A summary of the Malaysian Clinical Guidance on the management of postmenopausal and male osteoporosis, 2015

AbstractAimThis Clinical Guidance is aimed to help practitioners assess, diagnose and manage their patients with osteoporosis (OP), using the best available evidence.MethodsA literature search using PubMed (MEDLINE) and The Cochrane Library identified all relevant articles on OP and its assessment, diagnosis and treatment, from 2011, to update from the 2012 edition. The studies were assessed and the level of evidence assigned. For each statement, studies with the highest level of evidence were used to frame the recommendation.ResultsThis article summarizes the diagnostic and treatment pathways for postmenopausal and male OP, while addressing the risk-benefit ratio for OP treatment. Recognising the limitation of only depending on bone mineral density in assessing fracture risk, a move to assess 10 year fracture risk using tools such as FRAX, is recommended as a guide to decision-making on when to start treatment. A re-evaluation was done of the position of calcium supplementation and on the importance of vitamin D. There has been concern about the potential adverse effects of the long-term usage of bisphosphonates, which have been discussed fully. Algorithms for the management of postmenopausal and male OP have been updated.ConclusionsAdequate intake of calcium (1000 mg from both diet and supplements) and vitamin D (800 IU) daily remain important adjuncts in the treatment of OP. However, in confirmed OP, pharmacological therapy with anti-resorptives is the mainstay of treatment in both men and postmenopausal women. Patients need to be regularly assessed while on medication and treatment adjusted as appropriate

2′-O Methylation of Internal Adenosine by Flavivirus NS5 Methyltransferase

RNA modification plays an important role in modulating host-pathogen interaction. Flavivirus NS5 protein encodes N-7 and 2′-O methyltransferase activities that are required for the formation of 5′ type I cap (m7GpppAm) of viral RNA genome. Here we reported, for the first time, that flavivirus NS5 has a novel internal RNA methylation activity. Recombinant NS5 proteins of West Nile virus and Dengue virus (serotype 4; DENV-4) specifically methylates polyA, but not polyG, polyC, or polyU, indicating that the methylation occurs at adenosine residue. RNAs with internal adenosines substituted with 2′-O-methyladenosines are not active substrates for internal methylation, whereas RNAs with adenosines substituted with N6-methyladenosines can be efficiently methylated, suggesting that the internal methylation occurs at the 2′-OH position of adenosine. Mass spectroscopic analysis further demonstrated that the internal methylation product is 2′-O-methyladenosine. Importantly, genomic RNA purified from DENV virion contains 2′-O-methyladenosine. The 2′-O methylation of internal adenosine does not require specific RNA sequence since recombinant methyltransferase of DENV-4 can efficiently methylate RNAs spanning different regions of viral genome, host ribosomal RNAs, and polyA. Structure-based mutagenesis results indicate that K61-D146-K181-E217 tetrad of DENV-4 methyltransferase forms the active site of internal methylation activity; in addition, distinct residues within the methyl donor (S-adenosyl-L-methionine) pocket, GTP pocket, and RNA-binding site are critical for the internal methylation activity. Functional analysis using flavivirus replicon and genome-length RNAs showed that internal methylation attenuated viral RNA translation and replication. Polymerase assay revealed that internal 2′-O-methyladenosine reduces the efficiency of RNA elongation. Collectively, our results demonstrate that flavivirus NS5 performs 2′-O methylation of internal adenosine of viral RNA in vivo and host ribosomal RNAs in vitro

An update of the Malaysian Clinical Guidance on the management of glucocorticoid-induced osteoporosis, 2015

Objectives: This Clinical Guidance is aimed to help practitioners assess, diagnose and manage their patients with glucocorticoid-induced osteoporosis (GIO), using the best available evidence. Methods: A literature search using PubMed (MEDLINE) and The Cochrane Library identified all relevant articles on GIO and its assessment, diagnosis and treatment, from 2011, to update from the 2012 edition. The studies were assessed and the level of evidence assigned. For each statement, studies with the highest level of evidence were used to frame the recommendation. Results: Consider treatment early in all patients on glucocorticoids (GC) as fracture risk increases within 3–6 months of starting GC. The decision to start treatment for GIO depends on the presence of prior fracture, category of risk (as calculated using Fracture Risk Assessment Tool), daily dose and duration of GC treatment, age, and menopausal status. General measures include adequate calcium and vitamin D intake and reducing the dose of GC to the minimum required to achieve disease control. In patients on GC with osteoporotic fractures or confirmed osteoporosis on dual-energy X-ray absorptiometry, bisphosphonates are the first-line treatment. Treatment should be continued as long as patients remain on GC. Algorithms for the management of GIO in both pre- and post-menopausal women and men have been updated. Conclusions: In post-menopausal women and men above 50 years, bisphosphonates remain the mainstay of treatment in GIO. In pre-menopausal women and men below 50 years, bisphosphonates are recommended for those with a prevalent fracture or at very high risk only

Moss Flora of Lata Jarum Recreational Forest, Ulu Dong, Pahang

peer reviewedEighty-three species, two subspecies and nine varieties of mosses in 53 genera and 24 families are found in Lata Jarum Recreational Forest, Hulu Dong, Pahang. This figures resresent 16.8% of the 560 taxa at species level and below, 34% of the 156 genera and 55.8% of the 43 families of mosses reported for Peninsular Malaysia. The largest family of mosses recorded in this recreational forest is Calymperaceae with 25 taxa at species level and below or 26.6% of the total number reported and followed by the Sematophyllaceae which is represented by 10 species and one variety or 11.7%. Among the 94 taxa at species level and below, Philonotis mollis (Dozy & Molk.) Mitt. is reported for the first time for Pahang, whereas Erythrodontium julaceum (Hook. ex Schwägr.) Paris represents the second record for Pahang and Peninsular Malaysia

STABILIZATION OF DENGUE VIRUS POLYMERASE IN DE NOVO INITIATION ASSAY PROVIDES ADVANTAGES FOR COMPOUND SCREENING.

Dengue virus (DENV) NS5 protein comprises an N-terminal methyltransferase domain and a C-terminal RNA-dependent RNA polymerase domain (RdRp). DENV RdRp is responsible for viral RNA synthesis via a de novo initiation mechanism and represents an attractive target for anti-viral therapy. Herein we describe the characterization of its de novo initiation activities by PAGE analyses and the knowledge gained was used to develop a fluorescent-based assay. A highly processive and robust assay was achieved by addition of cysteine in the assay buffer. This stabilized the apo-enzyme, and rendered optimal de novo initiation activity whilst balancing its intrinsic terminal transferase activity. Steady-state kinetic parameters of the NTP and RNA substrates under these optimal conditions were determined for DENV1-4 FL NS5. Heavy metal ions such as Zn++ and Co++ as well as high levels of monovalent salts, suppressed DENV polymerase de novo initiation activities. This assay was validated with nucleotide chain terminators and used to screen two diverse small library sets. The screen data obtained was further compared with concurrent screens performed with a DENV polymerase elongation fluorescent assay utilizing pre-complexed enzyme-RNA. A higher hit-rate was obtained for the de novo initiation assay compared to the elongation assay (~2% versus ~0.1%). All the hits from the latter assay are also identified in the de novo initiation assay, indicating that the de novo initiation assay performed with the stabilized apo-enzyme has the advantage of providing additional chemical starting entities for inhibiting this enzyme

Electrocardiographic and Echocardiographic Insights From a Prospective Registry of Asian Elite Athletes

10.3389/fcvm.2021.799129FRONTIERS IN CARDIOVASCULAR MEDICINE