Effect of macronutrient composition on postprandial peptide YY levels.
Peptide YY (PYY) is released from the distal small intestine and colon after meals and reduces appetite by increasing satiety. The amount of PYY released is proportional to calories ingested. Fat ingestion has also been reported to stimulate PYY release. The objective of the study was to determine whether macronutrient composition influences postprandial serum PYY levels by comparing 1 wk of a weight-maintenance low-carbohydrate, high-fat (LCHF) diet with a low-fat, high-carbohydrate (LFHC) diet. In this randomized crossover study, 18 obese subjects (14 females, 4 males, mean body mass index 35.6 +/- 2.9 kg/m(2)) were randomly assigned initially to 1 wk of a weight-maintenance LCHF or LFHC diet, after which a test meal of identical composition was given and serum PYY levels were assessed for 2.5 h postprandially. After a 1-wk washout period, subjects were crossed over and retested. After 1 wk, mean postprandial area under the curve PYY after the LCHF test meal was 1.5-fold greater than after the LFHC test meal (P < 0.001). The LCHF diet led to 55% higher levels of postprandial serum PYY levels, compared with the LFHC diet (P = 0.005). These data show that a LCHF diet stimulates PYY secretion more than a LFHC diet in obese individuals.


Association of the HindIII Lipoprotein Lipase Gene Polymorphism with the Development of the Non-Biliary Acute Pancreatitis: a Pilot Study.
We studied the relationship between lipoprotein lipase (LPL) gene HindIII polymorphism and the development of acute pancreatitis in the Russian population. Whole blood samples were collected from 145 patients with acute non-biliary pancreatitis and 191 healthy individuals. Genotyping of LPL gene HindIII (rs320) polymorphism was performed by PCR with TaqMan assay. It was found that allele H+ (OR=0.63, 95%CI 0.41-0.96, p=0.03) and genotype H+/H+ (OR=1.79, 95%CI 1.06-3.04, p=0.03) were associated with the risk of acute non-biliary pancreatitis only in males. In this study, the relationship between HindIII polymorphism of LPL gene with the risk of acute non-biliary pancreatitis was revealed.


Structure Guided Design, Synthesis, and Biological Evaluation of Oxetane-Containing Indole Analogues.
The oxetane functional group offers a variety of potential advantages when incorporated within appropriate therapeutic agents as a ketone surrogate. OXi8006, a 2-aryl-3-aroyl-indole analogue, functions as a small-molecule inhibitor of tubulin polymerization that has a dual mechanism of action as both an antiproliferative agent and a tumor-selective vascular disrupting agent. Replacement of the bridging ketone moiety in OXi8006 with an oxetane functional group has expanded structure activity relationship (SAR) knowledge and provided insights regarding oxetane incorporation within this class of molecules. A new synthetic method using an oxetane-containing tertiary alcohol subjected to Lewis acid catalyzed conditions led to successful Friedel-Crafts alkylation and yielded fourteen new oxetane-containing indole-based molecules. This synthetic approach represents the first method to successfully install an oxetane ring at the 3-position of a 2-aryl-indole system. Several analogues showed potent cytotoxicity (micromolar GI50 values) against human breast cancer cell lines (MCF-7 and MDA-MB-231) and a pancreatic cancer cell line (PANC-1), although they proved to be ineffective as inhibitors of tubulin polymerization. Molecular docking studies comparing colchicine with the OXi8006-oxetane analogue 5m provided a rationale for the differential interaction of these molecules with the colchicine site on the tubulin heterodimer.


T cells redirected by a CD3ζ chimeric antigen receptor can establish self-antigen-specific tumour protection in the long term.
A majority of cancer deaths are because of an uncontrolled relapse of the disease despite initial remission after therapy, asking for strategies to control tumour cells in the long term. Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells showed promising success in primary tumour elimination; the capacity of such engineered T cells to establish enduring tumour protection is currently a matter of discussion, in particular as most targeted 'tumour-associated antigens' are self-antigens. To address the issue in a clinically relevant model that closely mimics the human situation, we recorded rejection of carcinoembryonic antigen (CEA)-positive pancreatic tumours in the CEA transgenic mouse that expressed CEA as self-antigen in healthy cells of the gastrointestinal tract. Adoptive therapy with CD8(+) T cells, which were redirected by a CEA-specific, low-affinity CAR with CD3ζ endodomain, eliminated CEA(+) tumours in a primary response; cured mice produced an efficient recall response in the long term towards CEA(+) tumour cells upon rechallenge. Secondary tumour rejection was CEA specific, mediated by engineered T cells and did not require host T cells. No toxicity towards healthy tissues with CEA expression was recorded. Data indicate that adoptive therapy with engineered T cells can establish self-antigen-specific tumour protection in the long term without autoimmunity.


Transglutaminase 2 activity promotes membrane resealing after mechanical damage in the lung cancer cell line A549.
Transglutaminase is a Ca2+-dependent enzyme catalyzing protein cross-linking reactions. We investigated the contribution of this enzyme to the resealing of the injured plasma membrane in animal cells, using a lung cancer-derived cell line, A549. After mechanical injury by razor-scratching, the level of membrane resealing was estimated by differential incorporation of dextrans labeled with two distinct fluorescent dyes. The recovery level was decreased in the presence of excess primary amine, as a competitive inhibitor of transglutaminase. We established a cell line that stably expresses shRNA (short hairpin RNA) to specifically inhibit the expression of TGase 2 (tissue-type isozyme of transglutaminase) and confirmed the suppressed resealing level in the cell. Furthermore, additional expression of TGase 2 rescued the ability for membrane resealing. These results show that, after mechanical damage, this enzyme appeared to contribute to membrane resealing.


Age at menarche in Sardinia (Italy).
The median age at menarche in 1080 Sardinian girls (ages 11.00-16.49 years) was calculated with the status quo method and probit analysis as 12.78 +/- 0.06 years.


Classification of cancers based on copy number variation landscapes.
Genomic alterations in DNA can cause human cancer. DNA copy number variants (CNV), as one of the types of DNA mutations, have been considered to be associated with various human cancers. CNVs vary in size from 1bp up to one complete chromosome arm. In order to understand the difference between different human cancers on CNVs, in this study, we developed a method to computationally classify six human cancer types by using only CNV level values. The CNVs of 23,082 genes were used as features to construct the classifier. Then the features are carefully selected by mRMR (minimum Redundancy Maximum Relevance Feature Selection) and IFS (Incremental Feature Selection) methods. An accuracy of over 0.75 was reached by using only the CNVs of 19 genes based on Dagging method in 10-fold cross validation. It was indicated that these 19 genes may play important roles in differentiating cancer types. We also analyzed the biological functions of several top genes within the 19 gene list. The statistical results and biological analysis of these genes from this work might further help understand different human cancer types and provide guidance for related validation experiments. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang.


Simultaneous extraction of diverse organic pollutants from environmental water using a magnetic covalent organic framework composite.
Polycyclic aromatic hydrocarbons (PAHs), tetracyclines (TCs), and triphenylmethane dyes (TDs) are common organic pollutants, which may threat the human health or natural microbial communities. In this work, we report a novel multifunctional sorbent based on core-shell magnetic carboxylate-functionalized covalent organic frameworks composites (Fe3O4@COF-COOH) for the simultaneous adsorption of these target analytes via mixed-mode solid phase extraction. The behaviors of the synthetic composite for the adsorption of PAHs, TCs, and TDs were evaluated based on the Freundlich and Langmuir isotherm models. In combination with quantum chemistry calculations, it was found that the multiple interactions including π-π stacking, hydrogen bonding, and electrostatic attractions were existed between COF-COOH and guest molecules. The extraction parameters were optimized, and a novel simultaneous absorption-stepwise desorption (SASD) strategy for the enrichment of PAHs, TCs, and TDs was proposed. By coupling with HPLC-DAD method, the validation results revealed good linearities (R2 ≥ 0.9882) for all analytes. High sensitivity with LODs within the range of 0.003-0.008, 0.02-0.06, and 0.006-0.008 μg L-1 were obtained for PAHs, TCs, and TDs, respectively. High recoveries ranging from 93.6 to 105.8% were obtained with intra-day RSDs of 2.2-6.3% and inter-day RSDs of 3.2-6.5%. The obtained results demonstrated that the proposed SASD strategy using Fe3O4@COF-COOH as sorbents can be extended to other aqueous solutions consisting of trace multi-target analytes.


More than the sum of their parts: A dyad-centered approach to understanding adolescent sexual behavior.
Research has documented multiple levels of influences on adolescent sexual behavior, but has generally focused less on the relational nature of this behavior. Studies with dyadic data have provided important findings on relationship process, including the role of gender in different-sex dyads. However, both of these bodies of literature typically utilize a variable-centered approach, which examines average influences of particular variables on sexual behavior. This study expands upon this research by presenting a dyad-centered approach to adolescent sexual behavior that can identify types of couples based on patterns of multidimensional risk and protective factors. I demonstrate the dyad-centered approach using data from different-sex dyads in the National Longitudinal Study of Adolescent to Adult Health to uncover profiles marked by individual, parent, peer, and religion predictors for both male and female partners. Analyses uncovered five classes of dyadic influences, four of which were marked by relative similarity between partners and one marked by lesser approval of sex for women compared to men. Dyads marked by both partners intending to have sex and being in a context that is more approving of sex were more likely to engage in sexual intercourse. Findings demonstrate the heterogeneity of influences and intentions to have sex among adolescent couples, and identify profiles of dyads who are more likely to engage in sexual intercourse. This approach can explicate dyadic processes involved in sexual behavior and the types of couples that exist in a population, leading to more tailored and efficacious interventions.


Routes of transmission of VIM-positive Pseudomonas aeruginosa in the adult intensive care unit-analysis of 9 years of surveillance at a university hospital using a mathematical model.
Hospital outbreaks of multidrug resistant Pseudomonas aeruginosa are often caused by Pseudomonas aeruginosa clones which produce metallo-β-lactamases, such as Verona Integron-encoded Metallo-β-lactamase (VIM). Although different sources have been identified, the exact transmission routes often remain unknown. However, quantifying the role of different transmission routes of VIM-PA is important for tailoring infection prevention and control measures. The aim of this study is to quantify the relative importance of different transmission routes by applying a mathematical transmission model using admission and discharge dates as well as surveillance culture data of patients. We analyzed VIM-PA surveillance data collected between 2010 and 2018 of two intensive-care unit (ICU) wards for adult patients of the Erasmus University Medical Center Rotterdam using a mathematical transmission model. We distinguished two transmission routes: direct cross-transmission and a persistent environmental route. Based on admission, discharge dates, and surveillance cultures, we estimated the proportion of transmissions assigned to each of the routes. Our study shows that only 13.7% (95% CI 1.4%, 29%) of the transmissions that occurred in these two ICU wards were likely caused by cross-transmission, leaving the vast majority of transmissions (86.3%, 95% CI 71%, 98.6%) due to persistent environmental contamination. Our results emphasize that persistent contamination of the environment may be an important driver of nosocomial transmissions of VIM-PA in ICUs. To minimize the transmission risk from the environment, potential reservoirs should be regularly and thoroughly cleaned and disinfected, or redesigned.


Evaluation of anti-microbial activities of ZnO, citric acid and a mixture of both against Propionibacterium acnes.
In this study, anti-microbial activities of ZnO of three different particle sizes of citric acid (CA) and of mixtures of ZnO and CA were confirmed against Propionibacterium acnes. ZnO with the smallest particle size showed relatively high anti-microbial activity by disc diffusion assay and broth macrodilution assay. The mixtures of ZnO and CA also showed relatively high anti-microbial activity when the particle size of ZnO was the smallest. Furthermore, anti-microbial activities of ZnO, CA and the mixtures of ZnO and CA were compared through the checkerboard assay. The results indicated that a 1 : 1 ratio of ZnO and CA resulted in the highest anti-microbial activity. The substances were confirmed to have synergic anti-microbial effects. With the time-kill curve assay, the mixture of ZnO-containing CA reduced the surviving microbial content the most after 24 h. The results of our study suggest that ZnO may not only be an anti-microbial ingredient for the prevention of and treatment of acne. The results of our study suggest that ZnO may be an anti-microbial ingredient for the prevention of and treatment of acne when mixed with CA.


High-resolution imaging of laser-produced plasmas at a wavelength of 130 A by a normal-incidence multilayer-mirror microscope.
Laser-produced plasmas were imaged by a microscope consisting of spherical, primary, and secondary mirrors in a Cassegrain-type optical configuration. The mirrors were coated with 40 periods of Mo and Si and had a peak reflectance of ∼60% at a wavelength of 130 Å. Nb, Au, and Al targets were irradiated by as many as 24 beams of the Omega laser at the Laboratory for Laser Energetics at the University of Rochester. The images were recorded on Kodak 101 film, and the resolution was limited by the 10-µm emulsion grain size. Two different secondary mirrors produced images with a magnification of 0.8 or 2.2, and a variety of plasma emission features were recorded with 5-µm (0.6-arcsec) resolution in the target plane. The possibility of operating a similar microscope in the wavelength region of 34-50 A is discussed.


Ripk3 signaling regulates HSCs during stress and represses radiation-induced leukemia in mice.
Receptor-interacting protein kinase 3 (Ripk3) is one of the critical mediators of inflammatory cytokine-stimulated signaling. Here we show that Ripk3 signaling selectively regulates both the number and the function of hematopoietic stem cells (HSCs) during stress conditions. Ripk3 signaling is not required for normal homeostatic hematopoiesis. However, in response to serial transplantation, inactivation of Ripk3 signaling prevents stress-induced HSC exhaustion and functional HSC attenuation, while in response to fractionated low doses of ionizing radiation (IR), inactivation of Ripk3 signaling accelerates leukemia/lymphoma development. In both situations, Ripk3 signaling is primarily stimulated by tumor necrosis factor-α. Activated Ripk3 signaling promotes the elimination of HSCs during serial transplantation and pre-leukemia stem cells (pre-LSCs) during fractionated IR by inducing Mlkl-dependent necroptosis. Activated Ripk3 signaling also attenuates HSC functioning and represses a pre-LSC-to-LSC transformation by promoting Mlkl-independent senescence. Furthermore, we demonstrate that Ripk3 signaling induces senescence in HSCs and pre-LSCs by attenuating ISR-mediated mitochondrial quality control.


Pathogenesis of FOLFOX induced sinusoidal obstruction syndrome in a murine chemotherapy model.
Sinusoidal obstruction syndrome (SOS) following oxaliplatin based chemotherapy can have a significant impact on post-operative outcome following resection of colorectal liver metastases. To date no relevant experimental models of oxaliplatin induced SOS have been described. The aim of this project was to establish a rodent model which could be utilised to investigate mechanisms underlying SOS to aid the development of therapeutic strategies. C57Bl/6 mice, maintained on a purified diet, were treated with intra-peritoneal FOLFOX (n=10), or vehicle (n=10), weekly for five weeks and culled one week following final treatment. Sections of the liver and spleen were fixed in formalin and paraffin embedded for histological analysis. The role of oxidative stress on experimental-induced SOS was determined by dietary supplementation with butylated hydroxyanisole and N-acetylcysteine. FOLFOX treatment was associated with the development of sinusoidal dilatation and hepatocyte atrophy on H&E stained sections of the liver in keeping with SOS. Immunohistochemistry for p21 demonstrated the presence of replicative senescence within the sinusoidal endothelium. FOLFOX induced endothelial damage leads to a pro-thrombotic state within the liver associated with upregulation of PAI-1 (p<0.001), vWF (p<0.01) and Factor X (p<0.001), which may contribute to the propagation of liver injury. Dietary supplementation with the antioxidant BHA prevented the development of significant SOS. We have developed the first reproducible model of chemotherapy induced SOS that reflects the pathogenesis of this disease in patients. It appears that the use of antioxidants alongside oxaliplatin based chemotherapy may be of value in preventing the development of SOS in patients with colorectal liver metastases.


Thymosin beta-4 upregulates anti-oxidative enzymes and protects human cornea epithelial cells against oxidative damage.
The ability to scavenge reactive oxygen species (ROS) is crucial for cornea epithelial cells to resist oxidative damage. The authors previously demonstrated that exogenous thymosin beta-4 (T beta(4)) was able to protect human cornea epithelial (HCE-T) cells against H(2)O(2)-induced oxidative damage, and its cellular internalisation was essential. The aim of this study is to further elucidate its protective mechanism. HCE-T cells with or without T beta(4) pretreatment were exposed to H(2)O(2), and the differences in caspase activity, intracellular ROS levels, cell viability, and the expression of anti-oxidative enzymes, were measured and compared. Besides reducing caspase-9 activation and intracellular ROS levels induced by H(2)O(2), treatment of T beta(4) could also increase cell viability and stimulate the expression of manganese superoxide dismutase (SOD) and copper/zinc SOD. Moreover, both transcription and translation levels of catalase were also upregulated by T beta(4) in the presence of exogenous H(2)O(2). Furthermore, it was demonstrated that the addition of catalase inhibitor abrogated the protective effect of T beta(4) against H(2)O(2)-induced oxidative damage. To the best of the authors' knowledge, this is the first report to show that T beta(4 )was capable of upregulating anti-oxidative enzymes in human corneal epithelial cells, and these findings further support its role in cornea protection.


The mycotoxin fumonisin B1 inhibits eukaryotic protein synthesis: in vitro and in vivo studies.
Inhibitory action of Fumonisin B(1) (FB(1)) on eukaryotic protein synthesis was investigated, both in animal and plant system, and was compared with cycloheximide. Inhibitory effect of FB(1 )was monitored in the TCA precipitable proteins of rabbit reticulocyte lysates exposed to various concentrations of the mycotoxin (0.0013-2.76 mM), using (35) S-methionine as a tracer. FB(1) inhibited the protein synthesis by 6%, at 0.0013 mM and by 88%, at a higher concentration of 2.76 mM. Cycloheximide at a concentration of 0.355 mM was found to inhibit protein synthesis by 88%. Inhibitory action of FB(1) (1 mg kg(-1) body mass and a higher dose of 10 mg kg(-1) body mass) or cycloheximide (10 mg kg(-1) body mass; positive controls), injected intra-peritoneally into BALB/c mice was studied using (14)C-L: -Leucine as a tracer. FB(1) at lower dose of 1 mg kg(-1) body mass inhibited protein synthesis in liver by 8% and at a higher dose of 10 mg kg(-1) body mass by 38% in the BALB/c mice, when compared to cycloheximide which inhibited protein synthesis by 61%. The effects of FB(1 )on protein synthesis in plant system was studied in germinated maize seedlings exposed to FB(1) at 0.9 microM, 0.009 mM and 0.09 mM concentrations, using (14)C-L: -Leucine as a tracer. Fumonisin B(1) at low, middle, and higher concentrations (0.9 microM, 0.009 mM, and 0.09 mM) inhibited protein synthesis in the seedlings by 4%, 12% and 22%, respectively. The inhibitory effects of FB(1) on the protein synthesis in the animal system in vitro and in vivo conditions, and in the plant system were found to be dose-dependent, though it was less potent compared to cycloheximide.


Comparison of two computer animated imaging programs for quantifying facial profile preference.
To establish the physical basis of subjective judgements of facial appearance, two novel computer-imaging programs differing in method of preparation and presentation of 5 features of the facial soft-tissue profile of 4 faces representing 4 different classifications of dental occlusion were compared. Images of facial soft tissue of 5 features were digitized and "animated" from 16 discrete distortions or morphed from the two extremes of each feature. 12 volunteer judges responded to both the "animated" and morphed presentations by pressing the computer mouse button when the image became acceptable and releasing the button when the image was no longer acceptable. They also pressed the mouse button when the most pleasing distortion appeared from either direction. Aggregating responses to counterbalanced trials and features across judges yielded high correlations between the programs for midpoint of acceptability. Although both programs provide reliable and valid measures of subjective acceptability of present and proposed changes in facial morphology, the new morphing program is more user-friendly than the "animated" method.


Asthma control in the Portuguese National Asthma Survey.
We aimed (1) to measure asthma control using a structure-questionnaire and patient self-perception of asthma-control in the Portuguese National Asthma Survey (INAsma) and (2) to study the relationship between asthma control and asthma-related quality of life. We analyze data of asthma patients from a cross-sectional, nationwide telephone interview study - INAsma. Controlled asthma was defined as CARAT global score >24 or CARAT lower airways score ≥16. Mini-AQLQ was used to measure quality of life. Two hundred and seven (56.9% [95%CI: 51.8-62.0]) of the 364 patients had controlled asthma. Most patients with non-controlled asthma (88%) perceived their disease as controlled. Patients with controlled asthma presented higher mini-AQLQ scores (median, P25-P75; 6.6, 6.0-6.9) than those with non-controlled asthma (4.9, 3.7-5.7) (p<0.001) and a significant positive correlation between CARAT and mini-AQLQ scores was observed (r=0.706; p<0.001). More than half of the Portuguese patients presented controlled asthma and showed significantly better asthma-related quality of life. Almost 9 out of 10 patients with non-controlled disease have poor perception of their asthma control, which may hinder them from seeking better asthma control.


Strength and duration of priming effects in normal subjects and amnesic patients.
In three separate experiments, we assessed the strength and duration of word completion effects in amnesic patients and two control groups. In Experiment 1 subjects studied words under a semantic orienting condition and were given tests of word completion and recognition memory after an immediate, 2-hr or 4-day delay. In the word completion test for Experiment 1, we presented three-letter word stems that could be completed to form several common words, one of which had been presented previously (e.g. MOT for MOTEL), and subjects completed each stem with the first word that came to mind. Priming effects were equivalent in amnesic patients and control subjects and they reached baseline levels within 2 hr. In Experiments 2 and 3, subjects studied words under either a semantic or a nonsemantic orienting condition, and word completion was tested at the same three delays using cues that uniquely specified the study words (e.g. JUI for JUICE; or A--A--In for ASSASSIN). In these experiments, amnesic patients exhibited both smaller and shorter lasting word completion effects than control subjects. Specifically, amnesic patients exhibited word completion effects that seldom lasted as long as 2 hr, whereas control subjects usually exhibited completion effects lasting 4 days. An important additional finding was that control subjects exhibited larger and longer-lasting word completion effects when tested under the semantic orienting condition than when tested under the nonsemantic orienting condition. Amnesic patients were not affected by this manipulation. Moreover, under the nonsemantic orienting condition, control subjects and amnesic patients performed similarly. The results show that word completion performance is not always fully intact in amnesic patients. Long-lasting word completion effects found in normal subjects may be mediated by declarative or elaborative retrieval processes, which are impaired in amnesic patients. If so, priming as measured by word completion methods is shorter lasting than recent studies of normal subjects would suggest.


The mechanism of reduction of cytochrome c as studied by pulse radiolysis.
1. The reaction of hydrated electrons with ferricytochrome c was studied using the pulse-radiolysis technique. 2. In 3.3 mM phosphate-buffer (pH 7.2), 100 mM methanol and at a concentration of cytochrome c of less than 20 muM the reduction kinetics of ferricytochrome c by hydrated electrons is a bimolecular process with a rate constant of 4.5-10-10 M-1-S-1 (21 degrees C). 3. At a concentration of cytochrome c of more than 20 muM the apparent order of the reaction of hydrated electrons with ferricytochrome c measured at 650 nm decreases due to the occurrence of a rate-determining first-order process with an estimated rate constant of 5-10-6s-1 (pH 7.2, 21 degrees C). 4. At high concentration of cytochrome c the reaction-time courses measured at 580 and 695 nm appear to be biphasic. A rapid initial phase (75% and 30% of total absorbance change at 580 and 695 nm, respectively), corresponding to the reduction reaction, is followed by a first-order change in absorbance with a rate constant of 1.3-10-5 S-1 (pH 7.2, 21 degrees C). 5. The results are interpreted in a scheme in which first a transient complex between cytochrome c and the hydrated electron is formed, after which the heme iron is reduced and followed by relaxation of the protein from its oxidized to its reduced conformation. 6. It is calculated that one of each three encounters of the hydrated electron and ferricytochrome c results in a reduction of the heme iron. This high reaction probability is discussed in terms of charge and solvent interactions. 7. A reduction mechanism for cytochrome c is favored in which the reduction equivalent from the hydrated electron is transmitted through a specific pathway from the surface of the molecule to the heme iron.


Effects of endurance training on a mitochondrial reticulum in limb skeletal muscle.
High voltage electron microscopy at 1500 kV, was used to examine the effects of endurance training on mitochondrial morphology in rat skeletal muscle. The soleus, deep portions of the vastus lateralis, and superficial portions of the vastus lateralis muscles were examined to represent slow-twitch-oxidative, fast-twitch-oxidative-glycolytic, and fast-twitch-glycolytic skeletal muscle fiber types, respectively. Muscle samples were removed from endurance trained and untrained control female Wistar rats (n = 6, each group). Tissues were fixed using standard electron microscopic techniques and sectioned transversely with respect to muscle fiber orientation to approximately, 0.5 micron thickness. The sections were stained on grids with uranyl acetate and Reynolds' lead citrate. Results confirmed the presence of a mitochondrial reticulum in all three skeletal muscle fiber types of both groups. Stereologic analyses indicated volume densities of intermyofibrillar mitochondria increased significantly (P less than 0.05) with endurance training in the three skeletal muscle fiber types. Surface-to-volume ratio of mitochondria was significantly decreased (P less than 0.05) after training only in the deep portion of the vastus lateralis muscle. It was concluded that the mitochondria in mammalian limb skeletal muscle are a reticulum which adapts to endurance training by proliferating.


Neoadjuvant dasatinib for muscle-invasive bladder cancer with tissue analysis of biologic activity.
Preclinical urothelial carcinoma models suggest activity of dasatinib, an oral SRC-family kinase (SFK) inhibitor. We sought to determine the feasibility and biologic activity of neoadjuvant dasatinib (Neo-D) in patients with muscle-invasive urothelial carcinoma of the bladder (miUCB) preceding radical cystectomy (RC). A prospective multisite phase II trial was conducted. Key eligibility criteria included: resectable miUCB (T2-T4a, N0, M0), and Eastern Cooperative Oncology Group performance status 0 to 1. Patients received oral Neo-D 100mg once daily for 28±7 days followed by RC 8 to 24 hours after the last dose. The primary end point was feasibility, defined as≥60% of patients with miUCB completing therapy without treatment-related dose-limiting toxicity (DLT). Pre- and posttreatment tumor immunohistochemistry of phosphorylated SFK (pSFK), Ki-67, and cleaved caspase (Cas)-3 results were analyzed by paired t test. The study completed full accrual with enrollment of 25 patients of whom 23 were evaluable for feasibility. The study achieved its primary end point with 15 patients (65%) completing therapy without treatment-related DLTs. DLTs included: fatigue (n = 2), pulmonary embolism, abdominal pain, supraventricular tachycardia, enteric fistula, hematuria, and dyspnea (n = 1 each). At RC, 5 patients (23%) had<pT2 disease. Analysis of pre- and posttreatment tumors demonstrated significantly decreased pSFK (P = 0.003) but no overall significant changes in Ki-67 or Cas3. In total, 4 cases demonstrated a nonsignificant decrease in Ki-67, of which 3 cases also demonstrated a decrease in pSFK and 2 cases had marginal increase in Cas3. Neo-D in miUCB patients was feasible and safe. Overall, significant inhibition of pSFK was observed without overall reduction of cellular proliferation or increase of apoptosis, although biologic anti-tumor activity may exist in a small subset of patients. These results highlight the potential utility of the neoadjuvant trial paradigm and suggest that clinical benefit of single-agent SFK inhibition in unselected patients with miUCB is unlikely.


Anxiety in ambulatory emergency patients.
The anxiety level of ambulatory emergency department patients without a diagnosis of a physical illness was studied. These patients were compared to a group with a diagnosis of nontraumatic surgical disease. Both the study group and the comparison group were found to have elevated anxiety levels. In addition, those with nonphysical illness had elevated levels of covert anxiety when compared to their overt levels (p less than .03) and when contrasted with the comparison group's covert levels ( p less than .03). In the treatment of all a patient's problems the psychosomatic illnesses evidenced by raised covert anxiety levels may require intensive treatment both within and without the emergency department.


Enabling ambulatory movement in wearable magnetoencephalography with matrix coil active magnetic shielding.
The ability to collect high-quality neuroimaging data during ambulatory participant movement would enable a wealth of neuroscientific paradigms. Wearable magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs) has the potential to allow participant movement during a scan. However, the strict zero magnetic field requirement of OPMs means that systems must be operated inside a magnetically shielded room (MSR) and also require active shielding using electromagnetic coils to cancel residual fields and field changes (due to external sources and sensor movements) that would otherwise prevent accurate neuronal source reconstructions. Existing active shielding systems only compensate fields over small, fixed regions and do not allow ambulatory movement. Here we describe the matrix coil, a new type of active shielding system for OPM-MEG which is formed from 48 square unit coils arranged on two planes which can compensate magnetic fields in regions that can be flexibly placed between the planes. Through the integration of optical tracking with OPM data acquisition, field changes induced by participant movement are cancelled with low latency (25 ms). High-quality MEG source data were collected despite the presence of large (65 cm translations and 270° rotations) ambulatory participant movements.


Automatic detection and recognition of nasopharynx gross tumour volume (GTVnx) by deep learning for nasopharyngeal cancer radiotherapy through magnetic resonance imaging.
In this study, we propose the deep learning model-based framework to automatically delineate nasopharynx gross tumor volume (GTVnx) in MRI images. MRI images from 200 patients were collected for training-validation and testing set. Three popular deep learning models (FCN, U-Net, Deeplabv3) are proposed to automatically delineate GTVnx. FCN was the first and simplest fully convolutional model. U-Net was proposed specifically for medical image segmentation. In Deeplabv3, the proposed Atrous Spatial Pyramid Pooling (ASPP) block, and fully connected Conditional Random Field(CRF) may improve the detection of the small scattered distributed tumor parts due to its different scale of spatial pyramid layers. The three models are compared under same fair criteria, except the learning rate set for the U-Net. Two widely applied evaluation standards, mIoU and mPA, are employed for the detection result evaluation. The extensive experiments show that the results of FCN and Deeplabv3 are promising as the benchmark of automatic nasopharyngeal cancer detection. Deeplabv3 performs best with the detection of mIoU 0.8529 ± 0.0017 and mPA 0.9103 ± 0.0039. FCN performs slightly worse in term of detection accuracy. However, both consume similar GPU memory and training time. U-Net performs obviously worst in both detection accuracy and memory consumption. Thus U-Net is not suggested for automatic GTVnx delineation. The proposed framework for automatic target delineation of GTVnx in nasopharynx bring us the desirable and promising results, which could not only be labor-saving, but also make the contour evaluation more objective. This preliminary results provide us with clear directions for further study.


Systematic review and meta-analyses on associations of endogenous testosterone concentration with health outcomes in community-dwelling men.
The overall study aim is to clarify the relation of endogenous sex hormones with major health outcomes in men. This paper reports a systematic review focusing on published estimates for testosterone associations. Community-dwelling men. 20 180 adult men participated in the final set of studies identified and selected from a systematic review. Eligible studies included prospective cohort studies with plasma or serum testosterone concentrations measured for adult men using mass spectrometry with at least 5 years of follow-up data and one of the specified outcome measures recorded. Only published or grey literature items written in English were considered. Planned prospective outcome measures: cardiovascular disease (CVD) events, CVD deaths, all-cause mortality, cancer deaths, cancer diagnoses, cognitive decline, dementia. Meta-analyses were of the most frequently reported outcomes in selected studies: CVD deaths and all-cause mortality. Succinct characterisations of testosterone associations with other outcomes are also presented. Screening of 1994 deduplicated items identified 9 suitable studies, with an additional 2 identified by colleagues (11 in total). Summary estimates of mean testosterone concentration and age at recruitment for 20 180 adult men were 15.4±0.7 nmol/L and 64.9±3.3 year. Despite considerable variation in mean testosterone, a metaregression estimated no significant dependence on mean age at recruitment among studies (slope=-0.03, 95% CI -0.11 to 0.06). Meta-analyses demonstrated negligible heterogeneity and no significant effect of a 5 nmol/L increase in testosterone on the risk of all-cause mortality (HR=0.96, 95% CI 0.89 to 1.03) or death from CVD (HR=0.95, 95% CI 0.83 to 1.08). Analyses of published estimates did not demonstrate associations of endogenous testosterone with CVD deaths or with all-cause mortality. Suggested further research includes the planned individual participant data meta-analyses for selected studies, enabling the investigation of non-linear summary effects. PROSPERO: CRD42019139668.


Delineating the molecular and histological events that govern right ventricular recovery using a novel mouse model of pulmonary artery de-banding.
The temporal sequence of events underlying functional right ventricular (RV) recovery after improvement of pulmonary hypertension-associated pressure overload is unknown. We sought to establish a novel mouse model of gradual RV recovery from pressure overload and use it to delineate RV reverse-remodelling events. Surgical pulmonary artery banding (PAB) around a 26-G needle induced RV dysfunction with increased RV pressures, reduced exercise capacity and caused liver congestion, hypertrophic, fibrotic, and vascular myocardial remodelling within 5 weeks of chronic RV pressure overload in mice. Gradual reduction of the afterload burden through PA band absorption (de-PAB)-after RV dysfunction and structural remodelling were established-initiated recovery of RV function (cardiac output and exercise capacity) along with rapid normalization in RV hypertrophy (RV/left ventricular + S and cardiomyocyte area) and RV pressures (right ventricular systolic pressure). RV fibrotic (collagen, elastic fibres, and vimentin+ fibroblasts) and vascular (capillary density) remodelling were equally reversible; however, reversal occurred at a later timepoint after de-PAB, when RV function was already completely restored. Microarray gene expression (ClariomS, Thermo Fisher Scientific, Waltham, MA, USA) along with gene ontology analyses in RV tissues revealed growth factors, immune modulators, and apoptosis mediators as major cellular components underlying functional RV recovery. We established a novel gradual de-PAB mouse model and used it to demonstrate that established pulmonary hypertension-associated RV dysfunction is fully reversible. Mechanistically, we link functional RV improvement to hypertrophic normalization that precedes fibrotic and vascular reverse-remodelling events.


Drosophila Helical factor is an inducible protein acting as an immune-regulated cytokine in S2 cells.
The innate immunity of Drosophila melanogaster is based on cellular and humoral components. Drosophila Helical factor (Hf), is a molecule previously discovered using an in silico approach and whose expression is controlled by the immune deficiency (Imd) pathway. Here we present evidence demonstrating that Hf is an inducible protein constitutively produced by the S2 hemocyte-derived cell line. Hf expression is stimulated by bacterial extracts that specifically trigger the Imd pathway. In absence of any bacterial challenge, the recombinant form of Hf can influence the expression of the antimicrobial peptides (AMPs) defensin but not drosomycin. These data suggest that in vitro Hf is an inducible and immune-regulated factor, with functions comparable to those of secreted vertebrate cytokines.


Microaggression and the adult stuttering experience.
Microaggressions are subtle insults, invalidations, or slights that target people due to their association with a marginalized group. Microaggressive experiences have been shown to degrade quality of life and corroborate negative stereotypes towards persons with disabilities. To date, minimal research has been dedicated to exploring microaggressions within adults who stutter. Seven adults who stutter participated in semi-structured focus group interviews similar to Keller and Galgay's (2010) qualitative investigation of microaggressions experienced by adults with a disability. Group interviews were transcribed and analyzed using QSR NVivo software to develop themes and subthemes. Eight major themes were identified within two supraordinate themes: Microaggressive Behavior (patronization, second-class status, perceived helplessness, workplace microaggression, clinical microaggression, denial of privacy) and Perception of Microaggressive Behavior (exoneration of listener, no or minimal microaggressive experience). Although patronization, second-class status, and helplessness were mentioned frequently by multiple participants, exoneration of the listener was the most frequently recurring theme. Based on these preliminary focus group interviews, stuttering-based microaggressions broadly resemble ableist microaggressions reported by Keller and Galgay (2010). Interviewees also expressed a reluctance to identify slights related to stuttering as microaggression and often characterized these incidents as unavoidable.


Muscarinic receptor activation potentiates the effect of spinal cord stimulation on pain-related behavior in rats with mononeuropathy.
Spinal cord stimulation (SCS) has proven to be a valuable treatment in neuropathic pain. Our previous animal experiments performed on rat models of SCS and ensuing clinical trials have demonstrated that intrathecal (i.t.) administration of subeffective doses of certain drugs may enhance the pain relieving effect of SCS in cases with unsatisfactory SCS outcome. Recently, an augmented release of spinal acetylcholine acting on muscarinic receptors has been shown to be one of the mechanisms involved in SCS. The present study was performed to examine whether cold hypersensitivity and heat hyperalgesia in rats with partial sciatic nerve injuries can be attenuated by SCS in the same way as tactile hypersensitivity and to explore a possibly synergistic effect of SCS and a muscarinic receptor agonist, oxotremorine. Rats with signs of neuropathy were subjected to SCS applied in awake, freely moving condition. Oxotremorine was administered intrathecally. Tactile, cold and heat sensitivities were assessed by using von Frey filaments, cold spray and focused radiant heat, respectively. Oxotremorine i.t. dose-dependently suppressed the tactile hypersensitivity. SCS markedly increased withdrawal thresholds (WTs), withdrawal latencies and cold scores. When combining SCS with a subeffective dose of oxotremorine i.t., the suppressive effect of SCS on the pain-related symptoms was dramatically enhanced in rats failing to obtain a satisfactory effect with SCS alone. In conclusion, the combination of SCS and a drug with selective muscarinic receptor agonistic properties could be an optional therapy, when SCS per se has proven inefficient.


Calcium and vitamin D status in the adolescent: key roles for bone, body weight, glucose tolerance, and estrogen biosynthesis.
This review paper highlights a number of important public health issues related to calcium and vitamin D status in adolescents. Dietary calcium intake has declined dramatically over the past several decades among adolescents, and inadequate serum vitamin D levels have been documented in up to 54% of teens. A recent trend of decreasing consumption of dairy foods, especially milk, has contributed to this problem. Calcium and vitamin D are critically important for bone mineral accrual during adolescence, and altered calcium homeostasis can impact optimal bone acquisition. Serum and cellular calcium concentrations are controlled, in part, by the actions of vitamin D. Newer research seeks to clarify the potential functions of calcium and vitamin D in the regulation of body weight, glucose tolerance, and ovarian function. Numerous observational studies have noted an inverse association between body weight, percent body fat, and dietary calcium intake; however, clinical trials evaluating the affect of increased calcium on weight loss have been mixed. There is a reduced incidence of insulin resistance syndrome with increasing dairy intake in overweight individuals, and serum 25 hydroxyvitamin D levels are positively correlated with insulin sensitivity. Vitamin D receptor is expressed in all calcium-regulated tissues, including the ovary; thus, calcium and vitamin D appear to be necessary for full ovarian function. This review paper will examine the important role of vitamin D and calcium in the regulation of bone, weight, glucose tolerance, and estrogen biosynthesis.


Novel approach for extinguishing large-scale coal fires using gas-liquid foams in open pit mines.
Coal fires are a serious threat to the workers' security and safe production in open pit mines. The coal fire source is hidden and innumerable, and the large-area cavity is prevalent in the coal seam after the coal burned, causing the conventional extinguishment technology difficult to work. Foams are considered as an efficient means of fire extinguishment in these large-scale workplaces. A noble foam preparation method is introduced, and an original design of cavitation jet device is proposed to add foaming agent stably. The jet cavitation occurs when the water flow rate and pressure ratio reach specified values. Through self-building foaming system, the high performance foams are produced and then infused into the blast drilling holes at a large flow. Without complicated operation, this system is found to be very suitable for extinguishing large-scale coal fires. Field application shows that foam generation adopting the proposed key technology makes a good fire extinguishment effect. The temperature reduction using foams is 6-7 times higher than water, and CO concentration is reduced from 9.43 to 0.092‰ in the drilling hole. The coal fires are controlled successfully in open pit mines, ensuring the normal production as well as the security of personnel and equipment.


Scintigraphy in prediction of the salivary gland function after gland-sparing intensity modulated radiation therapy for head and neck cancer.
To evaluate salivary gland scintigraphy in prediction of salivary flow following radiation therapy. Twenty patients diagnosed with head and neck cancer were treated with intensity modulated radiation therapy with an intention to spare the salivary gland function. The total quantitative saliva secretion was measured prior to and 6 and 12 months after therapy, and the function of the major salivary glands was monitored using Tc-99m-pertechnetate scintigraphy. Two models were designed for prediction of the post-treatment salivary flow: an average model, based on the average proportions of saliva produced by each of the four major glands in healthy subjects, and an individual model, based on saliva produced by each gland as measured by scintigraphy prior to therapy. These models were compared with volume-based (Lyman) normal tissue complication probability models using two published sets of model parameters. The D(50) for the parotid and the submandibular gland function assessed at 6 and 12 months after radiotherapy was approximately 39Gy. The scintigraphy-based individual model predicted well the measured post-treatment saliva flow rates. The correlation coefficient between the predicted stimulated and the measured saliva flow rate was 0.77 (p<0.0001) at 6 months and 0.55 (p=0.034) at 12 months after completion of radiotherapy. The relative changes in unstimulated and stimulated salivary flow rates showed similar dependency on the cumulative radiation dose. Salivary gland function assessed by scintigraphy prior to radiotherapy is useful in prediction of the residual salivary flow after radiotherapy.


The simultaneous quantitative determination of cephalothin and cefazolin in serum by high pressure liquid chromatography.
Conventional microbiological assay procedures for cephalosporins in serum do not allow the determination of serum concentrations if more than one cephalosporin is present in a single sample. An HPLC procedure has been developed which permits the simultaneous quantitative determination of cefazolin sodium and cephalothin sodium in serum. Reverse phase chromatography using methanol in 0.2 M ammonium acetate as the mobile phase was employed to separate and quantitate the two cephalosporins in a trichloroacetic acid supernatant solution prepared from serum.


Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 2: should capnography be routinely used during procedural sedation in the Emergency Department?
A short cut review was carried out to establish whether capnography should be routinely used during procedural sedation in Emergency Departments. 206 papers were found using the reported searches, of which nine presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is that capnography may provide early warning of ventilatory changes that could result in hypoxia.


Chronic liquid nutrition intake induces obesity and considerable but reversible metabolic alterations in Wistar rats.
We have previously described the development of substantial, but reversible obesity in Wistar rats fed with palatable liquid nutrition (Fresubin). In this study, we investigated changes in serum hormone levels, glycemia, fat mass, adipocyte size, and gene expression of adipokines and inflammatory markers in adipose tissue of Wistar rats fed by Fresubin (i) for 5 months, (ii) up to 90 days of age, or (iii) after 90 days of age to characterize metabolic alterations and their reversibility in rats fed with Fresubin. An intra-peritoneal glucose tolerance test was also performed to determine levels of serum leptin, adiponectin, insulin, and C-peptide in 2- and 4-month-old animals. In addition, mesenteric and epididymal adipose tissue weight, adipocyte diameter, and gene expression of pro- and anti-inflammatory adipokines and other markers were determined at the end of the study. Chronic Fresubin intake significantly increased adipocyte diameter, reduced glucose tolerance, and increased serum leptin, adiponectin, insulin, and C-peptide levels. Moreover, gene expression of leptin, adiponectin, CD68, and nuclear factor kappa B was significantly increased in mesenteric adipose tissue of Fresubin fed rats. Monocyte chemotactic protein 1 messenger RNA (mRNA) levels increased in mesenteric adipose tissue only in the group fed Fresubin during the entire experiment. In epididymal adipose tissue, fatty acid binding protein 4 mRNA levels were significantly increased in rats fed by Fresubin during adulthood. In conclusion, chronic Fresubin intake induced complex metabolic alterations in Wistar rats characteristic of metabolic syndrome. However, transition of rats from Fresubin to standard diet reversed these alterations.


Are young women and men with rheumatoid arthritis at risk for fragility fractures? A population-based study.
Older women and men with rheumatoid arthritis (RA) are at increased risk for fractures, but limited information is available on fracture risk in younger individuals with RA and whether such risk occurs early in the disease onset or only when older. We determined the risk for fractures in both young and older women and men following RA diagnosis. We studied a population-based inception cohort with RA from Olmsted County, Minnesota, USA. We identified 822 women and 349 men diagnosed with RA between 1955 and 2007 (308 women and 110 men diagnosed before age 50) and an equal number of paired non-RA subjects, matched by sex and birth year. Incident fractures were collected through review of complete (inpatient and outpatient) medical records available through the linkage system of the Rochester Epidemiology Project. The hazard ratio (HR; 95% CI) for a non-pathologic fracture occurring from no more than moderate trauma was 1.63 (1.36-1.96) for women and 1.40 (1.02-1.93) for men with RA. Findings were consistent for women and men diagnosed with RA at age ≥ 50 years [HR, 1.43 (1.16-1.77) and 1.34 (0.92-1.94), respectively], or at age < 50 years [HR, 2.34 (1.61-3.42) and 1.74 (0.91-3.30), respectively]. However, young women, but not young men, with RA were at increased fracture risk even before age 50 years (HR, 1.95 [1.08-3.51] and 0.82 [0.28-2.45], respectively). Young men with RA are at increased risk for fractures only when older, whereas young women with RA have an elevated fracture risk even while still young.


The application of sulfate radical-based advanced oxidation processes in hydrothermal treatment of activated sludge at different stages: A comparative study.
Integrating hydrothermal treatment (HT) and advanced oxidation processes (AOP) was proved to be a promising approach for improving sludge dewaterability. In this study, the EPS valorization under elevated temperature and sulfate radical-based AOP were investigated to clarify the valorization of organic matter in different EPS layers and its effects on the sludge dewaterability. Results indicated that the organic matters in the inner layer of EPS decreased sharply with the elevated temperature, and released into the soluble EPS. Sulfate radical-based AOP significantly accelerated the degradation of organics and microbial cells lysis, especially in the presence of ZVI. The protein with the higher hydrophobicity was detected under the AOP enhanced HT. A better synergistic effect on sludge dewaterability was obtained by integrated the AOP at the initial hydrothermal stage. 3D-EEM and parallel factor analysis indicated that the protein and microbial by-product like substances in tightly bound EPS significantly affected the dewaterability.


The frequencies of the serum amyloid A2 alleles in healthy (Turkish, Azerbaijan and Kazakh) populations.
The Amyloid A1 (AA1) and A2 (AA2) proteins, which result from proteolytic cleavage of the Serum Amyloid A1 (SAA1) and A2 (SAA2) proteins, are major protein components of the Amyloid A deposits found in secondary amyloidosis. This study determines frequency of serum amyloid A2 alleles (alpha, beta) in healthy Turkish, Azerbaijan and Kazakh subjects. Two hundred Turkish, sixty five Azerbaijan and sixty five Kazakh healthy individuals were studied by previously described the PCR-RFLP methods. Our data revealed that the frequencies of the alpha and beta alleles at the SAA2 locus in the Turkish healthy population were different when compared to those in Azerbaijan and Kazakh healthy populations (p = 0.014 and p = 0.02), respectively. In contrast, the difference between alpha and beta alleles at the SAA2 locus was not different in both Kazakh and Azerbaijan healthy populations (p = 0.882).


[Structure-based design, synthesis and evaluation of bioactivity of anti-P-gp peptide mimetic].
To design and evaluate the small peptide mimetic of anti-P-glycoprotein (P-gp) antibody (PHMA02). From the three dementional structure analysis of computer modeling of PHMA02 CDR loops, a small peptide mimetic was designed and determined by flow cytometry. Anti-P-gp peptide mimetic functionally similar to PHMA02 was developed. The peptide mimetic competitively inhibits PHMA02 binding to P-gp and partially block the P-gp function as a drug efflux pump in K562/A02 cells. Some special conformational properties of CDR loops of antibody might serve as lead structures for develop new biological peptide mimetics. Antibody-structure-based design would develop new drug in the future.


Group B streptococcus drug resistance in pregnant women in Iran: a meta-analysis.
Streptococcus (S.) agalactiae colonizes in the female genitourinary and lower gastrointestinal tracts and is responsible for a wide range of infections in newborns, pregnant women and non-pregnant adults. Therefore, antibiotic prophylaxis and infection treatment against S. agalactiae is important. The aim of this study was to determine the prevalence of S. agalactiae antibiotic resistance in Iranian patients, especially among pregnant women. A systematic literature search was conducted in PubMed, Scopus, Google Scholar and the Scientific Information Database (SID) databases by using related keywords and without any time limitation. A total of 26 studies reporting the prevalence of S. agalactiae antibiotic resistance in Iran met our predefined inclusion and exclusion criteria and were included in the meta-analysis. High rates of S. agalactiae antibiotic resistance in pregnant women were found against tetracycline (96.2%), trimethoprim-sulfamethoxazole (84.7%), cefotaxime (41.3%), clindamycin (26.8%) and erythromycin (21%). Additionally, resistance to penicillin (4.2%), ampicillin (2.7%), cefazolin (7.6%), vancomycin (2.4%), ceftriaxone (12.5%), ciprofloxacin (13.6%) and nitrofurantoin (0%) was low. Our results revealed that penicillin and ampicillin among penicillin-tolerant Iranian pregnant women, and vancomycin and cefazolin among penicillin-allergic women are still drugs of choice in intrapartum prophylaxis for preventing S. agalactiae vertical transmission and early-onset neonatal disease.


The potency of tissue-type plasminogen activator (TPA) determined with chromogen and clot-lysis assays.
An assessment was made of two methods for determining the potency of tissue-type plasminogen activator (TPA). A chromogenic microtitre plate assay was established which contained TPA, plasminogen, a synthetic plasmin substrate (H-D-valyl-L-leucyl-L-lysyl-p-nitroaniline dihydrochloride, S2251) and any one of the following stimulators: native fibrinogen, enzymatic and chemical digests of fibrinogen, poly-D-lysine (PDL) and chemical derivatives of the latter. The chromogen assay was compared with an automated clot-lysis (turbidimetric) assay for sensitivity, reproducibility and validity for potency determination. Reference preparations of TPA were titrated in both assays: in the chromogen assay the dose-response curves were non-parallel, whereas parallelism was observed in the clot-lysis assay. Thus, the chromogen assay was restricted in its applicability and disqualified from any routine regulatory use. The potency of individual lots of recombinant (r)TPA could only be estimated in International Units (IU) of TPA activity with the automated clot-lysis assay and the potency values obtained (IU/vial) were in remarkably close agreement with the manufacturers' values.


Surreptitious use of salicylates: a cause of chronic recurrent gastroduodenal ulcers.
We describe five patients who had chronic recurrent gastroduodenal ulcers and pain, intestinal obstruction, bleeding, or a combination of these symptoms. Four patients required surgical intervention because of a poor response to medical therapy. The ulcers recurred in all patients, despite evidence of achlorhydria in two of them. Although the patients denied the use of salicylates, all of them had therapeutic blood levels of salicylates. A salicylate level should be determined in patients with severe ulcer disease that is resistant to medical therapy or that is recurrent after appropriate surgical therapy when the presence of hypergastrinemia or hyperchlorhydria has been definitely excluded. A low serum level of uric acid can also be a clue to the abuse of salicylates.


[Cutaneous manifestations of sarcoidosis].
Skin manifestations of sarcoidosis occur in up to 30% of cases. This review summarizes and illustrates in detail the differences between specific and unspecific skin manifestations of sarcoidosis. Important differential diagnoses, such as tuberculosis, cutaneous lymphoma and syphilis have to be excluded. The indications for systemic treatment are primarily determined by the extent of organ involvement and also by the cosmetic impairment.


The possible relation between late pregnancy hypertension and 5-hydroxytryptamine levels in maternal blood.
The concentrations of the vasoactive substance, 5-hydroxytryptamine (5-HT), were estimated in whole blood samples from 12 pregnant women with hypertension in the third trimester. These were compared with a control group of 15 normotensive pregnant women of the same gestation. The hypertensive patients were admitted for observation and the whole blood 5-HT estimated again after four days bed rest: in all patients the blood pressure had, by this time, returned to within the normal range. No significant difference was found between the mean blood 5-HT concentrations of the hypertensive and the normotensive groups. A small, but not statistically significant, rise occurred in the hypertensive group after four days bed rest. Thus this study gave no evidence that 5-HT is implicated in hypertension in pregnancy.


The effect of formal feedback sessions on test security for a clinical practice examination using standardized patients.
To determine the effects of formal feedback on test security for a clinical practice examination administered to successive rotations over a year's time. A seven case clinical performance examination was administered to ten rotations of students throughout an academic year in a required Ambulatory Care Clerkship. Three of the cases were developed at Saint Louis University School of Medicine (SLU); four of the cases were developed by the National Board of Medical Examiners (NBME). Immediately following each examination, the examinees participated in a feedback session for just the three SLU cases: checklists were displayed, and details of the cases were discussed. No feedback on the four NBME cases was provided. Student performance in successive rotations on the three cases in which students were given detailed feedback by the faculty was compared with performance on the four cases in which no feedback was given. Data were collected from 119 students. The interaction of case and group was not significant, indicating no difference in the trend over the ten groups between the three cases for which feedback was provided and the four cases for which it was not. The results showed no significant increasing trend over the ten rotation groups for either cases where feedback was given or withheld. The results suggest that the formal feedback sessions did not pose a threat to test security.


Management of perimesencephalic nonaneurysmal subarachnoid hemorrhage: a national survey.
Perimesencephalic nonaneurysmal subarachnoid hemorrhage (NASAH) is a rare type of subarachnoid hemorrhage (SAH), usually associated with minor complications compared to aneurysmal SAH. Up to date, data is scarce and consensus on therapeutic management and follow-up diagnostics of NASAH is often missing. This survey aims to evaluate the clinical management among neurosurgical departments in Germany. 135 neurosurgical departments in Germany received a hardcopy questionnaire. Encompassing three case vignettes with minor, moderate and severe NASAH on CT-scans and questions including the in-hospital treatment with initial observation, blood pressure (BP) management, cerebral vasospasm (CV) prophylaxis and the need for digital subtraction angiography (DSA). 80 departments (59.2%) answered the questionnaire. Whereof, centers with a higher caseload state an elevated complication rate (Chi2 < 0.001). Initial observation on the intensive care unit is performed in 51.3%; 47.5%, 70.0% in minor, moderate and severe NASAH, respectively. Invasive BP monitoring is performed more often in severe NASAH (52.5%, 55.0%, 71.3% minor, moderate, severe). CV prophylaxis and transcranial doppler ultrasound (TCD) are performed in 41.3%, 45.0%, 63.8% in minor, moderate and severe NASAH, respectively. Indication for a second DSA is set in the majority of centers, whereas after two negative ones, a third DSA is less often indicated (2nd: 66.2%, 72.5%, 86.2%; 3rd: 3.8%, 3.8%, 13.8% minor, moderate, severe). This study confirms the influence of bleeding severity on treatment and follow-up of NASAH patients. Additionally, the existing inconsistency of treatment pathways throughout Germany is highlighted. Therefore, we suggest to conceive new treatment guidelines including this finding.


Cholinergic manipulations in the rat basolateral amygdaloid nucleus on locomotor activity induced by amphetamine.
Microinjections of cholinergic antagonists in the vicinity of the basolateral amygdaloid nucleus produced a marked reduction of amphetamine-induced hyperactivity when amphetamine was administered i.p. in relatively large doses (1.5 mg/kg). Cholinergic agonists enhanced locomotor activity induced by relatively small doses of amphetamine (0.5 mg/kg). These observations suggest that cholinergic activity in the amygdala modulates the locomotor response to amphetamine.


Endemic malaria in four villages of the Pakistani province of Punjab.
The prevalence of malaria in 4 villages 60 km south of Lahore, Punjab, where Anopheles culicifacies is the vector was estimated from blood films made during three mass malaria surveys (MS) and at 204 clinics (CS) held over 18 consecutive months. The highest parasite rate occurred during October 1984 when 43% of the CS population had parasitaemias. Plasmodium vivax predominated early in the major transmission season (23% and 15% vivax parasitaemias in August 1983 and 1984 respectively) whereas P. falciparum was the most common species later in the transmission season (an average falciparum prevalence of 37% in October and November 1984) and following the transmission season through March. Despite the proximity and habitat similarity of the 4 villages, both total and species malaria prevalence rates showed inter-village differences. Asexual stage and gametocyte parasite rates in children were 2 to 5 times higher than in adults. No increased mortality due to malaria was detected among the 4000 study population. Malaria was stable and endemic, albeit seasonally transmitted, in these 4 villages during 1983 and 1984.


Apoptosis inhibition can be threatening in Aβ-induced neuroinflammation, through promoting cell proliferation.
Neuronal apoptosis in neurodegenerative diseases is correlated with inflammatory reactions. The beneficial or detrimental role of apoptosis in neuroinflammation is unclear. In this study, we injected β-amyloid peptide into the rat cortex for induction of neuroinflammation in hippocampus. We observed an increase in TNF-α as an inflammatory cytokine and caspase3 and TUNEL-positive cells as apoptotic marker. As far as ability of TNF-α to induce apoptosis or activate NF-kβ, the question is what will happen if the balance between two pathways is disturbed by inhibition of apoptosis. Using caspase inhibitors, we inhibited apoptosis and assessed NF-kβ, Hsp 70 (a hallmark of cancer), cmyc (proto-oncogene) and p53 (tumor suppressor protein). There was an unexpected decrease in NF-kβ while Hsp70 and cmyc upregulated and p53 decreased. These results imply that inhibition of apoptosis due to increased susceptibility to abnormal mitosis may not provide a reliable strategy for treatment of neuroinflammatory diseases.


Suppressing Nitrite-oxidizing Bacteria Growth to Achieve Nitrogen Removal from Domestic Wastewater via Anammox Using Intermittent Aeration with Low Dissolved Oxygen.
Achieving nitrogen removal from domestic wastewater using anaerobic ammonium oxidation (anammox) has the potential to make wastewater treatment energy-neutral or even energy-positive. The challenge is to suppress the growth of nitrite-oxidizing bacteria (NOB). This study presents a promising method based on intermittent aeration with low dissolved oxygen to limit NOB growth, thereby providing an advantage to anammox bacteria to form a partnership with the ammonium-oxidizing bacteria (AOB). The results showed that NOB was successfully suppressed using that method, with the relative abundance of NOB maintained between 2.0-2.6%, based on Fluorescent in-situ Hybridization. Nitrogen could be effectively removed from domestic wastewater with anammox at a temperature above 20 °C, with an effluent total nitrogen (TN) concentration of 6.6 ± 2.7 mg/L, while the influent TN and soluble chemical oxygen demand were 62.6 ± 3.1 mg/L and 88.0 ± 8.1 mg/L, respectively.


Omp85(Tt) from Thermus thermophilus HB27: an ancestral type of the Omp85 protein family.
Proteins belonging to the Omp85 family are involved in the assembly of beta-barrel outer membrane proteins or in the translocation of proteins across the outer membrane in bacteria, mitochondria, and chloroplasts. The cell envelope of the thermophilic bacterium Thermus thermophilus HB27 is multilayered, including an outer membrane that is not well characterized. Neither the precise lipid composition nor much about integral membrane proteins is known. The genome of HB27 encodes one Omp85-like protein, Omp85(Tt), representing an ancestral type of this family. We overexpressed Omp85(Tt) in T. thermophilus and purified it from the native outer membranes. In the presence of detergent, purified Omp85(Tt) existed mainly as a monomer, composed of two stable protease-resistant modules. Circular dichroism spectroscopy indicated predominantly beta-sheet secondary structure. Electron microscopy of negatively stained lipid-embedded Omp85(Tt) revealed ring-like structures with a central cavity of approximately 1.5 nm in diameter. Single-channel conductance recordings indicated that Omp85(Tt) forms ion channels with two different conducting states, characterized by conductances of approximately 0.4 nS and approximately 0.65 nS, respectively.


Survey of knowledge, attitude and practice of healthcare professionals on dengue transmission, diagnosis and clinical classification.
To investigate the knowledge, attitudes, and practices of the healthcare professionals (HCPs) including physicians and nurses regarding dengue transmission, diagnosis and clinical classification using the warning signs of World Health Organization (WHO) 2009 classification. Out of 471 respondents from three countries, 80.9% of physicians and 74% of nurses did not receive previous training regarding the dengue infection. The majority of respondents could identify the primary dengue vector (86%), while only a third of HCPs knew the biting time of dengue mosquitoes. Only half of our respondents knew about immunity induced by serotypes; Moreover, half of our participants could determine the diagnostic tests. On the other hand, about 90% of the respondents took responsibility for talking to the patients about preventive measures. Our respondents also showed wide variations in definition of warning signs listed in the WHO 2009 classification. Multivariate analysis linked the impact of different cofactors including prior training on dengue infection, type of profession, frequency of taking care of dengue patients and country on how HCPs defined these warning signs. This study could declare the variation in employing the warning signs listed in the WHO 2009 classification. We have figured that most of the HCPs did not take prior training on the dengue viral infection; Also, we found gaps in the knowledge regarding various topics in dengue fever. This paper recommends the gathering of efforts to establish the proper knowledge of dengue infection and the warning signs listed by the WHO.


Age-related alterations to working memory and to pyramidal neurons in the prefrontal cortex of rhesus monkeys begin in early middle-age and are partially ameliorated by dietary curcumin.
Layer 3 (L3) pyramidal neurons in aged rhesus monkey lateral prefrontal cortex (LPFC) exhibit significantly elevated excitability in vitro and reduced spine density compared to neurons in young subjects. The time-course of these alterations, and whether they can be ameliorated in middle age by the powerful anti-oxidant curcumin is unknown. We compared the properties of L3 pyramidal neurons from the LPFC of behaviorally characterized rhesus monkeys over the adult lifespan using whole-cell patch clamp recordings and neuronal reconstructions. Working memory (WM) impairment, neuronal hyperexcitability, and spine loss began in middle age. There was no significant relationship between neuronal properties and WM performance. Middle-aged subjects given curcumin exhibited better WM performance and less neuronal excitability compared to control subjects. These findings suggest that the appropriate time frame for intervention for age-related cognitive changes is early middle age, and points to the efficacy of curcumin in delaying WM decline. Because there was no relationship between excitability and behavior, the effects of curcumin on these measures appear to be independent.


Toxic and trace elements in liver, kidney and meat from cattle slaughtered in Galicia (NW Spain).
The aims of this study were to determine the levels of some toxic and trace metals in cattle meat in Spain and to compare them with concentrations in cattle elsewhere and to maximum acceptable levels. Arsenic, cadmium, lead, copper and zinc concentrations in the liver, kidney and muscle (meat) from 438 calves (6-10 months old) and 56 cows (2-16 years old) slaughtered in Galicia (NW Spain) in 1996 were quantified. The arithmetic mean fresh weight concentrations in calf liver, kidney and muscle respectively were 0.043, 0.055, 0.004 mg/kg for arsenic, 0.032, 0.070, 0.001 mg/kg for cadmium, 0.053, 0.052, 0.009 mg/kg for lead, 64.6, 4.91, 0.677 mg/kg for copper and 47.7, 14.4, 47.8 mg/kg for zinc. In cows, these concentrations were 0.046, 0.068, 0.005 mg/kg (arsenic), 0.097, 0.458, 0.001 mg/kg (cadmium), 0.057, 0.066, 0.017 mg/kg (lead), 60.3, 3.67, 1.26 mg/kg (copper) and 59.8, 20.0, 52.7 mg/kg (zinc). Except for copper levels in the liver which were high, metal concentrations in cattle were generally low in Galicia and broadly similar to those in the rest of Europe, Australia and Canada. Arsenic, cadmium and lead concentrations in Galician cattle rarely exceeded acceptable maximum concentrations that have been adopted by many countries. Copper and zinc concentrations in Galician cattle did exceed acceptable maximum concentrations but the frequency with which this occurred depended upon which acceptable maximum concentration was used; regulatory values differ markedly between countries.


Effects of the simultaneous application of potassium and calcium on the soil-to-Chinese cabbage transfer of radiocesium and radiostrontium.
Pot experiments were carried out in a greenhouse to investigate how effectively the transfer of radiocesium and radiostrontium from soil to Chinese cabbage could be reduced by applying K and Ca simultaneously to the soil. The sources of these elements were KCl and Ca(OH)(2) at agrochemical grades. Varying dosages of K and Ca were tested for an acid loamy soil treated with a mixed solution of (137)Cs and (85)Sr at two different times - 3 d before sowing and 32 d after sowing. For the pre-sowing deposition, the soil-to-plant transfer of (137)Cs decreased sharply with increasing dosages of K and Ca (K/Ca, g m(-2)) from 4.8/46 up to 22.4/215 but the (85)Sr transfer had the greatest reduction at a dosage of 12.8/123. At this dosage, an about 60% reduction occurred for each radionuclide. Plant growth was inhibited from the dosage of 22.4/215, above which all the plants died young. Both dosages of 4.8/46 and 12.8/123 tested following the growing-time deposition produced around 95% reductions for (137)Cs and 50% reductions for (85)Sr. In the second year after the 12.8/123 applications, the effects for (85)Sr were almost the same as in the first year, whereas those for (137)Cs were diminished slightly for the pre-sowing deposition and markedly for the growing-time deposition. Considerably (K) or slightly (Ca) higher doses than 12.8/123 would be allowable for the maximum TF reductions achievable without a growth inhibition.


Perioperative glycaemic control for preterm infant with transient neonatal hyperglycaemia and gastroschisis.
Neonatal hyperglycaemia is a rare metabolic disorder. There are no reports of an association between neonatal hyperglycaemia and gastroschisis. This report presents preoperative and intraoperative management of blood sugar in a low birth weight Thai preterm neonate with gastroschisis and a diagnosis of neonatal hyperglycaemia. The patient underwent an emergency, multi-staged, surgical repair under general anaesthesia. Anaesthesiologists should be aware of possible perioperative dysglycaemic conditions in these patients. Proper timing of surgery and appropriate preanaesthetic preparation are necessary to reduce the morbidity and mortality related to hyperglycaemia and gastroschisis. The patient's guardian has given consent for the case report to be published.


Corneal endothelial safety following subconjunctival and intrastromal injection of bevacizumab for corneal neovascularization.
The purpose of this study is to determine the effect on endothelial cell density and morphology of combined subconjunctival and intracorneal injection of bevacizumab for the treatment of corneal neovascularization (NV). The charts and specular microscopy images of ten consecutive patients with corneal NV, who received combined subconjunctival+intracorneal injections of bevacizumab were reviewed. Patients received three injections of bevacizumab 25 mg/mL (1.25 mg/0.05 mL subconjunctival and 1.25 mg/0.05 mL intrastromal) 4-6 weeks apart. Endothelial cell counts (ECCs) and morphological changes were assessed by non-contact specular microscopy performed at baseline, 1 month after each injection and at 3 and 6 months after the last injection. There were no significant changes in ECCs (p = 0.663), coefficient of variation (p = 0.076), percentage of hexagonal cells (p = 0.931) or mean corneal thickness (p = 0.462) from pre-injection values to the 6-month follow-up values. There were no intraoperative or postoperative complications. In our series, the use of combined subconjunctival and intracorneal bevacizumab did not cause any decrease in ECCs or morphological alterations up to 6 months after the last of three injections. Further studies are required to confirm long-term safety in a larger sample population with longer follow-up, as well as the ideal dose, route of administration and frequency of bevacizumab administration.


A rapid-response alphanumeric paging design decreases door-to-balloon times in patients undergoing primary percutaneous coronary intervention for ST elevation acute myocardial infarction.
In acute ST elevation myocardial infarction (STEMI), rapid reperfusion of the infarcted artery improves cardiovascular outcomes; however, many hospitals have difficulty achieving recommended times. We hypothesized that a Rapid-Response Alphanumeric Paging Design (RAPiD) would reduce door-to-balloon time for primary percutaneous coronary intervention (PCI) in STEMI. A chest pain algorithm and interdisciplinary team was established in December 2000. In August 2002, RAPiD was instituted to transmit the diagnosis and location of a STEMI to the chest pain team through a speed-dial button. All patients presenting to our emergency department from February 2002 through July 2003 with STEMI were included. Exclusion criteria included lack of chest pain, cardiopulmonary arrest before PCI, and catheterization or PCI not performed. Outside-referral STEMI, in-patient STEMI, and failed thrombolysis patients were excluded. Data was obtained from medical records. Log transform of door-to-balloon (DTB) times was performed. Forty-seven events satisfied inclusion and exclusion criteria with 32 occurring after RAPiD (post-RAPiD). Fifteen events occurred during on-hours (8 am to 7 pm on weekdays). Mean untransformed DTB times pre- and post-RAPiD were 162 +/- 137 (standard deviation) minutes and 112 +/- 41 minutes. The main effects analysis of variance model showed a significant reduction in post-RAPiD DTB time (P = 0.03) with a mean reduction of 26% during off-hours and 20% during on-hours. The post-RAPiD estimate of mean DTB time, derived from the antilog of the log transform, was 96.7 minutes (95% confidence interval, 83.7-111.7). The institution of RAPiD in a hospital with a preexisting chest pain algorithm significantly decreases DTB times so as to satisfy current ACC/AHA guidelines.


Q&A: How do plants respond to cytokinins and what is their importance?
Cytokinins comprise a family of signaling molecules essential for regulating the growth and development of plants, acting both locally and at a distance. Although much is known about their biosynthesis and transport, important open questions remain.


One-step synthesis of yellow-emissive carbon dots with a large Stokes shift and their application in fluorimetric imaging of intracellular pH.
A new nanoprobe based on yellow-emissive carbon dots (Y-CDs) was developed for sensing full-range intracellular pH values. By using o-phenylenediamine as the raw material, Y-CDs with a quantum yield of 31% were prepared through a one-pot solvothermal carbonization method. The Y-CDs exhibited a distinctive fluorescence emission peak at 570 nm with excitation at 450 nm, showing a very large Stokes shift (120 nm). Notably, the nanoprobe revealed a linear relationship between fluorescence intensity and pH value within the range of pH 4.0 to 8.2, exhibiting the ability of this probe to monitor full-range intracellular pH variations. In addition, the nanosensor possessed excellent photostability and fluorescence reversibility in pH measurements and showed excellent selective detection of the influences of other biological species. The CD-based nanoprobe was successfully used to perform quantitative fluorescence imaging of intracellular pH variation, demonstrating its promise for application in cellular systems.


In vivo toxicometabolomics reveals multi-organ and urine metabolic changes in mice upon acute exposure to human-relevant doses of 3,4-methylenedioxypyrovalerone (MDPV).
3,4-Methylenedioxypyrovalerone (MDPV) is consumed worldwide, despite its potential to cause toxicity in several organs and even death. There is a recognized need to clarify the biological pathways through which MDPV elicits general and target-organ toxicity. In this work, a comprehensive untargeted GC-MS-based metabolomics analysis was performed, aiming to detect metabolic changes in putative target organs (brain, heart, kidneys and liver) but also in urine of mice after acute exposure to human-relevant doses of MDPV. Male CD-1 mice received binge intraperitoneal administrations of saline or MDPV (2.5 mg/kg or 5 mg/kg) every 2 h, for a total of three injections. Twenty-four hours after the first administration, target organs, urine and blood samples were collected for metabolomics, biochemical and histological analysis. Hepatic and renal tissues of MDPV-treated mice showed moderate histopathological changes but no significant differences were found in plasma and tissue biochemical markers of organ injury. In contrast, the multivariate analysis significantly discriminated the organs and urine of MDPV-treated mice from the control (except for the lowest dose in the brain), allowing the identification of a panoply of metabolites. Those levels were significantly deviated in relation to physiological conditions and showed an organ specific response towards the drug. Kidneys and liver showed the greatest metabolic changes. Metabolites related with energetic metabolism, antioxidant defenses and inflammatory response were significantly changed in the liver of MDPV-dosed animals, while the kidneys seem to have developed an adaptive response against oxidative stress caused by MDPV. On the other hand, the dysregulation of metabolites that contribute to metabolic acidosis was also observed in this organ. The heart showed an increase of fatty acid biosynthesis, possibly as an adaptation to maintain the cardiac energy homeostasis. In the brain, changes in 3-hydroxybutyric acid levels may reflect the activation of a neurotoxic pathway. However, the increase in metabolites with neuroprotective properties seems to counteract this change. Metabolic profiling of urine from MDPV-treated mice suggested that glutathione-dependent antioxidant pathways may be particularly involved in the compensatory mechanism to counteract oxidative stress induced by MDPV. Overall, this study reports, for the first time, the metabolic profile of liver, kidneys, heart, brain, and urine of MDPV-dosed mice, providing unique insights into the biological pathways of toxicity. Our findings also underline the value of toxicometabolomics as a robust and sensitive tool for detecting adaptive/toxic cellular responses upon exposure to a physiologically relevant dose of a toxic agent, earlier than conventional toxicity tests.


A general efficient implementation of the BSSE-free SCF and MP2 methods based on the chemical Hamiltonian approach.
We describe some details related to a new, general, and efficient implementation of the BSSE-free SCF and second-order Møller-Plesset perturbation theories of intermolecular interactions, based on the "Chemical Hamiltonian Approach" (CHA). The program is applicable for both open-shell and closed-shell systems and for an arbitrary number of interacting subsystems. With the new program the CHA method is faster than the usual "counterpoise correction" scheme for single point calculations, especially for clusters consisting of several molecules. The numerical results provided by these conceptually different schemes, however, have again found to be very close to each other. The CHA scheme is particularly good for providing truly BSSE-free MP2 data for intermolecular potentials.


Nanoscale patterning of metal nanoparticle distribution in glasses.
: We show that electric field imprinting technique allows for patterning of metal nanoparticles in the glass matrix at the subwavelength scale. The formation of glass-metal nanocomposite strips with a width down to 150 nm is demonstrated. The results of near-field microscopy of imprinted patterns are in good agreement with the performed numerical modeling. Atomic force microscopy reveals that imprinting also results in the formation of nanoscale surface profile with the height going down with the decrease of the strip width. The experiments prove the applicability of this technique for the fabrication of nanoscale plasmonic components.


Biomechanical Evaluation and Factorial Analysis of the 3-Dimensional Printing Self-Designed Metallic Reconstruction Plate for Mandibular Segmental Defect.
Reconstruction plates are frequently used to treat mandibular segmental defects. The aim of this study is to compare the biomechanical performance of a 3-dimensional-printed self-designed titanium alloy reconstruction plate with that of the traditional reconstruction plate in mandible reconstruction. The analyzed parameters of the self-designed reconstruction plate, including plate length (100 mm and 125 mm), plate thickness (2.1, 2.4, and 2.7 mm), and bone mass (100, 75, and 50%), were also evaluated. An artificial mandible with anatomical geometry was used to develop the self-designed reconstructed plate. Both in vitro experiments and finite element simulations were performed for the biomechanical comparison of the self-designed and traditional reconstruction plates. In finite element analysis, 3 major muscle forces of mandible movement were set as the loading condition, and the displacement of the condyle was fixed in all directions as the boundary condition. The biomechanical performances (stresses in the plate and strains in bone) of the self-designed reconstruction plate were superior to those of the traditional plate. Factorial analysis indicated that plate length and thickness had significant effects on decreasing stresses of the plate and mandibular bone. The self-designed reconstruction plate might have a benefit to reduce the stresses/strains in plate itself and surrounding bone.


Light and electron microscope immunocytochemical localization of 5- and 12-lipoxygenases and cyclooxygenase enzymes in human granulosa cells from preovulatory follicles.
Cellular and subcellular distribution of 5- and 12-lipoxygenases and cyclooxygenase enzymes were investigated in human granulosa cells from preovulatory follicles using light and electron microscope immunocytochemistry. The results demonstrated that all three enzymes are present in granulosa cells but not in minor contaminating red blood cells. While the distribution of cyclooxygenase and 12-lipoxygenase was relatively uniform among the granulosa cells, 5-lipoxygenase was not uniformly distributed among these cells. All three enzymes are present in microvillus plasma membranes, rough endoplasmic reticulum, cytoplasm, nuclear membranes and chromatin. In summary, 5- and 12-lipoxygenases and cyclooxygenase enzymes, which catalyze the transformation of arachidonic acid into different eicosanoids, are present in several subcellular organelles including nuclei of granulosa cells from preovulatory follicles.


[Epidemiology, diagnosis and treatment of head and neck cancers].
Cancers of the upper aerodigestive tracts are the fourth most common cancer in France. The main risk factors are smoking and alcohol. They do not necessarily present specific signs, making their early diagnosis difficult. A change in the patient's general condition is a late sign leading to a poor prognosis of the disease.


Infections in travellers arriving from Australia.
An unwell traveller whose itinerary has included Australia may be infected with agents that are uniquely found in that country or by more cosmopolitan agents that exist there. This brief review will discuss some of the more common or important infectious disease diagnoses and discuss some features that can be elicited on examination or from the history that would be useful in directing investigation and treatment. Diseases discussed include epidemic polyarthritis, dengue fever, Murray Valley encephalitis, melioidosis, leptospirosis, Buruli ulcer, scrub typhus and spotted fever.


Oxacillinase-181 Carbapenemase-Producing Klebsiella pneumoniae in Neonatal Intensive Care Unit, Ghana, 2017-2019.
We sequenced 29 carbapenemase-producing Klebsiella pneumoniae isolates from a neonatal intensive care unit in Ghana. Twenty-eight isolates were sequence type 17 with blaOXA-181 and differed by 0-32 single-nucleotide polymorphisms. Improved surveillance and infection control are needed to characterize and curb the spread of multidrug-resistant organisms in sub-Saharan Africa.


Ethanol and nitrous oxide produce withdrawal-induced convulsions by similar mechanisms in mice.
Twenty generations of selective breeding were used to produce lines (strains) of mice which differ markedly from one another in ethanol physical dependence development as indexed by handling-induced convulsions (HIC) induced by withdrawal from ethanol. These withdrawal seizure prone (WSP) and withdrawal seizure resistant (WSR) selection lines now differ by over 10-fold in HIC scores after equivalent exposure to intoxicating levels of ethanol via inhalation. Since handling-induced convulsions can be readily elicited following withdrawal from nitrous oxide, we sought to determine if the very large differences in ethanol withdrawal-induced HIC bred into these selection lines would generalize to nitrous oxide. Following a 60 min exposure to 75% nitrous oxide (in O2), a greater than 10-fold difference in HIC scores, and a 2-fold difference in tremor incidence was seen upon withdrawal in WSP vs. WSR mice. These findings closely parallel those seen with ethanol, and demonstrate that a large degree of commonality exists in the genes and the mechanisms determining these withdrawal signs. HIC elicited by nitrous oxide withdrawal were readily suppressed by ethanol, and HIC elicited by ethanol withdrawal were promptly suppressed by 75% nitrous oxide in WSP mice. Nitrous oxide also suppressed HIC and tremor associated with nitrous oxide withdrawal.


A host-guest interaction activated Bobbitt oxidant for highly efficient oxidation of alcohols.
Host-guest complexation using hydrogen-bonded macrocycles was found to enable activation of the Bobbitt oxidant reagent, which greatly facilitates the highly efficient oxidation of unactivated primary alcohols. This work provides a complementary approach to the activation of Bobbitt's salt with shape-persistent macrocycles in supramolecular catalysis.


Systems modelling methodology for the analysis of apoptosis signal transduction and cell death decisions.
Systems biology and systems medicine, i.e. the application of systems biology in a clinical context, is becoming of increasing importance in biology, drug discovery and health care. Systems biology incorporates knowledge and methods that are applied in mathematics, physics and engineering, but may not be part of classical training in biology. We here provide an introduction to basic concepts and methods relevant to the construction and application of systems models for apoptosis research. We present the key methods relevant to the representation of biochemical processes in signal transduction models, with a particular reference to apoptotic processes. We demonstrate how such models enable a quantitative and temporal analysis of changes in molecular entities in response to an apoptosis-inducing stimulus, and provide information on cell survival and cell death decisions. We introduce methods for analyzing the spatial propagation of cell death signals, and discuss the concepts of sensitivity analyses that enable a prediction of network responses to disturbances of single or multiple parameters.


Do older adults respond to cognitive behavioral therapy as well as younger adults? An analysis of a large, multi-diagnostic, real-world sample.
Older adults (OA; ≥55 years of age) are underrepresented in patients receiving cognitive-behavioral therapy (CBT). This study evaluates mental health outcomes for OA compared to younger adults (YA; <55 years of age) receiving CBT. This is a pre-post study comparing the effectiveness of CBT for OA (n = 99) and YA (n = 601) in a CBT service located in a university-affiliated tertiary care hospital in Canada. Data was collected between 2001 and 2021. Participants received a mean of 18.5 sessions (SD 10) of standard, evidence-based CBT with treatment integrity checks. The main outcome was clinically significant change, as measured by the Reliable Change Index (RCI). Secondary outcomes were change in the Global Severity Index (GSI-SCL) of the Symptoms Checklist-90 (Revised), and Clinical Global Improvement scores (CGI). The RCI allowed a comparison of treatment efficacy across diagnoses. Both groups experienced similar improvement on the RCI (2.92 [±3.64] vs. 3.15 [±4.86], p = 0.65). Furthermore, 39% of OA and 42% of YA no longer met criteria for their diagnoses. Groups did not differ with respect to changes in the GSI-SCL. The CGI severity comparison suggested that OA had milder illness. In all outcomes (RCI, CGI and GSI-SCL), participants improved over time. This real-world study analyzed a large sample of OA and YA undergoing CBT for various mental health conditions. Both groups were found to benefit equally.


Two dimensional iron metal-organic framework nanosheet with peroxidase-mimicking activity for colorimetric detection of hypoxanthine related to shrimp freshness.
Two dimensional iron metal-organic framework nanosheet (2D Fe MOF) was facilely synthesized at room temperature by simple stirring of iron salts and terephthalic acid ligand in a mixed solution containing triethylamine. Its morphology and structure were fully characterized by TEM, AFM, XPS and TEM element mapping. Then, its peroxidase-mimicking activity was studied by using H2O2 and 3, 3', 5, 5'- tetramethylbenzidine as substrate. Km and Vmax of 2D Fe MOF towards H2O2 were 0.02 mM and 2.08 × 10-8 M s-1, respectively. Through the formation of cascade reaction between xanthine oxidase and 2D Fe MOF, a visual method for hypoxanthine (Hx) detection was constructed to evaluate aquatic products freshness. After effective validation, this method presented wide linear range (5.0-500.0 μM), low limit of detection (3.29 μM), satisfied accuracy (recovery of 94.78-99.85%), and good selectivity. By using this method, Hx content in shrimp samples at different storage time were determined.


Advances in the development of amorphous solid dispersions: The role of polymeric carriers.
Amorphous solid dispersion (ASD) is one of the most effective approaches for delivering poorly soluble drugs. In ASDs, polymeric materials serve as the carriers in which the drugs are dispersed at the molecular level. To prepare the solid dispersions, there are many polymers with various physicochemical and thermochemical characteristics available for use in ASD formulations. Polymer selection is of great importance because it influences the stability, solubility and dissolution rates, manufacturing process, and bioavailability of the ASD. This review article provides a comprehensive overview of ASDs from the perspectives of physicochemical characteristics of polymers, formulation designs and preparation methods. Furthermore, considerations of safety and regulatory requirements along with the studies recommended for characterizing and evaluating polymeric carriers are briefly discussed.