The reporting quality of randomized controlled trials in pharmacotherapy for pituitary adenomas.

BACKGROUND: Medical therapy has become an increasingly important intervention owing to improvements in the multidisciplinary care for pituitary adenomas (PAs). This study aimed to assess the reporting quality of randomized controlled trials (RCTs) on PAs pharmacotherapy. METHODS: RCTs evaluating the efficacy of pharmacotherapy in PAs published in English between January 1, 1974, and December 31, 2022, were searched for and collected from PubMed and MEDLINE. The 2010 Consolidated Standards for Test Reports (CONSORT) statement-based 28 items overall quality score (OQS) was used to evaluate the overall quality of each report. RESULTS: Twenty-seven related RCTs including 1816 patients were retrieved. The median OQS score was 12 (range, 6-19) on a scale of 0 to 28. Important items, such as background, objectives, participants, interventions, and outcomes, were sufficiently reported in 100% (27/27) of the articles. Statistical methods were adequately described in 93% (25/27) of patients. However, RCTs underreported identification as randomized trials in the title (3/27, 11%), sample size, allocation concealment, implementation, ancillary analysis method, and Diagram and Ancillary analyses (1/27, 4%). The OQS of published RCTs has significantly increased since 2010 (P = .012). The multivariate final model showed significant associations between higher OQS and publication since 2010 and enrollment of more than 100 patients. CONCLUSIONS: The overall reporting quality of RCTs on pharmacotherapy in PAs was poor, based on the 2010 CONSORT statement. However, we noticed an improvement in the OQS over the years and identified the factors associated with a better report. Increased effort is necessary to raise awareness of these issues among writers, readers, reviewers, and editors.

Association between screen time and physical activity on mental health among preschoolers: a cross-sectional study from Southwest China.

BACKGROUND: Screen time and physical activity behaviors undergo development during early childhood and impact mental health. However, there is limited knowledge regarding the associations between physical activity, screen time, and mental health problems (MHP) in preschoolers. This study examines these associations using a large sample size and brief measures. METHODS: A multistage cluster stratified sampling method was used to conduct an observational cross-sectional study of 19,015 Chinese preschoolers in 2020. Information on physical activity, and screen time was collected by a self-administered questionnaire; MHP was assessed by the parent-reported Strengths and Difficulties Questionnaire (SDQ). Logistic regression models were used to obtain the odds ratios (ORs) and 95% confidence intervals (95% CIs) of preschoolers' MHP associated with screen time, total physical activities, moderate to vigorous physical activity (MVPA), and outdoor physical activities. RESULTS: A total of 19,015 participants from the 19,548 recruited population were included in the analyses (missing rate: 2.73%), 52.60% were boys. 64.01%, 57.96%, 35.98%, and 82.64% of preschoolers were reported to meet total physical activities, MVPA, and outdoor activities with screen time recommendations level. The results of multivariable-adjusted ORs (95% CIs) of preschoolers' MHP for comparisons of different levels of screen time (< 2 h/day, 2-4 h/day,≥4 h/day) show that screen time positively associated with MHP after adjusting for confounders (P < 0.05), but the association was not significant among girls with screen time ≥ 4 h/day. In addition, increased engagement in physical activity was reversely linked to MHP (P < 0.05). A stronger association between MHP and MVPA was observed in boys, however, this association was weakened when the total time spent engaging in MVPA exceeded two hours per day (P < 0.05). CONCLUSION: Less physical activity and more screen time positively relate to MHP, but the relationship differs by type of physical activity, total time, and gender. These findings provide novel insights and evidence supporting for guidelines on physical activity, screen time, and improvement of mental health for preschoolers.

Monounsaturated and polyunsaturated fatty acids concerning prediabetes and type 2 diabetes mellitus risk among participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to March 2020.

Objective: Unsaturated fatty acids (UFA) may be related to glycometabolism. While associations between UFA intake (especially their subtype) and prediabetes or type 2 diabetes mellitus (T2DM) need to be further studied. In this study, we aimed to evaluate the potential relation of UFA with prediabetes and T2DM. Methods: A total of 16,290 adults aged older than 18 years from the National Health and Nutrition Examination Survey (NHANES) from 2005 to March 2020 were included in the present analysis. Dietary intake was assessed by two day, 24-hour dietary recalls and daily intake of total monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA); four specific fatty acids of MUFA and seven specific fatty acids of PUFA were calculated. Prediabetes and T2DM were diagnosed by fasting glucose, glycohemoglobin, and self-reported medication or insulin. Rao-Scott modified chi-square tests, the Taylor series linearization method, and multivariable logistic regression analyses were applied to analyze the associations of dietary MUFA and PUFA intake with diabetes risk. Results: Of the participants, 44.34% had prediabetes and 13.16% had T2DM patients. From multivariate analysis, we found that intake of MUFA, PUFA, and some subtypes was negatively associated with the risk of prediabetes and T2DM in Americans. Compared with adults in the lowest tertile, those in the highest MUFA (PUFA) tertile had an approximately 50% (49%) and 69% (68%) lower risk of prediabetes and T2DM, respectively. Moreover, the effects of the subtypes of MUFA and PUFA on prediabetes and T2DM were different. Higher intakes of MFA 18:1, MFA 20:1, PFA 18:2, and PFA 18:3 and higher tertile intakes of MFA 16:1 and PFA 20:4 were related to a lower risk of prediabetes and T2DM. Similarly, the effects of MUFA, PUFA, and subtype on prediabetes and T2DM varied among different age groups, being weakened along with age. Conclusion: Our study suggested that total MUFA and PUFA intake might be essential in preventing prediabetes and T2DM, especially in Americans. However, this protective effect may decrease with age. Moreover, the effects of the specific UFA on prediabetes and T2DM need further consideration.

Association between daily screen time and risk of stroke among middle-aged and elderly people: research based on China health and nutrition survey.

Background: We aimed to explore the independent associations between screen time and the risk of stroke among Chinese adults based on the China Health and Nutrition Survey (CHNS). Methods: Data on Chinese adults aged older than 40 years from the CHNS in during 2004-2009 were selected. A total of 4,587 individuals were included in 2009, including screen time and the risk of stroke. Simultaneously, we traced the previous screen time to 2004 for those with outcome measures in 2009 (n = 2,100). Basic information, lifestyle, and screen behavior were obtained through face-to-face interviews and self-completed questionnaires. Anthropometric data collected included blood pressure, body weight, height, hip circumference, and waist circumference. Fasting blood was obtained for measurements of lipid and glucose levels. Cross-sectional analysis and cohort analysis were both performed using multivariate logistic regression. Results: Of all participants, 3,004 (65.49%) participants spent more than 2 h per day on screen time. Taking the men who spent less than 2 h on screen per day as reference, the crude odds ratio (OR) of the high risk of stroke was 1.53 [95% confidence interval (CI), 1.20-1.95] for the men who spent 2-3 h per day on screen and 2.37 (95% CI, 1.78-3.16) for the men who spent more than 3 h per day on screen. This difference remained significant after adjusting for confounding factors. No association was observed among women. However, in the cohort analysis with screen time in 2006 as the independent variable, the association between screen time and stroke risk was found both in men [OR, 1.83 (95% CI, 1.19-2.82)] and women [OR, 1.48 (95% CI, 1.10-1.99)]). Conclusion: We found that the high screen time was associated with an increased stroke risk, which was pronounced in men, warranting a universal need to limit screen time in order to improve health.

Occipital bone defect caused by neurofibromatosis type I: A case report.

RATIONALE: The synergistic effect between nonmalignant lesions can also cause a serious impact on patient survival. This disease involves different organ systems and presents with a variety of clinical manifestations, such as schwannoma, depigmentation, low-grade glioma, and skeletal abnormalities. We report a case of type I neurofibromatosis with an occipital bone defect. PATIENT CONCERNS: We report a case of a 50-year-old man with type I neurofibromatosis with occipital bone defect. DIAGNOSIS: The patient was accepted by the local hospital due to sudden right upper limb weakness accompanied by jitter without recognizable cause or inducement. A computerized tomography scan at a local hospital suggested subcutaneous neurofibromatosis with a left occipital cranial defect with thinning bone. On admission physical examination, diffuse multiple masses could be seen throughout the body and head of different sizes and composed of soft and tough textures. The largest one was located in the posterior occipital bone, approximately 8*8 cm in size, with a child tumor and tough texture. Multiple café-au-lait spots could be found on the chest and back, and multiple freckles can be seen in the armpit. The patient underwent surgery. Postoperative pathology showed a spindle cell tumor, which was determined to be neurofibromatosis type I according to immunopathology and clinical data. INTERVENTIONS: The patient was admitted for surgical treatment. During the operation, the scalp mass was completely abducted and the tumor tissue at the skull defect was sharply separated. Postoperative pathology showed that the peripheral margin and the bottom margin were cleaned. OUTCOMES: Computerized tomography and magnetic resonance imaging showed that the tumor was completely. There were not any surgical complications. The patient recovered well, was cured and was dismissed from the hospital. LESSONS: The synergistic effect between nonmalignant lesions can also cause a serious impact on patient survival to encourage early medical intervention. The clinical presentation of neurofibromatosis type I am usually nonmalignant, and in this case, involvement of the skull with bone defect is very rare. Therefore, it is necessary to accumulate relevant cases, reveal the pathogenesis of the disease, predict the development and outcome, and provide more evidence for early therapeutic intervention of similar patients in the future.

A method for adjusting MLC leaf positions outside a reference region for VMAT plans in a commercial treatment planning system.

Multileaf collimators (MLC) leaf positions in a volumetric modulated arc therapy (VMAT) plan is determined from inverse treatment planning process. On the isocenter plane, leaf projections should not be set too far out of projected PTV boundary. In this study we developed an automatic method of adjusting leaf positions outside a reference region of interest (ROI) for VMAT plans generated in Pinnacle treatment planning system (TPS). The proposed method consisted of a Pinnacle script and a Python program. It checked each MLC leaf position for all control points in a VMAT arc relative to a reference ROI created by adding a small margin to PTV. For leaves opened outside the reference ROI, the method adjusted their positions to reduce dose to normal tissue while maintaining PTV coverage and satisfying leaf position constraints. The deliverability and dose accuracy of the method was verified by applying it to 15 VMAT plans which were delivered in five different linacs in our department. Dosimetric improvement of the proposed method was analyzed for another group of 16 randomly selected VMAT plans. The average gamma passing rate using a 3%/3 mm criteria for the verification group of VMAT plans was 98.3% and all passing rates were above our internal passing threshold. Dosimetric improvement was observed for the evaluation group of VMAT plans. The method can improve normal tissue protection for VMAT plans. It can be safely applied in routine clinic work.

Optimization of isocenter position for multiple targets with nonuniform-margin expansion.

PURPOSE: The single isocenter for multiple-target (SIMT) technique has become a popular treatment technique for multiple brain metastases. We have implemented a method to obtain a nonuniform margin for SIMT technique. In this study, we further propose a method to determine the isocenter position so that the total expanded margin volume is minimal. MATERIALS AND METHOD: Based on a statistical model, the relationship between nonuniform margin and the distance d (from isocenter to target point), setup uncertainties, and significance level was established. Due to the existence of rotational error, there is a nonlinear relationship between the margin volume and the isocenter position. Using numerical simulation, we study the relationship between optimal isocenter position and translational error, rotational error, and target size. In order to find the optimal isocenter position quickly, adaptive simulated annealing (ASA) algorithm was used. This method was implemented in the Pinnacle3 treatment planning system and compared with isocenter at center-of-geometric (COG), center-of-volume (COV), and center-of-surface (COS). Ten patients with multiple brain metastasis targets treated with the SIMT technique was selected for evaluation. RESULTS: When the size of tumors is equal, the optimal isocenter obtained by ASA and numerical simulation coincides with COG, COV, and COS. When the size of tumors is different, the optimal isocenter is close to the large tumor. The position of COS point is closer to the optimal point than the COV point for nearly all cases. Moreover, in some cases the COS point can be approximately selected as the optimal point. The ASA algorithm can reduce the calculating time from several hours to tens of seconds for three or more tumors. Using multiple brain metastases targets, a series of volume difference and calculating time were obtained for various tumor number, tumor size, and separation distances. Compared with the margin volume with isocenter at COG, the margin volume for optimal point can be reduced by up to 27.7%. CONCLUSION: Optimal treatment isocenter selection of multiple targets with large differences could reduce the total margin volume. ASA algorithm can significantly improve the speed of finding the optimal isocenter. This method can be used for clinical isocenter selection and is useful for the protection of normal tissue nearby.

Combined systematic pharmacology and urine metabonomics to study the therapeutic mechanism of type 2 diabetic treated with the herbal pair of Salvia miltiorrhiza Bunge and Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep.

BACKGROUND: The herbal pair of Salvia miltiorrhiza Bunge and Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep (DG) is commonly used in the treatment of type 2 diabetes (T2DM) in traditional Chinese medicine (TCM). The drug pair DG was designed by Dr. Zhu chenyu to improve the treatment of T2DM. AIM: This study combined with systematic pharmacology and urine metabonomics to explore the mechanism of DG in the treatment of T2DM. METHODS: The therapeutic effect of DG on T2DM was evaluated by fasting blood glucose (FBG) and biochemical indexes. Systematic pharmacology was used to screen the active components and targets that may be related to DG. Metabonomics was established to find urinary metabolites and pathways that may be induced by DG. Finally, integrate the results of these two parts for mutual verification. RESULTS: FBG and biochemical indexes showed that DG could reduce FBG and adjust the related biochemical indexes. Metabolomics analysis indicated that 39 metabolites were related to DG for T2DM treatment. In addition, systematic pharmacology showed compounds and potential targets which were associated with DG. Finally, 12 promising targets were selected as targets for T2DM therapy by integrating the results. CONCLUSION: The combination of metabonomics and systematic pharmacology based on LC-MS is feasible and effective, which provides strong support for exploring the effective components and pharmacological mechanism of TCM.

Glioblastoma in the contralateral cerebral hemisphere with previous surgery for meningioma: A case report.

RATIONALE: Meningioma and glioblastoma (GBM) are 2 common intracranial tumors with different pathophysiologies and prognoses. It is rare for these 2 kinds of tumors to occur in the same patient. Most of the similar cases reported in the literature have been treated with radiotherapy, while cases without radiotherapy are rare. In particular, GBM in the contralateral cerebral hemisphere after resection of meningioma has not been reported. PATIENT CONCERNS: We present a case of a 66-years-old man with GBM in the right temporal lobe after previous resection of a benign meningioma of the left frontal lobe without radiotherapy. DIAGNOSES: The patient was admitted to our hospital for the first time because of right upper limb weakness. Brain magnetic resonance imaging indicated a space-occupying lesion in the left frontal area. Surgical treatment was performed, and postoperative pathology confirmed a meningioma. The patient was readmitted to the hospital 3 years after surgery of the meningioma due to a new lesion of the right temporal lobe and underwent reoperation. The postoperative pathological results showed GBM. INTERVENTIONS: The patient underwent 2 operations, and the postoperative pathologies were meningioma and GBM. In addition, the patient received concurrent chemoradiotherapy and 2 cycles of temozolomide adjuvant chemotherapy. OUTCOMES: During the last 4 months of follow-up, the patient was in good condition with no recurrence of the tumor. LESSONS: The development of GBM without radiotherapy after meningioma surgery is very rare, especially at different sites, and it is necessary to accumulate relevant cases to reveal the causes of the disease and provide more evidence for the treatment of similar patients in the future.

Association between food intake and mental health problems among preschoolers in China.

Objective: Our knowledge of associations between specific types of food and mental health problems in preschool children, an important developmental period, remains scarce. Using a large sample size and a brief measure, we aimed to examine associations between food groups and mental health problems in preschoolers. Methods: A descriptive cross-sectional study was conducted among 19,548 preschoolers in nine counties in China using a two-stage cluster sampling method. Information on food frequencies, physical activity, sedentary behavior, and sleep conditions was collected by a parent-reported questionnaire. Mental health status was assessed by a parent-reported Strength and Difficulty Questionnaire (SDQ). Height and weight were measured, and BMI was calculated. Relationships between specific types of food groups and mental health status were examined using multivariable regression modeling. Results: Of the present study sample, 47.45% of children were girls. Boys had higher scores relating to total difficulties, conduct problems, hyperactivity, and peer problems than girls but lower scores in emotional symptoms and prosocial behavior. Children with more types of food categories tended to get lower SDQ total scores even after adjusting for confounding variables (p < 0.0001). The subscale scores of SDQ varied depending on the types and numbers of food consumed. Notably, boys' mental health problems were more likely to be associated with their consumed food type. Processed meat frequency intake among boys and girls was positively related to prosocial behavior (Girls: pickled food: p = 0.003, fried food: p < 0.0001, barbecued food: p = 0.006, smoked food: p = 0.005; Boys: pickled food: p = 0.3, fried food: p < 0.0001, barbecued food: p = 0.006, smoked food: p = 0.005) and negatively associated with the SDQ total and the other subscale scores (Girls: pickled food: p ≤ 0.02, fried food: p ≤ 0.005 except for emotions (p = 0.1), barbecued food: p ≤ 0.047, smoked food: p ≤ 0.04 (except for emotions (p = 0.06) and conduct behaviors (p = 0.2)); Boys: pickled food: p < 0.01 except for hyperactivity (p = 0.5), fried food: p ≤ 0.005 except for emotions (p = 0.1), barbecued food: p ≤ 0.007 except for hyperactivity (p = 0.8), smoked food: p ≤ 0.001 except for hyperactivity (p = 0.1) and peer problem (p = 0.08)). Adequate intake frequency of confectionery (2-4 times/week) was beneficial to their emotions, conduct, and total difficulties and was also beneficial for peer and prosocial behavior for boys (Girls: emotions: p = 0.02, conduct: p = 0.02, hyperactivity: p = 0.4, peer: p = 0.06, total difficulties: p = 0.01, prosocial behavior: p = 0.1; Boys: emotions: p = 0.009, conduct: p = 0.0009, hyperactivity: p = 0.7, peer: p = 0.02: total difficulties: p = 0.003, prosocial behavior: p = 0.0002). Conclusion: Diverse food categories and adequate frequency of confectionery were found to be beneficial for children's mental health, with the exception of processed meat. These findings provide novel information and supportive data for children's dietary guidelines and the improvement of mental health.

Synthesis of the Magnetically Nanoporous Organic Polymer Fe3O4@SiO2-NH2-COP and Its Application in the Determination of Sulfonamide Residues in Surface Water Surrounding a Cattle Farm.

Efficient extractions of trace antibiotic residues in the environment are a key factor for accurate quantification of the residues. A new nanoporous material, namely, magnetically covalent organic polymer (MCOP, Fe3O4@SiO2-NH2-COP) was synthesized in this work and was used for magnetic solid-phase extraction (MSPE). The combination of MSPE with high-performance liquid chromatography separation together with ultraviolet detection (HPLC-UV) was established as an effective method for the determination of four sulfonamide (SA) residues in surface water surrounding a cattle farm. The synthesized magnetic material was characterized by SEM, TEM, FT-IR, magnetic properties measurement system (MPMS), and nitrogen gas porosimetry. The material possessed many attractive features, such as a unique microporous structure, a larger specific surface area (137.93 m2·g-1) than bare Fe3O4 (24.84 m2·g-1), high saturation magnetization (50.5 emu·g-1), open adsorption sites, and high stability. The influencing parameters, including pH, the used amount of MCOPs, the type of eluent, adsorption solution, and desorption time, were optimized. Under the optimized conditions, the method conferred good linearity ranges (R 2 ≥ 0.9990), low detection limits (S/N = 3, LOD, 0.10-0.25 µg·L-1), and satisfactory recoveries (79.7% to 92.2%). The enrichment factor (EF) for the four SAs was 34.13-38.86. The relative standard deviations of intraday (n = 5) and of interday (n = 3) were less than 4.8% and 8.9%, respectively. The equilibria between extraction and desorption for SAs could be reached within 150 s. The proposed method was sensitive and convenient for detecting SA residues in complex environmental matrices, and the successful application of the new MCOPs as an adsorbent was demonstrated.

Deriving Pulmonary Ventilation Images From Clinical 4D-CBCT Using a Deep Learning-Based Model.

Purpose: The current algorithms for measuring ventilation images from 4D cone-beam computed tomography (CBCT) are affected by the accuracy of deformable image registration (DIR). This study proposes a new deep learning (DL) method that does not rely on DIR to derive ventilation images from 4D-CBCT (CBCT-VI), which was validated with the gold-standard single-photon emission-computed tomography ventilation image (SPECT-VI). Materials and Methods: This study consists of 4D-CBCT and 99mTc-Technegas SPECT/CT scans of 28 esophagus or lung cancer patients. The scans were rigidly registered for each patient. Using these data, CBCT-VI was derived using a deep learning-based model. Two types of model input data are studied, namely, (a) 10 phases of 4D-CBCT and (b) two phases of peak-exhalation and peak-inhalation of 4D-CBCT. A sevenfold cross-validation was applied to train and evaluate the model. The DIR-dependent methods (density-change-based and Jacobian-based methods) were used to measure the CBCT-VIs for comparison. The correlation was calculated between each CBCT-VI and SPECT-VI using voxel-wise Spearman's correlation. The ventilation images were divided into high, medium, and low functional lung regions. The similarity of different functional lung regions between SPECT-VI and each CBCT-VI was evaluated using the dice similarity coefficient (DSC). One-factor ANONA model was used for statistical analysis of the averaged DSC for the different methods of generating ventilation images. Results: The correlation values were 0.02 ± 0.10, 0.02 ± 0.09, and 0.65 ± 0.13/0.65 ± 0.15, and the averaged DSC values were 0.34 ± 0.04, 0.34 ± 0.03, and 0.59 ± 0.08/0.58 ± 0.09 for the density change, Jacobian, and deep learning methods, respectively. The strongest correlation and the highest similarity with SPECT-VI were observed for the deep learning method compared to the density change and Jacobian methods. Conclusion: The results showed that the deep learning method improved the accuracy of correlation and similarity significantly, and the derived CBCT-VIs have the potential to monitor the lung function dynamic changes during radiotherapy.

Association of the VEGFR2 single nucleotide polymorphism rs2305948 with glioma risk.

BACKGROUND: Many studies have reported a relationship between the vascular endothelial growth factor receptor 2 single nucleotide polymorphism (SNP) rs2305948 and glioma, but their conclusions have been controversial. A meta-analysis was performed to assess the association between rs2305948 and glioma susceptibility. METHODS: Inclusion criteria and a strategy for screening of original literature were created. Eligible articles on the correlation between the SNP rs2305948 and glioma were identified in the PubMed, Embase, Web of Science, Cochrane Library, CNKI and Wanfang databases. After extracting the data, Stata 12. 0 software was used to perform statistical analysis under 5 genetic models and to calculate the combined odds ratio (OR) value and its 95% confidence interval (CI). RESULTS: Four case-control studies including 1595 cases and 1657 controls were entered into the study. The overall analysis showed that no obvious association existed between rs2305948 and glioma risk (allele: OR = 1.20, 95% CI = 0.93-1.54, P = .162; dominant: OR = 1.17, 95% CI = 0.93-1.46, P = .174; recessive: OR = 1.72, 95% CI = 0.94-3.15, P = .076; heterozygous: OR = 1.11, 95% CI = 0.94-1.30, P = .226; homozygous: OR = 1.74, 95% CI = 0.92-3.29, P = .088). The subgroup analysis suggested that the SNP rs2305948 was related to glioma susceptibility under allele, dominant, recessive and homozygote models in the Asian population (allele: OR = 1.34, 95% CI = 1.16-1.55, P < .001; recessive: OR = 2.24, 95% CI = 1.49-3.36, P < .001; homozygous: OR = 2.32, 95% CI = 1.54-3.50, P < .001). CONCLUSION: The vascular endothelial growth factor receptor 2 rs2305948 gene polymorphism may be related to glioma susceptibility in the Asian population. However, the association is not clear in non-Asian populations, for which there has been less research.

Obesity is a risk factor for central precocious puberty: a case-control study.

BACKGROUND: Obesity is an important underlying cause of central precocious puberty (CPP), but previous large studies are flawed by using just age and breast examination to diagnose CPP. We aimed to determine whether overweight and obesity in childhood increases hormonally diagnosed CPP. METHODS: Our retrospective, case-control study recruited 846 children diagnosed as having CPP and randomly sampled 1650 healthy control subjects in Xingtai Third Hospital in China between November 2018 and March 2021. Information was obtained from an electronic medical record and questionnaire investigated in the outpatient visit. Observations were made before the a priori hypothesis. Unconditional logistic regression for analysis was used to determine whether overweight and obesity status and duration of overweight/obesity were associated with CPP. RESULTS: Overweight and obesity were significantly associated with increased odds of CPP among girls, even after adjusting for birth weight, exclusive breastfeeding for 6 month, household income, maternal overweight, paternal overweight, and maternal menarche age (overweight: the adjusted odds ratio (aOR) (95%CI): 1.92 (1.16, 3.24), p = 0.02; obesity: aOR (95%CI): 1.78 (1.13, 3.48), p = 0.03). Furthermore, the effects of overweight and obesity were significant when ongoing for 1 to 2 years, 2 to 3 years, and greater than 3 years, but not at less than 1 year. For boys, association between obesity and increased odds of CPP was observed (aOR (95%CI): 1.68 (1.09, 3.75), p = 0.03). The effects of overweight and/or obesity were only significant when ongoing for greater than 2 years. CONCLUSIONS: Prolonged overweight and obesity in early childhood may be risk factors for CPP, especially in girls. Weight loss might be an important approach for the prevention of precocious puberty in children.

Abundance and Dynamic Distribution of Antibiotic Resistance Genes in the Environment Surrounding a Veterinary Antibiotic Manufacturing Site.

Background: Antibiotics releasing from the manufacturing sites to the surrounding environment has been identified as a risk factor for the development of antibiotic resistance of bacterial pathogens. However, the knowledge of the abundance and distribution of antibiotic resistance genes (ARGs) influenced by antibiotic pollution is still limited. Methods: In this work, the contamination by resistance genes of the environmental media including an urban river and soil along the river located near the sewage outlet of a veterinary antibiotic manufacturing site in Shijiazhuang, China, was assessed. The abundance and dynamic distribution of ARGs in different sampling points and during different seasons were analyzed using fluorescent quantitative PCR method (qPCR). Results: A total of 11 resistance genes, one integron and one transposon were detected in water and soils around the pharmaceutical factory, and among which, the sulfonamide resistance genes sul1 and ß-lactam resistance genes blaSHV were the most abundant genes. The relative abundance of ARGs in both river water and soil samples collected at the downstream of the sewage outlet was higher than that of samples collected at the upstream, non-polluted areas (p < 0.05). The mobile genetic elements (MGEs) integron in river was significantly correlated (p < 0.05) with the relative abundance of ARGs. Conclusions: The results indicate that the discharge of waste from antibiotic manufacturing site may pose a risk of horizontal transfer of ARGs.

Longitudinal Grouping of Target Volumes for Volumetric-Modulated Arc Therapy of Multiple Brain Metastases.

PURPOSE: Treatment of multiple brain metastases with single-isocenter volumetric modulated arc therapy causes unnecessary exposure to normal brain tissue. In this study, a longitudinal grouping method was developed to reduce such unnecessary exposure. MATERIALS AND METHODS: This method has two main aspects: grouping brain lesions longitudinally according to their longitudinal projection positions in beam's eye view, and rotating the collimator to 90° to make the multiple leaf collimator leaves conform to the targets longitudinally group by group. For 11 patients with multiple (5-30) brain metastases, two single-isocenter volumetric modulated arc therapy plans were generated using a longitudinal grouping strategy (LGS) and the conventional strategy (CVS). The prescription dose was 52 Gy for 13 fractions. Dose normalization to 100% of the prescription dose in 95% of the planning target volume was adopted. For plan quality comparison, Paddick conformity and the gradient index of the planning target volume, and the mean dose, the V100%, V50%, V25%, and V10% volumes of normal brain tissue were calculated. RESULTS: There were no significant differences between the LGS and CVS plans in Paddick conformity (p = 0.374) and the gradient index (p = 0.182) of the combined planning target volumes or for V100% (p = 0.266) and V50% (p = 0.155) of the normal brain. However, the V25% and V10% of the normal brain which represented the low-dose region were significantly reduced in the LGS plans (p = 0.004 and p = 0.003, respectively). Consistently, the mean dose of the entire normal brain was 12.04 and 11.17 Gy in the CVS and LGS plans, respectively, a significant reduction in the LGS plans (p = 0.003). CONCLUSIONS: The longitudinal grouping method can decrease unnecessary exposure and reduces the low-dose range in normal brain tissue.

Investigation of the microbial community structure and diversity in the environment surrounding a veterinary antibiotic production factory.

The ecological toxicity caused by antibiotic residues and resistance genes in the environment affects the community structures and activities of environmental microorganisms; the ecological toxicity effects of a long-term exposure to low doses antibiotic residues on microorganisms have not however been well-studied. In this work, sequence analysis and species annotation of the full-length 16S rRNA gene were carried out on the extracted whole genome by a 3-generation sequencing method to analyze the diversity of the microbial populations and the population differences among different sampling sites in the environment surrounding a veterinary antibiotic production factory. A total of 1720 OTUs (Operational Taxonomic Unit, OTU) were found, of which 1055 OTUs were in the river samples and 993 OTUs were in the soil samples. 643 and 438 bacterial strains were identified in the river water and soil samples respectively. The bacterial populations are classified into 29 phylum, 612 genus, and 849 species. The dominant phylum of bacteria was Proteobacteria, which was also the absolutely dominant phylum. Shannon diversity index of the bacteria showed that the bacterial abundance in downstream river was significantly higher than that in an upstream non-polluted area (P < 0.001), but the difference of bacterial abundance between soil samples was not significant. There were 61 biomarkers in the river water samples from different sampling points, and 14 biomarkers in soil samples. It was found by the difference statistics of the microbial community that there are multiple biomarkers between this veterinary drug production site and the upstream non-polluted area. Significant differences between multiple functional genes were also found in metabolic pathways of the microorganisms. A similar trend was found for the distribution of antibiotic resistance genes (ARGs). It is concluded that the population composition of microorganisms and diversity are likely related to antibiotic residues and to the distributions of ARGs in the environment surrounding the antibiotic production factory.

Determination of sulfa antibiotic residues in river and particulate matter by field-amplified sample injection-capillary zone electrophoresis.

In the present research, field-amplified sample injection-CZE (FASI-CZE) coupled with a diode array detector was established to determine trace level sulfa antibiotic. Sulfathiazole, sulfadiazine, sulfamethazine, sulfadimethoxine, sulfamethoxazole, and sulfisoxazole were selected as analytes for the experiments. The background electrolyte solution consisted of 70.0 mmol/L borax and 60.0 mmol/L boric acid (including 10% methanol, pH 9.1). The plug was 2.5 mmol/L borax, which was injected into the capillary at a pressure of 0.5 psi for 5 s. Then the sample was injected into the capillary at an injection voltage of -10 kV for 20 s. The electrophoretic separation was carried out under a voltage of +19 kV. The capillary temperature was maintained at 20˚C throughout the analysis, and six sulfonamides were completely separated within 35 min. Compared with pressure injection-CZE, the sensitivity of FASI-CZE was increased by 6.25-10.0 times, and the LODs were reduced from 0.2-0.5 to 0.02-0.05 µg/mL. The method was applied to the determination of sulfonamides in river water and particulate matter samples. The recoveries were 78.59-106.59%. The intraday and interday precisions were 2.89-7.35% and 2.77-7.09%, respectively. This provides a simpler and faster method for the analysis of sulfa antibiotic residues in environmental samples.

The Antagonism of 5-HT6 Receptor Attenuates Current-Induced Spikes and Improves Long-Term Potentiation via the Regulation of M-Currents in a Pilocarpine-Induced Epilepsy Model.

Recent studies have documented that reduced M-current promotes epileptogenesis and attenuates synaptic remodeling. Neurite growth is closely related to the level of 5-HT6 receptor (5-HT6R) in the central nervous system. However, little research is available regarding the relation between 5-HT6R and M-current and the role of 5-HT6R in M-current regulation. Herein, we found that the expression of 5-HT6R was notably increased and the expression of KNCQ2/3, the main components of the M channel, was decreased in a time-dependent manner in pilocarpine-induced chronic epileptic hippocampus. Interestingly, antagonism of 5-HT6R by SB271046 upregulated the expression of KCNQ2 but not KCNQ3. SB271046 greatly alleviated excitatory/inhibitory imbalance and improved the impaired LTP in the chronic epileptic hippocampus. Further mechanism exploration revealed that the above effects of SB271046 can be reversed by the M-channel inhibitor XE991, which also confirmed that SB271046 can indeed improve abnormal M current. These data indicate that the antagonism of 5-HT6R may decrease the excitability of hippocampal pyramidal neurons in chronic epileptic rats and improve the impaired long-term potentiation by upregulating the expression of KCNQ2 in the M-channel.

Personalized setting of plan parameters using feasibility dose volume histogram for auto-planning in Pinnacle system.

PURPOSE: The personalized setting of plan parameters in the Auto-Planning module of the Pinnacle treatment planning system (TPS) using the PlanIQ feasibility tool was evaluated for lung cancer conventional fractionated radiotherapy (CFRT). MATERIALS AND METHOD: We reviewed the records of ten patients with lung cancer who were treated with volumetric modulated arc therapy (VMAT). Three plans were designed for each patient: the clinically accepted manual plan (MP) and two automatic plans including one generated using the generic plan parameters in technique script (AP1) and the other generated using personalized plan parameters derived based on feasibility dose volume histogram (FDVH) in PlanIQ (AP2). The plans were assessed according to the dosimetric parameters, monitor units, and planning time. A plan quality metric (PQM) was defined according to the clinical requirements for plan assessment. RESULTS: AP2 achieved better lung sparing than AP1 and MP. The PQM value of AP2 (52.5 ± 14.3) was higher than those of AP1 (49.2 ± 16.2) and MP (44.8 ± 16.9) with P < 0.05. The monitor units of AP2 (585.9 ± 142.9 MU) was higher than that of AP1 (511.1 ± 136.5 MU) and lower than that of MP (632.8 ± 143.8 MU) with p < 0.05. The planning time of AP2 (33.2 ± 4.8 min) was slightly higher than that of AP1 (28.2 ± 4.0 min) and substantially lower than that of MP (72.9 ± 28.5 min) with P < 0.05. CONCLUSIONS: The Auto-Planning module of the Pinnacle system using personalized plan parameters suggested by the PlanIQ Feasibility tool provides superior quality for lung cancer plans, especially in terms of lung sparing. The time consumption of Auto-Planning was slightly higher with the personalized parameters compared to that with the generic parameters, but significantly lower than that for the manual plan.