Assessment of the reversibility of resistance in the absence of antibiotics and its relationship with the resistance gene's fitness cost: a genetic study with mcr-1.

BACKGROUND: The intensive use of antibiotics has resulted in strong natural selection for the evolution of antimicrobial resistance (AMR), but whether, and under what circumstances, the removal of antibiotics would result in a rapid reduction in AMR has been insufficiently explored. We aimed to test the hypothesis that in the simple, yet common, case of AMR conferred by a single gene, removing antibiotics would quickly reduce the prevalence of resistance if the AMR gene imposes a high fitness cost and costless resistance is extremely rare among its proximal mutants. METHODS: In this genetic study, to test our hypothesis, we used the mcr-1 gene in Escherichia coli, which confers resistance to the last-resort antibiotic colistin, as a model. A high-throughput reverse genetics approach was used to evaluate mcr-1 variants for their fitness cost and resistance levels relative to a non-functional construct, by measuring relative growth rates in colistin-free media and at 2 µg/mL and 4 µg/mL colistin. We identified costless resistant mcr-1 mutants, and examined their properties within the context of the sequential organisation of mcr-1's functional domains as well as the evolutionary accessibility of these mutations. Finally, a simple population genetic model incorporating the measured fitness cost was constructed and tested against previously published real-world data of mcr-1 prevalence in colonised inpatients in China since the 2017 colistin ban in fodder additives. FINDINGS: We estimated the relative growth rates of 14 742 mcr-1 E coli variants (including the wild type), 3449 of which were single-nucleotide mutants. E coli showed 73·8% less growth per 24 h when carrying wild-type mcr-1 compared with the non-functional construct. 6252 (42·4%) of 14 741 mcr-1 mutants showed colistin resistance accompanied by significant fitness costs, when grown under 4 µg/mL colistin selection. 43 (0·3%) mcr-1 mutants exhibited costless resistance, most of which contained multiple mutations. Among the 3449 single mutants of mcr-1, 3433 (99·5%) had a fitness cost when grown in colistin-free media, with a mean relative growth of 0·305 (SD 0·193) compared with the non-functional variant. 3059 (88·7%) and 1833 (53·1%) of 3449 single mutants outgrew the non-functional mcr-1 in the presence of 2 µg/mL and 4 µg/mL colistin, respectively. Single mutations that gave rise to costless mutants were rare in all three domains of mcr-1 (transmembrane domain, flexible linker, and catalytic domain), but the linker domain was enriched with cost-reducing and resistance-enhancing mutations and depleted with cost-increasing mutations. The population genetics model based on the experimental data accurately predicts the rapid decline in mcr-1 prevalence in real-world data. INTERPRETATION: Many identified costless resistant variants that consist of multiple mutations are unlikely to evolve easily in nature. These findings for colistin and mcr-1 might be applicable to other cases in which AMR entails a substantial fitness cost that cannot be mitigated in proximal mutants. FUNDING: National Natural Science Foundation of China, and National Key Research and Development Program of China.

Comprehensive Assessment of Ischemic Stroke in Nonhuman Primates: Neuroimaging, Behavioral, and Serum Proteomic Analysis.

Ischemic strokes, prevalence and impactful, underscore the necessity of advanced research models closely resembling human physiology. Our study utilizes nonhuman primates (NHPs) to provide a detailed exploration of ischemic stroke, integrating neuroimaging data, behavioral outcomes, and serum proteomics to elucidate the complex interplay of factors involved in stroke pathophysiology. We observed a consistent pattern in infarct volume, peaking at 1-month postmiddle cerebral artery occlusion (MCAO) and then stabilized. This pattern was strongly correlated to notable changes in motor function and working memory performance. Using diffusion tensor imaging (DTI), we detected significant alterations in fractional anisotropy (FA) and mean diffusivity (MD) values, signaling microstructural changes in the brain. These alterations closely correlated with the neurological and cognitive deficits that we observed, highlighting the sensitivity of DTI metrics in stroke assessment. Behaviorally, the monkeys exhibited a reliance on their unaffected limb for compensatory movements, a common response to stroke impairment. This adaptation, along with consistent DTI findings, suggests a significant impact of stroke on motor function and spatial perception. Proteomic analysis through MS/MS functional enrichment identified two distinct groups of proteins with significant changes post-MCAO. Notably, MMP9, THBS1, MB, PFN1, and YWHAZ were identified as potential biomarkers and therapeutic targets for ischemic stroke. Our results underscore the complex nature of stroke and advocate for an integrated approach, combining neuroimaging, behavioral studies, and proteomics, for advancing our understanding and treatment of this condition.

Medical behaviours and medication adherence of older hypertensive patients in different medical insurance programs in Beijing, China: a cross-sectional study.

BACKGROUND: Grassroots medical institutions are the primary "battlefield" of hypertension management based on hierarchical diagnosis and treatment policies in China. There is a considerable difference in the insured population and reimbursement ratio between different medical insurance programs. The management of hypertension directly affects the development trend of cardiovascular and cerebrovascular diseases. METHODS: To understand the difference between different medical insurance programs regarding the management of older hypertensive patients, all outpatients aged 60 and above with hypertension in the basic medical insurance database of Beijing, China, from April 1, 2019, to January 31, 2020, were included. Medical behaviours included patients' choice of hospital level, type of hospital, number of hospitals visited, grassroots medical institutions and cross-district visits. Medication adherence was evaluated by calculating the medication possession ratio of antihypertensive medications. First, we adopted a statistical description for medical behaviours and medication adherence. Then, multivariate logistic regression was used to analyse the influencing factors of medication adherence. RESULTS: This study included 1.29 million patients with Urban Employee Basic Medical Insurance (UEBMI) and 0.31 million patients with Urban‒Rural Resident Basic Medical Insurance (URRBMI). The proportions of patients with UEBMI who chose tertiary hospitals, comprehensive hospitals, grassroots medical institutions and cross-district visits were 25.84%, 56.09%, 57.34% and 39.32%, respectively, while those of patients with URRBMI were 11.14%, 60.59%, 81.28% and 6.07%, respectively. The medication adherence rates of men and women taking one medication were 61.04% and 55.86%, respectively. UEBMI patients who took their medication accounted for 62.36%, while only 40.27% of URRBMI patients adhered to their medication. The percentages of young-old, old-old and oldest-old patients who took their antihypertensive medications were 58.05%, 59.09% and 56.78%, respectively. The adherence to taking ≥ 2 medications (35.47%) was lower than that to taking one medication (58.33%). The medication adherence rates of patients with UEBMI and URRBMI for taking ≥ 2 medications were 37.21% and 27.45%, respectively. CONCLUSIONS: Patients with UEBMI were more inclined to choose tertiary hospitals and cross-district visits than patients with URRBMI. The adherence of patients with UEBMI was better than that of patients with URRBMI in China.

[Application of behavioral audiometry in subjective hearing assessment of children].

Objective:To explore the value and influencing factors of behavioral audiometry in subjective hearing assessment of children. Methods:The results of behavioral audiometry（visual reinforcement audiometry or play audiometry） of 1944 children（3888 ears） in the outpatient department from January 2012 to December 2015 were retrospectively analyzed. The subjective performance（" good ", "moderate", "poor", " unfinished "） was compared according to age and hearing level. SPSS 27.0 software was used for statistical analysis. Results:The subjective performance of children was "good" in 2791 ears（71.8%）, "moderate" in 411 ears（10.6%）, "poor" in 309 ears（7.9%） and " unfinished " in 377 ears（9.7%）. In visual reinforcement audiometry, the proportion of children who subjectively performed as "good" gradually increased with age, reaching the peak at 2 years old, and decreased with age after 2 years old. In play audiometry, the proportion of children who subjectively performed as "good" gradually increased with age, peaking at 4-5 years of age. The children who did not finish the test were mainly 1-3 years old. The reasons included uncooperation for 148 ears, crying for 95 ears, refusing to wear headphones for 57 ears, fatigue for 42 ears, lack of interest for 20 ears, not understanding for 14 ears, and distraction for 1 ear. Conclusion:Behavioral audiometry was helpful to assess children's subjective hearing, and children's subjective performance was good. In clinical work, more novel and attractive test materials and methods should be adopted or developed according to the physical and mental characteristics of young children.

Economic Burden of Major Diseases in China in 2013.

Studies on the economic burden of disease (EBD) can estimate the social benefits of preventing or curing disease. The majority of studies focus on the economic burden of a single or regional disease; however, holistic or national research is rare in China. Estimating the national EBD can provide evidence for policy makers. We used the top-down method to assess the economic burden of 30 types of diseases between urban and rural areas in China. The two-step model was used to evaluate the direct economic burden of disease (DEBD), while the human capital method was used to assess the indirect economic burden of disease (IEBD). The total economic burden of 30 types of diseases in China was between $13.39 and 803.00 billion in 2013. The average total economic burden of disease (TEBD) in cities was $81.39 billion, while diseases in villages accounted for $50.26 billion. The range of direct and indirect EBD was $5.77-494.52 billion, and the range in urban areas was $0.61-20.34 billion. The direct and indirect EBD in rural areas accounted for $5.88-277.76 billion and $0.59-11.39 billion, respectively. There was a large difference between the economic burden of different diseases. The economic burden of urban diseases was more significant than the burden for the rural. The top five most economically burdensome diseases were myocardial infarction coronary artery bypass, acute myocardial infarction, cerebral hemorrhage, acute upper gastrointestinal bleeding and acute appendicitis.

A multi-dimensional integration (MDI) strategy for MR T2 * mapping.

MRI signals are intrinsically multi-dimensional, and signal behavior may be orthogonal among different dimensions. Such dimensional orthogonality can be utilized to eliminate unwanted effects and facilitate mathematical simplicity during image processing for improved outcomes. In this work, we will demonstrate and analyze the principles and performance of a newly developed multi-dimensional integration (MDI) strategy in MR T2 * mapping. By constructing a complex signal function to extract the inter-echo signal changes, MDI solves an optimization problem by processing all signal dimensions (eg echoes, flip angles and coil channels) in one integrative step. MDI was compared with routine curve fitting methods on noise behavior, quantification accuracy and computational efficiency. All methods were tested and compared on simulation, phantom and knee data. Monte Carlo simulations were performed on simulation and all MRI data to investigate noise propagation from k space to T2 * maps. For phantom tests, T2 * values in regions of interest were extracted on a voxel-wise basis and analyzed using a paired t-test between scanning parameters and mapping methods, with p < 0.05 being significantly different. MDI facilitated a straightforward processing procedure, yielding homogeneous, high-signal-to-noise-ratio (SNR) and artifact-free T2 * maps without explicit coil combination or additional measures. Compared with routine fitting methods, MDI offered significantly (p < 0.05) improved SNR and quantitative accuracy/robustness, with two to three orders higher computational efficiency. MDI also represented low-SNR signals with low T2 * values, avoiding misinterpretation with long-T2 * species.

[Research progress on mechanisms of traditional Chinese medicine in prevention and treatment of postoperative peritoneal adhesion].

Peritoneal adhesion is one of the common complications after abdominal operation, which could seriously affect the quality of life in patients. Although the development of modern surgical technology and the improvement of doctors' operation level have reduced the incidence of peritoneal adhesion to a certain extent, due to the lack of special treatment drugs, the therapeutic effect still cannot meet the expectations and requirements of clinicians and patients. Traditional Chinese medicines(TCM) have unique advantages and remarkable curative effect in the treatment of peritoneal adhesion, and they can play an important role in regulating multiple pathological links. However, the relevant researches and product development of TCM against peritoneal adhesion have not attracted enough attention from industry scholars. As for the related work that has been carried out, most of the studies on the efficacy and mechanism are not thorough and systematic enough, seriously restricting the industrial development in this field. In this paper, the efficacy and mechanism were systematically described and summarized based on the review of papers in the recent years, so as to provide a reference for the thorough study of TCM in the prevention and treatment of peritoneal adhesions, and promote the deep development and industrialization process of related products.

Can integration reduce inequity in healthcare utilization? Evidence and hurdles in China.

BACKGROUND: Integration of medical insurance schemes has been prioritized as one of the key strategies to address inequity in China's health system. The first pilot attempt to integrate started in 2003 and later expanded nationwide. This study aims to assess its intended impact on inequity in inpatient service utilization and identify the main determinants contributing to its ineffectiveness. METHODS: A total of 49,365 respondents in the pilot integrated area and 77,165 respondents in the non-integration area were extracted from the Fifth National Health Services Survey. A comparative analysis was conducted between two types of areas. We calculate a concentration index (CI) and horizontal inequity index (HI) in inpatient service utilization and decompose the two indices. RESULTS: Insurance integration played a positive role in reducing inequality in inpatient service utilization to some extent. A 13.23% lower in HI, a decrease in unmet inpatient care and financial barriers to inpatient care in the pilot integrated area compared with the non-integration area; decomposition analysis showed that the Urban-Rural Residents Basic Medical Insurance, a type of integrated insurance, contributed 37.49% to reducing inequality in inpatient service utilization. However, it still could not offset the strong negative effect of income and other insurance schemes that have increased inequality. CONCLUSIONS: The earlier pilot attempt for integrating medical insurance was not enough to counteract the influence of factors which increased the inequality in inpatient service utilization. Further efforts to address the inequality should focus on widening access to financing, upgrading the risk pool, reducing gaps within and between insurance schemes, and providing broader chronic disease benefit packages. Social policies that target the needs of the poor with coordinated efforts from various levels and agencies of the government are urgently needed.

Assessment of serum Tim-3 and Gal-9 levels in predicting the risk of infection after kidney transplantation.

Infection remains a major cause of morbidity and mortality after kidney transplantation (KT). Reliable biomarkers to predict post-transplant infection are lacking. We investigated the predictive performance of pre- and post-transplant levels of T-cell immunoglobulin and mucin domain-3 (Tim-3) and Galectin-9 (Gal-9), two pleiotropic immunomodulatory molecules, in early identification of infection. Serum Tim-3 and Gal-9 were paired measured before and 30 days after transplantation (PTD 30) in 95 KT recipients (KTRs). The decline rates of Tim-3 and Gal-9 were calculated relative to pre-transplant levels. KTRs with infection history had significantly higher levels of PTD 30 Tim-3 and Gal-9, and slower decrease rates of Gal-9 compared to non-infected recipients, while no difference was observed between two groups regarding pre-transplant levels. The AUCs for predicting 1-year post-transplant infection were 0.653 and 0.711 for post-transplant Tim-3 and Gal-9, 0.664 and 0.670 for relative Tim-3 and Gal-9, respectively. After adjusting for potential confounders, PTD 30 Tim-3, Gal-9 and relative Gal-9 remained as independent risk factors for post-transplant infection. Our results suggested that PTD 30 Tim-3 and Gal-9 and relative decrease of Gal-9 were promising predictors for identifying KTRs with high risk of infection, while pre-transplant Tim-3 and Gal-9 showed no predictive power to infection.

HIV screening among patients seeking care at Xuanwu Hospital: A cross-sectional study in Beijing, China, 2011-2016.

OBJECTIVES: One-third of people living with HIV in China are still unaware of their status, so we sought to better understand HIV testing in the general hospital setting in China. METHODS: A cross-sectional study was conducted using the electronic medical records of all patients who attended Xuanwu Hospital in Beijing, January 1, 2011 to December 31, 2016. HIV screening and detection rates and characteristics of patients diagnosed with HIV were assessed. RESULTS: Overall, 235,961 patients were screened, for a screening rate of 1.4%. Although most were outpatients (98.4%), screening rate was higher among inpatients (70.0% versus 0.4%), and highest in internal medicine (36.1%) and surgery (33.3%) departments. A total of 140 patients were diagnosed with HIV, for a detection rate of 5.93 per 10,000. Detection rates were highest among outpatients (9.34 per 10,000), and patients attending the dermatology and sexually transmitted infection (STI) department (153.85 per 10,000). Most diagnoses were made among males (91.4%), aged 20-39 (67.1%), who reported becoming infected through homosexual contact (70.0%). CONCLUSIONS: HIV screening in China's general hospitals needs to be improved. More focus should be placed on screening outpatients, especially in the dermatology and STI department, and young men.

Efficient Using Durian Shell Hydrolysate as Low-Cost Substrate for Bacterial Cellulose Production by Gluconacetobacter xylinus.

Durian is one important tropical fruit with high nutritional value, but its shell is usually useless and considered as waste. To explore the efficient and high-value utilization of this agricultural and food waste, in this study, durian shell was simply hydrolyzed by dilute sulfuric acid, and the durian shell hydrolysate after detoxification was used for bacterial cellulose (BC) production by Gluconacetobacter xylinus for the first time. BC was synthesized in static culture for 10 days and the highest BC yield (2.67 g/L) was obtained at the 8th day. The typical carbon sources in the substrate including glucose, xylose, formic acid, acetic acid, etc. can be utilized by G. xylinus. The highest chemical oxygen demand (COD) removal (16.40%) was obtained at the 8th day. The highest BC yield on COD consumption and the highest BC yield on sugar consumption were 93.51% and 22.98% (w/w), respectively, suggesting this is one efficient bioconversion for BC production. Durian shell hydrolysate showed small influence on the BC structure by comparison with the structure of BC generated in traditional Hestrin-Schramm medium detected by FE-SEM, FTIR, and XRD. Overall, this technology can both solve the issue of waste durian shell and produce valuable bio-polymer (BC).

Expenditure of hospital care on cancer in China, from 2011 to 2015.

OBJECTIVE: A solid understanding of levels and trends of spending on cancer is important to evaluate whether our healthcare resources were wisely spent and to prioritize future resources for cancer treatment and prevention. However, studies on economic burden of cancers in China are scant and the results are inconsistent. METHODS: The Chinese hospital information database and nearly 350 million inpatient medical record data were used. As the ratios of cancer inpatient payments to total inpatient payments were mainly influenced by the grades and sites of hospitals, the estimates of payments of cancer inpatients in this study were stratified by hospital grades and provinces. Only the payments of cancer inpatients happened in grade 2, grade 3 and specialized cancer hospitals were included in the analyses. The total medical payments of cancers in China were estimated based on the ratios of outpatient payments to inpatient payments in specialized cancer hospitals. RESULTS: From 2011 to 2015, the payments of cancer inpatients in China have increased by 84.1% and the total inpatient payments reached 177.1 billion RMB in 2015, accounting for 4.3% of the total health expenditure in China. Based on the ratio of outpatient payments to inpatient payments, the total payments on cancer treatments in China were estimated to be 221.4 billion RMB in 2015. Among different cancer types, the highest payments were the treatment of trachea, bronchus and lung cancer. The major cancer inpatient payments (67.1% in 2015) spent in grade 3 general hospitals and this ratio increased continually from 2011 to 2015. The expenditure of cancer treatments also varies by region with the major expenditure in the eastern region of China. CONCLUSIONS: This study estimated the total payments of cancer treatments in China and analyzed how the money was spent on cancer treatments in the recent 5 years, which would provide information for decision makings on the allocation of resources to service provisioning, prevention strategies, research funding, and assessing whether the economic burden of cancer is affordable to the governments.

Influencing factors of inpatient expenditure pattern for cancer in China, 2015.

OBJECTIVE: We analyzed the proportion of cancer-caused hospitalization expenses in total hospitalization expenses from national authoritative data and explored influencing factors of the proportion so as to provide effective data information for more rational utilization of health resources. METHODS: Two-level lineal regression model was used to explore influencing factors of ratios of the cancer inpatient expenditure over the total inpatient expenditure of hospitals in China in 2015. A total of 40.76 million inpatient medical records were used to generate the outcome variables, while the explanatory variables were from hospital information database and China Health and Family Planning Statistical Yearbook and literatures. RESULTS: Inpatient expenditure pattern for cancer (IEPC) varied largely across provinces, ranging from 3.03% to 19.61%. The major sources of variability were from the differences of hospital level and number of beds. There was homogeneity within a province, while heterogeneity between the provinces. Rising one level of the hospital led to the increase of 0.475 natural logarithm units of IEPC averagely. The number of beds increasing 1,000 each made the natural logarithm of IEPC increase one unit averagely. CONCLUSIONS: Our study showed that a considerable proportion of IEPC variation could be explained by the differences of hospital level and number of beds. It implied that it is possible to estimate disease-specific ratio of inpatient expense taking into account key influencing factors in China. Furthermore, this study is an input to economic and financial analyses and provides evidence for future study on the national economic burden of cancer.

Integrative Cardiopulmonary Ultrasound for Interstitial Lung Disease Assessment: Correlation between Lung Ultrasound Performance and Cardiac Involvement.

The aims of this study were to apply integrative cardiopulmonary ultrasound (thoracic ultrasound) to the evaluation of patients with interstitial lung disease (ILD) and to determine the relationship between lung ultrasound signs and echocardiographic parameters such as systolic pulmonary artery pressure (SPAP) and various right ventricular parameters. ILD patients and healthy controls underwent lung ultrasound (LUS) and echocardiographic tests. In addition to traditional echocardiographic parameters, right ventricular free wall longitudinal strain (RVLS_FW) was measured using 2-D speckle-tracking echocardiography. The degree of pulmonary fibrosis or the disease severity of each ILD patient was scored with a semiquantitative scoring method, taking into account multiple LUS signs. Statistical analyses were performed to compare various parameters between ILD patients with and those without pulmonary hypertension. Correlations between the different parameters were then evaluated, and the LUS scores were used to predict pulmonary hypertension using a receiver operating characteristic curve analysis. Among the 90 patients who qualified for entry into this study, 30% (n = 27) had pulmonary hypertension. The patients with pulmonary hypertension had larger right ventricular dimensions, lower RVLS_FW and higher LUS scores. An effective correlation was found between ILD LUS scores and echocardiographic parameters, especially SPAP (r = 0.735, p < 0.001). The groups were comparable with respect to most echocardiographic parameters, with mild, moderate and severe pulmonary fibrosis, whereas SPAP was significantly higher in the moderate and severe groups. RVLS_FW was obviously reduced in the group with severe pulmonary fibrosis. Although RVLS_FW in the mild pulmonary fibrosis group was in the normal range, it was slightly reduced compared with that of the controls. A cutoff of more than 16 LUS points had 85.2% sensitivity and 80.3% specificity in predicting elevated SPAP (>36 mm Hg). Thoracic ultrasound is useful in the assessment of ILD. As ILD progresses, the structure or function of the right ventricle gradually deteriorates. LUS not only detects lung conditions in ILD, but also indirectly reflects SPAP and right ventricular function. Integrated use of LUS and echocardiography will provide an invaluable point-of-care imaging modality to facilitate the diagnosis, management and treatment of patients with ILD.

High-Resolution Transthoracic Ultrasonography for Assessment of Pleural Lines in Patients With Dyspnea With CT Comparison: An Observational Study.

OBJECTIVES: Detection of B-line in dyspneic patients is often accompanied by abnormal changes of pleural line on transthoracic ultrasonography (TUS). The aim of the study was to evaluate the relevance and diagnostic performance of pleural line abnormalities and B-lines detected on high-resolution TUS against the computed tomography (CT) findings. METHODS: Transthoracic ultrasonography was performed in patients admitted to the emergency department with dyspnea. The pleural line and accompanying B-line were assessed using a linear transducer. The TUS findings were assessed against the corresponding high-resolution CT findings in the same location, which were considered to be the gold standard. RESULTS: Out of a total of 116 patients, 68.1% had changes of the pleural line on TUS. The characteristic changes of the pleural line were classified into four types: slightly rough pleural line with confluent B-lines on TUS corresponded with CT findings of ground-glass opacity; irregular and interrupted pleural line with confluent B-lines corresponded with parenchymal infiltration; fringed pleural line with confluent B-lines corresponded with superimposed ground-glass and irregular reticular opacities; and fringed pleural line with scattered B-lines corresponded with irregularly thickened interlobular septa. Wavy pleural line indicated subpleural emphysema. The coexistence of more than one abnormal pleural line was also found in 31 cases (26.7%). CONCLUSIONS: High-resolution TUS may help in the initial assessment of lung pathology by its ability to identify pleural line abnormalities and B-lines that are shown to be associated with CT, which could add diagnostic value in the emergency evaluation of dyspneic patients.

Reproductive management through integration of PGD and MPS-based noninvasive prenatal screening/diagnosis for a family with GJB2-associated hearing impairment.

A couple with a proband child of GJB2 (encoding the gap junction protein connexin 26)-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our study aimed to develop a customized preconception-to-neonate care trajectory to fulfill this clinical demand by integrating preimplantation genetic diagnosis (PGD), noninvasive prenatal testing (NIPT), and noninvasive prenatal diagnosis (NIPD) into the strategy. Auditory and genetic diagnosis of the proband child was carried out to identify the disease causative mutations. The couple then received in-vitro-fertilization treatment, and eight embryos were obtained for day 5 biopsy. PGD was performed by short-tandem-repeat linkage analysis and Sanger sequencing of GJB2 gene. Transfer of a GJB2c.235delC heterozygous embryo resulted in a singleton pregnancy. At the 13th week of gestation, genomic DNA (gDNA) from the trio family and cell-free DNA (cfDNA) from maternal plasma were obtained for assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD showed the absence of chromosomal aneuploidy and GJB2-associated disease in the fetus, which was later confirmed by invasive procedures and postnatal genetic/auditory diagnosis. This strategy successfully prevented the transmission of hearing impairment in the newborn, thus providing a valuable experience in reproductive management of similar cases and potentially other monogenic disorders.

Cost-effectiveness analysis of an enteral nutrition protocol for children with common gastrointestinal diseases in China: good start but still a long way to go.

BACKGROUND: A standard nutrition screening and enteral nutrition (EN) protocol was implemented in January 2012 in a tertiary children's center in China. The aims of the present study were to evaluate the cost-effectiveness of a standard EN protocol in hospitalized patients. METHODS: A retrospective chart review was performed in the gastroenterology inpatient unit. We included all inpatient children requiring EN from January 1, 2010, to December 31, 2013, with common gastrointestinal (GI) diseases. Children from January 1, 2012, to December 31, 2013, served as the standard EN treatment group, and those from January 1, 2010, to December 31, 2011, were the control EN group. Pertinent patient information was collected. We also analyzed the length of hospital stay, cost of care, and in-hospital infection rates. RESULTS: The standard EN treatment group received more nasojejunal tube feedings. There was a tendency for the standard EN treatment group to receive more elemental and hydrolyzed protein formulas. Implementation of a standard EN protocol significantly reduced the time to initiate EN (32.38 ± 24.50 hours vs 18.76 ± 13.53 hours; P = .011) and the time to reach a targeted calorie goal (7.42 ± 3.98 days vs 5.06 ± 3.55 days; P = .023); length of hospital stay was shortened by 3.2 days after implementation of the standard EN protocol but did not reach statistical significance. However, the shortened length of hospital stay contributed to a significant reduction in the total cost of hospital care (13,164.12 ± 6722.95 Chinese yuan [CNY] vs 9814.96 ± 4592.91 CNY; P < .032). CONCLUSIONS: Implementation of a standard EN protocol resulted in early initiation of EN, shortened length of stay, and significantly reduced total cost of care in hospitalized children with common GI diseases.

Integrated water resources management and water users' associations in the arid region of northwest China: a case study of farmers' perceptions.

Water scarcity is a critical policy issue in the arid regions of northwest China. The local government has widely adopted integrated water resources management (IWRM), but lacks support from farmers and farm communities. We undertook a case study in the Minqin oasis of northwest China to examine farmers' responses to IWRM and understand why farmer water users' associations (WUAs) are not functioning effectively at the community level. Results of quantitative and qualitative surveys of 392 farmers in 27 administrative villages showed that over 70% of farmers disapprove of the IWRM market-based reforms. In particular, the failure of farmer WUAs can be attributed to overlapping organizational structures between the WUAs and the villagers' committees; mismatches between the organizational scale of the WUAs and practical irrigation management by the farmers themselves; marginalization of rural women in water decision-making processes; and the inflexibility of IWRM implementation. An important policy implication from this study is that rebuilding farmer WUAs is key to overcoming the difficulties of IWRM. The current water governance structure, which is dominated by administrative systems, must be thoroughly reviewed to break the vicious cycle of tension and distrust between farmers and the government.

Alterations of chemical composition, construction cost and payback time in needles of Masson pine (Pinus massoniana L.) trees grown under pollution.

Previous studies show that Masson pine (Pinus massoniana L.) stands grown at the industrially-polluted site have experienced unprecedented growth decline, but the causal mechanisms are poorly understood. In this study, to understand the mechanisms of growth decline of Mason pine strands under pollution stresses, we determined the reactive oxygen species levels and chemical composition of the current-year (C) and one-year-old (C + 1) needles, and calculated the needle construction costs (CCmass) of Masson pine trees grown at an industrially-polluted site and an unpolluted remote site. Pine trees grown at the polluted site had significantly higher levels of hydroxyl radical and superoxide anion in their needles than those grown at the unpolluted site, and the former trees eventually exhibited needle early senescence. The contents of lipids, soluble phenolics and lignins in C and C + 1 needles were significantly higher at the polluted site than at the unpolluted site, but the total amounts of non-construction carbohydrates were lower in non-polluted needles than in polluted needles. Elevated levels of the reactive oxygen species and early senescence in polluted needles together led to significant increases in CCmass and a longer payback time. We infer that the lengthened payback time and needle early senescence under pollution stress may reduce the Masson pine tree growth and consequently accelerate tree decline.

Sensitivity of Medicare claims data for measuring use of standard multiagent chemotherapy regimens.

PURPOSE: We sought to determine the accuracy with which Medicare billing data documents elderly Medicare cancer patients' receipt of common multiagent chemotherapy regimens. METHODS: We merged gold-standard clinical trial data from 406 elderly cancer patients known to be treated on 1 of 6 Cancer and Leukemia Group B (CALGB) breast, colorectal, and lung cancer trials (trial numbers; 9344, 9730, 9235,9732, 80203, 89803) with their Medicare claims data from Centers for Medicare and Medicaid Services (CMS). Comparing CMS chemotherapy codes to gold-standard CALGB treatment data, we estimated Medicare data's sensitivity at measuring the correct drugs and schedule for each of the multiagent chemotherapy regimens. RESULTS: Overall 92% (375/406) of CALGB patients had contemporaneous CMS claims indicating receipt of chemotherapy. The overall sensitivity of CMS ambulatory claims for documenting treatment with the correct drugs and on the correct schedule (ie, all drugs had to be billed on the same day) for the 5 common multiagent chemotherapy regimens was 78% (275/354) for those potentially treated in the ambulatory setting. The sensitivity was similar for all treatment regimens: carboplatin and paclitaxel 83%, 5-fluorouracil and leucovorin 80%, fluorouracil, leucovorin, and irinotecan (FOLFIRI) 76%, doxorubicin and cyclophosphamide 75%, and cisplatin and etoposide 75%. CONCLUSIONS: We correctly identified at least 3-quarters of elderly Medicare cancer patients treated on a clinical trial with standard first-line multiagent chemotherapy regimens in the ambulatory setting by applying coding algorithms to their CMS claims. The algorithms may be useful in identifying cohorts of elderly Medicare patients for observational studies of the comparative effectiveness of standard multiagent chemotherapy regimens.