Heterogeneous dynamics of ionic liquids from molecular dynamics simulations.
Molecular dynamics simulations have been performed to study the complex and heterogeneous dynamics of ions in ionic liquids. The dynamics of cations and anions in 1-ethyl-3-methyl imidazolium nitrate (EMIM-NO(3)) are characterized by van Hove functions and the corresponding intermediate scattering functions F(s)(k,t) and elucidated by the trajectories augmented by the use of singular spectrum analysis (SSA). Several time regions are found in the mean squared displacement of the ions. Change in the slope in a plot of the diffusion coefficient against temperature is found at around 410 K in the simulation. Heterogeneous dynamics with the presence of both localized ions and fast ions capable of successive jumps were observed at long time scales in the self-part of the van Hove functions and in the trajectories. Non-Gaussian dynamics are evidenced by the self-part of the van Hove functions and wave number dependence of F(s)(k,t) and characterized as Levy flights. Successive motion of some ions can continue even after several nanoseconds at 370 K, which is longer than the onset time of diffusive motion, t(dif). Structure of the long time dynamics of fast ions is clarified by the phase space plot of the successive motion using the denoised data by SSA. The continual dynamics are shown to have a long term memory, and therefore local structure is not enough to explain the heterogeneity. The motion connecting localized regions at about 370 K is jumplike, but there is no typical one due to local structural changes during jump motion. With the local motion, mutual diffusion between cation and anion occurs. On decreasing temperature, mutual diffusion is suppressed, which results in slowing down of the dynamics. This "mixing effect of cation and anion" is compared with the "mixed alkali effect" found in the ionics in the ionically conducting glasses, where the interception of paths by different alkali metal ions causes the large reduction in the dynamics [J. Habasaki and K. L. Ngai, Phys. Chem. Chem. Phys. 9, 4673 (2007), and references herein]. Although a similar mechanism of the slowing down is observed, strong coupling of the motion of cation and anion prevents complete interception unless deeply supercooled, and this explains the wide temperature region of the existence of the liquid and supercooled liquid states in the ionic liquid.


A Surprisingly Simple Electrostatic Model Explains Bent Versus Linear Structures in M(+)-RG2 Species (M = Group 1 Metal, Li-Fr; RG = Rare Gas, He-Rn).
It is found that a simple electrostatic model involving competition between the attractive dispersive interaction and induced-dipole repulsion between the two RG atoms performs extremely well in rationalizing the M(+)-RG2 geometries, where M = group 1 metal and RG = rare gas. The Li(+)-RG2 and Na(+)-RG2 complexes have previously been found to exhibit quasilinear or linear minimum-energy geometries, with the Na(+)-RG2 complexes having an additional bent local minimum [A. Andrejeva, A. M. Gardner, J. B. Graneek, R. J. Plowright, W. H. Breckenridge, T. G. Wright, J. Phys. Chem. A, 2013, 117, 13578]. In the present work, the geometries for M = K-Fr are found to be bent. A simple electrostatic model explains these conclusions and is able to account almost quantitatively for the binding energy of the second RG atom, as well as the form of the angular potential, for all 36 titular species. Additionally, results of population analyses are presented together with orbital contour plots; combined with the success of the electrostatic model, the expectation that these complexes are all physically bound is confirmed.


A descriptive study on demographic and behavioral characteristics of males and their responses to a male involvement intervention in Blantyre, Malawi.
Male involvement (MI) remains a key factor in the enrollment and retention of pregnant women in the Prevention of Mother to child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) services. The objective of this study was to describe the characteristics of men who accompanied their partners for PMTCT services and secondly, describe the reported reasons for the non-reporting by men for the services in Blantyre, Malawi. All men included in this analysis were partners of pregnant women enrolled in a MI in PMTCT randomized controlled trial (RCT), which took place in Blantyre, Malawi from 14 June 2013 to 24 February 2014. After randomization women were asked to invite their male partners for PMTCT services either through an invitation card or word of mouth invite. Descriptive statistics were tabulated using Stata. Of the 462 women randomized, 109 (23.59%) women came back to the clinic with their male partner following the intervention. The majority, 307 (66.5%) women returned to the clinic without their partners. Although most men accepted the intervention, some failed to accompany their partners because of work obligations, a lack of interest in accompanying their partners for the service, and others promised to report at the next clinic visit. The characteristics of men that reported were similar in the two groups, suggesting that demographic characteristics may not greatly influence their decision to be involved in PMTCT services. There is need to develop more flexible strategies to include men in PMTCT programmes.


Complete genome sequence of Haemophilus somnus (Histophilus somni) strain 129Pt and comparison to Haemophilus ducreyi 35000HP and Haemophilus influenzae Rd.
Haemophilus somnus can be either a commensal of bovine mucosal surfaces or an opportunistic pathogen. Pathogenic strains of H. somnus are a significant cause of systemic disease in cattle. We report the genome sequence of H. somnus 129Pt, a nonpathogenic commensal preputial isolate, and the results of a genome-wide comparative analysis of H. somnus 129Pt, Haemophilus influenzae Rd, and Haemophilus ducreyi 35000HP. We found unique genes in H. somnus 129Pt involved in lipooligosaccharide biosynthesis, carbohydrate uptake and metabolism, cation transport, amino acid metabolism, ubiquinone and menaquinone biosynthesis, cell surface adhesion, biosynthesis of cofactors, energy metabolism, and electron transport. There were also many genes in common among the three organisms. Our comparative analyses of H. somnus 129Pt, H. influenzae Rd, and H. ducreyi 35000HP revealed similarities and differences in the numbers and compositions of genes involved in metabolism, host colonization, and persistence. These results lay a foundation for research on the host specificities and niche preferences of these organisms. Future comparisons between H. somnus 129Pt and virulent strains will aid in the development of protective strategies and vaccines to protect cattle against H. somnus disease.


Bioluminescence Method for In Vitro Screening of Plasmodium Transmission-Blocking Compounds.
The sporogonic stage of the life cycle of Plasmodium spp., the causative agents of malaria, occurs inside the parasite's mosquito vector, where a process of fertilization, meiosis, and mitotic divisions culminates in the generation of large numbers of mammalian-infective sporozoites. Efforts to cultivate Plasmodium mosquito stages in vitro have proved challenging and yielded only moderate success. Here, we describe a methodology that simplifies the in vitro screening of much-needed transmission-blocking (TB) compounds employing a bioluminescence-based method to monitor the in vitro development of sporogonic stages of the rodent malaria parasite Plasmodium berghei Our proof-of-principle assessment of the in vitro TB activity of several commonly used antimalarial compounds identified cycloheximide, thiostrepton, and atovaquone as the most active compounds against the parasite's sporogonic stages. The TB activity of these compounds was further confirmed by in vivo studies that validated our newly developed in vitro approach to TB compound screening.


Evaluating construct equivalence of youth depression measures across multiple measures and multiple studies.
Construct equivalence of measures across studies is necessary for synthesizing results when combining data in meta-analysis or integrative data analysis. We discuss several assumptions required for construct equivalence, and review methods using individual-level data and item response theory (IRT) analysis for detecting or adjusting for violations of these assumptions. We apply IRT to data from 7 measures of depressive symptoms for 4,283 youth from 16 randomized prevention trials. Findings indicate that these data violate assumptions of conditional independence. Bifactor IRT models find that depression measures contain substantial reporter variance, and indicate that a single common factor model would be substantially biased. Separate analyses of ratings by youth find stronger evidence for construct equivalence, but factor invariance across sex and age does not hold. We conclude that data synthesis studies employing measures of youth depression should analyze results separately by reporter, explore more complex approaches to integrate these different perspectives, and explore methods that adjust for sex and age differences in item functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Fillet proximate composition, lipid quality, yields, and organoleptic quality of Mediterranean-farmed marine fish: A review with emphasis on new species.
Species diversification in Mediterranean mariculture involves various important fish that contribute to the diet of many human populations. These include meagres (Sciaenidae), flatfishes, mullets, and various sparids. Their quality aspects (yields, fillet proximate composition, and lipid quality) are discussed in this review. Their filleting yield is mostly 40-45%. The viscerosomatic index ranges from 1.5% to 14%, depending on species. Low muscle fat contents of flatfishes and meagres differentiate them from the rest of the farmed species. Farmed fish contain high n-3 polyunsaturates fatty acids (PUFA; 12.3-36.3% vs. 5.48-37.2% in the wild) and have higher muscle fat and n-6 PUFA contents (mainly 18:2 n-6) than their wild counterparts. The aquaculture management, diet, and season can affect fillet composition and fatty acids, while season (i.e. food availability and maturation) largely affects lipid quality in wild fish. Data on the sensory quality of Mediterranean-farmed species are mainly limited to whether specific management differentiates the sensory quality; thus, further development of tools for sensory analysis is required. Observations on the quality features in farmed Mediterranean fish indicate that species diversification can also provide product diversification based on different commercial weights and fillet quality specifications.


Clinically significant drug interactions among HIV-infected patients receiving antiretroviral therapy.
We conducted a cross sectional study of the outpatient medical records of 1000 HIV-infected patients receiving antiretroviral therapy (ART) in 2011 to determine the incidence of clinically significant drug interactions (CSDI). The severities of the CSDI were graded following the Micromedex" 2.0 database and the Department of Health and Human Services (DHHS) 2012 HIV treatment guidelines. Three hundred thirty-five patients (34%) had 554 episodes of CSDI. Of which 337 episodes (61%), 163 episodes (29%) and 54 episodes (10%) had grades 2, 3 and 4 severity CSDI, respectively. The CSDI were caused by protease inhibitor (PI)-based drug regimens in 79%, by efavirenz-based regimens in 34% and by nevirapine-based regimens in 10% (p<0.001). The three most common grade 4 CSDI were: a PI with simvastatin (n=24), simvastatin with gemfibrozil (n=24) and didanosine with allopurinol (n=2). The three most common grade 3 CSDI were: a PI with a statin drug except simvastatin (n=56), fenofibrate with a statin drug (n=28) and amlodipine with simvastatin (n=14). On multivariate analysis, risk factors associated with CSDI were: receiving a PI-based regimen (OR 14.44; 95% CI: 9.10-22.88), having dyslipidemia (OR 3.94; 95% CI: 1.89-8.21), having >5 items prescribed at a time (OR 1.80; 95% CI: 1.23-2.63), seeing a doctor >4 times a year (OR 1.72; 95% CI: 1.20-2.46), having hypertension (OR 0.60; 95% CI: 0.37-0.98), having a duration of receiving ART of >5 years (OR 0.46; 95% CI: 0.28-0.77) and having a CD4 count of >200 cells/mm3 (OR 0.46; 95%CI: 0.26-0.84). CSDI were common among HIV-infected patients receiving ARV in our outpatient clinic. Patients having a low CD, count, having dyslipidemia, receiving PI-based ART, having a frequent number of visits per year and having a large number of items prescribed at each visit had a greater chance of a CSDI.


Intraoperative development of pulmonary thromboembolism in a bedridden patient owing to a pelvic bone fracture with negative preoperative computed tomography pulmonary angiographic findings: A case report.
Pulmonary thromboembolism (PTE) is a potentially life-threatening condition with high morbidity and mortality, and computed tomographic pulmonary angiography (CTPA) is an important diagnostic tool for patients in whom PTE is suspected; however, intraoperative PTE is very difficult to diagnose and often has a rapid clinical course. We experienced a case of intraoperative PTE with persistent tachycardia refractory to conventional treatments despite negative preoperative CTPA findings. A 53-year-old man with a pelvic bone fracture who had been on bed rest for 10 days underwent open reduction and internal fixation under general anesthesia. He remained tachycardic (heart rate of 120 beats/min) despite treatments with fluid resuscitation, analgesics, and beta-blockers. Preoperative CTPA, computed tomography (CT) venography, and transthoracic echocardiography showed no signs of deep vein thrombosis and PTE. However, the levels of D-dimer were elevated. After the start of the surgery, tachycardia (heart rate between 100 and 110 beats/min) could not be treated with fluid resuscitation. Systolic blood pressure was maintained between 90 and 100 mm Hg using continuous infusion of phenylephrine. Ninety minutes after the surgery, systolic and diastolic blood pressures suddenly dropped from 100/60 to 30/15 mm Hg with a decrease in end-tidal carbon dioxide concentration from 29 to 13 mm Hg and development of atrial fibrillation. Arterial blood gas analysis revealed hypercapnia. Under the suspicion of PTE, cardiopulmonary resuscitation (CPR) was immediately initiated. Three CPR cycles raised the blood pressure back to 90/50 mm Hg with sinus tachycardia (115 beats/min). Transesophageal echocardiography showed right ventricular dysfunction and paradoxical septal motion. However, emboli were not found. Postoperative chest CT revealed massive PTE in both pulmonary arteries. Immediately, surgical embolectomy was performed uneventfully. The patient was discharged from the hospital 1 month later without any complications. The patient with moderate risk for PTE (heart rate > 95 beats/min and immobilization, surgery under general anesthesia, and lower limb fracture within 1 month) should be closely monitored and managed intraoperatively even if preoperative CTPA findings are negative. The development of PTE needs to be expected if tachycardia is refractory to conventional treatments.


Collective Domain Motion Facilitates Water Transport in SGLT1.
The human sodium-glucose cotransporter protein (SGLT1) is an important representative of the sodium solute symporters belonging to the secondary active transporters that are critical to the homeostasis of sugar, sodium, and water in the cell. The underlying transport mechanism of SGLT1 is based on switching between inward- and outward-facing conformations, known as the alternating access model, which is crucial for substrate transport, and has also been postulated for water permeation. However, the nature of water transport remains unclear and is disputed along the passive and active transport, with the latter postulating the presence of the pumping effect. To better examine the water transport in SGLT1, we performed a series of equilibrium all-atom molecular dynamics simulations, totaling over 6 μs of sample representative conformational states of SGLT1 and its complexes, with the natural substrates, ions, and inhibitors. In addition to elucidating the basic physical factors influencing water permeation, such as channel openings and energetics, we focus on dynamic flexibility and its relationship with domain motion. Our results clearly demonstrate a dependence of instantaneous water flux on the channel opening and local water diffusion in the channel, strongly supporting the existence of a passive water transport in SGLT1. In addition, a strong correlation found between the local water diffusion and protein domain motion, resembling the "rocking-bundle" motion, reveals its facilitating role in the water transport.


Ay-4166 increases the sensitivity of insulin secretion to glucose in isolated perfused rat pancreas.
To study the effect of a therapeutic dose (3 microM) of AY-4166 on the glucose-stimulated insulin secretion, the rat pancreas was perfused with 5 to 15 mM glucose. AY-4166 did not affect the basal insulin secretion at 5 mM glucose, and increased the first and second phases of insulin secretion stimulated by 7.5 to 15 mM glucose. The dose-response curve of the insulin secretion to glucose was shifted to the left side by AY-4166. These results suggest that AY-4166 ist not a stimulator releasing insulin independently of glucose concentrations, but a potentiator of insulin secretion.


Nosocomial spread of OXA-58-positive carbapenem-resistant Acinetobacter baumannii isolates in a paediatric hospital in Greece.
Twelve non-repetitive Acinetobacter baumannii isolates producing the carbapenem-hydrolysing oxacillinase OXA-58 were recovered from patients in the same paediatric hospital in Athens, Greece, between November 2003 and May 2005. All isolates were clonally related, but the bla(OXA-58) gene was not always plasmid-located and there were variations in the DNA sequences surrounding the OXA-58 gene in different isolates. This study emphasises the importance of the bla(OXA-58) carbapenemase gene in conferring carbapenem resistance among A. baumannii isolates in Greece.


Layer-by-Layer-Coated Cellulose Fibers Enable the Production of Porous, Flame-Retardant, and Lightweight Materials.
New sustainable materials produced by green processing routes are required in order to meet the concepts of circular economy. The replacement of insulating materials comprising flammable synthetic polymers by bio-based materials represents a potential opportunity to achieve this task. In this paper, low-density and flame-retardant (FR) porous fiber networks are prepared by assembling Layer-by-Layer (LbL)-functionalized cellulose fibers by means of freeze-drying. The LbL coating, encompassing chitosan and sodium hexametaphosphate, enables the formation of a self-sustained porous structure by enhancing fiber-fiber interactions during the freeze-drying process. Fiber networks prepared from 3 Bi-Layer (BL)-coated fibers contain 80% wt of cellulose and can easily self-extinguish the flame during flammability tests in vertical configuration while displaying extremely low combustion rates in forced combustion tests. Smoke release is 1 order of magnitude lower than that of commercially available polyurethane foams. Such high FR efficiency is ascribed to the homogeneity of the deposited assembly, which produces a protective exoskeleton at the air/cellulose interface. The results reported in this paper represent an excellent opportunity for the development of fire-safe materials, encompassing natural components where sustainability and performance are maximized.


[Drug-induced glaucoma].
Glaucoma is seen as a heterogeneous group of diseases characterized by optical neuropathy with associated visual field loss; one of the main risk factors for its development is increased intraocular pressure (IOP). In the case of drug-induced glaucoma (DIG), patients develop elevated IOP, optic neuropathy and visual field defects associated with the use of certain drugs. Corticosteroids are one of the most well-known classes of drugs that can cause an increase in IOP through the open-angle mechanism. Drug-induced glaucoma, which develops similarly to open-angle glaucoma, can also be caused by some non-steroidal anti-inflammatory agents, antibodies to the endothelial growth factor, etc. Classes of drugs that can cause angle-closure glaucoma include topical anticholinergic or sympathomimetic drops, tricyclic antidepressants, monoamine oxidase inhibitors, antihistamines, antiparkinsonian drugs, antipsychotic drugs, antispasmodics. Products containing sulfa group drugs can cause DIG due to a different closing angle mechanism involving a forward rotation of the ciliary body. It is important for medical practitioners to be aware of this unwanted drug reaction in order to prevent, detect and treat DIG. In the case of drug-induced increase in IOP, if the underlying disease allows discontinuation of drugs, this measure usually leads to normalization of IOP. In cases when the patient's IOP does not normalize after discontinuation of steroids or when they must continue to take corticosteroids, the administration of topical drugs for the treatment of glaucoma should be considered.


Mechanism of trichloroethylene-induced elevation of individual serum bile acids. I. Correlation of trichloroethylene concentrations to bile acids in rat serum.
The temporal relationship between trichloroethylene (TRI) and individual serum bile acids (SBA) has been investigated to gain insight into the mechanism of solvent-induced increases in SBA. Male Sprague-Dawley rats were treated with 1 mmol/kg TRI in corn oil, while control rats received only corn oil. Blood samples were collected from the abdominal aorta at 2, 4, 8, and 16 hr after dosing. Individual SBA were determined by high-performance liquid chromatography (HPLC). Liver and blood concentrations of TRI and one of its metabolites, trichloroethanol (TCEOH), were determined by gas chromatography. SBA levels reached their peak at 4 hr and returned to control levels by 16 hr. There was a relationship between SBA levels and TRI concentrations, which were also at their peak 4 hr after dosing. By 16 hr the levels were undetectable. However, peak blood concentrations of TCEOH were reached 8 hr after dosing, and remained high at 16 hr. Cholic acid and taurocholic acid showed the highest levels of bile acids. Some other bile acids were also elevated, including deoxycholic acid, taurodeoxycholic acid, ursodeoxycholic acid, chenodeoxycholic acid, and taurochenodeoxycholic acid. Determination of total bile acids in serum using an enzymatic/colorimetric method showed a similar pattern of response to that obtained with the HPLC analysis. The data are consistent with TRI having a rapid and specific effect on SBA levels by a mechanism other than liver cell damage.


The variant of pri-mir-26a-1 polymorphism is associated with decreased risk of betel quid-related oral premalignant lesions and oral squamous cell carcinoma.
This case-control study evaluated the association of the single nucleotide polymorphism rs7372209 (T>C) in pri-mir-26a-1 with the risk and progression of betel quid (BQ)-related oral premalignant lesions (OPLs) and oral squamous cell carcinoma (OSCC). In total, 597 BQ chewers were recruited: 196 healthy controls, 241 patients with OPLs, and 160 patients with OSCC. Genotypes were determined using the TaqMan real-time assay. The C/T + T/T genotypes and T allele in pri-mir-26a-1 were correlated with a decreased risk of BQ-related OPLs (P = .038 and .005, respectively), oral leukoplakia (P = .01 and .001, respectively), and advanced-stage OSCC (P = .021 and .004, respectively). The effects of the C/T + T/T genotypes and T allele on the decreased risk of OPLs were potent in the older age group (both Pinteraction < .001), heavy smokers (Pinteraction ≤ .003 and .006, respectively) and alcohol drinkers (Pinteraction ≤ .004 and .001, respectively). Furthermore, among patients with OSCC, the C/T + T/T genotypes and T allele were associated with a decreased risk of advanced pathologic stage (P = .032) and lymph node involvement (P = .017). BQ chewers carrying the T allele or C/T + T/T genotypes in pri-mir-26a-1 may have a decreased risk of oral leukoplakia, OPLs, and advanced-stage OSCC.


Amino- and Sulfo-Bifunctionalized Metal-Organic Frameworks: One-Pot Tandem Catalysis and the Catalytic Sites.
New MIL-101 metal-organic frameworks (MOFs) dually functionalized with amino and sulfo groups were fabricated by postsynthetic modification and used to catalyze one-pot deacetalization-Knoevenagel condensation. We proved that the MOFs take the zwitterionic form, with the catalytic acid site being the ammonium group rather than the sulfo one. The acid and base concentrations in the materials are correlated, and the ratio can be readily tuned to achieve optimal catalytic performance.


Formation of Defence Primary Healthcare: a new way of delivering firm base primary healthcare.
Following the Strategic Defence and Security Review of 2010, the UK Surgeon General was directed to merge the delivery of primary healthcare from the three single Service organisations to a unified Defence Primary Healthcare. Although front line clinical staff were to be preserved, considerable savings were to be made in headquarters staff. This was one of the largest UK military medicine changes in delivery for a generation. The changes were completed on time with the transfer of UK and overseas general practice, specialist community services and dentistry, with a later requirement to add healthcare for the Reserves. The first years of this initiative have been remarkably successful, and Defence Primary Healthcare (DPHC) has progressively increased performance in all the QOF criteria measured by Defence Statistics.


Doppler sonographic detection of reverse twin-twin transfusion after intrauterine death of the donor.
We report a "stuck" twin, in which a reverse blood shunt from the recipient to the donor was detected by Doppler sonography after death of the donor. This acute reverse transfusion caused intrauterine fetal distress and severe neonatal anemia of the surviving recipient. We believe that acute hemodynamic change after death of one fetus, in addition to causing a derangement in coagulation, causes immediate danger or subsequent organ damage for the surviving co-twin.


Wheelchair-mounted robotic arm to hold and move communication device.
Some individuals with disabilities who use wheelchairs utilize communication devices to control their environment. Such devices are typically mounted on a fixed arm in a manner that obstructs the line of sight of a user when navigating the wheelchair. Some individuals with disabilities who utilize wheelchairs have limited or no control of arm or head movement. Design of a user-controlled robotic arm which moves the communication device in and out of the user's line of sight would enable navigation of the wheelchair without removal of the communication device. Such a robotic device will be controlled by a push-button jelly switch. Positioning of this activation device will be located behind the user's left elbow. Design of a single-axis, rotary robotic arm to be installed on a Quantum Q6 Edge wheelchair is ongoing, and will be completed by February 2014. A working prototype will be completed before April 2014. It is expected that upon completion of the robotic arm, the device will successfully move an 8 lb. Dynavox Maestro communication device in and out of a user's line of sight by single-switch activation initiated by a user. The design presented in this report is patent pending.


[Diphtheria and Renaissance Spanish physicians].
Along the history of medicine, diphtheria has been the cause of many deadly epidemics. Up to the incorporation of microbiology in medicine and the definition of diphtheria provided by Bretonneau in 1826, this disease was studied with all types of sore throut into the galenic system. Spanish physicians in Renaissance started the way to its systematisation, taking it off the rest of sore throat types, with other laryngeal diseases, as it was known later as "croup", giving it the name of "garrotillo". They were the first to describe some important questions about this disease, as the specificity of the diphtheric pseudomembranes, the ineffective potential of salivary drops and the palsy of the soft palate.


Endoscopic colostomy with percutaneous colopexy: an animal feasibility study.
Indications for colostomy in colorectal diseases are obstruction of the large bowel, such as in cancer, diverticular disease in the acute phase, post-radiotherapy enteritis, complex perirectal fistulas, anorectal trauma and severe anal incontinence. Some critically ill patients cannot tolerate an exploratory laparotomy, and laparoscopic assisted colostomy also requires general anesthesia. To evaluate the feasibility, safety and efficacy of performing colostomy assisted by colonoscopy and percutaneous colopexy. Five pigs underwent endoscopic assisted colostomy with percutaneous colopexy. Animals were evaluated in post-operative days 1, 2, 5 and 7 for feeding acceptance and colostomy characteristics. On day 7 full colonoscopy was performed on animals followed by exploratory laparotomy. Average procedure time was 27 minutes (21-54 min). Postoperative mobility and feeding of animals were immediate after anesthesia recovery. Position of the colostomy, edges color, appearance of periostomal area, as well as its function was satisfactory in four animals. Retraction of colostomy was present in one pig. The colonoscopy and laparotomy control on the seventh day were considered as normal. A bladder perforation that was successfully repaired through the colostomy incision occurred in one pig. The main limitation of this study is its experimental nature. Endoscopic assisted colostomy with percutaneous colopexy proves to be a safe and effective method with low morbidity for performing colostomy in experimental animals, with possible clinical application in humans.


Elicitation of specific cytotoxic T cells by immunization with malaria soluble synthetic polypeptides.
We have studied the immunogenicity of Plasmodium falciparum circumsporozoite (CS) protein-derived synthetic polypeptides in mice. These synthetic peptides correspond to the N- and the C-terminal domains 22-125 and 289-390, respectively of the P. falciparum 7G8 isolate CS protein expressed on the sporozoite surface. They comprise what is believed to be the mature protein, except for the central repetitive B cell domain. BALB/c (H-2d) mice were immunized s.c. with 50 micrograms soluble CS polypeptides emulsified in IFA. After a single immunization, CS-specific helper and cytotoxic T lymphocytes (CTLs) could be obtained. The resultant CTLs obtained by in vitro restimulation of primed lymph node (LN) cells recognized H-2Kd target cells in the presence of short synthetic peptides defined in the present study. These epitopes are contained within the N- and C-terminal regions of the CS protein, and correspond to sequences 39-47 and 333-342. In addition, these CTLs can specifically lyse H-2d target cells transfected with the CS gene. These results suggest that, by immunization of mice with large soluble CS synthetic polypeptides in IFA, it is possible to obtain MHC class I-restricted T cell responses specific for the CS protein. This approach might be advantageous in the formulation of efficient malaria subunit vaccines.


Childhood acute and chronic immune-mediated polyradiculoneuropathies.
Immune-mediated polyradiculoneuropathies are divided into Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In children subacute inflammatory demyelinating polyradiculoneuropathy is included in CIDP. Immune polyradiculoneuropathies are not exclusively demyelinating, and axonal forms also responding favourably to immunotherapy occur. Evidence-based data on efficacy of therapy in children is lacking, relying on retrospective data, open label studies on small numbers of children, and mainly adult derived data. Immunotherapy (intravenous human immunoglobulin [IVIg] and plasmapheresis) shortens GBS recovery time with most children recovering completely. Childhood CIDP usually responds to corticosteroids and slow tapering is required to prevent relapses. IVIg and plasmapheresis are also effective. CIDP children resistant to steroids, IVIg, and steroid-dependent patients present a therapeutic challenge. Immunosuppressive agents including methotrexate, azathioprine and cyclosporine are helpful in some cases. Anecdotal reports of treatment with interferons alpha or beta and monoclonal antibodies against specific B-cell antigens (Rituximab, Alemtuzumab) have been described in limited case reports. Childhood CIDP prognosis is mostly favourable. However, a proportion of cases have residual neurological deficit.


Diagnosis and management of vascular injuries in the shoulder girdle of the overhead athlete.
Vascular injuries represent a rare cause of shoulder pain and functional limitation among overhead athletes. Complaints of heaviness, fatigue, paresthesias, and effort-related pain should prompt the sports medicine clinician to consider vascular pathology as a possible cause of such symptoms. Position-dependent compression of the subclavian and axillary vessels within the thoracic outlet may result in functional limitation and a decline in overhead athletic performance, particularly when symptoms occur in the dominant upper limb. Treatment options include physical therapy and (in the case of thrombus) thrombolysis, but surgical decompression of the neurovascular bundle is generally advocated. This article reviews the diagnosis and management of effort thrombosis (also known as Paget-Schroetter syndrome), arterial thoracic outlet syndrome, and entrapment of the posterior circumflex humeral artery within the quadrilateral space. Familiarity with these conditions may help to minimize the risk of delayed diagnosis and associated morbidity.


Cold agglutinins: specificity, idiotypy and structural analysis.
Cold agglutinins likely represent natural autoantibodies with precursors that arise early during ontogeny. Many use L chains derived from the germline kv325 gene, in association with H chains derived from the VHIV gene family. CAs probably represent an expression of the preimmune repertoire. The appearance of CAs in a variety of disorders may be due to the prevalence of CA B cell precursors, and the ubiquity of their target epitopes. CAs may arise independent of antigenic selection during Epstein-Barr virus infection in response to the expansion of immature B cells. In support, L chains bearing the markers for the kv325 gene are preferentially expressed during in vitro and in vivo Epstein-Barr virus infection. Certain CAs that arise in lymphoproliferative disorders represent a clonal expansion, produced by karyotypically abnormal lymphocytes. As such, antigenic selection may foster the early expansion of CA-producing clones. These cells are later more prone to become autonomous, and overt malignancy may then occur. Clues to the genetic origin of these antibodies are now being appreciated, but further study will be required to understand the defects responsible for the transformation of a natural autoantibody into a malignancy.


Regulation of root apical meristem development.
The establishment of the Angiosperm root apical meristem is dependent on the specification of a stem cell niche and the subsequent development of the quiescent center at the presumptive root pole. Distribution of auxin and the establishment of auxin maxima are early formative steps in niche specification that depend on the expression and distribution of auxin carriers. Auxin specifies stem cell niche formation by directly and indirectly affecting gene activities. Part of the indirect regulation by auxin may involve changes in redox, favoring local, oxidized microenvironments. Formation of a QC is required for root meristem development and elaboration. Many signals likely pass between the QC and the adjacent root meristem tissues. Disappearance of the QC is associated with roots becoming determinate. Given the many auxin feedback loops, we hypothesize that roots evolved as part of an auxin homeostasis mechanism.


A questionnaire survey on the diagnosis and treatment of Fabry nephropathy in clinical practice.
Fabry nephropathy is characterized by a deficiency of lysosomal alpha-galactosidase A, which results in proteinuria and kidney disease. The ineffectiveness of enzyme replacement therapy (ERT) for severe kidney failure highlights the need for early detection and meaningful markers. However, because the diagnosis and treatment of Fabry disease can vary according to the expertise of physicians, we evaluated the opinions of Korean specialists. A questionnaire regarding the management of Fabry nephropathy was emailed to healthcare providers with the experience or ability to treat individuals with Fabry nephropathy. Of the 70 experts who responded to the survey, 43 were nephrologists, and 64.3% of the respondents reported having treated patients with Fabry disease. Pediatricians are treating primarily patients with classic types of the disease, while nephrologists and cardiologists are treating more patients with variant types. Only 40.7% of non-nephrologists agreed that a kidney biopsy was required at the time of diagnosis, compared with 81.4% of nephrologists. Thirty-eight of 70 respondents (54.3%) reported measuring globotriaosylsphingosine (lyso-Gb3) as a biomarker. The most common period to measure lyso-Gb3 was at the time of diagnosis, followed by after ERT, before ERT, and at screening. For the stage at which ERT should begin, microalbuminuria and proteinuria were chosen by 51.8% and 28.6% of respondents, respectively. Nephrologists are more likely to treat variant Fabry disease rather than classic cases, and they agree that ERT should be initiated early in Fabry nephropathy, using lyso-Gb3 as a biomarker.


Efficient tumor synergistic chemoimmunotherapy by self-augmented ROS-responsive immunomodulatory polymeric nanodrug.
Immunotherapy has emerged as a promising therapeutic strategy for cancer therapy. However, the therapeutic efficacy has been distracted due to poor immunogenicity and immunosuppressive tumor microenvironment. In this study, a self-augmented reactive oxygen species (ROS) responsive nanocarrier with immunogenic inducer paclitaxel (PTX) and indoleamine 2,3-dixoygenase 1 (IDO1) blocker 1-methyl-D, L-tryptophan (1-MT) co-entrapment was developed for tumor rejection. The carrier was composed of poly (ethylene glycol) (PEG) as hydrophilic segments, enzyme cleavable 1-MT ester and ROS-sensitive peroxalate conjugation as hydrophobic blocks. The copolymer could self-assemble into prodrug-based nanoparticles with PTX, realizing a positive feedback loop of ROS-accelerated PTX release and PTX induced ROS generation. Our nanoparticles presented efficient immunogenic cell death (ICD) which provoked antitumor immune responses with high effector T cells infiltration. Meanwhile immunosuppressive tumor microenvironment was simultaneously modulated with reduced regulatory T cells (Tregs) and M2-tumor associated macrophages (M2-TAMs) infiltration mediated by IDO inhibition. The combination of PTX and 1-MT achieved significant primary tumor regression and reduction of lung metastasis in 4T1 tumor bearing mice. Therefore, the above results demonstrated co-delivery of immunogenic inducer and IDO inhibitor using the ROS amplifying nanoplatform with potent potential for tumor chemoimmunotherapy.


Effectiveness and short-term safety of modified sodium hyaluronic acid-carboxymethylcellulose at cesarean delivery: a randomized trial.
The rising cesarean birth rate has drawn attention to risks associated with repeat cesarean birth. Prevention of adhesions with adhesion barriers has been promoted as a way to decrease operative difficulty. However, robust data demonstrating effectiveness of such interventions are lacking. We report data from a multicenter trial designed to evaluate the short-term safety and effectiveness of a modified sodium hyaluronic acid (HA)-carboxymethylcellulose (CMC) absorbable adhesion barrier for reduction of adhesions following cesarean delivery. Patients who underwent primary or repeat cesarean delivery were included in this multicenter, single-blinded (patient), randomized controlled trial. Patients were randomized into either HA-CMC (N = 380) or no treatment (N = 373). No other modifications to their treatment were part of the protocol. Short-term safety data were collected following randomization. The location and density of adhesions (primary outcome) were assessed at their subsequent delivery using a validated tool, which can also be used to derive an adhesion score that ranges from 0-12. No differences in baseline characteristics, postoperative course, or incidence of complications between the groups following randomization were noted. Eighty patients from the HA-CMC group and 92 controls returned for subsequent deliveries. Adhesions in any location were reported in 75.6% of the HA-CMC group and 75.9% of the controls (P = .99). There was no significant difference in the median adhesion score; 2 (range 0-10) for the HA-CMC group vs 2 (range 0-8) for the control group (P = .65). One third of the HA-CMC patients met the definition for severe adhesions (adhesion score >4) compared to 15.5% in the control group (P = .052). There were no significant differences in the time from incision to delivery (P = .56). Uterine dehiscence in the next pregnancy was reported in 2 patients in HA-CMC group vs 1 in the control group (P = .60). Although we did not identify any short-term safety concerns, HA-CMC adhesion barrier applied at cesarean delivery did not reduce adhesion formation at the subsequent cesarean delivery.


AKI after pediatric cardiac surgery for congenital heart diseases-recent developments in diagnostic criteria and early diagnosis by biomarkers.
Acute kidney injury (AKI) after cardiac surgery in children with congenital heart disease is a common complication. AKI is also associated with high morbidity and mortality. The Kidney Diseases Improving Global Outcomes (KDIGO) criteria for AKI classification are now widely used for the definition of AKI. It is noteworthy that a statement about children was added to the criteria. Many studies aimed at finding useful biomarkers are now being performed by using these criteria. Clinicians should be aware of the recent progress in understanding AKI in children. Unlike adult patients, young age is one of the major risk factors for AKI in pediatric cardiac surgery. The mechanism of the development of AKI in children might be different from that in adults because the surgical procedure and CPB technique in pediatric patients are greatly different from those in adult patients. There are many biomarkers for early detection of AKI, and some of them are widely used in hospitals. One of the major benefits of such biomarkers is the rapidness of expression for detecting increases in their expression levels. Neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C, and albumin have been investigated in some studies, and the usefulness of these biomarkers for detection of AKI and diagnosis of disease severity has been shown. Although there are many interventions for preventing and treating AKI after cardiac surgery in children, there is still no specific effective treatment. Peritoneal dialysis is effective for only maintaining a negative fluid balance early after cardiac surgery. The long-term prognosis of AKI is an issue of interest. Although mortality and morbidity of AKI in the acute phase of disease remain high, the long-term condition in pediatric patients is relatively acceptable unlike in adults. KDIGO criteria are advocated as a diagnostic tool for common perception. Early recognition and intervention for AKI can be achieved by using several biomarkers. Further studies are needed to establish effective treatment for AKI.


Hydrogen bonding and pi-pi stacking in methylaminium 4',7-dihydroxyisoflavone-3'-sulfonate dihydrate and hexaaquairon(II) bis(4',7-diethoxyisoflavone-3'-sulfonate) tetrahydrate.
In methylaminium 4',7-dihydroxyisoflavone-3'-sulfonate dihydrate, CH6N+.C15H9O7S-.2H2O, 11 hydrogen bonds exist between the methylaminium cations, the isoflavone-3'-sulfonate anions and the solvent water molecules. In hexaaquairon(II) bis(4',7-diethoxyisoflavone-3'-sulfonate) tetrahydrate, [Fe(H2O)6](C19H17O7S)2.4H2O, 12 hydrogen bonds exist between the centrosymmetric [Fe(H2O)6]2+ cation, the isoflavone-3'-sulfonate anions and the solvent water molecules. Additional pi-pi stacking interactions generate three-dimensional supramolecular structures in both compounds.


Thin-plate spline analysis of the short- and long-term effects of rapid maxillary expansion.
The aim of this study was to investigate the short- and long-term effects induced by rapid maxillary expansion (RME) on the shape of the maxillary and circummaxillary structures by means of thin-plate spline (TPS) analysis. The sample consisted of 42 patients who were compared with a control sample of 20 subjects. The treated subjects underwent Haas-type RME, followed by fixed appliance therapy. Postero-anterior (PA) cephalograms were analysed for each treated subject at T1 (pre-treatment), T2 (immediate post-expansion), and T3 (long-term observation), and were available at T1 and T3 for the control group (CG). The mean age at T1 was 11 years and 10 months for both groups. The mean chronological ages at T3 were 20 years, 6 months for the treated group (TG) and 17 years, 8 months for the control group. The study focused on shape changes in the maxillary, nasal, zygomatic, and orbital regions. TPS analysis revealed significant shape changes in the TG. They consisted of an upward and lateral displacement of the two halves of the naso-maxillary complex as a result of active expansion in the short-term, and normalization of maxillary shape in the transverse dimension in the long-term (the initial transverse deficiency of the maxilla in the treated group was eliminated by RME therapy both in the short- and long-term). At the end of the observation period, the nasal cavities were larger when compared with both their pre-expansion configuration and the final configuration in the controls. RME with the Haas appliance appears to be an efficient therapeutic means to induce permanent favourable changes in the shape of the naso-maxillary complex.


Intestinal metabolism of fatty acids.
1. The effect of concentration on the oxidation and incorporation into lipids of lauric acid and linoleic acid by rings of rat small intestine has been studied in vitro. 2. In the absence of glucose, the oxidation of lauric acid in the range 0.01-5.0mm showed a maximum at 0.1mm. In the presence of glucose the maximum was at 0.5mm. The oxidation of linoleic acid in the presence of glucose increased throughout the concentration range 0.01-5.0mm. 3. The incorporation of lauric acid into lipids was maximal at 0.5-0.6mm in the presence of glucose, but at 10mm in the absence of glucose. At 0.8mm-lauric acid, in the presence of glucose, over 75% of the incorporated lauric acid was in triglycerides, but at 10mm they only contained 30%. The incorporation of glucose carbon into glycerides paralleled the incorporation of lauric acid. 4. In the range 0.01-2.5mm-linoleic acid the quantity incorporated into lipids increased. In the range 0.01-0.4mm linoleic acid was incorporated predominantly into triglycerides, but between 0.4 and 1.0mm most was in diglycerides, and between 2.5 and 5.0mm most was in monoglycerides. 5. The relationship of fatty acid concentration to the mechanism of absorption is discussed, together with the correlation between the distribution of the absorbed fatty acids within the tissue lipids and the lipase activity of intestinal mucosa.


Direct synthesis of shaped carbon nanoparticles with ordered cubic mesostructure.
Shaped, mesoporous carbon nanoparticles (MSP-3) were prepared in high yield by a simple direct synthesis using a block copolymer surfactant as the mesopore-directing agent and a colloidal crystal to mold the external shape of the particles. The product consisted of monodisperse nanocubes and uniform nanospheres or tetrapods. The nanocubes contained regularly spaced, cagelike mesopores. The orientation of the cubic unit cell describing the mesopore symmetry coincided with the templated external cube faces.


Dual factor delivery of CXCL12 and Exendin-4 for improved survival and function of encapsulated beta cells under hypoxic conditions.
A bioartifical pancreas (BAP) remains a promising approach for treating insulin-dependent diabetes. Several obstacles to the clinical implementation of a BAP remain, including hypoxia following implantation. Within native pancreatic islets, CXCL12 and glucagon-like peptide-1 (GLP-1) act in a paracrine fashion to promote the survival, function, and proliferation of β-cells. This work sought to investigate if the presentation of CXCL12 and delivery of a GLP-1 receptor analog, Exendin-4 (Ex-4), alone and in combination, conferred pro-survival and insulinotropic effects on an encapsulated β-cell line, βTC-tet, cultured under hypoxic conditions of 7.6 mmHg O2 . Our findings indicate that presentation of CXCL12 in the encapsulation matrix completely abrogated apoptosis under hypoxic conditions. Delivery of Ex-4 increased insulin secretion rate under both normoxic and hypoxic conditions, and additionally reduced apoptosis under hypoxic conditions. Furthermore, presentation of CXCL12 combined with Ex-4 delivery significantly increased insulin secretion rate under hypoxic conditions compared to delivery of Ex-4 alone. These findings demonstrate that the presentation of CXCL12 combined with the delivery of Ex-4 may constitute a promising strategy for supporting β-cell function and survival following transplantation.


Cdc2 expression in primary thyroid lymphoma: its relationship with biological aggressiveness and G2 cyclins.
Previous studies have demonstrated that the G2-M modulators contribute to the progression of human neoplasms. In this study, we investigated the expression of these modulators, cyclin-dependent kinase 1 (cdc2), and G2 cyclins, cyclin A and cyclin B1, in primary thyroid lymphoma. Cdc2 immunoexpression was observed in 51.0% of the 49 cases examined and was related to grade of malignancy, high Ki-67 labeling index, and aberrant p53 expression. The incidences of immunoexpression of cyclin A and cyclin B1 were 63.3% and 40.9%, respectively, and they were also related to the above three parameters. Furthermore, a correlation was found between the immunoexpression of cdc2 and G2 cyclins. These findings suggest that the cdc2 and G2 cyclins play an important role in the progression of thyroid malignant lymphoma.


Fe3O4@ABA-aniline-CuI nanocomposite as a highly efficient and reusable nanocatalyst for the synthesis of benzothiazole-sulfide aryls and heteroaryls.
Studying diaryl sulfides and benzothiazoles is important in organic synthesis because numerous natural and medicinal products contain these scaffolds. Over the past few years, research on the synthesis of compounds containing benzothiazole-sulfide aryls, as important biological molecules, has received significant attention. Multicomponent reactions are the most popular strategy for performing difficult reactions and the synthesis of complexed molecules such as benzothiazole-sulfide aryls. In this work, CuI was successfully immobilized on the surface of magnetic Fe3O4 nanoparticles modified with aniline and 4-aminobenzoic acid [Fe3O4@ABA-Aniline-CuI nanocomposite] and its catalytic activity was investigated in the preparation of a broad range of benzothiazole-sulfide aryls and heteroaryls through the one-pot three-component reactions of 2-iodoaniline with carbon disulfide and aryl or heteroaryl iodides in the presence of KOAc as base in PEG-400 as solvent. TEM and SEM images revealed that the shape of the Fe3O4@ABA-Aniline-CuI particles is spherical and the size of the particles is approximately between 12-25 nanometers.


Ligands and complexes based on piperidine and their exploitation of the ring opening polymerisation of rac-lactide.
A range of ligands based upon 2-(aminomethyl)piperidine have been successfully complexed to Mg(ii), Zn(ii) and group IV metal centres. These complexes have been characterised both in solution and solid state with different coordination geometries realised dependant on the nature of the ligand. For the Mg(ii) and Zn(ii) complexes, M(1-2)2, were isolated and analysed by DOSY NMR spectroscopy. These ligands also furnished diastereomeric group IV complexes, M(1-2)2(OiPr)2. Group IV salalen and salan complexes, M(4-5)(OR)2 were also found to be diastereomeric in nature, with either β-cis or α-cis geometriesrespectively. The tridentate ligand, 6H2, yielded five coordinate complexes with both Ti(iv) and Zr(iv). All complexes were screened for the ring opening polymerisation of rac-lactide under both solvent and melt conditions. For the Mg(ii) and Zn(ii) complexes, good activity was observed with Zn(1-2)2 demonstrating immortal polymerisation characteristics.


B cell differentiation and lymphocyte surface phenotype in late onset hypogammaglobulinaemia.
Lymphocyte function and cell surface phenotype were examined in fifteen patients with late onset hypogammaglobulinaemia. The percentage of surface immunoglobulin-positive B cells in fourteen of the fifteen patients was in the normal range. Patients' B cells expressed MHC class II antigens at normal levels. For one patient, there was relatively high sIgD and low sIgM expression on B cells; the rest of the patients did not differ from controls in surface immunoglobulin density. The proportion of B cells positive for CD5 in patients was comparable to normal controls, and considerably less than in cord blood. However, the pattern of immunoglobulin isotype secretion in vitro by patients' B cells closely paralleled responses of cord blood B cells. Spontaneous secretion of IgM and IgG by patients' B cells was very low. Following polyclonal activation in the presence of autologous T cells, cells from thirteen patients secreted IgM within the normal range in response to at least one activator. The response of patients' purified B cells to IL-2 and gamma-IFN was variable. For four of six tested, B cells cultured with IL-2 and gamma-IFN together with polyclonal activators secreted normal levels of IgM. B cells from the other two patients secreted little or no IgM in response to these cytokines. For fourteen patients, IgG secretion following polyclonal activation remained low both when B cells were cultured with T cells or with a combination of IL-2 and gamma-IFN. IgG subclass imbalance was seen in one patient, whose cells secreted an unusually high proportion of IgG3, and undetectable IgG2 and IgG4; this pattern was consistent whether T cell help was provided by autologous or allogeneic T cells. Similarly purified B cells from this patient showed deficient IgG2 and IgG4 production in response to IL-2 and gamma-IFN.


Hybrid approach combining chemometrics and likelihood ratio framework for reporting the evidential value of spectra.
Many chemometric tools are invaluable and have proven effective in data mining and substantial dimensionality reduction of highly multivariate data. This becomes vital for interpreting various physicochemical data due to rapid development of advanced analytical techniques, delivering much information in a single measurement run. This concerns especially spectra, which are frequently used as the subject of comparative analysis in e.g. forensic sciences. In the presented study the microtraces collected from the scenarios of hit-and-run accidents were analysed. Plastic containers and automotive plastics (e.g. bumpers, headlamp lenses) were subjected to Fourier transform infrared spectrometry and car paints were analysed using Raman spectroscopy. In the forensic context analytical results must be interpreted and reported according to the standards of the interpretation schemes acknowledged in forensic sciences using the likelihood ratio approach. However, for proper construction of LR models for highly multivariate data, such as spectra, chemometric tools must be employed for substantial data compression. Conversion from classical feature representation to distance representation was proposed for revealing hidden data peculiarities and linear discriminant analysis was further applied for minimising the within-sample variability while maximising the between-sample variability. Both techniques enabled substantial reduction of data dimensionality. Univariate and multivariate likelihood ratio models were proposed for such data. It was shown that the combination of chemometric tools and the likelihood ratio approach is capable of solving the comparison problem of highly multivariate and correlated data after proper extraction of the most relevant features and variance information hidden in the data structure.


Coronal pulp dimensions in noncarious and restored deciduous second molars: a radiovisiographic study.
The purpose of this study was to measure the coronal pulp dimensions in primary maxillary and mandibular second molars and to evaluate the influence on restorative procedures on them. Included in this study were 80 4-7 year-old male and female patients with occlusal or proximal restorations on primary maxillary or mandibular second molars and with noncarious antimeres. Radiovisiographic images were captured utilizing standard bitewing radiographs via the parallel cone technique. Morphometric analysis was performed using Dexis and AutoCAD 2000 software, and data was analyzed using student's t test (unpaired). A significant difference was found in crown and coronal pulp dimensions in noncarious (sound) primary maxillary and mandibular second molars, even though no significant reductions were found in restored primary second molars. Crown and coronal pulp dimensions were significantly greater in noncarious primary mandibular second molars than in maxillary second molars. The mesiodistal crown width of maxillary molars was greater in males than in females. Nonsignificant reductions were observed in amalgam restored primary maxillary and mandibular second molars over a period of six months. No significant difference in pulpal dimensions was observed when Class I restorations were compared with Class II restorations in either arch.


Protective effect of aqueous seed extract of Vitis Vinifera against oxidative stress, inflammation and apoptosis in the pancreas of adult male rats with diabetes mellitus.
Protective effects of Vitis Vinifera seed aqueous extract (VVSAE) against pancreatic dysfunctions and elevation of oxidative stress, inflammation and apoptosis in the pancreas in diabetes were investigated. Histopathological changes in the pancreas were examined under light microscope. Blood and pancreas were collected from adult male diabetic rats receiving 28days treatment with VVSAE orally. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin and lipid profile levels and activity levels of anti-oxidative enzymes (superoxide dismutase-SOD, catalase-CAT and glutathione peroxidase-GPx) in the pancreas were determined by biochemical assays. Histopathological changes in the pancreas were examined under light microscopy and levels of insulin, glucose transporter (GLUT)-2, tumor necrosis factor (TNF)-α, Ikkβ and caspase-3 mRNA and protein were analyzed by real-time PCR (qPCR) and immunohistochemistry respectively. Radical scavenging activity of VVSAE was evaluated by in-vitro anti-oxidant assay while gas chromatography-mass spectrometry (GC-MS) was used to identify the major compounds in the extract. GC-MS analyses indicated the presence of compounds that might exert anti-oxidative, anti-inflammatory and anti-apoptosis effects. Near normal FBG, HbAIc, lipid profile and serum insulin levels with lesser signs of pancreatic destruction were observed following administration of VVSAE to diabetic rats. Higher insulin, GLUT-2, SOD, CAT and GPx levels but lower TNF-α, Ikkβ and caspase-3 levels were also observed in the pancreas of VVSAE-treated diabetic rats (p<0.05 compared to non-treated diabetic rats). The extract possesses high in-vitro radical scavenging activities. In conclusions, administration of VVSAE to diabetic rats could help to protect the pancreas against oxidative stress, inflammation and apoptosis-induced damage while preserving pancreatic function near normal in diabetes.


The potential removal of imidacloprid from water by heat-treated kerolites.
The adsorption of imidacloprid [1-(6-chloro-3-pyridinylmethyl)-N-nitroimidazolidin-2-ylideneamine] on heat-treated kerolite samples at 110 degrees C (K-110), 200 degrees C (K-200), 400 degrees C (K-400) and 600 degrees C (K-600) from pure water solution at 25 degrees C has been studied. The evolution of the surface properties of the kerolite samples, such as specific surface area and porosity, after heat treatment were analysed. The clays were characterised by using FTIR spectroscopy, X-ray diffraction, thermogravimetric and differential thermogravimetric analysis, surface analysis and Hg porosimetry. The experimental adsorption data points were fitted to the Freundlich equation in order to calculate the adsorption capacities (Kf) of the samples; Kf values ranged from 242 mg kg(-1) for the K-110 sample to 1005 mg kg(-1) for the K-600 sample. The values obtained for the removal efficiency (R) ranged from 62.8% for K-110 to 87.2% for K-600. The adsorption experiments showed that the stronger the heat treatment, the more effective was the adsorption of imidacloprid from pure water. This work shows the potential use of heat-activated kerolite for the removal of imidacloprid from environmental waters and drinking water resources.


Patterns of Care and Treatment Outcomes for Outpatient Daptomycin-Containing Regimens in Osteomyelitis.
Use of daptomycin at doses ≥ 6 mg/kg for treatment of osteomyelitis is increasing in clinical practice; unfortunately, limited data are available to guide optimal dosing and duration. The objective of this study was to assess daptomycin dosing and duration regimens for osteomyelitis treatment. This was a retrospective, multi-site, cohort study conducted in an integrated healthcare delivery system. Nonpregnant patients ≥ 18 years of age with osteomyelitis diagnosed between November 1, 2003 and June 30, 2011, ≥ 2 weeks outpatient daptomycin therapy, and ≥ 1 month of follow-up were included. Daptomycin doses < 6 mg/kg and ≥ 6 mg/kg at durations of < 6 weeks and ≥ 6 weeks were examined with univariate and multivariate analyses to assess treatment success and all-cause mortality. A total of 247 patients were included, with 39 (15.8%), 37 (15.0%), 107 (43.3%), and 64 (25.9%) receiving < 6 mg/kg and ≥ 6 weeks, < 6 mg/kg and < 6 weeks, ≥ 6 mg/kg and ≥ 6 weeks, and ≥ 6 mg/kg and < 6 weeks of daptomycin therapy, respectively. Patients had a mean age of 58 years and had received prior vancomycin therapy (65.6%). Patients receiving < 6 weeks of therapy were less likely to experience treatment success compared with ≥ 6 weeks (41.5% vs 25.3%, adjusted odds ratio = 0.55; 95% confidence interval = 0.31-0.98) independent of duration. There were no differences across groups in mortality after adjustment. In a diverse clinical population, daptomycin for treatment of osteomyelitis of 6 weeks or longer duration was associated with success independent of dose. This finding supports longer treatment with daptomycin as a first-line agent in antimicrobial stewardship initiatives.


Limited clinical relevance of imaging techniques in the follow-up of patients with advanced chronic lymphocytic leukemia: results of a meta-analysis.
The clinical value of imaging is well established for the follow-up of many lymphoid malignancies but not for chronic lymphocytic leukemia (CLL). A meta-analysis was performed with the dataset of 3 German CLL Study Group phase 3 trials (CLL4, CLL5, and CLL8) that included 1372 patients receiving first-line therapy for CLL. Response as well as progression during follow-up was reassessed according to the National Cancer Institute Working Group1996 criteria. A total of 481 events were counted as progressive disease during treatment or follow-up. Of these, 372 progressions (77%) were detected by clinical symptoms or blood counts. Computed tomography (CT) scans or ultrasound were relevant in 44 and 29 cases (9% and 6%), respectively. The decision for relapse treatment was determined by CT scan or ultrasound results in only 2 of 176 patients (1%). CT scan results had an impact on the prognosis of patients in complete remission only after the administration of conventional chemotherapy but not after chemoimmunotherapy. In conclusion, physical examination and blood count remain the methods of choice for staging and clinical follow-up of patients with CLL as recommended by the International Workshop on Chronic Lymphocytic Leukemia 2008 guidelines. These trials are registered at http://www.isrctn.org as ISRCTN 75653261 and ISRCTN 36294212 and at http://www.clinicaltrials.gov as NCT00281918.


EFF_D_SVM: a robust multi-type brain tumor classification system.
Brain tumors are one of the most threatening diseases to human health. Accurate identification of the type of brain tumor is essential for patients and doctors. An automated brain tumor diagnosis system based on Magnetic Resonance Imaging (MRI) can help doctors to identify the type of tumor and reduce their workload, so it is vital to improve the performance of such systems. Due to the challenge of collecting sufficient data on brain tumors, utilizing pre-trained Convolutional Neural Network (CNN) models for brain tumors classification is a feasible approach. The study proposes a novel brain tumor classification system, called EFF_D_SVM, which is developed on the basic of pre-trained EfficientNetB0 model. Firstly, a new feature extraction module EFF_D was proposed, in which the classification layer of EfficientNetB0 was replaced with two dropout layers and two dense layers. Secondly, the EFF_D model was fine-tuned using Softmax, and then features of brain tumor images were extracted using the fine-tuned EFF_D. Finally, the features were classified using Support Vector Machine (SVM). In order to verify the effectiveness of the proposed brain tumor classification system, a series of comparative experiments were carried out. Moreover, to understand the extracted features of the brain tumor images, Grad-CAM technology was used to visualize the proposed model. Furthermore, cross-validation was conducted to verify the robustness of the proposed model. The evaluation metrics including accuracy, F1-score, recall, and precision were used to evaluate proposed system performance. The experimental results indicate that the proposed model is superior to other state-of-the-art models.


Tissue engineered bone using select growth factors: A comprehensive review of animal studies and clinical translation studies in man.
There is a growing socio-economic need for effective strategies to repair damaged bone resulting from disease, trauma and surgical intervention. Bone tissue engineering has received substantial investment over the last few decades as a result. A multitude of studies have sought to examine the efficacy of multiple growth factors, delivery systems and biomaterials within in vivo animal models for the repair of critical-sized bone defects. Defect repair requires recapitulation of in vivo signalling cascades, including osteogenesis, chondrogenesis and angiogenesis, in an orchestrated spatiotemporal manner. Strategies to drive parallel, synergistic and consecutive signalling of factors including BMP-2, BMP-7/OP-1, FGF, PDGF, PTH, PTHrP, TGF-β3, VEGF and Wnts have demonstrated improved bone healing within animal models. Enhanced bone repair has also been demonstrated in the clinic following European Medicines Agency and Food and Drug Administration approval of BMP-2, BMP-7/OP-1, PDGF, PTH and PTHrP. The current review assesses the in vivo and clinical data surrounding the application of growth factors for bone regeneration. This review has examined data published between 1965 and 2013. All bone tissue engineering studies investigating in vivo response of the growth factors listed above, or combinations thereof, utilising animal models or human trials were included. All studies were compiled from PubMed-NCBI using search terms including 'growth factor name', 'in vivo', 'model/animal', 'human', and 'bone tissue engineering'. Focus is drawn to the in vivo success of osteoinductive growth factors incorporated within material implants both in animals and humans, and identifies the unmet challenges within the skeletal regenerative area.


Single monosomy as a relatively better survival factor in acute myeloid leukemia patients with monosomal karyotype.
Monosomal karyotype (MK) defined by either ⩾2 autosomal monosomies or single monosomy with at least one additional structural chromosomal abnormality is associated with a dismal prognosis in patients with acute myeloid leukemia (AML). It was detected in 174 of 3041 AML patients in South Korean Registry. A total of 119 patients who had received induction therapy were finally analyzed to evaluate the predictive factors for a positive prognosis. On multivariate analysis, single monosomy, the absence of abn(17p), ⩾10% of cells with normal metaphase and the achievement of a complete remission (CR) after induction therapy were significant factors for more favorable outcomes. Especially, single monosomy remained as a significantly independent prognostic factor for superior survival in both patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR and who did not. Allo-HSCT in CR improved overall survival significantly only in patients with a single monosomy. Our results suggest that MK-AML may be biologically different according to the karyotypic subtype and that allo-HSCT in CR should be strongly recommended to patients with a single monosomy. For other patients, more prudent treatment strategies should be examined. Furthermore, the biological mechanism by which a single monosomy influences survival should be investigated.


Effects of the multi-channeled oral irrigation (MCOI) unit in preventing dental plaque formation and gingivitis: A randomized controlled trial.
To evaluate the efficacy of COMORAL a new multi-channeled oral irrigation (MCOI) unit with pulsating water jet, in plaque score reduction and gingivitis. This was a single-blinded clinical randomized controlled trial (NCT05031260). Forty-two healthy subjects between 18 to 35 years old were initially recruited, and the control group (n = 20) and the intervention group (n = 17) were randomly assigned. Both groups were asked to brush their teeth one or two times a day without any supplementary oral hygiene products while the intervention group used COMORAL 3 times a day, 5 days a week. Clinical indices including gingival index (GI), plaque index (PI), bleeding on probing (BOP), pocket depth (PD), gingival recession (GR), and clinical attachment loss (CAL) were obtained at the baseline (D0), day 14 (D14), and day 28 (D28). Saliva was collected to examine the presence of periodontal pathogens. The repeated measures analysis of variance or generalized estimating equation was used to compare the interaction between groups and time points. The independent t-test or Mann-Whitney test were used for intergroup differences at each time point. At V0, PI, GI, BOP, and PD scores showed no differences between the two groups. At V1 and V2, these scores showed significant difference between two groups (P < 0.05) such that the intervention group showed gradual decreases while the control group showed no change. There were no differences in GR, CAL, and periodontal pathogens between the two groups. COMORAL showed improvement in reducing gingival inflammation and dental plaque formation adjuvant to routine toothbrushing in healthy adults. The results of this study can be useful to clinicians when selecting oral hygiene devices that can help improve patients' routine oral hygiene practice and their overall oral health.


Naringin protects cardiomyocytes against hyperglycemia-induced injuries in vitro and in vivo.
We previously reported that naringin (NRG) protects cardiomyocytes against high glucose (HG)-induced injuries by inhibiting the MAPK pathway. The aim of this study was to test the hypothesis that NRG prevents cardiomyocytes from hyperglycemia-induced insult through the inhibition of the nuclear factor kappa B (NF-κB) pathway and the upregulation of ATP-sensitive K(+) (KATP) channels. Our results showed that exposure of cardiomyocytes to HG for 24h markedly induced injuries, as evidenced by a decrease in cell viability and oxidative stress, and increases in apoptotic cells as well as the dissipation of mitochondrial membrane potential (MMP). These injuries were markedly attenuated by the pretreatment of cells with either NRG or pyrrolidine dithiocarbamate (PDTC) before exposure to HG. Furthermore, in streptozotocin (STZ)-induced diabetic rats and in HG-induced cardiomyocytes, the expression levels of caspase-3, bax and phosphorylated (p)-NF-κB p65 were increased. The increased protein levels were ameliorated by pretreatment with both NRG and PDTC. However, the expression levels of bcl-2 and KATP and superoxide dismutase (SOD) activity were decreased by hyperglycemia; the expression level of Nox4 and the ADP/ATP ratio were increased by hyperglycemia. These hyperglycemia-induced indexes were inhibited by the pretreatment of cardiomyocytes with NRG or PDTC. In addition, in STZ-induced diabetic rats, we also observed that NRG or PDTC contributed to protecting mitochondrial injury and myocardium damage. This study demonstrated that NRG protects cardiomyocytes against hyperglycemia-induced injury by upregulating KATP channels in vitro and inhibiting the NF-κB pathway in vivo and in vitro.


N-in-1 dosing pharmacokinetics in drug discovery: experience, theoretical and practical considerations.
N-in-1 (or cassette) dosing pharmacokinetics (PK) has been used in drug discovery for rapid assessment of PK properties of new chemical entities. However, because of potential for drug-drug interactions this procedure is still controversial. This study was to retrospectively evaluate the N-in-1 dosing approach in drug discovery with an emphasis on the potential for drug-drug interactions. The systemic clearance, volume of distribution, oral bioavailability, and renal excretion of the 31 lead compounds in rats, dogs or chimpanzees were significantly correlated between the N-in-1 dosing and discrete studies with r values of 0.69, 0.91, 0.53, and 0.83 (p < 0.005 for all), respectively. PK parameters for 11 quality control compounds which were involved in 194 N-in-1 studies for screening approximately 1000 compounds had coefficient of variations of less than 70%. The intrinsic microsomal clearances generated from the N-in-1 and discrete incubations were nearly identical (r = 0.97, p < 0.0001). The intrinsic clearances of quality control compound from the N-in-1 incubations were consistent with its discrete CL(int) estimate (cv: 5.4%). Therefore, N-in-1 dosing is a useful approach in drug discovery to quickly obtain initial PK estimates. Potential drug-drug interactions that result in confounding PK estimates do not occur as frequently as expected.


Disrupting the IL-36 and IL-23/IL-17 loop underlies the efficacy of calcipotriol and corticosteroid therapy for psoriasis.
Psoriasis is one of the most common skin inflammatory diseases worldwide. The vitamin D3 analog calcipotriol has been used alone or in combination with corticosteroids in treating plaque psoriasis, but how it suppresses psoriatic inflammation has not been fully understood. Using an experimental mouse psoriasis model, we show that topical calcipotriol inhibited the pivotal IL-23/IL-17 axis and neutrophil infiltration in psoriatic skin, and interestingly, such effects were mediated through the vitamin D receptor (VDR) in keratinocytes (KCs). We further reveal that IL-36α and IL-36γ, which have recently emerged as key players in psoriasis pathogenesis, were effectively repressed by calcipotriol via direct VDR signaling in mouse KCs. Accordingly, calcipotriol treatment suppressed IL-36α/γ expression in lesional skin from patients with plaque psoriasis, which was accompanied by a reduced IL-23/IL-17 expression. In contrast, dexamethasone indirectly reduced IL-36α/γ expression in mouse psoriatic skin through immune cells. Furthermore, we demonstrate that calcipotriol and dexamethasone, in combination, synergistically suppressed the expression of IL-36α/γ, IL-23, and IL-17 in the established mouse psoriasis. Our findings indicate that the combination of calcipotriol and corticosteroid efficiently disrupts the IL-36 and IL-23/IL-17 positive feedback loop, thus revealing a mechanism underlying the superior efficacy of calcipotriol and corticosteroid combination therapy for psoriasis.


Palliative Care in Adolescents and Young Adults With Cancer.
Palliative care (PC) aims to improve quality of life (QOL) for patients with serious illness and their families by recognizing and alleviating the physical, emotional, social, existential, and spiritual suffering of patients and their communities. Because adolescents and young adults (AYAs, age 15-39 years) with cancer commonly report distress across all these domains and because that distress translates to their QOL during and after their cancers, PC is particularly relevant for this population. Here, we review the evidence for PC among AYAs with cancer, including its rationale, gaps, opportunities, and implications for care delivery. For example, nearly 90% of AYAs with cancer report distressing symptoms during their treatment, those who survive report ongoing unmet psychosocial and physical health needs, and those who die from their cancers are highly likely to receive medically intense care that is discordant with their goals and values. AYA communication and decision making can be challenging because of ethical and developmental considerations regarding the patient's autonomy and competing priorities of patients and caregivers. PC interventions (including primary PC delivered by oncologists, routine PC subspecialty care, symptom tracking, advance care planning, and psychosocial programs promoting AYA resilience) are all associated with improved patient-centered outcomes. However, PC is inconsistently integrated into AYA oncology care, and access to PC programs is not equitable; marginalized groups continue to experience poorer outcomes. Ongoing and future research and clinical initiatives must continue to bridge these gaps. Improving the QOL of AYAs with cancer is a shared goal of the larger clinical oncology community, and including PC in AYA cancer care delivery can help attain that goal.


Portable treatment technologies for urgent care.
In recent years UK government policy has increased the provision of urgent care in the community. As part of this initiative the emergency ambulance service is gradually changing from an organisation designed to convey patients to hospital to a professional group capable of assessing urgency and delivering the appropriate treatment to the patient. This paper explores the portable technology requirements needed to support the new professional roles and draws on examples from ambulance trusts (emergency care practitioner services), primary care (out-of-hours general practitioner services and minor injuries units), and acute trusts (emergency departments) to investigate the workplace layout and clinical activities, including the use of equipment and consumables. It describes the iterative process used to develop the design specification for portable technologies using a qualitative exploratory methodological framework with data collected at stakeholder workshops, responder bag audits, clinical treatment observations and design decision groups. The results are discussed as a three-level technology system for: personal kit; assessment packages (and storage for other clinical treatment packages), a clinical workspace. Future developments are predicted to improve diagnostic and decision-making services through both miniaturisation (eg, portable diagnostic imaging) and improved real-time support (communication systems). This study has provided empirical research for portable technology requirements in urgent care.


Virtual Breakthrough Series, Part 1: Preventing Catheter-Associated Urinary Tract Infection and Hospital-Acquired Pressure Ulcers in the Veterans Health Administration.
In 2014 the Veterans Health Administration (VHA) of the Department of Veterans Affairs (VA) implemented a Virtual Breakthrough Series (VBTS) collaborative to help VHA facilities prevent hospital-acquired conditions: catheter-associated urinary tract infection (CAUTI) and hospital-acquired pressure ulcers (HAPUs). During the prework phase, participating facilities assembled a multidisciplinary team, assessed their current system for CAUTI or HAPU prevention, and examined baseline data to set improvement aims. The action phase consisted of educational conference calls, coaching, and monthly team reports. Learning was conducted via phone, web-based options, and e-mail. The CAUTI bundle focused on four key principles: (1) avoidance of indwelling urinary catheters, (2) proper insertion technique, (3) proper catheter maintenance, and (4) timely removal of the indwelling catheter. The HAPU bundle focused on assessment and inspection, pressure-relieving surfaces, turning and repositioning, incontinence management, and nutrition/hydration assessment and intervention. For the 18 participating units, the mean aggregated CAUTI rate decreased from 2.37 during the prework phase to 1.06 per 1,000 catheter-days during the action (implementation) phase (p < 0.001); the rate did not change for CAUTI nonparticipating sites. HAPU data were available only for 21 of the 31 participating units, whose mean aggregated HAPU rate decreased from 1.80 to 0.99 from prework to continuous improvement (p < 0.001). Staff education and documentation improvement were the most frequently implemented changes. This project helped improve CAUTI and HAPU rates in the VHA and presents a promising model for implementing a virtual model for improvement.


Beneficial Effects of Magnesium Treatment on Heart Rate Variability and Cardiac Ventricular Function in Diabetic Rats.
Diabetes mellitus induces life-threatening cardiovascular complications such as cardiac autonomic neuropathy and ventricular dysfunction and is associated with hypomagnesemia. In this study, we investigated the short-term effects of magnesium (Mg2+) treatment on streptozotocin (STZ)-induced diabetic cardiac complications. Adult Wistar rats were treated once with STZ (50 mg/kg, intraperitoneally [ip]) or vehicle (citrate) and then daily for 7 days with MgSO4 (270 mg/kg, ip) or saline. On the eighth day, in vivo tail-pulse plethysmography was recorded for heart rate variability (HRV) analysis, and ex vivo Langendorff-based left ventricular (LV) pressure-volume parameters were measured using an intraventricular balloon. Measurements of plasma lipid and Mg2+ levels as well as blood glucose and cardiac tissue Mg2+ levels were also performed. Treatment with Mg2+ prevented diabetes-induced alterations in the standard deviation of the averages of normal-to-normal (NN) intervals (SDANN), root mean square differences of successive NN intervals (RMSSD), heart rate, and low-frequency (LF) power-high-frequency (HF) power ratio. In addition, Mg2+ restored orthostatic stress-induced changes in SDANN, RMSSD, and LF-HF ratio in diabetic rats. In isolated hearts, Mg2+ reversed the diabetes-induced decrease in LV end-diastolic elastance and the right shift of end-diastolic equilibrium volume intercept, without altering LV-developed pressure or end-systolic elastance. However, Mg2+ did not prevent the elevation in blood glucose, total cholesterol, and triglycerides or the decrease in high-density lipoprotein cholesterol in diabetes. Plasma- or cardiac tissue Mg2+ was not different among the treatment groups. These results suggest that Mg2+ treatment may attenuate diabetes-induced reduction in HRV and improve LV diastolic distensibility, without preventing hyperglycemia and dyslipidemia. Thus, Mg2+ may have a modulatory role in the early stages of diabetic cardiovascular complications.


Adhesins and invasins of pathogenic Escherichia coli.
Pathogenic E. coli cause both intestinal and extra-intestinal infections in humans and animals. Bacteria must be able to adhere to host cells if they are to colonize and to invade their hosts. Numerous E. coli adhesins with different morphological features and receptor specificities have been identified. Many bacteria produce several adhesins with different receptor specificities. Although not all adhesin receptors have been identified yet, it appears that adhesins generally behave as lectins, recognizing oligosaccharide residues of glycoproteins or glycolipids. This review summarizes recent advances concerning host tissue colonization properties, providing new insights into adhesive organelle biogenesis in pathogenic E. coli and into the development of reservoirs of pathogenic bacteria in the host. To limit the length of this review, I will use examples of structural characteristics and invasive properties of a few bacterial adherence factors: type 1 pili, Afa adhesive sheath and some outer membrane adhesins.


Framingham risk score inadequately predicts cardiac risk in young patients presenting with a first myocardial infarction.
The Framingham Risk Score (FRS) is a well-validated epidemiologic tool used to assess the risk for a fi rst cardiac event. Because young patients presenting with a fi rst myocardial infarction (MI) tend to have less significant risk profiles compared with older patients, we hypothesized that FRS may underestimate cardiac risk in these patients. We studied 1267 patients between January 2002 and November 2007 presenting with a fi rst MI. Patients with pre-existing diabetes mellitus and vascular disease were excluded. FRS was calculated for each patient. Patients were divided based on their age: group A (<40 years), group B (40 to 64 years) and group C (> or =65 years). The mean age was 54.7 +/- 11 years, 88.4% of the patients were males. Younger patients were more likely to be assigned with lower scores. Based on FRS, 63.0%, 29.3% and 14.2% of group A, B and C patients were classified as low risk (10-year risk for cardiac events<10%) respectively, P <0.001. The sensitivity of FRS in identifying at least intermediate risk subjects (10-year risk for cardiac events >10%) was 37.0% in group A vs 85.8% in group C (P <0.001). The incidence of newly diagnosed diabetes mellitus was higher in younger patients (12.0% vs 13.2% vs 7.1 % in groups A, B and C respectively, P = 0.027). FRS inadequately predicts cardiac risk in young patients presenting with a fi rst MI. This could be because a significant proportion of these young patients have undiagnosed diabetes mellitus, a coronary artery disease risk equivalent.


[Radioimmunologic method for the measurement of plasmatic LH in humans (author's transl)].
A simple radioimmunologic method for the measurement of plasmatic LH concentration is described. This procedure utilizes a second antibody for the separation by precipitation of the bound from the free hormone. LH is labelled with 125I by means of a modified Greenwood and Hunter Chloramine T procedure. Three reference compounds, LER-907, MRC 68/40 and 2nd IRP-HMG, have been compared. The daily plasma concentrations of LH along the menstrual cycle in 12 young normal women and the changes induced by 100 mug LHRH were measured, validating the method used since it is capable of detecting the expected variations.


Ethnic variations on gestational diabetes mellitus and evidence-based first-line interventions.
To analyze the cultural and ethnic impact of gestational diabetes mellitus (GDM), report the associated complications, and investigate how lifestyle interventions are effective in preventing these associated complications. A literature review was conducted using online databases like CINAHL and Cochrane review. Findings were limited to journal articles published between 2012 and 2017. Irrelevant and relevant articles were determined by research topic, specific population, and type of interventions. Due to the growing rate of Hispanics, this ethnic group will have the most impact of GDM. There is a link between the prevalence of GDM and being classified as obese or overweight among women of childbearing age. Differences in perinatal outcomes were noted in different ethnicities especially between Hispanic and Caucasian women. Higher prevalence of GDM did not equal higher impact. In fact, the ethnicity with the highest rate tends to have the lowest impact. Lifestyle interventions reduced the rate and impact of complications of GDM. There is ethnic variation on the impact of GDM, with the Hispanic women having the most prevalence. Lifestyle interventions such as diet and exercise should be the first-line therapy for all women with GDM.


Theoretical Predictions of a New ∼14 kDa Core-Mass Thiolate-Protected Gold Nanoparticle: Au68(SR)36.
As an important intermediate link between the smaller and larger size thiolate-protected gold nanoparticles (RS-AuNPs), the molecular formula and atomic structure of the ∼14 kDa core-mass RS-AuNP species (containing around 70 core gold atoms) have not been determined unambiguously. In this work, we theoretically predict an unprecedented ∼14 kDa core-mass AuNP species, denoted as Au68(SR)36, which is composed a symmetric, face-centered-cubic (fcc) 68-gold atom framework. The fcc gold kernel in the Au68(SR)36 is made of eight 13-atom Au-cubotahedrons sharing 12 square faces, showing a standard 2 × 2 × 2 magic cube formula. The Au68(SR)36 is thought to be a key intermediate NP bridging the evolution of Au44(SR)28 and Au92(SR)44. The DFT calculations indicate the Au68(SR)36 has a sizable HOMO-LUMO gap of 0.98 eV and relative high thermodynamic stability. The fcc 68-atom gold framework in the Au68(SR)36 also presents a new candidate to address the atomic structure of recently reported water-soluble mercaptobenzoic acid protected Au68NPs.


A long term results of external beam radiation therapy in hemophilic arthropathy of the ankle in children.
Bleeding into joint space is critical to develop hemophilic arthropathy. To reduce the frequency of bleeding in the ankle joint of children with hemophilic arthropathy, low dose external beam irradiation was performed for 37 patients. Among them, 35 patients followed-up for longer than 1 yr (median 87 months) were enrolled for analysis. The average number of bleedings per month was 3.6 during one year prior to radiation therapy. After radiation therapy, it was decreased to 2.1 during the first year, after then it was maintained in the range of 1.0 to 1.5 until the tenth year. The bleeding frequency was reduced to 42% at the first year and it was maintained in the range of 58% to 73% from the second to the tenth year. Especially the patients who had 3 or more bleedings per month, and who had MRI score more than 3 showed significant decreases. During the follow-up period, growth disturbances and secondary malignancies were not found. External beam radiotherapy can be considered for the hemophilic patients with surgical or isotope therapies are not amenable.


Effects of the aerial parts of Orostachys japonicus and its bioactive component on hepatic alcohol-metabolizing enzyme system.
In the course of screening medicinal plants that modulate hepatic alcohol-metabolizing enzymes and lipid peroxidation, effects of the methanol extract (ME) of Orostachys japonicus and its major bioactive compound, gallic acid (GA), were investigated in rats treated with 10% ethanol solution for 6 weeks. The ME and GA greatly enhanced the activities of hepatic alcohol dehydrogenase (ADH), the microsomal ethanol-oxidizing system (MEOS), and aldehyde dehydrogenase (ALDH) in a dose-dependent manner, but had no effect on catalase. The hepatic lipid peroxide level increased by ethanol administration was moderately reduced by treatment with ME or GA. The results suggest that the detoxification of hepatic alcohol by O. japonicus ME under our experimental conditions was due to the enhanced activities of the alcohol-oxidizing enzymes, ADH, MEOS, and ALDH. In addition, GA may be partly responsible for the effects.


Study of PET Detector Performance with Varying SiPM Parameters and Readout Schemes.
The spatial resolution performance characteristics of a monolithic crystal PET detector utilizing a sensor on the entrance surface (SES) design is reported. To facilitate this design, we propose to utilize a 2D silicon photomultiplier (SiPM) array device. Using a multi-step simulation process, we investigated the performance of a monolithic crystal PET detector with different data readout schemes and different SiPM parameters. The detector simulated was a 49.2mm by 49.2mm by 15mm LYSO crystal readout by a 12 by 12 array of 3.8mm by 3.8mm SiPM elements. A statistics based positioning (SBP) method was used for event positioning and depth of interaction (DOI) decoding. Although individual channel readout provided better spatial resolution, row-column summing is proposed to reduce the number of readout channels. The SiPM parameters investigated include photon detection efficiency (PDE) and gain variability between different channels; PDE and gain instability; and dark count noise. Of the variables investigated, the PDE shift of -3.2±0.7% and gain shift of -4±0.9% between detector testing and detector calibration had the most obvious impact on the detector performance, since it not only degraded the spatial resolution but also led to bias in positioning, especially at the edges of the crystal. The dark count noise also had an impact on the intrinsic spatial resolution. No data normalization is required for PDE variability of up to 12% FWHM and gain variability of up to 15% FWHM between SiPM channels. Based upon these results, a row-column summing readout scheme without data normalization will be used. Further, we plan to cool our detectors below room temperature to reduce dark count noise and to actively control the temperature of the SiPMs to reduce drifts in PDE and gain.


Paraimmunoblastic variant of small lymphocytic lymphoma/leukemia.
We report 16 cases of a distinctive, biologically aggressive variant of small lymphocytic lymphoma/leukemia (SLL/L) that is characterized by the diffuse proliferation of cells normally comprising the pseudoproliferation centers (so-called paraimmunoblasts). Demographically, the patients differed in no significant regard from patients with SLL/L of usual type. Rapidly progressive, generalized lymphadenopathy was the dominant clinical finding in 15 of the 16 patients; one patient presented with symptoms related to lymphomatous involvement of the stomach and regional lymph nodes. Splenomegaly was observed in five patients. Seven patients, two of whom had a history of indolent-phase chronic lymphocytic leukemia, had an absolute lymphocytosis at diagnosis. In most patients, bone marrow involvement was noted at diagnosis. It consisted predominantly of small lymphocytic infiltrates indistinguishable from those observed in SLL/L of usual type; significant paraimmunoblastic infiltration was infrequent and generally occurred late in the disease course. Immunohistochemical and cytogenetic study further substantiated the hypothesized relationship of these cases to SLL/L. Findings included (a) coexpression of sIg and Leu-1 antigen in the majority of cases and (b) the presence of a t(11;14) (q13;q32) chromosome translocation in two of three cases with analyzable metaphases. Although treatment protocols were not uniform, follow-up data indicated an accelerated clinical course. Eleven patients have died of their disease between 3 and 39 months after diagnosis; the median survival was 28 months.


p53 gene family p51(p63)-encoded, secondary transactivator p51B(TAp63alpha) occurs without forming an immunoprecipitable complex with MDM2, but responds to genotoxic stress by accumulation.
p51(p63), a member of the p53 tumor suppressor gene family, generates multiple isoforms, including the potent and less potent transactivators p51A(TAp63gamma) and p51B(TAp63alpha), respectively, the latter poorly characterized for its protein features and functions. When constitutively expressed in 1-2-3 mouse erythroleukemic cells, p51B(TAp63alpha) appeared as a broad band with an approximate molecular mass of 85 kDa in Western blot. When cells were exposed to genotoxic stress by UV-C irradiation or by DNA-damaging drugs, including actinomycin D, bleomycin, and eptoposide, the protein accumulated intracellularly without an increase in its mRNA. Unlike p53 and p51A(TAp63gamma), however, p51B(TAp63alpha) did not activate p21(waf1) gene expression, nor did it induce apoptosis or hemoglobin production. While wild-type p53 was precipitated by an anti-MDM2 antibody, p51B(TAp63alpha) was not detectable in the MDM2 immunoprecipitates from the producer cells. After treatment with okadaic acid, a Ser/Thr phosphatase inhibitor, p51B(TAp63alpha) increased its apparent molecular mass and protein content. A 26S proteasome inhibitor, MG132 (N-CBZ-Leu-Leu-leu-al), also increased p51B(TAp63alpha) retention in an either transient or constitutive expression system. Without an interaction with MDM2, p51B(TAp63alpha) may be degraded by proteasome under normal cellular circumstances but stabilized under genotoxic stress by a posttranscriptional mechanism which might involve Ser/Thr phosphorylation.


Effects of topical administration of levocabastine on psychomotor and cognitive function.
The possible central nervous system effects of topical administration of levocabastine, a new H1-antagonist, were investigated in a double-blind, placebo-controlled, crossover study using a battery of objective and subjective tests. These were carried out in 12 volunteers up to five hours postapplication. Neither the recommended (0.5 mg/mL) nor the four times higher (2.0 mg/mL) concentration level was found to be distinguishable from placebo, while the verum (triprolidine 10 mg) was significantly worse, on both objective and subjective measures.