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Introduction Hyperparathyroidism is a risk factor of osteoporosis. Excess parathyroid hormone (PTH) accelerates bone loss via bone reabsorption and increases the risk of fragility fracture. Fragility fractures are associated with serious consequences in older patients. [1] This study aimed to look at the prevalence of hyperparathyroidism and vitamin D deficiency in geriatric patients (age >60) who presented with hip fractures in an Irish tertiary hospital. Methods Data was collected from Irish hip fracture Database (IHFD) and the Ortho-geriatric Electronic Patient Medical System (EPMS) between July 2019 and April 2020 (n=207). Demographic data and bone health profile (PTH, Vitamin D, and Calcium) were analysed using SPSS for statistical analysis. Results The median age of patients was 81 years (SD 8.7), and 68.3% of patients were female. Median 10-year probability of major osteoporotic and hip fracture risk is 22.5% and 12.2%, respectively. 29.9% was diagnosed with hyperparathyroidism with prevalence of primary and secondary hyperparathyroidism of 6.7% and 23.1%, respectively. The majority of these (87.3%) were normocalcaemic hyperparathyroidism. 50.7% were vitamin D deficient, with 11.5% being severely deficient (Vitamin D Conclusion The prevalence of hyperparathyroidism is higher in the hip fracture group than in the general population. [2] Vitamin D deficiency is also prevalent in this group. FRAX score indicated significant proportion of patients with high major osteoporosis and hip fracture risks. Routine bone health profile checks in this high-risk group allow early identification and management of hyperparathyroidism and vitamin D depletion, which can potentially reduce the risk of future fracture. Reference: 1. Bukata SV, DiGiovanni BF, Friedman SM, Hoyen H, Kates A, Kates SL, Mears SC, Mendelson DA, Serna Jr FH, Sieber FE, Tyler WK. A guide to improving the care of patients with fragility fractures. Geriatric Orthopaedic Surgery & Rehabilitation. 2011 Jan;2(1): 5-37.2. Press DM, Siperstein AE, Berber E, Shin JJ, Metzger R, Jin J, Monteiro R, Mino J, Swagel W, Mitchell JC. The prevalence of undiagnosed and unrecognized primary hyperparathyroidism: a population-based analysis from the electronic medical record. Surgery. 2013 Dec 1;154(6): 1232-8 Presentation: No date and time listed

Background Early in the pandemic, transmission risk from asymptomatic infection was unclear, making it imperative to monitor infection in workplace settings. Further, data on SARS-CoV-2 seroprevalence within university populations has been limited. Methods We performed a longitudinal study of University research employees on campus July-December 2020. We conducted questionnaires on COVID-19 risk factors, RT-PCR testing, and SARS-CoV-2 serology using an in-house spike RBD assay, laboratory-based Spike NTD assay, and standard nucleocapsid platform assay. We estimated prevalence and cumulative incidence of seroconversion with 95% confidence intervals using the inverse of the Kaplan-Meier estimator. Results 910 individuals were included in this analysis. At baseline, 6.2% (95% CI 4.29–8.19) were seropositive using the spike RBD assay; four (0.4%) were seropositive using the nucleocapsid assay, and 44 (4.8%) using the Spike NTD assay. Cumulative incidence was 3.61% (95% CI: 2.04–5.16). Six asymptomatic individuals had positive RT-PCR results. Conclusions Prevalence and incidence of SARS-CoV-2 infections were low; however, differences in target antigens of serological tests provided different estimates. Future research on appropriate methods of serological testing in unvaccinated and vaccinated populations is needed. Frequent RT-PCR testing of asymptomatic individuals is required to detect acute infections, and repeated serosurveys are beneficial for monitoring subclinical infection.

The swelling and nutrient release behaviors of a novel hydrogel blend of hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), and sodium alginate (NaAlg) was investigated to determine its applicability as an agricultural soil conditioner. Hydrogel swelling and nutrient release data were obtained over time at varying temperatures and pH conditions. The experimental data were fit into the power law, Tsai and Strieder, and Johansson’s models to determine the kinetic parameters for the swelling behavior and nutrient release. Under the experimental swelling conditions, the maximum and minimum swelling capacities of the hydrogel blend were 322.9245% and 228.0483%, respectively. The data fit to the power law suggested that a pseudo Fickian behavior describes the diffusion mechanism. The data fit to the Tsai and Strieder and Johansson’s models provided the experimental values for the α and temperature correlation as 3.69×10-5 and 0.0278, respectively, which implies that the diffusion behavior within the hydrogel does not vary significantly within the temperature range. Lastly, the inconsistency observed in the nutrient release behaviors at varying pH suggested that additional trials may be required in order to establish a clearer relation between pH and nutrient release behavior.

Background Meconium ileus (MI) affects up to 20% of newborns with cystic fibrosis (CF). We compared clinical outcomes between Australian paediatric CF patients with and without meconium ileus (non-MI). Methods This was a retrospective case-control study of MI and non-MI patients in New South Wales, Australia, from 1988 to 2010. MI patients were matched 1:1 with pancreatic insufficient non-MI patients for age, sex and CF clinic. Clinical measurements, nutrition and gastrointestinal outcomes over this period were compared between groups using linear mixed models for continuous variables to account for age. Results There were 162 matched pairs (N=324, 52% female) with mean (SD) age of 15.3 (8.2) and 14.9 (7.9) years for MI and non-MI patients respectively (P=0.6). MI patients aged 5-23 had poorer FEV1% compared to non-MI patients (estimate -0.070 SE [0.02], P=0.003). There were no significant differences in P. aeruginosa isolation rates; however S. aureus isolation rates were lower in MI patients (72%) compared to non-MI (82%) (OR 0.6 [0.3-1.0], P=0.03). Chronic colonisation rates for P. aeruginosa and S. aureus were not significantly different between groups. MI patients aged 2-20 had significantly lower BMI Z-scores over time (estimate -0.25 SE [0.1], P=0.02). MI patients were more likely to receive oral feed supplements (OR 2.8 [1.4-6.1], P=0.003) and gastrostomy formation (OR 4.4 [1.1-24.6], P=0.02). Conclusions CF patients with MI may have worse lung function, growth and nutrition than non-MI patients over time. Meconium ileus may be an early poor prognostic factor for CF.

This paper analyzed the translations of three English Christmas carols of Silent Night, Away In A Manger, and The First Noel, as the most popular carols that have been translated into many languages, adopted from the hymnal book by the Church of Jesus Christ of Latter-day Saints. The English versions were compared with their Chinese and Indonesian translations. The analysis was performed by classifying the stanzas individually based on Guerra (2012) fifteen translation strategies. Identification of equivalence as the most common strategy in the Chinese translation could be because of numerous “unnatural” English expressions in Chinese language and culture, whereas for the Indonesian translation, omission was the most common strategy, which helped to retain completeness, or the overall meaning of the stanzas, or completeness. Omission was also used to leave out redundant or insensible information throughout the translated carols in both languages and contributed to successful maintenance the original rhythm and rhyme in the translation of the three carols. Findings of this study could be further validated by analysing more Christmas carols in Chinese and Indonesian Languages, and other languages. Researchers could also look precisely into the cultural elements that could potentially affect this type of translation.

DNA polymerase β is a 39 kDa enzyme that is a major component of Base Excision Repair in human cells. The enzyme comprises two major domains, a 31 kDa domain responsible for the polymerase activity and an 8 kDa domain, which bind ssDNA and has a deoxyribose phosphate (dRP) lyase activity. DNA polymerase β was shown to be phosphorylated in vitro with protein kinase C (PKC) at serines 44 and 55 (S44 and S55), resulting in loss of its polymerase enzymic activity, but not its ability to bind ssDNA. In this study, we investigate the potential phosphorylation-induced structural changes for DNA polymerase β using molecular dynamics simulations. The simulations show drastic conformational changes of the polymerase structure as a result of S44 phosphorylation. Phosphorylation-induced conformational changes transform the closed (active) enzyme structure into an open one. Further analysis of the results points to a key hydrogen bond and newly formed salt bridges as potential drivers of these structural fluctuations. The changes observed with S55/44 and S55 phosphorylation were less dramatic and the integrity of the H-bond was not compromised. Thus the phosphorylation of S44 is the major contributor to structural fluctuations that lead to loss of enzymatic activity.

DNA polymerase β is a 39kDa enzyme that is a major component of Base Excision Repair in human cells. The enzyme comprises two major domains, a 31kDa domain responsible for the polymerase activity and an 8kDa domain, which bind ssDNA and has a deoxyribose phosphate (dRP) lyase activity. DNA polymerase β was shown to be phosphorylated in vitro with protein kinase C (PKC) at serines 44 and 55 (S44 and S55), resulting in loss of its polymerase enzymic activity, but not its ability to bind ssDNA. In this study, we investigate the potential phosphorylation-induced structural changes for DNA polymerase β using molecular dynamics. The simulations show drastic conformational changes of the polymerase structure as a result of S44 phosphorylation. Phosphorylation-induced conformational changes transform the closed (active) enzyme structure into an open one. Further analysis of the results points to a key hydrogen bond and newly formed salt bridges as potential drivers of these structural fluctuations. The changes observed with S44/55 and S55 phosphorylation were less dramatic than S44 and the integrity of the H-bond was not compromised. Thus the phosphorylation of S44 is likely the major contributor to structural fluctuations that lead to loss of enzymatic activity.

The Hippo signaling pathway, which is implicated in the regulation of organ size, has emerged as a potential target for the development of cancer therapeutics. YAP, TAZ (transcription co-activators) and TEAD (transcription factor) are the downstream transcriptional machinery and effectors of the pathway. Formation of the YAP/TAZ-TEAD complex leads to transcription of growth-promoting genes. Conversely, disrupting the interactions of the complex decreases cell proliferation. Herein, we screened a 1000-member fragment library using Thermal Shift Assay and identified a hit fragment. We confirmed its binding at the YAP/TAZ-TEAD interface by X-ray crystallography, and showed that it occupies the same hydrophobic pocket as a conserved phenylalanine of YAP/TAZ. This hit fragment serves as a scaffold for the development of compounds that have the potential to disrupt YAP/TAZ-TEAD interactions. Structure-activity relationship studies and computational modeling were also carried out to identify more potent compounds that may bind at this validated druggable binding site. ASTAR (Agency for Sci., Tech. and Research, S’pore) NMRC (Natl Medical Research Council, S’pore) Published version

For simulation-based work, researchers often have limited hardware capacities and budgets, so they create a low-cost parallel computing platform using PCs and commodity hardware, assembled and configured as a Beowulf-class computing cluster. Here, an astute approach (for a molecular dynamics simulation example) greatly improves performance through hardware upgrades and other tricks.

Many environmental pollutions are caused by the abundance of xenobiotic compounds in nature. For instance, halogenated compounds released from chemical industries were proven to be toxic and recalcitrant in the environment. However, haloalkanoic acid dehalogenases can catalyse the removal of halides from organic haloacids and thus have gained interest for bioremediation and synthesis of industrial chemicals. This study presents the first structural model and the key residues of the non-stereospecific haloalkanoic acid dehalogenase, DehE, from Rhizobium sp. RC1. The enzyme was built using a homology modelling technique; the structure of DehI from Pseudomonas putida PP3 was used as a template, because of its homology to DehE. The structure of DehE consists of only α-helices. Twelve conserved residues that line the active site were identified: Trp34, Ala36, Phe37, Asn114, Tyr117 Ala187, Ser188, Asp189, Tyr265, Phe268, Ile269, and Ile272. These residues are consistent with the residues found in the ac...

Background: Ataxia telangiectasia(A-T) is a progressive disease with the leading causes of death being respiratory diseases and cancer. Some aspects of lung disease are attributable to neurological decline and include an inefficient dys-coordinated cough. Sniff nasal inspiratory pressure(SNIP) is an easy, simple measure of inspiratory muscle strength. SNIP values in children ≥6 years are similar to those measured in healthy adults. Peak cough flow(PCF) is a method of measuring cough effectiveness. In children >12 years airway clearance is compromised at a PCF of Methods: Best of 3 PCF(since May 2011), and best of 10-20 SNIP(since May 2014) measurements were recorded from children attending the national paediatric A-T clinic. Results: Conclusion: Most children with A-T were able to perform SNIP and PCF manoeuvres. 79% children have reduced PCF ;More boys than girls have values >2 SD below the reference population for SNIP.

Currently, there is no three-dimensional structure of D-specific dehalogenase (DehD) in the protein database. We modeled DehD using ab initio technique, performed molecular dynamics (MD) simulation and docking of D-2-chloropropionate (D-2CP), D-2-bromopropionate (D-2BP), monochloroacetate (MCA), monobromoacetate (MBA), 2,2-dichloropropionate (2,2-DCP), d,l-2,3-dichloropropionate (d,l-2,3-DCP), and 3-chloropropionate (3-CP) into the DehD active site. The sequences of DehD and D-2-haloacid dehalogenase (HadD) from Pseudomonas putida AJ1 have 15% sequence similarity. The model had 80% of the amino acid residues in the most favored region when compared to the crystal structure of DehI from Pseudomonas putida PP3. Docking analysis revealed that Arg107, Arg134 and Tyr135 interacted with D-2CP, and Glu20 activated the water molecule for hydrolytic dehalogenation. Single residue substitutions at 25-30 °C showed that polar residues of DehD were stable when substituted with nonpolar residues and showed a decrease in activity within the same temperature range. The molecular dynamics simulation of DehD and its variants showed that in R134A variant, Arg107 interacted with D-2CP, while in Y135A, Gln221 and Arg231 interacted with D-2CP. It is our emphatic belief that the new model will be useful for the rational design of DehDs with enhanced potentials.

The structure of psychrophilic chitinase (CHI II) from Glaciozyma antarctica PI12 has yet to be studied in detail. Due to its low sequence identity (

DNA polymerase β is a 39 kDa enzyme that is a major component of Base Excision Repair in human cells. The enzyme comprises two major domains, a 31 kDa domain responsible for the polymerase activity and an 8 kDa domain, which bind ssDNA and has a deoxyribose phosphate (dRP) lyase activity. DNA polymerase β was shown to be phosphorylated in vitro with protein kinase C (PKC) at serines 44 and 55 (S44 and S55), resulting in loss of its polymerase enzymic activity, but not its ability to bind ssDNA. In this study, we investigate the potential phosphorylation-induced structural changes for DNA polymerase β using molecular dynamics simulations. The simulations show drastic conformational changes of the polymerase structure as a result of S44 phosphorylation. Phosphorylation-induced conformational changes transform the closed (active) enzyme structure into an open one. Further analysis of the results points to a key hydrogen bond and newly formed salt bridges as potential drivers of these structural fluctuations. The changes observed with S55/44 and S55 phosphorylation were less dramatic and the integrity of the H-bond was not compromised. Thus the phosphorylation of S44 is the major contributor to structural fluctuations that lead to loss of enzymatic activity.

Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin-angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls forAGTvariants (P=0.05) but not forACEandAGTR1. Haplotype TCG of theAGTwas associated with increased risk of T2DM (OR 1.92, 95% CI 1.15–3.20, permutedP=0.012); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of theAGTvariants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk.

Oil dispersion of AgI/Ag2S salts as a new electroactive material for potentiometric sensing of iodide and cyanide is reported. This type of material offers attractive features which can be used in the future for various chemical and biological modifications. The composition of the sensing membrane was optimized to be 5:1 (w/w) silver salt to paraffin oil. The sensor had a Nernstian response to iodide with a slope of +57.5±1.4 mV per decade (25 °C), a linear working range of pI− 2.0–6.5 and a fast response time of 30 s. The sensor, likewise, exhibited high sensitivity (69.1±4.1 mV per decade) to cyanide ions, excellent linearity (r=0.999), a linear working range of pCN− 2.6–4.7 and an average response time of 1 min. The sensor can be used repeatedly in measuring iodide solutions without the need for surface renewal and polishing. However, in the presence of cyanide solutions, it gives reproducible results only upon renewal of the surface.

This paper reports a process used for the microfabrication of an array of hollow microneedles. The purpose of the array is for painless transdermal drug delivery. The fabrication process uses wet bulk silicon technology and copper electroplating technology. First, a microneedle array mold on -oriented silicon was fabricated by wet anisotropic etching using KOH solution, then the silicon mold was electroplated with copper. After which, the hollow copper microneedle array was released by a lift-off process or by etching off the silicon mold in KOH solution. The hollow copper microneedle array has been mounted on a polycarbonate platform, which consist of laser ablated cavities and channel for external connection to drug source. In consideration of the contour of human’s skin and the geometry of the microneedle tip, which has walls of sloping gradient corresponding to the (111)-planes, the height of the microneedle array is 200 μm. Two arrays of hollow copper microneedle were fabricated. They have square base of dimensions 390 μm and 400 μm and square tips of size 100 μm and 120 μm with square holes of size 88 μm and 94 μm respectively. Both arrays have microneedle tips at 1900 μm apart from one another and consist of 10 × 10 microneedle tips.

Summary: birgHPC, a bootable Linux Live CD has been developed to create high-performance clusters for bioinformatics and molecular dynamics studies using any Local Area Network (LAN)-networked computers. birgHPC features automated hardware and slots detection as well as provides a simple job submission interface. The latest versions of GROMACS, NAMD, mpiBLAST and ClustalW-MPI can be run in parallel by simply booting the birgHPC CD or flash drive from the head node, which immediately positions the rest of the PCs on the network as computing nodes. Thus, a temporary, affordable, scalable and high-performance computing environment can be built by non-computing-based researchers using low-cost commodity hardware. Availability: The birgHPC Live CD and relevant user guide are available for free at http://birg1.fbb.utm.my/birghpc. Contacts: shahir@utm.my; teonghan@gmail.com