Investigation of the photolysis process of benzo(a)anthracene (BaA) on polyvinyl chloride (PVC) and polystyrene (PS) microplastics: Plastics aging effect, transformation products and toxicity assessment.

Microplastics (MPs) and persistent pollutants (POPs) are new pollutants that are extensively studied worldwide. To fill the gaps that the degradation processes and mechanisms of polycyclic aromatic hydrocarbons (PAHs) on the surface of most MPs are still unclear, the photochemical transformation of benzo(a)anthracene (BaA) on polyvinyl chloride (PVC) MPs and polystyrene (PS) MPs in water were investigated and compared. The photolysis of BaA on the surface of PS in water proceeded easier than that on PVC within the 48 h irradiation period, with the pseudo-first-order rate constant of 0.0489 min-1 and 0.0181 min-1, respectively, which can be ascribed to the smaller particle size and more OH production of PS MPs. Due to the light competition between the chromophore and BaA as well as the light-shielding effect, aged MPs showed an inhibitory effect on the degradation of BaA compared with pristine MPs. For BaA/PVC MPs system, the degradation of BaA in real water was not significantly affected by coexisting ions and humic acid (HA) (p < 0.05), while slight inhibitory effect on the degradation of BaA appeared for PS MPs in different water matrices (UP: 86.97 %, YR: 84.47 %, PR: 81.42 % and HR: 83.21 %). According to the electron paramagnetic resonance (EPR) test, quenching experiment and probe experiment, the relative contribution of direct photolysis (PVC: 82.02 %; PS: 69.54 %) and indirect photolysis (PVC: 17.98 %; PS: 30.46 %) was confirmed. A total of 14 products were identified, and the product types were not affected by plastics aging. The results of the toxicity assessment indicated that although some intermediate products remained toxic to aquatic organisms, the toxicity of most products was lower than that of BaA. This study provides new insights into the environmental fate of PAHs and the role of MPs in the photolysis process of contaminants in surface water.

Efficacy and safety of Lianhua Qingwen capsules combined with standard of care in the treatment of adult patients with mild to moderate COVID-19 (FLOSAN): protocol for a randomized, double-blind, international multicenter clinical trial.

Background: Effective anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs are not only the next defense after vaccines but also the key part of establishing a multi-tiered coronavirus disease 2019 (COVID-19) prevention and control system. Previous studies had indicated that Lianhua Qingwen (LHQW) capsules could be an efficacious Chinese patent drug for treating mild to moderate COVID-19. However, pharmacoeconomic evaluations are lacking, and few trials have been conducted in other countries or regions to evaluate the efficacy and safety of LHQW treatment. So, this study aims to explore the clinical efficacy, safety, and economy of LHQW for treating adult patients with mild to moderate COVID-19. Methods: This is a randomized, double-blind, placebo-controlled, international multicenter clinical trial protocol. A total of 860 eligible subjects are randomized at a 1:1 ratio into the LHQW or placebo group to receive two-week treatment and follow-up visits on days 0, 3, 7, 10, and 14. Clinical symptoms, patient compliance, adverse effects, cost scale, and other indicators are recorded. The primary outcomes will be the measured median time to sustained improvement or resolution of the nine major symptoms during the 14-day observation period. Secondary outcomes regarding clinical efficacy will be evaluated in detail on the basis of clinical symptoms (especially body temperature, gastrointestinal symptoms, smell loss, and taste loss), viral nucleic acid, imaging (CT/chest X-ray), the incidence of severe/critical illness, mortality, and inflammatory factors. Moreover, we will assess health care cost, health utility, and incremental cost-effectiveness ratio (ICER) for economic evaluation. Discussion: This is the first international multicenter randomized controlled trial (RCT) of Chinese patent medicine for the treatment of early COVID-19 in accordance with WHO guidelines on COVID-19 management. This study will help clarify the potential efficacy and cost-effectiveness of LHQW in the treatment of mild to moderate COVID-19, facilitating decision-making by healthcare workers. Registration: This study is registered at the Chinese Clinical Trial Registry, with registration number: ChiCTR2200056727 (date of first registration: 11/02/2022).

The serum uric acid is longitudinally related to patients global assessment of disease activity in male patients with axial spondyloarthritis.

OBJECTIVES: To investigate longitudinal relationship between serum uric acid (SUA) and disease activity among Chinese males with axial spondyloarthritis (axSpA). METHODS: Two-year data from the NASA study cohort of male patients with axial spondyloarthritis were analyzed. Patients global assessment of disease activity (PtGA), BASDAI, ASDAS-CRP, BASFI, and SF-36 were used as the outcomes. The autoregressive Generalized Estimation Equation (GEE) model was used to investigate the longitudinal relationship between SUA and the above outcomes. Age and gender and symptom duration were tested as effect modifiers or confounders. RESULTS: In total, 102 male axSpA patients were included, 33.3% of who were hyperuricemia at baseline. Over time,serum uric acid levels associated with the global assessment of patient global assessment of disease activity (PtGA)[P=0.041, ß=-2.059,95%CI(-4.032, -0.086)], SF-36: Vitality (VT) [P=0.01, ß=1.751, 95%CI (0.415,3.087)], SF-36: Social Functioning (SF)[P=0.002, ß= 2.968,95%CI (1.067,4.869)]). And these relationgships were independent of age, symptom duration, baseline uric acid levels, and medication use. CONCLUSIONS: In summary, SUA levels is longitudinally related to PtGA and mental health assessment. Age, gender and symptom duration do not have an impact on the relationships.

Association between staff turnover and nursing home quality - evidence from payroll-based journal data.

BACKGROUND: Staff turnover is considered an important indicator of nursing home quality. We used auditable staffing data from the Centers for Medicare & Medicaid Services (CMS) Payroll-Based Journal (PBJ) system to calculate turnover measures for nurse staff and administrators and examined the relationship between turnover and nursing home quality. METHODS: Our analyses included data from 13,631 nursing homes that submitted complete staffing data through PBJ for 2018Q3 - 2019Q4. We identified turnover based on gaps in days worked by eligible employees, allowing us to calculate turnover measures that do not depend on termination dates reported by nursing homes, which are not captured in PBJ. We linked staff turnover measures to nursing home quality measures and star ratings published on CMS' Care Compare website in January 2020 and examined the relationship between turnover and quality of care. We used ordinary least squared models for continuous outcomes and ordered logit models for categorical outcomes, controlling for facility, and county characteristics. RESULTS: Mean annual turnover rates were about 44% for RNs and 46% for total nurse staff. On average, there was one administrator leaving each nursing home during this period although about half of nursing homes had no administrator turnover. Turnover rates varied greatly across nursing homes. For-profit and larger nursing homes had higher turnover rates. Higher turnover was consistently associated with lower quality of care. CONCLUSIONS: Our study highlights the importance of staff turnover due to its relationship to nursing home quality. In January 2022, CMS started posting turnover measures on Care Compare to allow consumers to use this information in their assessment of nursing home quality and to motivate nursing homes to implement innovative strategies to retain staff. While these actions are challenging, they are nonetheless warranted for improving the quality of care for nursing home residents.

Development and Application of the Placebo Response Model in Clinical Trials for Primary Sjögren's Syndrome.

This study aimed to develop a placebo response model for pharmaceutical clinical trials of primary Sjogren's syndrome,and to quantitatively analyze the distribution and related factors influencing the placebo response to further optimize the design of clinical trials and evaluate the results of single-arm clinical trials. Public databases, including PubMed, Embase, and Cochrane Library were searched for reports on randomized placebo-controlled trials for Sjögren's syndrome which used the change from baseline in ESSDAI score as the primary outcome. The model-based meta-analysis method was used to evaluate the time course and the related influencing factors of the placebo response for ESSDAI in such clinical trials. A virtual placebo control group was constructed based on the final placebo response model to determine the treatment efficacy of belimumab and cyclosporine A for primary Sjögren's syndrome in a single-arm study. A total of 12 studies involving 450 subjects were included in the analysis. The established model described the time-course characteristics of the changes in ESSDAI score from the baseline in the 48 weeks placebo group. We found that the onset time of placebo response was approximately 12 weeks, and its efficacy plateaued at 48 weeks. The baseline ESSDAI score had a significant effect on the maximum value of the placebo response; the maximum value of the placebo response decreased by 0.552 for every 1 score rise in the baseline ESSDAI score. The efficacy of belimumab and cyclosporine A in the single-arm trial was comparable to that of the placebo response at the same baseline; no significant therapeutic advantage was observed. The placebo response model established in this study could provide a basis for designing clinical trials for primary Sjogren's syndrome in the future. It may also provide a reliable external efficacy control standard for single-arm clinical trials.

Association of Participation in the Oncology Care Model With Medicare Payments, Utilization, Care Delivery, and Quality Outcomes.

IMPORTANCE: In 2016, the US Centers for Medicare & Medicaid Services initiated the Oncology Care Model (OCM), an alternative payment model designed to improve the value of care delivered to Medicare beneficiaries with cancer. OBJECTIVE: To assess the association of the OCM with changes in Medicare spending, utilization, quality, and patient experience during the OCM's first 3 years. DESIGN, SETTING, AND PARTICIPANTS: Exploratory difference-in-differences study comparing care during 6-month chemotherapy episodes in OCM participating practices and propensity-matched comparison practices initiated before (January 2014 through June 2015) and after (July 2016 through December 2018) the start of the OCM. Participants included Medicare fee-for-service beneficiaries with cancer treated at these practices through June 2019. EXPOSURES: OCM participation. MAIN OUTCOMES AND MEASURES: Total episode payments (Medicare spending for Parts A, B, and D, not including monthly payments for enhanced oncology services); utilization and payments for hospitalizations, emergency department (ED) visits, office visits, chemotherapy, supportive care, and imaging; quality (chemotherapy-associated hospitalizations and ED visits, timely chemotherapy, end-of-life care, and survival); and patient experiences. RESULTS: Among Medicare fee-for-service beneficiaries with cancer undergoing chemotherapy, 483 319 beneficiaries (mean age, 73.0 [SD, 8.7] years; 60.1% women; 987 332 episodes) were treated at 201 OCM participating practices, and 557 354 beneficiaries (mean age, 72.9 [SD, 9.0] years; 57.4% women; 1 122 597 episodes) were treated at 534 comparison practices. From the baseline period, total episode payments increased from $28 681 for OCM episodes and $28 421 for comparison episodes to $33 211 for OCM episodes and $33 249 for comparison episodes during the intervention period (difference in differences, -$297; 90% CI, -$504 to -$91), less than the mean $704 Monthly Enhanced Oncology Services payments. Relative decreases in total episode payments were primarily for Part B nonchemotherapy drug payments (difference in differences, -$145; 90% CI, -$218 to -$72), especially supportive care drugs (difference in differences, -$150; 90% CI, -$216 to -$84). The OCM was associated with statistically significant relative reductions in total episode payments among higher-risk episodes (difference in differences, -$503; 90% CI, -$802 to -$204) and statistically significant relative increases in total episode payments among lower-risk episodes (difference in differences, $151; 90% CI, $39-$264). The OCM was not significantly associated with differences in hospitalizations, ED visits, or survival. Of 22 measures of utilization, 10 measures of quality, and 7 measures of care experiences, only 5 were significantly different. CONCLUSIONS AND RELEVANCE: In this exploratory analysis, the OCM was significantly associated with modest payment reductions during 6-month episodes for Medicare beneficiaries receiving chemotherapy for cancer in the first 3 years of the OCM that did not offset the monthly payments for enhanced oncology services. There were no statistically significant differences for most utilization, quality, and patient experience outcomes.

Disease burden from COVID-19 symptoms among inpatients at the temporary military hospitals in Wuhan: a retrospective multicentre cross-sectional study.

OBJECTIVES: We aimed to establish a set of disability weights (DWs) for COVID-19 symptoms, evaluate the disease burden of inpatients and analyse the characteristics and influencing factors of the disease. DESIGN: This was a multicentre retrospective cross-sectional descriptive study. SETTING: The medical records generated in three temporary military hospitals in Wuhan. PARTICIPANTS: Medical records of 2702 inpatients generated from 5 February to 5 April 2020 were randomly selected for this study. PRIMARY AND SECONDARY OUTCOME MEASURES: DWs of COVID-19 symptoms were determined by the person trade-off approach. The inpatients' medical records were analysed and used to calculate the disability-adjusted life years (DALYs). The mean DALY was evaluated across sex and age groups. The relationship between DALY and age, sex, body mass index, length of hospital stay, symptom duration before admission and native place was determined by multiple linear regression. RESULTS: For the DALY of each inpatient, severe expiratory dyspnoea, mild cough and sore throat had the highest (0.399) and lowest (0.004) weights, respectively. The average synthetic DALY and daily DALY were 2.29±1.33 and 0.18±0.15 days, respectively. Fever and fatigue contributed the most DALY at 31.36%, whereas nausea and vomiting and anxiety and depression contributed the least at 7.05%. There were significant differences between sex and age groups in both synthetic and daily DALY. Age, body mass index, length of hospital stay and symptom duration before admission were strongly related to both synthetic and daily DALY. CONCLUSIONS: Although the disease burden was higher among women than men, their daily disease burdens were similar. The disease burden in the younger population was higher than that in the older population. Treatment at the hospitals relieved the disease burden efficiently, while a delay in hospitalisation worsened it.

Differentiating Westlake Longjing tea from the first- and second-grade producing regions using ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics in combination with chemometrics.

There are numerous articles published for geographical discrimination of tea. However, few research works focused on the authentication and traceability of Westlake Longjing green tea from the first- and second-grade producing regions because the tea trees are planted in a limited growing zone with identical cultivate condition. In this work, a comprehensive analytical strategy was proposed by ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based untargeted metabolomics coupled with chemometrics. The automatic untargeted data analysis strategy was introduced to screen metabolites that expressed significantly among different regions. Chromatographic features of metabolites can be automatically and efficiently extracted and registered. Meanwhile, those that were valuable for geographical origin discrimination were screened based on statistical analysis and contents in samples. Metabolite identification was performed based on high-resolution mass values and tandem mass spectra of screened peaks. Twenty metabolites were identified, based on which the two-way encoding partial least squares discrimination analysis was built for geographical origin prediction. Monte Caro simulation results indicated that prediction accuracy was up to 99%. Our strategy can be applicable for practical applications in the quality control of Westlake Longjing green tea.

The Effects of Chains on the Measurement of Competition in the Nursing Home Industry.

Consistently accounting for more than 50% of the nursing homes in the United States, corporate chains have played an important role in the industry for several decades. However, few studies have explicitly considered the role of chains in measuring competition in nursing home markets. In this study, we use a newly developed database tracking common ownership over a period of nearly two decades to compare chain-adjusted and unadjusted measures of competition at the county and 25 km fixed-radius levels and explore how the differences would affect the assessment of local market structure. On average, the chain-adjusted Herfindahl-Hirschman Indexes (HHIs) are about 0.02 higher than the unadjusted HHIs. Each year, about 20% to 22% of the counties would appear more concentrated when recalculating HHIs accounting for common ownership. Evidence suggests that nursing home chains tend to focus more on expanding access to new markets within a state than to increasing market power within a smaller local market.

Full-Reference Stability Assessment of Digital Video Stabilization Based on Riemannian Metric.

Assessing the quality of the motion stability is important to evaluating the performance of video stabilization algorithms. This paper presents a novel quality assessment scheme for the video motion stability in a full-reference (FR) manner. Given ideally stable videos and their corresponding shaky videos, our method measures the geodesic distance between motion paths of the stable and the stabilized videos. Due to the use of the Riemannian metric defined on the manifold of spatial transformations, our method enables the intrinsic and faithful measurement on pairwise motion disparities. To facilitate the FR assessment, a data set of stable and shaky videos is constructed by directly capturing realistic stable/shaky videos with a customized device. Then, digital video stabilization algorithms can be run on shaky videos to obtain the stabilized sequence of frames, whereupon their performances are evaluated by using our stability assessment. The experiments demonstrate that our stability assessment gains good concordance with the subjective assessment.

Nursing Home Chain Affiliation and Its Impact on Specialty Service Designation for Alzheimer Disease.

Specialty care units (SCUs) in nursing homes (NHs) grew in popularity during the 1990s to attract residents while national policies and treatment paradigms changed. Alzheimer disease has consistently been the dominant form of SCU. This study explored the extent to which chain affiliation, which is common among NHs, affected SCU bed designation. Using data from the Online Survey Certification and Reporting (OSCAR) from 1996 through 2010 with 207 431 NH-year observations, we described trends and compared chain-affiliated NHs with independent NHs. Designation of beds for Alzheimer disease SCUs grew from 1996 to 2003 and then declined. At the peak, 19.6% of all NHs had at least one Alzheimer disease SCU bed. In general, chain affiliation promoted Alzheimer disease SCU bed designation across time, chain size, and NH profit status. During the period of largest growth from 1996 to 2003, the likelihood of designation of Alzheimer disease SCU beds was 1.55 percentage points higher among for-profit NHs affiliated with large chains than independent for-profit NHs ( P < .001) and remained 1.28 percentage points higher from 2004 to 2010. However, chain-affiliated NHs generally had a lower percentage of residents with dementia than independent NHs. For example, although for-profit NHs affiliated with large chains had more Alzheimer disease SCU beds, they had nearly 3% fewer residents with dementia than independent NHs ( P < .001). We conclude that organizational decisions to designate beds for Alzheimer disease SCUs may be related to marketing strategies to attract residents since adoption of Alzheimer disease SCUs has fluctuated over time, but did not appear driven by demand.

User roles and contributions during the new product development process in collaborative innovation communities.

Collaborative innovation (co-innovation) community emerges as a new product design platform where companies involve users in the new product development (NPD) process. Large numbers of users participate and contribute to the process voluntarily. This exploratory study investigates the heterogeneous roles of users based on a global co-innovation project in online community. Content analysis, social network analysis and cluster method are employed to measure user behaviors, distinguish user roles, and analyze user contributions. The study identifies six user roles that emerge during the NPD process in co-innovation community: project leader, active designer, generalist, communicator, passive designer, and observer. The six user roles differ in their contribution forms and quality. This paper contributes to research on co-innovation in online communities, including design team structure, user roles and their contribution to design task and solution, as well as user value along the process. In addition, the study provides practices guidance on implementing project, attracting users, and designing platform for co-innovation community practitioners.

Decolorization of azo dye C.I. Reactive Black 5 by ozonation in aqueous solution: influencing factors, degradation products, reaction pathway and toxicity assessment.

In this study, ozonation treatment of C.I. Reactive Black 5 (RB5) was investigated at various operating parameters. The results showed that the aqueous solution initially containing 200 mg/L RB5 was quickly decolorized at pH 8.0 with an ozone dose of 3.2 g/h. Reaction intermediates with m/z 281, 546, 201, 350, 286 and 222 were elucidated using liquid chromatography-mass spectrometry, while sulfate ion, nitrate ion and three carboxylic acids (i.e., oxalic acid, formic acid, and acetic acid) were identified by ion exchange chromatography. Thus, the cleavage of the azo bond and the introduction of OH groups in the corresponding positions were proposed as the predominant reaction pathway. The detachment of sulfonic groups was also commonly observed during the ozonation treatment. The proposed degradation mechanism was confirmed by frontier electron density calculations, suggesting the feasibility of predicting the major events in the whole ozonation process with the computational method. Compared with RB5 degradation, the reduction of total organic carbon (TOC) proceeded much more slowly, and approximately 54% TOC was removed after 4 h of ozonation. Acute toxicity tests with Photobacterium phosphoreum showed that the toxicity of reaction solution was firstly increased and then decreased to a negligible level after 160 min.

Coverage of different health insurance programs and medical costs associated with chronic hepatitis C infection in mainland China: a cross-sectional survey in 20 provinces.

BACKGROUND: Hepatitis C virus (HCV) imposes a considerable disease burden in China, with at least 10 million people chronically infected. Little is known about the financial impact of the HCV epidemic, nor about the extent to which various forms of insurance are providing HCV patients with financial protection. A cross-sectional multi-site study was conducted to acquire data that will aid policy-makers and other stakeholders in developing effective strategies to address this situation. METHODS: At 29 hospitals across China, inpatients and outpatients with chronic HCV were surveyed about their insurance coverage and medical costs. Percentages, means and medians were calculated, and differences in continuous variables among multiple groups were analyzed using the Kruskal-Wallis test or Wilcoxon two-sample test. RESULTS: Many inpatients (N = 593) and outpatients (N = 523) reported being covered by one of three major types of government health insurance, but 13 % of inpatients and 43 % of outpatients reported having no insurance. Among inpatients, the total median cost per hospitalization per patient was 8212 Renminbi (RMB). The category of expenditure with the highest median cost per hospitalization was Western medicine, followed by lab tests and Chinese medicine. The median cost per hospitalization was far higher for patients who had hepatocellular carcinoma than for those with less severe forms of liver disease. Outpatient antiviral therapy costs ranged from a median of 377 RMB for ribavirin to a median of 37,400 RMB for pegylated interferon-alpha for up to one year of treatment. CONCLUSIONS: For uninsured chronic HCV patients in China, inpatient and outpatient costs may be financially devastating. Research is needed on how different approaches to financing HCV treatment and care might improve health outcomes as well as achieve cost savings by enabling more people to be cured of HCV.

Assessment of the embryotoxicity of four Chinese herbal extracts using the embryonic stem cell test.

Rhizoma Atractylodes macrocephala, Radix Isatidis, Coptis chinensis and Flos Genkwa are common herbal remedies used by pregnant woman in China. In this study, their potential embryotoxicity was assessed using the embryonic stem cell test (EST) and a prediction model. The potential embryotoxicity of the herbs was based on three endpoints: the concentrations of the compounds that inhibited the proliferation of 50% of embryonic stem cells (ESCs) (IC50ES), the concentrations that inhibited 50% of 3T3 cells (IC503T3), and the concentrations that inhibited the differentiation of 50% of ESCs (ID50ES). The results revealed that Rhizoma Atractylodes macrocephala and Radix Isatidis are non-embryotoxic compounds. Coptis chinensis extracts appeared to demonstrated weak embryotoxicity, and Flos Genkwa exhibited strong embryotoxicity. These results may be useful in guiding the clinical use of these herbs and in expanding the application of the EST to the field of traditional Chinese medicine.

Pharmacokinetic properties and bioequivalence of two sulfadoxine/pyrimethamine fixed-dose combination tablets: a parallel-design study in healthy Chinese male volunteers.

BACKGROUND: Sulfadoxine/pyrimethamine fixed-dose combination (FDC) tablet is the long-acting portion of the antimalaria product Artecospe(®), coblister containing artesunate tablets plus sulfadoxine/pyrimethamine FDC tablets. This study was conducted to support the efficacy and tolerability of the sulfadoxine/pyrimethamine FDC tablet in the World Health Organization's (WHO) Prequalification of Medicines Programme, as well as to obtain marketing authorization in China. OBJECTIVE: The aim of the present study was to compare the pharmacokinetic profiles between a new generic and the branded reference formulation of sulfadoxine/pyrimethamine FDC tablets, and to assess the bioequivalence of the 2 products in healthy Chinese volunteers. METHODS: This single-dose, open-label, randomized, parallel-group study was conducted in healthy Chinese male volunteers who were randomly assigned (1:1) to receive a single 1500/75-mg dose (3 × 500/25-mg tablets) of either the test or reference formulation after a 12-hour overnight fast. Seventeen blood samples were obtained over a 168-hour interval, and plasma concentrations of sulfadoxine and pyrimethamine were determined by 2 separate validated liquid chromatography-isotopic dilution mass spectrometry methods. Pharmacokinetic properties (C(max), AUC(0-72), AUC(0-168), and T(max)) were calculated and analyzed statistically. The 2 formulations were to be considered bioequivalent if 90% CIs for the log-transformed ratios of C(max) and AUC(0-72) were within the predetermined bioequivalence range of 80% to 125%, in accordance with the guidelines of WHO and China's Food and Drug Administration (FDA). Tolerability was evaluated throughout the study by vital signs, physical examinations, clinical laboratory tests, 12-lead ECGs, and subject interviews on adverse events (AEs). RESULTS: Forty-six healthy subjects completed the study. The mean values of sulfadoxine C(max) (183.07 and 165.15 mg/L), AUC(0-72) (11,036.52 and 10,536.78 mg/L/h), and AUC(0-168) (22,247.05 and 21,761.02 mg/L/h) were not significantly different between the test and reference formulations, respectively. The same was true for pyrimethamine (0.55 and 0.58 mg/L, 29.85 and 31.44 mg/L/h, and 56.18 and 59.27 mg/L/h, respectively). The 90% CIs for the log-transformed ratios of C(max), AUC(0-72), and AUC(0-168) of both sulfadoxine (105.4%-116.6%, 99.3%-110.6%, and 96.4%-108.1%) and pyrimethamine (88.8%-100.9%, 89.5%-101.0%, and 88.3%-101.6%) were within the acceptance limits for bioequivalence. A total of 7 mild AEs were reported in 7 subjects (15.2%). CONCLUSIONS: The findings from this single-dose (1500/75-mg) study suggest that the test and reference formulations of sulfadoxine/pyrimethamine FDC 500/25-mg tablet have similar pharmacokinetic profiles both in terms of rate and extent of absorption. The formulations met WHO's and China's FDA regulatory criteria for bioequivalence in these healthy Chinese volunteers under fasting conditions. Both formulations were generally well-tolerated.

Simulation of the pharmacokinetics of bisoprolol in healthy adults and patients with impaired renal function using whole-body physiologically based pharmacokinetic modeling.

AIM: To develop and evaluate a whole-body physiologically based pharmacokinetic (WB-PBPK) model of bisoprolol and to simulate its exposure and disposition in healthy adults and patients with renal function impairment. METHODS: Bisoprolol dispositions in 14 tissue compartments were described by perfusion-limited compartments. Based the tissue composition equations and drug-specific properties such as log P, permeability, and plasma protein binding published in literatures, the absorption and whole-body distribution of bisoprolol was predicted using the 'Advanced Compartmental Absorption Transit' (ACAT) model and the whole-body disposition model, respectively. Renal and hepatic clearances were simulated using empirical scaling methods followed by incorporation into the WB-PBPK model. Model refinements were conducted after a comparison of the simulated concentration-time profiles and pharmacokinetic parameters with the observed data in healthy adults following intravenous and oral administration. Finally, the WB-PBPK model coupled with a Monte Carlo simulation was employed to predict the mean and variability of bisoprolol pharmacokinetics in virtual healthy subjects and patients. RESULTS: The simulated and observed data after both intravenous and oral dosing showed good agreement for all of the dose levels in the reported normal adult population groups. The predicted pharmacokinetic parameters (AUC, C(max), and T(max)) were reasonably consistent (<1.3-fold error) with the observed values after single oral administration of doses ranging from of 5 to 20 mg using the refined WB-PBPK model. The simulated plasma profiles after multiple oral administration of bisoprolol in healthy adults and patient with renal impairment matched well with the observed profiles. CONCLUSION: The WB-PBPK model successfully predicts the intravenous and oral pharmacokinetics of bisoprolol across multiple dose levels in diverse normal adult human populations and patients with renal insufficiency.

Hierarchical construction of self-standing anodized titania nanotube arrays and nanoparticles for efficient and cost-effective front-illuminated dye-sensitized solar cells.

We report on the influence of hierarchical structures, constructed via layer-by-layer assembly of self-standing titania nanotube arrays and nanoparticles, upon charge recombination and photoelectric performance of front-illuminated dye-sensitized solar cells. Both nanotubes and nanoparticles were produced by anodization rather than additionally employing other methods, providing low cost and great simplicity. Electrochemical impedance spectroscopy under AM 1.5 illumination indicates the construction of hybrid morphology has superior recombination characteristics and a longer electron lifetime than nanoparticulate systems. This enhancement with the incorporation of anodized titania nanoparticles with 1D architectures is unprecedented for solar cells. Owing to the better light harvesting efficiency, extended electron lifetime and desirable electron extraction, the short-circuit photocurrent density of solar cell is 18.89 mA cm(-2) with an overall power conversion efficiency of 8.80% and an incident photon-to-current conversion efficiency of 84.6% providing a very promising candidate for sustainable energy production with a high performance/cost ratio.

Assessment criteria for rotated stereociliary bundles in the guinea pig cochlea.

OBJECTIVE: Our study examined the relationship between variant stereociliary bundles of cochlear outer hair cells (OHCs) and auditory function to analyze assessment criteria for rotated stereociliary bundles in the guinea pig cochlea. METHODS: Auditory brainstem response and distortion product otoacoustic emission (DPOAE) were recorded on 100 guinea pigs. Variant hair cells were identified and counted by scanning electron and light microscopy. RESULTS: The most common variation observed was rotation of stereociliary bundles in the first-row OHCs (OHC1), with most 13.3% variant OHC1 rotated 90 degrees and a few 2.5% rotated 180 degrees. Occasionally, the length and angle of the 2 arms of an OHC deviated from the norm. The auditory brainstem response threshold of affected animals increased only slightly, 20- to 30-dB sound pressure level. More importantly, amplitude of DPOAE increased significantly (40.5 dB sound pressure level). CONCLUSION: Our study suggests that rotation of stereociliary bundles in the cochlear OHC was found to be prevalent in 28% of the animals. We established the assessment criteria for rotated stereociliary bundles that were more than 10% OHC1 rotated. This hair bundle seemed to be rotated by 90 degrees from the normal orientation and was accompanied with changes of auditory function. Increased amplitude of DPOAE is associated with the variation of rotated OHC that might result in hearing loss.

Tympanometry assessment of 61 inbred strains of mice.

Otitis media (OM) accounts for more than 20 million clinic visits in the United States every year. Resistance to antibiotics has hampered current management of the disease. Identification of genetic factors underlying susceptibility to OM is greatly needed in order to develop alternative treatment strategies. Genetically defined inbred mouse strains offer a powerful tool for dissecting genetic and environmental factors that may lead to OM in mice. Here, we report a study of middle ear function of 61 genetically diverse inbred strains of mice using tympanometry. Of the 61 inbred strains tested, the 129P1/ReJ, 129P3/J, 129S1/SvImJ, 129X1/SvJ, A/HeJ, BALB/cJ, BUB/BnJ, C57L/J, EL/SuzSeyFrkJ, FVB/NJ, I/LnJ, LP/J, NZB/BlNJ, PL/J and YBR/Ei strains exhibited tympanograms that were statistically different from other healthy strains according to parameters including middle ear pressure, volume and compliance. These differences are most likely the result of genetic factors that, when understood, will facilitate prevention and treatment of otitis media in humans. In addition, a negative correlation between age and compliance of the tympanic membrane was discovered. This is the first report to successfully use tympanometry to measure mouse middle ear function, which has been a challenge for the hearing research field because of the mouse's tiny ear size.