Vitamin D supplementation lowers thrombospondin-1 levels and blood pressure in healthy adults

Introduction: Vitamin D insufficiency, defined as 25-hydroxyvitamin D (25(OH)D) levels < 75nmol/L is associated with cardio-metabolic dysfunction. Vitamin D insufficiency is associated with inflammation and fibrosis, but it remains uncertain whether these anomalies are readily reversible. Therefore, we aimed to determine the effects of vitamin D supplementation on markers of: 1) nitric oxide (NO) signaling, 2) inflammation, and 3) fibrosis, in healthy volunteers with mild hypovitaminosis. Methods: Healthy volunteers (n = 35) (mean age: 45 ± 11 years) with 25(OH)D levels <75nmol/L, received vitamin D supplementation (Ostelin ® capsules 2000IU) for 12 weeks. Resting systolic and diastolic blood pressures (BP) were assessed. Routine biochemistry was examined. Plasma concentrations of asymmetric dimethylarginine (ADMA), thrombospondin-1 (TSP-1), plasminogen activator inhibitor-1 (PAI-1), hs-CRP, activin-A, and follistatin-like 3 (FSTL3) were quantitated. Results: Vitamin D administration for 12 weeks significantly increased 25-(OH)D levels (48.8 ± 16 nmol/L to 100.8 ± 23.7 nmol/L, p<0.001). There was significant lowering of systolic and diastolic BP, while there was no significant change in lipid profiles, or fasting insulin. Plasma concentrations of ADMA, hs-CRP, PAI-1, activin A, and FSTL-3 did not change with vitamin D supplementation. However, there was a marked reduction of TSP-1 (522.7 ± 379.8 ng/mL vs 206.7 ± 204.5 ng/mL, p<0.001). Conclusions: Vitamin D supplementation in vitamin D insufficient, but otherwise healthy individuals markedly decreased TSP-1 levels and blood pressure. Since TSP-1 suppresses signaling of NO, it is possible that the fall in BP is engendered by restoration of NO effect.Anjalee T. Amarasekera, Bahador Assadi-Khansari, Saifei Liu, Marilyn Black, Greer Dymmott, Natasha M. Rogers, Aaron L. Sverdlov, John D. Horowitz, Doan T. M. Ng

Ranking the importance of quality variables in determination of price for plantation grown Teak (Tectona grandis) timber

Tectona grandis is one of the major plantation species in Sri Lanka which was introduced in 17th century. Teak timber is preferably used for furniture, joinery, decorative and parquet industries as a super luxury timber. State Timber Corporation (STC) involves in marketing of state timber resources from Forest Department plantations. Among all other timbers, Teak round wood at STC depots shows the highest sales in every year. When buying timber, customers assess the quality by visual observation of surface characteristics such as log dimensions and visible defects. If the log is inferior in quality the buyer would bid and buy it at a lower price than the marked price at auctions. Hence, the buyers‟ preference is indirectly reflected by the achieved price (selling price). In the present study, an attempt was made to study the relationship between the achievable price and the quality attributes of Teak logs. Such studies are useful as there is a lack of information on the impact of timber quality on timber price in the case of high demanding species such as teak. This information is extremely important to improve financial return of Teak management through realistic timber management concepts.A set of randomly selected logs representing a total quantity of 116079 cubic decimeters (dm3) were used as the sample. The dimensions, surface defects and end defects (size and quality variables) of each graded Teak log were measured and recorded. Length, mid girth, diameter at top end, butt end and middle of the log, total number of knots, presence of hollows and their diameter, depth and position, bend fraction, shape of the log, heartwood percentage, presence of splits, felling damages, heart rot and region where the logs were produced were the independent variables used in the study. Achieved prices for the selected logs were taken from STC records. Based on multiple linear regressions, a price-quality model was derived to explain the buyers‟ preference by means of log size and quality variables.Among the seventeen independent variable classes, only the “mid girth”, the “length”, the “number of knots per meter”, the “average knot diameter”, the “hollow position”, the “bend fraction”, the “log shape” and the “heart rot” contributed significantly to explain the buyers‟ preference. Above variables were ranked according to their order of affiliation and the ranking showed that the “mid girth” is the most important timber quality variable, followed by “length”, “number of knots per meter”, “hollow at top end &amp;/or middle”, “bend fraction greater than 1.0”, “irregular log shape”, “average knot diameter” and “heart rot”.

Ranking the importance of quality variables in determination of price for plantation grown Teak (Tectona grandis) timber

Tectona grandis is one of the major plantation species in Sri Lanka which was introduced in 17th century. Teak timber is preferably used for furniture, joinery, decorative and parquet industries as a super luxury timber. State Timber Corporation (STC) involves in marketing of state timber resources from Forest Department plantations. Among all other timbers, Teak round wood at STC depots shows the highest sales in every year. When buying timber, customers assess the quality by visual observation of surface characteristics such as log dimensions and visible defects. If the log is inferior in quality the buyer would bid and buy it at a lower price than the marked price at auctions. Hence, the buyers‟ preference is indirectly reflected by the achieved price (selling price). In the present study, an attempt was made to study the relationship between the achievable price and the quality attributes of Teak logs. Such studies are useful as there is a lack of information on the impact of timber quality on timber price in the case of high demanding species such as teak. This information is extremely important to improve financial return of Teak management through realistic timber management concepts.A set of randomly selected logs representing a total quantity of 116079 cubic decimeters (dm3) were used as the sample. The dimensions, surface defects and end defects (size and quality variables) of each graded Teak log were measured and recorded. Length, mid girth, diameter at top end, butt end and middle of the log, total number of knots, presence of hollows and their diameter, depth and position, bend fraction, shape of the log, heartwood percentage, presence of splits, felling damages, heart rot and region where the logs were produced were the independent variables used in the study. Achieved prices for the selected logs were taken from STC records. Based on multiple linear regressions, a price-quality model was derived to explain the buyers‟ preference by means of log size and quality variables.Among the seventeen independent variable classes, only the “mid girth”, the “length”, the “number of knots per meter”, the “average knot diameter”, the “hollow position”, the “bend fraction”, the “log shape” and the “heart rot” contributed significantly to explain the buyers‟ preference. Above variables were ranked according to their order of affiliation and the ranking showed that the “mid girth” is the most important timber quality variable, followed by “length”, “number of knots per meter”, “hollow at top end &amp;/or middle”, “bend fraction greater than 1.0”, “irregular log shape”, “average knot diameter” and “heart rot”.

Synthesis, structural characterization, antimicrobial and cytotoxic effects of aziridine, 2-aminoethylaziridine and azirine complexes of copper(II) and palladium(II).

The synthesis, spectroscopic and X-ray structural characterization of copper(II) and palladium(II) complexes with aziridine ligands as 2-dimethylaziridine HNCH2CMe2 (a), the bidentate N-(2-aminoethyl)aziridines C2H4NC2H4NH2 (b) or CH2CMe2NCH2CMe2NH2 (c) as well as the unsaturated azirine NCH2CPh (d) are reported. Cleavage of the cyclometallated Pd(II) dimer [μ-Cl(C6H4CHMeNMe2-C,N)Pd]2 with ligand a yielded compound [Cl(NHCH2CMe2)(C6H4CHMe2NMe2-C,N)Pd] (1a). The reaction of the aziridine complex trans-[Cl2Pd(HNC2H4)2] with an excess of aziridine in the presence of AgOTf gave the ionic chelate complex trans-[(C2H4NC2H4NH2-N,N′)2Pd](OTf)2 (2b) which contains the new ligand b formed by an unexpected insertion and ring opening reaction of two aziridines (“aziridine dimerization”). CuCl2 reacted in pure HNC2H4 or HNCH2CMe2 (b) again by “dimerization” to give the tris-chelated ionic complex [Cu(C2H4NC2H4NH2-N,N′)3]Cl2 (3b) or the bis-chelated complex [CuCl(C2H2Me2NC2H2Me2NH2-N,N′)2]Cl (4c). By addition of 2H-3-phenylazirine (d) to PdCl2, trans-[Cl2Pd(NCH2CPh)2] (5d) was formed. All new compounds were characterized by NMR, IR and mass spectra and also by X-ray structure analyses (except 3b). Additionally the cytotoxic effects of these complexes were examined on HL-60 and NALM-6 human leukemia cells and melanoma WM-115 cells. The antimicrobial activity was also determined. The growth of Gram-positive bacterial strains (S. aureus, S. epidermidis, E. faecalis) was inhibited by almost all tested complexes at the concentrations of 37.5–300.0 μg mL−1. However, MIC values of complexes obtained for Gram-negative E. coli and P. aeruginosa, as well as for C. albicans yeast, mostly exceeded 300 μg mL−1. The highest antibacterial activity was achieved by complexes 1a and 2b. Complex 2b also inhibited the growth of Gram-negative bacteria. Graphical abstract: Synthesis, structural characterization, antimicrobial and cytotoxic effects of aziridine, 2-aminoethylaziridine and azirine complexes of copper(ii) and palladium(ii

Hybrid SPECT/CT for the assessment of a painful hip after uncemented total hip arthroplasty

Background The diagnosis of hip pain after total hip replacement (THR) represents a highly challenging question that is of increasing concern to orthopedic surgeons. This retrospective study assesses bone scintigraphy with Hybrid SPECT/CT for the diagnosis of painful THR in a selected cohort of patients. Methods Bone SPECT/CT datasets of 23 patients (mean age 68.9 years) with a painful hip after THR were evaluated. Selection of the patients required an inconclusive radiograph, normal serum levels of inflammatory parameters (CRP and ESR) or a negative aspiration of the hip joint prior to the examination. The standard of reference was established by an interdisciplinary adjudication-panel using all imaging data and clinical follow-up data (>12 month). Pathological and physiological uptake patterns were defined and applied. Results The cause of pain in this study group could be determined in 18 out of 23 cases. Reasons were aseptic loosening (n = 5), spine-related (n = 5), heterotopic ossification (n = 5), neuronal (n = 1), septic loosening (n = 1) and periprosthetic stress fracture (n = 1). In (n = 5) cases the cause of hip pain could not be identified. SPECT/CT imaging correctly identified the cause of pain in (n = 13) cases, in which the integrated CT-information led to the correct diagnosis in (n = 4) cases, mainly through superior anatomic correlation. Loosening was correctly assessed in all cases with a definite diagnosis. Conclusions SPECT/CT of THA reliably detects or rules out loosening and provides valuable information about heterotopic ossifications. Furthermore differential diagnoses may be detected with a whole-body scan and mechanical or osseous failure is covered by CT- imaging. SPECT/CT holds great potential for imaging-based assessment of painful prostheses

Public attitudes towards automated external defibrillators: results of a survey in the Australian general population

BackgroundSwift defibrillation by lay responders using automated external defibrillators (AEDs) increases survival in out-of-hospital cardiac arrest (OHCA). This study evaluated newly designed yellow–red vs. commonly used green–white signage for AEDs and cabinets and assessed public attitudes to using AEDs during OHCA.MethodsNew yellow–red signage was designed to enable easy identification of AEDs and cabinets. A prospective, cross-sectional study of the Australian public was conducted using an electronic, anonymised questionnaire between November 2021 and June 2022. The validated net promoter score investigated public engagement with the signage. Likert scales and binary comparisons evaluated preference, comfort and likelihood of using AEDs for OHCA.ResultsThe yellow–red signage for AED and cabinet was preferred by 73.0% and 88%, respectively, over the green–white counterparts. Only 32% were uncomfortable with using AEDs, and only 19% indicated a low likelihood of using AEDs in OHCA.ConclusionThe majority of the Australian public surveyed preferred yellow–red over green–white signage for AED and cabinet and indicated comfort and likelihood of using AEDs in OHCA. Steps are necessary to standardise yellow–red signage of AED and cabinet and enable widespread availability of AEDs for public access defibrillation

Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes

BACKGROUND:DNA methylation is affected by the activities of the key enzymes and intermediate metabolites of the one-carbon pathway, one of which involves homocysteine. We investigated the effect of the well-known genetic variant associated with mildly elevated homocysteine: MTHFR 677C>T independently and in combination with other homocysteine-associated variants, on genome-wide leukocyte DNA-methylation. METHODS:Methylation levels were assessed using Illumina 450k arrays on 9,894 individuals of European ancestry from 12 cohort studies. Linear-mixed-models were used to study the association of additive MTHFR 677C>T and genetic-risk score (GRS) based on 18 homocysteine-associated SNPs, with genome-wide methylation. RESULTS:Meta-analysis revealed that the MTHFR 677C>T variant was associated with 35 CpG sites in cis, and the GRS showed association with 113 CpG sites near the homocysteine-associated variants. Genome-wide analysis revealed that the MTHFR 677C>T variant was associated with 1 trans-CpG (nearest gene ZNF184), while the GRS model showed association with 5 significant trans-CpGs annotated to nearest genes PTF1A, MRPL55, CTDSP2, CRYM and FKBP5. CONCLUSIONS:Our results do not show widespread changes in DNA-methylation across the genome, and therefore do not support the hypothesis that mildly elevated homocysteine is associated with widespread methylation changes in leukocytes

Snake Bite in South Asia: A Review

Snake bite is one of the most neglected public health issues in poor rural communities living in the tropics. Because of serious misreporting, the true worldwide burden of snake bite is not known. South Asia is the world's most heavily affected region, due to its high population density, widespread agricultural activities, numerous venomous snake species and lack of functional snake bite control programs. Despite increasing knowledge of snake venoms' composition and mode of action, good understanding of clinical features of envenoming and sufficient production of antivenom by Indian manufacturers, snake bite management remains unsatisfactory in this region. Field diagnostic tests for snake species identification do not exist and treatment mainly relies on the administration of antivenoms that do not cover all of the important venomous snakes of the region. Care-givers need better training and supervision, and national guidelines should be fed by evidence-based data generated by well-designed research studies. Poorly informed rural populations often apply inappropriate first-aid measures and vital time is lost before the victim is transported to a treatment centre, where cost of treatment can constitute an additional hurdle. The deficiency of snake bite management in South Asia is multi-causal and requires joint collaborative efforts from researchers, antivenom manufacturers, policy makers, public health authorities and international funders

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p