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In Taiwan, there were only 799 confirmed COVID-19 cases in 2020. The unique backdrop amidst a pandemic and promotion of nonpharmaceutical interventions generated some distinct changes in the epidemiology of common respiratory pathogens. In this study, we aimed to investigate the dynamic changes in respiratory pathogens in children during 2020.We performed a retrospective cohort study at a tertiary hospital in southern Taiwan during 2020. Patients aged 0-18 years who visited the pediatric emergency department were enrolled. Children who presented with clinical symptoms (fever or respiratory illness) and received nasopharyngeal swabs for multiplex polymerase chain reaction (PCR) were included in our analysis. We also compared respiratory syncytial virus (RSV) trends from previous years by PCR and lateral flow immunochromatographic assays from 2017 to 2020.A total of 120 children were tested. The overall detection rate was 55%. With strengthened restrictions, the detection rate dropped from 70% to 30%. However, non-enveloped viruses (rhinovirus/enterovirus and adenovirus) were in constant circulation. Upon easing prevention measures, the detection rate remained above 60%, and an outbreak of an enveloped virus (RSV and parainfluenza virus) was noted. Compared with 2017-2019, the cyclical RSV epidemic was delayed, with a large surge in late 2020.We observed a constant circulation of non-enveloped viruses when strict nonpharmaceutical interventions were employed and a delayed surge of enveloped viruses during the easing of restrictions. Continuous surveillance and monitoring of the evolutionary dynamics of respiratory viruses is important, while easing restrictions requires balanced judgment.

Staphylococcus argenteus is generally more susceptible to antibiotic treatments than Staphylococcus aureus; however, the study showed that the daptomycin/vancomycin-resistant S. argenteus was isolated from a patient with repeated antibiotic treatments. In this study, the methicillin- and vancomycin-susceptible S. argenteus isolates were used to characterize the phenotypes of S. argenteus after vancomycin passages in vitro.Eleven S. argenteus isolates were used for passaging under different concentrations of vancomycin. The minimal inhibitory concentration (MIC) of vancomycin was determined by the agar dilution assay, and the biofilm mass of the passaged variants was quantified by the crystal violet staining assay and observed under the confocal microscope.The MIC of vancomycin for eight of 11 S. argenteus isolates was increased from ≤2 µg/mL to ≤4-8 µg/mL after vancomycin passages. Two variants with the high-level vancomycin-intermediate (vancomycin MIC ≤8 µg/mL) phenotype were identified, and the parental strains of these variants did not have the heterogeneous vancomycin-intermediate population determined by the population profile analysis. Further, three S. argenteus isolates showed an increase in biofilm production and icaA transcription after the low-dose (2 µg/mL) vancomycin passages.S. argenteus is capable of acquiring a vancomycin-tolerant phenotype and/or converting to a strong biofilm producer after vancomycin passages, which could contribute to the decrease of their antibiotic susceptibility.

Summary An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of individuals with ulcerative colitis (UC) require colectomy within 5 years of diagnosis, but polygenic risk scores (PRSs) utilizing findings from genome-wide association studies (GWASs) are unable to provide meaningful prediction of this adverse status. By contrast, in Crohn disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a transcriptional risk score (TRS). Here, we demonstrate that a measured TRS based on bulk rectal gene expression in the PROTECT inception cohort study has a positive predictive value approaching 50% for colectomy. Single-cell profiling demonstrates that the genes are active in multiple diverse cell types from both the epithelial and immune compartments. Expression quantitative trait locus (QTL) analysis identifies genes with differential effects at baseline and week 52 follow-up, but for the most part, differential expression associated with colectomy risk is independent of local genetic regulation. Nevertheless, a predicted polygenic transcriptional risk score (PPTRS) derived by summation of transcriptome-wide association study (TWAS) effects identifies UC-affected individuals at 5-fold elevated risk of colectomy with data from the UK Biobank population cohort studies, independently replicated in an NIDDK-IBDGC dataset. Prediction of gene expression from relatively small transcriptome datasets can thus be used in conjunction with TWASs for stratification of risk of disease complications.

Objective To investigate the effects of perturbation-based pinch task training on the sensorimotor performance of the upper extremities of patients with chronic stroke via a novel vibrotactile therapy system. Design A single-blinded randomized controlled trial. Setting A university hospital. Participants Patients with chronic stroke (N=19) randomly assigned into either an experimental group or a control group completed the study. Interventions In addition to 10 minutes of traditional sensorimotor facilitation, each participant in the experimental group received 20 minutes of perturbation-based pinch task training in each treatment session, and the controls received 20 minutes of task-specific motor training twice a week for 6 weeks. Main Outcome Measures The scores for the primary outcome, Semmes-Weinstein monofilament (SWM), and those for the secondary outcomes, Fugl-Meyer Assessment (FMA), amount of use, quality of movement (QOM) on the Motor Activity Log (MAL) scale, and box and block test (BBT), were recorded. All outcome measures were recorded at pretreatment, post treatment, and 12-week follow-up. Results There were statistically significant between-group differences in the training-induced improvements revealed in the SWM results (P=.04) immediately after training and in the BBT results (P=.05) at the 12-week follow-up. The changes in muscle tone and in the QOM, SWM, and BBT scores indicated statistically significant improvements after 12 sessions of treatment for the experimental group. For the control group, a significant statistical improvement was found in the wrist (P Conclusions This study indicated that the perturbation-based pinch task training has beneficial effects on sensory restoration of the affected thumb in patients with chronic stroke.

We report 4 cases of neonatal sepsis caused by Streptococcus gallolyticus. The clinical course was quite similar to early-and late-onset group B streptococcus disease. None of the mothers had group B streptococcus (GBS) colonization on prenatal screening nor received intrapartum antibiotics. We proposed the sporadic distribution of S. gallolyticus sepsis among neonates was partly due to relatively low colonization rate in adults compared with GBS. Species determination of S. gallolyticus may not be available using conventional microbiological methods and may contribute to underestimation or misclassification. In our series, we highlighted the importance of S. gallolyticus as an important pathogen in neonatal sepsis deserving further surveillance.

Background & Aims Recent literature has implicated a key role for mast cells in murine models of colonic inflammation, but their role in human ulcerative colitis (UC) is not well established. A major advance has been the identification of mrgprb2 (human orthologue, MRGPX2) as mediating IgE-independent mast cell activation. We sought to define mechanisms of mast cell activation and MRGPRX2 in human UC. Methods Colon tissues were collected from patients with UC for bulk RNA sequencing and lamina propria cells were isolated for MRGPRX2 activation studies and single-cell RNA sequencing. Genetic association of all protein-altering G-protein coupled receptor single-nucleotide polymorphism was performed in an Ashkenazi Jewish UC case-control cohort. Variants of MRGPRX2 were transfected into Chinese hamster ovary (CHO) and human mast cell (HMC) 1.1 cells to detect genotype-dependent effects on β-arrestin recruitment, IP-1 accumulation, and phosphorylated extracellular signal–regulated kinase. Results Mast cell-specific mediators and adrenomedullin (proteolytic precursor of PAMP-12, an MRGPRX2 agonist) are up-regulated in inflamed compared to uninflamed UC. MRGPRX2 stimulation induces carboxypeptidase secretion from inflamed UC. Of all protein-altering GPCR alleles, a unique variant of MRGPRX2, Asn62Ser, was most associated with and was bioinformatically predicted to alter arrestin recruitment. We validated that the UC protective serine allele enhances β-arrestin recruitment, decreases IP-1, and increases phosphorylated extracellular signal–regulated kinase with MRGPRX2 agonists. Single-cell RNA sequencing defines that adrenomedullin is expressed by activated fibroblasts and epithelial cells and that interferon gamma is a key upstream regulator of mast cell gene expression. Conclusion Inflamed UC regions are distinguished by MRGPRX2-mediated activation of mast cells, with decreased activation observed with a UC-protective genetic variant. These results define cell modules of UC activation and a new therapeutic target.

Background: Clostridium difficile infection (CDI) is increasing in children. We aimed to compare the clinical characteristics between CDI and colonization and to identify the risk factors for severe diseases of CDI in children. Method: We retrospectively reviewed 124 children (1–18 years old) from 2011 to 2018. CDI was defined as diarrhea (≥3 loose stool in the past 24 h) with confirmed toxigenic strain. Colonization was defined as presence of C. difficile without clinical symptoms. Severe diseases included ileus, acute kidney injury, gastrointestinal bleeding or mortality. Patients younger than 1 year old and coinfections with other enteric pathogens were excluded. Results: Among 124 patients with C. difficile identified, 49 of them fulfilled CDI definition and 75 had C. difficile colonization. Children with CDI were more likely to present with watery (74% vs. 1%, p

Chamaecyparis obtusa var. formosana is a species indigenous to Taiwan and has been used as a medicinal plant. It has been claimed that the hot water extracts of C. obtusa var. formosana leaves (CoLE) with flavonoids and proanthocyanidins have anti-oxidant and anti-hyperglycemic activities in vitro. This study further examines the anti-hyperglycemic activity of CoLE and its possible mechanisms in hyperglycemic rats. Hyperglycemia of rats was induced by streptozotocin (STZ) and high-fat diets (HFD). Hyperglycemic rats treated orally with 30 and 150 mg/kg CoLE were classified into LCO and HCO groups, respectively. After three-month treatment, both LCO and HCO groups showed improved glucose metabolism in oral glucose tolerance and postprandial blood glucose tests. Decrease in HOMA-IR, leptin and adiponectin levels of the HCO group revealed amelioration of insulin and leptin resistance. Obesity and accumulation of visceral fats induced by STZ and HFD could be alleviated in both HCO and LCO groups. These anti-diabetic effects might be contributed by inhibition of intestinal digested enzymes and protein tyrosine phosphatases (PTPases). Although other studies are necessary, these findings suggest that CoLE could be potentially used as a health complement for treating diabetes without significant toxicity.

Pore size and connectivity of artificial bone scaffolds play key role in regulating cell ingrowth and vascularization during healing. The objective of this study was to develop a novel process for preparing 3D pore-interconnected open-cell bone substitutes with varying pore sizes. This was achieved by thermal-induced expansion, drying, then sintering the mixture of biphasic calcium phosphate (BCP) and a thermal responsive porogen comprising chitosan (CS) and hydroxypropyl methyl cellulose (HPMC). The interpolymer complexes (IPCs) of CS/HPMC were prepared and investigated by FT-IR. The mixtures of IPCs/BCP were heated up to 100 °C for analyzing their thermal expansion properties. This resulted in ~13% and ~42% volume increment for IPC-1/BCP and IPC-2/BCP, respectively, while ~230% volume increased in the case of IPC-3/BCP (therefore chosen for sintering bone blocks). Heating rate-dependent (0.20–0.25 °C/min range) sintering profiles for IPC-3/BCP were utilized to produce BCP bone blocks. Gasification of IPC during sintering resulted in the formation of interconnected porous structures, and the morphology was investigated by SEM, revealing varying sizes ranging from 106 ± 13 μm to 1123 ± 75 μm. The pore size range of bone blocks from 235 ± 46 μm to 459 ± 76 μm portrayed significantly high MC3T3-E1 cell viability with prominent filopodial extensions, and elongated cells, depicting efficient biocompatibility. Therefore, the process for preparing porous interconnected 3D bone blocks were feasible, thereby serving as an alternative for potential bone tissue engineering applications.

We report a 7-year-old girl who got Mycoplasma pneumoniae infection with prolonged fever. Macrolide was used on day 14 of illness but fever persisted with progressive lung consolidation. Oral prednisolone was administered on day 33 then fever subsided with dramatically clinical improvement (decreased CRP and resolution of lung consolidation). In this case, delayed effective antibiotic treatment with inflammation may be the major factor contributing to the fever rather than ongoing infection.

Background Most qualitative studies on caregivers of cancer patients have explored the experiences of family members and friends in Western or European countries. Little is known about the experience of spousal caregivers of patients recently diagnosed with cancer in a Chinese population. Aim The aim of this study was to explore the lived experience of spouses of patients recently diagnosed with cancer in Taiwan. Methods This qualitative study analysed focus groups interview data using thematic analysis. Participants were purposively sampled from a medical hospital in central Taiwan. Four focus group interviews were conducted; 15 spousal caregivers participated. Findings Research findings from the spouses, seven husbands and eight wives, included four main themes: handling emotions to make decisions quickly, experiencing meaningful support from a right and good physician, struggling with changes in daily life, and placing a peaceful mindset at the centre of life. Discussion Chinese collectivistic culture expects family members to make medical decisions and filter information a patient receives. Spousal caregivers informed patients about their cancer in order to avoid or reduce the amount of psychological harm. Spouses' strong commitments to caregiving provided them with power and motivation to continue caregiving. A peaceful mindset, influenced by the traditional Chinese philosophy of Buddhism, was considered critical for prolonging the patient's life and maintaining the caregiver's emotional health. Conclusions It is important for healthcare professionals to understand Chinese cultural influences and concerns of spousal caregivers when caring for Chinese patients to manage patients and caregivers effectively.

Background: The emergence of multiple-antibiotic-resistant (MAR) Salmonella has been a serious threat worldwide. Salmonella can invade into host cells and evade the attacks of host humoral defenses and antibiotics. Thus, a new antibacterial agent capable of inhibiting intracellular Salmonella is highly needed. Methods: The anti-intracellular activity and cytotoxicity of drugs on intracellular bacteria and macrophages were assayed using intracellular CFU assay and MTT cell viability assay, respectively. The uptake of gentamicin into macrophage and the effect of autophagy inhibitor on loxapine's anti-intracellular Salmonella activity were assessed by using image-based high-content system. The expression of bacterial genes was measured by real-time PCR. The efflux pump activity of bacteria was measured by Hoechst accumulation assays. Results: With our efforts, an antipsychotic drug, loxapine, was identified to exhibit high potency in suppressing intracellular MAR S. Typhimurium, Staphylococcus aureus, Shigella flexneri or Yersinia enterocolitica. Subsequent investigations indicated that loxapine's anti-intracellular bacteria activity was not associated with increased penetration of gentamicin into bacteria and macrophages. Loxapine didn't inhibit bacterial growth in broth at concentration up to 500 μM and has no effect on Salmonella's type III secretion system genes' expression. Blockage of autophagy also didn't reverse loxapine's anti-intracellular activity. Lastly, loxapine suppressed bacterial efflux pump activity in all bacteria tested. Conclusion: Altogether, our data suggested that loxapine might suppress intracellular bacteria through inhibiting of bacterial efflux pumps. In light of its unique activity, loxapine represents a promising lead compound with translational potential for the development of a new antibacterial agent against intracellular bacteria. Keywords: Phenothiazine, Autophagy, Efflux pump, Type III secretion system, High-content assay

Impact of papaya extract (PaExt) and high pressure processing (HPP) on survival of Salmonella spp., meat quality and microstructure of chicken breast meat was studied. Samples have been pre-treated with PaExt (0.3%, w/w) in 1, 3 and 5 h, respectively, then followed by 350 and 450 MPa (10 min, 4 °C) HPP treatment. More than 6 log CFU/g of Salmonella were inactivated by 3 or 5 h pre-treatment with PaExt followed by 450 MPa HPP treatment. The Salmonella cells injured by PaExt and HPP tended to take longer time to recover in 16-days storage tests. Regarding meat quality, the color parameters (L*, a* and b* values) and pH value were significantly increased in all pressurized groups. Scanning electron microscopy (SEM) images showed the muscle fibers and connective tissues were severely degraded in the 5 h PaExt and HPP combined treatment. This process may enhance the microbial safety and tenderization of chicken breast meat.

Context Little is known about cancer-related symptoms in terms of prevalence, severity, and distress among patients with cancer in Indonesia because of a lack of a valid and reliable scale. Objectives To translate and validate the Memorial Symptom Assessment Scale (MSAS) among cancer patients in Indonesia. Methods Two procedures consisting of forward-backward translation and validation were conducted. The validation process including pretesting involved 34 cancer patients, and the psychometric testing of the Indonesian version of MSAS (MSAS-I) involved 207 cancer patients. Internal consistency, test-retest reliability, construct, and concurrent validity of the MSAS-I were established. Results Cronbach's alpha coefficients for the total scale and subscales of the MSAS-I ranged from 0.75 to 0.87. The interclass correlations for test-retest reliability ranged from 0.80 to 0.89. A two-factor structure in the MSAS-I was produced by exploratory factor analysis, and the two factors accounted for 28.34% of the cumulative variance. In addition, the concurrent validity was demonstrated by the significant associations between the subscales of the MSAS-I and their corresponding subscales in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, with r = −0.25 to −0.65 (all P Conclusion The MSAS-I presents a valid and reliable scale for assessing symptom frequency, severity, and distress among patients with cancer in Indonesia. Implication for Nursing The MSAS-I can assess physical and psychological symptoms during cancer treatment. In addition, the MSAS-I may facilitate in measuring the effectiveness of symptom management strategies.

The aim of this study was to develop PEGylated phosphatidylcholine (PC)-rich nanovesicles (phosphatiosomes) carrying ciprofloxacin (CIPX) for lung targeting to eradicate extracellular and intracellular methicillin-resistant Staphylococcus aureus (MRSA). Soyaethyl morphonium ethosulfate (SME) was intercalated in the nanovesicle surface with the dual goals of achieving strengthened bactericidal activity of CIPX-loaded phosphatiosomes and delivery to the lungs. The isothermal titration calorimetry (ITC) results proved the strong association of SME phosphatiosomes with pulmonary surfactant. We demonstrated a superior anti-MRSA activity of SME phosphatiosomes compared to plain phosphatiosomes and to free CIPX. A synergistic effect of CIPX and SME nanocarriers was found in the biofilm eradication. SME phosphatiosomes were readily engulfed by the macrophages, restricting the intracellular MRSA count by 1-2 log units. SME phosphatiosomes efficiently accumulated in the lungs after intravenous injection. In a rat model of lung infection, the MRSA burden in the lungs could be decreased by 8-fold after SME nanosystem application.

Apoptosis induced by nanosecond pulsed electric field (nsPEF) has been demonstrated in non-small lung cancerous cells by the observation of field-induced change in cell morphology (swelling and blebbing), phosphatidylserine externalization and change in viability, whereas such field effect was harmless in normal lung cells. Lengthening of autofluorescence lifetime of nicotinamide adenine dinucleotide, decrease of mitochondrial membrane potential, activation of caspases, and generation of reactive oxygen species such as superoxide anion and singlet oxygen were clearly observed only in cancerous cells with application of nsPEF, indicating that the field-induced apoptotic cell death is initiated intrinsically in mitochondria. The finding implicated that electric field effect may be a key mechanism in “cell-competition” between normal and cancerous cells to facilitate the elimination of transformed cancerous cells from surrounding normal cells, and a new insight in “photodynamic action” to kill cancerous cells, which is a root of photodynamic therapy, has been provided.

Silica-based materials have extensive biomedical applications owing to their unique physical, chemical, and biological properties. Recently, increasing studies have examined the mechanisms involved in biosilicification to develop novel, fine-tunable, eco-friendly materials and/or technologies. In this review, we focus on recent developments in bio-templated silica synthesis and relevant applications in drug delivery systems, tissue engineering, and biosensing.

Direct analysis in real time coupled to Q-orbitrap tandem mass spectrometry (DART-MS) without requiring preparatory procedures was used to directly detect trace amounts of illegal street drugs, namely p-chloroamphetamine, p-fluoromethamphetamine, γ-hydroxybutyrate, ketamine, methamphetamine, 3,4-methylenedioxypyrovalerone, p-methylethcathinone, methylone, and nimetazepam, in solution and also in real drug samples. Exact mass determination of the drug samples was completed in less than 1min. With the ability to rapidly identify drugs, this technique shows great potential as a useful analytical tool in the analysis of illicit street drugs, and has the significant advantages of simplicity and sensitivity without the sample preparation needed by other methods.

Photo-induced processes have high potential in in situ patterning and controlling living cells, whose developments are introduced and recent progresses by utilizing femtosecond laser are described. Photochemical and photothermal surface modification performed by conventional light and nanosecond laser irradiation is summarized and their applicability is considered. Femtosecond laser ablation has superior features due to its photomechanical mechanism, which is confirmed by ultrafast spectroscopy and imaging of a model film under laser ablation. Femtosecond laser ablation of physiological solutions generates shockwave and cavitation bubbles, which is employed for patterning and manipulating living cells. Femtosecond laser ablation fabricating cytophobic and cytophilic domains enable us to form living cell patterns and to study cell migration and cell–cell interaction. Finally summary and perspective are presented.

To comprehend the merits of a Manual Tactile Test (MTT) in assessing hand sensorimotor functions by exploring the relations among 3 subtests along with the precision pinch performances for patients with peripheral nerve injuries (PNIs); and to understand the accuracy of the MTT by constructing the sensitivity and specificity of the test for patients with PNI.Case-control study.Hospital and local community.Patients with PNI (n=28) were recruited along with age-, sex-, and handedness-matched healthy controls (n=28) (N=56).Not applicable.The Semmes-Weinstein monofilament, moving and static 2-point discrimination, roughness differentiation, stereognosis and barognosis subtests of the MTT, and precision pinch performance were used to examine the sensory and sensorimotor status of the hand.The worst results in all sensibility tests were found for the patients with PNI (P.001) in comparison with the controls. Multiple linear regression analysis showed the MTT was a better indicator for predicting the sensorimotor capacity of hands in the patients with PNI (r(2)=.189, P=.003) than the traditional test (r(2)=.088, P=.051). The results of the receiver operating characteristic curve estimation show that the area under the curve was .968 and .959 for the roughness differentiation and stereognosis subtests, respectively, and .853 for the barognosis subtest, therefore revealing the accuracy of the MTT in assessing sensorimotor status for patients with PNI.This study indicates that the MTT is highly accurate and a significant predictor of sensorimotor performance in hands of patients with PNI. The MTT could therefore help clinicians obtain a better understanding of the sensorimotor and functional status of the hand with nerve injuries.

Studies have demonstrated that exposure to extreme outdoor temperatures increases cardiovascular disease mortality and morbidity. However, people spend 80%–90% of their time indoors, and the cumulative effects of exposure to high or low temperature on the risk of cardiovascular diseases had not been considered. This study investigated the cumulative effects of high or low indoor temperature exposure on the risk of cardiovascular diseases. We estimated indoor temperatures by using a prediction model of indoor temperature from a previous study and further calculated the cumulative degree hours at different indoor temperature ranges. Samples of emergency department visits due to cardiovascular diseases were collected from the Longitudinal Health Insurance Database (LHID) from 2000 to 2014 in Taiwan. We used a distributed lag nonlinear model to analyze the data. Our data demonstrated a significant risk of emergency department visits due to cardiovascular diseases at 27, 28, 29, 30, and 31 °C when cooling cumulative degree hours exceeded 62, 43, 16, 1, and 1 during the hot season (May to October), respectively, and at 19, 20, 21, 22, and 23 °C when heating cumulative degree hours exceeded 1, 1, 1, 11, and 33 during the cold season (November to April), respectively. Cumulative degree hours were different according to gender and age groups. Policymakers should further consider the cumulative effects to prevent hot- or cold-related cardiovascular diseases for populations.

In this study, a coupled Eulerian-Lagrangian (CEL) technique was used to investigate the dynamic behaviors of granular material, including the collapse of a granular column and the interaction between granular flow and a rigid barrier. The CEL technique, combining Eulerian and Lagrangian algorithms, is capable of overcoming mesh distortions of conventional finite element approaches. By validating well-established experiments, the development of progressive failure in the granular column can be accurately simulated using the equations of state (EOS) and Bingham plastic constitutive models, and the granular flow impact force on the rigid barrier based on the small-scale CEL model shows good agreement with the data measured in flume tests. The impact force simulated by the CEL technique was compared with the predictions of empirical hydrostatic and hydrodynamic models, which are the approaches generally used to estimate the granular flow impact force in engineering practice. In addition, a normalized parameter S Velocity was proposed to obtain a representative velocity and height of the granular flow from the CEL analysis to improve the accuracy of empirical approaches. The proposed parameter could benefit the in-situ monitoring of potential granular flow disasters and demonstrates the applicability of the CEL technique in practical engineering.

Protein microparticles have received attention as drug delivery systems because of their high protein stability and prolonged release in vivo. However, most current preparation processes introduce chemical crosslinkers, which often lead to protein inactivation and limit drug efficacy in delivery systems. In this study, we employed the well-known hexahistidine (His)-tag recombinant protein technology and a metal-triggerable collagen-mimetic peptide to enhance the binding strength between the protein and metal ion and fine-tuned the protein drug release. His-tagged proteins self-assembled to form microparticles (∼2 μm) upon zinc ion treatment and sustained protein drug release was achieved in physiological saline. The results also indicated that by adjusting the peptide concentration and N- and C-terminal hexahistidine-tags, protein release could be controlled. Moreover, no protein denaturation was observed. We developed a universal strategy for facile protein microparticle fabrication under mild conditions and we demonstrated its potential as a therapeutics formulation with tunable protein release.

A strong edge-coloring of a graph is a function that assigns to each edge a color such that two edges within distance two apart receive different colors. The strong chromatic index of a graph is the minimum number of colors used in a strong edge-coloring. This paper determines strong chromatic indices of cacti, which are graphs whose blocks are cycles or complete graphs of two vertices. The proof is by means of jellyfish graphs.

Photodynamic therapy, that is, excitation of a photosensitizer with light to generate reactive oxygen species such as singlet oxygen, has emerged as a noninvasive technique for cancer theranostics. However, the clinical use of many photosensitizers is impeded by their hydrophobicity, the nonspecific damage they cause to normal tissues, and their susceptibility to environmental degradation. In this study, we developed a simple electrostatic adsorption strategy to fabricate aptamer-silica nanocomposites by sequentially functionalizing nanocomposites with the cell surface-associated mucin 1 aptamer for tumor targeting and a hydrophilic photosensitizer, methylene blue, for photodynamic therapy applications. We investigated the relationship between the biophysical properties and cellular uptake of such nanocomposites to improve their formulation. Effective generation of singlet oxygen was achieved with a low photosensitizer dosage (0.5 μM) and a short, low-power irradiation (1 min, 10 mW/cm(2)). With the current strategy, the efficiency of photodynamic therapy was determined by the cellular uptake of nanocomposites and the targeting molecules used.

Photoaging is recognized as the factor damaging skin-barrier function. The aim of this study was to examine the impact of ultraviolet (UV) irradiation on the cutaneous penetration of soft nanoparticles, including nanostructured lipid carriers (NLCs) and poly(lactic-co-glycolic acid) polymer nanoparticles (PNs). In vitro cutaneous permeation of retinoic acid (RA) carried by nanoparticles was evaluated. In vivo nude mouse skin distribution of topically applied nanoparticles was observed by fluorescence and confocal microscopies. The association of nanoparticles with cultured keratinocytes was measured by flow cytometry and fluorescence microscopy. The average diameter and surface charge were 236 nm and −32 mV for NLCs, and 207 nm and −12 mV for PNs. The ultrastructural images of skin demonstrated that the application of UV produced a loss of Odland bodies and desmosomes, the organelles regulating skin-barrier function. UVA exposure increased skin deposition of RA regardless of nanoparticle formulation. UVB did not alter RA deposition from nanoparticles as compared to the non-treated group. Exposure to UVA promoted RA delivery into hair follicles from NLCs and PNs by 4.2- and 4.9-fold, respectively. The in vivo skin distribution also showed a large accumulation of Nile red-loaded nanoparticles in follicles after UVA treatment. The soft nanoparticles were observed deep in the dermis. PNs with higher lipophilicity showed a greater association with keratinocytes compared to NLCs. The cell association of PNs was increased by UVA application, whereas the association between NLCs and keratinocytes was reduced two times by UVA. It was concluded that both follicles and intercellular spaces were the main pathways for nanoparticle diffusion into photodamaged skin.

This study develops an antenatal care information system to assist women during pregnancy. We designed and implemented the system as both a web-based service and a multi-platform application for smartphones and tablets. The proposed system has three novel features: (1) web-based maternity records, which contains concise explanations of various antenatal screening and diagnostic tests; (2) self-care journals, which allow pregnant women to keep track of their gestational weight gains, blood pressure, fetal movements, and contractions; and (3) health education, which automatically presents detailed information on antenatal care and other pregnancy-related knowledge according to the women's gestational age. A survey was conducted among pregnant women to evaluate the usability and acceptance of the proposed system. In order to prove that the antenatal care was effective, clinical outcomes should be provided and the results are focused on a usability evaluation.

Using polymeric surfaces is a novel way to control crystallization. However, the mechanism is still ambiguous. In the present study, chitosan (CS) films that were doped with different molecules were employed to investigate the impact of surface chemistry on the heterogeneous crystallization behavior of acetaminophen (APAP). Crystal growth rate and crystallization kinetic measurements of APAP on various substrates were performed. Fourier transform infrared spectroscopy was used to probe intermolecular interactions between APAP and CS films. The results were interpreted with the aid of molecular simulations. It was found that substrates with more hydrogen bonding groups that could interact with APAP promoted its crystallization.

Objective To estimate the lifetime gain in the health-related quality of life (HRQOL) from early detection of cervical cancer. Methods A consecutive, cross-sectional sample of 421 patients with cervical cancer was administered the World Health Organization Quality of Life-brief version questionnaires. A nationwide sample of 22,543 patients with invasive cervical cancer (ICC) was collected from the national cancer registry for estimation of lifetime survival function from 1998 to 2007, which was further multiplied by the ratio of HRQOL score functions for patients with ICC and patients with carcinoma in situ (CIS), and summed up over lifetime to obtain expected relative-quality-adjusted survival. The difference between lifetime survival and the expected relative-quality-adjusted survival gives the expected total dissatisfied time during the life course. Results In comparison with patients with CIS postconization, patients with ICC showed consistently lower scores in the physical and psychological domains and that of sexual life after adjustment for other risk factors. The expected years of life lost for an invasive cancer was 6.48 years using the general population as the reference cohort, while the durations of equivalent to living with a very dissatisfied HRQOL were 1.71 and 0.25 for the physical and psychological domains, respectively, and 1.47 years for sexual life. Validation of the extrapolation method based on a subcohort followed from the 6th to the 13th year shows a relative bias of 0.4%. Sensitivity analysis with 37,000 CIS cases as the reference cohort yields a similar result. Conclusions Early detection of cervical cancer not only avoids premature mortality but also prevents long-term living under lower HRQOL scores, including sexual life.

To investigate how the severity levels revealed in a nerve conduction study (NCS) affect the results of the Manual Tactile Test (MTT) for patients with carpal tunnel syndrome (CTS), and to examine the relationships between the results of the MTT and precision pinch performance.Case-control studies.Hospital and local community.Patients with CTS (N=70) with 119 affected hands were studied. A control group matched by age, sex, and hand dominance was also recruited.Not applicable.CTS severity was determined based on NCS findings. The MTT, traditional sensory tests, and precision pinch performance were used to examine the functional sensory status of the hand from different perspectives.The patients with CTS exhibited deterioration in all of the sensibility tests (P.001). The results showed that the MTT could classify subgroups of severity in CTS (P.001). A moderate correlation was found between the results of the MTT and precision pinch performance (r=.526-.585, P.001). Multiple linear regression analysis showed that the MTT results were useful indicators for predicting precision pinch performance and differentiating severity in subjects with CTS (r(2)=.376 and .323, respectively).The findings indicate that the MTT could be a valid and useful assessment for hand sensibility and prehensile pinch performance in patients with CTS.

A core principle of organic farming is the reliance on internal nutrient recycling, favoring nutrient sources produced on farms (e.g.,manures) as opposed to those that are not (e.g., processed fertilizers, municipal compost). Soil fertility management varies tremendously among organic vegetable production systems, potentially with large effects on crop productivity, the environment, and trade-offs between them. We compared four certified organic systems using manure, municipal waste compost, and/or processed fertilizers to grow a mix of vegetable crops with variable nutrient demand. The four systems added nutrients to meet recommended nitrogen (N) inputs, estimated phosphorus (P) removal, or both, with different trade-offs expected between crop yields and environmental impacts depending on the imbalance in N:P ratio between fertility sources and crop removal. Municipal compost minimized trade-offs between yields and environmental impacts for crops with a low N demand (e.g.,beet). In these systems, we observed higher carbon inputs (2–6 fold), and lower residual soil N (40–50%) and nitrous oxide (N2O) emissions (50–75%) compared to systems based on manures or processed fertilizers. In contrast, the manure-based system had the highest crop yields when N demand was high (e.g., cauliflower), but also the highest environmental impacts. Using processed fertilizers instead of manure typically lowered N2O emissions (45%) and P surpluses (85%), but it also reduced yields (10%). Overall, our results confirm the need to develop high-yielding organic vegetable systems that minimize environmental impacts and the challenge of minimizing farm-scale yield-environment trade-offs without relying on off-farm fertility sources.

This research investigates the impact of hotel employees' core self-evaluations on their service effort and service sabotage behaviors. Included is examination of leader-member exchange moderating relationships. The study was conducted with the participation of employees of eight Taiwanese five-star hotels. Convenience sampling was used in obtaining data from 295 employees. Analysis using regression based methods shows that (1) stronger employee core self-evaluations are associated with higher service effort; (2) stronger employee core self-evaluations are negatively related to service sabotage; (3) leader-member exchange moderates the relationship between employee core self-evaluations and service effort; and (4) leader-member exchange moderates the relationship between employee core self-evaluations and service sabotage. Implications for managerial practice, research limitations and future research directions are discussed.

To (1) develop the Manual Tactile Test (MTT) for evaluating the hand perception to distinguish objects' characteristics; (2) establish the reliability and validity of the MTT for patients with carpal tunnel syndrome (CTS); and (3) integrate a normative database into the test.Cohort and case-control studies.Hospital and local community.Participants included patients with CTS (n=70) and healthy volunteers (n=125). Twenty young volunteers were enrolled to evaluate the reliability of the test. Seventy patients with CTS and 70 age- and sex-matched controls were recruited to establish the discriminate validity and receiver operating characteristic (ROC) curves for the MTT. A normative database was constructed from 125 healthy, right-handed participants.Not applicable.The MTT was designed to discriminate the characteristics of the objects' weight (barognosis test), texture (roughness differentiation test), and shape (stereognosis test) via active hand exploration. The times required discriminating the characteristics of objects and the accuracy of judgment were recorded and analyzed.High Cronbach alpha values (.83-.91) and small coefficient of variation (.10-.16) values showed that the MTT is a reliable testing tool. The results significantly discriminated the patients from the control group (P.001). The sensitivity and specificity were .64 to .81 and .73 to .76, respectively, for the 3 subtests. The ROC curve area for the 3 subtests ranged from .70 to .84. The results of the MTT obtained from 125 healthy subjects showed that age significantly affects hand perceptive function (P.001).The MTT is a reliable, accurate, and valid tool for determining the impairment of manual touch sensibility for CTS and can help clinicians understand age-related degradation in sensorimotor control of the hand in the elderly population.

Implant-associated bacterial infections are one of the most serious complications in orthopedic surgery. Treatment of these infections often requires multiple operations, device removal, long-term systemic antibiotics, and extended rehabilitation, and is frequently ineffective, leading to worse clinical outcomes and increased financial costs. In this study, we evaluated silver nanoparticle/poly(DL-lactic-co-glycolic acid) (PLGA)-coated stainless steel alloy(SNPSA) as a potential antimicrobial implant material. We found that SNPSA exhibited strong antibacterial activity in vitro and ex vivo, and promoted MC3T3-E1 pre-osteoblasts proliferation and maturation in vitro. Furthermore, SNPSA implants induced osteogenesis while suppressing bacterial survival in contaminated rat femoral canals. Our results indicate that SNPSA has simultaneous antimicrobial and osteoinductive properties that make it a promising therapeutic material in orthopedic surgery.