Co-occurrence of multiple kdr mutations (F1534C, V1016I, V410L) in Aedes aegypti from coastal areas in Ghana and assessment of the role of mosquito coil in causing pyrethroid resistance.
The rapid spread of knockdown-resistance (kdr) mutations in Africa calls for monitoring and investigation into the cause of pyrethroid resistance to inform management strategies. This study investigated the pyrethroid resistance profile of Aedes aegypti from coastal towns in Ghana and the impact of mosquito coil, a popular household pyrethroid-based anti-mosquito tool, on the development of pyrethroid resistance. Susceptibility to deltamethrin and the presence of kdr mutations was determined in adult female mosquitoes reared from larvae. Furthermore, the LT50 of a mosquito coil (0.08% meperfluthrin) against a laboratory colony was determined, and the value was used as a sublethal dose in an experimental study. The laboratory colony of Ae. aegypti was exposed to the sublethal dose of the coil once per generation for six generations (F6). The susceptibility of the exposed colony to deltamethrin (0.05%) was determined. The Ae. aegypti populations from the coastal towns were resistant to deltamethrin with co-occurrence of F1534C, V1016I and V410L kdr mutations. In the experimental study, the LT50 (95% CI) of the selected colony against the coil rose from 8 minutes (95% CI; 6-9) at F0 to 28 minutes (95% CI; 23-34) at F6. Nonetheless, deltamethrin caused similar mortalities in the selected and control colonies. The mutant allele frequencies of 1534C and 410L were similar but 1016I was higher in the selected colony (17%) than in the control (5%). However, the increased tolerance to the coil and high mutant allele frequency of 1016I in the selected colony did not affect the mosquito's resistance level to deltamethrin insecticide. Further study is needed to elucidate the role of pyrethroid-based mosquito coils in the development of insecticide resistance in mosquito vectors.


Breast Cancer Invasion and Metastasis by mPRα Through the PI3K/Akt Signaling Pathway.
Invasive breast cancer is the most common type of malignancy in women worldwide. However, the mechanism responsible for breast cancer metastasis is still unclear and needs further illustration. It has been proven that matrix metallopeptidase 9 (MMP-9) promotes metastasis of the cancer cells. However, the interaction between mPRα and MMP-9 has not been studied. Therefore, in the present research, the effect of MMP-9 on the malignant progression of invasive breast cancer promoted by membrane progesterone receptorα (mPRα) was investigated. The results showed that the protein expression of mPRα, p-Akt and MMP-9 increased in the cancerous tissues compared to that of the noncancerous breast tissue. Furthermore, a positive correlation was found between mPRα and C-erbB-2, as well as the number of involved local lymph nodes. On the other hand, a negative correlation was observed between mPRα and estrogen receptors (ER) along with progesterone receptors (PR). Similarly, a positive association was found between MMP-9 and the number of involved local lymph nodes. Besides, the high expression of MMP-9 also had a positive correlation with the tumor size. However, the high level of MMP-9 had a negative correlation with ER and PR. In addition, there was a positive correlation between mPRα and p-Akt together with MMP-9. The results confirm that mPRα was a major marker of harmful prognosis and it promoted the expression of MMP-9 during invasion to the local lymph nodes through the pathway of PI3K/Akt. The present study provided a novel therapeutic strategy to inhibit breast cancer growth by preventing mPRα signaling pathway.


Chloroquine allows the secretion of internalized 125I-epidermal growth factor from fibroblasts.
Incubation of cells with labelled hormone in the presence of the lysosomotropic agent chloroquine produces an enhanced intracellular accumulation of hormone and receptor. Using a pulse-chase paradigm in which cell surface receptors were labelled with 125I-EGF at 4 degrees C, it was found that when 100 microM chloroquine was present in the 37 degrees C chase medium intact hormone was accumulated in the medium. Without chloroquine, low molecular weight (mw) degradation products were found in the medium. The processes of receptor-mediated endocytosis and subcellular distribution of 125I-EGF-receptor complexes were unchanged by chloroquine. The source of the intact hormone accumulating in the medium was therefore an intracellular compartment(s). The 125I-EGF released from the cells could rebind to surface receptors and be re-internalized; rebinding was inhibited by unlabelled EGF or Concanavalin A in the incubation medium. The concentration of unlabelled EGF required to inhibit rebinding was more than three orders of magnitude greater than the amount of 125I-EGF whose rebinding was inhibited. Thus, the 125I-EGF released from intracellular sites was rebound preferentially over exogenous EGF. The possible pathways for secretion of intact 125I-EGF and mechanisms of its preferential rebinding are discussed.


Adsorption of chromium(III) on lignin.
In order to assess the possibility of using lignin to remove Cr(III) from waters, the adsorption of Cr(III) on lignin isolated from black liquor, a waste product of the paper industry, was investigated. The influences of pH, lignin dosage, contact time, ionic strength, Cr(III) concentration and other metals were investigated. The Cr(III) adsorption was strongly dependent on pH and adsorbent dosage, but independent of ionic strength and other metal ions. The adsorption kinetic data can be described well with pseudo-second-order model and the equilibrium data can be well fitted using Langmuir two-surface model with a maximum adsorption capacity of 17.97 mg/g. Cr(III) adsorption on lignin was mainly through the ion-exchange mechanism and formed inner-sphere complexes with lignin. Successful application in removing Cr(III) was achieved by using a real wastewater sample. This study indicates that lignin has the potential to become an effective and economical adsorbent for the removal of Cr(III) from wastewaters.


Alterations in regional contractility following cardiopulmonary bypass with intraoperative ischemia.
Coronary occlusion during cardiopulmonary bypass has been used in place of aortic occlusion to perform coronary artery anastomoses, but this procedure on distal myocardial function has not been evaluated. Regional myocardial function was examined with the use of ultrasonic crystals in 20 dogs subjected to this technique to compare normothermic and hypothermic (30 degrees C) bypass in both beating and fibrillating hearts. We found a significant decline in the velocity of contraction of the distal segment in fibrillating compared to bearing hearts (p less than 0.01). Hypothermia prevented this decline in the beating, but not the fibrillating, hearts. With respect to contractile function in the distal myocardial segment, local occlusion techniques cause an injury similar to that reported for aortic cross-clamping.


Development and validation of a short tool to assess the awareness of hypertensive disorders of pregnancy: a cross-sectional study among pregnant women in Lebanon.
Hypertensive disorders of pregnancy (HDPs) are responsible for most perinatal and fetal mortality. Few programs are patient-centered during pregnancy, thereby increasing the risks of misinformation and misconceptions among pregnant women and, as a result, malpractices. This study aims to develop and validate a form to assess the knowledge and attitudes of pregnant women about HDPs. A cross-sectional pilot study was conducted over 4 months, targeting 135 pregnant women from 5 obstetrics and gynecology clinics. A self-reported survey was developed and validated, and an awareness score was generated. The mean maternal age of the participants was 27.3 (5.3) years. About 80% of the participants reported that they monitored their weight during pregnancy, and 70.4% monitored their blood pressure, out of which 73.8% performed it at the doctor's clinic only. Overall, participants had a total score of 16.9 (3.1) over 25 with higher attitude scores than knowledge scores. Less than half of the patients (45.2%) knew the cut-off for hypertension. With respect to knowledge statements, higher scores were noted for statements related to the symptoms of HDPs, and lower scores were reported for statements related to some HDP complications. Older women and those who monitored their blood pressure during pregnancy had significantly higher awareness scores. Those working had higher awareness of HDPs (67.4%), whereas about half of nonworkers (53.9%) showed lower awareness scores (P=.019). Pregnant women had moderate awareness of HDPs. The short 25-item tool developed in the present study can be used in obstetric clinics to explore the awareness of women of HDPs.


Alkaline earth metals (Be, Mg, Ca) doped hexamine complexant with enhanced electronic and nonlinear optical properties.
Organic complexant hexamine (hexamethylenetetramine, HMTA) is doped with alkaline earth (AE) metals, and new complexes are designed systematically to explore their nonlinear optical (NLO) properties by carrying out DFT calculations. Optimization of afresh designed geometries has shown their sufficient thermodynamic stability. Moreover, the energy band gap of pure HMTA is 10.62 eV which is reduced up to 2.63 eV for our doped complexes. This shows that alkaline earth metals are effective in enhancing the electronic properties of a system. Time-dependent DFT calculations are achieved, and results show that higher absorption maxima (λmax) along with small transition energies (ΔE) have significantly increased the hyperpolarizability (β0) values (21,338-220,585 au). This higher hyperpolarizability is an elementary prerequisite for improved NLO response of a material. Transition density matrix (TDM) analysis, density of states (DOS) analysis, and electron density difference map (EDDM) studies are executed to get information about electronic distribution, crucial transitions, and electron transfer properties. As a result of these findings, it can be concluded that alkaline earth metal-doped HMTA might be a competitor for NLO materials with remarkable optical and electronic properties and better future applications in the field of optoelectronics.


Sensory electroneurographic parameters and clinical recovery of sensibility in sutured human nerves.
A total of 37 patients with traumatic transection of median or ulnar nerves at the wrist (total 41 nerves) were examined clinically and electrophysiologically 4-59 months after primary or secondary suture or grafting. There was a significant increase of cumulative amplitude with the time after suture, whereas maximum sensory nerve conduction velocity and maximum amplitude of nerve action potentials did not reveal such a correlation. The recovery of two-point discrimination, vibration threshold and sensibility scored according to the scale of Nicholson and Seddon were also not related to the passage of time after operation. Though there were significant correlations between cumulative amplitude and both two-point discrimination and recovery of sensibility, electrophysiological parameters were shown to be inadequate predictors of clinical recovery.


The use of PowerPrep and HRGC/HRMS for biological monitoring of exposure to PCDD, PCDF and dl-PCB in Poland.
The aim of this study was to design the optimized laboratory protocol as a tool for human biomonitoring of selected Persistent Organic Pollutants (POPs) in Poland. In this study, we present the method developed for the determination of 29 congeners of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dl-PCBs), as well as individual results of the measurements in 40 human breast milk samples collected in central Poland in 2008-2010. The protocol of sample preparation and quantitative analysis of PCDD/Fs and dl-PCBs was optimized for the isotopic dilution method with high resolution gas chromatography/high resolution mass spectrometry HRGC/HRMS. Fat content in the extracts was determined gravimetrically. The results were corrected by fat content in the samples. The average sum of PCDD/F and dl-PCBs in the human milk samples from the urban area was 7.429 WHO-TEQpg/g fat (with the range 0.431-14.27), and in the rural area it was 6.448pg WHO-TEQ/g fat (0.539-12.61). The results obtained in this study indicate that the mothers were exposed uniformly to PCDD/Fs and PCBs regardless of location. The significant difference of p<0.1 between the milk samples from the urban and rural mothers in 2,3,7,8-TCDD; 1,2,37,8,9-HxCDD and 2,3,4,6,7-HxCDF were observed. For the other 14 PCDD/F and 12 dl-PCB congeners, the observed differences were not significant. The total WHO-TEQ values are lower in comparison with the average results in Europe from the fourth round of a WHO-coordinated study.


Scheloribatid mites as the source of pumiliotoxins in dendrobatid frogs.
The strawberry poison frog Dendrobates pumilio (Anura: Dendrobatidae) and related poison frogs contain a variety of dendrobatid alkaloids that are considered to be sequestered through the consumption of alkaloid-containing arthropods microsympatrically distributed in the habitat. In addition to ants, beetles, and millipedes, we found that adults of two species of oribatid mites belonging to the cohort Brachypylina, trophically a lower level of animal than ants and beetles, contain dendrobatid alkaloids. Gas chromatography/mass spectrometry (GC/MS) of hexane extracts of adult Scheloribates azumaensis (Oribatida: Acari) revealed the presence of not only pumiliotoxin 251D (8-hydroxy-8-methyl-6-(2'-methylhexylidene)-1-azabicyclo[4.3.0]nonane), but also precoccinelline 193C and another coccinelline-type alkaloid. From the corresponding extracts of an unidentified Scheloribates sp., pumiliotoxin 237A (8-hydroxy-8-methyl-6-(2'-methylpentylidene)-1-azabicyclo[4.3.0]nonane) was detected as a minor component, and identified by synthesis. The presence of related alkaloids, namely deoxypumiliotoxin 193H, a 6,8-diethyl-5-propenylindolizidine, and tentatively, a 1-ethyl-4-pentenynylquinolizidine, were indicated by the GC/MS fragmentation patterns, along with at least another six unidentified alkaloid components. Thus, one possible origin of pumiliotoxins, coccinellid alkaloids, and certain izidines found in poison frogs may be mites of the genus Scheloribates and perhaps related genera in the suborder Oribatida.


Nickel-Catalyzed Formal Homocoupling of Methoxyarenes for the Synthesis of Symmetrical Biaryls via C-O Bond Cleavage.
A new method has been developed for the nickel-catalyzed homocoupling of methoxyarenes via C-O bond cleavage using a diboron reagent. The use of 1,3-dicyclohexylimidazol-2-ylidene as a ligand was found to be critical to the success of the reaction. This new method allows the synthesis of a wide range of biaryl compounds.


Magnetic resonance imaging of the collateral ligaments of the thumb.
Injury to the ulnar collateral ligament of the metacarpal phalangeal joint of the thumb can usually be diagnosed on the basis of a combination of history, radiographic examination, and clinical stress testing of the joint when appropriate. Occasionally, when the patient is seen late and the diagnosis is doubtful, stress evaluation may be ill-advised because a nondisplaced ligament may be displaced in the process. We had recent experience with three patients in whom the use of magnetic resonance imaging was helpful in diagnosing a displaced ulnar collateral ligament in two cases, and an intraligamentous injury in the other. These studies were conducted at no charge to the patient as part of institutional investigational research. The current cost of this technology is prohibitive for routine use; however, when it becomes less expensive, it may be helpful as a diagnostic tool.


Molecular characterization of three plasmids from Bifidobacterium longum.
The complete nucleotide sequences for pNAC1 (3538bp) from strain RW048 as well as for pNAC2 (3684bp) and pNAC3 (10,224bp) from strain RW041 of Bifidobacterium longum were determined. The largest ORF (repB) of pNAC1 encodes a putative protein similar to those involved in a rolling-circle (RC) replication mechanism, which was confirmed by demonstration of single-strand intermediates in the host cell. The putative RepB gene product of pNAC2 is most similar to the replication protein of pDOJH10L and pKJ36. A second gene (mob) is similar to mobilization proteins involved in conjugation. Plasmid pNAC3 is the largest bifidobacterial plasmid to be sequenced to date. Of the eight putative gene products coded by pNAC3, one is similar to replication proteins (RepB), and another (Orf2) to putative transfer proteins (Tra). Bifidobacterial plasmids were divided into five groups based on Rep amino acid sequence homology and the results suggest a new plasmid family for B. longum.


Therapeutic effect of finasteride through its antiandrogenic and antioxidant role in a propionic acid-induced autism model: Demonstrated by behavioral tests, histological findings and MR spectroscopy.
Autism is a clinically defined neurodevelopmental disorder with unknown origin characterized by significant social, communication and behavioral challenges. Although it can be a lifelong condition, treatments can help alleviate symptoms and enhance a patient's quality of life. We aimed to assess the therapeutic potential of finasteride in autism with biochemical markers, histopathological evaluation, behavioral tests and radiological imaging. Propionic acid (PPA) was injected intraperitoneally into 20 out of 30 rats for 5 days to establish an autism model. Rats were randomly assigned into four groups: control group (no procedure was applied, n = 10), placebo group (intraperitoneal PPA + 1 ml/kg/day % 0.9 NaCl saline was given via oral gavage for 15 days, n = 10) and treated group (intraperitoneal PPA + 5 mg/kg/day of finasteride was given via oral gavage for 15 days, n = 10). After 4 days of behavioral tests, magnetic resonance spectroscopy (MRS) was performed for measuring creatine and lactate levels. All animals were sacrificed for histopathological examination and biochemical analysis of brain tissue. MDA, NFκB, TNF-α, IL-2, IL-17A and lactate levels in brain homogenates were significantly increased in the placebo group compared to the control group, while Nfr2 levels were decreased; and the levels of all biochemical markers were reversed by finasteride treatment. A significant improvement was observed in autism-like behaviors in rats treated with finasteride compared to the placebo group. Further, the creatine and lactate levels in corpus striatum in MRS, the neuronal counts and glial activity of the hippocampus and cerebellum were closer to the control group in the finasteride-treated group compared to the placebo group. Finasteride led significant improvement in autism-like symptoms with its antioxidant effect through Nrf2 modulation in addition to its anti androgen effect.


Acute poisoning in children in Ethiopia: a cross-sectional study.
Acute poisoning is a global pediatric emergency problem. However, a wide variation in patterns of acute poisoning and associated factors across different geographical regions was stated. As a result, our research focused on the investigation of acute poisoning in children. An Institutional-based Retrospective study design was conducted at the University of Gondar comprehensive specialized hospital from October 2016 to October 2020. The analysis of the data was performed via SPSS Version 25. Furthermore, multiple logistic regression analysis was recruited. A P-value ≤ 0.05 was declared as statistically significant. Our study's prevalence of acute poisoning was 82/5489 (1.5%). 53 (64.6%) of patients were males. Of the total patients who had the diagnosis of poisoning, 54 (65.9%) came from rural areas. Venom was the most frequent offending agent (26.8%) and oral ingestion was the most common route of exposure (70.7%). Of the total patients who had the diagnosis of poisoning, 54 (65.9%) came from rural areas. Venom was the most frequent offending agent (26.8%), followed by insecticides (organophosphates) (21.5%). Accidental poisoning was the most common mode of poisoning more often than intentional (75.6-24.4%). The digestive tract (oral ingestion) (69.5%) was the commonest route of poisoning, followed by the cutaneous (skin bite) (24.4%). Death was three times more likely in the rural population than in urban residents [AOR 2.9 (1.21-13.7); P value 0.046]. Appropriate emergency care is the mainstay of the supportive management protocol for childhood poisoning.


Paralysis of the small bowel resembling mechanical intestinal obstruction.
In some instances, particularly in the neonate, paralytic ileus affects predominantly the small bowel, thus resembling intestinal obstruction. Localized paralysis of the small bowel occurs secondary to regional events in a segment of gut and resembles mechanical obstruction even more closely. In localized paralysis the bowel lumen is usually dilated without abrupt distal transition to collapsed intestines. If there is radiographic and clinical recognition of localized, transitory bowel paralysis, surgery is usually unnecessary.


Behcet's disease with uveitis in Taiwan.
Behcet's disease is a multisystemic inflammatory disease which may lead to blindness. The purpose of this study was to describe and compare the clinical features and visual outcome of Behcet's uveitis in Taiwan. The medical charts of 227 consecutive patients (414 eyes) with Behcet's uveitis who were seen in the Uveitis Clinic of Taipei Veterans General Hospital were reviewed: 96 patients (group A) between 1984 and 1993 and 131 (group B) between 1994 and 2003. The male-to-female ratio was 1.6. The mean age at the time of uveitis onset was 30.8 years. Males were most affected in the 3rd and 4th decades and females in the 2nd to 5th decades. There were more skin and gastrointestinal lesions in males, and less skin and genital lesions in group B. HLA-B51 antigen was found in 35.7% of patients. Treatment with cyclosporin, azathioprine and methotrexate was more frequent in group B. Uveitis occurred bilaterally in 83.9% of patients. At the first visit, potential visual acuity (VA) was 0.1 or less in 24.7% of eyes in males and 11.4% in females. The mean time from presentation to loss of useful vision (> 0.1) was 51 months in 19.1% of eyes. Kaplan-Meier survival analysis estimated the risks of losing useful vision at 5, 10 and 15 years as being 22.6%, 43.0% and 58.5%, respectively. VA at the first and last visits were better and VA deterioration slower in group B. Visual outcome is poorer in males than in females and has improved in the recent decade, but still a significant proportion of patients lose their vision quickly. The number of new patients has not decreased.


Evaluation of montelukast in 8 to 14 year old children with mild persistent asthma and compared with inhaled corticosteroids.
To determine the clinical effectiveness, tolerability and reliability of montelukast and to compare this drug with inhaled corticosteroids. We performed a randomized, 14-week, 2-period, prospective parallel group study. After a 2-week run-in period, patients received treatment for 12 weeks. Sixty-three clinically stable outpatients aged 8 to 14 years with a history of mild persistent asthma for at least 1 year and a forced expiratory volume in one second (FEV1) greater than 80 % of the predicted value were evaluated. Montelukast produced improvement in airway obstruction, daily symptom scores, total daily as-needed beta-agonist use, nocturnal awakenings, percentage of days and percentage of patients with asthma exacerbations, and urinary leukotriene E4 levels. These beneficial effects were similar to those produced by inhaled corticosteroids. There were no significant adverse effects requiring treatment discontinuation. Montelukast may be a well-tolerated and effective therapeutic option in 8 to 14-year-old patients with mild persistent asthma.


Molecular dynamics at the endocytic portal and regulations of endocytic and recycling traffics.
Endocytic and recycling pathways involve the transportation of soluble and transmembrane cargos to destinations within the cell or back to the plasma membrane for reuse. Common mechanistic themes for the traffic pathways in eukaryotic cells from yeast to mammalian cells are well-conserved, manifested by the molecular choreography of cargo segregation, membrane budding and coating, pinching off of the invaginated vesicle, cytoskeleton-mediated vesicle motility and fusion with target compartments. Here, we discuss recent insights into the spatiotemporal dynamics of endocytic machinery at the plasma membrane and the molecular details of bifurcating traffics at the endosome either to the lysosome or to the trans-Golgi network (TGN).


The time enzyme in melatonin biosynthesis in fish: Day/night expressions of three aralkylamine N-acetyltransferase genes in three-spined stickleback.
In vertebrates, aralkylamine N-acetyltransferase (AANAT; EC 126.96.36.199) is a time-keeping enzyme in melatonin (Mel) biosynthesis. Uniquely in fish, there are several AANAT isozymes belonging to two AANAT subfamilies, AANAT1 and AANAT2, which are encoded by distinct genes. The different substrate preferences, kinetics and spatial expression patterns of isozymes indicate that they may have different functions. In the three-spined stickleback (Gasterosteus aculeatus), there are three genes encoding three AANAT isozymes. In this study, for the first time, the levels of aanat1a, aanat1b and aanat2 mRNAs are measured by absolute RT-qPCR in the brain, eye, skin, stomach, gut, heart and kidney collected at noon and midnight. Melatonin levels are analysed by HPLC with fluorescence detection in homogenates of the brain, eye, skin and kidney. The levels of aanats mRNAs differ significantly within and among organs. In the brain, eye, stomach and gut, there are day/night variations in aanats mRNAs levels. The highest levels of aanat1a and aanat1b mRNAs are in the eye. The extremely high expressions of these genes which are reflected in the highest Mel concentrations at this site at noon and midnight strongly suggest that the eye is an important source of the hormone in the three-spined sticklebacks. A very low level of aanat2 mRNA in all organs may suggest that AANAT1a and/or AANAT1b are principal isozymes in the three-spine sticklebacks. A presence of the isozymes of defined substrate preferences provides opportunity for control of acetylation of amines by modulation of individual aanat expression and permits the fine-tuning of indolethylamines and phenylethylamines metabolism to meet the particular needs of a given organ.


Upper limb electromyographic analysis of manual wheelchair transfer techniques in individuals with spinal cord injury: A systematic review.
The objective of this study is to determine the upper limb muscle electromyographic (EMG) activity required during various manual wheelchair transfers in the population of spinal cord injury (SCI). This review included observational studies reporting the (EMG) activity of upper limb muscles during wheelchair transfers in people with SCI. We searched electronic databases and reference lists of relevant literature between 1995 and March 2022 with English language limits, yielding 3870 total articles. Two independent researchers performed data extraction and conducted quality assessment using two checklists, the Modified Downs and Blacks and National Heart, Lung, and Blood Institute for observational cohort and cross-sectional studies. After eligibility screening, seven studies were included in this review. The sample size ranged from 10 to 32 participants aged 31-47 years. They assessed four types of transfers and mostly evaluated six upper limb muscles were biceps, triceps, anterior deltoid, pectoralis major, latissimus dorsi and ascending fibres of the trapezius. The peak EMG value indicated that muscle recruitment varied in both upper limbs according to the task demand, and the highest activity was seen during the lift-pivot transfer phase. Because of the data heterogeneity, a meta-analysis of study results was not feasible. There were various ways of reporting the upper limb EMG muscle activity profile across all the included studies with a limited sample size. The crucial role of upper limb muscles during different types of manual wheelchair transfers was interpreted in this review. This is essential for predicting functional independence of individuals with SCI and warranting optimal rehabilitation strategies for wheelchair transfer skills.


Epinephrine restores platelet functions inhibited by ticagrelor: A mechanistic approach.
Ticagrelor, an antagonist of the platelet adenosine diphosphate (ADP)-P2Y12 receptor is recommended for patients with acute coronary syndromes. However, ticagrelor exposes to a risk of bleeding, the management of which is challenging because platelet transfusion is ineffective, and no antidote is yet available. We hypothesized that the vasopressor drug epinephrine could counter the antiplatelet effects of ticagrelor and restore platelet functions. We assessed in vitro the efficiency of epinephrine in restoring platelet aggregation inhibited by ticagrelor and investigated the underlying mechanisms. Washed platelet aggregation and secretion were measured upon stimulation by epinephrine alone or in combination with ADP, in the presence or absence of ticagrelor. Mechanistic investigations used P2Y1 and phosphoinositide 3-kinase (PI3K) inhibitors and included vasodilator-stimulated phosphoprotein (VASP) and Akt phosphorylation assays as well as measurement of Ca2+ mobilisation. We found that epinephrine restored ADP-induced platelet aggregation, but not dense granule release. Epinephrine alone failed to induce aggregation whereas it fully induced VASP dephosphorylation and Akt phosphorylation regardless of the presence of ticagrelor. In the presence of ticagrelor, blockage of the P2Y1 receptor prevented restoration of platelet aggregation by the combination of epinephrine and ADP, as well as intracellular Ca2+ mobilisation. In combination with ADP, epinephrine induced platelet aggregation of ticagrelor-treated platelets through inhibition of the cAMP pathway and activation of the PI3K pathway, thus enabling the P2Y1 receptor signalling and subsequent Ca2+ mobilisation. This proof-of-concept study needs to be challenged in vivo for the management of bleeding in ticagrelor-treated patients.


Finerenone and Heart Failure Outcomes by Kidney Function/Albuminuria in Chronic Kidney Disease and Diabetes.
In patients with type 2 diabetes (T2D), risks of cardiovascular mortality and heart failure (HF) increase with decreasing kidney function (estimated glomerular filtration rate [eGFR]) and increasing albuminuria (urine albumin-to-creatinine ratio [UACR]). Finerenone, a selective, nonsteroidal mineralocorticoid receptor antagonist, improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and T2D in FIDELITY (Finerenone in Chronic Kidney Disease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis). This study sought to evaluate the effects of finerenone on HF outcomes by eGFR and/or UACR categories. FIDELITY included 13,026 patients with T2D and CKD (UACR 30-5,000 mg/g and eGFR ≥25 mL/min/1.73 m2) randomized to finerenone or placebo. Time-to-event outcomes were first hospitalization for heart failure (HHF), cardiovascular death or first HHF, recurrent HHF, and cardiovascular death or recurrent HHF, analyzed in subgroups by baseline eGFR (<60 and ≥60 mL/min/1.73 m2) and/or UACR (<300 and ≥300 mg/g). Compared with placebo, finerenone significantly reduced risk of first HHF (HR: 0.78 [95% CI: 0.66-0.92]; P = 0.003), cardiovascular death or first HHF (HR: 0.83 [95% CI: 0.74-0.93]; P = 0.002), recurrent HHF (HR: 0.79 [95% CI: 0.64-0.96]; P = 0.021), and cardiovascular death or recurrent HHF (HR: 0.82 [95% CI: 0.72-0.95]; P = 0.006). The risk of outcomes increased across baseline eGFR and UACR categories; lowest incidences were seen in patients with an eGFR ≥60 mL/min/1.73 m2 and a UACR <300 mg/g. Finerenone improved HF outcomes irrespective of baseline eGFR and/or UACR categories (all P interaction values >0.10). Compared with placebo, finerenone improved HF-related outcomes in patients with CKD and T2D, with consistent benefits across eGFR and/or UACR categories. (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD], NCT02540993; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Chronic Kidney Disease [FIGARO-DKD], NCT02545049).


Synthesis of a New Chelating Iminophosphorane Derivative (Phosphazene) for U(VI) Recovery.
A new synthetic chelating N-hydroxy-N-trioctyl iminophosphorane (HTIP) was prepared through the reaction of trioctylphosphine oxide (TOPO) with N-hydroxylamine hydrochloride in the presence of a Lewis acid (AlCl3). Specifications for the HTIP chelating ligand were successfully determined using many analytical techniques, 13C-NMR, 1H-NMR, FTIR, EDX, and GC-MS analyses, which assured a reasonable synthesis of the HTIP ligand. The ability of HTIP to retain U(VI) ions was investigated. The optimum experimental factors, pH value, experimental time, initial U(VI) ion concentration, HTIP dosage, ambient temperature, and eluents, were attained with solvent extraction techniques. The utmost retention capacity of HTIP/CHCl3 was 247.5 mg/g; it was achieved at pH = 3.0, 25 °C, with 30 min of shaking and 0.99 × 10-3 mol/L. From the stoichiometric calculations, approximately 1.5 hydrogen atoms are released during the extraction at pH 3.0, and 4.0 moles of HTIP ligand were responsible for chelation of one mole of uranyl ions. According to kinetic studies, the pseudo-first order model accurately predicted the kinetics of U(VI) extraction by HTIP ligand with a retention power of 245.47 mg/g. The thermodynamic parameters ΔS°, ΔH°, and ΔG° were also calculated; the extraction process was predicted as an exothermic, spontaneous, and advantageous extraction at low temperatures. As the temperature increased, the value of ∆G° increased. The elution of uranium ions from the loaded HTIP/CHCl3 was achieved using 2.0 mol of H2SO4 with a 99.0% efficiency rate. Finally, the extended variables were used to obtain a uranium concentrate (Na2U2O7, Y.C) with a uranium grade of 69.93% and purity of 93.24%.


Analysis of monosaccharides, fatty constituents and rare O-acetylated sialic acids from gonads of the starfish Asterias rubens.
A previous study (Bergwerff et al., Biochimie 74 (1992) 25-37) reported that sialic acids present in Asterias rubens gonads were essentially composed of 8-methyl-N-glycolylneuraminic acid (Neu5Gc8Me), a large part of it being acetylated in position 9. Using GC/MS of heptafluorobutyrate derivatives (Zanetta et al., Glycobiology 11 (2001) 663-676) on the chloroform/methanol soluble and insoluble fractions, we showed that most sialic acids were found in the latter and demonstrated that all sialic acids were derived from N-glycolylneuraminic acid, most of them being 8-methylated, but that the majority were also acetylated in position 4 or 7 (or both positions). GC/MS analyses of the constituents liberated using acid-catalysed methanolysis verified that major glycoprotein-bound glycans were N-linked and of the gluco-oligomannosidic type. Major fatty acids were poly-unsaturated (especially C20:4) and long-chain bases were C22:1 phytosphingosine and C22:2 6-hydroxysphingenine. Major monosaccharides found in the chloroform/methanol extract (quinovose and fucose) were derived from steroidal saponins.


Influence of the dwarf mouse mutation on skeletal and cardiac myosin isoforms. Effect of one injection of thyroxine on skeletal and cardiac muscle phenotype.
The dwarf mutant is an autosomal recessive mutation of the mouse which causes a defective development of those anterior pituitary cells responsible for the production of thyroid-stimulating hormone, growth hormone, and prolactin. These mice are thus genetically hypothyroid and provide a model system in which one can investigate the influence of thyroid hormone on the transitions of the myosin heavy chain isoforms. We have carried out a qualitative and quantitative investigation of the myosin heavy chain isoforms present at various developmental stages and following one injection of 1 microgram of thyroxine. Myosin heavy chains were identified by nondissociating gel electrophoresis, localized by indirect immunofluorescence, and quantitated by the enzyme-linked immunosorbent assay technique. We find that in skeletal muscle, the appearance of the adult fast myosin heavy chain is severely retarded, that the neonatal myosin heavy chain is never totally eliminated, and that there is an overall increase in the number of fibers containing slow myosin heavy chain. In cardiac tissue the adult phenotype is never attained and beta-cardiac myosin heavy chain remains the predominant isoform. A single injection of 1 microgram of thyroxine was sufficient to cause a slight acceleration in the appearance of the adult fast myosin heavy chain in skeletal muscle, but only after 6-8 days. However, in the cardiac muscle, one injection of thyroxine resulted in a more rapid but transient expression of the alpha-cardiac myosin heavy chain, suggesting that the mechanism of action of thyroid hormone is different in these two tissues.


An 18-year review of sports groin injuries in the elite hockey player: clinical presentation, new diagnostic imaging, treatment, and results.
This is a retrospective study of 98 hockey players who underwent 107 surgical explorations for refractory lower abdominal and groin pain that prevented them from playing hockey at an elite level. Retrospective chart review combined with a complete follow-up examination and questionnaire. The players were treated in an ambulatory care university tertiary care centre. A total of 98 elite hockey players underwent 107 surgical groin explorations for intractable groin pain preventing their play. Follow-up was 100%. Each player had repair of a tear of the external oblique muscle and fascia reinforced by a Goretex mesh. The ilioinguinal nerve was resected in each patient. There was absence of groin pain on the return to play hockey at an elite level. In all, 97 of 98 players returned to play after the surgical procedures. No morbidity was attributed to division of the ilioinguinal nerve. Surgical exploration of the involved groin with repair of the torn external oblique muscle and division of the ilioinguinal nerve has resulted in resolution of refractory groin pain and return to play in the elite hockey player. The surgical procedure is associated with a low morbidity. Recent observations on dynamic ultrasound show promise in accurately diagnosing this injury.


Cation flux in the ehrlich ascites tumor cell. Evidence for Na+-for-Na+ and K+-for-K+ exchange diffusion.
In a previous study, evidence was presented for an external Na+-dependent, ouabain-insensitive component of Na+ efflux and an external K+-dependent component of K+ efflux in the Ehrlich ascites tumor cell. Evidence is now presented that these components are inhibited by the diuretic furosemide and that under conditions of normal extracellular Na+ and K+ they represent Na+-for-Na+ and K-+for-K+ exchange mechanisms. Using 86Rb to monitor K+ movements, furosemide is shown to inhibit an ouabain-insensitive component of Rb+ influx and a component of Rb+ efflux, both representing approx. 30 percent of the total flux. Inhibition of Rb+ efflux is greatly reduced by removal of extracellular K+. Furosemide does not alter steady-state levels of intracellular K+ and it does not prevent cells depleted of K+ by incubation in the cold from regaining K+ upon warming. Using 22Na to monitor Na+ movements, furosemide is shown to inhibit an ouabain-insensitive component of unidirectional Na+ efflux which represents approx. 22 percent of total Na+ efflux. Furosemide does not alter steady-state levels of intracellular Na+ and does not prevent removal of intracellular Na+ upon warming from cells loaded with Na+ by preincubation in the cold. The ability of furosemide to affect unidirectional Na+ and K+ fluxes but not net fluxes is consistent with the conclusion that these components of cation movement across the cell membrane represent one-for-one exchange mechanisms. Data are also presented which demonstrate that the uptake of alpha-aminoisobutyrate is not affected by furosemide. This indicates that these components of cation flux are not directly involved in the Na+-dependent amino acid transport system A.


Multimodality PET and Near-Infrared Fluorescence Intraoperative Imaging of CEA-Positive Colorectal Cancer.
Molecular imaging is a major diagnostic component for cancer management, enabling detection, staging of disease, targeting therapy, and monitoring the therapeutic response. The coordination of multimodality imaging techniques further enhances tumor localization. The development of a single agent for real-time non-invasive targeted positron emission tomography (PET) imaging and fluorescence guided surgery (FGS) will provide the next generation tool in the surgical management of cancer. The humanized anti-CEA M5A-IR800 "sidewinder" (M5A-IR800-SW) antibody-dye conjugate was designed with a NIR 800 nm dye incorporated into a PEGylated linker and conjugated with the metal chelate p-SCN-Bn-deferoxamine (DFO) for zirconium-89 PET imaging (89Zr, half-life 78.4 h). The dual-labeled 89Zr-DFO-M5A-SW-IR800 was evaluated for near infrared (NIR) fluorescence imaging, PET/MRI imaging, terminal tissue biodistribution, and blood clearance in a human colorectal cancer LS174T xenograft mouse model. The 89Zr-DFO-M5A-SW-IR800 NIR fluorescence imaging showed high tumor targeting with normal liver uptake. Serial PET/MRI imaging was performed at 24 h, 48 h, and 72 h and showed tumor localization visible at 24 h that persisted throughout the experiment. However, the PET scans showed higher activity for the liver than the tumor, compared to the NIR fluorescence imaging. This difference is an important finding as it quantifies the expected difference due to the sensitivity and depth of penetration between the 2 modalities. This study demonstrates the potential of a pegylated anti-CEA M5A-IR800-Sidewinder for NIR fluorescence/PET/MR multimodality imaging for intraoperative fluorescence guided surgery.


Bis(2-, 3-, 4-carboxyethylpyridinium) hexafluorosilicates as potential caries prophylactic agents.
Interaction of 2-, 3-, 4-carboxyethylpyridines (L1, L2, L3) with fluorosilicic acid results in the corresponding bis(pyridinium) hexafluorosilicates I-III, characterized by elemental analysis, IR, 1 H, 19 F nuclear magnetic resonance (NMR), and mass spectrometry, solubility data, and X-ray crystallography. Crystallographic data: Fdd2, Z = 8, a = 28.610(2) Å, b = 18.8378(14) Å, c = 7.3236(5) Å (I); P-1, Z = 1, a = 6.2712(4) Å, b = 7.1706(5) Å, c = 10.9721(7) Å, α = 102.514(6)°, β = 97.037(5)°, γ = 93.640(6)° (II); P21 /c, Z = 2, a = 10.0345(6) Å, b = 9.8734(5) Å, c = 9.4704(6) Å, β = 94.347(6)° (III). The dominant intermolecular contacts from the Hirshfeld surface analysis are H… F/F… H, H… H, and H… O/O… H with percentages of 33.3%-34.5%, 26.4%-30.0%, and 16.0%-21.8%. The infrared spectra for I-III exhibit stretching vibrations ν(N+ H) at 3300-3050 cm-1 ; stretching and deformation vibrations ν(SiF) and δ(SiF2 ) for [SiF6 ]2- anions are registered near 740 cm-1 and in the range of 480-440 cm-1 . In the 19 F NMR spectra of aqueous solutions of I-III, strong singlet signals of the [SiF6 ]2- anion were registered at δ(F) = -133.35 ppm (I), -131.43 ppm (II), -129.02 ppm (III) with two satellites due to the spin-spin interaction 29 Si-19 F (J(29 Si-19 F) = 107.5 Hz (II), 107.6 Hz (III)). I-III reveal high solubility in water and dimethyl sulfoxide and very poor solubility in methanol and ethanol. All compounds demonstrate noticeable anticaries activity and absence of hepatotoxic effects, and bis(3-carboxyethylpyridinium) hexafluorosilicate II displays the highest caries-preventive efficacy, which significantly exceeds values for the reference preparations, NaF and (NH4 )2 [SiF6 ].


A novel methodology for perception-based portfolio management.
Selecting and investing in stock market with right proportions is one of the major challenges. Majority of the investors end up losing their invested equity capital due to uncertainty in the market. The present study provides a novel framework for novice investors to construct portfolio based on multicriteria decision making techniques under fuzzy environment. The scores obtained from these techniques were used to introduce two non-dimensional parameters for categorization of risky and non-risky assets. Three perceptions portfolios were constructed based on the proposed non-dimensional parameters along with fractional lion clustering algorithm. In order to demonstrate the proposed framework, an illustrative application is included in equity portfolio selection. The returns and risks of these perception based portfolios are compared to major Index funds for validating the efficiency and are found to overpower the Index funds with significant margins by maintaining the risk comparable to Index funds. Further, Markowitz based efficient frontier is plotted for better understanding of optimal returns and risk for perception based investment.


An evaluation of training for lay providers in the use of Motivational Interviewing to promote academic achievement among urban youth.
This study examined training outcomes for lay service providers who participated in a Motivational Interviewing (MI) training program designed to help increase intrinsic motivation and academic achievement among urban low-income and minority youth. Seventeen lay academic advisors received 16 hours of training in MI. Two, two-hour booster sessions plus five, two- hour weekly group supervision sessions were conducted with lay advisors over a period of seven months. One-hundred percent of lay advisors (n =17) participated in all training, booster sessions and assessments. Seventy-one percent of lay advisors (n=12) completed all group supervision sessions and submitted tapes for review. MI training was associated with increased knowledge of MI principles among lay service providers; increased proficiency in responding to simulated clients in an MI consistent style; increased use of MI adherent behaviors in sessions with real clients and maintenance of high motivation to use MI from pretest to posttest. Although lay advisors increased their knowledge of MI, further training is required for advisors to increase competence in delivering MI. Overall, Implications for using MI in the context of school-based settings is discussed.


Marine n-3 fatty acids: basic features and background.
There is some evidence from epidemiology that intake of n-3 polyunsaturated fatty acids (PUFA) from seafood may protect against coronary artery disease (CAD). This hypothesis is further supported from animal data showing a beneficial effect of n-3 PUFA on thrombosis and atherosclerosis in animals fed fish oils in most, but not all, studies. There are several mechanisms by which an increased intake of marine n-3 PUFA may protect against CAD; the most universal finding is a reduction of plasma triglycerides. It is puzzling, however, that a very low amount of n-3 PUFA, with no known beneficial biochemical effects, seems to be cardioprotective. It has therefore been of paramount interest to perform clinical trials. Such evidence and trials are discussed in later chapters, and the results have been very encouraging.


[Effect of low-energy helium-neon laser on the biological properties of Mycobacterium tuberculosis].
The results of experimental studies of M. tuberculosis biological properties tested in guinea pigs which were subjected to different doses of helium-neon laser radiation are given. The functional evidence is compared with the results of electron microscopic study of the irradiated culture. The investigation revealed that laser radiation caused changes in biological properties of M. tuberculosis. A decrease in growth properties and virulence was found to be related to a radiation dose. It is suggested that a drop in the biological activity of M. tuberculosis under laser radiation be associated with its influence on the Mycobacterium lipid layer which contains a cord-factor and responsible for their virulence.


In vitro effect of burned pasture soil on eggs and free-living larvae of ruminant gastrointestinal nematodes.
Gastrointestinal nematodes are the most expensive agent of disease currently facing the livestock production industry. Spending the beginning of their life cycle as eggs and free-living larvae, nematodes are vulnerable to a multitude of external environmental factors. Fire is a naturally occurring force of nature that has both destructive and reconstructive effects on soil characteristics which nematode stages rely on for survival. The aim of this project was to evaluate in vitro the effect of burned pasture soil (200 °C and 500 °C) on the free-living stages of ruminant nematodes. We tested the effect of burned soil on the ability of eggs to hatch and produce infective larvae, and then tested survival of infective larvae within burned soil. Adding burned soil (500 °C) to larval cultures improved larval yield compared to larval cultures containing raw soil or soil burned at a lower heat (200 °C), and raw soil improved longer term survival of infective larvae. We were able to recover significantly more larvae from samples with low soil content either as raw or soil burned at 200 °C, when compared with samples with soil burned at 500 °C. This study has shown that the survival of gastrointestinal nematodes at the L3 stage is negatively impacted by the addition of soil burned at 500 °C. Although this temperature is closest to that of a medium intensity wildfire, which is a typically destructive process in agriculture, it reduces the number of infective GIN larvae available for animals to ingest. These experiments enable us to address in vitro if post-fire soil conditions alter the number of infective larvae available on pasture, and thus the infectivity of the pasture to livestock.


Complex formation equilibria of polyamine ligands with copper(II) and zinc(II).
A comprehensive study of the protonation equilibria of a series of polyamine ligands along with their complex formation equilibria with Cu2+ and Zn2+ is reported in this work. The primary aim of this study has been the achievement of homogeneous thermodynamic data on these ligands, in order to evaluate their influence on the homeostatic equilibria of essential metal ions (Cu2+ and Zn2+) in biological fluids. These polyamines are largely used as linkers in the building of chelating agents for iron overload. Potentiometric and spectrophotometric techniques were used for the characterization of protonation and complex formation constants. In addition, the characterization of the formed complexes is discussed together with selected solid-state crystal structures, remarking the influence of the length of the chain and of the linear or tetradentate tripod nature of the polyamine ligands on the stability of the complexes.


Cowpea mosaic virus RNAs have neither m7GpppN ... nor mono-, di- or triphosphates at their 5' ends.
32P-labeled cowpea mosaic virus (CPMV) RNAs were analyzed for their 5' termini by three different fingerprinting standard procedures. These analyses showed unequivocally that CPMV RNAs lack a structure like m7GpppN ... at their 5' termini. In addition, neither mono-, di- or triphosphorylated [(p)(p)pN ....] termini were found in the respective fingerprints. The inability to label the 5' termini treatment with gamma-32P-ATP and polynucleotide kinase, either per se or after pretreatment with alkaline phosphatase, strongly suggests the absence of a free 5'-OH and a free 5'-phosphate at the 5' terminal nucleotide in CPMV RNAs. The various analyses also showed that no 2' -O-methylated nucleotides, N6-methyladenosines or pseudo-uridines are present in CPMV RNAs.


Current activities and future directions of the cancer registration system in Japan.
Cancer surveillance is essential for implementing evidence-based cancer control programs, and cancer registries provide core information for cancer surveillance. In 2006, the Cancer Control Act was approved in Japan and it is clear that the national government will take the initiative in promoting cancer control programs, including cancer registries. There are three types of cancer registries: population-based, hospital-based, and site-specific cancer registries. Although each has its own aim and function, the population-based cancer registry is the only one that can provide cancer incidence data. Currently, 35 of the 47 prefectures in Japan, and one city (Hiroshima) have population-based cancer registries; however, there are two major issues with these registries, i.e., standardization of procedures and completeness of incidence data. In order to improve the level of standardization, the Japan Cancer Surveillance Research Group has developed a standard registry system in which standardized procedures are implemented; this system is currently being disseminated into several registries. To improve completeness of incidence data, it is planned, first, to establish hospital-based cancer registries at designated cancer-care hospitals (a newly developed hospital network to provide standardized high-quality cancer care). This strategy will be effective in rural areas, where most cancer patients are covered by designated cancer-care hospitals, but in urban areas additional action will be needed. In 2006, the Center for Cancer Control and Information Services (CIS) was launched at the National Cancer Center. It is expected that the CIS will play a central role in improving the quality of the cancer surveillance system in Japan.


Preparation of 4-([2,2':6',2″-terpyridin]-4'-yl)-N,N-diethylaniline Ni(II) and Pt(II) complexes and exploration of their in vitro cytotoxic activities.
Two metal complexes of NiLCl2 (1) and [PtLCl]Cl (2) with 4-([2,2':6',2″-terpyridin]-4'-yl)-N,N-diethylaniline (L) were synthesized and characterized. 1 and 2 exhibited selective cytotoxicity to T-24 cells more than L, compared with the normal liver cell line (HL-7702). Various experiments showed that L, 1 and 2 caused T-24 cell cycle arrest at S phase, as shown by the down-regulation of cdc25 A, cyclin A, cyclin B and CDK2 and the up-regulation of p21, p27 and p53. Furthermore, complexes 1 and 2, especially complex 2, acted as telomerase inhibitors targeting c-myc G-quadruplex DNA and triggered cell apoptosis. In addition, 1 and 2 also caused mitochondrial dysfunction. Taken together, we found that 1 and 2 exerted their cytotoxic activity mainly via inhibiting telomerase by interaction with c-myc quadruplex and disruption of mitochondrial function.


Synthesizing diffusion tensor imaging from functional MRI using fully convolutional networks.
Medical image synthesis can simulate a target modality of interest based on existing modalities and has the potential to save scanning time while contributing to efficient data collection. This study proposed a three-dimensional (3D) deep learning architecture based on a fully convolutional network (FCN) to synthesize diffusion-tensor imaging (DTI) from resting-state functional magnetic resonance imaging (fMRI). fMRI signals derived from white matter (WM) exist and can be used for assessing WM alterations. We constructed an initial functional correlation tensor image using the correlation patterns of adjacent fMRI voxels as one input to the FCN. We considered T1-weighted images as an additional input to provide an algorithm with the structural information needed to synthesize DTI. Our architecture was trained and tested using a large-scale open database dataset (training n = 648; testing n = 293). The average correlation value between synthesized and actual diffusion tensors for 38 WM regions was 0.808, which significantly improves upon an existing study (r = 0.480). We also validated our approach using two open databases. Our proposed method showed a higher correlation with the actual diffusion tensor than the conventional machine-learning method for many WM regions. Our method synthesized DTI images from fMRI images using a 3D FCN architecture. We hope to expand our method of synthesizing various other imaging modalities from a single image source.


SMC1A facilitates gastric cancer cell proliferation, migration, and invasion via promoting SNAIL activated EMT.
Structural maintenance of chromosomes protein 1 A (SMC1A) is a crucial subunit of the cohesion protein complex and plays a vital role in cell cycle regulation, genomic stability maintenance, chromosome dynamics. Recent studies demonstrated that SMC1A participates in tumorigenesis. This reseach aims to explore the role and the underlying mechanisms of SMC1A in gastric cancer (GC). RT-qPCR and western blot were used to examine the expression levels of SMC1A in GC tissues and cell lines. The role of SMC1A on GC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) were analyzed. Furthermore,the mechanism of SMC1A action was investigated. SMC1A was highly expressed in GC tissues and cell lines. The high expression of SMC1A indicated the poor overall survival of GC patients from Kaplan-Meier Plotter. Enhancing the expression of SMC1A in AGS cells remarkably promoted cell proliferation in vitro and in vivo, migration and invasion, Conversely, knockdown of SMC1A in HGC27 cells inhibited cell proliferation, migration and invasion. Moreover, it's observed that SMC1A promoted EMT and malignant cell behaviors via regulating SNAIL. Our study revealed that SMC1A promotes EMT process by upregulating SNAIL, which contributes to gastric cancer cell proliferation, migration and invasion. Therefore, targeting SMC1A may be a potential strategy to improve GC therapy.


Effects of vitamin A supplementation on child mortality: evidence from Nepal's 2001 Demographic and Health Survey.
To assess the effect of Nepal's vitamin A supplementation programme on child mortality at age 12-59 months. Logistic regression, applied to retrospective data from Nepal's 2001 Demographic and Health Survey. After a number of potentially confounding variables are controlled, the effect of 100% community-level vitamin A coverage since the child's birth, relative to no coverage, is to reduce the odds of dying at age 12-59 months by slightly more than half (OR = 0.47, P = 0.03). The estimated beneficial effect of vitamin A supplementation on child mortality is larger than that found in most earlier clinical studies. This larger effect may be due mainly to the other health-related activities undertaken by the female community health volunteers who distribute vitamin A capsules.


Developmental toxicity and cardiac effects of butyl benzyl phthalate in zebrafish embryos.
Phthalic acid esters (PAEs), commonly called phthalates, have become ubiquitous environment pollutants. Studies have focused on reproductive toxicity, neurotoxicity, teratogenicity, tumourigenesis, and mutagenesis of phthalates. However, relatively little is known about the phthalates effects on the heart. Butyl benzyl phthalate (BBP), a member of PAEs, is classified by the US Environmental Protection Agency as a priority environmental pollutant. We studied the developmental toxicity of BBP, especially its effects on the heart development, in zebrafish (Danio rerio) embryos. Embryos at 4hr post-fertilization (hpf) were exposed to 0, 0.1, 0.6 and 1.2mg/L BBP until 72hpf. BBP caused abnormalities in embryo morphology, including yolk-sac edema, spinal curvature, tail deformity, uninflated swim bladder and cardiac defects. Exposure to 0.6mg/L BBP significantly increased the malformation rate, caused growth inhibition, increased the cardiac malformation rate as well as the distance between the sinus venosus (SV) and bulbus arteriosus (BA), and reduced the heart rate of embryos. Exposure to 1.2mg/L BBP significantly affected all endpoints, except survival rate at 24hpf. To preliminarily elucidate the potential mechanism of heart developmental toxicity caused by BBP, we examined the expression of two genes related to heart development, Nkx2.5 and T-box transcription factor 5, by real-time quantitative PCR. The expression of the two genes was dose-dependently downregulated with BBP. BBP could induce developmental toxicity, with adverse effects on the heart development in zebrafish embryos, and alter the expression of genes related to heart development.


Apologizing for the past: German science and Nazi medicine.
Recently, religious organisations, governments and public institutions have begun to offer apologies for historical wrongs. Can they legitimately do so? Departing from the tendency, Professor Hubert Markl, President of the Max Planck Society, has offered strong reasons for not apologizing for the crimes of medical scientists who experimented on human subjects during the Nazi era. He argues that only the perpetrators can meaningfully apologize. Markl's position is considered and rejected in favour of the view that apologies by proxy for historical wrongs are justifiable and should be made by institutions that have the authority to do so.


Biochemical and autoradiographic study of cerebral protein synthesis with [18F]-and [14C]fluorophenylalanine.
Fluorine-18-labeled ortho or para isomers of L-fluorophenylalanine were used in double-label experiments together with L-[3H]phenylalanine for amino acid incorporation into cerebral proteins of Mongolian gerbil brain. It was demonstrated by qualitative regional comparison of the 18F and 3H autoradiographic images that L-p-[18F]fluorophenylalanine is incorporated into proteins and exhibits a regional cerebral protein synthesis pattern. To a minor extent, L-p-fluorophenyl[3-14C]alanine and L-o-[18F]fluorophenylalanine are hydroxylated in vivo to form labeled tyrosine or tyrosine analogues that are incorporated into cerebral proteins as well. The advantage and validity of the application of L-p-[18F]fluorophenylalanine with positron emission tomography for noninvasive studies of cerebral protein synthesis in humans are evaluated on the basis of an experimental animal approach.


Direct injection green chromatographic method for simultaneous quantification of amoxicillin and amikacin in maternity hospital wastewater (Sagar, India).
Amoxicillin (AMO) and amikacin (AMK) are broad-spectrum antibiotics that are most preferably given post-delivery (normal and cesarian) in the maternity hospitals located in Sagar city (Madhya Pradesh), India. Both the antibiotics make their way through sewage/drainage systems into the environment in the form of metabolized and unmetabolized compounds. Growing concern about the contamination of wastewater by antibiotics requires fast, sensitive and eco-friendly techniques. Therefore a simple, rapid and environmental friendly chromatographic method has been developed for simultaneous determination of AMO and AMK in maternity hospital wastewater samples. A micellar liquid chromatographic (MLC) method was developed with a C18 column (250 mm × 4.6 mm), sodium dodecyl sulphate (SDS; 0.15 M), 1-butanol (7%) as a modifier, pH 5 and photo diode detector (PDA) at 270 nm and 256 nm for AMO and AMK respectively. The method was fast with analysis time below 9 min. In the present MLC method, linearities (r > 0.998), limits of quantification in the range of 0.02-0.04 μg/mL, repeatabilities, and intermediate precision below 4.9% were adequate for the quantification of AMO and AMK. The proposed method can be utilized to detect and quantify both the antibiotics in various samples by hospitals, pharmaceutical companies, pollution control board, municipal corporations, etc.


Unraveling the deterioration mechanism of dough during whole wheat flour processing: A case study of gluten protein containing arabinoxylan with different molecular weights.
This study aims to the effect of arabinoxylan (AX) on gluten quality. Ultrasonic treatment is utilized to degrade water unextractable arabinoxylans (WUAX) from wheat bran, which obtains three molecular weights of AX. The results indicate that the shear viscosity and particle size of AX were decreased and the ζ-potential was increased after ultrasonic treatment. Analysis of the gluten shows that the free SH of gluten with 6% WUAX, SAX10, and SAX30 (ultrasound duration for 10 min and 30 min) was increased by 51.9%, 48.1%, and 17.0%, respectively, whereas the free SH of 2% SAX30-gluten was increased by 19.8%. Furthermore, WUAX impaired the viscoelasticity properties of gluten, while SAX30 improved the viscoelasticity of gluten. WUAX induced the open, fragile, and discontinuous structure of gluten. On the contrary, SAX30 promoted the formation of the compact and regular gluten structure. Overall, ultrasonic as a non-chemical treatment could be used to improve the quality of whole-wheat foods.


Expectant Management Before In vitro Fertilization in Women Aged 39 or Above and Unexplained Infertility Does Not Decrease Live Birth Rates Compared to Immediate Treatment.
Unexplained infertile couples can have further expectant management before starting assisted reproductive treatments. However, ovarian reserve and in vitro fertilization (IVF) outcomes rapidly decline after 39 years or more. It is thus important to clarify whether a waiting policy is also appropriate for women of advanced age. Couples who had access to a waiting list for approximately 1 year before receiving reimbursed public IVF were compared with those paying for access to immediate treatment. To allow for comparisons between these two strategies, we followed up couples who opted to pay for 1 year after the last embryo transfer from their first cycle. We calculated the proportion of live births in both groups and compared these using logistic regression models and a two-sample Z test for equality of proportions. Six hundred thirty-five couples were evaluated. Out of 359 couples in the immediate group, 70 (19.5%) had a live birth of which 11 after natural conception and 59 after IVF. Out of 276 couples in the waiting group, 57 (20.7%) had a live birth of which 37 after natural conception and 20 after IVF. There was no statistically significant difference between the two strategies in terms of the crude cumulative live birth rate (cLBR). The adjusted odds ratio of 0.69 (95%CI:0.39-1.22) did not change this conclusion as our sensitivity analyses. The cLBR for the 'waiting before IVF' and the 'immediate' strategies were similar. Further studies are needed to better characterize couples affected by unexplained infertility in order to individualize treatment strategies.


Effect of hydrophobic detergent on lipid absorption in the rat and on lipid and sterol balance in the swine.
The effects of hydrophobic detergent on fat absorption in the rat were determined under two conditions. In the first, a high dose of detergent was given in a test lipid meal to rats not previously exposed to this agent. A marked delay in digestion of triglyceride in association with malabsorption was observed. In the second, a relatively small dose of detergent was given to rats pretreated with dietary supplement of detergent. No delay of digestion or uptake was observed but absorbed, reesterified lipid was noted to accumulate in the mucosa. Morphologic studies showed abnormal collections of fat droplets in the enterocytes. Sterol and fat balance studies were done on swine on chronic dietary detergent supplement. Mild steatorrhea with excess fecal excretion of neutral sterols was observed. It is concluded that hydrophobic detergents can have an inhibitory effect on both intraluminal and intracellular events of fat absorption.


Heart failure in rheumatoid arthritis: rates, predictors, and the effect of anti-tumor necrosis factor therapy.
We sought to determine the frequency of heart failure in patients with rheumatoid arthritis, and to determine its predictors, particularly the use of anti-tumor necrosis factor (TNF) therapy. Rheumatoid arthritis (n = 13,171) and osteoarthritis (n = 2568) patients were studied during a 2-year period ending in June 2002. The diagnosis of heart failure was based on self-report or review of medical records. Propensity scores were used to adjust for the risk of anti-TNF (infliximab and etanercept) prescription. Heart failure was more common among patients with rheumatoid arthritis (3.9% [n = 461]) than in those with osteoarthritis (2.3% [n = 87]), after adjusting for differences in demographic characteristics. Patients with rheumatoid arthritis had similar risk factors for heart failure (e.g., hypertension, prior myocardial infarction, diabetes, advanced age) as persons in population-based studies. Heart failure was significantly (P <0.05) less common in anti-TNF-treated patients (3.1% [180/5832]) than in the remaining patients (3.8% [281/7339]), even after adjusting for baseline differences. In the absence of pre-existing cardiovascular disease, the risk of heart failure was low (0.4% [24/6251]) and was not related to anti-TNF therapy. Our results suggest that rheumatoid arthritis increases the risk of heart failure, which may be ameliorated by anti-TNF therapies.


Metered-dose inhalers: do emergency health care providers know what to teach?
To evaluate the ability of emergency health care providers and patients to demonstrate the proper use of metered-dose inhalers (MDIs). Prospective cross-sectional survey. Five Midwestern community teaching hospitals. One hundred eighty-five health care providers, comprising emergency medicine house staff (n = 60), attending emergency physicians (n = 50), and ED nurses (n = 75). Also recruited were 100 consecutive ED patients with clinical history of asthma being treated with at least one MDI for more than 3 months. We surveyed patients and health care providers to assess their knowledge of and ability to use a conventional MDI. The subject's technique of using a placebo inhaler was graded by a trained observer using a checklist of six essential steps. Forty-one percent (76 of 185) of health care providers and 49% (49 of 100) of ED asthma patients performed at least five steps correctly (P = .24). There were no significant differences in performance scores among the emergency medicine house staff (42%), attending emergency physicians (34%), and ED nurses (45%). Only 15% of all health care providers and 17% of asthma patients were able to describe how to estimate the amount of medicine left in the canister. These results suggest that many patients use MDIs improperly. Emergency physicians, house staff, and nurses responsible for instructing patients in optimal inhaler use may lack even rudimentary skills with these devices.


Electrically induced release of radiolabeled histamine from rat hippocampal slices: opposing roles for H1- and H2-receptors.
Rat hippocampal slices were preloaded with 3H-histamine and superfused with physiological medium and electrically stimulated in the absence (S1) and in the presence (S2) of drugs. The electrically evoked 3H-overflow consisted mainly of histamine, was Ca++ dependent and completely blocked by tetrodotoxin, all pointing towards an impulse triggered neuronal release. Mepyramine, promethazine and diphenhydramine the H1-antagonists, inhibited the stimulation evoked histamine release in a dose dependent manner. Burimamide and cimetidine, the H2-antagonists, enhanced the stimulation induced release of histamine whereas dimaprit, the H2-antagonist, had the opposite effect. Histamine by itself did not influence its own release. The observations indicate an opposing role for H1- and H2-receptors in modulating spike induced histamine release and represents a functional consequence of the stimulation of the receptors.


New approaches, bioavailability and the use of chelates as a promising method for food fortification.
Food fortification has been used for many years to combat micronutrient deficiencies; the main challenge with food fortification is the combination of a bioavailable, affordable fortificant with the best (food) vehicle as a carrier to reach at-risk populations. This paper considers mineral deficiencies, especially iron, food fortification, target populations, and the use of chelates in food fortification, as well as different types of mineral-chelate complexes, advantages and limitations of previous trials, methods used for analysis of these complexes, bioavailability of minerals, factors influencing it, and methods particularly those in vitro for predicting outcomes. Three innovative methods (encapsulation, nanoparticulation, and chelation) were explored, which aim to overcome problems associated with conventional fortification, especially those affecting organoleptic properties and bioavailability; but often lead to the emergence of new limitations (for example instability, impracticality and high costs) requiring further research.


Evolution of complexity in the viral world: the dawn of a new vision.
Recent sequencing of the genomes of numerous large viruses provide for unprecedented opportunities to study the emergence and evolution of complexity in the virus world. This special issue of Virus Research explores trends in the evolution of complex genomes in most major classes of viruses.


Adherence to the Mediterranean diet and incident frailty: Results from a longitudinal study.
The aim of the current prospective study was to examine the relationship between adherence to the Mediterranean diet and incident frailty. 1075 Greek community-dwelling older adults from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) were included in the present longitudinal analysis. Adherence to the Mediterranean diet was evaluated through the MedDietScore, calculated from the information participants provided on a validated food frequency questionnaire. Frailty was assessed using two multidomain tools: the Frailty Index (FI) and the Tilburg Frailty Indicator (TFI). Analysis of the incidence of frailty as a function of the baseline MedDietScore was performed using Cox proportional hazards models. Additionally, Generalized Estimating Equations (GEE) models were used to explore whether the baseline MedDietScore was associated with the change in the total number of frailty criteria met by participants over time. In testing for a dose-response association between Mediterranean diet and frailty, the MedDietScore was treated either as a continuous variable or as tertiles of low, medium and high adherence to MeDi. 176 and 131 participants developed incident frailty, as measured with the FI and TFI respectively. Each unit of MedDietScore was associated with a 5% (ΗR 0.95, 95% CI 0.91-0.99, p = 0.012) and 10% (ΗR 0.90, 95% CI 0.86-0.95, p ≤ 0.001) decrease in the risk of incident frailty when measured with the FI and TFI respectively. Compared with participants reporting low adherence to the Mediterranean diet (lowest tertile), those with high adherence (highest tertile) had a 41% (ΗR 0.59, 95% CI 0.38-0.91, p = 0.017) and a 57% (ΗR 0.43, 95% CI 0.27-0.70, p ≤ 0.001) lower risk of incident frailty as measured with the FI and TFI respectively. After excluding from the analyses participants diagnosed with dementia at baseline or follow-up, the same results were obtained: each unit of MedDietScore was associated with a 5% (HR 0.95 CI 0.91-0.99, p = 0.023) and a 10% (HR 0.90 CI 0.86-0.94, p ≤ 0.001) decrease in the risk of incident frailty as measured with the FI and TFI respectively. The present longitudinal study showed that non-frail community-dwelling older adults with high adherence to the Mediterranean dietary pattern had a significantly lower incidence of frailty.


Phylogenetic Analysis of Torque Teno Virus in Thalassemic Children in Egypt.
Torque teno virus (TTV) is a ubiquitous virus that is commonly associated with blood transfusion. The main aims of this study were to evaluate the incidence of TTV in polytransfused children with thalassemia and to determine for the first time the prevalent TTV genotypes in Egypt. TTV was detected in 2 groups by nested PCR: the first group comprised 200 children with thalassemia, and the second included age- and sex-matched healthy children with no history of blood transfusion. TTV was detected in 60 and 57%, respectively, of the children with thalassemia and the healthy children. Among the TTV-positive children with thalassemia, 71.6% were HCV positive. No hepatitis B surface antigen was detected in the thalassemic children. Significant elevations of alanine transaminase and aspartate transaminase were found in TTV-positive patients with thalassemia compared to TTV-negative patients. Phylogenetic analysis of sequenced TTV isolates showed close relationships to genotypes 1 and 2. TTV is highly prevalent among children with thalassemia in Egypt, with a relatively high infection rate also detected among healthy children.


The influence of proximity of prenatal services on small-for-gestational-age birth.
Some studies suggest that prenatal services may decrease the risk of poor fetal growth for full-term infants, but have not examined the influence of the availability of community health and social services. The availability of prenatal services may have a stronger effect among women already at high risk of a small-for-gestational-age (SGA) birth. Singleton full-term (> or = 37 weeks gestation) California births for 1997-98 (n = 744,736) were geocoded to maternal Census tract of residence. Women were placed into one of three demographic risk groups utilizing combinations of maternal age, marital status, parity, and education. SGA was defined as birthweight less than the 10th percentile for gestational age. Locations of WIC sites, prenatal care providers, and perinatal outreach programs were geocoded. Multilevel logistic regression was used to model the influence of community health care services on SGA, adjusting for additional maternal and community factors. There was no association between SGA and community services available for either high- or low-risk women, in either unadjusted or adjusted models. The addition of maternal prenatal care utilization to models did not change the results. Maternal residence near prenatal services was not associated with SGA, regardless of demographic risk; other community factors may warrant consideration.


Overexpression of Rb and E2F-1 in ataxia-telangiectasia lymphocytes.
AT cells exhibit defective cell cycle regulation following DNA damage. Previous studies have shown that induction of p53 and p21 proteins are delayed in response to ionizing radiation, resulting in the failure of G1/S checkpoint in AT cells. In this study, further investigation of the molecular mechanisms underlying G1/S phase progression in AT cells was conducted. Exponentially growing normal and AT cells were exposed to 2 Gy of ionizing radiation and the expression levels and functional activities of Rb and E2F-1 proteins were determined. We observed overexpression of hyperphosphorylated Rb and E2F-1 proteins in AT cells, which was unaffected post-irradiation. Furthermore, gel shift assays showed that E2F-1-DNA binding was constitutive in AT cells, whereas it was inhibited in control cells following exposure to ionizing radiation. The data suggests that abnormalities in the function of Rb and E2F-1 proteins may also be responsible for the failure of AT cells to arrest in the G1/S checkpoint in response to DNA damage.


Nitrate consumption preserves HFD-induced skeletal muscle mitochondrial ADP sensitivity and lysine acetylation: A potential role for SIRT1.
Dietary nitrate supplementation, and the subsequent serial reduction to nitric oxide, has been shown to improve glucose homeostasis in several pre-clinical models of obesity and insulin resistance. While the mechanisms remain poorly defined, the beneficial effects of nitrate appear to be partially dependent on AMPK-mediated signaling events, a central regulator of metabolism and mitochondrial bioenergetics. Since AMPK can activate SIRT1, we aimed to determine if nitrate supplementation (4 mM sodium nitrate via drinking water) improved skeletal muscle mitochondrial bioenergetics and acetylation status in mice fed a high-fat diet (HFD: 60% fat). Consumption of HFD induced whole-body glucose intolerance, and within muscle attenuated insulin-induced Akt phosphorylation, mitochondrial ADP sensitivity (higher apparent Km), submaximal ADP-supported respiration, mitochondrial hydrogen peroxide (mtH2O2) production in the presence of ADP and increased cellular protein carbonylation alongside mitochondrial-specific acetylation. Consumption of nitrate partially preserved glucose tolerance and, within skeletal muscle, normalized insulin-induced Akt phosphorylation, mitochondrial ADP sensitivity, mtH2O2, protein carbonylation and global mitochondrial acetylation status. Nitrate also prevented the HFD-mediated reduction in SIRT1 protein, and interestingly, the positive effects of nitrate ingestion on glucose homeostasis and mitochondrial acetylation levels were abolished in SIRT1 inducible knock-out mice, suggesting SIRT1 is required for the beneficial effects of dietary nitrate. Altogether, dietary nitrate preserves mitochondrial ADP sensitivity and global lysine acetylation in HFD-fed mice, while in the absence of SIRT1, the effects of nitrate on glucose tolerance and mitochondrial acetylation were abrogated.


Effect of body size and body composition on survival in peritoneal dialysis patients.
Using 24-hour urinary creatinine excretion as a measure of muscle mass, we examined whether body composition influences the survival of incident peritoneal dialysis (PD) patients. We hypothesized that patients with high body mass index (BMI) and low muscle mass might be considered to have high levels of body fat. Using serum creatinines and creatinine clearances reported on Medical Evidence Form 2728, 24-hour urinary creatinine was calculated in 10 140 incident PD patients with normal (18.5 - 24.9 kg/m2) or high (> or = 25 kg/m2) BMI. Patients were classified as low and normal/high muscle mass groups based on the 25th percentile of 24-hour urinary creatinine (0.64 g/day). In multivariable parametric survival models, compared to the normal BMI-normal/high muscle mass patients, high BMI-normal/high muscle mass patients had lower hazard of all-cause [hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.83 - 0.97] and cardiovascular (HR 0.88, 95% CI 0.79 - 0.97) death; high BMI patients with low muscle mass had higher hazard of all-cause (HR 1.29, 95% CI 1.17 - 1.42) and cardiovascular (HR 1.21, 95% CI 1.06 - 1.39) death. Both body size and body composition influence survival of incident PD patients. As incident PD patients with high BMI and normal or high muscle mass have the best survival, PD patients should be encouraged to gain muscle mass rather than fat mass.


Comparative evaluation of MALDI-TOF MS and 16S rRNA gene sequencing for the identification of clinically relevant anaerobic bacteria: critical evaluation of discrepant results.
The main study objective was to evaluate the correlation between matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing results for the identification of anaerobes. A retrospective study was conducted of all anaerobic bacteria isolated from clinically significant specimens. MALDI-TOF (Bruker Byotyper) and 16S rRNA gene sequencing were performed in all strains. Identifications were considered correct when the concordance with gene sequencing was ≥99%. The study included 364 isolates of anaerobic bacteria: 201 (55.2%) Gram-negative and 163 (44.8%) Gram-positive, mostly belonging to the genus Bacteroides. Isolates were largely obtained from blood cultures (128/35.4%) and intra-abdominal samples (116/32.1%). Overall, 87.3% of isolates were identified at species level using the version 9 database (89.5% of Gram-negative and 84.6% of Gram-positive anaerobic bacteria). All isolates belonging to the species B. fragilis sensu stricto were correctly identified by MALDI-TOF MS, but five cases of Phocaeicola (Bacteroides) dorei were misidentified as Phocaeicola (Bacteroides) vulgatus; all Prevotella isolates were correctly identified at the genus level, and most were correctly identified at the species level. Among Gram-positive anaerobes, 12 Anaerococcus species were not identified by MALDI-TOF MS, while six cases identified as Peptoniphilus indolicus were found to belong to other genera/species. MALDI-TOF is a reliable technique for identifying most anaerobic bacteria, although the database needs frequent updating to identify rare, infrequent, and newly discovered species.


A novel tropoelastin-based resorbable surgical mesh for pelvic organ prolapse repair.
Pelvic organ prolapse is a common condition that affects 1 in 4 women across all age groups. It is mainly caused by vaginal birth injury and can be exacerbated by obesity and increased age. Until recently, treatment strategies often used non-degradable synthetic meshes for reconstructive surgery. However, owing to their frequent, unacceptable rate of adverse events such as mesh erosion, transvaginal meshes have been banned in many countries. Recent reports have highlighted the urgent need for biocompatible design of meshes for a safe and effective treatment in the long term. This study reports the design and evaluation of a novel, elastin based degradable mesh using an ovine model of POP as a potential surgical treatment. Elastin is a protein component of the ECM and provides elasticity to tissues throughout the body. Tropoelastin, the monomer subunit of elastin, has been used with success in electrospun constructs as it is a naturally cell interactive polymer. Biomaterials that incorporate tropoelastin support cell attachment and proliferation, and have been proven to encourage elastogenesis and angiogenesis in vitro and in vivo. The biological properties of tropoelastin were combined with the physical properties of PCL, a degradable synthetic polymer, with the aim of producing, characterizing and assessing the performance of continuous tropoelastin:PCL electrospun yarns. Using a modified spinneret electrospinning system and adjusting settings based on relative humidity, four blends of tropoelastin:PCL yarns were fabricated with concentration ratios of 75:25, 50:50, 25:75 and 0:100. Yarns were assessed for ease of manufacture, fibrous architecture, protein/polymer content, yarn stability - including initial tropoelastin release, mechanical strength, and ability to support cell growth. Based on overall favorable properties, a mesh woven from the 50:50 tropoelastin:PCL yarn was implanted into the vagina of a parous ewe with vaginal wall weakness as a model of pelvic organ prolapse. This mesh showed excellent integration with new collagen deposition by SEM and a predominant M2 macrophage response with few pro-inflammatory M1 macrophages after 30 days. The woven tropoelastin:PCL electrospun mesh shows potential as an alternative to non-degradable, synthetic pelvic organ prolapse mesh products.


In-depth approach for identifying crash causation patterns and its implications for pedestrian crash prevention.
A pedestrian crash occurs due to a series of contributing factors taking effect in an antecedent-consequent order. One specific type of antecedent-consequent order is called a crash causation pattern. Understanding crash causation patterns is important for clarifying the complicated growth of a pedestrian crash, which ultimately helps recommend corresponding countermeasures. However, previous studies lack an in-depth investigation of pedestrian crash cases, and are insufficient to propose a representative picture of causation patterns. In this study, pedestrian crash causation patterns were discerned by using the Driving Reliability and Error Analysis Method (DREAM). One hundred and forty-two pedestrian crashes were investigated, and five pedestrian pre-crash scenarios were extracted. Then, the crash causation patterns in each pre-crash scenario were analyzed; and finally, six distinct patterns were identified. Accordingly, 17 typical situations corresponding to these causation patterns were specified as well. Among these patterns, the pattern related to distracted driving and the pattern related to an unexpected change of pedestrian trajectory contributed to a large portion of the total crashes (i.e., 27% and 24%, respectively). Other patterns also played an important role in inducing a pedestrian crash; these patterns include the pattern related to an obstructed line of sight caused by outside objects (9%), the pattern that involves reduced visibility (13%), and the pattern related to an improper estimation of the gap distance between the vehicle and the pedestrian (10%). The results further demonstrated the inter-heterogeneity of a crash causation pattern, as well as the intra-heterogeneity of pattern features between different pedestrian pre-crash scenarios. Conclusions and practical applications: Essentially, a crash causation pattern might involve different contributing factors by nature or dependent on specific scenarios. Finally, this study proposed suggestions for roadway facility design, roadway safety education and pedestrian crash prevention system development.


IMA: an R package for high-throughput analysis of Illumina's 450K Infinium methylation data.
The Illumina Infinium HumanMethylation450 BeadChip is a newly designed high-density microarray for quantifying the methylation level of over 450 000 CpG sites within human genome. Illumina Methylation Analyzer (IMA) is a computational package designed to automate the pipeline for exploratory analysis and summarization of site-level and region-level methylation changes in epigenetic studies utilizing the 450K DNA methylation microarray. The pipeline loads the data from Illumina platform and provides user-customized functions commonly required to perform exploratory methylation analysis for individual sites as well as annotated regions. IMA is implemented in the R language and is freely available from http://www.rforge.net/IMA.


[Cloning of Blastocystis sp subtype 3 small-subunit ribosomal DNA].
Different sub-types or genetic variations of Blastocystis sp. are thought to play a role in the differential symptoms caused by the parasite or asymptomatic cases. In this study, it was aimed to clone a fragment of SSUrDNA gene of Blastocystis from a patient in order to define its phylogenetic subtype. In this study, DNA isolation from the stool of a Blastocystis infected patient was performed. Blastocystis specific primers were used to amplify a SSUrDNA genomic fragment. The amplified DNA fragment was cloned into a plasmid and sequenced using plasmid specific primers. The obtained DNA sequence was analyzed using BLAST and a phylogenetic tree was constructed using the software MEGA. It was found that the Blastocystis isolate in our study is subtype 3. Cloning and sequencing of the target genomic region is suggested for phylogenetic analysis studies.


Civilian Airway Trauma: A Single-Institution Experience.
Injuries to the airway in the neck and thorax are uncommon, but may be potentially life threatening. The objective of this study is to determine the clinical characteristics and outcomes for patients with airway injury. From 1974 to 2014, a prospectively entered trauma database at a Level 1 trauma center was accessed to identify patients with injuries to the larynx, cervical trachea, or thoracic airway. Hospital charts were reviewed to obtain data on demographics, presentation, injury management, in-hospital and long-term morbidity and in-hospital mortality. Multivariate logistic regression was used to estimate predictors of mortality and long-term vocal cord morbidity. Data are expressed as N (%). One hundred and twenty patients were included (median injury severity score: 19 [interquartile range: 10-27]). There were 65 (54 %) blunt and 55 (46 %) penetrating injuries, with 90 (75 %) suffering multiple injuries. Sixteen (13 %) patients died from associated injuries (7: in ER; 9: after admission). Injuries were located in the cervical airway [101 (84 %)], thoracic airway [21 (18 %)], or both [2 (2 %)]. Eighty-six (72 %) patients were managed surgically. Predictors of in-hospital mortality included hemodynamic instability (OR 6.54, 95 % CI 1.11-37.14), GCS < 8 upon presentation (OR 4.35, 95 % CI 3.24-5.41), and head trauma (OR 4.10, 95 % CI 1.91-6.30). Fracture of cricoid or thyroid cartilages was a strong predictor of long-term vocal cord injury (OR 3.93, 95 % CI 1.25-12.59). Airway trauma remains a major challenge for early diagnosis, airway control, and management of both acute life-threatening injury and long-term morbidity.


Anti-atherosclerotic function of Astragali Radix extract: downregulation of adhesion molecules in vitro and in vivo.
Atherosclerosis is considered to be a chronic inflammatory disease. Astragali Radix extract (ARE) is one of the major active ingredients extracted from the root of Astragalus membranaceus Bge. Although ARE has an anti-inflammatory function, its anti-atherosclerotic effects and mechanisms have not yet been elucidated. Murine endothelial SVEC4-10 cells were pretreated with different doses of ARE at different times prior to induction with tumor necrosis factor (TNF)-α. Cell adhesion assays were performed using THP-1 cells and assessed by enzyme-linked immunosorbent assay, western blotting and immunofluorescence analyses to detect the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), phosphorylated inhibitor of κB (p-iκB) and nuclear factor (NF)-κB. We also examined the effect of ARE on atherosclerosis in the aortic endothelium of apolipoprotein E-deficient (apoE(-/-)) mice. TNF-α strongly increased the expression of VCAM-1 and ICAM-1 accompanied by increased expression of p-iκB and NF-κB proteins. However, the expression levels of VCAM-1 and ICAM-1 were reduced by ARE in dose- and time-dependent manners, with the strongest effect at a dose of 120 μg/ml incubated for 4 h. This was accompanied by significantly decreased expression of p-iκB and inhibited activation of NF-κB. Immunofluorescence analysis also revealed that oral administration of ARE resulted in downregulation of adhesion molecules and decreased expression of macrophages in the aortic endothelium of apoE(-/-) mice. ARE could suppress the inflammatory reaction and inhibit the progression of atherosclerotic lesions in apoE(-/-) mice. This study demonstrated that ARE might be an effective anti-inflammatory agent for the treatment of atherosclerosis, possibly acting via the decreased expression of adhesion molecules.


Limb immobilization alters functional electrophysiological parameters of sciatic nerve.
Immobilization, used in clinical practice to treat traumatologic problems, causes changes in muscle, but it is not known whether changes also occur in nerves. We investigated the effects of immobilization on excitability and compound action potential (CAP) and the ultrastructure of the rat sciatic nerve. Fourteen days after immobilization of the right leg of adult male Wistar rats (n=34), animals were killed and the right sciatic nerve was dissected and mounted in a moist chamber. Nerves were stimulated at a baseline frequency of 0.2 Hz and tested for 2 min at 20, 50, and 100 Hz. Immobilization altered nerve excitability. Rheobase and chronaxy changed from 3.13 ± 0.05 V and 52.31 ± 1.95 µs (control group, n=13) to 2.84 ± 0.06 V and 59.71 ± 2.79 µs (immobilized group, n=15), respectively. Immobilization altered the amplitude of CAP waves and decreased the conduction velocity of the first CAP wave (from 93.63 ± 7.49 to 79.14 ± 5.59 m/s) but not of the second wave. Transmission electron microscopy showed fragmentation of the myelin sheath of the sciatic nerve of immobilized limbs and degeneration of the axon. In conclusion, we demonstrated that long-lasting leg immobilization can induce alterations in nerve function.


Modeling premature occurrence of acute coronary syndrome with atherogenic and thrombogenic risk factors and gene markers in extended families.
The interaction between genetic and environmental risk factors in determining premature cardiovascular events has been largely investigated in case-control association studies. By contrast, few family based analyses have been performed so far. From a series of 2936 subjects aged 45-64, we selected probands who died for a premature (<50 years) ischemic heart disease (IHD) and with at least one family member with a history of IHD also occurring under the age of 50. Ninety-four families from 32 pedigrees including 296 subjects were identified. In this population, we analyzed the relationship between background risk factors [age, gender, the G1691A polymorphisms of factor V gene, the C677T polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, the 844ins68bp polymorphisms of the cystathionine-beta-synthase (CBS) gene, and the apolipoprotein E (APOE) polymorphisms] and environmental risk factors, both atherogenic (smoke, hypertension, diabetes, dyslipidemia, obesity) and thrombogenic (smoke, homocysteine, fibrinogen) by a Markov block-recursive modeling approach. None of the studied polymorphisms had an independent direct effect on the risk of IHD. As opposed to atherogenic factors, thrombogenic factors (homocysteine and fibrinogen) turned out to be possible mediators of the indirect effect of the MTHFR gene on IHD risk (OR: 1.30; 95% CI: 1.01-1.69, for every 8 mm increase in plasma levels of homocysteine in TT-carriers compared with CT/CC-carriers (OR: 1.11; 95% CI: 1.01-1.22), for every 20 g L(-1) increase in plasma levels of fibrinogen in TT-carriers compared with CT/CC-carriers). Plasma levels of homocysteine and fibrinogen may be interpreted as intermediate factors mediating the effect of predisposing genes on the risk premature cardiovascular disease.