980-an. Walau bagaimanapun, berdasarkan kajian literatur yang dilakukan, terdapat tiada kajian yang dilakukan tentang pengaruh Internet terhadap kesedaran autisme terutamanya dalam golongan dewasa awal. Kajian ini melihat kepada faktor demografi bagi kadar penggunaan Internet dan sama ada golongan dewasa awal mempunyai pengetahuan atau kesedaran tentang autisme ataupun tidak. Kajian ini juga meneroka pengaruh Internet dalam aspek meningkatkan pengetahuan dan kesedaran tentang autisme. Peserta kajian teridir daripada 285 orang dewasa awal, berumur 19 hingga 29 tahun dari Bangi, Batu Caves dan Senggarang. Melalui kajian ini, pengkaji mengetahui bahawa ramai golongan dewasa awal mempunyai serba sedikit pengetahuan tentang autisme tetapi mempunyai kesedaran yang rendah

The Fusion of CLEC12A and MIR223HG Arises from a trans-Splicing Event in Normal and Transformed Human Cells

Chimeric RNAs are often associated with chromosomal rearrangements in cancer. In addition, they are also widely detected in normal tissues, contributing to transcriptomic complexity. Despite their prevalence, little is known about the characteristics and functions of chimeric RNAs. Here, we examine the genetic structure and biological roles of CLEC12A-MIR223HG, a novel chimeric transcript produced by the fusion of the cell surface receptor CLEC12A and the miRNA-223 host gene (MIR223HG), first identified in chronic myeloid leukemia (CML) patients. Surprisingly, we observed that CLEC12A-MIR223HG is not just expressed in CML, but also in a variety of normal tissues and cell lines. CLEC12A-MIR223HG expression is elevated in pro-monocytic cells resistant to chemotherapy and during monocyte-to-macrophage differentiation. We observed that CLEC12A-MIR223HG is a product of trans-splicing rather than a chromosomal rearrangement and that transcriptional activation of CLEC12A with the CRISPR/Cas9 Synergistic Activation Mediator (SAM) system increases CLEC12A-MIR223HG expression. CLEC12A-MIR223HG translates into a chimeric protein, which largely resembles CLEC12A but harbours an altered C-type lectin domain altering key disulphide bonds. These alterations result in differences in post-translational modifications, cellular localization, and protein–protein interactions. Taken together, our observations support a possible involvement of CLEC12A-MIR223HG in the regulation of CLEC12A function. Our workflow also serves as a template to study other uncharacterized chimeric RNAs

The Fusion of CLEC12A and MIR223HG Arises from a trans-Splicing Event in Normal and Transformed Human Cells

Chimeric RNAs are often associated with chromosomal rearrangements in cancer. In addition, they are also widely detected in normal tissues, contributing to transcriptomic complexity. Despite their prevalence, little is known about the characteristics and functions of chimeric RNAs. Here, we examine the genetic structure and biological roles of CLEC12A-MIR223HG, a novel chimeric transcript produced by the fusion of the cell surface receptor CLEC12A and the miRNA-223 host gene (MIR223HG), first identified in chronic myeloid leukemia (CML) patients. Surprisingly, we observed that CLEC12A-MIR223HG is not just expressed in CML, but also in a variety of normal tissues and cell lines. CLEC12A-MIR223HG expression is elevated in pro-monocytic cells resistant to chemotherapy and during monocyte-to-macrophage differentiation. We observed that CLEC12A-MIR223HG is a product of trans-splicing rather than a chromosomal rearrangement and that transcriptional activation of CLEC12A with the CRISPR/Cas9 Synergistic Activation Mediator (SAM) system increases CLEC12A-MIR223HG expression. CLEC12A-MIR223HG translates into a chimeric protein, which largely resembles CLEC12A but harbours an altered C-type lectin domain altering key disulphide bonds. These alterations result in differences in post-translational modifications, cellular localization, and protein–protein interactions. Taken together, our observations support a possible involvement of CLEC12A-MIR223HG in the regulation of CLEC12A function. Our workflow also serves as a template to study other uncharacterized chimeric RNAs

Preliminary survey of knowledge, attitudes and practices among nurses regarding seasonal influenza and influenza vaccination

Health care workers are  at risk of influenza through occupational exposure. Uptake of influenza vaccine is poor even in countries where it is provided free. We sought to determine the knowledge, attitudes and practices regarding seasonal influenza and barriers for vaccination among nurses in Colombo. A cross sectional survey was carried out from February to March 2020 on 97 randomly selected nurses. Level of knowledge was measured using a scoring system. Only a few (n=7; 7.2%) nurses had been immunized against influenza. Overall knowledge regarding influenza and vaccines was average in most nurses (n=53; 55%). The majority (n=62; 63.9%) believed the vaccine was safe and 79.4% (n=77) were willing to be vaccinated if vaccine is provided free. However, 15 of these 77 (19.5%) were reluctant to be vaccinated annually. Identified barriers for vaccination were the perception that the vaccine was not essential, doubt about its efficacy, fear of vaccines and side effects. Knowledge should be improved, and misconceptions and fears need to be addressed through health education and promotion.</p

Experimental study of the bio-additives in biodiesel fuel on performance and emissions characteristics of diesel engine

Among the alternative fuels the Bio diesel is one the most common and familiar to all. It’s biodegradable, environment friendly as well as suitable source, to meet the future energy crises. The main concern of this experimental analysis is to reach a tentative goal, how this fuel can be utilised with maximum effective way. To find this ,an experiment data analysis of different parameter such as break power, break mean effective pressure consumption, emission characteristic (NOx, HC,CO. etc.), is done through bio diesel fuel and also compared with ordinary diesel which is also known as standard diesel. Despite years of improvement attempts, the key issue in using bio based fuels is oxidation stability, stoichiometric point, bio-fuel composition, antioxidants on the degradation and much oxygen with comparing to diesel gas oil. Thus, the improvement of emission exhausted from diesel engines fuelled by biodiesel is urgently required to meet the future stringent emission regulations. This investigation is carried out through 20 HP eddy current dynamometer and load cell arrangement which is controlled by a DYNOMAXtm software computer in case of finding the break power and BMEP respectively. And the emission characteristics are observed using Airrex HG-540 exhaust analysers finally the result is compared with diesel engine which is run by standard diesel. Di Methyl Poly siloxane (DMPS) additive and D20 palm oil methyl formula was used in this studies. The final result implied that the bio diesel with some additives with (CP10+DMPS Power) and (JC15+ DMPS) shows best performance and reduce the exhaust emission including CO. Thus the decision may be taken, 10% - 15% blended bio diesel with DMPS additive as a best alternative fuel considering all the view aspects and alternatives

Association of Methylentetraydrofolate Reductase (MTHFR) 677 C > T gene polymorphism and homocysteine levels in psoriasis vulgaris patients from Malaysia: a case-control study

<p>Abstract</p> <p>Background</p> <p>The methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the reduction of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate and methyl donors. The methyl donors are required for the conversion of homocysteine to methionine. Mutation of MTHFR 677 C > T disrupts its thermostability therefore leads to defective enzyme activities and dysregulation of homocysteine levels.</p> <p>Methods</p> <p>This case-control study (n = 367) was conducted to investigate the correlation of the MTHFR gene polymorphism [NM_005957] and psoriasis vulgaris amongst the Malaysian population. Overnight fasting blood samples were collected from a subgroup of consented psoriasis vulgaris patients and matched controls (n = 84) for the quantification of homocysteine, vitamin B₁₂and folic acid levels.</p> <p>Results</p> <p>There was no significant increase of the MTHFR 677 C > T mutation in patients with psoriasis vulgaris compared with controls (<it>χ</it>²= 0.733, p = 0.392). No significant association between homocysteine levels and MTHFR gene polymorphism in cases and controls were observed (F = 0.91, df = 3, 80, p = 0.44). However, homocysteine levels in cases were negatively correlated with vitamin B₁₂(r = -0.173) and folic acid (r = -0.345) levels. Vitamin B₁₂and folic acid levels in cases were also negatively correlated (r = -0.164).</p> <p>Conclusions</p> <p>Our results indicate that there was no significant association between the MTHFR gene polymorphism and psoriasis vulgaris in the Malaysian population. There was no significant increase of the plasma homocysteine level in the psoriasis patients compared to the controls.</p

Digoxin treatment reactivates in vivo radioactive iodide uptake and correlates with favorable clinical outcome in non-medullary thyroid cancer

Purpose Non-medullary thyroid cancer (NMTC) treatment is based on the ability of thyroid follicular cells to accumulate radioactive iodide (RAI). However, in a subset of NMTC patients tumor dedifferentiation occurs, leading to RAI resistance. Digoxin has been demonstrated to restore iodide uptake capacity in vitro in poorly differentiated and anaplastic NMTC cells, termed redifferentiation. The aim of the present study was to investigate the in vivo effects of digoxin in TPO-Cre/LSL-Braf(V600E) mice and digoxin-treated NMTC patients. Methods Mice with thyroid cancer were subjected to 3D ultrasound for monitoring tumor growth and I-124 PET/CT for measurement of intratumoral iodide uptake. Post-mortem analyses on tumor tissues comprised gene expression profiling and measurement of intratumoral autophagy activity. Through PALGA (Dutch Pathology Registry), archived tumor material was obtained from 11 non-anaplastic NMTC patients who were using digoxin. Clinical characteristics and tumor material of these patients were compared to 11 matched control NMTC patients never treated with digoxin. Results We found that in mice, tumor growth was inhibited and I-124 accumulation was sustainably increased after short-course digoxin treatment. Post-mortem analyses revealed that digoxin treatment increased autophagy activity and enhanced expression of thyroid-specific genes in mouse tumors compared to vehicle-treated mice. Digoxin-treated NMTC patients exhibited significantly higher autophagy activity and a higher differentiation status as compared to matched control NMTC patients, and were associated with favourable clinical outcome. Conclusions These in vivo data support the hypothesis that digoxin may represent a repositioned adjunctive treatment modality that suppresses tumor growth and improves RAI sensitivity in patients with RAI-refractory NMTC.Diabetes mellitus: pathophysiological changes and therap