Insights from a community-based survey on factors influencing acceptance and uptake of Paxlovid (nirmatrelvir and ritonavir) as a COVID-19 antiviral medication in Singapore.

INTRODUCTION: Antiviral treatment can reduce the burden of COVID-19. But utilisation can be suboptimal, even in a setting like Singapore where it is fully subsidized for those with selected medical conditions and older adults (≥ 50 years). We hence investigated the factors affecting awareness, acceptance, and initiative to request Paxlovid. METHODS: We assessed the Paxlovid awareness, factors impacting its uptake in a survey conducted from August 2022 to September 2022 through the SOCRATES cohort. Multivariable logistic regression was used to investigate associations between sociodemographics, perceptions, and attitudes with the key study outcomes. RESULTS: Among respondents to the Paxlovid survey, 54% were aware of Paxlovid. On being provided essential details about Paxlovid, 75% reported they would likely be receptive to taking it if prescribed, and 38% indicated the initiative to request for it if it was not suggested by their doctors. Factors associated with awareness of Paxlovid include aged 40 years old and above, higher education, citing websites as an information source, greater trust in healthcare providers (aOR: 1.65, 95% CI 1.26 - 2.15) and government communications (aOR: 0.69, 95% CI 0.55 - 0.86), and higher perceived risk of COVID-19 infection (aOR: 1.25, 95% CI 1.10 - 1.42). Factors associated with acceptance to take Paxlovid include male gender, citing trust in healthcare providers (aOR: 1.49, 95% CI 1.11 - 1.99) and government communications (aOR: 1.38, 95% CI 1.09 - 1.76), and higher perceived severity of COVID-19 (aOR: 1.23, 95% CI 1.07 - 1.42). Factors associated with initiative to request Paxlovid include male gender, having pre-existing diabetes and higher perceived severity of COVID-19 (aOR: 1.24, 95% CI 1.09 - 1.40). The most common reasons for why respondents might not take Paxlovid were concerns about side effects (64%), concerns about costs (29%), and the perception that COVID-19 is a mild (25%). CONCLUSION: The majority of our respondents would take Paxlovid if it was prescribed to them, but a much smaller proportion would have the initiative to request for this. Key factors that may influence uptake are COVID-19 threat perceptions, trust in healthcare and government, and perceptions of the drug's side effects and cost.

Development of Injectable Calcium Sulfate and Self-Setting Calcium Phosphate Composite Bone Graft Materials for Minimally Invasive Surgery.

The demand of bone grafting is increasing as the population ages worldwide. Although bone graft materials have been extensively developed over the decades, only a few injectable bone grafts are clinically available and none of them can be extruded from 18G needles. To overcome the existing treatment limitations, the aim of this study is to develop ideal injectable implants from biomaterials for minimally invasive surgery. An injectable composite bone graft containing calcium sulfate hemihydrate, tetracalcium phosphate, and anhydrous calcium hydrogen phosphate (CSH/CaP paste) was prepared with different CSH/CaP ratios and different concentrations of additives. The setting time, injectability, mechanical properties, and biocompatibility were evaluated. The developed injectable CSH/CaP paste (CSH/CaP 1:1 supplemented with 6% citric acid and 2% HPMC) presented good handling properties, great biocompatibility, and adequate mechanical strength. Furthermore, the paste was demonstrated to be extruded from a syringe equipped with 18G needles and exerted a great potential for minimally invasive surgery. The developed injectable implants with tissue repairing potentials will provide an ideal therapeutic strategy for minimally invasive surgery to apply in the treatment of maxillofacial defects, certain indications in the spine, inferior turbinate for empty nose syndrome (ENS), or reconstructive rhinoplasty.

Evidence for Cross-Protection Against Subsequent Febrile Respiratory Illness Episodes From Prior Infections by Different Viruses Among Singapore Military Recruits 2009-2014.

BACKGROUND: Few studies have evaluated the relative cross-protection conferred by infection with different groups of viruses through studies of sequential infections in humans. We investigated the presence of short-lived relative cross-protection conferred by specific prior viral infections against subsequent febrile respiratory illness (FRI). METHODS: Men enlisted in basic military training between December 2009 and December 2014 were recruited, with the first FRI as the study entry point. ResPlex II assays and real-time polymerase chain reaction assays were used to detect viral pathogens in nasal wash samples, and survival analyses were performed to determine whether infection with particular viruses conferred short-lived relative cross-protection against FRI. RESULTS: Prior infection with adenovirus (hazard ratio [HR], 0.24; 95% confidence interval [CI], .14-.44) or influenza virus (HR, 0.52; 95% CI, .38-.73) conferred relative protection against subsequent FRI episode. Results were statistically significant even after adjustment for the interval between enlistment and FRI (P < .001). Adenovirus-positive participants with FRI episodes tended to be protected against subsequent infection with adenovirus, coronavirus, enterovirus/rhinovirus, and influenza virus (P = .062-.093), while men with influenza virus-positive FRI episodes tended be protected against subsequent infection with adenovirus (P = .044) and influenza virus (P = .081). CONCLUSION: Prior adenovirus or influenza virus infection conferred cross-protection against subsequent FRI episodes relative to prior infection due to other circulating viruses.

Transport of polymeric nanoparticulate drug delivery systems in the proximity of silica and sand.

The contamination of the environment with traditional therapeutics due to metabolic excretion, improper disposal, and industrial waste has been well-recognized. However, knowledge of the environmental distribution and fate of emerging classes of nanomedicine is scarce. This work investigates the effect of surface chemistry of polymeric nanoparticulate drug delivery systems (PNDDS) on their adsorption dynamics and transport in the vicinity of environmentally relevant surfaces for a concentration comparable with hospital and pharmaceutical manufacturing effluents. To this end, five different types of paclitaxel-based nanomedicine having different polymer stabilizers were employed. Their transport behavior was characterized via quartz crystal microbalance, sand column, spectrofluorometry, and dynamic light scattering techniques. PNDDS having positive zeta-potential displayed strong adsorption onto silica surfaces and no mobility in porous media of quartz sand, even in the presence of humic acid. The mobility of negatively charged PNDDS strongly depended on the amount and type of salt present in the aqueous media: Without any salt, such PNDDS demonstrated no adsorption on silica surfaces and high levels of mobility in sand columns. The presence of CaCl2 and CaSO4, even at low ionic strengths (i.e. 10 mM), induced PNDDS adsorption on silica surfaces and strongly limited the mobility of such PNDSS in sand columns.

Temporally controlled modulation of FGF/ERK signaling directs midbrain dopaminergic neural progenitor fate in mouse and human pluripotent stem cells.

Effective induction of midbrain-specific dopamine (mDA) neurons from stem cells is fundamental for realizing their potential in biomedical applications relevant to Parkinson's disease. During early development, the Otx2-positive neural tissues are patterned anterior-posteriorly to form the forebrain and midbrain under the influence of extracellular signaling such as FGF and Wnt. In the mesencephalon, sonic hedgehog (Shh) specifies a ventral progenitor fate in the floor plate region that later gives rise to mDA neurons. In this study, we systematically investigated the temporal actions of FGF signaling in mDA neuron fate specification of mouse and human pluripotent stem cells and mouse induced pluripotent stem cells. We show that a brief blockade of FGF signaling on exit of the lineage-primed epiblast pluripotent state initiates an early induction of Lmx1a and Foxa2 in nascent neural progenitors. In addition to inducing ventral midbrain characteristics, the FGF signaling blockade during neural induction also directs a midbrain fate in the anterior-posterior axis by suppressing caudalization as well as forebrain induction, leading to the maintenance of midbrain Otx2. Following a period of endogenous FGF signaling, subsequent enhancement of FGF signaling by Fgf8, in combination with Shh, promotes mDA neurogenesis and restricts alternative fates. Thus, a stepwise control of FGF signaling during distinct stages of stem cell neural fate conversion is crucial for reliable and highly efficient production of functional, authentic midbrain-specific dopaminergic neurons. Importantly, we provide evidence that this novel, small-molecule-based strategy applies to both mouse and human pluripotent stem cells.

HTRA2 variations in Taiwanese Parkinson's disease.

Mutations in HTRA2 have been reported to associate with Parkinson's disease (PD). This study investigates if the genetic variants in HTRA2 contribute to Taiwanese PD. HTRA2 cDNA fragments from 80 patients with early-onset PD (onset ≤50 years) were sequenced. The identified variants were further examined for a cohort of PD and ethnically matched controls. A novel heterozygous R36W was identified in one early-onset and two late-onset PD patients, which was absent in 606 normal controls. The clinical features and 99mTc-TRODAT-1 SPECT image of the early-onset patient carrying R36W were similar to that of idiopathic PD. The R36W mutation of the patient was inherited from his mother whose SPECT revealed asymmetric reduction of 99mTc-TRODAT-1 uptake in the left striatum, suggesting that the defect of the nigrostriatal pathway may be attributable to the R36W in this family. Protein subcellular fractionation further revealed that R36W affected the processing of the proprotein after transport into mitochondria. Although the functional assays are promising, a larger cohort of both cases and controls should be screened to clarify the role of R36W in Taiwanese PD pathogenicity.

Investigating the therapeutic effects of novel compounds targeting inflammatory IL-1ß and IL-6 signaling pathways in spinocerebellar ataxia type 3.

At least seven dominantly inherited spinocerebellar ataxias (SCA) are caused by expansions of polyglutamine (polyQ)-encoding CAG repeat. The misfolded and aggregated polyQ-expanded proteins increase reactive oxygen species (ROS), cellular toxicity, and neuroinflammation in the disease pathogenesis. In this study, we evaluated the anti-inflammatory potentials of coumarin derivatives LM-021, LMDS-1, LMDS-2, and pharmacological chaperone tafamidis using mouse BV-2 microglia and SCA3 ataxin-3 (ATXN3)/Q75-GFP SH-SY5Y cells. The four tested compounds displayed anti-inflammatory activity by suppressing nitric oxide (NO), interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α production, and CD68 antigen (CD68) and histocompatibility-2 (MHCII) expression in lipopolysaccharides (LPS)/interferon (IFN)-γ-stimulated BV-2 microglia. In retinoic acid-differentiated ATXN3/Q75-GFP-expressing SH-SY5Y cells inflamed with LPS/IFN-γ-primed BV-2 conditioned medium, treatment with test compounds mitigated the increased caspase 1 activity and lactate dehydrogenase release, reduced ROS and ATXN3/Q75 aggregation, and promoted neurite outgrowth. Examination of IL-1ß and IL-6-mediated signaling pathways revealed that LM-021, LMDS-1, LMDS-2, and tafamidis decreased NLR family pyrin domain containing 1 (NLRP1), c-Jun N-terminal kinase/c-Jun proto-oncogene (JNK/JUN), inhibitor of kappa B (IκBα)/P65, mitogen-activated protein kinase 14/signal transducer and activator of transcription 1 (P38/STAT1), and/or Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling. The study results suggest the potential of LM-021, LMDS-1, LMDS-2, and tafamidis in treating SCA3 and probable other polyQ diseases.

Effects of Chitosan on Chondrocytes Derived from Human Nasal Septal Cartilage.

BACKGROUND/AIM: The aim of this study was to evaluate the influence of chitosan on the growth of nasal septal chondrocytes (NSCs). The final goal was to establish a novel methodology to enhance nasal septal cartilage regeneration. MATERIALS AND METHODS: Human NSCs were isolated and their morphology was examined using Alcian blue staining and observed by light microscopy. The isolated NSCs were grown with various concentrations of chitosan and the expression of COL2A1 was investigated. RESULTS: NSCs were successfully isolated from nasal septal cartilage. Co-culture with 0.2% of chitosan greatly enhanced proliferation of NSCs compared to control cells. However, 0.5% of chitosan was harmful to NSCs, resulting in cell detachment from the culture plate. Furthermore, the addition of 0.2% chitosan significantly improved the expression of COL2A1 in NSCs. CONCLUSION: To our knowledge, this is the first report to demonstrate that chitosan could effectively guide the attachment and growth of human NSCs. Chitosan appears to be a promising additive for NSC culture, which sets the stage for studying tissue regeneration in nasal septal cartilage deficiency, rhinoplasty, and craniofacial reconstruction.

In vitro studies of factors affecting debridement of dental implants by tricalcium phosphate powder abrasive treatment.

Peri-implantitis is a common complication characterized by inflammation in tissues surrounding dental implants due to plaque accumulation, which can lead to implant failure. While air flow abrasive treatment has been found to be effective for debriding implant surfaces, little is known about the factors that affect its cleaning capacity. This study systematically examined the cleaning capacity of air powder abrasive (APA) treatment with ß-tricalcium phosphate (ß-TCP) powder, using various powder jetting strengths and different particle sizes. Three sizes of ß-TCP powder (S, M, and L) were prepared, and different powder settings (low, medium, and high) were tested. The cleaning capacity was determined by quantifying ink removal, which simulated biofilm removal from the implant surfaces at different time points. The results of the systematic comparisons showed that the most efficient cleaning of implant surfaces was achieved using size M particles with medium setting. Additionally, the amount of powder consumed was found to be critical to cleaning efficiency, and the implant surfaces were altered in all tested groups. These systematically analyzed outcomes may provide insights into the development of potential non-surgical strategies for treating peri-implant diseases.

Intelligent Performance Evaluation in Rowing Sport Using a Graph-Matching Network.

Rowing competitions require consistent rowing strokes among crew members to achieve optimal performance. However, existing motion analysis techniques often rely on wearable sensors, leading to challenges in sporter inconvenience. The aim of our work is to use a graph-matching network to analyze the similarity in rowers' rowing posture and further pair rowers to improve the performance of their rowing team. This study proposed a novel video-based performance analysis system to analyze paired rowers using a graph-matching network. The proposed system first detected human joint points, as acquired from the OpenPose system, and then the graph embedding model and graph-matching network model were applied to analyze similarities in rowing postures between paired rowers. When analyzing the postures of the paired rowers, the proposed system detected the same starting point of their rowing postures to achieve more accurate pairing results. Finally, variations in the similarities were displayed using the proposed time-period similarity processing. The experimental results show that the proposed time-period similarity processing of the 2D graph-embedding model (GEM) had the best pairing results.

Distinct Expression of Surface and Genetic Biomarkers in Prostate Cancer Cell Lines.

BACKGROUND/AIM: Surface biomarkers, such as CD44 and CD133, have been demonstrated to be expressed in prostate cancer cells, and our previous study has shown that prostate cancer cell lines could be divided into three groups according to the single and combined expression pattern of CD44 and 133. In order to refine prognostication in prostate cancer cells, we further investigated genetic biomarkers, prostate cancer antigen 3 (PCA3), kallikrein 4 (KLK4), and KLK9 in different prostate cancer cell lines. MATERIALS AND METHODS: CWR22Rv1, PC3, and DU145 cell lines were cultured until 95% confluence. The single expression of CD44 or CD133 and their combined expression were analyzed by flow cytometry, and gene expression of b-actin, PCA3, KLK4, and KLK9 was analyzed by real-time polymerase chain reaction. RESULTS: The single expression of CD133 was less than 4% in all cell lines examined. PC3 and DU145 cells displayed a high expression of CD44 (>91%), whereas CWR22Rv1 was the only cell line that demonstrated a high co-expression of both CD44 and CD133 (>91%). In addition, PC3 and DU145 displayed low expression of PCA3, KLK4, and KLK9 when compared with their own b-actin expression. In contrast, CWR22Rva showed high expression of PCA3 and KLK4 although KLK9 expression was also low. CONCLUSION: Both surface and genetic biomarkers should be validated for a more accurate prognosis in prostate cancer.

Effect of Lactobacillus plantarum PS128 on neuromuscular efficiency after a half-marathon.

Introduction: Lactobacillus plantarum PS128 (PS128) could be considered an antioxidant supplement to reduce muscle fatigue and improve exercise capacity recovery after vigorous exercise. Purpose: The purpose of this study is to investigate the effect of PS128 on muscle fatigue and electromyography (EMG) activity after a half-marathon (HM). Methods: The experimental design used a repeated-measures design with a double-blind approach. The participants either took two capsules of PS128 for 4 weeks as the PS128 group (PSG, n = 8) or took two capsules of a placebo for 4 weeks as the placebo group (PLG, n = 8) to ensure counterbalancing. The time points of the maximal voluntary isometric contraction (MVIC) and EMG activity test were set before probiotics were taken (baseline), 48 h before HM (Pre), and immediately at 0 h, 3 h, 24 h, 48 h, 72 h, and 96 h after HM. Results: EMG activity included median power frequency (MDF), integrated EMG (iEMG), and neuromuscular efficiency (peak torque/iEMG). The MVICs of knee extensors, analyzed by using an isokinetic dynamometer, showed a decrease from the Pre to 0 h (p = 0.0001), 3 h (p < 0.0001), 24 h (p < 0.0001), 48 h (p < 0.0001), 72 h (p = 0.0002), and 96 h (p = 0.0408) time points in the PLG. Sidak's multiple comparisons tests showed that the PLG was significantly lower than the PSG at 0 h (p = 0.0173), 3 h (p < 0.0001), 24 h (p < 0.0001), 48 h (p < 0.0001), 72 h (p < 0.0001), and 96 h (p = 0.0004) time points. The MDF of vastus medialis oblique (VMO) in the PLG was significantly decreased 24 h after HM and significantly lower than that in the PSG at all times points after HM. The iEMG of VMO in the PLG was significantly decreased 48 h after HM and significantly lower than that in the PSG at 0 h, 3 h, 24 h, 48 h, and 72 h after HM. Conclusion: The PS128 supplementation may prevent the decrease in MDF, iEMG, and peak torque after vigorous exercise. Recreational runners may consider implementing a probiotic supplementation regimen as a potential strategy to mitigate muscle fatigue following HM.

Evaluating Pull-Out Strength of Barbed Suture In Vitro by Using Porcine Tissue and Polydimethylsiloxane (PDMS).

Using barbed thread lifting for facial rejuvenation has become popular these days due to its minimally invasive procedures with reduced complications. However, only limited studies regarding its mechanical properties for face suspension were published. The aim of this study was to evaluate suture-holding ability regarding its facelift property, and different specimens were tested in order to establish an in vitro model. Fresh porcine tissue and the synthetic material polydimethylsiloxane (PDMS) were selected to simulate human skin for evaluating barbed suture pull-out strength by the universal material testing machine. The results showed that the pull-out strength of barbs between different porcine tissues varied without consistency. By contrast, PDMS (30:1) showed more consistent pull-out strength in each testing, and the average maximum load force was close to porcine tissue. Furthermore, after submerging barbed sutures in PBS for 0 days (T0), 7 days (T7) and 14 days (T14), a trend of decreased average maximum load force, displacement and force of 1.5 mm/2 mm/3 mm displacement could be detected by in vitro testing with PDMS (30:1). These results provide support for using PDMS (30:1) to evaluate suture pull-out strength and holding/lifting capacities in vitro to obtain consistent and objective information for evaluating substantial equivalence of devices. The established in vitro method could be used for the future development of barbed thread lifting technology.

Preparation and Characterization of Extracellular Matrix Hydrogels Derived from Acellular Cartilage Tissue.

Decellularized matrices can effectively reduce severe immune rejection with their cells and eliminated nucleic acid material and provide specific environments for tissue repair or tissue regeneration. In this study, we prepared acellular cartilage matrix (ACM) powder through the decellularization method and developed ACM hydrogels by physical, chemical, and enzymatic digestion methods. The results demonstrated that the small size group of ACM hydrogels exhibited better gel conditions when the concentration of ACM hydrogels was 30 and 20 mg/mL in 1N HCl through parameter adjustment. The data also confirmed that the ACM hydrogels retained the main components of cartilage: 61.18% of glycosaminoglycan (GAG) and 78.29% of collagen, with 99.61% of its DNA removed compared to samples without the decellularization procedure (set as 100%). Through turbidimetric gelation kinetics, hydrogel rheological property analysis, and hydrogel tissue physical property testing, this study also revealed that increasing hydrogel concentration is helpful for gelation. Besides, the ex vivo test confirmed that a higher concentration of ACM hydrogels had good adhesive properties and could fill in cartilage defects adequately. This study offers useful information for developing and manufacturing ACM hydrogels to serve as potential alternative scaffolds for future cartilage defect treatment.

Investigation and Characterization of Factors Affecting Rheological Properties of Poloxamer-Based Thermo-Sensitive Hydrogel.

Poloxamers are negatively temperature-sensitive hydrogels and their hydrophilic groups interact with water molecules at lower temperatures (liquid phase) while their hydrophobic groups interact more strongly with increases in temperature causing gelation. To investigate the factors affecting the rheological properties of poloxamers, various parameters including different poloxamer P407 concentrations, poloxamers P407/P188 blending ratios and additives were examined. The results presented a clear trend of decreasing gelling temperature/time when P407 was at higher concentrations. Moreover, the addition of P188 enhanced the gelling temperature regardless of poloxamer concentration. Polysaccharides and their derivatives have been widely used as components of hydrogel and we found that alginic acid (AA) or carboxymethyl cellulose (CMC) reduced the gelling temperature of poloxamers. In addition, AA-containing poloxamer promoted cell proliferation and both AA -and CMC-containing poloxamer hydrogels reduced cell migration. This study investigated the intriguing characteristics of poloxamer-based hydrogel, providing useful information to compounding an ideal and desired thermo-sensitive hydrogel for further potential clinical applications such as development of sprayable anti-adhesive barrier, wound-healing dressings or injectable drug-delivery system for cartilage repair.

Impact of shock wave lithotripsy on heart rate variability in patients with urolithiasis.

The physiological response of the cardiac autonomic nervous system during shock wave lithotripsy (SWL) remains unclear. Heart rate variability (HRV) is an index of cardiac autonomic balance. This study aimed to analyze HRV during SWL in patients with urolithiasis. Electrocardiograms of patients who underwent SWL were obtained. Recordings were obtained before and after SWL. For each time point, the recordings were obtained continuously for 6 min, after which R wave-to-R wave (RR) intervals were extracted. The time digital sequence derived from RR intervals was the HRV signal. Time-domain analysis revealed that the mean of RR intervals (MRR) and standard deviation of normal beat-to-normal beat (NN) intervals (SDNN), but not the square root of the mean squared difference of successive NNs (RMSSD) or triangular interpolation of NN intervals (TINN), significantly increased during SWL. The increase in SDNN persisted after SWL but MRR returned to the initial level. Frequency-domain analysis revealed that very low frequency (VLF), low frequency (LF), and LF/high frequency (HF) ratio significantly increased after SWL, while there was no statistically significant difference in HF. Thus, the patients had significantly high MRR and SDNN during SWL and significantly high SDNN, VLF, LF, and LF/HF ratio after SWL. SWL could alter the functioning of the cardiac autonomic nervous system, resulting in reduction in sympathetic activity and increase in parasympathetic activity. Further studies with larger samples are required to confirm these findings and understand the underlying mechanisms.

Photodissociation dynamics of ClOOCl at 248.4 and 308.4 nm.

The dynamics of ClOOCl photodissociation at 248.4 and 308.4 nm was studied with photofragment translational spectroscopy. At 248.4 nm photoexcitation, the observed products are Cl, O(2), ClO and O. Product translational energy distributions P(E) and anisotropy parameters ß were deduced from the measured time-of-flight spectra of the Cl, O(2), and ClO photoproducts. The photodissociation mechanisms have been discussed and compared with available theoretical results. Synchronous and fast sequential breaking of the two Cl-O bonds may both contribute to the dissociation. The relative product yields for [ClO]: [Cl] was measured to be 0.15 ± 0.04:1. The relative amounts of [O]:[O(2)] products were estimated to be 0.12:1. The branching ratios among the Cl + O(2) + Cl:ClO + ClO:ClO + Cl + O product channels were estimated to be 0.82:0.08:0.10. At 308.4 nm excitation, time-of-flight spectra of the O(2) and ClO photoproducts were recorded while there was interference from Cl(2) impurity in detecting the Cl product. Nonetheless, the observed ClO yield relative to the O(2) yield at 308.4 nm is 1.5 times that at 248.4 nm. The branching ratio between the Cl + O(2) + Cl:ClO + ClO product channels was estimated to be 0.81:0.19 at 308.4 nm. This result suggests that the ClO product may contribute a noticeable yield in the photolysis of ClOOCl at the atmospherically important wavelengths above 300 nm.

ATP13A2 variability in Taiwanese Parkinson's disease.

Mutations in ATP13A2 have been reported to associate with Parkinson's disease (PD). This study investigates the contribution of genetic variants in ATP13A2 to Taiwanese PD. ATP13A2 cDNA fragments from 65 early onset PD (onset <50 years) were sequenced. The identified variants were validated in a cohort of PD (n = 493) and ethnically matched controls (n = 585). A novel heterozygous G1014S, located at the conserved seventh transmembrane domain of ATP13A2 protein, was identified in an early onset PD patient, which was absent in 585 normal controls. Additionally, a reported heterozygous A746T was found in two PD patients and four controls. The clinical features and 99mTc-TRODAT-1 single photon emission computed tomography (SPECT) image of the patients carrying G1014S and A746T were similar to that of idiopathic PD. One normal control with A746T showed an asymmetric reduction of 99mT TRODAT-1 uptake in the right striatum. Under oxidative stress or apoptotic stimulus, lymphoblastoid cells carrying either A764T or G1014S showed increased caspase 3 activity compared with the controls. The rates of decay for G1014S and A746T proteins were more or less reduced in cycloheximide chase experiment. In silico modeling of G1014S exhibited a more stable feature than wild-type, and G1014S is mislocalized mainly in the intralysosomal space, which is coherent with the prediction of prohibiting N-myristoylation and membrane association. We therefore hypothesize that rare variants of ATP13A2 may contribute to PD susceptibility in Taiwan. The role played by ATP13A2 variants in PD remains to be clarified.

Preparation and Characterization of Moldable Demineralized Bone Matrix/Calcium Sulfate Composite Bone Graft Materials.

Demineralized bone matrix (DBM) is a decalcified allo/xenograft retaining collagen and noncollagenous proteins, which has been extensively used because of its osteoconductive and osteoinductive properties. Calcium sulfate (CaSO4, CS) is a synthetic bone substitute used in bone healing with biocompatible, nontoxic, bioabsorbable, osteoconductive, and good mechanical characteristics. This study aims to prepare a DBM/CS composite bone graft material in a moldable putty form without compromising the peculiar properties of DBM and CS. For this purpose, firstly, porcine femur was defatted using chloroform/methanol and extracted by acid for demineralization, then freeze-dried and milled/sieved to obtain DBM powder. Secondly, the α-form and ß-form of calcium sulfate hemihydrate (CaSO4·0.5H2O, CSH) were produced by heating gypsum (CaSO4·2H2O). The morphology and particle sizes of α- and ß-CSH were obtained by SEM, and their chemical properties were confirmed by EDS, FTIR and XRD. Furthermore, the DBM-based graft was mixed with α- or ß-CSH at a ratio of 9:1, and glycerol/4% HPMC was added as a carrier to produce a putty. DBM/CSH putty possesses a low washout rate, good mechanical strength and biocompatibility. In conclusion, we believe that the moldable DBM/CSH composite putty developed in this study could be a promising substitute for the currently available bone grafts, and might have practical application in the orthopedics field as a potential bone void filler.

Influence of Antibiotic-Loaded Acrylic Bone Cement Composition on Drug Release Behavior and Mechanism.

Periprosthetic joint infection (PJI) is a devastating complication after total joint replacement with considerable morbidity and large economic burdens. Antibiotic-Loaded Bone Cement (ALBC) has been developed as a valuable tool for local administration and is becoming one of the most effective methods for the prevention and treatment of orthopedic infections. Controlling antibiotic release from ALBC is critical to achieve effective infection control, however, the antibiotic elution rates are generally low, and the mechanisms are poorly understood. Thus, the present study aims to investigate the effects of the basic acrylic bone cement components, including liquid/powder (monomer-to-polymer) ratios, radiopacifier, initiator, and doses of antibiotics on the porosity, antibiotic elution rates and mechanical properties of polymethylmethacrylate (PMMA) based ALBC. The obtained results from the in vitro studies suggested that a reduction in the liquid/powder ratio and an increase in the radiopacifier ratio and gentamicin doses led to increased porosity and release of antibiotic, while the initiator ratio exerted no effect on elution rates. In conclusion, we hope that by varying the composition of ALBC, we could considerably enhance the antibiotic elution rates by increasing porosity, while maintaining an adequate mechanical strength of the bone cements. This finding might provide insights into controlling antibiotic release from ALBC to achieve effective infection control after total joint replacement surgery.