Effect of labetalol on preload in acute myocardial infarction with systemic hypertension.
We assessed the effects of labetalol on pulmonary wedge pressure (PWP) and other hemodynamic variables in 18 patients with acute myocardial infarction (AMI) and systemic hypertension (systolic blood pressure greater than 150 mm Hg). According to the initial value of PWP, the patients were separated into two groups of nine patients each: Group 1 (PWP greater than or equal to 15 mm Hg) and Group 2 (PWP less than or equal to 12 mm Hg). Labetalol was infused at increasing rates to lower systolic blood pressure below 130 mm Hg; this optimal rate (mean rates for Groups 1 and 2: 1.8 and 2.1 mg/min, respectively) was maintained for 1 h. Hemodynamic variables were measured before and after 1 h of infusion. Labetalol normalized blood pressure in both groups by a significant decrease in total systemic resistance [22% (p less than 0.001) and 13% (p less than 0.02)] and in cardiac index [17% (p less than 0.005) and 12% (p less than 0.02)]. While the hemodynamic responses were rather similar in both groups, the PWP decreased significantly (from 22 to 15 mm Hg, p less than 0.01) in Group 1, but did not change significantly in Group 2 (from 7 to 10 mm Hg, NS). The possible mechanisms behind these different responses are discussed. We conclude that labetalol is an effective drug for treating systemic hypertension in AMI which acutely decreases total systemic resistance and preload in patients with moderate left ventricular failure.


The role of tumor necrosis factor in viral disease.
Tumor Necrosis Factor (TNF) is one of the many cytokines that comprise a complex intertwined network of biological response modifiers that takes on extreme significance as the host response to infectious diseases. Soluble factors such as Interleukin-2 and Interferon-gamma released by T cells and Interleukin-1, Interleukin-6 and TNF released by monocytes have been shown to play key roles in proliferation, activation and differentiation of immune cells. It has also become evident that development of treatment modalities for infectious diseases is complicated by the complexity of this cytokine network. In the last decade numerous reports have presented data, often conflicting, which clearly demonstrate a role for TNF in the response to infections caused by viruses. This review summarizes this rapidly growing volume of data, discussing consistencies and discrepancies as appropriate. By better understanding the role of TNF in the host immune response, it may be possible to modulate this complex network for the benefit of the host in its battle against viral infection.


Multiplexed quantification of 63 proteins in human urine by multiple reaction monitoring-based mass spectrometry for discovery of potential bladder cancer biomarkers.
Three common urological diseases are bladder cancer, urinary tract infection, and hematuria. Seventeen bladder cancer biomarkers were previously discovered using iTRAQ - these findings were verified by MRM-MS in this current study. Urine samples from 156 patients with hernia (n=57, control), bladder cancer (n=76), or urinary tract infection/hematuria (n=23) were collected and subjected to multiplexed LC-MRM/MS to determine the concentrations of 63 proteins that are normally considered to be plasma proteins, but which include proteins found in our earlier iTRAQ study. Sixty-five stable isotope-labeled standard proteotypic peptides were used as internal standards for 63 targeted proteins. Twelve proteins showed higher concentrations in the bladder cancer group than in the hernia and the urinary tract infection/hematuria groups, and thus represent potential urinary biomarkers for detection of bladder cancer. Prothrombin had the highest AUC (0.796), with 71.1% sensitivity and 75.0% specificity for differentiating bladder cancer (n=76) from non-cancerous (n=80) patients. The multiplexed MRM-MS data was used to generate a six-peptide marker panel. This six-peptide panel (afamin, adiponectin, complement C4 gamma chain, apolipoprotein A-II precursor, ceruloplasmin, and prothrombin) can discriminate bladder cancer subjects from non-cancerous subjects with an AUC of 0.814, with a 76.3% positive predictive value, and a 77.5% negative predictive value. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry.


Synthesis and Biological Evaluation of Norcantharidin Derivatives Possessing an Aromatic Amine Moiety as Antifungal Agents.
Based on the structure of naturally produced cantharidin, different arylamine groups were linked to the norcantharidin scaffold to provide thirty six compounds. Their structures were confirmed by melting point, ¹H-NMR, (13)C-NMR and HRMS-ESI studies. These synthetic compounds were tested as fungistatic agents against eight phytopathogenic fungi using the mycelium growth rate method. Of these thirty six derivatives, seven displayed stronger antifungal activity than did norcantharidin, seven showed higher activity than did cantharidin and three exhibited more significant activity than that of thiabendazole. In particular, 3-(3'-chloro-phenyl)carbamoyl norcantharidate II-8 showed the most significant fungicidal activity against Sclerotinia fructigena and S. sclerotiorum, with IC50 values of 0.88 and 0.97 μg/mL, respectively. The preliminary structure-activity relationship data of these compounds revealed that: (1) the benzene ring is critical for the improvement of the spectrum of antifungal activity (3-phenylcarbamoyl norcantharidate II-1 vs norcantharidin and cantharidin); (2) among the three sites, including the C-2', C-3' and C-4' positions of the phenyl ring, the presence of a halogen atom at the C-3'position of the benzene ring caused the most significant increase in antifungal activity; (3) compounds with strongly electron-drawing or electron-donating groups substitutions were found to have a poor antifungal activity; and (4) compared with fluorine, bromine and iodine, chlorine substituted at the C-3' position of the benzene ring most greatly promoted fungistatic activity. Thus, compound II-8 has emerged as new lead structure for the development of new fungicides.


Ventricular repolarization instability quantified by instantaneous frequency of ECG ST intervals.
Ventricular repolarization instabilities have been documented to be closely linked to arrhythmia development. The electrocardiogram (ECG) ST interval can be used to measure ventricular repolarization. Analyzing the duration variation of the ST intervals can provide new information about the arrhythmogenic vulnerability. In this work, we propose a new method based on mean instantaneous frequency (IF) of the ST intervals to quantitatively evaluate the risk of sudden cardiac deaths (SCDs). Two spectral bands, i.e. the low-frequency band (LF, 0-0.15 Hz) and the high-frequency band (HF, 0.15-0.5 Hz), are considered in this paper. Based on IF estimates, the ECG recordings from three MIT-BIH databases that represent different risk levels of SCD occurrence are used, and their mean IFs in the LF and HF bands are calculated. The statistical results show that healthy subjects have a higher mean IF in the HF band and a lower mean IF in the LF band. The experimental results are the opposite for patients with malignant ventricular arrhythmia. The proposed mean IF can represent an indirect measure of intrinsic ventricular repolarization instability and can mark cardiac instability associated with SCDs.


Development and validation of a LC-MS/MS method for simultaneous determination of six glucocorticoids and its application to a pharmacokinetic study in nude mice.
In this study, a simple, rapid and sensitive LC-MS/MS analytical method for simultaneous determination of six glucocorticoids including 21-hydroxy deflazacort (21-OH DFZ), prednisolone (PNL), betamethasone (BET), beclomethasone (BEC), triamcinolone acetonide (TCA), budesonide (BUD) in nude mice plasma was developed and validated. Using testosterone as internal standard, the plasma samples were prepared by precipitation with acetonitrile and separated using an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with a mobile phase composed of acetonitrile and 0.1 % (v/v) formic acid aqueous solution by gradient elution at a flow rate of 0.3 mL/min. Quantitation was performed on a triple quadruple tandem mass spectrometer by multiple reaction monitoring in positive electrospray ionization mode. Calibration curves were developed over the range of 1-400 ng/mL for TCA, 5-2000 ng/mL for 21-OH DFZ, BET, BEC as well as BUD, and 10-2000 ng/mL for PNL. The accuracy, precision, matrix effect, recovery and stability were validated to be within acceptable criteria. The method was successfully applied to a preclinical pharmacokinetic (PK) study of the six GCs on female nude mice after a single oral dose of 1 mg/kg. The PK profiles of all the six GCs were described by two-compartment model with first-order absorption rate.


A comparative study between open versus laparoscopic Hartmann reversal: A single-center experience and analysis.
As one of the most challenging procedures in colorectal surgery, Hartmann reversal (HR) carries a burden of morbidity and mortality. We report our experience and compare open and laparoscopic HR.Between December 2012 and January 2020, 30 patients who underwent Hartmann reversal were reviewed. All patients either received laparoscopic or open reversal.Of the 87 patients who underwent Hartmann operation (HO), 30 patients received HR (Laparoscopic Hartmann Reversal, [LHR], n = 20; Open Hartmann Reversal, Open Hartmann Reversal [OHR], n = 10). There were 15 males and 15 female patients. The mean operation time was 223.8 minutes (range 115-350 minutes) with mean blood loss of 252.5 mL (range 0-700 mL). There was no conversion from LHR to OHR, and there was no ileostomy formation. Mean time to flatus was 5.0 days (range 2-13 days). There were 15 early postoperative complications and 5 late postoperative complications, but only 1 case of grade 3A. No anastomosis leakage was reported.HR is an operation that can be performed safely in well-selected patients. Minimally invasive techniques, such as LHR, is an attractive option resulting in shorter operation time, less blood loss, less pain, and shorter hospital stay.


The effect of eccentric exercise on intrinsic and reflex stiffness in the human hand.
The purpose of this work was to determine the effect of strenuous eccentric exercise on joint stiffness and to separate joint stiffness into components due to intrinsic muscle mechanics and delayed reflex muscle activation. Subjects performed 100 maximal eccentric contractions, using the first dorsal interosseus muscle to abduct the index finger while undergoing a 20 degrees displacement of the metacarpophalangeal joint. Joint stiffness was measured 24 h later during 15% and 65% maximal voluntary contraction and during electrical muscle stimulation at 15% of maximal voluntary contraction torque. Joint stiffness can be varied by changing voluntary muscle activation and thereby serves an important role in joint stabilization. Eccentric exercise has been shown to result in muscle fiber injury, reducing maximal muscle force. However, it is not known whether intrinsic muscle stiffness or reflex stiffness is also affected. Displacements of 3 degrees amplitude were used to estimate joint stiffness about the neutral angle of the index finger. The difference between measurements made during voluntary muscle activation and electrical muscle stimulation was used to obtain reflex stiffness. There was no change in the passive joint stiffness nor was there any change in either the intrinsic or reflex stiffness at 15% maximal voluntary contraction. However, intrinsic stiffness for the electrically stimulated muscle was higher post-exercise than pre-exercise, while active joint stiffness at 65% maximal voluntary contraction (comprising intrinsic and reflex stiffness) was lower. The observed mechanical changes are compatible with the hypothesis that type II muscle fibers are more susceptible to injury than type I muscle fibers, which have higher intrinsic stiffness. Muscle stiffness is important for maintaining mechanical stability of a joint. The effects of eccentric exercise on muscle stiffness are likely analogous to the effects of muscle injury, making this a good model for biomechanical changes associated with muscle injury.


The Role of Complement in Hereditary Angioedema.
Low levels of C1 inhibitor, the main inhibitor of the classic complement system, result in paroxysmal angioedema attacks that can be incapacitating or even life-threatening in affected individuals. Molecular defects in the gene for C1 inhibitor cause hereditary angioedema. In recent years, new insights in the pathways leading to angioedema due to a deficiency of C1 inhibitor have been gathered. Bradykinin, which is formed upon activation of the kallikrein-kinin system under insufficient regulation by C1 inhibitor, plays a crucial role. Whereas C1 inhibitor also occupies a central mediatory role in other plasma systems, such as the contact activation system of coagulation and the fibrinolytic plasminogen-plasmin system, a C1 inhibitor deficiency may also cause enhanced activation of these pathways. Novel therapeutic modalities for treatment and prevention of hereditary angioedema are now available, such as different forms of C1 inhibitor concentrate and novel agents that interfere in the kallikrein-kinin system.


Successful argon laser photocoagulation of diffuse epithelial ingrowth following concomitant persistent pupillary membrane removal and phacoemulsification.
A 57-year-old woman had concomitant surgery of persistent pupillary membrane removal and uneventful phacoemulsification through the same temporal clear corneal incision in her left eye. Short axial lengths (right eye, 21.08 mm; left eye, 20.39 mm) with shallow angles were noted bilaterally, and other findings were not remarkable. The patient experienced angle-closure attacks 3 and 7 months postoperatively. At the second angle-closure attack, diffuse epithelial ingrowth was observed. The epithelial ingrowth covered the intraocular lens surface in the interpupillary area, the iris surface surrounding the pupil, and the temporal anterior chamber angle, but did not reach the corneal endothelial incision. After observation of iris blanching with laser photocoagulation, argon laser photocoagulation was applied to the epithelium covering the iris and angle 7 times during the following month. The epithelial ingrowth was completely removed and did not recur during the 36-month follow-up. No author has a financial or proprietary interest in any material or method mentioned.


"Molecular Nanoclusters": A 2-nm-Sized {Mn29} Cluster with a Spherical Structure.
The comproportionation reaction between MnII and MnVII sources in the presence of 3,3-dimethylacrylic acid and azides has led to a new {Mn29} molecular cluster with a spherical structure and dimensions of ∼2.2 nm, comparable in size to the smallest classical and magnetic nanoparticles.


Development of a highly selective EP2-receptor agonist. Part 2: identification of 16-hydroxy-17,17-trimethylene 9beta-chloro PGF derivatives.
Further chemical modification of 1a and 2 was undertaken to identify a more chemically stable selective EP2-receptor agonist for development as a clinical candidate. 9beta-chloro PG analogues 4a-e and 5a, c-e were found to be potent and selective EP2-receptor agonists. Among them, the compound 4aLy, which is a chemically stabilized lysine salt of 4a, exhibited an excellent profile both in biological activities and physicochemical properties. The agonist 4aLy was found to suppress uterine motility in anesthetized pregnant rats, while PGE2 stimulated uterine motility. Structure-activity relationships (SARs) are discussed.


CXCL13 blockade attenuates lupus nephritis of MRL/lpr mice.
The chemokine CXC ligand 13 protein (CXCL13) is reported to closely related to the disease activity and severity of systemic lupus erythematosus (SLE), moreover, the level of CXCL13 was markedly raised in kidney tissues of lupus nephritis (LN) patients. The aim of the present study was to explore whether the blockade of CXCL13 has therapeutic effects on murine LN. MRL/lpr mice received 50μg anti-CXCL13 neutralizing antibody or isotype IgG by intraperitoneal injection everyday for six weeks, and renal damage of each group was determined. Our results showed that the blockade of CXCL13 significantly reduced urine protein, serum creatinine, and dramatically attenuated renal pathology injury. Treatment with anti-CXCL13Ab also reduced serum anti-dsDNA level, renal immune complex deposition as well as inflammatory cytokines secretion. Meanwhile, Th17/Treg ratio in spleens of MRL/lpr mice was significantly decreased by the blocking of CXCL13. These findings suggested that CXCL13 may be a promising target for the therapy of LN.


Indicators of the maximum radiation dose to the skin during percutaneous coronary intervention in different target vessels.
To evaluate whether the maximum radiation dose to the patient's skin (MSD) can be estimated during percutaneous coronary intervention (PCI) procedures, we investigated the relationship between the MSD and fluoroscopic time, dose-area product (DAP), and body weight, separately analyzing the relationships for different target vessels. Many cases of skin injury caused by excessive radiation exposure during cardiac intervention procedures have been reported. However, real-time maximum-dose monitoring of the skin is unavailable for many cardiac intervention procedures. We studied 197 consecutive PCI procedures that involved a single target vessel and were conducted. The DAP was measured, and the MSD was calculated by a skin-dose mapping software program (Caregraph). The target vessels of the PCI procedures were divided into four groups based on the AHA classification system: AHA 5-10, left anterior descending artery domain (LAD), AHA 11-15, left circumflex artery domain (LCx), AHA 1-3 = R 1-3, and AHA 4 = R 4. The correlation coefficient (r) between the MSD and fluoroscopic time was higher for the right coronary artery (RCA) vessels (R 1-3, 0.852; R 4, 0.715) than for the left coronary artery (LCA) vessels (LAD, 0.527; LCx, 0.646), and the r value between the MSD and DAP was higher for the RCA vessels (R 1-3, 0.871; R 4, 0.898) than for the LCA vessels (LAD, 0.628; LCx, 0.694). Similarly, the correlation coefficient between the MSD and weight x fluoroscopic time (WFP) was higher for the RCA vessels (R 1-3, 0.874; R 4, 0.807) than for the LCA vessels (LAD, 0.551; LCx, 0.735). The DAP and WFP can be used to estimate the MSD during PCI in the RCA but not in the LCA, especially the LAD.


Immunohistochemical detection of SWC3, CD2, CD3, CD4 and CD8 antigens in paraformaldehyde fixed and paraffin embedded porcine lymphoid tissue.
Identification of the different cell types of the immune system is important for in situ studies on the pathogenesis of infectious diseases in various animals, including the pig. Unfortunately, many monoclonal anti-leukocyte antibodies are only useful for staining frozen tissue sections with inherent poor tissue morphology, and are not readily adapted to formaldehyde fixed and paraffin embedded tissue with well preserved morphology. Seven well characterised monoclonal antibodies against porcine leukocyte antigens were tested on neutral buffered paraformaldehyde fixed and paraffin embedded porcine tissue sections using the highly sensitive tyramide signal amplification system. Combining this method with different antigen retrieval techniques enabled us to detect CD2, CD3, CD4, CD8 and SWC3 antigen expressing cells in porcine lymphoid tissue. Thus, we describe herein methods for the detection of several major cell types of the porcine immune system in fixed tissue with optimal preservation of histological details.


Papás Saludables, Niños Saludables: Perspectives From Hispanic Parents and Children in a Culturally Adapted Father-Focused Obesity Program.
Qualitatively assess culturally adapted lifestyle intervention, Papás Saludables, Niños Saludables (PSNS; Healthy Dads, Healthy Kids), for Hispanic fathers and children. Semistructured interviews of parents and children after participation in 10-week PSNS program for Hispanic fathers and children. Qualitative data double-coded inductively and deductively until consensus reached. Total of 26 fathers, 26 mothers, and 45 children interviewed. Parents and children had positive feedback about program content on culturally relevant nutrition and physical activity and reported improved father-child bonding. Mothers noted increased involvement among fathers in child's well-being. Participants suggested lengthening the program. Papás Saludables, Niños Saludables is an innovative approach with promise in engaging Hispanic fathers and children in a lifestyle program that emphasizes the role of fathers in children's lifestyle behaviors. Familism, respeto (respect), and promoting father-child relationships were important to engage fathers. Results from this study will inform future trials of PSNS and help identify ways to increase engagement of Hispanic men in other programs.


Prenylated PALM2 Promotes the Migration of Esophageal Squamous Cell Carcinoma Cells Through Activating Ezrin.
Proteins containing a CAAX motif at the C-terminus undergo prenylation for localization and activity and include a series of key regulatory proteins, such as RAS superfamily members, heterotrimeric G proteins, nuclear lamina protein, and several protein kinases and phosphatases. However, studies of prenylated proteins in esophageal cancer are limited. Here, through research on large-scale proteomic data of esophageal cancer in our laboratory, we found that paralemmin-2 (PALM2), a potential prenylated protein, was upregulated and associated with poor prognosis in patients. Low-throughput verification showed that the expression of PALM2 in esophageal cancer tissues was higher than that in their paired normal esophageal epithelial tissues, and it was generally expressed in the membrane and cytoplasm of esophageal cancer cells. PALM2 interacted with the two subunits of farnesyl transferase (FTase), FNTA and FNTB. Either the addition of an FTase inhibitor or mutation in the CAAX motif of PALM2 (PALM2C408S) impaired its membranous localization and reduced the membrane location of PALM2, indicating PALM2 was prenylated by FTase. Overexpression of PALM2 enhanced the migration of esophageal squamous cell carcinoma cells, whereas PALM2C408S lost this ability. Mechanistically, PALM2 interacted with the N-terminal FERM domain of ezrin of the ezrin/radixin/moesin (ERM) family. Mutagenesis indicated that lysine residues K253/K254/K262/K263 in ezrin's FERM domain and C408 in PALM2's CAAX motif were important for PALM2/ezrin interaction and ezrin activation. Knockout of ezrin prevented enhanced cancer cell migration by PALM2 overexpression. PALM2, depending on its prenylation, increased both ezrin membrane localization and phosphorylation of ezrin at Y146. In summary, prenylated PALM2 enhances the migration of cancer cells by activating ezrin.


The prevalence of Helicobacter pylori in the Hispanic population affected by hyperemesis gravidarum.
The purpose of this study was to determine the prevalence of Helicobacter pylori seropositivity in pregnant Hispanics affected by hyperemesis gravidarum. This was a prospective cross-sectional study conducted over a 22-month period. Serum from pregnant Hispanics affected by hyperemesis gravidarum and unaffected Hispanics matched for age, gravidity, parity, and country of origin were tested for H pylori immunoglobulin G (IgG). IgG levels specific for H pylori were determined by enzyme-linked immunosorbent assay (ELISA). Assuming the background prevalence of H pylori serum positivity in the Hispanic population is approximately 60%, 38 patients in each group were needed to detect a 30% difference in affected patients versus controls with a power of 80% and P = .05. Statistical analysis was performed using Yate's chi-square, Student t test, Mann-Whitney U, and binary logistic regression. A total of 82 patients between the ages of 18 to 39 years were enrolled. Of 40 patients diagnosed with hyperemesis gravidarum, 26 (65%) were seropositive for H pylori compared with 28 of 42 (67%) unaffected controls (P = 1.0). There were no statistical differences in maternal age or countries of origin between the 2 groups. The overall prevalence of H pylori seropositivity in this patient population is 66%. In pregnant Hispanics affected by hyperemesis gravidarum, H pylori seropositivity is not increased compared with unaffected controls.


Daphnane-type diterpenoids from Euphorbia fischeriana Steud and their cytotoxic activities.
Two new daphnane-type diterpenoids fischerianin A (1) and fischerianin B (2), as well as two known ones langduin A (3) and langduin A6 (4), were isolated from the extracts of Euphorbia fischeriana Steud dry roots. Their structures including the absolute stereochemistry were determined by various spectroscopic methods and comparing their experimental and calculated CD spectra. 1 and 2 harbor a ketal group and a 9,13-oxide bridge in their C ring which is rare in daphnane-type diterpenoids. In cytotoxic assays, moderately inhibitory activities of 1-4 against human cancer cell lines (human malignant melanoma cell line, A375; human liver carcinoma cell line, HepG2; human promyelocytic leukemia cell line, HL-60; human Caucasian chronic myelogenous leukemia cell line, K562; human cervix epithelioid carcinoma cell line, HeLa) were observed, with IC50 values ranging from 5.31 to 21.46 μM.


Neoadjuvant chemoradiation may be associated with improved pathologic response in pancreatic cancer.
Neoadjuvant therapy is increasingly utilized in the management of pancreatic adenocarcinoma. The type of neoadjuvant therapy and its effect on pathologic response remains understudied. A retrospective review was performed on patients who underwent neoadjuvant therapy followed by pancreatectomy. Multivariable regressions were used to determine associations between neoadjuvant therapy regimens and pathologic response. Seventy-five patients with pathologic responses available for review received FOLFIRINOX (61%) or gemcitabine with nab-paclitaxel (39%). Demographics, histologic differentiation, and utilization of chemoradiation were similar between the groups. Multivariable logistic regression demonstrated that chemoradiation was associated with an increased likelihood of a complete or near-complete pathologic response and a decreased rate of lymphovascular invasion and lymph node positivity. Neither chemotherapy regimen nor number of cycles administered were associated with pathologic response. Neoadjuvant chemoradiation may be associated with complete or near-complete pathologic response regardless of chemotherapy regimen in pancreatic cancer patients.


3-((+-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and phencyclidine produce a deficit of passive avoidance retention in rats.
3-((+-)-2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), phencyclidine (PCP) and diazepam were evaluated for their ability to produce a deficit for a single trial step-through passive avoidance response in rats. Pretraining administration with CPP at doses ranging from 2.0 to 10.0 mg/kg s.c. significantly decreased retention latencies 24 h after passive avoidance training. Similar effects were found with PCP at doses ranging from 0.5 to 1.7 mg/kg s.c. and diazepam at doses between 5.0-18.0 mg/kg s.c. Pretraining administration with the benzodiazepine antagonist, RO15-1788 at doses between 0.1-15 mg/kg s.c., did not alter retention latencies. Co-administration of RO15-1788 (0.01-15.0 mg/kg s.c.) with CPP (6.0 mg/kg s.c.) or PCP (1.0 mg/kg s.c.) failed to block decreases in latencies. However, when RO15-1788 was co-administered with diazepam (9.0 mg/kg s.c.) a dose-related antagonism of diazepam's effects were found. These results suggest that the behavioral actions of CPP and PCP on passive avoidance retention are not mediated via the benzodiazepine receptor complex.


Establishment of Actinorhizal Symbiosis in Response to Ethylene, Salicylic Acid, and Jasmonate.
Phytohormones play a crucial role in regulating plant developmental processes. Among them, ethylene and jasmonate are known to be involved in plant defense responses to a wide range of biotic stresses as their levels increase with pathogen infection. In addition, these two phytohormones have been shown to inhibit plant nodulation in legumes. Here, exogenous salicylic acid (SA), jasmonate acid (JA), and ethephon (ET) were applied to the root system of Casuarina glauca plants before Frankia inoculation, in order to analyze their effects on the establishment of actinorhizal symbiosis. This protocol further describes how to identify putative ortholog genes involved in ethylene and jasmonate biosynthesis and/or signaling pathways in plant, using the Arabidopsis Information Resource (TAIR), Legume Information System (LIS), and Genevestigator databases. The expression of these genes in response to the bacterium Frankia was analyzed using the gene atlas for Casuarina-Frankia symbiosis (SESAM web site).


Clopidogrel response up to six months after acute myocardial infarction.
High on-treatment platelet reactivity (HTPR) despite clopidogrel therapy is associated with adverse cardiac events after acute myocardial infarction (AMI). Most studies to date have assessed clopidogrel response at a single time point before or after percutaneous coronary intervention (PCI). It is unclear, however, whether the HTPR phenotype is stable over time. Therefore, we aimed to examine response to clopidogrel in patients with AMI treated with PCI over a 6-month period. Patients (n = 57) with AMI treated with PCI were assessed for response to clopidogrel at 3 time points: in hospital, 30 days, and 6 months after index hospitalization. Response to clopidogrel was determined by the VerifyNow P2Y12 assay (reported as P2Y12 response units) and multiple electrode aggregometry (MEA; reported as aggregation units). HTPR was defined as ≥235 P2Y12 response units or ≥47 aggregation units. Patients' mean age was 54.5 ± 10.9 years, 91% were men, 19% had diabetes, and 74% were admitted with ST-segment elevation MI. HTPR based on MEA was observed in 22.8% of patients in hospital, 26.3% at 30 days, and 17.5% at 6 months (p = NS). HTPR based on the VerifyNow assay was observed in 38.6% of patients in hospital, 28.1% at 30 days, and 33.3% at 6 months (p = NS). Individual HTPR phenotypic assignment at baseline was stable in 73.7% (based on MEA) and 70.2% (based on VerifyNow) of patients at 6-month follow-up. In conclusion, this is the first study evaluating the stability of clopidogrel response over time after AMI. Rates of HTPR to clopidogrel therapy appear to be relatively stable up to 6 months after AMI.


Biochemical characterisation of the chlamydial MurF ligase, and possible sequence of the chlamydial peptidoglycan pentapeptide stem.
Chlamydiaceae are obligate intracellular bacteria that do not synthesise detectable peptidoglycan although they possess an almost complete arsenal of genes encoding peptidoglycan biosynthetic activities. In this paper, the murF gene from Chlamydia trachomatis was shown to be capable of complementing a conditional Escherichia coli mutant impaired in UDP-MurNAc-tripeptide:D-Ala-D-Ala ligase activity. Recombinant MurF from C. trachomatis was overproduced and purified from E. coli. It exhibited ATP-dependent UDP-MurNAc-X-γ-D-Glu-meso-A(2)pm:D-Ala-D-Ala ligase activity in vitro. No significant difference of kinetic parameters was seen when X was L-Ala, L-Ser or Gly. The L-Lys-containing UDP-MurNAc-tripeptide was a poorer substrate as compared to the meso-A(2)pm-containing one. Based on the respective substrate specificities of the chlamydial MurC, MurE, MurF and Ddl enzymes, a sequence L-Ala/L-Ser/Gly-γ-D-Glu-meso-A(2)pm-D-Ala-D-Ala is expected for the chlamydial pentapeptide stem, with Gly at position 1 being less likely.


Compensatory head posture and neck problems: is there an association? A cohort study of nystagmus patients.
The aims of this study were twofold: to investigate if a compensatory head posture due to nystagmus causes long-term neck problems or adversely effects quality of life and to survey ophthalmologists on their opinions and management of these patients. A case-controlled study was carried out to assess the range of neck movements in patients with compensatory head posture due to congenital nystagmus. Exclusion criteria included known neck problems, vertebrobasilar insufficiency, and age less than 16 years. Neck movements were assessed using an inclinometer. Quality of life and disability was assessed using the American Academy of Orthopaedic Surgeons' Cervical Spine Questionnaire. One hundred and fifty consultant ophthalmologists throughout the United Kingdom were surveyed via a postal questionnaire. The range of motion in these patients (n=20) was limited when compared to matched controls especially for lateral flexion (P=0.001) and extension (P=0.003). However, despite limited movement, patients did not perceive a disability and there was no adverse effect on quality of life. In all 55% of ophthalmologists believed compensatory head posture due to nystagmus leads to long-term neck problems. About 46% had personal experience of patients with long-term neck problems due to nystagmus. Eighty-four per cent were influenced in their decision to operate by the presence of a head posture. Significant restriction in neck movements exists in nystagmus patients with compensatory head posture, although this does not appear to adversely affect quality of life.


Analysis of different materials subjected to open-air explosions in search of explosive traces by Raman microscopy.
Post-explosion scenes offer such chaos and destruction that evidence recovery and detection of post-blast residues from the explosive in the surrounding materials is highly challenging and difficult. The suitability of materials to retain explosives residues and their subsequent analysis has been scarcely investigated. Particularly, the use of explosive mixtures containing inorganic oxidizing salts to make improvised explosive devices (IEDs) is a current security concern due to their wide availability and lax control. In this work, a wide variety of materials such as glass, steel, plywood, plastic bag, brick, cardboard or cotton subjected to open-air explosions were examined using confocal Raman microscopy, aiming to detect the inorganic oxidizing salts contained in explosives as black powder, chloratite, dynamite, ammonium nitrate fuel oil and ammonal. Post-blast residues were detected through microscopic examination of materials surfaces. In general, the more homogeneous and smoother the surface was, the less difficulties and better results in terms of identification were obtained. However, those highly irregular surfaces were the most unsuitable collectors for the posterior identification of explosive traces by Raman microscopy. The findings, difficulties and some recommendations related to the identification of post-blast particles in the different materials studied are thoroughly discussed.


The relationship between perceived competence and perceived workplace bullying among registered nurses: A cross sectional survey.
Workplace bullying is one of the most prevalent work-related psychological and physical issues in health care facilities. Workplace bullying has detrimental effects not only on the bullied person/persons but also on health care facilities and care quality and patient safety. To examine the prevalence of workplace bullying and the relationship between workplace bullying and perceived competence among Jordanian registered nurses working in private hospitals DESIGN: A cross-sectional survey study. Data were collected from registered nurses working in seven private hospitals in the Capital of Amman. Participants were 269 registered nurses who had a minimum of a bachelor degree, passed the hospital's competency nursing examinations, able to read and understand English, and were able and willing to complete the survey. The Negative Act Questionnaire-Revised, and Nurse Professional Competence scale were used for data collection. Multiple linear regression analysis was conducted to assess predictors of greater reporting of perceived workplace bullying. Almost 43% of the participants perceived themselves to be victims of severe workplace bullying while more than 31% perceived themselves to be victims of occasional workplace bullying. Person-related bullying was the most frequently reported type of workplace bullying followed by work-related bullying. Age, gender, and sum score on Nurse Professional Competence scale explained significant amount of variance in perceived workplace bullying. The majority of Jordanian nurses working in private hospitals perceive themselves as victims of either occasional or severe workplace bullying. Amongst all related variables, perceived competence is the most significant predictor of perceived workplace bullying.


Respiratory syncytial virus inhibitors. Part 2: Benzimidazol-2-one derivatives.
Structure-activity relationships for a series of benzimidazol-2-one-based inhibitors of respiratory syncytial virus are described. These studies focused on structural variation of the benzimidazol-2-one substituent, a vector inaccessible in a series of benzotriazole derivatives on which 2 is based, and revealed a broad tolerance for substituent size and functionality.


[Role of intercellular adhesion molecule-1 and E-selectin in the pathogenesis of ovarian hyperstimulation syndrome].
To explore the ICAM-1 and E-selectin in patients with OHSS and clarifying its role in pathogenesis of the syndrome. 20 patients were included in the research and 20 control patients with stimulating ovarian cycle for the purposes of ART, during the period from 01.01.2004 till 01.01.2005 years in the center of ART-MU-Varna and Department of Obstetrics and Gynecology-IVF-ward-MU-Ben-Gurion, Israel. The patients were divided into 3 subgroups according to the degree of OHSS by the classification of Golan- mild, moderate, severe. The method of ELISA was used to record the values of the factors under research. Six patients with severe OHSS, showed increase in the value of the ICAM-1 and somebody of them, showed low level of E-selectin testing in serum and ascitic fluid in comparison with the control group and the rest of the patient with OHSS. OHSS is a life-threatening complication in which the main pathophysiology factor is the increased of capillary permeability. ICAM-1 are expressed on human granulosa cells and by the vascular endothelium after the stimulation by inflammatory cytokines and acts as a mediator of the cohesion with the lymphoid cells. E-selectin is produced by the endothelium after cytokine activation. The soluble forms of these molecules are found in serum, follicular fluid during the COH, as well as in ascitic fluid in severe OHSS. In our research adhesion molecules- ICAM-1 are correlated to the OHSS, especially in the severe forms of the syndrome.


Hospital admissions trends for severe hypoglycemia in diabetes patients in Spain, 2005 to 2015.
To analyze hospital admissions trends, inpatient mortality, and mean length of hospital stay due to hypoglycemia in patients with diabetes in Spain from 2005 to 2015. National Institute of Statistics provided information on hospital discharge and mortality. Hospital admissions due to severe hypoglycemia were identified using ICD-9 codes. Age-adjusted admission and mortality rates were stratified by sex and year. Joinpoint regression models were used to estimate trends. Admissions rates per 100,000 population were higher for men than women in 2005 (30.2, 95%CI:29.3, 31.0 versus 21.5, 95%CI:20.9, 22.1) and 2015 (23.7, 95%CI:23.0, 24.4 versus 13.2, 95%CI:12.7, 13.6). Mortality per 100,000 population was also higher for men in both years (2005: 9.4, 95%CI:7.8, 11.0 versus 8.6, 95%CI:7.4, 9.8; 2015: 6.4, 95%CI:5.3, 7.6 versus 4.1, 95%CI:3.3, 4.8). Mortality dropped 5.2 percentage points annually (95%CI:-8.4, -1.9) in men and 7.0 percentage points annually (95%CI:-8.7, -5.2) in women from 2005 to 2015. Mean length of hospital stay changed only for women: 7.8 days (95%CI:7.5, 8.0) to 6.7 days (95%CI:6.4, 6.9). Hospital admissions and inpatient mortality due to hypoglycemia in diabetes patients decreased from 2005 to 2015. This trend was more pronounced in women. Mean length of hospital stay decreased in women.


Image noise-based dose adaptation in dynamic volume CT of the heart: dose and image quality optimisation in comparison with BMI-based dose adaptation.
To compare the image quality and radiation dose using image-noise (IN)-based determination of X-ray tube settings compared with a body mass index (BMI)-based protocol during CT coronary angiography (CTCA). Two hundred consecutive patients referred for CTCA to our institution were divided into two groups: BMI-based, 100 patients had CTCA with the X-ray tube current adjusted to the patient's BMI while maintaining a fixed tube potential of 120 kV; IN-based, 100 patients underwent imaging with the X-ray tube current and voltage adjusted to the IN measured within the mid-left ventricle on a pre-acquisition trans-axial image. Two independent cardiac radiologists performed blinded image quality assessment with quantification of the IN and signal-to-noise ratio (SNR) from the mid-LV and qualitative assessment using a three-point score. Radiation dose (CTDI and DLP) was recorded from the console. Results showed: IN (HU): BMI-based, 30.1 ± 9.9; IN-based, 33.1 ± 6.7; 32 % variation reduction (P = 0.001); SNR: BMI-based, 18.6 ± 7.1; IN-based, 15.4 ± 3.7; 48 % variation reduction (P < 0.0001). Visual scores: BMI-based, 2.3 ± 0.6; IN-based, 2.2 ± 0.5 (P = 0.54). Radiation dose: CTDI (mGy), BMI-based, 22.68 ± 8.9; IN-based, 17.16 ± 7.6; 24.3 % reduction (P < 0.001); DLP (mGy.cm), BMI-based, 309.3 ± 127.5; IN-based, 230.6 ± 105.5; 25.4 % reduction (P < 0.001). Image-noise-based stratification of X-ray tube parameters for CTCA results in 32 % improvement in image quality and 25 % reduction in radiation dose compared with a BMI-based protocol. • Image quality and radiation dose are closely related in CT coronary angiography. • So too are the image quality, radiation dose and body mass index (BMI). • An image-noise-based CTCA protocol reduces the radiation dose by 25 %. • It improves inter-patient image homogeneity by 32 %.


Ion mobility spectrometry focusing on speciation analysis of metals/metalloids bound to carbonic anhydrase.
In the present work, traveling wave ion mobility spectrometry-mass spectrometry (TWIMS-MS) was applied to speciation analysis of metalloproteins. The influence of pH on complexation conditions between some metals and bovine carbonic anhydrase was evaluated from pH 6 to 9, as well as the time involved in their complexation (0-24 h). Employing TWIMS-MS, two conformational states of bovine carbonic anhydrase were observed with charge states of +12 and +11; these configurations being evaluated in terms of the folded state of the apo form and this protein (at charge state +11) being linked to barium, lead, copper, and zinc in their divalent forms. Metalloprotein speciation analysis was carried out for copper (Cu(+) and Cu(2+)), lead (Pb(2+) and Pb(4+)), and selenium (Se(4+) and Se(6+)) species complexed with bovine carbonic anhydrase. Mobilities of all complexed species were compared, also considering the apo form of this protein.


Malignant fibrous histiocytoma in a patient with history of treated retinoblastoma.
Retinoblastoma is one of the most important childhood tumors with genetic implications and necessity for family counseling and long term follow up. We are presenting a 22 year-old Saudi male with history of bilateral retinoblastoma, who was initially treated by enucleation of his left eye. The histopathology showed a moderately differentiated tumor with vitreous seeding and he received chemotherapy in addition to radiotherapy to his right eye. He presented 20 years later with a right orbital tumor, frozen globe and proptosis. The excisional biopsy of his orbital mass revealed a spindle cell sarcoma with features of malignant fibrous histiocytoma. His clinical and radiological findings are presented together with the histopathologic features of his orbital tumor and brief review of secondary tumors in retinoblastoma patients.


Mobile Sensor Application for Kinematic Detection of the Knees.
To correctly measure the knee joint angle, this study utilized a Qualisys motion capture system and also used it as the reference to assess the validity of the study's Inertial Measurement Unit (IMU) system that consisted of four IMU sensors and the Knee Angle Recorder software. The validity was evaluated by the root mean square (RMS) of different angles and the intraclass correlation coefficient (ICC) values between the Qualisys system and the IMU system. Four functional knee movement tests for ten healthy participants were investigated, which were the knee flexion test, the hip and knee flexion test, the forward step test and the leg abduction test, and the walking test. The outcomes of the knee flexion test, the hip and knee flexion test, the forward step test, and the walking test showed that the RMS of different angles were less than 6°. The ICC values were in the range of 0.84 to 0.99. However, the leg abduction test showed a poor correlation in the measurement of the knee abduction-adduction movement. The IMU system used in this study is a new good method to measure the knee flexion-extension movement.


[Constituents of Umbilicus ruperstris (Salisb.) Dandy (Crassulaceae)].
In the Umbilicus rupestris (Salisb.) Dandy, spontaneous in Genoa country, are present two heterosides with keratolytical action. The most aboundant is identical with venusol.


Reversal of acquired cisplatin resistance by nicotinamide in vitro and in vivo.
At a concentration of 2.5 mM, nicotinamide (NA), an inhibitor of poly(ADP-ribose) polymerase (PARP), significantly potentiated the cytotoxicity of cisplatin (DDP) in a DDP-resistant rat ovarian tumor cell line (O-342/DDP) in vitro, whereas the same treatment had no substantial effect on DDP's cytotoxic activity against the DDP-sensitive parental line (O-342). Furthermore, in a nude mouse model where the O-342/DDP tumor grew intraperitoneally, whereas DDP given alone at 1 mg/kg x 3 exhibited no antitumor activity as compared with control values due to the resistance, NA given at a nontoxic dose (5 mmol/kg x3) significantly increased the mean survival time (MST) of the tumor-bearing NMRI nude mice from 20.7 days in the DDP-treated group to 29.0 days in the combination group. Mechanism studies showed that endogenous PARP activity (incorporation of tritiated nicotinamide adenine dinucleotide, [3H]-NAD) was 2.6 times higher in O-342/DDP than in O-342 cells and that the presence of 2.5 mM NA during the incubation with the isotope resulted in 73.3% inhibition of the enzyme activity in O-342/DDP cells but in only about 30% inhibition in the sensitive line. However, treatment with NA during and after DDP exposure failed to produce any significant effect on the formation of DNA single-strand breaks (SSB) but decreased the induction of DNA interstrand cross-links (ISCL) by DDP in the sensitive and resistant cell lines. These results suggest that NA might have some clinical potential in reversing DDP resistance, and further studies are therefore warranted to confirm the resistance-reversing effect of NA in other DDP-resistant cell lines.


Description of a new technique for reimplanting the anomalous right pulmonary artery.
Anomalous origin of the right pulmonary artery from the ascending aorta is a rare congenital lesion with a high mortality and morbidity if early diagnosis is not made and correction is not undertaken. We describe the repair of such a lesion using a double-trapdoor technique of pulmonary artery reimplantation.


[Using 9-color Flow Cytometry Immunophenotyping to Detect Activation and Apoptosis of Human TCR Vβ Lymphocyte Subpopulations in Peripheral Blood Samples].
To establish an assay using 9-color flow cytometry immunophenotyping to detect activation and apoptosis of human TCR Vβ lymphocyte subpopulations in peripheral blood samples. We used 5 antibodies (CD3, CD4, CD8, CD95, CD69), phospholipids binding proteins Annexin V, TCR Vβ Repertoire Kit and nucleus dye DAPI to establish a 9-color flow cytometry assay. Peripheral blood samples were taken from eight healthy people for test of antibodies and determination of optimal PMT and staining method (single-stained vs stained with all but one antibody). Appropriate detecting voltage, antibody concentration and compensation methods were determined. The distribution of TCR Vβ subgroup in our samples was consistent with the TCR Vβ Repertoire Kit instruction and other published literature. We have established a effective easy using 9-color flow cytometry immunophenotyping to detect human TCR Vβ lymphocyte subpopulations in peripheral blood samples.


Mycobacterium tuberculosis survival and biofilm formation studies: effect of D-amino acids, D-cycloserine and its components.
D-amino acids play an important role in cell wall peptidoglycan biosynthesis. Mycobacterium tuberculosis D-amino acid oxidase deletion led to reduced biofilm-forming ability. Other recent studies also suggest that the accumulation of D-amino acids blocks biofilm formation and could also disperse pre-formed biofilm. Biofilms are communities of bacterial cells protected by extracellular matrix and harbor drug-tolerant as well as persistent bacteria. In Mycobacterium tuberculosis, biofilm formation or its inhibition by D-amino acids is yet to be tested. In the present study, we used selected D-amino acids to study their role in the prevention of biofilm formation and also if D-cycloserine's activity was due to presence of D-Serine as a metabolite. It was observed that D-serine limits biofilm formation in Mycobacterium tuberculosis H37Ra (Mtb-Ra), but it shows no effect on pre-formed biofilm. Also, D-cycloserine and its metabolic product, hydroxylamine, individually and in combination, with D-Serine, limit biofilm formation in Mtb-Ra and also disrupts existing biofilm. In summary, we demonstrated that D-alanine, D-valine, D-phenylalanine, D-serine, and D-threonine had no disruptive effect on pre-formed biofilm of Mtb-Ra, either individually or in combination, and D-cycloserine and its metabolite hydroxylamine have potent anti-biofilm activity.


A highly sensitively "off-on-off" fluorescence probe for detection of aluminum ion and water as well as application in Chinese Baijiu.
Developing highly sensitive fluorescent probe for Al3+ and H2O detection is highly desirable, due to aluminum toxicity poses a significant threat to public health. On the other hand, the determination of water content holds immense significance in a wide range of fields such as food processing, pharmaceutical manufacturing. In this paper, a novel acylhydrazone-based fluorescent probe P was successfully synthesized and characterized for the sequential detection of Al3+ and water in alcohols. The probe P exhibited a remarkable "turn-on" response towards Al3+ by emitting yellow fluorescence at 567 nm, with high selectivity and large Stokes shift (147 nm). Meanwhile, the in situ formed P-Al3+ complex demonstrated significant solvatofluorochromic characteristic, which could be utilized as a second probe for detecting water via fluorescence quenching with low detection limit in alcohols (0.008%, methanol; 0.013%, ethanol; 0.013%, isopropanol; 0.037%, n-butanol; vol.%) and acetonitrile (0.072%, vol.%). Moreover, the P-Al3+ complex was able to detect the alcoholic strength of Chinese Baijiu without the interference of other alcohols, providing an excellent recovery rate (100.0-107.0%). Different Chinese Baijius, with various alcoholic strength, could be distinguished by simple test strips. Furthermore, the P-Al3+ complex could also analyze the water content in organic solvents .


Percutaneous ethanol injection therapy: a surgery-sparing treatment for primary hyperparathyroidism.
To describe our 3-year experience in the long-term efficacy and safety of percutaneous ethanol injection therapy (PEIT), as an alternative to surgery for the management of patients with primary hyperparathyroidism (p-HPT). Prospective study with a mean follow-up of 19.6 +/- 10.6 months. Our study population included 19 consecutive high risk patients with p-HPT, who met the criteria for surgery. Under ultrasonic guidance, ethanol (95%) was injected into parathyroid glands with a volume of >or= 0.15 cm(3). With the aim of normalizing intact parathormone (iPTH) values, repeated ethanol injections were carried out, in an interval of 2 weeks, until normalization of iPTH was reached or until no residual blood supply was detected by ultrasound in the gland. Biochemical parameters were monitored throughout the study. At 6-month follow-up, normalization of iPTH levels (10-65 ng/l) was achieved in 11 (58%) patients (responders). Of the eight remaining patients (nonresponders), six patients had reduced (but not normalized) iPTH levels and two patients required parathyroid surgery. Seventeen (11 responders and 6 nonresponders) of the 19 patients (89.5%) became normocalcaemic (serum Ca <or= 2.57 mmol/l) and remained so for a mean follow-up of 21 months (8-39 months). The odds ratio (P < 0.05) of response vs. no response to PEIT was 16.7-fold for pretreatment iPTH < 200 vs. > 200 ng/l. The only complication was a transient dysphonia noticed in three patients. PEIT is a safe and effective nonsurgical treatment for patients with p-HPT, who are unsuitable for surgical intervention.


Treating cancerous large airway stenosis with staging radioactive particle implantation guided by computed tomography and fiber bronchoscopy: a clinical study.
The purpose of this study is to investigate the clinical effectiveness of staging radioactive particle implantation guided by computed tomography (CT) and fiber-optic bronchoscopy in treating cancerous large airway stenosis. A total of 102 patients were included; 57 had undergone staging radioactive particle implantation guided by CT and fiber bronchoscopy and 45 did not. Patients were evaluated by CT and fiber-optic bronchoscopy to determine the feasibility of the implantation of radioactive seeds for the treatment of cancerous large airway stenosis. The treatment planning system (TPS) was used to plan the doses. Radioactive seeds were implanted using fiber-optic bronchoscopy. One week later, CT-guided implantation of radioactive seeds was performed. The clinical evaluation showed complete, partial, slight, and non-response in 38, 14, 5, and 0 patients, respectively. None of the patients were found with serious complications. The diameter of the affected airway, Karnofsky score, dyspnea index, survival, and quality of life of the patients in both groups was significantly higher and significantly different after the treatment (P < 0.05). The dyspnea index was significantly lower in the treatment group as compared with the control group (P < 0.001). CT- and fiber bronchoscopy-guided staging radioactive particle implantation has definite treatment effectiveness in treating cancerous large airway stenosis. It should be widely used in clinical practices.


Carrier-free functionalized multidrug nanorods for synergistic cancer therapy.
We developed carrier-free multidrug nanocrystals (MDNCs) for the combination chemotherapy with synergistic effect, improved tolerance and imaging capability for cancer treatment. Three widely used hydrophobic drugs, methotrexate (MTX), 10-hydroxycamptothecin (HCPT) and paclitaxel (PTX), were prepared into one nanorod, and then conjugated with poly(ethylene glycol) (PEG) to improve their water dispersity and bio-environmental stability. It should be noted that only trace amount of PEG was used for surface modification, which ensures a high drug loading capacity of the resulting PEGylated MDNCs. In vitro studies showed that the MDNCs revealed an obviously higher cytotoxicity than individual drugs in the same dose and suppressed drug resistance against PTX resistant MCF-7/ADR cancer cells, indicating its synergistic effect and improved tolerance. After in vivo intravenous injection, the MDNCs exhibits a synergetic in vivo therapeutic effect and possesses obviously superior antitumor effect compared to free multidrugs treatment group and individual drug treatment groups, and no statistically significant weight loss was observed. The MDNCs can also gain imaging capabilities by encapsulated with an organic dye, which render the multidrug nanorod an all-in-one processing system for cancer diagnosis and treatment.


H/C atomic ratio as a smart linkage between pyrolytic temperatures, aromatic clusters and sorption properties of biochars derived from diverse precursory materials.
Biochar is increasingly gaining attention due to multifunctional roles in soil amelioration, pollution mitigation and carbon sequestration. It is a significant challenge to compare the reported results from world-wide labs regarding the structure and sorption of biochars derived from various precursors under different pyrolytic conditions due to a lack of a simple linkage. By combining the published works on various biochars, we established a quantitative relationship between H/C atomic ratio and pyrolytic temperature (T), aromatic structure, and sorption properties for naphthalene and phenanthrene. A reverse sigmoid shape between T and the H/C ratio was observed, which was independent of the precursors of biochars, including the ash contents. Linear correlations of Freundlich parameters (N, log Kf) and sorption amount (log Qe, log QA) with H/C ratios were found. A rectangle-like model was proposed to predict the aromatic cluster sizes of biochars from their H/C ratios, and then a good structure-sorption relationship was derived. These quantitative relationships indicate that the H/C atomic ratio is a universal linkage to predict pyrolytic temperatures, aromatic cluster sizes, and sorption characteristics. This study would guide the global study of biochars toward being comparable, and then the development of the structure-sorption relationships will benefit the structural design and environmental application of biochars.


Adult patients with congenital heart disease and pulmonary arterial hypertension: first open prospective multicenter study of bosentan therapy.
Endothelin receptor antagonism has been introduced as an effective oral therapy of patients with idiopathic pulmonary arterial hypertension. In view of the pathophysiologic and histologic similarities between idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD), there is a rationale for treating these patients with the oral dual (ET(A)/ET(B)) endothelin receptor antagonist bosentan. Thirty-three patients with PAH-CHD (43 +/- 14 years, 23 with Eisenmenger syndrome) were treated with bosentan for a mean of 2.1 +/- 0.5 years. Efficacy was assessed by a panel of tests, including New York Heart Association functional class, 6-minute walking distance, and echocardiographic and hemodynamic parameters. Mean 6-minute walking distance increased from 362 +/- 105 to 434 +/- 68 m (P = .001). New York Heart Association class also improved significantly (3.1 to 2.4, P = .0001). This was associated with slight trends in improvements of transcutaneous oxygen saturation (86% +/- 7% to 88% +/- 7%, P = .13) and maximum oxygen uptake (13.2 +/- 4.0 to 14.9 +/- 2.5, P = .18). Right ventricular systolic pressure measured by echocardiographic decreased from 111 +/- 32 to 106 +/- 22 mm Hg (P = .001). Bosentan treatment was well tolerated by all patients. Long-term bosentan treatment in adult patients with PAH-CHD was well tolerated and improved functional status as well as exercise capacity. These findings have to be corroborated by controlled studies that are presently ongoing.


Expression of a recombinant anticoagulant C-type lectin-like protein ACFI in Pichia pastoris: heterodimerization of two subunits is required for its function.
ACFI is an anticoagulant C-type lectin-like protein (CLP) isolated from Agkistrodon acutus venom. To investigate the function of ACFI and its subunits, the cDNAs of two subunits were transformed and expressed in Pichia pastoris separately or together by a novel strategy using two vectors with different selectable markers. The results showed that recombinant homodimers were secreted when the subunits were expressed alone, while heterodimers (rACFI) were secreted when two subunits were co-expressed. The secreted proteins were purified from culture supernatants in one step by metal-chelating affinity chromatography with the yields of 1-4 mg/L. PAGE and ELISA showed that rACFI competed the binding of native ACFI for human factor X and IX with affinities of 1.6 and 30 nM, respectively. In addition, rACFI prolonged the activated partial thromboplastin time (APTT) in a concentration dependent manner as same as native ACFI. However, recombinant alpha or beta homodimers completely lost these activities, indicating the heterodimerization of two subunits is required for its function. It also suggests that P. pastoris is a promising system for structure-function studies of snake CLPs.


High-dose chemotherapy and autologous bone marrow transplantation for myeloma.
In three studies we have attempted to increase the complete remission rate in a series of patients with multiple myeloma under the age of 69. A CR rate of 27% was seen in 63 patients treated with intravenous high-dose melphalan 140 m/m2 with or without the addition of high-dose methyl prednisolone 1 g/m2 for 5 days (in 22 patients). In a third study a CR rate of 50% was seen in 50 patients treated in a programme in which vincristine, adriamycin and methyl prednisolone was first given and patients then received high-dose melphalan 140-200 mg/m2 with an autologous bone marrow transplant where possible. Median remission duration in the first two studies was 19 months with a median survival of 5 years. A definition of complete remission in myeloma is proposed.


Validity, specificity, feasibility and acceptability of a brief pediatric distress thermometer in outpatient clinics.
Psychosocial distress is under-recognized in children with cancer and other serious medical illnesses because of a focus on pressing medical concerns. This study assessed the validity, inter-rater reliability, sensitivity/specificity, acceptability, and feasibility of administration of a pediatric distress thermometer (DT) designed to screen for the presence of psychosocial distress in youth with serious medical illnesses. Two hundred eighty-one patient-caregiver-provider triads were enrolled from two hospital outpatient clinics. Patients diagnosed with cancer and other life-threatening diseases, caregivers, and providers completed the DT and a DT acceptability rating. Patients and caregivers completed standardized measures of anxiety, depression, pain, and fatigue. Providers completed a measure of disease severity. Data collectors completed a feasibility rating. The DT was significantly correlated with both caregiver and patient reports of depression, anxiety, pain, and fatigue, exhibiting concurrent validity. Parent, child, and caregiver report demonstrated significant, moderate inter-rater reliability, with lower concordance between raters in the youngest age group. The DT is a sensitive instrument for screening of psychosocial distress when compared with the selected gold standard (Brief Symptom Inventory 18 depression subscale and the Children's Depression Inventory). The DT is not highly specific but quickly identifies those in need of further psychosocial assessment. Screening, using an adapted pediatric DT, is valid, feasible, and acceptable to patients, caregivers, and medical providers across chronic medical illnesses. As patient and caregiver reports are not always concordant, both patient and caregiver report of distress are important for the provider to obtain clinically meaningful information to guide interventions. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.


How do the parietal lobes direct covert attention?
In cases of unilateral parietal damage patients have trouble with stimuli in the visual hemifield on the side opposite the lesion (contralesional). This deficit is clear when they are first cued to attend to a location on the side of the lesion (ipsilesional) and then given a target on the opposite side of fixation. Our first experiments indicated that these patients do worse when cued to a location in either field and then given a target in the contralesional as compared to the ipsilesional direction. The results of this experiment can be accounted for by a representational or a directional view. A second experiment seeks to discriminate between the two. The results tend to favor the directional view.


Metabolic Profiling Using Stable Isotope Tracing Reveals Distinct Patterns of Glucose Utilization by Physiologically Activated CD8+ T Cells.
Naive CD8+ T cells differentiating into effector T cells increase glucose uptake and shift from quiescent to anabolic metabolism. Although much is known about the metabolism of cultured T cells, how T cells use nutrients during immune responses in vivo is less well defined. Here, we combined bioenergetic profiling and 13C-glucose infusion techniques to investigate the metabolism of CD8+ T cells responding to Listeria infection. In contrast to in vitro-activated T cells, which display hallmarks of Warburg metabolism, physiologically activated CD8+ T cells displayed greater rates of oxidative metabolism, higher bioenergetic capacity, differential use of pyruvate, and prominent flow of 13C-glucose carbon to anabolic pathways, including nucleotide and serine biosynthesis. Glucose-dependent serine biosynthesis mediated by the enzyme Phgdh was essential for CD8+ T cell expansion in vivo. Our data highlight fundamental differences in glucose use by pathogen-specific T cells in vivo, illustrating the impact of environment on T cell metabolic phenotypes.


Evidence for two populations of hair bundles in the sea anemone, Nematostella vectensis.
Cytochalasin D (CD) was employed to disrupt F-actin within stereocilia of anemone hair bundles. CD treatment decreases the abundance of hair bundles (by 85%) while significantly impairing predation. The remaining hair bundles are 'CD-resistant.' Surprisingly, the morphology and F-actin content of resistant hair bundles are comparable to those of untreated controls. However, the resistant hair bundles fail to respond normally to the N-acetylated sugar, NANA, by elongating. Instead, they remain at resting length. Immediately after CD treatment, when only CD-resistant hair bundles are present, nematocyst discharge is normal into targets touched to tentacles in the absence of vibrations (i.e., baseline) but fails to increase normally in the presence of nearby vibrations at 56Hz, a key frequency. After CD treatment, the abundance of hair bundles recovers to control levels within three hours. At 2h after CD treatment, when CD-resistant and CD-sensitive hair bundles are both present, but a full-recovery is not yet complete, somewhat enhanced discharge of nematocysts occurs into targets touched to tentacles in the presence of nearby vibrations at 56Hz (at least as compared to the response of CD-treated animals to contact with test probes in the absence of vibrations). Additionally, at 2h after CD-treatment, prey capture recovers to normal. Thus, two populations of hair bundles may be present on tentacles of sea anemones: those that are CD-resistant and those that are CD-sensitive. The functions of these hair bundles may be distinct.


Comparison of Grouping Schemes for Exposure to Total Dust in Cement Factories in Korea.
The purpose of this study was to evaluate grouping schemes for exposure to total dust in cement industry workers using non-repeated measurement data. In total, 2370 total dust measurements taken from nine Portland cement factories in 1995-2009 were analyzed. Various grouping schemes were generated based on work process, job, factory, or average exposure. To characterize variance components of each grouping scheme, we developed mixed-effects models with a B-spline time trend incorporated as fixed effects and a grouping variable incorporated as a random effect. Using the estimated variance components, elasticity was calculated. To compare the prediction performances of different grouping schemes, 10-fold cross-validation tests were conducted, and root mean squared errors and pooled correlation coefficients were calculated for each grouping scheme. The five exposure groups created a posteriori by ranking job and factory combinations according to average dust exposure showed the best prediction performance and highest elasticity among various grouping schemes. Our findings suggest a grouping method based on ranking of job, and factory combinations would be the optimal choice in this population. Our grouping method may aid exposure assessment efforts in similar occupational settings, minimizing the misclassification of exposures.


Learning Curve of Surgeons Performing Laparoscopic Ovarian Tissue Transplantation in Women with Premature Ovarian Insufficiency: A Statistical Process Control Analysis.
To analyze patient safety in laparoscopic ovarian tissue transplantation surgery by tracking the rate of postoperative complications and the learning curves of the surgeons by statistical process control analysis. A retrospective study. A university-affiliated hospital. A total of 100 patients with premature ovarian insufficiency who underwent ovarian tissue cryopreservation by vitrification and then autologous transplantation of frozen-thawed ovarian tissues with in vitro activation. Ovarian tissue cryopreservation, in vitro activation, and transplantation. We assessed the surgery complications, differences in total surgery time, transplantation time, and transplantation time per ovarian sheet in operations performed by 3 experienced laparoscopic surgeons. Surgeon A performed 80 operations; surgeon B, 29 operations; and surgeon C, 20 operations. Complications occurred in 1.55% of the procedures. Although all 3 surgeons' performance never fell below the unacceptable failure limit, only surgeon A became competent after 66 cases. The laparoscopic ovarian tissue transplantation surgery was generally safe given that the postoperative complications were infrequent (1.55%). Although the performance of all 3 surgeons was acceptable, only surgeon A attained the level of competency after 66 cases. The transplantation method may not be the key factor for reducing surgery time in this surgery. An efficient ovarian tissue transplantation team is more important in reducing the surgery time than the surgeon's surgical technique alone.


Genomic analysis of Poxviridae and exploring qualified gene sequences for phylogenetics.
The members of the Poxviridae family are globally distributed all over the world and can cause infectious diseases. Although genome sequences are publicly available for representative isolates of all genera, studies on the criteria for genome-based classification within the Poxviridae family have rarely been reported. In our study, 60 Poxviridae genomes were re-annotated using Prokka. By using BLAST filtration and MCScanX, synteny and similarity of whole genomic amino acid sequences were visualized. According to the analysis pattern, the Chordopoxvirinae and Entomopoxvirinae subfamilies can be subdivided into five and two categories respectively, which is consistent with the phylogenetic tree constructed based on whole genomic amino acid sequences and Poxvirus core genes. Finally, four genes (Early transcription factor, DNA-directed RNA polymerase, RNA polymerase-associated transcription-specificity factor and DNA-dependent RNA polymerase) were selected from Poxvirus core genes by substitution saturation analysis and phylogenetic tree verification. Phylogenetic trees constructed based on single gene and concatenated sequences of the four selected genes showed that the classification of subgroups was consistent with the phylogenetic trees based on genome. Conclusion: a new method based on the similarity of whole genomic amino acid sequences was proposed for Poxviridae taxon demarcation, and the use of the four selected qualified genes will help make phylogenic identification of newly discovered Poxviridae isolates more convenient and accurate.


A fast and reliable method for semi-automated planimetric quantification of dental plaque in clinical trials.
To develop a simple and reproducible method for semi-automated planimetric quantification of dental plaque. Plaque from 20 healthy volunteers was disclosed using erythrosine, and fluorescence images of the first incisors, first premolars, and first molars were recorded after 1, 7, and 14 days of de novo plaque formation. The planimetric plaque index (PPI) was determined using a semi-automated threshold-based image segmentation algorithm and compared with manually determined PPI and the Turesky modification of the Quigley-Hein plaque index (TM-QHPI). The decrease of tooth autofluorescence in plaque-covered areas was quantified as an index of plaque thickness (TI). Data were analysed by analysis of variance (ANOVA) and Pearson correlations. The high contrast between teeth, disclosed plaque, and soft tissues in fluorescence images allowed for a fast threshold-based image segmentation. Semi-automated PPI is strongly correlated with manual planimetry (r = 0.92; p < .001) and TM-QHPI recordings (r = 0.88; p < .001), and may exhibit a higher discriminatory power than TM-QHPI due to its continuous scale. TI values corresponded to optically perceived plaque thickness, and no differences were observed over time (p > .05, ANOVA). The proposed semi-automated planimetric analysis based on fluorescence images is a simple and efficient method for dental plaque quantification in multiple images with reduced human input.


Use of oil-in-water emulsions to control fungal deterioration of strawberry jams.
This work aimed to control the fungal deterioration of strawberry jams. The antifungal activity of the clove, cinnamon leaf, lemon and mandarin essential oils and their effectiveness in oil-in-water emulsions were evaluated. According to the results obtained, only clove and cinnamon leaf oils were selected to prepare emulsions. All the tested emulsions were stable, independently the amount of polymer and essential oil used. Essential oil loss was affected by the amount of polymer employed to prepare the emulsions. The oil-in-water emulsions with 5.0mg/g xanthan gum, and with 0.55mg/g clove or 0.65mg/g cinnamon leaf essential oil, were used for the in vivo tests. The jams prepared with the oil-in-water emulsions showed a lower fungal decay compared with jams without emulsion. The present work demonstrated that emulsions can be employed to prevent strawberry jam mould spoilage.


Masking by internally generated noise and protection by middle ear muscle activity.
Gross auditory nerve action potentials to high-frequency clicks were recorded bilaterally from awake cats with unilaterally tenotomized middle ear muscles (MEM) during eating and during control quiet periods. Masking by internally generated noise associated with eating increased with decreases in click intensity, but did not differ in ears with intact and tenotomized MEM. Under the conditions of this study, non-reflex MEM activity does not appear to provide protection against masking by internally generated noise.


Determination of structural topology of a membrane protein in lipid bilayers using polarization optimized experiments (POE) for static and MAS solid state NMR spectroscopy.
The low sensitivity inherent to both the static and magic angle spinning techniques of solid-state NMR (ssNMR) spectroscopy has thus far limited the routine application of multidimensional experiments to determine the structure of membrane proteins in lipid bilayers. Here, we demonstrate the advantage of using a recently developed class of experiments, polarization optimized experiments, for both static and MAS spectroscopy to achieve higher sensitivity and substantial time-savings for 2D and 3D experiments. We used sarcolipin, a single pass membrane protein, reconstituted in oriented bicelles (for oriented ssNMR) and multilamellar vesicles (for MAS ssNMR) as a benchmark. The restraints derived by these experiments are then combined into a hybrid energy function to allow simultaneous determination of structure and topology. The resulting structural ensemble converged to a helical conformation with a backbone RMSD ~0.44 Å, a tilt angle of 24° ± 1°, and an azimuthal angle of 55° ± 6°. This work represents a crucial first step toward obtaining high-resolution structures of large membrane proteins using combined multidimensional oriented solid-state NMR and magic angle spinning solid-state NMR.


Genistein Improves the Major Depression through Suppressing the Expression of miR-221/222 by Targeting Connexin 43.
Recent studies have indicated the possibility that genistein may improve depression via regulating the expression of miR221/222. This study is to explore whether genistein could improve depression by altering miR-221/222 levels and investigate the possible mechanisms involved in the improvement effect of genistein. The animal model of depression was established through unpredictable chronic mild stress. Nest building test and splash test were adapted to evaluate the effects of genistein on depressive symptoms in mice. qRT-PCR and western blot analysis were used to detect the expression of miR-221/222 and connexin 43 (Cx43) in the prefrontal cortex of the mice. In vitro, U87-MG astrocytes were treated with genistein and the expression of miR-221/222 and Cx43 was measured. The dual-luciferase reporter assay was used to verify whether Cx43 was a direct target of miR-221/222. The behavioral tests showed that genistein could significantly reduce depression symptoms of mice, and this remission was not affected by gender. Genistein in vivo and in vitro could reduce increased levels of miR-221 and miR-222 in the prefrontal cortex of depressed mice, while upregulate Cx43 expression. Dual-luciferase reporter assay suggested Cx43 was directly regulated by miR-221/222 in astrocytes. Genistein can play its antidepressant effect through down-regulating miR-221/222 by targeting Cx43.


D,L-Glyceraldehyde 3-phosphate breakdown in the presence of selenalysine.
Selenalysine is more effective than lysine both on glyceraldehyde 3-P transformation into methylglyoxal and on subsequent methylglyoxal polymerization.


Preparation and characterization of PLLA/chitosan-graft-poly (ε-caprolactone) (CS-g-PCL) composite fibrous mats: The microstructure, performance and proliferation assessment.
In order to achieve the electrospinning of chitosan in common organic solvents, amino-reserved CS-g-PCL was synthesized by one-step method. PLLA and dichloromethane/ethanol (CH2Cl2/EtOH) solvent were chosen to prepare a series of different compositions of PLLA/CS-g-PCL mats (8/2, 6/4, 4/6, 2/8 wt/wt%) by electrospinning. The SEM showed that the smooth defect-free and uniform nanofibers were collected except PLLA/CS-g-PCL 2/8 and pure CS-g-PCL, and the fiber diameter was decreased from 828 nm to 461 nm with the increasing content of CS-g-PCL. The mechanical properties of composite mats have decreased with increasing CS-g-PCL content, but much higher than neat PLLA. The water contact angle, water absorption rate, water-vapor transmission rate and in vitro degradation behavior were 129°-19°, 109%-482%, 1945-2517 g m-2 day-1 and 4-14%, respectively. The addition of CS-g-PCL imparted PLLA/CS-g-PCL electrospun mats on better properties, improving the nature defects of PLLA. The in vitro cell culture studies showed that PLLA/CS-g-PCL 6/4 exhibited a higher in vitro biocompatibility and a better ability for cell attachment, spreading, and proliferation, comparing with PLLA mats. Herein, PLLA/CS-g-PCL 6/4 electrospun mats with excellent performance, was considered the potential application as wound dressing in skin tissue engineering.


Diabetes Connect: Developing a Mobile Health Intervention to Link Diabetes Community Health Workers With Primary Care.
Community health worker (CHW) interventions can help improve diabetes self-management and health outcomes. There is limited evidence on how to effectively integrate CHW programs with primary care efforts. Mobile health technology (mHealth) can connect CHWs to members of the health care team and enhance care. We tested a model for the integration of a CHW-delivered mHealth intervention to improve diabetes self-management. Seventy-two African American patients with diabetes were followed using the mHealth tool. This project partnered an academic institution, a safety-net clinic, and African American churches. The integration of mHealth technology into CHW programs was successfully achieved and readily accepted.


Regulatory properties of human erythrocyte hexokinase during cell ageing.
Human red blood cell hexokinase exists in multiple molecular forms with different isoelectric points but similar kinetic and regulatory properties. All three major isoenzymes (HK Ia, Ib, and Ic) are inhibited competitively with respect to Mg.ATP by glucose 6-phosphate (Ki = 15 microM), glucose 1,6-diphosphate (Ki - 22 microM), 2,3-diphosphoglycerate (Ki = 4 mM), ATP (Ki = 1.5 mM), and reduced glutathione (Ki = 3 mM). All these compounds are present in the human erythrocyte at concentrations able to modify the hexokinase reaction velocity. However, the oxygenation state of hemoglobin significantly modifies their free concentrations and the formation of the Mg complexes. The calculated rate of glucose phosphorylation, in the presence of the mentioned compounds, is practically identical to the measured rate of glucose utilization by intact erythrocytes (1.43 +/- 0.15 mumol h-1 ml red blood cells-1). Hexokinase in young red blood cells is fivefold higher when compared with the old ones, but the concentration of many inhibitors of the enzyme is also cell age-dependent. Glucose 6-phosphate, glucose 1,6-diphosphate, 2,3-diphosphoglycerate, ATP, and Mg all decay during cell ageing but at different rates. The free concentrations and the hemoglobin and Mg complexes of both ATP and 2,3-diphosphoglycerate with hemoglobin in the oxy and deoxy forms have been calculated. This information was utilized in the calculation of glucose phosphorylation rate during cell ageing. The results obtained agree with the measured glycolytic rates and suggest that the decay of hexokinase during cell ageing could play a critical role in the process of cell senescence and destruction.


Parenteral treprostinil induction for rapid attainment of therapeutic doses of oral treprostinil.
Oral treprostinil slows disease progression and improves exercise capacity in pulmonary arterial hypertension; however, titration can be prolonged. Published data suggests prostacyclin-naïve patients achieve total daily oral treprostinil doses of about 6 mg by Week 16, while those on prior parenteral treprostinil reach higher doses at the same timepoint. EXPEDITE (NCT03497689), a single-arm, multicenter study, assessed the efficacy of rapid parenteral treprostinil induction to quickly reach higher doses of oral treprostinil for the treatment of pulmonary arterial hypertension. Parenteral treprostinil was titrated for 2-8 weeks, followed by cross-titration of oral treprostinil. The primary endpoint was percentage of patients reaching ≥12 mg daily of oral treprostinil at Week 16. Secondary endpoints included clinical changes from baseline to Week 16. Twenty-nine prostacyclin-naïve patients were included in efficacy analyses. At Week 16, the mean daily oral treprostinil dose was 16.4 mg; 79% of patients met the primary endpoint. From baseline to Week 16, median REVEAL Lite 2 score improved (decreased) from 6 to 3.5 (p = 0.0006). Statistically significant improvements were also seen in World Health Organization Functional Class, N-terminal-pro brain natriuretic peptide levels, 6-minute walk distance, right atrial area, Borg Dyspnea Score, and emPHasis-10 score. Favorable trends were seen in risk stratification, echocardiography parameters, disease symptoms, and treatment satisfaction. Short-course parenteral treprostinil induction resulted in oral treprostinil doses over twice those reported in de novo initiations and may be a useful approach to quickly achieve the therapeutic benefits of oral treprostinil.


Post-embryonic development of the Malpighian tubules in Apis mellifera (Hymenoptera) workers: morphology, remodeling, apoptosis, and cell proliferation.
The honeybee Apis mellifera has ecological and economic importance; however, it experiences a population decline, perhaps due to exposure to toxic compounds, which are excreted by Malpighian tubules. During metamorphosis of A. mellifera, the Malpighian tubules degenerate and are formed de novo. The objective of this work was to verify the cellular events of the Malpighian tubule renewal in the metamorphosis, which are the gradual steps of cell remodeling, determining different cell types and their roles in the excretory activity in A. mellifera. Immunofluorescence and ultrastructural analyses showed that the cells of the larval Malpighian tubules degenerate by apoptosis and autophagy, and the new Malpighian tubules are formed by cell proliferation. The ultrastructure of the cells in the Malpighian tubules suggest that cellular remodeling only occurs from dark-brown-eyed pupae, indicating the onset of excretion activity in pupal Malpighian tubules. In adult forager workers, two cell types occur in the Malpighian tubules, one with ultrastructural features (abundance of mitochondria, vacuoles, microvilli, and narrow basal labyrinth) for primary urine production and another cell type with dilated basal labyrinth, long microvilli, and absence of spherocrystals, which suggest a role in primary urine re-absorpotion. This study suggests that during the metamorphosis, Malpighian tubules are non-functional until the light-brown-eyed pupae, indicating that A. mellifera may be more vulnerable to toxic compounds at early pupal stages. In addition, cell ultrastructure suggests that the Malpighian tubules may be functional from dark-brown-eyed pupae and acquire greater complexity in the forager worker bee.


Enhanced photo-Fenton degradation of tetracycline hydrochloride by 2, 5-dioxido-1, 4-benzenedicarboxylate-functionalized MIL-100(Fe).
Heterogeneous photo-Fenton technology has drawn tremendous attention for removal of recalcitrant pollutants. Fe-based metal-organic frameworks (Fe-MOFs) are regarded to be superior candidates in wastewater treatment technology. However, the central metal sites of the MOFs are coordinated with the linkers, which reduces active site exposure and decelerates H2O2 activation. In this study, a series of 2, 5-dioxido-1, 4-benzenedicarboxylate (H2DOBDC)-functionalized MIL-100(Fe) with enhanced degradation performance was successfully constructed via solvothermal strategy. The modified MIL-100(Fe) displayed an improvement in photo-Fenton behaviors. The photocatalytic rate constant of optimized MIL-100(Fe)-1/2/3 are 2.3, 3.6 and 4.4 times higher compared with the original MIL-100(Fe). The introduced H2DOBDC accelerates the separation and transfer in photo-induced charges and promotes Fe(II)/Fe(III) cycle, thus improving the performance. •OH and •O2- are main reactive radicals in tetracycline (TCH) degradation. Dealkylation, hydroxylation, dehydration and dealdehyding are the main pathways for TCH degradation.


More about Thraulodes Ulmer, 1920 (Ephemeroptera: Leptophlebiidae) from the Brazilian Amazonia: three new species, a new record and a gynandromorph report.
Three new species of Thraulodes Ulmer (Ephemeroptera: Leptophlebiidae) from Brazilian Amazonia are described: Thraulodes yara n. sp., Thraulodes yaciara n. sp. and Thraulodes ykamiaba n. sp., all based on imagoes. All three new species can be easily recognized by general color pattern and genitalia morphology. Thraulodes alboniger Kluge, 2020, known only from Peru, is recorded in Brazil. A remarkable gynandromorph case is presented for T. yara n. sp.


Geoenvironmental factors related to high incidence of human urinary calculi (kidney stones) in Central Highlands of Sri Lanka.
An area with extremely high incidence of urinary calculi was investigated in the view of identifying the relationship between the disease prevalence and the drinking water geochemistry. The prevalence of the kidney stone disease in the selected Padiyapelella-Hanguranketa area in Central Highlands of Sri Lanka is significantly higher compared with neighboring regions. Drinking water samples were collected from water sources that used by clinically identified kidney stone patients and healthy people. A total of 83 samples were collected and analyzed for major anions and cations. The anions in the area varied in the order HCO3 (-) > Cl(-) > SO4 (2-) > NO3 (-) and cations varied in the order Ca(2+) > Mg(2+) > Na(+) > K(+) > Fe(2+). The dissolved silica that occurs as silicic acid (H4SiO4) in natural waters varied from 8.8 to 84 mg/L in prevalence samples, while it was between 9.7 and 65 mg/L for samples from non-prevalence locations. Hydrogeochemical data obtained from the two groups were compared using the Wilcoxon rank-sum test. It showed that pH, total hardness, Na(+), Ca(2+) and Fe(2+) had significant difference (p < 0.005) between water sources used by patients and non-patients. Elemental ratio plots, Gibbs' plot and factor analysis indicated that the chemical composition of water sources in this area is strongly influenced by rock-water interactions, particularly the weathering of carbonate and silicate minerals. This study reveals a kind of association between stone formation and drinking water geochemistry as evident by the high hardness/calcium contents in spring water used by patients.


Proline provides site-specific flexibility for in vivo collagen.
Fibrillar collagens have mechanical and biological roles, providing tissues with both tensile strength and cell binding sites which allow molecular interactions with cell-surface receptors such as integrins. A key question is: how do collagens allow tissue flexibility whilst maintaining well-defined ligand binding sites? Here we show that proline residues in collagen glycine-proline-hydroxyproline (Gly-Pro-Hyp) triplets provide local conformational flexibility, which in turn confers well-defined, low energy molecular compression-extension and bending, by employing two-dimensional 13C-13C correlation NMR spectroscopy on 13C-labelled intact ex vivo bone and in vitro osteoblast extracellular matrix. We also find that the positions of Gly-Pro-Hyp triplets are highly conserved between animal species, and are spatially clustered in the currently-accepted model of molecular ordering in collagen type I fibrils. We propose that the Gly-Pro-Hyp triplets in fibrillar collagens provide fibril "expansion joints" to maintain molecular ordering within the fibril, thereby preserving the structural integrity of ligand binding sites.


The relationship between headache and preeclampsia: a case-control study.
Pregnancy-induced hypertension with proteinuria (preeclampsia-PE) is linked to increased vascular reactivity, increased vasoconstrictors, endothelial damage and platelet hyperaggregation, which are also typical features of migraine patients. Thus, we investigated the association between headache and PE. In a case-control study, we evaluated the occurrence of primary headache forms in 75 women with a recent history of PE. Seventy-five controls were selected from women having uneventful pregnancy at term. Both groups were matched for age and parity. Subjects' headache history was evaluated by using an ad hoc structured questionnaire. The International Headache Society criteria for primary headaches were applied to diagnose the specific form of headache. In PE cases, gestational age at parturition was 34.2+/-3.8 weeks and birthweight was 1820+/-746 g, whereas in controls they were 39.3+/-1.5 weeks and 3365+/-437 g, respectively (P < 0.01). Sixty-six (44%) subjects suffered from headache. Headache was significantly more frequent in PE (47/75) than in controls (19/75), OR 4.95 (95% CI, 2.47-9.92). Migraine without aura was more frequently present in cases than in controls while episodic tension-type headache was equally distributed among groups. Fifty-two patients met the criteria of severe PE. The number of patients suffering from headache was significantly higher in severe patients (39 cases, 75%) than in those with moderate PE (8 cases, 34.8%), OR = 5.63 (95% CI, 1.97-16.03). With respect to controls, PE patients reported a more frequent onset at menarche, more menstrually related attacks and an increased rate of improvement during pregnancy. This study shows that there is a strong association between migraine history and PE development, namely with the severe form of PE.


Ruptured Basilar Tip Aneurysm in a Patient with Bilateral Internal Carotid Artery Occlusion Successfully Treated with Bilateral Superficial Temporal Artery-Middle Cerebral Artery Anastomoses: Case Report.
Some ruptured intracranial aneurysms concomitant with major artery occlusion may not be amenable for standard clipping or coiling due to the specific hemodynamic conditions. The long-term effect of flow reduction therapy for such aneurysms is largely unknown. A 45-year-old woman presented with subarachnoid hemorrhage due to a ruptured basilar tip aneurysm. Angiography revealed that the bilateral internal carotid arteries were hypoplastic and that the anterior circulation was fed by the collateral flow through the bilateral posterior communicating arteries and the posterior choroidal arteries. Endovascular treatment failed because it was extremely difficult to secure the catheter at the neck of the aneurysm and insert the coil safely because it was a small aneurysm with a wide neck. In addition, direct clipping was risky due to the location and projection of the aneurysm. We therefore adopted the 2-stage bilateral superficial temporal artery-middle cerebral artery bypass to alleviate the vascular demand on the anterior circulation, with the aim of reducing the hemodynamic stress to the basilar bifurcation. The patient had no rebleeding for 4 years after surgery, with gradual shrinkage of the aneurysm. All the possible treatment options should be carefully assessed because the long-term effect of the flow alternation method to prevent rebleeding has not been proved. However, our case suggests that the strategy of reducing the hemodynamic stress at the parent artery may be effective even in selected cases of ruptured aneurysms for which standard clipping or coiling is not feasible.


Big data suggest strong constraints of linguistic similarity on adult language learning.
When adults learn new languages, their speech often remains noticeably non-native even after years of exposure. These non-native variants ('accents') can have far-reaching socio-economic consequences for learners. Many factors have been found to contribute to a learners' proficiency in the new language. Here we examine a factor that is outside of the control of the learner, linguistic similarities between the learner's native language (L1) and the new language (Ln). We analyze the (open access) speaking proficiencies of about 50,000 Ln learners of Dutch with 62 diverse L1s. We find that a learner's L1 accounts for 9-22% of the variance in Ln speaking proficiency. This corresponds to 28-69% of the variance explained by a model with controls for other factors known to affect language learning, such as education, age of acquisition and length of exposure. We also find that almost 80% of the effect of L1 can be explained by combining measures of phonological, morphological, and lexical similarity between the L1 and the Ln. These results highlight the constraints that a learner's native language imposes on language learning, and inform theories of L1-to-Ln transfer during Ln learning and use. As predicted by some proposals, we also find that L1-Ln phonological similarity is better captured when subcategorical properties (phonological features) are considered in the calculation of phonological similarities.


The roles of ventilation and perfusion in lung metabolism.
The lung, like other viable organs, requires the adequate supply of oxygen and metabolic substrates for its functional and structural integrity. Therefore, we studied the metabolic and ultrastructural consequences in the canine lung following bronchial and/or pulmonary arterial occlusions. The results indicate that the lung can maintain its bioenergetic levels for 5 hours with either the ventilation or perfusion alone. Ultrastructural changes appear to precede metabolic alterations measured. When both the ventilation and perfusion were interrupted, rapid biochemical and structural deteriorations occurred, whereas the combinations of alveolar obliteration and hypoxemia, induced with low F102, produced intermediate damage. The implications of these findings on the pathogenesis and evolution of acute respiratory distress syndrome, on the lung preservation for transplantation, and on the rationale for membrane oxygenator support are discussed.


Energy simulation and CFD coupled analysis for the optimal operation of combined convection and radiant air conditioning considering dehumidification.
The use of radiant panels in homes has increased recently because they do not cause a drafty feeling, unlike air conditioners. However, air conditioners are more power-efficient than radiant panels and have a higher coefficient of performance (COP). Therefore, combining radiant panels and air conditioning can provide an optimal solution for thermal control in residences. Energy simulation (ES) and computational fluid dynamics (CFD) can be used to simulate such environments. ES is suitable for non-steady state calculations, and combined with appropriate modeling, enables an accurate estimation of power consumption. Effective dehumidification becomes necessary, during summer as the relative humidity in a room increases. Both air conditioners and radiant panels can achieve this. This study developed a simulation tool that incorporates the effects of dehumidification. Based on a relative evaluation, a case was proposed where both energy efficiency and comfort were satisfied by jointly using air conditioners and radiant panels. The study found that a small number of panels could achieve the most balanced operation. The results of this study can serve as a reference for general housing, and the developed simulation tool can be applied to product development and building material design.