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Rivers are of increasing concern as sources of atmospheric methane (CH4), while estimates of global CH4 emissions from rivers are poorly constrained due to a lack of representative measurements in tropical and subtropical latitudes. Measurements of complete CH4 flux components from subtropical rivers draining agricultural watersheds are particularly important since these rivers are subject to large organic and nutrient loads. Two-year measurements of CH4 fluxes were taken to assess the magnitude of CH4 emissions from the Lixiahe River (a tributary of the Grand Canal) draining a subtropical rice paddy watershed in China. Over the two-year period, annual CH4 emissions averaged 29.52 mmol m-2 d-1, amounting to 10.78 mol m-2 yr-1, making the river a strong source of atmospheric CH4. The CH4 emissions from rivers during the rice-growing season (June-October) accounted for approximately 70% of the annual total, with flux rates at 1-2 orders of magnitude greater than those for rice paddies in this area. Ebullition contributed to 44-56% of the overall CH4 emissions from the rivers and dominated the emission pathways during the summer months. Our data highlight that rivers draining agricultural watersheds may constitute a larger component of anthropogenic CH4 emissions than is currently documented in China. | [
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Insect chitinases play an indispensable role in shedding old cuticle during molting. Targeting chitinase inhibition is a promising pest control strategy. Of ChtI, a chitinase from the destructive insect pest Ostrinia furnacalis (Asian corn borer), has been suggested as a potential target for designing green pesticides. A 4,5,6,7-tetrahydrobenzo[ b]thiophene-3-carboxylate scaffold was previously obtained, and further derivatization generated the lead compound 1 as Of ChtI inhibitor. Here, based on the predicted binding mode of compound 1, the pocket-based lead optimization strategy was applied. A series of analogues was synthesized, and their inhibitory activities against Of ChtI were evaluated. Compound 8 with 6- tert-pentyl showed preferential inhibitory activity with a Ki value of 0.71 M. Their structure-activity relationships suggested that the compound with larger steric hindrance at the 6-nonpolar group was essential for inhibitory activity due to its stronger interactions with surrounding amino acids. This work provides a strategy for designing potential chitinase inhibitors. | [
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] |
The development of new methods for rapid and effective detection of bisulfite (HSO3-) in food samples and imaging of HSO3- intake in animals is of significant importance due to the key roles of HSO3- in food quality assurance and community health. In this work, a new responsive fluorescence probe, EQC, is reported for the quantitative detection of HSO3- in food samples and visualization of HSO3- intake in animals. Upon addition of HSO3-, the UV-vis absorption and red emission of EQC were significantly decreased within 120 s. The changes in absorption and emission spectra of EQC were rationalized by theoretical computations. The proposed reaction mechanism of EQC with HSO3- was confirmed by high-resolution mass spectrometry (HRMS) and spectroscopic titration measurements. EQC has the advantages of high sensitivity, selectivity (a detection limit of 18.1 nM), and fast response toward HSO3-, which enable rapid and effective HSO3- detection in buffer solution. The practical applications of EQC were demonstrated by the detection of HSO3- in food samples and the imaging of HSO3- intake in live animals. | [
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Anthocyanidin synthase from Vitis vinifera ( VvANS) catalyzes the in vitro transformation of the natural isomer of leucocyanidin, 2 R,3 S,4 S- cis-leucocyanidin, into 2 R,4 S-flavan-3,3,4-triol ([M + H]+, m/ z 323) and quercetin. The C3-hydroxylation product 2 R,4 S-flavan-3,3,4-triol is first produced and its C3,C4-dehydration product is in tautomeric equilibrium with (+)-dihydroquercetin. The latter undergoes a second VvANS-catalyzed C3-hydroxylation leading to a 4-keto-2 R-flavan-3,3-gem-diol which upon dehydration gives quercetin. The unnatural isomer of leucocyanidin, 2 R,3 S,4 R- trans-leucocyanidin, is similarly transformed into quercetin upon C3,C4-dehydration, but unlike 3,4- cis-leucocyanidin, it also undergoes some C2,C3-dehydration followed by an acid-catalyzed hydroxyl group extrusion at C4 to give traces of cyanidin. Overall, the C3,C4- trans isomer of leucocyanidin is transformed into 2 R,4 R-flavan-3,3,4-triol (M + 1, m/ z 323), (+)-DHQ, (-)-epiDHQ, quercetin, and traces of cyanidin. Our data bring the first direct observation of 3,4- cis-leucocyanidin- and 3,4- trans-leucocyanidin-derived 3,3-gem-diols, supporting the idea that the generic function of ANS is to catalyze the C3-hydroxylation of its substrates. No cyanidin is produced with the natural cis isomer of leucocyanidin, and only traces with the unnatural trans isomer, which suggests that anthocyanidin synthase requires other substrate(s) for the in vivo formation of anthocyanidins. | [
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Mitochondria play an essential part in fighting against pathogen infection in the defense responses of fruits. In this study, we investigated the reactive oxygen species (ROS) production, energy metabolism, and changes of mitochondrial proteins in harvested muskmelon fruits ( Cucumis melo cv. Yujinxiang) inoculated with Trichothecium roseum. The results indicated that the fungal infection obviously induced the H2O2 accumulation in mitochondria. Enzyme activities were inhibited in the first 6 h postinoculation (hpi), including succinic dehydrogenase, cytochrome c oxidase, H+-ATPase, and Ca2+-ATPase. However, the activities of Ca2+-ATPase and H+-ATPase and the contents of intracellular adenosine triphosphate (ATP) were improved to a higher level at 12 hpi. A total of 42 differentially expressed proteins were identified through tandem mass tags-based proteomic analyses, which are mainly involved in energy metabolism, stress responses and redox homeostasis, glycolysis and tricarboxylic acid cycle, and transporter and mitochondria dysfunction. Taken together, our results suggest that mitochondria play crucial roles in the early defense responses of muskmelons against T. roseum infection through regulation of ROS production and energy metabolism. | [
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Niduterpenoids A (1) and B (2), two sesterterpenoids with a highly congested hexacyclic 5/5/5/5/3/5 carbon skeleton but no unsaturated functional group, were isolated from Aspergillus nidulans. Their structures were determined by a combination of spectroscopic data and single-crystal X-ray diffraction analyses. Compounds 1 and 2 present the first examples of sesterterpenoids with a hexacyclic carbon ring system. Compound 1 showed no cytotoxicity but abolished 17-estradiol-induced cell proliferation (IC50 = 11.42 0.85 M). | [
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In recent decades, there have been increasing reports of insect resistance in Bacillus thuringiensis (Bt) crops. Alternative use of Cry toxins, with high insecticidal activity and different mechanisms of action, may be an important strategy to manage this resistance. Cry9 protein, with high toxicity to the lepidopteran pests and no cross-resistance with commercial Cry1 proteins, is a valuable relevant resource. A novel insecticidal protein, MP1489, subsequently named as Cry9Cb1, with 88% amino acid sequence identity with Cry9Ca1, was identified from Bt strain SP663; it exhibited high insecticidal activity against Plutella xylostella, Ostrinia furnacalis, and Chilo suppressalis and no cross-resistance with Cry1Fa in Ostrinia furnacalis. Its minimal active fragments against Plutella xylostella and Ostrinia furnacalis were identified to be 72T-657V and 68D-655A, respectively; food-safety assessment showed no sequence homology with any known allergen and rapid degradation and inactivation by both heat and the gastrointestinal environment. Therefore, Cry9Cb1 is proposed to have a brilliant prospect as an insecticidal protein in agriculture. | [
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We investigated the clinical efficacy of pinhole soft contact lenses for presbyopia correction. Twenty participants with presbyopia wore pinhole soft contact lenses in the non-dominant eye for 2weeks. Manifest refraction, Goldmann binocular visual field tests, contrast sensitivity tests, and biomicroscopic examinations were performed along with evaluations of questionnaire responses and the binocular corrected distance visual acuity (CDVA), distance-corrected near visual acuity (DCNVA), distance-corrected intermediate visual acuity (DCIVA), and depth of focus, both before and after 2weeks of lens wear. DCNVA at 33 and 40 cm and DCIVA at 50 and 70 cm showed significant improvements after pinhole lens wear (P-value: <0.001, <0.001, <0.001, and 0.046, respectively), with no changes in the binocular visual field and binocular CDVA. Contrast sensitivities under photopic and mesopic conditions decreased at some frequencies; however, visual function questionnaire scores significantly improved (all P-values <0.001). These findings suggest that pinhole contact lenses effectively correct presbyopia. | [
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A nanoparticulate system; cubosomes has been suggested to support the controlled release of Telmisartan (TEL), a poorly water-soluble medication. Four distinctive formulae were selected according to the results of three estimated responses. The liquid cubosomes were successfully adsorbed onto Aerosil 380 to form granules. The formulae were evaluated for their flow properties. The best granules were compressed into tablets suitable for oral administration. The tablets were evaluated for its performance. The in vivo study of the best selected cubosomal tablets was checked after oral administration in the blood of albino rabbits utilizing an HPLC method. Results revealed that the highest EE was shown in formulae C5 (59.68 1.3). All the prepared formulae had particle size less than 500 nm with PDI < 0.5 and the highest zeta potential results were observed in C5, C7, C9, C11 and C12 (>30 mv). A7 and A9 prepared using Aerosil 380 showed a perfect flowability. After 1 h of dissolution testing, the commercial product showed a 66% drug release while the release of all cubosomal formulae didn't exceed 35% during the first hour reaching a 85% of the drug released at the end of 24 h. A7 was selected for the in vivo study; Tmax of TEL absorption is increased for cubosomal formula by three folds indicating sustained release pattern. The relative bioavailability is also increased by 2.6 fold. The investigation proposed the rationality of cubosome to figure an effective controlled release tablets to improve its bioavailability and expand its activity. | [
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] |
For the handling of active pharmaceutical ingredients (APIs) and production of medicinal products in shared facilities, the European Medicines Agency (EMA) has introduced the determination of permitted daily exposure (PDE) values to provide limits for cross-contamination. APIs have a desired pharmacological effect in the patient who intendedly uses a certain medicinal product. However, this effect is undesired in a patient that receives this API unintendedly as a cross-contamination of another medicinal product. In particular, for approved APIs for human use, a multitude of data is available on the pharmacological activity as well as adverse effects, which have to be taken into account in PDE setting. Thus, the setting of PDEs for APIs needs a structured scientific evaluation of all properties and identification of the most critical effect, which is the basis for PDE calculation. In this publication, we provide guidance on points for consideration when setting PDEs for APIs, or when evaluating the quality of documents describing the derivation of PDEs received, e.g. by third parties. | [
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Objective: Impaired awareness of hypoglycemia (IAH) is a risk factor for severe hypoglycemia in patients with type 1 diabetes (T1D) not using a continuous glucose monitoring (CGM) system. The current study investigated the prevalence of IAH and its relationship with severe hypoglycemia in T1D patients using CGM systems. Methods: This cross-sectional observational study enrolled 135 patients with T1D and ongoing real-time CGM use. A survey was conducted to assess hypoglycemia awareness with the Gold, Clarke, and Pedersen-Bjergaard questionnaires and the 6-month history of severe hypoglycemia. Other diabetes histories and the CGM glucose data were collected. Results: The Gold, Clarke, and Pedersen-Bjergaard questionnaires demonstrated the overall prevalence of IAH/abnormal awareness to be 33.3%, 43.7%, and 77.0%, respectively. Participant age and duration of T1D were consistently related to IAH or hypoglycemia unawareness with all three questionnaires (P<.05). Amongst the patients using CGM for >6 months, 24.5% were found to have at least one episode of severe hypoglycemia in the preceding 6 months. IAH identified by the Gold and Clarke questionnaires and hypoglycemia unawareness identified by the Pedersen-Bjergaard questionnaire were related to 6-, 4.63-, and 5.83-fold increased risk of severe hypoglycemia (P = .001, .004, and .013), respectively. IAH identified by the Gold/Clarke questionnaires was associated with a longer duration of CGM glucose <54 mg/dL and higher glucose coefficients of variation (P<.05). Conclusion: IAH is highly prevalent and related to a higher risk for severe hypoglycemia in T1D patients using CGM. Abbreviations: CGM = continuous glucose monitoring; CI = confidence interval; HAAF = hypoglycemia-associated autonomic failure; HbA1c = hemoglobin A1C; IAH = impaired awareness of hypoglycemia; T1D = type 1 diabetes. | [
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] |
Objective: We aimed to describe the natural history of the rare clinical syndrome of transient osteoporosis (TO) and ascertain potential risk factors. Methods: Retrospective cohort study of adults with TO at Mayo Clinic, Rochester, Minnesota, over 15 years. Adults with acute-onset joint pain worsened by weight bearing and bone marrow edema on magnetic resonance imaging were included; exclusion criteria were trauma, tumors, rheumatic diseases, avascular necrosis, infection, and hyperesthesia. Results: Thirty-three patients with TO were identified: 20 males, median age at diagnosis 47 years, and median body mass index 28 kg/m2. Median time to diagnosis was 2 months, and time to symptom resolution was 4 months. All cases involved the lower extremity, with the majority affecting the hip. Most patients (79%) had at least one possible identified risk factor. The most frequent risk factor was low bone mineral density (BMD) in 13 patients (39% of cohort). Of the 16 patients with BMD measure, 8 had low BMD at a site other than TO. The next most frequent risk factors were sudden limb overuse and more than one episode of TO, observed in 30%, followed by a disorder of bone and mineral metabolism in 27%. Conclusion: TO affects middle-age men more than women, primarily involves weight-bearing joints, and usually resolves with conservative management. Its etiology remains unclear; however, the common presence of risk factors, abnormalities in bone and mineral laboratories, and decrease in BMD suggest that systemic factors may be important in its development. Abbreviations: AVN = avascular necrosis; BMD = bone mineral density; DXA = dual-energy X-ray absorptiometry; MRI = magnetic resonance imaging; TO = transient osteoporosis. | [
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Objective: Albiglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), reduces glycated hemoglobin with a low risk of hypoglycemia in patients with type 2 diabetes. The relationship between GLP-1RAs and risk of pancreatitis is unresolved. This independent, rigorous, expert review of the albiglutide HARMONY Phase III clinical program examined suspected cases of acute pancreatitis. Methods: An independent pancreatitis adjudication committee (PAC), composed of physicians with expertise in gastroenterology and pancreatic disease, was prospectively established to review cases of suspected acute pancreatitis in the HARMONY studies. Results: Patients treated in Phase III trials with albiglutide (n = 2,365), or active or placebo comparators (n = 2,530), averaged 56 years of age with a mean 8.3-year diabetes duration. Across the 8 studies, the PAC reviewed potential cases of treatment-emergent acute pancreatitis in 43 patients. Definite or probable acute pancreatitis was adjudicated for 11 patients (8 albiglutide; 3 active comparators). Most of these were considered by the PAC to be at least possibly related to study treatment (6 of 8 albiglutide cases and 2 of 3 active comparator cases). Both cases in the active comparator group adjudicated as definite or probable pancreatitis with at least a possible relationship to study treatment were in patients treated with a GLP-1RA. The frequency of pancreatitis was higher among patients treated with albiglutide (6/2,365, 0.3%) than with placebo (0/486, 0%) or active comparators (2/2,062, 0.08%). Conclusion: In the HARMONY Phase III program, adjudicated cases of acute pancreatitis were uncommon. However, within the limitations of available data, the incidence of acute pancreatitis with albiglutide appears to be within the range described for other studies of GLP-1RAs. Abbreviations: AE = adverse event; CI = confidence interval; DPP-4 = dipeptidyl peptidase-4; GLP-1 = glucagon-like peptide-1; GLP-1RA = glucagon-like peptide-1 receptor agonist; MH-OR = Mantel-Haenszel odds ratio; OR = odds ratio; PAC = pancreatitis adjudication committee; SAE = serious adverse event; ULN = upper limit of normal. | [
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] |
Objective: To evaluate the effect of raloxifene on prolactin (PRL) levels in addition to dopamine agonist (DA) therapy in patients with prolactinoma. Methods: We conducted a retrospective chart review of 14 patients with prolactinoma on stable dose of DA for 6 months who received raloxifene 60 mg daily, as PRL could not be normalized despite being on fairly high doses of DA. Patients were informed that raloxifene is not approved by the Food and Drug Administration for prolactinoma treatment. PRL level was measured at 1 to 6 months after starting raloxifene and at 1 to 3 months following its discontinuation. Raloxifene was stopped in 8 out of 14 patients after 2 (1 to 6) months of treatment as the absolute change in PRL level was felt to be small. Results: The median age and female/male sex ratios were 50 years (range 18 to 63 years), 6/8 respectively. The baseline DA dose was 3 mg/week (0.5 to 7 mg/week) for cabergoline and 15 mg/day for bromocriptine. Ten patients had an absolute and percentage decrease in PRL of 8.3 ng/mL (1.5 to 54.2 ng/mL) and 25.9% (8 to 55%) from baseline, respectively, after 1 to 6 months on raloxifene treatment. Among 10 patients with a decrease in PRL level, 2 (20%) achieved PRL normalization. Two patients had no change in PRL and two patients had an increase in PRL level by 22.8 ng/mL and 8.8 ng/mL (47% and 23.6%), respectively. Conclusion: Raloxifene was associated with a 25.9% (8 to 55%) decrease in PRL level in 10/14 (71%) patients with prolactinoma who were on stable doses of DA including 2 patients (14%) who achieved normoprolactinemia. Abbreviations: CV = coefficient of variation; DA = dopamine agonist; FSH = follicule-stimulating hormone; LH = luteinizing hormone; PRL = prolactin; PTTG = pituitary tumor transforming gene. | [
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Objective: Semaglutide is a glucagon-like peptide 1 (GLP-1) analog for the once-weekly treatment of type 2 diabetes (T2D). In the global SUSTAIN clinical trial program, semaglutide demonstrated superior glycated hemoglobin (HbA1c) and body weight reductions versus comparators. This post hoc analysis compared the proportion of patients achieving combined reductions in glycemia and body weight versus comparators. Methods: A total of 5,119 subjects with T2D in the phase 3 SUSTAIN 1 through 5 and 7 trials, from 33 countries, were included in this post hoc analysis. Subjects received subcutaneous semaglutide 0.5 or 1.0 mg, placebo or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg, insulin glargine, dulaglutide 0.75 or 1.5 mg). The main endpoint was a composite of ?1.0% HbA1c reduction and ?5.0% weight loss at end of treatment. Results: Significantly greater proportions of subjects achieved the composite endpoint with semaglutide 0.5 (25 to 38%) and 1.0 mg (38 to 59%) versus comparators (2 to 23%). More subjects treated with semaglutide versus comparators achieved ?1.0% HbA1c reductions (58 to 77% and 75 to 83% for semaglutide 0.5 and 1.0 mg versus 12 to 68%) and ?5.0% weight loss (37 to 46%, 45 to 66% versus 4 to 30%). Proportions of subjects achieving targets were significantly higher with semaglutide 1.0 versus 0.5 mg in four of five trials. Semaglutide was well tolerated, with a safety profile similar to other GLP-1 receptor agonists. Conclusion: Significantly more subjects achieved both ?1.0% HbA1c reduction and ?5.0% weight loss with once-weekly subcutaneous semaglutide treatment versus comparators in the SUSTAIN trials. A dose-dependent effect was observed with semaglutide. Abbreviations: AE = adverse event; CV = cardiovascular; ER = extended release; GLP-1 = glucagon-like peptide 1; GLP-1 RA = glucagon-like peptide 1 receptor agonist; HbA1c = glycated hemoglobin; OAD = oral antidiabetic drug; sc = subcutaneous; T2D = type 2 diabetes. | [
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] |
Objective: Because they share genetic and environmental factors with patients with diabetes, the first-degree relatives (FDRs) of patients with diabetes exhibit early signs of metabolic abnormalities. The present study aimed to investigate the correlation between family history of diabetes in FDRs and metabolic syndrome (MS), as well as changes in related risk factors. Methods: The present study population was a part of the baseline survey from the REACTION study. FDRs were defined as individuals having one or more FDRs with diabetes. MS and its components were defined according to the 2007 Joint Committee for Developing Chinese Guidelines. Results: A total of 2,692 individuals with an average age of 57.24 8.35 years were enrolled in the present study. The prevalence of MS in FDRs (36.44%) was significantly higher than that in non-FDRs (25.28%; P<.001). FDRs accounted for 13.37%, 14.32%, 16.67%, 22.47%, 23.53%, and 25.58% of subjects with 0 to 5 MS components, showing an increasing trend (P for trend <.001). After adjusting for gender and age, partial correlation analyses showed significant associations of first-degree family history of diabetes with MS-related indexes (all P<.05). After adjusting for gender, age, lifestyle habits, and total metabolic traits, the first-degree family history of diabetes remained an independent factor that was positively associated with MS (odds ratio, 1.765; P<.001). Conclusion: A first-degree family history of diabetes predisposes individuals to developing MS and stands out as an independent risk factor for MS even without considering the subsequent effects of hyperglycemia. Abbreviations: BMI = body mass index; DBP = diastolic blood pressure; FDR = first-degree relative; FPG = fasting plasma glucose; HbA1c = glycated hemoglobin A1c; HDL-c = high-density-lipoprotein cholesterol; LDL-c = low-density-lipoprotein cholesterol; MAP = mean arterial pressure; MS = metabolic syndrome; OR = odds ratio; SBP = systolic blood pressure; TC = total cholesterol; TG = triglyceride; WC = waist circumference; WHR = waist-to-hip ratio; 2hPG = 2-hour plasma glucose. | [
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Objective: Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). We aimed to compare the risk of malignancy (ROM) of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) on fine-needle aspiration cytology (FNAC), before and after the reclassification, in a large cohort of patients. Methods: We analyzed 5,625 consecutive FNAC samples performed in 2012-2014 and selected category III (atypia of undetermined significance [AUS]/follicular lesion of undetermined significance [FLUS]), IV (follicular neoplasm [FN]/suspicious for a follicular neoplasm [SFN]), V (suspicious for malignancy [SFM]), and VI (malignant) of the BSRTC. We reviewed the histology of operated patients and compared ROM before and after the introduction of the NIFTP category. Results: A total of 772 patients were identified and 45% underwent surgery (n = 348). There were 180 cases of AUS/FLUS (10 NIFTP), 114 cases of FN/SFN (2 NIFTP), 29 cases of SFM (3 NIFTP), and 25 cases of BSRTC VI (no NIFTP). Exclusion of NIFTP from malignant lesions resulted in a relative and absolute decrease in the ROM in AUS/FLUS (15.2% and 5.5%, respectively), FN/SFN (7.6% and 1.8%, respectively) and SFM (14.2% and 10.3%, respectively) categories. Among the NIFTP patients, 93% underwent total thyroidectomy and 20% received radioiodine. Conclusion: Reclassification of noninvasive EFVPTC as NIFTP resulted in a decrease in overall ROM, and the BSRTC categories most affected were III and V. Abbreviations: AUS = atypia of undetermined significance; BSRTC = Bethesda System for Reporting Thyroid Cytopathology; EFVPTC = encapsulated follicular variant of papillary thyroid carcinoma; FLUS = follicular lesion of undetermined significance; FN = follicular neoplasm; FNAC = fine-needle aspiration cytology; FVPTC = follicular variant of papillary thyroid carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid carcinoma; ROM = risk of malignancy; SFM = suspicious for malignancy; SFN = suspicious for a follicular neoplasm. | [
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] |
Objective: It is unclear whether acute weight loss or the chronic trajectory of weight loss after bariatric surgery is associated with long-term type 2 diabetes mellitus (T2DM) glycemic improvement. This ancillary study of the Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial aimed to answer this question. Methods: In STAMPEDE, 150 patients with T2DM were randomized to bariatric surgery, and 96 had 5-year follow-up. Data post-Roux-en-Y gastric bypass (RYGB, n = 49) and sleeve gastrectomy (SG, n = 47) were analyzed. We defined percent weight loss in the first year as negative percent decrease from baseline weight to lowest weight in the first year. Percent weight regain was positive percent change from lowest weight in the first year to fifth year. Weight change was then correlated with cardiometabolic (CM) and glycemic outcomes at 5 years using Spearman rank correlations and multivariate analysis. Results: In both RYGB and SG, less weight loss in the first year positively correlated with higher 5-year glycated hemoglobin (HbA1c) (RYGB, = +0.13; P<.001 and SG, = 0.14; P<.001). In SG, greater weight regain from nadir positively correlated with higher HbA1c ( = 0.06; P = .02), but not in RYGB. Reduced first-year weight loss was also correlated with increased 5-year triglycerides ( = 1.81; P = .01), but not systolic blood pressure. Weight regain did not correlate with CM outcomes. Conclusion: Acute weight loss may be more important for T2DM glycemic control following both RYGB and SG as compared with weight regain. Clinicians should aim to assist patients with achieving maximal weight loss in the first year post-op to maximize long-term health of patients. Abbreviations: BMI = body mass index; HbA1c = glycated hemoglobin; RYGB = Roux-en-Y gastric bypass; SBP = systolic blood pressure; SG = sleeve gastrectomy; STAMPEDE = Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently; T2DM = type 2 diabetes mellitus; TG = triglyceride. | [
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Objective: A previous Trinidadian survey highlighted the investigative and therapeutic approaches selected by general practitioners (GPs) in managing thyrotoxicosis. The main objective of this study was to compare practice with existing guidelines. Methods: In this cross-sectional study a pretested de novo questionnaire was self-administered to GPs throughout Trinidad. The survey evaluated GPs' choices in management of thyrotoxicosis cases and compared their responses to the 2016 American Thyroid Association guidelines as well as with those previously reported locally. Results: A total of 159 completed questionnaires were analyzed (59% response rate). Thyroid stimulating hormone was the preferred (94%) biochemical test to confirm thyrotoxicosis etiology. A combination of ultra-sound and thyroid scintigraphy, thyroid ultrasound alone, and scintigraphy only were the testing options selected by 41%, 38%, and 12%, respectively. Generally medical therapy with antithyroid drugs was the preferred treatment option with 86% of respondents selecting this option for the index case of newly diagnosed female Graves disease. The greatest proportion of respondents that selected radioactive iodine (RAI) was 35% for both the index case as well as the male equivalent. Surgery was the most popular option at 25% for patients with a toxic multinodular goiter. Having access to RAI and scintigraphy was reported by 32% and 28%, respectively. Conclusion: GPs appear to be constrained to making rational choices based upon availability rather than what the guidelines recommend. In the absence of formal continuing medical education for GPs on thyrotoxicosis, dissemination of guidelines at the primary care level may reduce this gap. Abbreviations: ATA = American Thyroid Association; ATD = antithyroid drugs; CME = continued medical education; GP = general practitioner; RAI = radioactive iodine; SURG = surgery; T4 = thyroxine; TSH = thyroid-stimulating hormone. | [
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Objective: To investigate the effect of age and gender on basal and food-stimulated serum calcitonin (CT), parathyroid hormone (PTH), and gastrin levels among healthy adults. Methods: Ninety-six healthy adults (76 men and 20 women) aged between 21 and 43 years were recruited. Serum CT, PTH, and gastrin levels were measured after a 9-hour overnight fast, and 1 and 3 hours postprandially. Results: PTH levels decreased early and increased late after feeding. This change was significant in men but not in women. CT levels increased in response to food intake in men but not in women. Gastrin levels were significantly increased after feeding in both men and women. Mean basal and food stimulated CT, PTH, and gastrin levels did not significantly differ between genders. Fasting and post-prandial PTH levels were higher while gastrin levels were lower in older subjects (>30 years old) compared to younger subjects (?30 years old). Fasting and postprandial CT levels were not significantly different between age groups. Conclusion: Age had a significant effect on fasting and food-stimulated PTH and gastrin hormone levels. The effect of age on PTH levels was independent of baseline vitamin D levels. Men showed significant changes in CT and PTH levels in response to feeding compared to women, although the mean hormone levels were not significantly different between men and women. Abbreviations: CT = calcitonin; MTC = medullary thyroid carcinoma; PTH = parathyroid hormone; SD = standard deviation. | [
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] |
Objective: Preservation of parathyroid function is one of the primary tenets of endocrine surgery. For patients with thyroid disease, an inadvertently compromised parathyroid gland is routinely autotransplanted into the neck at the time of surgery. By contrast, for patients with parathyroid disease secondary to hyperplasia, the timing of auto-transplantation needs to be further considered in order to balance the risks between persistent disease and permanent hypocalcemia. Cryopreservation preserves cellular function and permits the storage of parathyroid tissue for potential re-implantation at a later date in patients who develop hypoparathyroidism. Methods: In this paper, we review the process of cryopreservation, with particular emphasis on the regulatory issues involved in establishing a local service, tissue processing, billing and reimbursements, outcome (functionality), and complications. Results: A detailed description of the technique as performed at our institution is described and illustrated. Conclusion: Cryopreservation affords surgical insurance against the disastrous sequelae of permanent hypoparathyroidism. Our techniques are easy to adopt with only a modest initial investment of time and money, particularly for institutions that already cryopreserve other tissue types. Abbreviations: PTH = parathyroid hormone; RMPI = Roswell Park Memorial Institute; RPMI-SSS = RPMI-serum substitute supplement. | [
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] |
Objective: To report the rate of candidate actionable somatic mutations in patients with locally advanced and metastatic gastro-enteropancreatic (GEP) neuroendocrine tumors (NET) and of other genetic alterations that may be associated with tumorigenesis. Methods: A phase II mutation targeted therapy trial was conducted in patients with advanced well-differentiated G1/G2 GEP-NET. Mutations found in the mTOR pathway-associated genes led to treatment with the mTOR inhibitor everolimus, and were defined as actionable. Tumor deoxyribonucleic acid (DNA) from GEP-NET were sequenced and compared with germline DNA, using the OncoVAR-NET assay, designed for hybrid capture sequencing of 500 tumor suppressor genes and oncogenes. Somatic variants were called and copy-number (CN) variant analysis was performed. Results: Thirty patients (14 small-intestine, 8 pancreatic, 3 unknown primary NET, and 5 of other primary sites) harbored 37 lesions (4 patients had DNA of multiple lesions sequenced). Only 2 patients with sporadic NET (n = 26) had an actionable mutation leading to treatment with everolimus. Driver somatic mutations were detected in 18 of 30 patients (21/37 lesions sequenced). In the remaining samples without a driver mutation, CN alterations were found in 11/16 tumors (10/12 patients), including CN loss of chromosome (Chr) 18 (P<.05), CN gain of Chr 5, and loss of Chr 13. CN losses in Chr 18 were more common in patients without driver mutations detected. Pronounced genetic heterogeneity was detected in patients with multiple lesions sequenced. Conclusion: Genome-wide DNA sequencing may identify candidate actionable genes and lead to the identification of novel target genes for advanced well-differentiated GEP-NET. Abbreviations: Chr = chromosome; CN = copy number; DNA = deoxyribonucleic acid; FDA = Food and Drug Administration; GEP = gastro-enteropancreatic; MEN-1 = multiple endocrine neoplasia syndrome type 1; mTOR = mammalian target of rapamycin; NET = neuroendocrine tumor; PFS = progression-free survival; PNET = pancreatic neuroendocrine tumors; SINET = small-intestine neuroendocrine tumor. | [
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] |
Objective: To explore the relationship between serum bilirubin concentration and clinicopathologic features and renal outcome in biopsy-diagnosed diabetic nephropathy (DN) in patients with type 2 diabetes mellitus. Methods: In this retrospective study, 118 patients with DN were enrolled. Participants were divided into two groups according to their median baseline serum bilirubin concentration: Group 1 (serum bilirubin ?7.5 mol /L); Group 2 (serum bilirubin >7.5 mol /L). Basic clinical parameters were measured at the time of renal biopsy, and the relationships between serum bilirubin and the clinicopathologic features and renal outcome were analyzed. Results: Patients in Group 1 often had inferior renal function. Compared with Group 2, the glomerular classification and interstitial inflammation were more severe in subjects of Group 1, while arteriolar hyalinosis and interstitial fibrosis and tubular atrophy (IFTA) were comparable between the groups. Serum bilirubin was negatively correlated with the severity of the glomerular classification, interstitial inflammation, and IFTA. In the prognostic analysis, higher serum bilirubin level was associated with a lower risk of progression to end-stage renal disease, which was independent of the effects of age, gender, duration of diabetes, anemia, serum glucose, and hypertension but not of estimated glomerular filtration rate (hazard ratio, 0.406; 95% confidence interval, 0.074 to 2.225; P = .299). Conclusion: Our study showed a negative correlation between serum bilirubin level and renal pathologic lesions in patients with DN; serum bilirubin showed an inverse association with DN progression, but this was not independent. Abbreviations: CI = confidence interval; CKD = chronic kidney disease; DM = diabetes mellitus; DN = diabetic nephropathy; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; HbA1c = glycated hemoglobin; HO-1 = heme oxygenase 1; HR = hazard ratio; IFTA = interstitial fibrosis and tubular atrophy; log-BIL = log-transformed baseline serum bilirubin; T2DM = type 2 diabetes mellitus. | [
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] |
Objective: Early identification and management of prediabetes is critical to prevent progression to diabetes. We aimed to assess whether prediabetes is appropriately recognized and managed among patients with impaired fasting glucose (IFG). Methods: We carried out an observational study of Olmsted County residents evaluated at the Mayo Clinic between 1999-2017. We randomly selected 108 subjects with biochemical criteria of IFG and 105 normoglycemic subjects. We reviewed their health records at baseline (1999-2004) and during follow up (2005-2017) collecting demographic and clinical data including vitals, diagnoses, laboratory, and medications associated with cardiovascular comorbidities. The main outcome was documentation of any recognition of prediabetes and management recommendations (lifestyle changes and/or medications). Results: At baseline (1999-2004), 26.85% (29/108) of subjects with IFG were recognized as having prediabetes, and of these 75.86% (22/29) received management recommendations with 6.9% (2/29) getting metformin. During follow-up (2005-2017), 26.67% (28/105) of initial cohort of normoglycemic subjects developed incident IFG and of these, 85.71% (24/28) were recognized as having prediabetes, and 58.33% (14/24) received management recommendations. During the entire study period, 62.50% (85/136) were recognized as having prediabetes of which 75.29% (64/85) had documented management recommendations. High body mass index (BMI) (?35) was associated with increased recognition (odds ratio [OR] 3.66; confidence interval [CI] 1.065, 12.500; P = .0395), and normal BMI (<25) was associated with a lack of recognition (OR 0.146; CI 0.189, 0.966; P = .0413). Conclusion: Despite evidence supporting the efficacy of lifestyle changes and medications in managing prediabetes, this condition is not fully recognized in routine clinical practice. Increased awareness of diagnostic criteria and appropriate management are essential to enhance diabetes prevention. Abbreviations: BMI = body mass index; CI = confidence interval; EHR = electronic health records; FBG = fasting blood glucose; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; OR = odds ratio. | [
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] |
Objective: Previous studies found that exposure to famine was associated with a higher risk of metabolic syndrome and fatty liver in adult women. In the present study, we investigated the relationship between exposure to the Chinese famine in early life and thyroid function and nodules in adulthood. Methods: We retrospectively analyzed the data of subjects who underwent routine physical check-up in the Public Health Center of our hospital in 2017. Subjects were divided into 3 groups: post-, pre-, and nonexposed groups. The basal metabolic rate (BMR) was estimated by the revised Harris-Benedict formulation. The serum levels of thyroid hormones were detected. Thyroid ultrasonography was performed by experienced technicians. The diagnosis of thyroid nodules was according to the Thyroid Imaging Reporting and Data System (TI-RADS). Results: Compared to nonexposed subjects, the postnatally exposed subjects had a significantly lower level of thyroxine, and statistically higher ultrasensitive thyroid stimulating hormone (P<.05). There was no significant difference in thyroid autoimmune antibodies between groups exposed to the famine and the nonexposed group (P>.05). There were no statistical differences in heart rate and BMR among these groups (P>.05). Exposure to the famine did not affect either the numbers of thyroid nodules, the TI-RADS score of thyroid nodules, or the maximal diameters of thyroid nodules. Conclusion: Our results indicate a significant association between famine exposure in early life and down-regulated thyroid function in adulthood. Postnatal famine exposure may be more vulnerable to nutrient deficiency and lead to restricted thyroid development in later life. Abbreviations: BMR = basal metabolic rate; FT3 = free triiodothyronine; FT4 = free thyroxine; IDD = iodine deficiency disorder; T3 = triiodothyronine; T4 = thyroxine; TG-Ab = thyroglobulin antibody; TI-RADS = Thyroid Imaging Reporting and Data System; uTSH = ultrasensitive thyroid stimulating hormone. | [
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Objective: Parathyroid carcinoma (PC) is a rare endocrine malignancy with a poor prognosis. The optimal surgical procedure and prognostic factors for PC remain controversial. Methods: Clinical information and parafibromin staining results from 53 patients with PC were reviewed retrospectively from 1997 to 2018. Immunohistochemical staining for parafibromin was performed on formalin-fixed, paraffin-embedded tissue samples. The influence of clinical parameters, surgical procedure, and parafibromin staining of tumor tissues on prognosis were evaluated. Results: A total of 53 patients with PC were enrolled in this study. The male to female ratio was 1.94:1. En bloc resection was performed as initial surgery for 18 patients (34.0%), and 35 patients (66.0%) underwent local resection. Parafibromin staining was negative in the tumor tissues of 24 PC patients (45.3%). Thirty-three patients suffered from local recurrence or distant metastasis, and overall mortality was 16/53 at a median follow-up time of 80 months (range, 7 to 282 months). Cox proportional hazards analysis showed that negative parafibromin staining (hazard ratio [HR], 4.13; 95% confidence interval [CI], 1.73 to 9.87; P = .001) was related to recurrence or metastasis and that age >50 years (HR, 5.66; 95% CI, 1.58 to 20.31; P = .008) was related to mortality. The extent of resection was not related to recurrence or overall survival. Conclusion: The majority of PC patients have a relatively long survival with multiple recurrences. Absence of parafibromin staining was a factor that influenced PC recurrence. The main factor influencing PC outcomes may be the biological characteristics rather than surgical extent. Abbreviations: CI = confidence interval; DFS = disease-free survival; HR = hazard ratio; OS = overall survival; PC = parathyroid carcinoma; WHO = World Health Organization. | [
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] |
Objective: The management of large nonsecreting adrenal tumors (at least 4 cm) is still a matter of debate as it is unclear whether imaging, especially 18F-fluorodeoxyglucose (FDG), can be used to characterize their potential malignancy. Moreover, the risk of new hypersecretion in nonoperated tumors is uncertain. Our aim was to better characterize these large adrenal incidentalomas. Methods: Patients followed in our center for a nonsecreting large (at least 4 cm) adrenal incidentaloma, with an initial computed tomography (CT) and 18F-FDG positron emission tomography (PET) CT, were retrospectively included. Patients who were not operated after initial diagnosis had to be followed with clinical, biological, and imaging evaluations for at least 3 years or until delayed surgery. Results: Eighty-one patients were included in the study: 44 patients (54.3%) had initial surgery while 37 were followed, including 21 (25.9%) who were operated after a mean of 19 months. Among the 65 operated patients, 13 (20%) had a malignant lesion (3 with metastasis, and 10 with adrenocortical carcinoma). Unenhanced CT <10 showed 85.6% sensitivity and 78.8% specificity; all had a 18F-FDG uptake ratio >1.5. Among the 24 patients who were followed for at least 3 years, 5 (20.8%) finally presented hypercortisolism (4 subclinical). Conclusion: As expected, large adrenal tumors are at a higher risk of malignancy. The combination of unenhanced CT <10 and 18F-FDG PET ratio <1.5 prove to be reassuring and might lead to a close follow-up rather than immediate surgery. Hormonal follow-up should be focused on the risk of hypercortisolism. Abbreviations: CI = confidence interval; CT = Computed Tomography; ENSAT = European Network for the Study of Adrenal Tumors; ESE = European Society of Endocrinology; FDG = fluorodeoxyglucose; HU = Hounsfield units; PET = positron emission tomography; ROI = regions of interest; SUV = standard uptake value. | [
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Objective: To investigate in vivo correlates of erectile dysfunction (ED) in male patients with acromegaly. Methods: Fifty-one male patients with acromegaly were assessed by the International Index of Erectile Function-5 and Acromegaly Quality of Life (Acro-QoL) questionnaires. The measurement of serum nitric oxide (NO) were performed in patients and age-matched nonacromegalic controls. Results: Among 51 patients analyzed, 32 (62.7%) had ED. Patients with ED showed lower Acro-QoL scores regarding global (69.8 17.7 versus 79.4 11.2; P = .035) and personal relationship dimensions (59.6 22.1 versus 76.8 17.6; P = .012) than non-ED patients. ED patients were older (44.5 11.2 years versus 33.2 8.5 years; P = .04) and showed higher growth hormone (GH) levels (15.5 g/L [interquartile range of 9.5 to 34.5 g/L] versus 5.9 g/L [interquartile range of 3.4 to 13.9 g/L]; P = .001) compared to non-ED patients. The cutoff values for identifying ED were 7.9 g/L for random GH and 5.3 g/L for GH nadir after oral administration of 75 g of glucose. There was no significant difference in total testosterone levels between the two groups (6.36 4.24 nmol/L versus 9.54 5.50 nmol/L; P = .299). The NO levels in patients with acromegaly were significantly lower than those in nonacromegalic controls (8.77 1.78 mol/L versus 19.19 5.02 mol/L, respectively; P = .049). Furthermore, the NO levels were even lower in ED patients than those in non-ED patients (5.14 0.98 mol/L versus 12.09 3.44 mol/L; P = .027). Conclusion: Our study showed that ED is prevalent in male acromegalic patients and may be associated with systemic endothelial dysfunction induced by excessive GH. Further studies investigating the mechanism of GH and ED are required. Abbreviations: Acro-QoL = Acromegaly Quality of Life; ED = erectile dysfunction; FSH = follicle-stimulating hormone; GH = growth hormone; IGF-1 = insulin-like growth factor 1; IIEF-5 = international index of erection function-5; LH = luteinizing hormone; MRI = magnetic resonance imaging; NO = nitric oxide; OGTT = oral glucose tolerance test; QoL = quality of life; ROC = receiver operating characteristic. | [
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] |
Objective: This study aimed to assess the impact of multidisciplinary process improvement interventions on glycemic control in the inpatient setting of an urban community hospital, utilizing the daily simple average as the primary glucometric measure. Methods: From 2010-2014, five process of care interventions were implemented in the noncritical care inpatient units of the study hospital. Interventions included education of medical staff, implementation of hyperglycemia and hypoglycemia protocols, computerized insulin order entry, and coordination of meal tray delivery with finger stick and insulin administration. Unpaired t tests compared pre- and postintervention process measures. Simple average daily glucose measure was the primary glucometric outcome. Secondary outcome measures included frequency of hyperglycemia and hypoglycemia. Glucose outcomes were compared with an in-network hospital that did not implement the respective interventions. Results: A total of 180,431 glucose measurements were reported from 4,705 and 4,238 patients from the intervention and comparison hospitals, respectively. The time between bolus-insulin administration and breakfast tray delivery was significantly reduced by 81.7 minutes (P<.00005). The use of sliding scale insulin was sustainably reduced. Average daily glucose was reduced at both hospitals, and overall rates of hypoglycemia were low. Conclusion: A multidisciplinary approach at an urban community hospital with limited resources was effective in improving and sustaining processes of care for improved glycemic control in the noncritical care, inpatient setting. Abbreviations: IQR = interquartile range; JMC = Jacobi Medical Center; NCBH = North Central Bronx Hospital. | [
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Objective: The aim of this study was to evaluate levothyroxine (LT4) replacement daily doses in patients with central hypothyroidism (CeH) and compare them with those adequate for patients with primary hypothyroidism (P-HYPO). Methods: We included 53 patients with CeH and 57 with P-HYPO, matched by sex, age, weight, and body mass index, in the period of 1 year. At the time of inclusion, all presented a stable and adequate dose of LT4 for at least 3 months, considering as adequate the dose associated with normal thyroid-stimulating hormone (TSH) levels and free thyroxine (T4) in P-HYPO patients, and free T4 levels in CeH patients. Results: The absolute daily dose of LT4 differed significantly between the two groups, 103.0 27.1 g (CeH) and 89.3 32.0 g (P-HYPO) (P = .017), even after adjustment for age, gender, and free T4 (P = .04). The LT4 dose adjusted to weight was also higher after adjustment for age, gender and free T4 (P = .04), with an average of 1.3 0.4 g/kg (CeH) and 1.2 0.4 g/kg (P-HYPO). Sheehan syndrome patients had a lower absolute daily dose of LT4 (P = .001), and patients who underwent pituitary radiotherapy required higher doses (P = .008). There was no difference in the daily dose of LT4 according to other pituitary hormone deficiencies. Conclusion: The results reinforce the relevance of a careful individualization of LT4 replacement in CeH management and the need for new markers for proper LT4 replacement therapy in such cases. Abbreviations: BMI = body mass index; CeH = central hypothyroidism; GH = growth hormone; LT4 = levothyroxine; P-HYPO = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone. | [
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] |
Objective: Clinical trial data demonstrates improved glycemic control with hybrid close loop (HCL) insulin delivery systems, yet limited real-world data exists. Data from the inaugural cohort of patients initiating a HCL system (Medtronic MiniMed 670G, Medtronic Canada, Brampton, ON) at a university medical center was used to examine real-world utilization and glycemic control following a standardized implementation process. Methods: Data from 34 adult patients with type 1 diabetes were obtained from pump downloads at 4 time points: (1) previous insulin pump, (2) HCL in manual-mode, (3) 2 weeks after HCL auto-mode transition, and (4) 6 to 12 weeks after initiation of HCL. In-person training by certified diabetes educators was performed across 3 sessions with phone and electronic messaging following auto-mode start. Results: Mean self-monitored blood glucose (SMBG) per day increased from 5.15 baseline to 6.49 at 6 to 12 weeks (P<.05) with 3.26 sensor calibrations per day. Time-in-auto-mode was 79.3% at 2 weeks and 72.3% at final follow-up, with 82% of patients spending >50% of time in auto-mode. There were 8.2 auto-mode exits over the final 14-day download. Time-in-target was 67.3% in manual-mode, 73.4% at 2 weeks (P = .09), and 71.7% by 6 to 12 weeks (P = .06). Hemoglobin A1c (HbA1c) decreased by 0.51% (P = .02), while total daily dose and % basal did not change. Patients with HbA1c <7.0% (53 mmol/mol) at baseline spent more time-in-target than those with HbA1c ?7.0% (53 mmol/mol; 78.0% versus 67.5%) despite spending less time-in-auto-mode (66.5% versus 74.8%). Conclusion: These data illustrate real-world implementation of HCL technology using a structured education program within a major medical center. Overall benefit may vary based on baseline characteristics such as HbA1c. Abbreviations: CDE = certified diabetes educator; HbA1c = hemoglobin A1c; HCL = hybrid closed loop; SMBG = self-monitored blood glucose. | [
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Objective: To summarize the characteristics of patients with pituitary stalk thickening, analyze the association between pituitary stalk width and hypopituitarism, and develop a diagnostic model to differentiate neoplastic and inflammatory origins. Methods: A total of 325 patients with pituitary stalk thickening in a tertiary teaching hospital between January 2012 and February 2018 were enrolled. Basic characteristics and hormonal status were evaluated. Indicators to predict etiology in patients with histologic diagnoses were analyzed. Results: Of the 325 patients, 62.5% were female. Deficiency in gonadotropin was most common, followed by corticotropin, growth hormone, and thyrotropin. The increase in pituitary stalk width was associated with a risk of central diabetes insipidus (odds ratio [OR], 3.57; P<.001) and with a combination of central diabetes insipidus and anterior pituitary deficiency (OR, 2.28; P = .029). The cut-off pituitary stalk width of 4.75 mm had a sensitivity of 69.2% and a specificity of 71.4% for the presence of central diabetes insipidus together with anterior pituitary deficiency. Six indicators (central diabetes insipidus, pattern of pituitary stalk thickening, pituitary stalk width, neutrophilic granulocyte percentage, serum sodium level, and gender) were used to develop a model having an accuracy of 95.7% to differentiate neoplastic from inflammatory causes. Conclusion: Pituitary stalk width could indicate the presence of anterior pituitary dysfunction, especially in central diabetes insipidus patients. With the use of a diagnostic model, the neoplastic and inflammatory causes of pituitary stalk thickening could be preliminarily differentiated. Abbreviations: APD = anterior pituitary dysfunction; AUC = area under the curve; CDI = central diabetes insipidus; GH = growth hormone; MRI = magnetic resonance imaging; OR = odd ratio; PHBS = posterior hypophyseal bright spots; PST = pituitary stalk thickening; PSW = pituitary stalk width. | [
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] |
PURPOSE: The efficacy and safety of retropubic and transobturator tension-free vaginal tape mid urethral slings remain controversial in patients with stress urinary incontinence and risk factors for recurrence. We compared the techniques after initial mid urethral sling insertion in select groups, including patients with obesity, intrinsic sphincter deficiency, pelvic organ prolapse and recurrent stress urinary incontinence.MATERIALS AND METHODS: We used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement to report the methods and results of the current review. Randomized controlled trials and observational studies were included. We assessed the objective and subjective cure rates, and the complication rate using the OR with the 95% CI. The protocol of the current meta-analysis was registered on PROSPERO (No. CRD42018102233).RESULTS: We retrieved 28 studies in a total of 2,607 patients to compare the efficacy and safety of retropubic vs transobturator tension-free vaginal tape in select groups (mean followup 26.9 months). Meta-analysis of the objective cure rate showed the significant superiority of retropubic compared to transobturator tension-free vaginal tape in patients overall (OR 3.37, 95% CI 2.55-4.43, p <0.00001, I2 = 37%) and in each subpopulation. The subjective cure rate of retropubic tension-free vaginal tape was also significantly superior to that of transobturator tension-free vaginal tape in in patients overall (OR 2.01, 95% CI 1.45-2.80, p <0.0001, I2 = 0%) and in those with intrinsic sphincter deficiency and recurrent stress urinary incontinence after mid urethral sling insertion. There was no significant difference in overall complications between retropubic and transobturator tension-free vaginal tape (OR 1.22, 95% CI 0.89-1.66, p = 0.21, I2 = 0%).CONCLUSIONS: The meta-analysis showed the superiority of retropubic tension-free vaginal tape over transobturator tension-free vaginal tape in terms of the objective and subjective cure rates in patients with obesity, intrinsic sphincter deficiency, pelvic organ prolapse and recurrent stress urinary incontinence after mid urethral sling insertion. Retropubic tension-free vaginal tape also has morbidity comparable to that of transobturator tension-free vaginal tape. | [
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The apicomplexan centrosome has a unique bipartite structure comprising an inner and outer core responsible for the nuclear cycle (mitosis) and budding cycles (cytokinesis), respectively. Although these two cores are always associated, they function independently to facilitate polyploid intermediates in the production of many progeny per replication round. Here, we describe the function of a large coiled-coil protein in Toxoplasma gondii, TgCep250, in connecting the two centrosomal cores and promoting their structural integrity. Throughout the cell cycle, TgCep250 localizes to the inner core but, associated with proteolytic processing, is also present on the outer core during the onset of cell division. In the absence of TgCep250, stray centrosome inner and outer core foci were observed. The detachment between centrosomal inner and outer cores was found in only one of the centrosomes during cell division, indicating distinct states of mother and daughter centrosomes. In mammals, Cep250 processing is required for centrosomal splitting and is mediated by Nek phopsphorylation. However, we show that neither the nonoverlapping spatiotemporal localization of TgNek1 and TgCep250 nor the distinct phenotypes upon their respective depletion support conservation of this mechanism in Toxoplasma. In conclusion, TgCep250 has a tethering function tailored to the unique bipartite centrosome in the Apicomplexa. | [
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Mitochondria are essential and dynamic organelles undergoing constant fission and fusion. The primary players in mitochondrial morphology (MFN1/2, OPA1, DRP1) have been identified, but their mechanism(s) of regulation are still being elucidated. ARL2 is a regulatory GTPase that has previously been shown to play a role in the regulation of mitochondrial morphology. Here we demonstrate that ELMOD2, an ARL2 GTPase-activating protein (GAP), is necessary for ARL2 to promote mitochondrial elongation. We show that loss of ELMOD2 causes mitochondrial fragmentation and a lower rate of mitochondrial fusion, while ELMOD2 overexpression promotes mitochondrial tubulation and increases the rate of fusion in a mitofusin-dependent manner. We also show that a mutant of ELMOD2 lacking GAP activity is capable of promoting fusion, suggesting that ELMOD2 does not need GAP activity to influence mitochondrial morphology. Finally, we show that ELMOD2, ARL2, Mitofusins 1 and 2, Miros 1 and 2, and mitochondrial phospholipase D (mitoPLD) all localize to discrete, regularly spaced puncta along mitochondria. These results suggest that ELMOD2 is functioning as an effector downstream of ARL2 and upstream of the mitofusins to promote mitochondrial fusion. Our data provide insights into the pathway by which mitochondrial fusion is regulated in the cell. | [
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] |
PURPOSE: Multiple factors are associated with lower urinary tract symptoms and sleep disturbance is well known to be associated with nocturia. The association between sleep disturbance and lower urinary tract symptoms has not been sufficiently elucidated. We evaluated the impact of sleep disturbance on lower urinary tract symptoms, especially voiding symptoms, in the Nagahama Study.MATERIALS AND METHODS: The Nagahama Study is a prospective cohort study of healthy individuals. Among them study participants 50 years old or older who completed the I-PSS (International Prostate Symptom Score) questionnaire and a sleep problem questionnaire were included in this analysis and followed for 5 years. Sleep disturbance was stratified into poor sleep quality, sleep restriction and sleep medication use. We analyzed the association between sleep disturbance and worsening of lower urinary tract symptoms adjusted by various clinical factors on multivariate logistic regression analysis.RESULTS: Among the 5,297 participants the prevalence of lower urinary tract symptoms at baseline was 23% and the prevalence rates of poor sleep quality, sleep restriction and sleep medication were 20%, 6% and 7%, respectively. Participants with poor sleep quality, sleep restriction or sleep medication use had a significantly greater incidence of lower urinary tract symptoms and voiding symptoms than those without such characteristics (p <0.01). Poor sleep quality and sleep medication use were significantly associated with worsening lower urinary tract symptoms as defined by an I-PSS score increase of 4 or greater (OR 1.23, p = 0.03, and 1.67, p <0.01), and with worsening voiding symptoms, defined as an increase of 3 or greater (OR 1.35, p <0.005, and 1.85, p <0.001, respectively).CONCLUSIONS: Sleep disturbance was significantly associated with the presence of lower urinary tract symptoms in a cross-sectional manner and with worsening lower urinary tract symptoms longitudinally. | [
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Mislabelling in fish products is a highly significant emerging issue in world fish trade in terms of health and economic concerns. DNA barcoding is an efficient sequencing-based tool for detecting fish species substitution but due to DNA degradation, it is in many cases difficult to amplify PCR products of the full-length barcode marker (~650 bp), especially in severely processed products. In the present study, a pair of universal primers targeting a 198 bp sequence of the mitochondrial 16s rRNA gene was designed for identification of fish species in the processed fish products commonly consumed in Malaysia. The specificity of the universal primers was tested by both in-silico studies using bioinformatics software and through cross-reaction assessment by practical PCR experiments against the DNA from 38 fish species and 22 other non-target species (animals and plants) and found to be specific for all the tested fish species. To eliminate the possibility of any false-negative detection, eukaryotic endogenous control was used during specificity evaluation. The developed primer set was validated with various heat-treated (boiled, autoclaved and microwaved) fish samples and was found to show high stability under all processing conditions. The newly developed marker successfully identified 92% of the tested commercial fish products with 96-100% sequence similarities. This study reveals a considerable degree of species mislabelling (20.8%); 5 out of 24 fish products were found to be mislabelled. The new marker developed in this work is a reliable tool to identify fish species even in highly processed products and might be useful in detecting fish species substitution thus protecting consumers' health and economic interests. | [
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] |
Two-dimensional (2D) substrate rigidity promotes myosin II activity to increase traction force in a process negatively regulated by tropomyosin (Tpm) 2.1. We recently discovered that actomyosin contractility can increase intracellular pressure and switch tumor cells from low-pressure lamellipodia to high-pressure lobopodial protrusions during three-dimensional (3D) migration. However, it remains unclear whether these myosin II-generated cellular forces are produced simultaneously, and by the same molecular machinery. Here we identify Tpm 1.6 as a positive regulator of intracellular pressure and confirm that Tpm 2.1 is a negative regulator of traction force. We find that Tpm 1.6 and 2.1 can control intracellular pressure and traction independently, suggesting these myosin II-dependent forces are generated by distinct mechanisms. Further, these tropomyosin-regulated mechanisms can be integrated to control complex cell behaviors on 2D and in 3D environments. | [
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Previously, we had shown that high magnitude stretch (HMS), rather than low magnitude stretch (LMS), induced significant apoptosis of skeletal muscle C2C12 myoblasts. However, the molecular mechanism remains obscure. In this study, we found that p53 protein accumulated in the nucleus of LMS-loaded cells, whereas it translocated into mitochondria of HMS-loaded cells. Knocking down endogenous p53 by shRNA abrogated HMS-induced apoptosis. Furthermore, we demonstrated that overaccumulation of reactive oxygen species (ROS) during HMS-inactivated AKT that was activated in LMS-treated cells, which accounted for the distinct p53 subcellular localizations under HMS and LMS. Blocking ROS generation by N-acetylcysteine (NAC) or overexpressing constitutively active AKT vector (CA-AKT) inhibited HMS-incurred p53 mitochondrial translocation and promoted its nuclear targeting. Moreover, both NAC and CA-AKT significantly attenuated HMS-induced C2C12 apoptosis. Finally, we found that Ser389 phosphorylation of p53 was a downstream event of ROS-inactivated AKT pathway, which was critical to p53 mitochondrial trafficking during HMS stimuli. Transfecting p53-shRNA C2C12s with the mutant p53 (S389A) that was unable to target p53 to mitochondria underwent significantly lower apoptosis than transfection with wild-type p53. Altogether, our study uncovered that mitochondrial localization of p53, resulting from p53 Ser389 phosphorylation through ROS-inactivated AKT pathway, prompted C2C12 myoblast apoptosis during HMS stimulation. | [
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Integrin 64 is an essential, dynamic adhesion receptor for laminin 332 found on epithelial cells, required for formation of strong cell-extracellular matrix (ECM) adhesion and induced migration, and coordinated by regions of the 4C cytoplasmic domain. 4E, a unique splice variant of 4 expressed in normal tissue, contains a cytoplasmic domain of 231 amino acids with a unique sequence of 114 amino acids instead of 4C's canonical 1089 amino acids. We determined the distribution of 64E within normal human glandular epithelium and its regulation and effect on cellular biophysical properties. Canonical 64C expressed in all basal cells, as expected, while 64E expressed within a subset of luminal cells. 64E expression was induced by three-dimensional culture conditions, activated Src, was reversible, and was stabilized by bortezomib, a proteasome inhibitor. 64C expressed in all cells during induced migration, whereas 64E was restricted to a subset of cells with increased kinetics of cell-cell and cell-ECM resistance properties. Interestingly, 64E presented in "ringlike" patterns measuring ?1.75 ? 0.72 microns and containing actin and CD9 at cell-ECM locations. In contrast, 64C expressed only within hemidesmosome-like structures containing BP180. Integrin 64E is an inducible adhesion isoform in normal epithelial cells that can alter biophysical properties of cell-cell and cell-ECM interactions. | [
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] |
PURPOSE: Patients with bladder cancer who undergo intestinal urinary diversion may be at increased risk for bone fractures thought to be secondary to chronic metabolic acidosis and ensuing bone loss. Our main objective was to assess whether patients who undergo intestinal urinary diversion are at increased risk for fracture.MATERIALS AND METHODS: Patients who underwent intestinal urinary diversion between 1994 and 2014 in Ontario, Canada were identified using linked administrative databases. Patients were categorized as undergoing diversion for bladder cancer or nonbladder cancer causes and matched 4:1 to a healthy cohort. We determined incidence rates of the incidence of fractures per 100 person-years. Multivariable Cox proportional hazards models were used to evaluate the impact of intestinal urinary diversion on the risk of fracture.RESULTS: Overall 4,301 patients with and 907 without bladder cancer underwent intestinal urinary diversion. The fracture incidence rate was significantly greater in the bladder cancer and nonbladder cancer cohorts compared to respective matched controls. In the bladder cancer cohort vs matched controls there were 4.41 vs 2.63 fractures per 100 person-years and in the nonbladder cancer cohort vs matched controls there were 5.67 vs 3.51 fractures per 100 person-years (each p <0.001). On multivariable analysis patients who underwent intestinal urinary diversion for bladder cancer or nonbladder cancer reasons had significantly shorter fracture-free survival compared to the respective matched cohorts (HR 1.48, IQR 1.35-1.63, and HR 1.48, IQR 1.31-1.69, respectively).CONCLUSIONS: Our results demonstrated that regardless of age patients with intestinal urinary diversion are at increased risk for bone fractures compared to the general population. Our findings are in line with previous reports and support the need for bone health monitoring. | [
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] |
PURPOSE: Kidney stones are a source of significant morbidity which have been shown to negatively impact health related quality of life. We sought to understand the association between health related quality of life, socioeconomic status and race among patients with kidney stones.MATERIALS AND METHODS: Patients with stones at a total of 11 stone centers across the United States completed the WISQOL (Wisconsin Stone Quality of Life questionnaire). The patient ZIP Code was used to estimate household income. A mixed effects regression model was constructed for analysis with ZIP Code as the random intercept.RESULTS: A total of 2,057 stone formers completed the WISQOL. Lower income was independently associated with significantly lower health related quality of life ( = 0.372, p = 0.014), as were nonwhite race ( = -0.299, p = 0.001), unemployed work status ( = -0.291, p = 0.008), female gender ( = -0.204, p <0.001), body mass index greater than 40 kg/m2 ( = -0.380, p <0.001), 5 or more medical comorbidities ( = -0.354, p = 0.001), severe recurrent stone formation ( = -0.146, p = 0.045), enrollment at an acute care visit, or a preoperative or postoperative appointment ( = -0.548, p <0.001) and recent stone symptoms ( = -0.892, p <0.001).CONCLUSIONS: Lower income, nonwhite race and unemployed work status were independently associated with lower health related quality of life among patients with kidney stones. While clinical characteristics such as body mass and stone disease severity were also associated with health related quality of life, this study shows that socioeconomic factors are similarly important. Further research to understand the specific mechanisms by which socioeconomic status and race impact health may lend insight into methods to optimize clinical treatment of stone formers and patients with other chronic diseases. | [
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] |
PURPOSE: The aims of this investigation were to examine how often outpatient visits addressing urinary incontinence in women with self-reported incontinence symptoms occur and to explore characteristics associated with an outpatient visit for incontinence.MATERIALS AND METHODS: We studied the records of 18,576 women from the Nurses' Health Study who were 65 years old or older, reported prevalent incontinence symptoms in 2012 on a mailed questionnaire and were linked with Medicare utilization data. We compared demographic, personal and clinical characteristics in women with and without claims for outpatient visits for urinary incontinence. In logistic regression models we controlled for potential confounding factors, including age, race, parity, body mass index, medical comorbidities, smoking status, health seeking behavior, disability, physical function and geographic region.RESULTS: In this linkage between symptom report and insurance claims data we found that only 16% of older women with current incontinence symptoms also had an outpatient visit addressing incontinence in the prior 2 years. In multivariable adjusted models severe vs slight incontinence (OR 3.75, 95% CI 3.10-4.53) and urgency vs stress incontinence (OR 1.80, 95% CI 1.56-2.08) were the strongest predictors of undergoing outpatient evaluation.CONCLUSIONS: Overall only a small percent of women who report urinary incontinence symptoms also have medical outpatient visits for incontinence, which is a marker of care seeking. Our study highlights the discordance between the high prevalence of incontinence in older women and the lack of clinical assessment despite symptoms even among nurses with high health care literacy. | [
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] |
The aim of this study was to assess the Al dietary exposure of young Chinese children aged 0-3years via formulae, complementary foods and wheat-based foods. Al residue data were obtained from the national food contamination monitoring programme from 2013 to 2016, encompassing 13,833 samples of 12 food items with a detection rate of 76.0%. Food consumption data were gathered from the China National Food Consumption Survey conducted in 2015, comprising 20,172 children aged 0-3years old. The mean dietary exposure to Al for the general population of young Chinese children was estimated at 0.76 mg/kg bw/week, which does not exceed the PTWI. The 97.5th percentile intakes of Al reached 3.42 mg/kg bw/week, more than 1.7 times the PTWI. Wheat-based foods contributed 80.5% of the Al intake for the general population of young Chinese children, while formulae and complementary foods accounted for 19.5% of the total intake. The dietary intake of Al from formulae and complementary foods accounted for 6.0% and 1.6% of PTWI, respectively. These findings suggested that dietary exposure to Al among the general population of young Chinese children was lower than the PTWI and that there are no health concerns related to this level of Al intake. However, more attention should be placed on the health risks associated with Al exposure from wheat-based foods for young consumers with high food consumption in China (97.5th percentile). | [
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] |
PURPOSE: We systematically characterized gene expression, inflammation and neovascularization in patients with interstitial cystitis/bladder pain syndrome to obtain biological evidence supporting diagnosis and classification.MATERIALS AND METHODS: We sequenced RNA obtained from bladder mucosal biopsies of 33 patients with 3 subtypes of interstitial cystitis/bladder pain syndrome, including Hunner lesions in 12, no Hunner lesions in 11 but with glomerulations and neither Hunner lesions nor glomerulations in 10, and 9 controls. Differentially expressed genes of each subtype were searched to identify subtype specific biological pathways and candidate genes important for pathogenesis. Candidate genes were validated by quantitative polymerase chain reaction and immunohistochemistry. Digital immunohistochemical quantification was performed to assess subepithelial lymphoplasmacytic cell and microvessel density. Relationships between candidate gene over expression and symptom severity were explored.RESULTS: Patients with Hunner lesions showed a distinct gene expression profile associated with significant up-regulation of biological processes involving immune responses and infection, and an increase in subepithelial lymphoplasmacytic cell and microvessel density. Over expression of 2 candidate genes, VEGF and BAFF, correlated with symptom severity. Meanwhile, the gene expression profiles of patients with the 2 subtypes without Hunner lesions were similar to those of controls. No difference in biological pathways or subepithelial lymphoplasmacytic cell and microvessel density were detected between these 2 subtypes and controls.CONCLUSIONS: Interstitial cystitis/bladder pain syndrome with Hunner lesions shows distinct genomic and histological features associated with immune responses and infection. In addition, VEGF and BAFF are potential disease biomarkers and therapeutic targets. This subtype should be considered separate from the syndrome. | [
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BACKGROUND: In non-endemic countries, malaria risk is addressed by selectively testing or deferring at-risk donors. These policy decisions were made using a variety of decision-making frameworks prior to the development of the Alliance of Blood Operators Risk Based Decision-Making Framework. It is unclear whether the range of items assessed in the decision-making process would be increased if the Framework were used. We compared assessments considered in France, England and Australia for decisions to implement selective testing, plus donor selection criteria (Canada and the USA included) with those recommended by the Framework.MATERIALS AND METHODS: Elements of the Framework were identified: the intervention, safety threat, availability threat, donor impact, financial implications, risk communication, stakeholder and regulatory aspects. Decisions about selective testing and donor selection criteria were analysed separately. Assessments were compared against elements of the Framework and the level of concern for considerations rated.RESULTS: Sufficiency of the blood supply (plus safety in France) were the drivers for selective testing; main trade-offs were high operational impact and cost. In three donor criteria examples, transfusion-transmitted malaria cases prompted the change. Social concerns were high in France and Australia, political/regulatory concerns influenced decisions in France, Australia and Canada, while sufficiency was a consideration in Canada and the USA. Decision trade-offs involved moderate operational impact.DISCUSSION: The assessments considered in each country were generally consistent with the assessments recommended by the Framework. When data supported quantified risk assessment, safety and operational feasibility had the greatest weight. When risk was not well defined, contextual factors such as social and political concern had greater weight. | [
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Patient blood management (PBM) is the timely application of evidence-informed medical and surgical concepts designed to maintain haemoglobin concentration, optimise haemostasis, and minimise blood loss in an effort to improve patient outcomes. The aim of this consensus statement is to provide recommendations on the prevention and treatment of postpartum haemorrhage as part of PBM in obstetrics. A multidisciplinary panel of physicians with expertise in obstetrics, anaesthesia, haematology, and transfusion medicine was convened by the Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis (NATA) in collaboration with the International Federation of Gynaecology and Obstetrics (FIGO), the European Board and College of Obstetrics and Gynaecology (EBCOG), and the European Society of Anaesthesiology (ESA). Members of the task force assessed the quantity, quality and consistency of the published evidence, and formulated recommendations using the system developed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group. The recommendations in this consensus statement are intended for use by clinical practitioners managing perinatal care of women in all settings, and by policy-makers in charge of decision making for the update of clinical practice in health care establishments. | [
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The reliable prediction of transport and attenuation of dissolved-phase contamination in the unsaturated zone is a complex and multi-process problem. Based on the adsorption properties of soil samples to solutes, the soil column test and laboratory analysis were carried out in this study. The effects of the loam inter-layer on the migration and breakthrough of the characteristic pollutant benzene and non-absorbent Br- were studied. The results showed that the relatively high clay content of the inter-layer significantly changed the BTC (breakthrough curve). It not only delayed the migration time of benzene into the aquifer but also to some extent produced an attenuation effect, effectively reducing the content of the characteristic pollutants through the unsaturated zone. The dispersion coefficient was obtained through the measured Br-. The theoretical values were calculated and compared with the experimental data by using a one-dimensional unsaturated solute transport equation. The result was basically consistent, which proved the validity and reliability of the model. Through the BTC of benzene, the retardation factor was obtained and used to describe the influence of the loam inter-layer on the migration and breakthrough, which could provide the basis for the accurate modeling of groundwater remediation projects. | [
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Passive sampling (PS) is a very useful approach for the monitoring of emerging contaminants in environmental matrices, showing greater sensitivity than can be achieved by current best practice - grab sampling - and is applicable to a wide variety of compounds. An EU Directive (2013/39/EC) has added substances to the existing Water Framework Directive (WFD) Priority Substance list. Investigation into PS in the monitoring of these compounds is necessary to show the potential of this technique in supporting monitoring requirements under the WFD. A catchment-based approach evaluated the occurrence of these compounds in Irish surface waters. This work deals with the challenges associated with the use of PS in a legislative context, and for routine monitoring of emerging contaminants. Looking at a number of sites across Ireland, upstream and downstream of wastewater treatment plants, the focus was on polar analytes and polar PS (POCIS). With method limits of detection (LODs) of 0.001 mg L-1 pharmaceuticals and endocrine disrupting chemicals (EDCs) were found in water and passive samples alike, whereas the polar pesticides were not often detected or were below the annual average environmental quality standard levels. The results of this study show the potential for PS as a monitoring technique for emerging and watch-list chemicals. | [
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Infiltration and inflow (I/I) of extraneous water in separate sewer systems are serious concerns in urban water management for their environmental, social and economic consequences. Effective reduction of I/I requires knowing where excess water ingress and illicit connections are located. The present study focuses on I/I detection in the foul sewer network of a catchment in Trondheim, Norway, during a period without snowmelt or groundwater infiltration. Fiber-optic distributed temperature sensing (DTS) was used for the first time in Norway to detect I/I sources in tandem with closed-circuit television inspection (CCTV) and smoke testing. DTS was an accurate and feasible method for I/I detection, though it cannot identify exact types of failure and sources of I/I. Therefore, other complementary methods must be used, e.g. CCTV or smoke testing. However, CCTV was not completely useful in confirming the DTS results. This study provides practical insights for the rehabilitation and repair of sewer networks that suffer from the undesirable I/I of extraneous water. | [
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Toxic heavy metals and organic pollutants simultaneously exist in the wastewater of some industries. This study explores reduction of toxic divalent nickel ions, from either nitrate or sulfate salts, coupled with naphthalene (NA) degradation using titania photocatalyst in an efficient photo-sono reactor. A synergism appears when reduction and degradation treatments occur simultaneously in the media. With initial concentrations of [Ni(II)]0 = 5 mg/L and [NA]0 = 10 mg/L, under dominant mild conditions, removal efficiencies of 54.5% and 56.6% were obtained for Ni(II) and NA, respectively, when nickel nitrate was used. These efficiencies were enhanced to 59.2% and 57.5%, respectively, with nickel sulfate, all after 90 min operation. For evaluating the mechanism of reactions, reactive oxygen species analysis on solutions as well as Fourier transform infrared, scanning electron microscopy and Brunauer-Emmett-Teller analyses on the titania nanoparticles, before and after usage, was performed. The reaction kinetics was also followed for individual species in the mixed solution and, accordingly, the energy consumption was evaluated for one order of magnitude decrease in pollutant concentration. The high performance of the used method was revealed in comparison to the similar reported reduction/degradation processes. | [
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] |
The main goal of the present study was to enhance the rhizobacterium potential in a horizontal subsurface flow constructed wetland system planted with Phragmites australis, through environmentally friendly biological approaches. The bioinoculation of antagonist bacteria has been used to promote higher rhizosphere competence and improve pathogenic bacteria removal from wastewater. The experiment was performed both with single and sequential bioinoculation. The results showed that strain PFH1 played an active role in pathogenic bacteria removal, remarkably improving inactivation kinetics of the pathogenic tested bacterium Salmonella typhi in the plant rhizosphere. The single bioinoculation of selected bacteria into the rhizosphere of P. australis improved the kinetics of S. typhi inactivation by approximately 1 U-Log10 (N/N0) (N is the number of viable cultured bacteria at time t, N0 is the number of viable and cultivable bacteria at time t0) compared to the control. By a series of multi-bioinoculations, the enhancement of pathogenic bacteria reduction compared to the inhibition rate in the pilot-scale control was of 2 U-Log10(N/N0). These findings suggested that this strain represents a promising candidate to enhance water purification in constructed wetlands. | [
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Pulsed light (PL) is a type of photonic technology characterized by intense short light pulses that enhance the speed of photochemical reactions, and which might be useful as light source in advanced oxidation processes. This work aimed to test PL as light source for the degradation of the dye malachite green (MG) by combining PL with H2O2. To this end, the effect of dye and H2O2 concentrations and pH on the degradation rate of MG was studied and a degradation pathway was proposed. Dye degradation followed a pseudo-first order kinetics; it increased with low initial dye concentration, high H2O2 concentration and low pH. Complete decolourization was achieved after 35 light pulses (75 J/cm2), with a degradation rate of 0.0710 cm2/J. The degradation was initiated by the attack of hydroxyl radicals to the central carbon of MG generating 4-(dimethylamino)benzophenone (DLBP) followed by the addition of hydroxyl radicals to the non-amino aromatic ring of DLBP and the demethylation of the amino group. Results indicate that PL technology has potential to be implemented to decrease the environmental impact of dyeing industries. | [
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] |
A continuous hydrogen and methane production system in a two-stage process has been investigated to increase energy recovery rate from molasses wastewater in this study. This system consisted of a continuous stirred-tank reactor for hydrogen production and an internal circulation (IC) reactor for methane production, and was studied under the influent organic loading rate (OLR) of 18, 24, 30 and 36kg COD/(m3d) (COD: chemical oxygen demand). The maximum volumetric hydrogen production rate of 2.41 L/(Ld) was obtained at the OLR of 30kg COD/(m3d) with a hydrogen content of 42%, and the maximum volumetric methane production rate of 2.4 L/(Ld) with a methane content of 74.45% was obtained at the OLR of 36kg COD/(m3d) using the effluents of hydrogen fermentation as substrate. The maximum of 71.06% of the molasses wastewater energy was converted to biogas (hydrogen and methane) at the OLR of 30kg COD/(m3d). | [
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In this paper, a stormwater fee specifically for small municipalities was developed through a simplification of the Equivalent Residential Unit (ERU) system, which is the main method applied in the United States. The Simplified ERU is based on the amount of impervious area and the fee considers the operations and maintenance costs, besides having a single class of billing. It was applied in Santo Amaro da Imperatriz city, located in the southern region of Brazil, which can be classified as a small city. The value of the Simplified ERU (294.32 m2) was similar to the average impervious area in the United States (269.42 m2) and it was equivalent to $0.28 per square meter (within the range of other countries' fees). The method proved to be a feasible and rapid technique for funding stormwater services, and its simplicity allows its application in different locations. This funding model can generate revenue to address current stormwater problems, such as the lack of funding for existing drainage infrastructure, and contribute to downstream flooding reduction. This paper also intends to encourage discussion about the methods for designing a stormwater fee in the academic community, which is still incipient. | [
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Antibiotics, as emerging contaminants, are of global concern due to the development of antibiotic resistant microorganisms. Current wastewater treatment technology cannot efficiently remove sewage antibiotics and therefore new low-cost technologies are needed. Adsorption is a widely used process for removal of substances, and the search for efficient, low-cost adsorbents is ongoing. In this work, termite feces treated with H2SO4 (FT/H2SO4) were used as a low-cost adsorbent for removal of norfloxacin (NOR) present in aqueous medium. Termite feces were treated with H2SO4 at a ratio of 1:1 for 24 h, at 100 C. The parameters contact time, initial NOR concentration, medium pH and temperature were evaluated. The optimum adsorption pH was 8.0. The pseudo-second-order model was found to best represent the kinetics of NOR adsorption. The maximum adsorption capacity, calculated from the Sips isotherm model, was 104.4 mg/g at 55 C. The positive values of H0 (change in enthalpy) confirm the endothermic nature of the adsorption. The results show that FT/H2SO4 is an efficient adsorbent for removal of NOR present in aqueous medium. The adsorption capacity is higher than those reported in the literature for other low-cost adsorbents. | [
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This study represents the first attempt to chemically modify wheat straw (WS) using 3-chloropropyltrimethoxysilane (CPTMS) and (1,4-diazabicyclo[2.2.2]octane) (DABCO). Field emission scanning electron micrographs (FESEM), energy dispersive spectroscopy (EDS), thermogravimetric analysis (TGA) and Fourier transform infrared (FTIR) spectra confirmed the successful morphological and structural modification of WS and the thermal stability of the modified WS (MWS). The MWS was used to remove nitrate from water. The optimum conditions of nitrate adsorption onto MWS were examined by conducting batch experiments. The results indicated that 85% of nitrate was removed under the conditions of initial nitrate concentration = 20 mg L-1, initial solution pH = 7, contact time = 10 min, MWS dosage = 2 g L-1 and temperature ? 25 C. The kinetic adsorption data were best fitted to the general order model and the adsorption process occurred in three distinct stages. The equilibrium adsorption data were well described by the Langmuir isotherm. Additionally, separation factor values were smaller than 1, implying that the adsorption process was favorable. The presence of competing anions impeded the nitrate adsorption in the order of sulfate > chloride > bicarbonate> phosphate. Thermodynamic parameters suggested that the adsorption process was exothermic, feasible and spontaneous in nature. Overall, the MWS could achieve efficient removal of nitrate under the simplest operating conditions. | [
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This study aims at defining a methodology to evaluate Ks reductions of gravel material constituting constructed wetland (CW) bed matrices. Several schemes and equations for the Lefranc's test were compared by using different gravel sizes and at multiple spatial scales. The falling-head test method was implemented by using two steel permeameters: one impervious (IMP) and one pervious (P) on one side. At laboratory scale, mean K values for a small size gravel (8-15 ? 10-2 m) measured by the IMP and the P permeameters were equal to 19,466 m/d and 30,662 m/d, respectively. Mean Ks values for a big size gravel (10-25 ? 10-2 m) measured by the IMP and the P permeameters were equal to 12,135 m/d and 20,866 m/d, respectively. Comparison of Ks values obtained by the two permeameters at laboratory scale as well as a sensitivity analysis and a calibration, lead to the modification of the standpipe equation, to evaluate also the temporal variation of the horizontal Ks. In particular, both permeameters allow the evaluation of the Ks decreasing after 4 years-operation and 1-1.5 years' operation of the plants at full scale (filled with the small size gravel) and at pilot scale (filled with the big size gravel), respectively. | [
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] |
It is of interest to develop a novel fabrication method of a mineral adsorbent for wastewater treatment to remove the combination of heavy metal ions and refractory organic contaminants. The crosslinking agent stearyl trimethyl ammonium chloride was added into a suspension of montmorillonite and graphene oxide to implement their recombination to fabricated graphene oxide-montmorillonite nanocomposite (GMN). The fabricated nanocomposite was characterized by X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller analysis and zeta potential. Results indicated that GMN exhibited a honeycomb texture, providing the chemical reaction site for the simultaneous adsorption of Pb2+ and p-nitrophenol (PNP). Factors including pH value, contact time, contact temperature and GMN dosage in the adsorption process were crucial for both Pb2+ adsorption and PNP adsorption. The optimum adsorption capacities of Pb2+ and PNP onto GMN were 19.39 mgg-1 and 14.90 mgg-1 under the condition of pH = 6, contact temperature 55 C, contact time 60 min and GMN dosage 0.10 g, respectively. Data from experimental studies on simultaneous adsorption was well described by the pseudo-second-order model. The implementation of this work shows that GMN is a promising material for application in the simultaneous removal of heavy metal ions and refractory organic contaminants. | [
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China has achieved significant progress on wastewater treatment and aquatic environmental protection. However, leakage (in- and exfiltration) of sewer systems is still an issue. By using the statistical data of water and wastewater in 2016 in China, and the person loads (PLs) of water and wastewater in Singapore, the leakage fractions of hydraulic flow, organic carbon (COD), nitrogen (N) and phosphorus (P) mass loading, and in-sewer COD biological removal in the sewer systems of China (except Hong Kong, Macau and Taiwan), Shanghai, Guangzhou and Beijing were reported for the first time. The fractions of hydraulic flow infiltration (13%, Shanghai and Guangzhou) and exfiltration (39%, China) were calculated. Except Beijing, whose sewer networks are under appropriate management with small leakage fractions, the exfiltration fractions of COD (including in-sewer biological COD removal) ranged from 41% (Shanghai) to 66% (China) and averaged 55%; N ranged from 18% (Shanghai) to 48% (China) and averaged 33%; and P ranged from 23% (Shanghai and Guangzhou) to 44% (China) and averaged 30%. The exfiltrated sewage, COD, N and P not only wastes resources, but also contaminates the aquatic environment (especially groundwater) and contributes to 'black and odorous water bodies'. In- and exfiltration in the sewer network leads to low influent COD concentration, C/N ratio and high inorganic solids and inert particulate COD concentrations of many municipal wastewater treatment plants (WWTPs) causing high cost for nutrient removal, poor resource recovery, additional reactor/settler volume requirement and other operational problems. Therefore, tackling sewer leakage is of primary importance to today's environment in China. Recommendations for the inspection of sewer systems and the rehabilitation of damaged sewers as well as the development of design and operation guidelines of municipal WWTPs tailored to the specific local sewage characteristics and other conditions are proposed. | [
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Contribution of specific interactions between human enteric viruses and wastewater suspended solids on human enteric virus removal by microfiltration was studied. A cross-flow microfiltration system was used with rotavirus HAL1166 and Enterobacter cloacae SENG-6 as the model virus and wastewater suspended solid. Cleavage of rotavirus HAL1166 protein VP4 by trypsin produces the VP8* subunit, which specifically interacts with histo-blood group antigen (HBGA). In the presence of Enterobacter cloacae SENG-6, the trypsin-treated rotavirus concentration reduced with time (R2 > 0.6) compared to the reduction of non-trypsin treated rotavirus. Calculation of the gel/cake layer deposited on the membrane, consisting of Enterobacter cloacae SENG-6 and either trypsin-treated or non-trypsin treated rotavirus HAL1166, revealed that the microflocs consisting of trypsin-treated rotavirus and Enterobacter cloacae SENG-6 have lower porosity and permeability, displaying higher resistance to virus passage through the membrane. The results provide evidence that specific wastewater suspended solids-human enteric virus interaction can contribute to increasing the removal of human enteric viruses by microfiltration. | [
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The effects of salinity on the photodegradation and mineralization of sulfonamides in the UV/TiO2 system were investigated. The goals of this study were to analyze the effects of pH and salinity on the sulfonamide concentration and total organic carbon (TOC) during the removal of sulfonamides in a UV/TiO2 system. Four sulfonamides - sulfadiazine (SDZ), sulfamethizole (SFZ), sulfamethoxazole (SMX) and sulfathiazole (STZ) - were selected as parent compounds. The photodegradation and mineralization rates of sulfonamides in the UV/TiO2 system satisfy pseudo-first-order kinetics. Direct photolysis degraded sulfonamides but sulfonamides cannot be mineralized. The photodegradation and mineralization rate constants in all experiments followed the order pH 5 > pH 7 > pH 9. At pH 5, the mineralization rate constants of SMX, SFZ, SDZ and STZ were 0.015, 0.009, 0.012 and 0.011 min-1, respectively. The addition of NaCl inhibited the mineralization of the four tested sulfonamides more than it inhibited their photodegradation. The inhibitory effect of chloride ions on the removal of sulfonamides in the UV/TiO2 system was attributed to the scavenging by chloride ions of hydroxyl radicals (HO•) and holes and the much lower reactivity of chlorine radicals thus formed, even though the chlorine radicals were more abundant than HO•. | [
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Efavirenz is one of the antiretroviral drugs widely used to treat the human immunodeficiency virus. Antiretroviral drugs have been found to be present in surface water and wastewater. Due to complexity of environmental samples, solid-phase extraction (SPE) is used for isolation and pre-concentration of antiretroviral drugs prior to their chromatographic analysis. However, the commercially available SPE sorbents lack selectivity, which tends to prolong the analysis time. Therefore, in this study a molecularly imprinted polymer was synthesized for the specific recognition of efavirenz and then applied as the SPE sorbent for its extraction from wastewater and surface water samples. The imprinted and non-imprinted polymers were synthesized using a bulk polymerization technique where efavirenz was used as the template, 2-vinylpyridine as functional monomer, 1,1'-azobis-(cyclohexanecarbonitrile) as initiator, ethylene glycol dimethacrylate as cross-linker and toluene:acetonitrile (9:1, v/v) as the porogenic solvent mixture. The characterization was performed using Fourier transform infrared spectroscopy, scanning electron microscopy, Brunauer-Emmett-Teller, elemental analysis, and thermogravimetric analysis techniques. Results showed better selectivity of molecularly imprinted polymer to efavirenz than did non-imprinted polymer. The analysis was performed using high performance liquid chromatography equipped with a photo-diode array detector. The analytical method gave a detection limit of 0.41 g/L and the analyte recovery of 81% in wastewater. The concentrations found in wastewater ranged from 2.79 to 120.7 g/L, while in surface water they were between 0.975 and 2.88 g/L. Therefore, the results of this study show a strong need for a detailed screening of efavirenz in major water utilities in the country. | [
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Many technologies have been proposed to oxidize chromium, such as roasting-water leaching technology and hydrometallurgical methods such as pressure oxidative leaching coupled with oxygen, ozone, permanganate and ferrate, but the problems associated with the high temperature, low overall resource utilization efficiency, high energy consumption, and the environmental pollution, still remain unsolved. This paper focuses on the oxidation process of chromium (III) with hydrogen peroxide (H2O2) in an alkaline medium. The effect of parameters including dosage of H2O2, dosage of NaOH, reaction time, reaction temperature and stirring rate on the oxidation efficiency of chromium were investigated. The oxidation efficiency was significantly affected by the dosage of H2O2 and NaOH, reaction time and reaction temperature took second place; last was the stirring rate. Oxidation efficiency was nearly 100% under the optimal conditions: volume ratio of H2O2 to mass of Cr2(SO4)3 of 2.4 mL/g, mass ratio of NaOH to Cr2(SO4)3 0.6 g/g, reaction time of 90 min, reaction temperature of 90 C and stirring rate of 500 rpm. | [
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Soil erosion, which has been recently shown to significantly perturb carbon cycling, occurs naturally but can be either enhanced or reduced by human activities. However, the impacts of soil erosion on terrestrial contaminant cycles remain unclear. Here, we select eight trace elements, i.e., arsenic, cadmium, chromium, copper, nickel, lead, zinc, and mercury, to examine the erosional impacts of the elements' fate and transport across China. By synthesizing the detailed distribution of soil erosion fluxes, soil element inventories, and diverse modeling methods, we reveal that while human activities have reduced the lateral transport of these elements in the Loess Plateau (Central North China, a 56% decline in the past two decades with a range of 46% to 110%) due to soil conservation projects, they have increased these transport fluxes in China's major karst regions (Southwest China, a 84% increase with a range of 55% to 150%) because of severe rocky desertification. These fluxes have completely overwhelmed the soil conservation efforts in the Loess Plateau. Fluxes of these elements into aquatic environments from Southwest China reached 46% of the total input in China in 2010. These fluxes were higher than the inputs from point sources in the region by a factor of 50 because of impacts of excessive agricultural cultivation and geographical and climatic factors. These findings indicate the enormous perturbation of terrestrial contaminant cycles caused by soil erosion in karst regions and demonstrate the need for long-term sustainable management of soil erosion and contaminant discharge to protect fragile terrestrial ecosystems. | [
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A growing awareness of the wider environmental significance of diffuse sediment pollution in interconnected river-lake systems has generated the need for reliable provenance information. Owing to their insufficient ability to distinguish between multiple sources, common sediment source apportionment methods would rarely be a practical solution. On the basis of the inseparable relationships between sediment and adsorbed microorganisms, community-based microbial source tracking may be a novel method of identifying dominant sediment sources in the era of high-throughput sequencing. Dongting Lake was selected as a study area as it receives considerable sediment import from its inflowing rivers during the flood season. This study was conducted to characterize the bacterial community composition of sediment samples from the inflow-river estuaries and quantify their sediment microbe contributions to the central lake. Metagenomic analysis revealed that the community compositions of source sediment samples were significantly different, allowing specific sources to be identified with the machine learning classification program SourceTracker. A modified analysis using SourceTracker found that the major contributors to three major lake districts were the Songzi, Zishui, and Xinqiang Rivers. The impacts of hydrodynamic conditions on source apportionment were further verified and suggested the practicability of this method to offer a systematic and comprehensive understanding of sediment sources, pathways, and transport dynamics. Finally, a novel framework for sediment source-tracking was established to develop effective sediment management and control strategies in river-lake systems. | [
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In this study, Alg-Gly-Ala-Val-Leu-His (RGAVLH) obtained from pine nut ( Pinus koraiensis Sieb. et Zucc.) protein was chosen to investigate the phenomenon of immunomodulatory activity improvement upon pulsed electric field (PEF) processing. The influence of electric field intensity on immunomodulatory activity of RGAVLH was evaluated using RAW 264.7 cells. It was found that RGAVLH can not only significantly ( p < 0.05) improve the capability of macrophage phagocytosis but also promote the production of nitric oxide. RGAVLH treated under an electric field intensity of 40 kV/cm exhibited the best immunomodulatory activity. The primary and secondary structures of PEF-treated peptides were analyzed by mid-infrared (MIR) spectroscopy, Raman spectroscopy, circular dichroism spectroscopy, and one-dimensional/two-dimensional nuclear magnetic resonance spectroscopy. After PEF treatment, the primary structure of RGAVLH was not influenced, as evaluated by MIR and Raman spectra. In addition, the content of -sheet was decreased and active hydrogen was changed in PEF-treated RGAVLH solution. Moreover, the long-range connectivity between CH (3.39 ppm) and NH (8.24 ppm) was enhanced by PEF. Therefore, the improvement of the immunomodulatory activity of RGAVLH might result from the changes of the spatial state and spatial force in the peptide solution system. | [
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Diphenyl phosphate (DPHP) is an aryl phosphate ester (APE) used as an industrial catalyst and chemical additive and is the primary metabolite of flame retardant APEs, including triphenyl phosphate (TPHP). Minimal DPHP-specific toxicity studies have been published despite ubiquitous exposure within human populations following metabolism of TPHP and other APEs. Therefore, the objective of this study was to determine the potential for DPHP-induced toxicity during embryonic development. Using zebrafish as a model, we found that DPHP significantly increased the distance between the sinus venosus and bulbus arteriosis (SV-BA) at 72 h postfertilization (hpf) following initiation of exposure before and after cardiac looping. Interestingly, pretreatment with d-mannitol mitigated DPHP-induced effects on SV-BA length despite the absence of DPHP effects on pericardial area, suggesting that DPHP-induced cardiac defects are independent of pericardial edema formation. Using mRNA-sequencing, we found that DPHP disrupts pathways related to mitochondrial function and heme biosynthesis; indeed, DPHP significantly decreased hemoglobin levels in situ at 72 hpf following exposure from 24 to 72 hpf. Overall, our findings suggest that, similar to TPHP, DPHP impacts cardiac development, albeit the potency of DPHP is significantly less than TPHP within developing zebrafish. | [
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Exposure to air pollution from solid-fuel cookstoves is a leading risk factor for premature death; however, the effect of fuel moisture content on air pollutant emissions from solid-fuel cookstoves remains poorly constrained. The objective of this work was to characterize emissions from a rocket-elbow cookstove burning wood at three different moisture levels (5%, 15%, and 25% on a dry mass basis). Emissions of carbon dioxide (CO2), carbon monoxide (CO), methane, fine particulate matter (PM2.5), PM2.5 elemental carbon (EC), PM2.5 organic carbon, formaldehyde, acetaldehyde, benzene, toluene, ethylbenzene, and xylenes were measured. Emission factors (EFs; gMJdelivered-1) for all pollutants, except CO2 and EC, increased with increasing fuel moisture content: CO EFs increased by 84%, PM2.5 EFs increased by 149%, formaldehyde EFs increased by 216%, and benzene EFs increased by 82%. Both modified combustion efficiency and the temperature at the combustion chamber exit decreased with increasing fuel moisture, suggesting that the energy required to vaporize water in the fuel led to lower temperatures in the combustion chamber and lower gas-phase oxidation rates. These results illustrate that changes in fuel equilibrium moisture content could cause EFs for pollutants such as PM2.5 to vary by a factor of 2 or more across different geographic regions. | [
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] |
We introduce a method for the detection of weak interactions of small molecules such as metabolites or medicaments that contain deuterated methyl groups with proteins in solution. The technique relies on long-lived imbalances of spin state populations, which are generated by dissolution dynamic nuclear polarization (D-DNP) and feature lifetimes that depend on the frequency of internal rotation of deuterated methyl groups. We demonstrate the technique for interactions between deuterated dimethyl sulfoxide (DMSO- d6) and bovine serum albumin (BSA) or trypsin, where the methyl group rotation is slowed down upon protein binding, which causes a marked reduction in the lifetime of the population imbalances. | [
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BACKGROUND: Noise from wind turbines (WTs) is reported as more annoying than traffic noise at similar levels, raising concerns as to whether WT noise (WTN) increases risk for cardiovascular disease, as observed for traffic noise.OBJECTIVES: We aimed to investigate whether long-term exposure to WTN increases risk of myocardial infarction (MI) and stroke.METHODS: We identified all Danish dwellings within a radius 20 times the height of the closest WT and 25% of the dwellings within [Formula: see text] the height of the closest WT. Using data on WT type and simulated hourly wind at each WT, we estimated hourly outdoor and low frequency (LF) indoor WTN for each dwelling and derived 1-y and 5-y running nighttime averages. We used hospital and mortality registries to identify all incident cases of MI ([Formula: see text]) and stroke ([Formula: see text]) among all adults age 25-85 y ([Formula: see text]), who lived in one of these dwellings for [Formula: see text] over the period 1982-2013. We used Poisson regression to estimate incidence rate ratios (IRRs) adjusted for individual- and area-level covariates.RESULTS: IRRs for MI in association with 5-y nighttime outdoor WTN [Formula: see text] (vs. [Formula: see text]) dB(A) and indoor LF WTN [Formula: see text] (vs. [Formula: see text]) dB(A) were 1.21 [95% confidence interval (CI): 0.91, 1.62; 47 exposed cases] and 1.29 (95% CI: 0.73, 2.28; 12 exposed cases), respectively. IRRs for intermediate categories of outdoor WTN [24-30, 30-36, and [Formula: see text] vs. [Formula: see text]] were slightly above the null and of similar size: 1.08 (95% CI: 1.04, 1.12), 1.07 (95% CI: 1.00, 1.12), and 1.06 (95% CI: 0.93, 1.22), respectively. For stroke, IRRs for the second and third outdoor exposure groups were similar to those for MI, but near or below the null for higher exposures.CONCLUSIONS: We did not find convincing evidence of associations between WTN and MI or stroke. https://doi.org/10.1289/EHP3340. | [
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] |
BACKGROUND: Noise from wind turbines (WTs) is associated with annoyance and, potentially, sleep disturbances.OBJECTIVES: Our objective was to investigate whether long-term WT noise (WTN) exposure is associated with the redemption of prescriptions for sleep medication and antidepressants.METHODS: For all Danish dwellings within a radius of [Formula: see text] heights and for 25% of randomly selected dwellings within a radius of [Formula: see text] heights, we estimated nighttime outdoor and low-frequency (LF) indoor WTN, using information on WT type and simulated hourly wind. During follow-up from 1996 to 2013, 68,696 adults redeemed sleep medication and 82,373 redeemed antidepressants, from eligible populations of 583,968 and 584,891, respectively. We used Poisson regression with adjustment for individual and area-level covariates.RESULTS: Five-year mean outdoor nighttime WTN of [Formula: see text] was associated with a hazard ratio (HR) = 1.14 [95% confidence interval (CI]: 0.98, 1.33) for sleep medication and HR = 1.17 (95% CI: 1.01, 1.35) for antidepressants (compared with exposure to WTN of [Formula: see text]). We found no overall association with indoor nighttime LF WTN. In age-stratified analyses, the association with outdoor nighttime WTN was strongest among persons [Formula: see text] of age, with HRs (95% CIs) for the highest exposure group ([Formula: see text]) of 1.68 (1.27, 2.21) for sleep medication and 1.23 (0.90, 1.69) for antidepressants. For indoor nighttime LF WTN, the HRs (95% CIs) among persons [Formula: see text] of age exposed to [Formula: see text] were 1.37 (0.81, 2.31) for sleep medication and 1.34 (0.80, 2.22) for antidepressants.CONCLUSIONS: We observed high levels of outdoor WTN to be associated with redemption of sleep medication and antidepressants among the elderly, suggesting that WTN may potentially be associated with sleep and mental health. https://doi.org/10.1289/EHP3909. | [
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] |
OBJECTIVES: To evaluate the influence of cone beam CT (CBCT) volume orientation on alveolar bone measurements for dental implant planning using CBCT in patients with different facial profiles.METHODS: 74 CBCT volumes were selected from a database and classified according to the facial profile of the patient. Height and width measurements of the alveolar bone were carried out with the volume of the mandible in two different orientations: occlusal plane and mandibular base parallel to the horizontal plane. The data were subjected to the mixed model methodology for repeated measures, through the PROC MIXED procedure. Multiple comparisons were performed by Tukey Kramer test ( = 0.05).RESULTS: Alveolar bone width was significantly greater when the CBCT volume was oriented with the mandibular base parallel to the horizontal plane, for all facial profiles (p ? 0.05). Alveolar bone height was significantly higher (p ? 0.05) for dolichofacial individuals when compared to that of mesofacial and brachyfacial individuals, who did not differ significantly between each other (p > 0.05), regardless of the CBCT volume orientations used in this study.CONCLUSIONS: CBCT-based alveolar bone width is increased when the image volume is oriented with the mandibular base parallel to the horizontal plane and dolichofacial individuals present greater alveolar bone height. | [
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] |
OBJECTIVE: To evaluate outcomes and toxicity profiles after re-irradiation in patients with pelvic recurrence of anorectal cancer.METHODS: 25 anorectal cancer patients who received re-irradiation for pelvic recurrence between 2005 and 2015 were included. For initial treatment, all patients underwent surgical resection and preoperative or postoperative radiotherapy.RESULTS: The median follow-up duration was 21.5 months (range, 2.9-84.4). After a median of 43.3 months (range, 11.7-218.5), patients received re-irradiation with a median dose of 45 Gy (range, 36-60). The equivalent dose in 2 Gy fractions (EQD2) of re-irradiation-calculated using / = 10 Gy-ranged from 34.5 to 84.0 Gy (median, 46.4). Surgical resection was performed for 11 patients, and 14 patients received concurrent chemotherapy with re-irradiation. The 3-year local progression-free survival was 29.7%. The 3-year overall survival was 49.7%. Concurrent chemotherapy with re-irradiation and re-irradiation doses >50 Gy EQD2/=10 were significant prognostic factors for local progression free survival and overall survival according to multivariate analysis. 90% (9 of 10) of patients with symptoms had improvement after re-irradiation. Among 23 patients available for evaluation of late toxicity, 12 developed late toxicities. There were no Grade 4 late toxicities, and 6 patients had Grade 3 late toxicities (small bowel obstruction, bowel perforation and fistula).CONCLUSION: Re-irradiation for pelvic recurrence of anorectal cancer improved symptoms of patients but the rate of late toxicity was high. Further investigation for patient selection is required.ADVANCES IN KNOWLEDGE: Re-irradiation could be considered as a possible option for pelvic recurrence of anorectal cancer in selected patients. | [
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OBJECTIVES: Diagnostic role of MRI in Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is well documented. Recent studies have shown the relevance of MRI in detailing the pelvic anatomy, particularly small Mullerian remnants. The results are, however, not consistent and reproducibility of MRI features has not been confirmed. The aim of our study was to evaluate the detailed pelvic anatomy in patients with MRKH syndrome and to calculate the interobserver agreement of the MRI features.METHODS: The study was carried out on female patients, aged 15-30 years, with primary amenorrhea. Following clinical, gynaecological, endocrinological, ultrasound and chromosomal work-up and a provisional diagnosis of MRKH syndrome, MRI pelvis was performed on 25 patients using a 1.5 T scanner. MRI images were retrospectively reviewed by two radiologists for a detailed evaluation of Mullerian structures (uterine buds, fibrous bands, midline triangular soft tissue), vagina, and ovaries. coefficient was calculated as a measure of interobserver agreement.RESULTS: Interobserver agreement was good to excellent (: 0.7788 0.2168 to 1 0) for uterine buds and their characteristics, vagina, ovaries and associated renal/vertebral anomalies; poor to fair for fibrous bands (: 0.2857 0.3273 to 0.6032 0.2149) and good for midline triangular soft tissue (: 0.7826 0.1474).CONCLUSION: MRI is capable of providing key pre-operative anatomical information in MRKH syndrome non-invasively. There is good to excellent interobserver agreement for MRI features of most of the surgical relevant structures.ADVANCES IN KNOWLEDGE: MRI features of salient preoperative anatomical structures are reproducible between observers. | [
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] |
OBJECTIVE: To evaluate the effect of transcutaneous electrical acupuncture stimulation (TEAS) on pregnancy outcomes in patients with recurrent implantation failure (RIF) undergoing in vitro fertilisation (IVF).METHODS: A total of 122 women with RIF undergoing fresh embryo transfer cycle IVF were randomly allocated to a TEAS or mock TEAS (MTEAS) group. Gonadotrophin therapy using a long protocol was provided in both groups. TEAS consisted of 30 min of stimulation (9-25 mA, 2 Hz) at SP6, CV3, CV4 and Zigong from day 5 of the ovarian stimulation cycle once every other day until the day of embryo transfer. The patients in the control group received MTEAS. Implantation, clinical pregnancy and live birth rates were compared.RESULTS: In the TEAS group, the implantation rate, clinical pregnancy rate and live birth rate (24.3%, 32.8% and 27.9%, respectively) were significantly higher than in the MTEAS group (12.1%, 16.4% and 13.1%, respectively).CONCLUSIONS: TEAS significantly improves the clinical outcomes of subsequent IVF cycles among women who have experienced RIF.TRIAL REGISTRATION NUMBER: ChiCTR-TRC-14004730. | [
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Artificial intelligence (AI) has had a huge impact on our lives. In this study, we suggest that when people interact with AI, they regard the AI as a social actor and apply interpersonal relationship norms. This study employed a 2 ? 2 between-subjects design to identify the effects of an AI's relationship type and gender on a human's response to an AI speaker (relationship type: friend vs. servant; gender: male vs. female). Findings show that the relationship type has a significant effect on warmth and pleasure but not on competence. The gender of the AI showed no significant effects on competence, warmth, or pleasure when controlling for the participants' gender. In addition, the results indicate that anthropomorphism fully mediated the relationship between both warmth and pleasure and the type of relationship with AI. Our findings suggest that AI is regarded as a social actor, and the characteristics of AI should be considered as they influence the response to AI. | [
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] |
OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has better normal-tissue sparing compared with 3-dimensional conformal radiation (3DCRT). We sought to assess the impact of radiation technique on pathological and clinical outcomes in locally advanced non-small cell lung cancer (LANSCLC) treated with a trimodality strategy.METHODS: Retrospective review of LANSCLC patients treated from August 2012 to August 2018 at Sheba Medical Center, Israel. The trimodality strategy consisted of concomitant chemoradiation to 60 Gray (Gy) followed by completion surgery. The planning target volume (PTV) was defined by co-registered PET/CT. Here we compare the pathological regression, surgical margin status, local control rates (LC), disease free (DFS) and overall survival (OS) between 3DCRT and IMRT.RESULTS: Our cohort consisted of 74 patients with mean age 62.9 years, male in 51/74 (69%), adenocarcinoma in 46/74 (62.1%), stage 3 in 59/74 (79.7%) and chemotherapy in 72/74 (97.3%). Radiation mean dose: 59.2 Gy (SD 3.8). Radiation technique : 3DCRT in 51/74 (68.9%), IMRT in 23/74 (31%). Other variables were similar between groups.Major pathological response (including pathological complete response or less than 10% residual tumor cells) was similar: 32/51 (62.7%) in 3DCRT and 15/23 (65.2%) in IMRT, p=0.83. Pathological complete response (pCR) rates were similar: 17/51 (33.3%) in 3DCRT and 8/23 (34.8%) in IMRT, p=0.9. Surgical margins were negative in 46/51 (90.1%) in 3DCRT vs. 17/19 (89.4%) in IMRT (p=1.0).The 2-year LC rates were 81.6% (95% CI 69-89.4%); DFS 58.3% (95% CI 45.5-69%) and 3-year OS 70% (95% CI57-80%). Comparing radiation techniques, there were no significant differences in LC (p=0.94), DFS (p=0.33) and OS (p=0.72).CONCLUSION: When used to treat LANSCLC in the neoadjuvant setting, both IMRT and 3DCRT produce comparable pathological and clinical outcomes.ADVANCES IN KNOWLEDGE: This study validates the real-world effectiveness of IMRT compared to 3DCRT. | [
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] |
Degenerative disc disease (DDD) is the main cause of low back pain, and the ingrowth of new blood vessels is one of its pathological features. The stromal cell-derived factor 1 (SDF1)/CXCR7 signaling axis plays a role in these physiological and pathological activities. The aims of this study were to explore whether this signaling axis participates in the angiogenesis of degenerated intervertebral discs (IVDs) and to define its underlying mechanism. In this study, we cocultured human nucleus pulposus cells (NPCs) and vascular endothelial cells (VECs) and regulated the expression of SDF1/CXCR7 to investigate the effect of VEC angiogenesis by NPCs. The results revealed that angiogenesis was enhanced with increased SDF1 and that angiogenesis was weakened with the inhibition of CXCR7. We found that PI3K/AKT was involved in the downstream pathway in the coculture. VEC angiogenesis induction by NPCs was enhanced with an increase in pAKT or a decrease in PTEN. We conclude that the SDF1/CXCR7 signaling axis plays a role in the angiogenesis of degenerated IVD through the PI3K/AKT pathway. | [
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OBJECTIVE: To examine the imaging capability of a novel small field of view hybrid gamma camera (HGC) using 125I seeds prior to surgical use.METHODS: The imaging performance of the camera system was assessed quantitatively and qualitatively at different source depths, source to collimator distances (SCD), activity levels, acquisition times and source separations, utilising bespoke phantoms.RESULTS: The system sensitivity and spatial resolution of the HGC for 125I were 0.41 cps/MBq (at SCD 48 mm) and 1.53 0.23 mm (at SCD 10 mm) respectively. The camera was able to detect the 125I seed at a SCD of 63 mm (with no scattering material in place) in images recorded within a 1-min acquisition time. The detection of the seeds beneath scattering material (simulating deep-seated tumours) was limited to depths of less than 20 mm beneath the skin surface with a SCD of 63 mm and seed activity of 2.43 MBq. Subjective assessments of the hybrid images acquired showed the capability of the HGC for localising the 125I seeds.CONCLUSION: This preliminary ex vivo study demonstrates that the HGC is capable of detecting 125I seeds and could be a useful tool in radioactive seed localisation with the added benefit of providing hybrid optical images for guiding breast conserving surgery.ADVANCES IN KNOWLEDGE: The SFOV HGC could provide high resolution fused optical-gamma images of 125I radioactive seeds indicating the potential use in intraoperative surgical procedure such as RSL. | [
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] |
OBJECTIVE: Prostate cancer represents the second most common malignancy in the world and majority of patients have diagnosis of localized disease. The aim of the present study was to compare two cohorts of patients treated with moderate hypofractionation (MHRT) or stereotactic body radiation therapy (SBRT).METHODS: We included patients treated between 2010 and 2015. Inclusion criteria were: adenocarcinoma of the prostate; class risks low or intermediate; WHO performance status 0-2. We evaluated rectal, gastrointestinal toxicity and genitourinary. Measures of outcome were biochemical disease-free survival and overall survival. Propensity score was used to approximate the balance in covariates.RESULTS: 209 patients were included, treated with MHRT (n = 109) or SBRT (n = 100). Median follow-up time was 37.4 months. Rates of biochemical disease-free survival at 1- and 3 years were 100 and 95%, respectively. There was no significant difference between the two groups (p = 0.868). Rates of overall survival at 1- and 3 years were 100 and 97.1%, respectively with no differences between the two groups (p = 0.312). After propensity scoring matching, no differences were observed in terms of acute and late rectal and gastrointestinal toxicity. While mild genitourinary side-effects were more common in SBRT group (45.5% vs 19.5 %), Grade 2 and 3 toxicity was increased after MHRT (11.7% vs 2.6 %; p = 0.029).CONCLUSIONS: Moderate hypofractionation and SBRT are two effective and safe options for the treatment of low- and intermediate-risk prostate cancer. The analysis showed no difference in terms of disease's control and survival but increased moderate and severe toxicity after MHRT.ADVANCES IN KNOWLEDGE: Moderate hypofractionation and SBRT are comparable in terms of efficacy while moderate and severe toxicity is more common in the first one. | [
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OBJECTIVES: Dental CBCT exposure parameters should be optimized according to patient-specific indications, mainly for children that are most vulnerable to harmful effects of ionizing radiation. The aim of this study was to determine optimized kV settings for paediatric acquisitions for a dental CBCT device.METHODS: Clinical and quantitative evaluations of image quality were performed using 5 and 10 years old (y/o) anthropomorphic phantoms. Technical evaluation was performed with the SEDENTEXCT-IQ phantom. Images were obtained using a PaX-i3D Green CBCT (Vatech, Korea) device, combining tube voltages ranging from 85 to 110 kV and 2 fields of view (FOVs: 21 ? 19 and 12 ? 9 cm), while maintaining the radiation dose fixed by adjusting the mA accordingly. Clinically, observers assessed images based on overall quality, sharpness, contrast, artefacts, and noise. For quantitative evaluation, mean grey value shift, % increase standard deviation, % beam-hardening and contrast-to-noise ratio were calculated. For technical evaluation, segmentation accuracy, contrast-to-noise ratio and full width at half maximum were measured. Biplot graphs were used to choose representative parameters, from which the best kV was selected for each protocol and evaluation. kV values that had no statistical differences (p > 0.05) with the best kV chosen were considered as having the same quality.RESULTS: Clinically, 95 kV was found as a cut-off value. From the quantitative aspect, 85 kV (p < 0.05) showed the worst quality, except in 12 ? 9 cm 5 y/o. Technically, 85 and 110 kV in the large FOV showed significantly worse quality for the large FOV.CONCLUSION: For paediatric indications, 95 kV or higher (and correspondingly low mA values) was found as optimal. | [
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] |
Aim: To investigate the associations with the 21-gene recurrence score (RS) and effect of adjuvant radiotherapy (RT) for early-stage breast cancer after breast conserving surgery. Methods: We included 13,246 patients in the SEER database. Results: Patients with a higher RS were independently related to nonreceipt of RT (p < 0.001). In both the traditional and Trial Assigning Individualized Options for Treatment (TAILORx) RS cut-offs, the receipt of RT was not related to better breast cancer-specific survival in low- and high-risk RS groups, but was independently related to better breast cancer-specific survival in intermediate-risk RS group before (p =0.029) and after (p =0.001) propensity score matching. Conclusion: The 21-gene-RS may impact the decision-making of adjuvant RT in early-stage breast cancer after breast conserving surgery. The survival benefit of adjuvant RT may be limited to patients with intermediate-risk RS. | [
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The Qianhua Mutton Merino (QHMM) is a new variety of sheep (Ovis aries) with improved meat performance compared with the traditional Small Tail Han (STH) sheep variety. We recently reported the transcriptome profiling of longissimus muscle tissues between QHMM and STH sheep. In the present study, we aimed to evaluate key micro (mi)RNA-mRNA networks associated with sheep muscle growth and development. We used miRNA sequencing to obtain longissimus muscle miRNA profiles from QHMM and STH sheep. We identified a total of 153 known sheep miRNAs, of which 4 were differentially expressed (DE) between the 2 sheep varieties. We combined these results with mRNA library data to build an miRNA-mRNA network, including 26 target genes of the 4 DE miRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that 26 target genes were significantly enriched in 86 biological processes, including muscle organogenesis, myoblast migration, cell proliferation, and adipose tissue development, and in 9 metabolic pathways, including carbohydrate, nucleotide, and amino acid metabolic pathways. oar-miR-655-3p and its target gene ACSM3 and oar-miR-381-5p and its target gene ABAT were selected for subsequent analysis based on GO and KEGG analyses. The binding sites of oar-miR-655-3p with ACSM3 and oar-miR-381-5p with ABAT were validated by a dual-luciferase reporter gene detection system. This represents the first integrative analysis of miRNA-mRNA networks in QHMM and STH muscles and suggests that DE miRNAs, especially oar-miR-655-3p and oar-miR-381-5p, play crucial roles in muscle growth and development. | [
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] |
Nopal is used in Mexico as both food and traditional medicine for metabolic diseases. Our aim was to analyze the effect of the chronic administration of mucilage fiber extracted from nopal (Opuntia ficus indica; 500 mg/kg body weight per day) on male Wistar rats on a high-fructose diet (HFD). After which three groups were administered one of the following for 30 days: whole-fresh nopal mixed in water, mucilage, and control. Metabolic and hemodynamic parameters (triglycerides, cholesterol, fasting glucose, oral glucose tolerance test, blood pressure, and abdominal circumference) were determined. Rats administered nopal and mucilage had lower levels of triglycerides and diastolic arterial pressure than control, but only nopal had significant differences. Furthermore, systolic and diastolic pressure were higher in the control group. Thus, whole nopal and mucilage improve metabolic parameters in rats fed a HFD. | [
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] |
Our previous studies have demonstrated antioxidant and cytoprotective properties of red ginseng oil (RGO). However, the role of RGO in models of intestinal inflammation has not been elucidated. In this study, we evaluated the chemopreventive effect of RGO in a mouse model of azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis and explored its underlying mechanisms. Male C57BL/6 mice were intraperitoneally injected with a single dose of AOM (10 mg/kg), followed by 1.5% DSS in drinking water for 7 days to produce colon carcinogenesis. RGO at 10 or 100 mg/kg was orally given for 17 weeks. RGO supplementation reduced the plasma nitric oxide (NO) concentration as well as lipid peroxidation and inhibited the production of proinflammatory factors such as inducible NO synthase, cyclooxygenase-2, interleukin 1, IL-6, and tumor necrosis factor- in the mouse colitis tissue. Increased phosphorylation levels of p65 and IB by AOM/DSS exposure were attenuated by the presence of RGO. In addition, RGO supplementation induced the activity of primary antioxidant enzymes such as superoxide dismutase and catalase as well as the expression of nuclear factor erythroid 2-related factor 2-mediated antioxidant enzyme hemeoxygenase-1 in the colons of AOM/DSS-treated mice. These findings indicate that RGO may be a potent natural chemopreventive agent for ameliorating inflammatory bowel diseases. | [
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Many studies have shown that plants can be therapeutic alternatives in the prevention or treatment of various diseases. Among these, green coffee may present different pharmacological effects related to the regulation of glycemia and lipid metabolism and is related to the prevention of cardiovascular diseases. The objective of our study was to evaluate the effects of using green and ripe coffee on the metabolic profile and muscular enzymes after the practice of physical exercises in Wistar rats. We included six groups: G1 (control group), G2 (group submitted to swimming), G3 (group that consumed green coffee), G4 (group that consumed green coffee and was submitted to swimming), G5 (group that consumed ripe coffee), and G6 (group that consumed ripe coffee and was submitted to swimming). Our results showed that there was a significant reduction in the percentage of visceral fat in G3, G5, and G6. We did not observe significant modifications in glycemia, lipids, lactate dehydrogenase, ferric reducing ability of plasma, and ferric-xylenol orange. The levels of creatine phosphokinase showed a reduction in the groups G2 and G4. No significant differences were found in the atherogenic indices. There is a global demand for natural compounds that can be safe, cheap, related to minimum side effects, and provide health benefits. Our results show that the use of green or ripe coffee may contribute to reduce the percentage of visceral fat and consequently may protect against further complications once this tissue produces proatherogenic hormones. Furthermore, green coffee may play a role in protecting muscle injury after the practice of physical exercises. | [
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Nonalcoholic fatty liver disease is a progressive disease involving the accumulation of lipid droplets in the liver. In this study, we investigated the anti-hepatosteatosis effects of fermented Cordyceps militaris extract (CME) in AML-12 hepatocytes. Although the levels of adenosine and cordycepin were reduced in the extracts of CM grown on germinated soybean (GSCE) and fermented CM grown on germinated soybean (GSC) by Pediococcus pentosaceus ON188 (ON188E), the expression of fatty acid oxidation (FAO) genes were upregulated only by GSC-ON188E treatment in a dose-dependent manner. In contrast, a lipogenic gene, stearoyl Coenzyme A desaturase 1, was downregulated by ON188E. Formation of intracellular lipid droplets by the addition of oleic acid was reduced by ON188E to levels observed in WY14643-treated cells. When cells were treated with ON188E, sphingosine kinase 2 mainly responsible for hepatic sphingosine 1-phosphate (S1P) synthesis was upregulated and S1P was elevated. Collectively, the fermented GSC extract activates FAO through elevation of S1P synthesis and has potential as a therapeutic for hepatosteatosis. | [
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The present study was conducted to investigate the effects of dietary amylose and amylopectin ratio on growth performance, meat quality, postmortem glycolysis and muscle fibre type transformation of finishing pigs. Twenty-four barrows (Duroc ? Landrace ? Yorkshire) with an average initial body weight of 61.7 2.01 kg were randomly assigned to four dietary treatments with amylose: amylopectin ratios of 1:1 (HD), 1:2 (MD), 1:3 (CD) and 1:4 (LD). The results showed that the average daily weight gain of finishing pigs tended to reduce with the ratio of amylose and amylopectin decreased (p = 0.09). Diet LD increased the pH24h value and decreased the shear force in longissimus dorsi (LM) compared with diet HD (p < 0.05). Diet LD decreased the lactate content and the HK-2 mRNA abundance and increased the mRNA abundance of ATP5B in LM compared with diet HD (p < 0.05). Higher mRNA abundance of MyHC I and lesser abundance of MyHC IIb in LM were found in pigs fed diet CD and LD than those fed diet HD (p < 0.05). Furthermore, pigs fed diet LD had higher mRNA abundances of PGC-1 and PPAR in LM than other groups (p < 0.05). These results suggested that diet with low amylose and amylopectin ratio could improve meat quality of finishing pigs via delaying muscle glycolysis capacity and shifting muscle fibre types. | [
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Prostatism and erectile dysfunction (ED) are highly prevalent and closely comorbid. Prescription treatments are limitingly expensive but robust in mechanisms of action (MoA). Nutritional supplements (NS) are low-cost but inadequately supported by evidence. Do any NS use robust MoA? Could their efficacy be amplified via dosing, concentration of active principles, and/or use in combination? The goal is to develop an effective NS for prostatism and ED using the MoA of prescription treatments. Literature reviews were conducted on dietary supplements for prostatism or ED and MoA of relevant drugs. The most promising NS employing these MoA were chosen. A pilot study of a prototype combination was conducted. A protocol was created for an adequate dose-response trial to test the NS combination in men with ED and prostatism. The main measures were response rates, International Prostate Symptom Score, and International Index of Erectile Function. For drugs, the MoAs best proven for prostatism and ED were nitric oxide augmentation, mild androgen inhibition, and anti-inflammatory effects. The following NS best simulate these MoA and are best supported for efficacy; for prostatism: beta sitosterol; for ED: panax ginseng, arginine, and citrulline. Pilot clinical data provided support. A plan for a formal dose-response clinical trial was approved by a central institutional review board. NS using effective MoA might suffice for prostatism and ED. Pilot testing of a combination NS with the best-supported MoA supported further development. A dose-response trial should be conducted using adequate doses of L-citrulline, beta-sitosterol, ginseng, and vitamin D3. | [
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Vascular calcification (VC) is a process in which calcium phosphate crystals deposit within the intima and middle membrane of the vascular wall. Rosmarinic acid (RA) is a common phenolic compound. It possesses antioxidation, anti-inflammatory, antimicrobial effects. Our experiment aims to investigate the role and molecular mechanism of RA in VC. Rats were fed high-fat feed and injected with vitamin D3 to establish a VC model. -Glyerophosphate ( GP) was selected to stimulate rat aortic smooth muscle cells (VSMCs) in order to establish the cell calcification model. Kits were used to detect the antioxidant index and calcification index. RA significantly reduced the levels of ALP, MDA, Ca, and P but increased SOD levels. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to detect various antioxidant-related genes and calcified genes on an mRNA and protein level. The results showed that nuclear factor red cell-2 related factors (Nrf2), haem oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase (NQO1), and osteoprotegerin (OPG) were up regulated by RA at both the mRNA and protein levels, but kelch-like ECH-associated protein 1 (Keap1), nuclear factor kappa B(NF-B), cadherin associated protein (-catenin) and osteogenic transcription factor (Runx2) expression at both the mRNA and protein levels was significantly inhibited. Microscopic examination showed that RA significantly decreased the content of calcified nodules and the production of reactive oxygen species (ROS). When Nrf2 is disturbed, the role of RA is significantly blocked. Our results showed that RA can improve VC by regulating the Nrf2 pathway. | [
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Neuropathic pain (NP) is associated with chronic hyperglycemia and emotional disorders such as depression in diabetic patients, complicating the course of treatment. Drugs currently used to treat NP have undesirable side effects, so research on other natural sources has been required. -caryophyllene (BCP), a natural sesquiterpene found in some food condiments and considered an agonist to cannabinoid receptor type 2, could have potential therapeutic effects to treat conditions such as NP and emotional disorders. For this reason, we assessed whether BCP modulates nociception, anxiety, and depressive-like behavior in streptozotocin (STZ)-induced experimental diabetic BALB/c female mice. BCP was orally chronic administrated (10 mg/kg/60 L). Pain developed with STZ was evaluated with von Frey filament test, SMALGO, and hot plate test. Anxiety and depression-like behavior were assessed by marbles test, forced swim test, and tail suspension test. BCP significantly reduced glycemia in experimental diabetic mice. The pain was also mitigated by BCP administration. Depression-like behavior assessed with tail suspension test was attenuated with orally chronic BCP administration. Substance P and cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF-), and interleukin-6 (IL-6) were also attenuated with BCP administration. NP was positively correlated with substance P and IL-6 and IL-1 release. Our data using an orally chronic BCP administration in the STZ challenged mice to suggest that glycemia, diabetes-related NP, and depressive-like behavior could be prevented/reduced by dietary BCP. | [
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High prevalence of endometriosis was reported in Asian women as a result of their traditionally high intake of soy foods during infancy. Soy is widely used in infant feeding after weaning from breast milk or cow milk. This study thus aimed to determine to what extent soy intake before puberty may contribute to the development of endometriosis. For this purpose, immature (6-week old) female rats were fed with various soy formulas (0%, 10%, 20%, 30%, 40%, 50%, and 60%). Normal control animals were fed with a soy-free diet. At 13 weeks of age, animals (except the normal control) underwent a transplantation surgery to establish endometriosis. Estradiol valerate and oxytocin were used to induce pelvic pain. Endometrial implant levels of glutathione (GSH) and malondialdehyde (MDA) allowed estimating tissue oxidative status. Physiological ovarian function was assessed by histological analysis of ovaries. Results showed that soy-fed animals grew faster than animals receiving a soy-free diet (P < .001). In animals supplemented with more than 10% of soy, the intensity of pelvic pain increased (P < .001) as well as the volume of ectopic foci. In addition, tissue levels of MDA and GSH increased (P < .001). The ovarian function was altered and the number of luteinized unruptured follicles increased. In conclusion, although animals supplemented with soy at the prepubertal stage displayed a good growth performance, regular soy consumption may promote the development and progress of endometriosis in adulthood, especially when soy content in food is more than 10%. | [
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] |
Background: In the setting of pancreatic ductal adenocarcinoma (PDAC), para-aortic lymph node (PALN) involvement is considered as a metastasis disease. To date, no morphological examination can effectively identify lymph node metastasis, and a significant number of patients undergo futile invasive laparotomy for PALN involvement. From an oncological point of view, laparoscopy represents a better approach for PALN sampling. The main aim of the study is to propose a laparoscopic PALN sampling first approach. We describe the surgical technique and demonstrate its technical feasibility as a routine approach as the first surgical step before pancreaticoduodenectomy for localized PDAC. Materials and Methods: During a first step of staging laparoscopy, PALN sampling was done for 31 patients with localized PDAC between November 2015 and February 2017. Demographic data and intraoperative, postoperative, and pathological criteria were evaluated. The surgical technique is described in detail. Results: The median operative time was 35 (range 18-65) minutes. The median number of PALN analyzed per patient was 2 (range 1-5). Four (13%) of 31 patients had positive PALN in frozen section analysis. No severe complication was reported for patients with positive PALN, receiving laparoscopic exploration and PALN sampling. The median hospital stay for patients with positive PALN was 2 (range 1-7) days. Conclusion: To avoid futile laparotomy, a staging laparoscopy is usually carried out. We report the feasibility and safety of laparoscopic PALN sampling and suggest its systematic realization during staging laparoscopy as a first step in patients with localized PDAC before pancreaticoduodenectomy. | [
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Development of antibiotic resistance can be achieved either by mutation or by acquiring a resistance gene from foreign sources, with some resistance genes likely originating in microbial populations to counteract antibiotics present in natural ecosystems. In this study, we describe the first report of a strain of nonclinical multidrug-resistant Stenotrophomonas sp. strain G4 with high-level resistance to colistin and meropenem, phylogenetically distinct from well-studied multiple drug-resistant species of Stenotrophomonas maltophilia. As the high-level colistin resistance of this strain was of great concern, the genome of this strain was completely sequenced. Only one chromosome was identified, and no plasmids were found. Chromosomal gene variants and other potential genetic determinants conferring resistance to colistin and meropenem were comparatively analyzed, and results showed that strain G4 harbored two putative colistin resistance determinants (named mcr-5.3 and mcr-8.2) and four extended-spectrum -lactamase genes. In addition, 12 genes potentially encoding seven different types of efflux pumps were identified, which may have a major role in acquisition/transfer of colistin resistance. Our discovery of multiple antibiotic resistance determinants in this environmental strain extensively expands our understanding of the extent of dissemination of colistin and meropenem resistance. | [
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] |
PURPOSE: We report multi-institutional outcomes in patients who underwent urethroplasty with a rectal mucosa graft.MATERIALS AND METHODS: We used the TURNS (Trauma and Urologic Reconstructive Network of Surgeons) database to identify patients who underwent urethral reconstruction with transanal harvest of a rectal mucosa graft. We reviewed preoperative demographics, stricture etiology, previous management and patient outcomes.RESULTS: We identified 13 patients from April 2013 to June 2017. Median age at surgery was 54 years. The stricture etiology was lichen sclerosus in 6 of 13 patients (46%), idiopathic in 2 (15%), hypospadias in 1 (7%), prior gender confirming surgery in 3 (23%) and rectourethral fistula after radiation for prostate cancer in 1 (7%). Prior procedures included failed urethroplasty with a buccal mucosa graft in 9 of 13 patients (69%), direct vision internal urethrotomy in 2 (15%) and none in 2 (15%). Median stricture length was 13 cm. Stricture location in the 9 cisgender patients was panurethral in 5 (56%), bulbopendulous in 2 (22%) and bulbar in 2 (22%). It was located at the junction of the fixed urethra extending into the neophallus in all 3 patients (100%) who underwent prior gender confirming surgery. Mean rectal mucosa graft length for urethroplasty was 10.6 cm (range 3 to 16). Repair types included dorsal or ventral onlay, or 2-stage repair. Stricture recurred at a median followup of 13.5 months in 2 of 13 patients (15%). Postoperative complications included glans dehiscence, urethrocutaneous fistula and compartment syndrome in 1 patient each (7%). No rectal or bowel related complications were reported.CONCLUSIONS: Urethral reconstruction with a transanal harvested rectal mucosa graft is a safe technique when a buccal mucosa graft is unavailable or not indicated. | [
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Quantitative trait loci (QTLs) qMi-C11 and qMi-C14 impart a high level of resistance to Meloidogyne incognita in cotton. Breeders had previously backcrossed both QTLs into the susceptible Coker 201 to create the highly resistant M-120 RNR, and we crossed Coker 201 and M-120 RNR to create near-isogenic lines with either qMi-C11 or qMi-C14. Previous work suggests different modes of action for qMi-C11 and qMi-C14. To document individual and combined effects of the QTLs on nematode development and reproduction, Coker 201 (neither QTL), M-120 RNR (both QTLs), CH11 near isoline (qMi-C11), and CH14 near isoline (qMi-C14) were inoculated with M. incognita. At 4, 8, 12, 16, 20, 25, and 30 days after inoculation (DAI), roots were stained to observe nematode developmental stages (second-stage juvenile [J2], swollen second-stage juvenile [SJ2], third-stage juvenile [J3], fourth-stage juvenile [J4], and female), and the number of galls was counted. At 20, 25, 30, and 40 DAI, M. incognita eggs were harvested and counted. At 30 DAI, 80% of the nematodes on Coker 201 were female compared with 50, 40, and 33% females on CH14, CH11, and M-120 RNR, respectively, and greater proportions of nematodes remained in J2 in M-120 RNR (41%), CH11 (58%), and CH14 (27%) than in Coker 201 (9%). More nematodes progressed to J3 or J4 on Coker 201 and CH14 than on CH11 or M-120 RNR. Coker 201 and CH14 had more galls than M-120 RNR. Coker 201 had more eggs than the other genotypes at 30 DAI. Nematode development beyond J2 or SJ2 was significantly reduced by qMi-C11, and development beyond J3 or J4 was significantly reduced by qMi-C14. This study confirms that qMi-C11 and qMi-C14 act at different times and have different effects on the development of M. incognita, and therefore, they have different modes of action. | [
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Powdery mildews (PMs) are important plant pathogens causing widespread damage. Here, we report the first draft genome of Erysiphe pulchra, the causative agent of PM of flowering dogwood, Cornus florida. The assembled genome was 63.5 Mbp and resulted in formation of 19,442 contigs (N50 = 11,686 bp) that contained an estimated 6,860 genes with a genome coverage of 62?. We found 102 candidate secreted effector proteins (CSEPs) in E. pulchra similar to E. necator genes that are potentially involved in disease development. This draft genome is an initial step for understanding the evolutionary history of the PMs and will also provide insight into evolutionary strategies that led to the wide host expansion and environmental adaptations so effectively employed by the PM lineages. | [
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] |
Background/Purpose: During laparoscopic excision of choledochal cysts (CDCs), if duodenum injury is encountered, conversion to open repair of duodenal injury is often the standard approach. This study evaluates if it is safe to repair the duodenal injury laparoscopically in CDC children. Materials and Methods: CDC children who underwent single-incision laparoscopic repair for iatrogenic duodenal injury between October 2013 and September 2018 were reviewed. According to the pathophysiology, duodenal injuries were categorized into two subtypes: Type 1: injury caused by severe adhesions between perforation site at distal CDC and the duodenum; Type 2: anatomical variation, that is, distal CDC shared the common wall with the duodenum. A transabdominal wall suture was placed through distal end of CDC. Relying on the adhesion between distal CDC and duodenum, the injured duodenum can be clearly exposed when the assistant pulled on the retraction suture. The duodenal injury was repaired by a two-layer 5-0 polydioxanone running suture. The distal CDC was transected after repair was accomplished. Results: Five children were reviewed (Type 1: n = 4, Type 2: n = 1). Median age at surgery was 1.2 years. Median operative time was 4.0 hours. Median postoperative hospital stay was 7 days. Median duration of full diet resumption and drainage were 5 days, respectively. Median follow-up period was 31 months. Liver function tests and serum amylase levels were normalized within 1 year. None of patients had intestinal leak, anastomotic stenosis, bile leak, cholangitis, pancreatic leak, pancreatitis, or adhesive intestinal obstruction. Conclusions: Single-incision laparoscopic repair for iatrogenic duodenal injury in CDC children is safe and effective. | [
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: Left ventricular thrombus (LVT) is a commonly seen complication of myocardial infarction and it also can be seen because of hypertrophic cardiomyopathies, nonischemic dilated cardiomyopathies, malignancies, and so on. Guidelines suggest the use of warfarin for left ventricular thrombi, but recent case reports show that direct oral anticoagulants (DOACs) are beginning to be used for this complication. DOACs are strong alternatives for warfarin because of their efficacy and safety even though there is no randomized controlled trial that proves the effect of DOACs against LVT. In this article, we gather the case reports of DOACs against left ventricular thrombi in various conditions. | [
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