Comparison of the effects of genistein and zoledronic acid on the bone loss in OPG-deficient mice.
Using osteoprotegerin (OPG)-knockout mice, we demonstrated that in vivo the effects of both genistein and 17beta-estradiol (E2) on bone metabolism were completely abolished. In contrast, zoledronic acid could effectively suppress bone resorption and prevent bone loss. The anti-resorptive effects of E2 on bone metabolism are considered to be mediated via modulation of the osteoblast-derived paracrine factor OPG. Recently, the phytoestrogen genistein was found to suppress bone resorption by enhancing osteoblastic production of OPG. However, the mechanism underlying the in vivo effects of E2 and genistein on bone is not entirely understood, and a central question in this regard is whether E2 regulates bone metabolism via an OPG-dependent pathway. After mating heterozygous (OPG+/-) mice, homozygous (OPG-/-) and wild-type (WT) with a mixed C57BL/6J x 129/SV background were obtained. The study involved 6-week-old female OPG-/- (n=40) and WT mice (n=8). The OPG-/- mice were randomly divided into 5 groups (n=8 per group) as follows: (1) genistein-treated mice (Gen) that were subcutaneously injected with genistein at a maximal dose (0.8 mg/day); (2) E2-treated mice (E2) that were subcutaneously injected with E2 at a dose (0.03 microg/day); (3) DMSO control mice (DMSO) that were subcutaneously injected with a mixture of dimethylsulfoxide (DMSO) and polyethyleneglycol-300; (4) zoledronic acid-treated mice (Zol) that were subcutaneously injected with zoledronic acid at a dose of (150 microg/kg) twice per week; and (5) H2O control mice that were subcutaneously injected with sterilized water twice per week. The doses of genistein, estrogen and zoledronic acid were selected based on the results of dose-response effect of agents on bone versus uterus in OPG-/- mice. The mice were sacrificed 6 weeks after this intervention. The microarchitecture of the trabecular and cortical bone was assessed by performing microcomputed tomography (micro-CT) for the right proximal tibia. The bone mineral density (BMD) of the left femur was measured by dual-energy X-ray absorptiometry (DXA). The biomechanical parameters of the right femur were determined by a three-point bend testing. Serum levels of bone alkaline phosphatase (B-ALP), tartarate-resistant acid phosphatase-5b (TRACP-5b), and receptor activator of nuclear factor kappaB ligand (RANKL) were determined by performing ELISA. DXA analysis revealed that the total BMD of the femur was not significantly altered in the Gen, E2, H2O, and DMSO groups. The three-point bending test revealed no significant differences in the biomechanical parameters, including ultimate loading, ultimate stress, stiff index, and elastic modulus, and micro-CT analysis revealed that the microarchitectural parameters of the trabecular bone (vBMD, tBMD, BVF, BSF, SMI, Tb.N, Conn.D, Tb.Sp, and Tb.Th) and cortical bone (Ct.Th, Mm, In.Pm, Ot.Pm, Ma.Ar, Ct.Ar, Tt.Ar, Ct.BMD, and Ct.BMC) did not differ among the groups. Genistein and E2 treatment did not alter the serum TRACP-5b, B-ALP, or RANKL levels. However, in addition to increasing the bone mass, zoledronic acid could effectively improve biomechanical parameters and could completely prevent deterioration of the bone architecture in the OPG-/- mice. The effects of genistein and E2 on bone metabolism in vivo were lost completely in OPG-deficient mice, suggesting that the effect of these agents on bone metabolism seems to be entirely dependent on OPG. In contrast, zoledronic acid could effectively suppress bone resorption and completely prevent the bone loss in the OPG-/- mice--an effect that is likely to be independent of the OPG pathway.


Unicompartmental knee arthroplasty is associated with lower proportions of surgical site infection compared with total knee arthroplasty: A retrospective nationwide database study.
This study aimed to clarify the association between types of knee arthroplasty (KA) (total knee arthroplasty (TKA) or unicompatmental knee arthroplasty (UKA)) and surgical site infection (SSI) with adjustment for various factors, using a Japanese national database. Data on 181,608 patients who underwent unilateral primary KA for osteoarthritis from 2010 to 2017 were obtained from the Japanese Diagnosis Procedure Combination database. SSI was identified based on International Classification of Diseases 10th Revision codes. Deep SSI (i.e. periprosthetic joint infection (PJI)) was identified as SSI treated with surgical procedures. Multivariable logistic regression analyses for SSI and PJI were performed, in which dependent variables included types of KA, patient backgrounds (sex, age, body mass index (BMI), smoking status, comorbidities), and seasonality. Eight percent of analyzed patients underwent UKA, while 92% underwent TKA. The proportions of SSI and PJI after UKA were 0.9% and 0.3%, respectively, both of which were lower than those after TKA (1.9% and 0.6%) (P < 0.001). Multivariable analyses showed lower proportions of SSI for UKA (adjusted odds ratio, 0.47; 95% confidence interval, 0.37-0.60; P < 0.001) and PJI (adjusted odds ratio, 0.47; 95% confidence interval, 0.34-0.65; P < 0.001) than TKA. Other factors associated with both SSI and PJI included male sex, BMI >30 kg/m2, renal dysfunction and summer season. UKA was associated with lower proportions of SSI and PJI than TKA. Surgeons should carefully consider the indication of UKA before performing TKA, especially in patients with knee unicompartmental osteoarthritis who are at a high risk for SSI or PJI.


Glucose enhances human macrophage LOX-1 expression: role for LOX-1 in glucose-induced macrophage foam cell formation.
Lectin-like oxidized LDL receptor-1 (LOX-1) is a newly identified receptor for oxidized LDL that is expressed by vascular cells. LOX-1 is upregulated in aortas of diabetic rats and thus may contribute to the pathogenesis of human diabetic atherosclerosis. In this study, we examined the regulation of human monocyte-derived macrophage (MDM) LOX-1 expression by high glucose and the role of LOX-1 in glucose-induced foam cell formation. Incubation of human MDMs with glucose (5.6 to 30 mmol/L) enhanced, in a dose- and time-dependent manner, LOX-1 gene and protein expression. Induction of LOX-1 gene expression by high glucose was abolished by antioxidants, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), nuclear factor-kappaB (NF-kappaB), and activated protein-1 (AP-1) inhibitors. In human MDMs cultured with high glucose, increased expression of PKCbeta2 and enhanced phosphorylation of extracellular signal-regulated protein kinase 1/2 was observed. Activation of these kinases was inhibited by the antioxidant N-acetyl-L-cysteine (NAC) and by the PKCbeta inhibitor LY379196. High glucose also enhanced the binding of nuclear proteins extracted from human MDMs to the NF-kappaB and AP-1 regulatory elements of the LOX-1 gene promoter. This effect was abrogated by NAC and PKC/MAPK inhibitors. Finally, high glucose induced human macrophage-derived foam cell formation through a LOX-1-dependent pathway. Overall, these results demonstrate that high glucose concentrations enhance LOX-1 expression in human MDMs and that this effect is associated with foam cell formation. Pilot data showing that MDMs of patients with type 2 diabetes overexpress LOX-1 support the relevance of this work to human diabetic atherosclerosis.


Effects of variation in physical effort on frontalis EMG activity.
The physiological mechanisms underlying forehead muscle biofeedback for stress reduction are not well understood. A common hypothesis considers the frontales to be "key muscles" uniquely indexing the degree of tension present in the general musculature. We tested this hypothesis under conditions ranging from relaxation to maximum physical effort. The hypothesis was not supported. Changes in forehead muscle activity were limited primarily to reflecting changes in head and neck muscle tension.


Detection of NDM Variants (bla NDM-1, bla NDM-2, bla NDM-3) from Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae: First Report from Nepal.
Increasing burden of carbapenem resistance among Enterobacterales is attributable to their ability to produce carbapenemase enzymes like metallo-beta-lactamase (MBL), Klebsiella pneumoniae carbapenemase (KPC), and OXA-type. This study aimed to determine the prevalence of carbapenemases and MBL genes ((bla NDM-1, bla NDM-1 and bla NDM-3) among E. coli and K. pneumoniae isolates. A total of 2474 urine samples collected during the study period (July-December 2017) were processed at the microbiology laboratory of Kathmandu Model Hospital, Kathmandu. Isolates of E. coli and K. pneumoniae were processed for antimicrobial susceptibility testing (AST) by disc diffusion method. Carbapenem-resistant isolates were subjected to Modified Hodge Test (MHT) for phenotypic confirmation, and inhibitor-based combined disc tests for the differentiation of carbapenemase (MBL and KPC). MBL-producing isolates were screened for NDM genes by polymerase chain reaction (PCR). Of the total urine samples processed, 19.5% (483/2474) showed the bacterial growth. E. coli (72.6%; 351/483) was the predominant isolate followed by K. pneumoniae (12.6%; 61/483). In AST, 4.4% (18/412) isolates of E. coli (15/351) and K. pneumonia (3/61) showed resistance towards carbapenems, while 1.7% (7/412) of the isolates was confirmed as carbapenem-resistant in MHT. In this study, all (3/3) the isolates of K. pneumoniae were KPC-producers, whereas 66.7% (10/15), 20% (3/15) and 13.3% (2/15) of the E. coli isolates were MBL, KPC and MBL/KPC (both)-producers, respectively. In PCR assay, 80% (8/10), 90% (9/10) and 100% (10/10) of the isolates were positive for bla NDM-1, bla NDM-2 and bla NDM-3, respectively. Presence of NDM genes among carbapenemase-producing isolates is indicative of potential spread of drug-resistant variants. This study recommends the implementation of molecular diagnostic facilities in clinical settings for proper infection control, which can optimize the treatment therapies, and curb the emergence and spread of drug-resistant pathogens.


Quantitative assessment of microbicide-induced injury in the ovine vaginal epithelium using confocal microendoscopy.
The development of safe topical microbicides that can preserve the integrity of cervicovaginal tract epithelial barrier is of great interest as this may minimize the potential for increased susceptibility to STI infections. High resolution imaging to assess epithelial integrity in a noninvasive manner could be a valuable tool for preclinical testing of candidate topical agents. A quantitative approach using confocal fluorescence microendoscopy (CFM) for assessment of microbicide-induced injury to the vaginal epithelium was developed. Sheep were treated intravaginally with one of five agents in solution (PBS; 0.02% benzalkonium chloride (BZK); 0.2% BZK) or gel formulation (hydroxyethyl cellulose (HEC); Gynol II nonoxynol-9 gel (N-9)). After 24 hours the vaginal tract was removed, labeled with propidium iodide (PI), imaged, then fixed for histology. An automated image scoring algorithm was developed for quantitative assessment of injury and applied to the data set. Image-based findings were validated with histological visual gradings that describe degree of injury and measurement of epithelial thickness. Distinct differences in PI staining were detected following BZK and N-9 treatment. Images from controls had uniformly distributed nuclei with defined borders, while those after BZK or N-9 showed heavily stained and disrupted nuclei, which increased in proportion to injury detected on histology. The confocal scoring system revealed statistically significant scores for each agent versus PBS controls with the exception of HEC and were consistent with histology scores of injury. Confocal microendoscopy provides a sensitive, objective, and quantitative approach for non-invasive assessment of vaginal epithelial integrity and could serve as a tool for real-time safety evaluation of emerging intravaginal topical agents.


Application of liquid-liquid-liquid microextraction and high-performance liquid-chromatography for the determination of sulfonamides in water.
This work presents a novel liquid-liquid-liquid microextraction (LLLME) technique for the extraction of sulfonamides from aqueous systems; it combines with high-performance liquid-chromatography-ultraviolet absorbance detection (HPLC/UV). In this experiment the sulfonamides were successively extracted from a donor phase (i.e., a water sample) into several microliters of an organic phase and then from the organic phase into an acceptor phase (i.e., an aqueous extract) by LLLME. The following separation and quantitative analyses were performed using HPLC/UV with 265 nm detection. Extraction condition such as solvent identity, agitation, extraction time, acceptor phase NaOH concentration, donor phase pH, and salt addition were optimized. Relative standard deviation (RSD, 2.6-5.3%), coefficient of estimation (R2, 0.9972-0.9999), and method detection limit (MDL, 0.11-0.77 ng mL(-1)) were achieved under the selected conditions. The proposed method was successfully applied to the analyses of three practical water samples and the relative recoveries of sulfonamides from the spiked water samples were in the range of 86.2-108.7%. The proposed method also confirms microextraction to be robust to monitoring trace levels of sulfacetamide, sulfadiazine, sulfathiazole, sulfamerazine, sulfadimidine, sulfamonomethoxine, sulfamethoxazole, and sulfaquinoxaline in aqueous samples.


Polyethylene sebacate-doxorubicin nanoparticles for hepatic targeting.
The present study discusses polyethylene sebacate (PES)-doxorubicin (DOX) nanoparticles (PES-DOX NP) using pullulan as asialoglycoprotein receptor (ASGPR) ligand for hepatic targeting. Pullulan, a hydrophilic polymer served as ligand and as stealth agent. PES-DOX NP were prepared by modified nanoprecipitation using PES and Gantrez AN 119 (Gantrez), as complexing agent in the organic phase, while DOX was dissolved in the aqueous phase. Pullulan was adsorbed on the formed nanoparticles (PES-DOX-PUL). Intimate association of PES and Gantrez, and ionic complexation of DOX with Gantrez (confirmed by FTIR), coupled with rapidity of nanoprecipitation resulted in nanoparticles with high entrapment efficiency and high drug loading. Nanoparticles were successfully freeze dried. Drug release from PES NP followed zero order kinetics. PES-DOX NP and PES-DOX-PUL exhibited low hemolytic potential and good serum stability. Comparative biodistribution study in rats using (99m)Tc labeled formulations revealed higher blood concentration and lower liver concentration of PES-DOX-PUL, confirming the long circulating nature of PES-DOX-PUL, and thereby the possibility of improved targeting to hepatocytes. Nanoparticles revealed lower DOX concentration in the heart suggestive of low cardiotoxicity. Our study presents a radically different yet simple approach for the design of PES-DOX nanoparticles with high drug loading for improved therapy in hepatic cancer.


Tolerability of the SQ-standardised grass sublingual immunotherapy tablet in patients treated with concomitant allergy immunotherapy: a non-interventional observational study.
The majority of allergic patients are poly-sensitized. For causal treatment by allergy immunotherapy (AIT) a single or few allergen products containing the clinically most relevant allergens are applied, but few data on tolerability of multiple application of AIT is available. The aim of our study was to investigate safety and tolerability in patients who started treatment by sublingual immunotherapy (SLIT) with the standardised SQ(®) grass SLIT-tablet and were treated with concomitant AIT products. In a non-interventional, open-label, observational study in Germany treatment of patients with the SQ(®) grass SLIT-tablet and concomitant AIT (SCIT or SLIT) was documented between January 2012 and January 2014. Patients were followed at visits at first administration of the SQ(®) grass SLIT-tablet and after 1-3 months of treatment. Tolerability of the treatment with the SQ(®) grass SLIT-tablet and concomitant AIT were assessed by the physician and administration of AIT and adverse events (AEs) were recorded by the patients in diaries. AEs and adverse drug reactions (ADRs) were coded by using the Medical Dictionary for Regulatory Activities. In total, 181 patients were documented by 48 allergists and 160 patients treated with a concomitant AIT (SCIT 130, SLIT 30). AEs were reported in 58 (36.3 %) patients with concomitant AIT, and AEs considered related with the SQ(®) grass SLIT-tablet in 49 (30.6 %) and with concomitant AIT in 18 (11.3 %) patients. Treatment was discontinued due to ADRs in 12 (7.5 %) patients and severity of ADRs was assessed mild or moderate in 29 (18.1 %), and severe in 20 (12.5 %) patients. Most common reactions were localised at the application site of the SQ(®) grass SLIT-tablet as oral pruritus, throat irritation, oedema mouth and paraesthesia oral; no serious ADRs were reported. Overall tolerability of the SQ(®) grass SLIT-tablet if given with concomitant AIT was assessed as "good" or "very good" by 91.0 % of patients and 91.6 % of physicians. In comparison to data from previous studies no increase in frequency of AEs or change in the tolerability profile was observed when SLIT with the SQ(®) grass SLIT-tablet was administered with concomitant SCIT or SLIT.


[Differential diagnostic problems in pulmonary embolism caused by x-ray findings].
Using two case-histories it is shown that atypical radiological findings caused the delay in diagnosis of pulmonary embolism depsite clinical signs (such as fever and intermittent dyspnoea; cyanosis, haemoptoe and cough reflex were absent). The exact diagnosis was finally established after having excluded all diseases, which were of greater probability on the grounds of the x-ray findings.


Association between single-nucleotide polymorphisms in serotonin receptor 2A and melatonin receptor 1A genes and pain after root canal treatment.
This study aimed to investigate whether single-nucleotide polymorphisms (SNPs) in the genes encoding 5-HTR2A (5-Hydroxytryptamine (serotonin) receptor 2A) and MTNR1A (melatonin receptor 1A) may contribute to postoperative pain perception after root canal treatment. We hypothesised that SNPs in HTR2A and MTNR1A genes were associated with postoperative pain after root canal treatment. This genetic cohort study enrolled patients with single-rooted teeth diagnosed with pulp necrosis and asymptomatic apical periodontitis before root canal treatment. Root canal treatment was performed in one session using a standardized protocol. Postoperative pain and tenderness were assessed using a visual analogue scale (recorded every day for 7 days and on the 14th and 30th days after root canal treatment). Genomic DNA was extracted from saliva and used to genotype the SNPs in HTR2A (rs4941573 and rs6313) and MTNR1A (rs6553010, rs6847693 and rs13140012) using real-time polymerase chain reaction. Genotypes were compared using univariate and multivariate Poisson regression with generalized estimating equations (p < .05). In total, 108 patients were enrolled in this study. The SNPs rs6553010 (MTNR1A), rs4941573 and rs6313 (HTR2A) were associated with an increased risk of developing pain after root canal treatment (p < .05). This study suggests that SNPs in HTR2A and MTNR1A influence pain response after root canal treatment.


Effect of amphetamine on long-term retention of verbal material.
A series of five experiments was conducted to investigate the temporal aspects of human memory consolidation of symbolic material through the administration of amphetamine. Subjects had to recall or recognise unrelated words from a previously presented list. The first experiments support the conjecture, based on animal studies, that amphetamine enhances long-term memory performance. Subsequently, enhancement is demonstrated with oral administration before learning, as well as with intramuscular injection after learning. It is shown that improved recall cannot be explained solely by general arousal or attentional processes, but must be due to consolidation. By introducing different test delays we show that consolidation of symbolic material can be modulated by amphetamine during the 1st hour after learning. In a final experiment we demonstrate that the memory enhancement applies to recall as well as to recognition. The implications of the present results are discussed in the context of recent research on LTP processes.


[Valorisation of brachytherapy and medico-economic considerations].
Economic data in the literature for brachytherapy are still sparse and heterogeneous, with few controlled prospective studies and a perspective most often limited to those of the provider (health insurances). Moreover, these observation and conclusions are difficult to generalize in France. The prospective health economic studies performed in France in the framework of a national program to sustain innovative and costly therapies (STIC program) launched by the French cancer national institute are therefore of most importance. With the exception of prostate brachytherapy with permanent seeds, the valorisation of the brachytherapy activity by the French national health insurance does not take into account the degree of complexity and the real costs supported by health institutions (i.e. no specific valorisation for 3D image-based treatment planning and dose optimization and for the use of pulsed dose rate brachytherapy).


CT imaging of intrathoracic lymph nodes in dogs with bronchoscopically administered iodinated nanoparticles.
The purpose of the study was to determine if airway instillation of iodinated nanoparticles results in contrast material enhancement of tracheobronchial lymph nodes in dogs. Eight dogs underwent intrabronchial instillation of iodinated nanoparticles; six dogs received 900 mg each, and two dogs received 450 mg each. Spiral computed tomography (CT) was then performed 2-34 days later. CT scans obtained 2 days after instillation showed the presence of contrast material within the lung parenchyma but no nodal enhancement. Scans obtained 6-34 days after instillation showed enhancement of the right, left, and middle tracheobronchial lymph nodes (analogous to the mediastinal nodes in humans). Mean nodal attenuation on CT images was 117 HU +/- 43, and the mean nodal volume was 129 mm3 +/- 113. Histologic specimens of the nodes showed macrophage hyperplasia. Iodinated nanoparticles instilled into small airways are transported to the tracheobronchial lymph nodes, where they result in contrast enhancement.


A morphological study of the collateral reinnervation of the cat's canine tooth.
We examined the morphologic characteristics of the collateral reinnervation of the cat's canine tooth pulp. Collateral reinnervation was stimulated in six adult cats by transecting the ipsilateral inferior alveolar nerve and preventing it from regenerating by sealing the ligated nerve inside a nylon tube. The apices of the canine teeth were examined after 15 weeks using electron microscopy and each axon was counted and measured. Compared with contralateral control teeth, the collateral reinnervation consisted of fewer myelinated fibers and in five animals the number of nonmyelinated fibers was also smaller. In one animal the nonmyelinated count on the operated side exceeded that on the control side. The total number of axons was 33.5% of the number in control teeth, considerably fewer than seen after reinnervation by regenerating fibers in previous experiments. The structural characteristics of the collateral fibers were similar to those of regenerating nerve fibers. Compared with controls the myelinated collateral fibers were smaller and had thinner myelin sheaths. There were more nonmyelinated fibers containing only one axon. More nonmyelinated fibers had exposure of part of their axolemma to the extracellular space and there was also an increase in axoaxonal apposition.


Self-medication of regular headache: a community pharmacy-based survey.
This observational community pharmacy-based study aimed to investigate headache characteristics and medication use of persons with regular headache presenting for self-medication. Participants (n = 1205) completed (i) a questionnaire to assess current headache medication and previous physician diagnosis, (ii) the ID Migraine Screener (ID-M), and (iii) the Migraine Disability Assessment questionnaire. Forty-four percentage of the study population (n = 528) did not have a physician diagnosis of their headache, and 225 of them (225/528, 42.6%) were found to be ID-M positive. The most commonly used acute headache drugs were paracetamol (used by 62% of the study population), NSAIDs (39%), and combination analgesics (36%). Only 12% of patients physician-diagnosed with migraine used prophylactic migraine medication, and 25% used triptans. About 24% of our sample (n = 292) chronically overused acute medication, which was combination analgesic overuse (n = 166), simple analgesic overuse (n = 130), triptan overuse (n = 19), ergot overuse (n = 6), and opioid overuse (n = 5). Only 14.5% was ever advised to limit intake frequency of acute headache treatments. This study identified underdiagnosis of migraine, low use of migraine prophylaxis and triptans, and high prevalence of medication overuse amongst subjects seeking self-medication for regular headache. Community pharmacists have a strategic position in education and referral of these self-medicating headache patients.


Minimally Invasive Anterolateral Ligament Reconstruction in the Setting of Anterior Cruciate Ligament Injury.
Recent evidence on the anatomy, function, and biomechanical properties of the anterolateral ligament has led to the recognition of the importance of this structure in the rotational control of the knee. This article describes a technique that allows for minimally invasive anterolateral ligament reconstruction as a complement to most techniques of anterior cruciate ligament reconstruction. A gracilis tendon autograft is harvested and prepared in a double-strand, inverted V-shaped graft. The graft is percutaneously placed through a femoral stab incision, and each strand is then passed deep to the iliotibial band, emerging through each tibial stab incision. After the femoral-end loop graft is fixed, the tibial fixation of each strand is performed in full extension for optimal isometry.


Salvage treatment for local or local-regional recurrence after initial breast conservation treatment with radiation for ductal carcinoma in situ.
The present study evaluated the outcome of salvage treatment for women with local or local-regional recurrence after initial breast conservation treatment with radiation for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. The study cohort consisted of 90 women with local only first failure (n=85) or local-regional only first failure (n=5). The histology at the time of recurrence was invasive carcinoma for 53 patients (59%), non-invasive carcinoma for 34 patients (38%), angiosarcoma for one patient (1%), and unknown for two patients (2%). The median follow-up after salvage treatment was 5.5 years (mean=5.8 years; range=0.2-14.2 years). The 10-year rates of overall survival, cause-specific survival, and freedom from distant metastases after salvage treatment were 83%, 95%, and 91%, respectively. Adverse prognostic factors for the development of subsequent distant metastases after salvage treatment were invasive histology of the local recurrence and pathologically positive axillary lymph nodes. These results demonstrate that local and local-regional recurrences can be salvaged with high rates of survival and freedom from distant metastases. Close follow-up after initial breast conservation treatment with radiation is warranted for the early detection of potentially salvageable local and local-regional recurrences.


Three-Dimensional Graphene: A Biocompatible and Biodegradable Scaffold with Enhanced Oxygenation.
Owing to its high porosity, specific surface area and three-dimensional structure, three-dimensional graphene (3D-C) is a promising scaffold material for tissue engineering, regenerative medicine as well as providing a more biologically relevant platform for living organisms in vivo studies. Recently, its differentiation effects on cells growth and anti-inflammation properties have also been demonstrated. Here, we report a complete study of 3D-C as a fully adequate scaffold for tissue engineering and systematically analyze its biocompatibility and biodegradation mechanism. The metabolic activities of liver cells (HepG2 hepatocarcinoma cells) on 3D-C are studied and our findings show that cell growth on 3D-C has high cell viability (> 90%), low lactate production (reduced by 300%) and its porous structure also provides an excellent oxygenation platform. 3D-C is also biodegradable via a 2-step oxidative biodegradation process by first, disruption of domains and lift off of smaller graphitic particles from the surface of the 3D-C and subsequently, the decomposition of these graphitic flakes. In addition, the speed of the biodegradation can be tuned with pretreatment of O2 plasma.


10t,12c-conjugated linoleic acid inhibits lipopolysaccharide-induced cyclooxygenase expression in vitro and in vivo.
Previous data demonstrated that conjugated linoleic acid (CLA) reduced eicosanoid release from select organs. We hypothesized that one active CLA isomer was responsible for the reduced prostaglandin release and that the mechanism was through the inhibition of inducible cyclooxygenase-2 (COX-2). Here, we examined the effects of 10t,12c-CLA and 9c,11t-CLA on COX-2 protein/mRNA expression, prostaglandin E(2) (PGE(2)) production, and the mechanism by which CLA affects COX-2 expression and prostaglandin release. The COX-2 protein expression level was inhibited 80% by 10t, 12c-CLA and 26% by 9c,11t-CLA at 100 microM in vitro. PGE(2) production was decreased from 5.39 to 1.12 ng/2 x 10(6) cells by 10t,12c-CLA and from 5.7 to 4.5 ng/2 x 10(6) cells by 9c,11t-CLA at 100 microM. Mice fed 10t,12c-CLA but not 9c,11t-CLA were found to have a 34% decrease in COX-2 protein and a 43% reduction of PGE(2) release in the lung. 10t,12c-CLA reduced COX-2 mRNA expression level by 30% at 100 microM in vitro and by 30% in mouse lung in vivo. Reduced COX-2 mRNA was attributable to an inhibition of the nuclear factor kappaB (NF-kappaB) pathway by 10t,12c-CLA. These data suggested that the inhibition of NF-kappaB was one of the mechanisms for the reduced COX-2 expression and PGE(2) release by 10t,12c-CLA.


High NO2/NOx emissions downstream of the catalytic diesel particulate filter: An influencing factor study.
Diesel vehicles are responsible for most of the traffic-related nitrogen oxide (NOx) emissions, including nitric oxide (NO) and nitrogen dioxide (NO2). The use of after-treatment devices increases the risk of high NO2/NOx emissions from diesel engines. In order to investigate the factors influencing NO2/NOx emissions, an emission experiment was carried out on a high pressure common-rail, turbocharged diesel engine with a catalytic diesel particulate filter (CDPF). NO2 was measured by a non-dispersive ultraviolet analyzer with raw exhaust sampling. The experimental results show that the NO2/NOx ratios downstream of the CDPF range around 20%-83%, which are significantly higher than those upstream of the CDPF. The exhaust temperature is a decisive factor influencing the NO2/NOx emissions. The maximum NO2/NOx emission appears at the exhaust temperature of 350°C. The space velocity, engine-out PM/NOx ratio (mass based) and CO conversion ratio are secondary factors. At a constant exhaust temperature, the NO2/NOx emissions decreased with increasing space velocity and engine-out PM/NOx ratio. When the CO conversion ratios range from 80% to 90%, the NO2/NOx emissions remain at a high level.


Silymarin inhibits the lipogenic pathway and reduces worsening of non-alcoholic fatty liver disease (NAFLD) in mice.
The role of silymarin in hepatic lipid dysfunction and its possible mechanisms of action were investigated. To evaluate the effects of silymarin on hepatic and metabolic profiles in mice fed with 30% fructose for 8 weeks. We evaluated the antioxidant profile of silymarin; mice consumed 30% fructose and were treated with silymarin (120 mg/kg/day or 240 mg/kg/day). We performed biochemical, redox status, and histopathological assays. RT-qPCR was performed to detect ACC-1, ACC-2, FAS, and CS expression, and western blotting to detect PGC-1α levels. Silymarin contains high levels of phenolic compounds and flavonoids and exhibited significant antioxidant capacity in vitro. In vivo, the fructose-fed groups showed increased levels of AST, ALT, SOD/CAT, TBARS, hepatic TG, and cholesterol, as well as hypertriglyceridaemia, hypercholesterolaemia, and increased ACC-1 and FAS. Silymarin treatment reduced these parameters and increased mRNA levels and activity of hepatic citrate synthase. These results suggest that silymarin reduces worsening of NAFLD.


The conscious access hypothesis: origins and recent evidence.
Consciousness might help to mobilize and integrate brain functions that are otherwise separate and independent. Evidence for this 'conscious access hypothesis' was described almost two decades ago, in a framework called global workspace theory. The theory had little impact at first, for three reasons: because consciousness was controversial; the evidence, though extensive, was indirect; and integrative theory was unfashionable. Recent neuroimaging evidence appears broadly to support the hypothesis, which has implications for perception, learning, working memory, voluntary control, attention and self systems in the brain.


Planned or emergent? An evaluation of a Master's in Health Professions Education programme.
Programme developers have the responsibility of ongoing programme renewal and evaluation to ensure that curricula remain responsive to rapidly changing educational and healthcare contexts. In reporting on programmes, significant emphasis is often placed on content and outcomes of Master's in Health Professions Education (MHPE) programmes. However, less emphasis has been placed on meaningful evaluation of all aspects of these programmes, particularly from a student perspective including what worked and what needs to be enhanced, as well as any emergent or unplanned factors. As the number of established MHPE programmes increases, so does the need for evaluation models that consider programme complexity. In this article we consider a MHPE programme against a model that provided scope for going beyond 'did it work?' Our intention was to determine whether the renewed MPhil in HPE programme was implemented as planned, and to which extent it achieved the planned outcomes. This programme evaluation was conducted in an interpretive paradigm. We collected qualitative data at two points. Firstly, at the start of students' first-year with voluntary participation in focus groups and secondly, a year later with voluntary participation in individual interviews. Two members of the research team performed the initial thematic analysis of both the focus group interviews and the individual interviews. Thereafter, the full author team worked collaboratively discussing the themes until we reached consensus, looking specifically to identify any "emergent" factors. We identified three themes in the student data related to the process of implementing the new programme and the outcomes from it, including those aspects that could be regarded as emergent or unplanned: balancing work, personal lives and studies; managing the hybrid learning approach; and the scholarly journey. While many of the outcomes of the renewed programme were met, not all manifested as had been planned. The experience of the programme differed from one student to the next such that at the end of the two years they were at different points in their scholarly journeys. We realised that although we sought to be pedagogically sound in the process of curriculum renewal, we did not take into account the complex matrix of influences that sit outside the formal curriculum. Future renewal activities should intentionally and sensitively consider those factors, both planned and emergent, that influence a student's journey towards becoming a scholarly teacher and teaching scholar.


GABA Receptor SNPs and Elevated Plasma GABA Levels Affect the Severity of the Indian ASD Probands.
Altered signaling of the chief inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), has been speculated in the etiology of autism spectrum disorder (ASD). We have investigated the association of six GABAA-receptor genetic variants and plasma GABA levels with ASD. Subjects were recruited based on the DSM, and CARS2-ST and ADI-R assessed disease severity. Peripheral blood was collected from the ASD probands (N = 251), their parents, and ethnically matched controls (N = 347). A positive correlation between the CARS2-ST and ADI-R scores was observed; domain scores of ADI-R were higher in the severe group categorized by the CARS2-ST. GABRB3 rs1432007 "A," GABRG3 rs897173 "A," and GABRA5 rs140682 "T" showed significant association with ASD. Trait scores were influenced by rs1432007 "AA" and rs140682 "TT." GABA level was significantly higher in the probands than the age-matched controls. Our findings indicate an influence of GABA in the etiology of ASD in the Indian probands.


Dynamic light-scattering study on changes in flexibility of filamentous bacteriophage Pf1 with temperature.
The temperature dependence of the flexibility of bacteriophage Pf1 was investigated by dynamic light scattering, and the following results were obtained: The gamma/K2 values measured at 1 degree-25 degrees C and at various K values were T/eta-scaled to 20 degrees C, where gamma is the first cumulant of the field correlation function of scattered light, K is the length of the scattering vector, T is the absolute temperature, and eta is the solvent viscosity at T. And it was found that the scaled gamma/K2 values at low K values were independent of temperature, whereas those at high K values increased sigmoidally and reversibly against temperature. This suggests that the virion is more flexible at temperatures above the transition temperature Tt. This characteristic temperature Tt depended on the pH of the suspension: Tt = 11 degrees C at pH 6.9 and Tt = 8 degrees C at pH 8.2.


Significance of systolic-phase imaging on full-phase ECG-gated CT angiography to detect intimal tears in aortic dissection.
For patients with aortic dissection (AD) and intramural hematoma (IMH), the optimal cardiac phase to detect intimal tears (IT) and ulcer-like projections (ULP) on retrospective electrocardiogram (ECG)-gated computed tomography angiography (CTA) remains unclear. The purpose of this study was to compare the accuracy of retrospective ECG-gated CTA for detecting IT in AD and ULP in IMH between each cardiac phase. A total of 75 consecutive patients with AD and IMH of the thoracic aorta were enrolled in this single-center retrospective study. The diagnostic performance to detect IT and ULP in the thoracic aortic regions (including the ascending aorta, aortic arch, and proximal and distal descending aorta) was compared in each cardiac phase on retrospective ECG-gated CTA. In the systolic phase (20%), the accuracy, sensitivity, and specificity to detect IT in AD was 64% (95% confidence interval [CI] 56-72%), 69% (95%CI 60-78%), and 25% (95%CI 3.3-45%), respectively. In the diastolic phase (70%), the accuracy, sensitivity, and specificity to detect IT in AD was 52% (95%CI 43-60%), 52% (95%CI 42-61%), and 50% (95%CI 25-75%), respectively. The accuracy to detect IT in AD on ECG-gated CTA was significantly higher in the systolic phase than that in the diastolic phase (P = 0.025). However, there were no differences in the accuracy (83%; 95%CI 78-89%), sensitivity (71%; 95%CI 62-80%), or specificity (100%; 95%CI 100%) to detect ULP in IMH between the cardiac cycle phases. Although it is currently recommended for routine diagnosis of AD and IMH, single-diastolic-phase ECG-gated CTA has risk to miss some IT in AD that are detectable in the systolic phase on full-phase ECG-gated CTA. This information is critical for determining the optimal treatment strategy for AD.


PROSPER partnership delivery system: Effects on adolescent conduct problem behavior outcomes through 6.5 years past baseline.
We report long-term effects of the PROSPER delivery system for universal evidence-based preventive interventions on adolescent conduct problem behaviors (CPBs). A cluster randomized trial included 28 school districts assigned to PROSPER or a control condition. Community-based teams in PROSPER condition school districts selected evidence-based interventions-a family-focused intervention in sixth grade and a school-based intervention the next year; follow-up assessments were conducted through 12th grade. CPBs were measured with 12 self-report items derived from the National Youth Survey. Intervention-control differences were tested via a multi-level Zero-Inflated Poisson (ZIP) model. Differences were significant from 9th through 12th grades; Relative Reduction Rates were between 10.1% and 14.5%. The intervention group was delayed in reaching a 10th grade reference level of CPBs by 10.7 months. Moderation analyses indicated stronger effects for early substance initiators. Findings suggest that the PROSPER delivery system has the potential to reduce CPBs in general populations.


Epithelioid sarcoma in children and adolescents: a report of four cases.
Epithelioid sarcoma is an uncommon soft tissue tumor, most prevalent in the extremities of young adults. Youth has been described as a favorable prognostic factor. We describe four patients (two children aged 10 years and two adolescents aged 18 years) with extremity epithelioid sarcoma. Both 10-year-old children had rapid disease evolution and died 3 and 6 months after the diagnosis was made. Both tumors were strict diploid at DNA flow cytometry, but one had an abnormal karyotype (trisomy 2). Both adolescents are disease-free 18 months and 18 years after combined treatment consisting of local resection, regional lymph node dissection, and isolated regional perfusion with cytostatic agents.


Intention to leave the workplace among nurses working with cancer patients in acute care hospitals in Sweden.
To examine associations between perceived leadership and intention to leave the workplace due to job dissatisfaction among registered nurses (RNs) who care for patients with cancer. We also examine intention to leave in relation to proportion of cancer patients, length of time in practice, perceived adequacy of cancer care education, and burnout. The data originated from the Swedish component of RN4CAST, based on a survey of RNs working with in-patient care in all acute care hospitals in Sweden. The 7412 RNs reporting ≥10% patients with cancer on their unit were included in this analysis. Data were collected on perceptions of work environment, burnout, future employment intentions, and demographic characteristics. Additional questions related to cancer care. About 1/3 of all RNs intended to leave their workplace within the next year. Intention to leave was more prevalent among RNs reporting less favourable perceptions of leadership, who had worked ≤ two years as RN, who reported having inadequate cancer care education, and with higher burnout scores. Associations between leadership and intention to leave were stronger among RNs in the profession > two years, who reported having adequate cancer care education, and with lower burnout scores. Perception of leadership is strongly associated with intention to leave among RNs in both specialized and general cancer care. This suggests a crucial area for improvement in order to reduce turnover rates.


Females with hip-related pain display altered lower limb mechanics compared to their healthy counterparts in a drop jump task.
Hip-related pain describes femoroacetabular impingement syndrome, acetabular dysplasia, and other hip pain conditions without clear morphological features. Movement strategies in this population, notably sex-related patterns, are poorly understood and may provide insights into why females report more pain and worse function. This study examined the sex-related differences during a drop vertical jump task between those with hip-related pain and healthy controls. Patients with hip-related pain and healthy controls completed five repetitions of a drop jump while their kinematics and kinetics were recorded using a motion capture system and force plates. Hip, knee, and ankle joint angles and external joint moments during landing were used in general estimating equations for comparison of group by sex by limb interactions. Time series data were further investigated using statistical parametric mapping. Females with hip-related pain had 9.1° less hip flexion (P = .041) and 9.2° less knee flexion (P = .024) than healthy females, and 8.3° less knee flexion than male counterparts with hip-related pain (P = .039). Males demonstrated 1.4° less hip flexion on the affected side compared to their uninvolved side (P = .004). Statistical parametric mapping results showed significant differences in knee flexion angle for females with hip-related pain compared to healthy females (P = .042). There were no significant differences in hip, knee, or ankle moments. Females with hip-related pain showed kinematic patterns distinct from healthy controls. Sex may be an important variable of interest in characterizing movement impairments in this population and movement impairments may be an appropriate target for intervention for these patients.


Orientation and Conformation of Proteins at the Air-Water Interface Determined from Integrative Molecular Dynamics Simulations and Sum Frequency Generation Spectroscopy.
Understanding the assembly of proteins at the air-water interface (AWI) informs the formation of protein films, emulsion properties, and protein aggregation. Determination of protein conformation and orientation at an interface is difficult to resolve with a single experimental or simulation technique alone. To date, the interfacial structure of even one of the most widely studied proteins, lysozyme, at the AWI remains unresolved. In this study, molecular dynamics (MD) simulations are used to determine if the protein adopts a side-on, head-on, or axial orientation at the AWI with two different forcefields, GROMOS-53a6 + SPC/E and a99SB-disp + TIP4P-D. Vibrational sum frequency generation (SFG) spectroscopy experiments and spectral SFG calculations validate consistency between the structure determined from MD and experiments. Overall, we show with strong agreement that lysozyme adopts an axial conformation at pH 7. Further, we provide molecular-level insight as to how pH influences the binding domains of lysozyme resulting in side-on adsorption near the isoelectric point of the lysozyme.


[Damage control orthopedics].
In the management of patients with multiple injuries, the concept of damage control orthopedics (DCO) is still a matter of controversy. Thus, the clinical value of DCO remains unclear and should be evaluated on an evidence-based level by a review of the current literature. The work of various authors has demonstrated an association between injury severity and the clinical immuno-inflammatory response and its prognostic relevance regarding organ dysfunction or organ failure and clinical outcome. Research data published by the authors and other investigators have clearly demonstrated an additional inflammatory response caused by surgical trauma which is significantly higher after primary intramedullary fracture treatment than after external fracture stabilization. In contrast, a generally minor inflammatory response seems to be associated with intramedullary nailing for secondary conversion osteosynthesis. Three retrospective cohort studies have shown a reduction of organ dysfunction and an improvement of survival with the DCO approach. Simultaneously, it was demonstrated that primary external fracture fixation and secondary conversion to definite osteosynthesis is not associated with an increased rate of local or systemic complications. The advocates of DCO claim that patients with multiple injuries including severe brain and chest injuries as well as those with an unstable cardiopulmonary or circulatory condition are at high risk of developing a severe systemic immuno-inflammatory reaction during early total fracture care. Therefore, they recommend primary minimally invasive external fracture stabilization in these patients to avoid additional surgical trauma and that definitive secondary fracture care should be performed after medical stabilization of the patient in intensive care.


Chronic thromboembolic pulmonary hypertension: evaluation with 64-detector row CT versus digital substraction angiography.
The aim of the study was to evaluate the role of 64-row CT in the diagnostic workup of patients with chronic thromboembolic pulmonary hypertension (CTEPH) using digital substraction angiography (DSA) as the method of diagnostic reference. CT and DSA studies of 27 patients (54 main, 162 lobar and 540 segmental arteries) with a clinical suspicion of CTEPH were included in this retrospective and blinded analysis. Axial images and multiplanar thin maximum intensity projections (MIPs) (3mm) were consequently used for exact image interpretation whereas additional reconstructed thick MIPs gave an overview of the entire vascular tree comparable to DSA. Sensitivity and specificity of CT regarding CTEPH-related pathological changes in general were 98.3% and 94.8% at main/lobar level and 94.1% and 92.9% at segmental level, respectively. Sensitivity and specificity of CT regarding the different pathological criteria of CTEPH (complete obstruction, intimal irregularities, bands and webs, indirect signs) were 88.9-100% and 96.1-100% at main/lobar level and 84.3-90.5% and 92-98.7% at segmental level, respectively. Our results show that CT is an accurate and reliable non-invasive alternative to conventional DSA in the diagnostic workup in patients with CTEPH.


Reduction of metmyoglobin derivatives by dithionite ion.
The rate constants for reduction by dithionite of a number of metmyoglobin species Mb+X(X=H2O, imidazole, OH-, F-, N3-, CNO-, SCN-, HCO2-, NO2-, and CN-) were measured at 25 degrees by stopped flow spectrophotometry. The dependence of the rate was [S2O42-]1/2, and the SO2- radical was considered to be the active reductant. Except for X=imidazole and CN-, reduction occurred through dissociation of Mb+X. Values for the dissociative rate constant obtained from dithionite reduction were in good agreement with those obtained directly. Reduction of the dissociated fragment (assumed Mb+H2O) by SO2- is 3+/-1 X 10(6) M-1S-1 at pH 8.2 for all Mb+X species examined. Reduction of Mb+ imidazole and Mb+CN- occurs directly with SO2-, and Mb0CN- (Mb0, deoxymyoglobin) is characterized as an intermediate in reduction of the latter.


Phase angle as an index of physiological status: validating bioelectrical assessments of hydration and cell mass in health and disease.
Bioelectrical impedance (BI) is a practical method to assess body composition in health and disease. This method relies on the passive conduction of an applied, safe, low-level alternating current through water and electrolytes in the body. Using a phase-sensitive device, BI yields measurements of impedance (Z) and its components, resistance (R) and reactance (Xc), that are related geometrically as phase angle (PhA). In vitro studies provide empirical evidence relating BI measurements to physiological variables. Cooking raw food samples results in greater decreases in PhA, predominantly Xc, with smaller reductions R indicating destruction of cell membrane integrity with simultaneous movement of fluid from intracellular to extracellular space. Infusion of saline into a cell-free model shows a proportional decrease in R with increases in volume. Saline infusion in a composite model of cells disproportionately decreases Xc and PhA, compared to R, demonstrating greater relative expansion of extracellular water (ECW) with a lesser relative increase in total fluid volume. Surgical patients treated with fluid infusion and diuresis demonstrate changes in Xc predominantly indicating relative changes in ECW with lesser variations in R indicating fluctuations in total fluid volume. Proteomics studies disclose strong independent associations of PhA with protein markers of fluid overload and protein proliferation. Interpretations of PhA measurements for body cell mass should be examined in the context of hydration status.


Testicular weight, tubular diameter and number of Sertoli cells in rats are decreased after early prepubertal administration of an LHRH-antagonist; the quality of spermatozoa is not impaired.
To suppress gonadotropin secretion during the sensitive period in development of the testes, immature male rats were treated with an antagonist of luteinizing hormone-releasing hormone (LHRH; ORG. 30276) from postnatal days 6-15. Previously, it has been demonstrated that this treatment results in delayed pubertal development, decreased testicular weight, impaired fertility and adult sexual behavior. In the present experiments it was investigated whether the decreased testicular weight was correlated with morphological changes in the testis. Also, by using an artificial insemination technique, the biological activity of spermatozoa of adult male rats, treated during early prepuberty with the LHRH antagonist (LHRH-A), was tested. The present results demonstrated a decrease in the diameter of the testicular tubuli of LHRH-A-treated rats. The number of Sertoli cells per tubular cross-section was also smaller. But qualitatively no differences could be observed in the testis. All stages of maturation of the seminiferous epithelium were equally frequently represented in LHRH-A-treated males compared with controls. Artificial insemination using spermatozoa obtained from the epididymis of LHRH-A-treated rats, resulted in a pregnancy rate of 100%, similar to the control rate. From the present data, we conclude that the infertility in adult male rats, treated with an antagonist to LHRH during prepubertal life, does not result from malfunction in the maturational processes in the germinal cells and the testes as a whole, despite the observation of changes in the testicular morphology. The infertility of LHRH-A-treated male rats can be explained by the observed impairment of sexual behavior. We suggest, that a central action of the antagonist of LHRH when administered to immature male rats may lead to permanent changes in the development of sexual behavior.


Proteomic analysis reveals exercise training induced remodelling of hepatokine secretion and uncovers syndecan-4 as a regulator of hepatic lipid metabolism.
Non-alcoholic fatty liver disease (NAFLD) is linked to impaired lipid metabolism and systemic insulin resistance, which is partly mediated by altered secretion of liver proteins known as hepatokines. Regular physical activity can resolve NAFLD and improve its metabolic comorbidities, however, the effects of exercise training on hepatokine secretion and the metabolic impact of exercise-regulated hepatokines in NAFLD remain unresolved. Herein, we examined the effect of endurance exercise training on hepatocyte secreted proteins with the aim of identifying proteins that regulate metabolism and reduce NAFLD severity. C57BL/6 mice were fed a high-fat diet for six weeks to induce NAFLD. Mice were exercise trained for a further six weeks, while the control group remained sedentary. Hepatocytes were isolated two days after the last exercise bout, and intracellular and secreted proteins were detected using label-free mass spectrometry. Hepatocyte secreted factors were applied to skeletal muscle and liver ex vivo and insulin action and fatty acid metabolism were assessed. Syndecan-4 (SDC4), identified as an exercise-responsive hepatokine, was overexpressed in the livers of mice using adeno-associated virus. Whole-body energy homeostasis was assessed by indirect calorimetry and skeletal muscle and liver metabolism was assessed using radiometric techniques. Proteomics analysis detected 2657 intracellular and 1593 secreted proteins from mouse hepatocytes. Exercise training remodelled the hepatocyte proteome, with differences in 137 intracellular and 35 secreted proteins. Bioinformatic analysis of hepatocyte secreted proteins revealed enrichment of tumour suppressive proteins and proteins involved in lipid metabolism and mitochondrial function, and suppression of oncogenes and regulators of oxidative stress. Hepatocyte secreted factors from exercise trained mice improved insulin action in skeletal muscle and increased hepatic fatty acid oxidation. Hepatocyte-specific overexpression of SDC4 reduced hepatic steatosis, which was associated with reduced hepatic fatty acid uptake, and blunted pro-inflammatory and pro-fibrotic gene expression. Treating hepatocytes with recombinant ectodomain of SDC4 (secreted form) recapitulated these effects with reduced fatty acid uptake, lipid storage and lipid droplet accumulation. Remodelling of hepatokine secretion is an adaptation to regular exercise training that induces changes in metabolism in the liver and skeletal muscle. SDC4 is a novel exercise-responsive hepatokine that decreases fatty acid uptake and reduces steatosis in the liver. By understanding the proteomic changes in hepatocytes with exercise, these findings have potential for the discovery of new therapeutic targets for NAFLD.


Protein kinases and phosphatase inhibitors mediating long-term desensitization of glutamate receptors in cerebellar Purkinje cells.
Long-term desensitization of the AMPA-selective glutamate receptors in Purkinje cells was examined in rat cerebellar slices by means of the wedge recording method. It was not induced by application of AMPA alone, but occurred regularly when slices were conditioned by perfusion with 0.5 mM 8-bromo-cGMP (but not cAMP derivatives) or the protein phosphatase inhibitors, okadaic acid and calyculin A. Phorbol esters also showed a similar effect. The 8-bromo-cGMP desensitization was antagonized by KT5823, an inhibitor of protein kinase G, while the effect of calyculin A was inhibited by polymyxin B, H-7, or K252a. These results suggest that AMPA receptors are persistently desensitized due to concerted action of both an agonist and an enzymatic system involving protein kinases G and C and a protein phosphatase inhibitor.


P63 and Ki-67 Expression in Dentigerous Cyst and Ameloblastomas.
P63 gene is a member of TP53 and its homologous gene family. Its expression was observed in some odontogenic lesions, more expression in aggressive lesions. This study aimed to investigate the possible diagnostic impact of P63 protein on dentigerous cysts and various types of ameloblastoma. Its expression with Ki-67 proliferation marker was also compared. This cross-sectional retrospective study was enrolled on 25 cases of dentigerous cyst including 21 unicystic ameloblastomas and 17 conventional ameloblastomas. The expression of P63 and Ki-67 was assessed by immunohistochemical (IHC) examinations. Data were analyzed by employing Mann-Whitney and correlation coefficient tests. P63 expression was significantly higher in ameloblastoma than unicystic ameloblastoma and dentigerous cysts. There was no significant difference between unicystic ameloblastoma and dentigerous cyst in P63 expression. A 90% cut-off point was obtained for basal layer which gave 88% sensitivity and 78% specificity to distinguish more invasive lesions from others. There was not any correlation between P63 and Ki-67 immunostaining in the three study groups. More aggressiveness and more invasiveness of odontogenic lesions depicted higher rate and also more intensive expression of P63. Moreover, the expression of P63 protein had not any correlation with Ki-67 protein in dentigerous cysts and ameloblastomas.


A note on the synonomy of Bothriocephalus acheilognathi Yamaguti, 1934, B. aegyptiacus Rysavý and Moravec, 1975 and B. kivuensis Baer and Fain, 1958.
Examination of stained and mounted syntype and topotype specimens of Bothriocephalus aegyptiacus Rysavý and Moravec 1974, syntype specimens of B. kivuensis Baer and Fain 1958, and paratype specimens of B. acheilognathi Yamaguti 1934 showed there to be no characters which could be used to differentiate the three species. A scanning electron microscope study of the scolices of paratype specimens of B. aegyptiacus, syntype specimens of B. kivuensis and specimens of B. acheilognathi also revealed no differences. It is therefore suggested that the three species are synonymous, with priority given to the name B. acheilognathi.


3D biodegradable shape changing composite scaffold with programmable porous structures for bone engineering.
This study developed a biodegradable composite porous polyurethane scaffold based on polycaprolactone and polyethylene glycol by sequentialin-situfoaming salt leaching and freeze-drying process with responsive shape changing performance. Biomineral hydroxyapatite (HA) was introduced into the polyurethane matrix as inorganic fillers. Infrared spectroscopy results proved a successful synthesis, scanning electron microscopy showed that the scaffold's porosity decreased with the addition of HA while the average pore size increased. X-ray diffraction and differential scanning calorimetry showed that the addition of HA lowered the melting point of the scaffold, resulting in a transition temperature close to the human body temperature. From the bending experiments, it could be demonstrated that PUHA20 has excellent shape memory performance with shape fixity ratio >98.9% and shape recovery ratio >96.2%. Interestingly, the shape-changing capacity could be influenced by the porous structures with variation of HA content. The shape recovery speed was further accelerated when the material was immersed in phosphate buffered saline at 37 °C. Additionally,in vitromineralization experiments showed that the scaffold incorporating HA had good osteoconductivity, and implantation assessment proved that scaffolds had goodin vivobiocompatibility. This scaffold is a promising candidate for implantation of bone defects.


Cargo-mediated recruitment of the endocytic adaptor protein Sla1 in S. cerevisiae.
Endocytosis of plasma membrane proteins is mediated by their interaction with adaptor proteins. Conversely, emerging evidence suggests that adaptor protein recruitment to the plasma membrane may depend on binding to endocytic cargo. To test this idea, we analyzed the yeast adaptor protein Sla1, which binds membrane proteins harboring the endocytic signal NPFxD via the Sla1 SHD1 domain. Consistently, SHD1 domain point mutations that disrupted NPFxD binding caused a proportional reduction in Sla1-GFP recruitment to endocytic sites. Furthermore, simultaneous SHD1 domain point mutation and deletion of the C-terminal LxxQxTG repeat (SR) region linking Sla1 to coat proteins Pan1 and End3 resulted in total loss of Sla1-GFP recruitment to the plasma membrane. These data suggest that multiple interactions are needed for recruitment of Sla1 to the membrane. Interestingly, a Sla1 fragment containing just the third SH3 domain, which binds ubiquitin, and the SHD1 domain displayed broad surface localization, suggesting plasma membrane recruitment is mediated by interaction with both NPFxD-containing and ubiquitylated plasma membrane proteins. Our results also imply that a Sla1 NPF motif adjacent to the SR region might regulate the Sla1-cargo interaction, mechanistically linking Sla1 cargo binding to endocytic site recruitment.


EBNA1 may prolong G(2)/M phase and sensitize HER2/neu-overexpressing ovarian cancer cells to both topoisomerase II-targeting and paclitaxel drugs.
We have shown previously that the Epstein-Barr virus nuclear antigen-1 (EBNA1) can act as a transforming suppressor in the HER2/neu-overexpressing ovarian cancer cells. In the present study, by using flow cytometric analysis, we demonstrate that EBNA1 could prolong G(2)/M phase and sensitize to Taxol-induced apoptosis in the EBNA1-expressing ovarian cancer cell stable transfectants. In addition, EBNA1 could also significantly increase topoisomerase IIalpha protein expression, indicating that the up-regulation of topoisomerase IIalpha may be one of the mechanisms by which EBNA1 enhances the sensitivity of ovarian cancer cells to topoisomerase II-targeting anticancer drugs, such as VP-16 and Adriamycin. These data suggest that EBNA1 not only prolongs cell cycle at G(2)/M phase and up-regulates topoisomerase IIalpha expression in HER2/neu-overexpressing ovarian cancer cells, but also increases cellular apoptosis through sensitization of cancer cells to topoisomerase II-directing anticancer drugs.


Gyrification abnormalities in childhood- and adolescent-onset schizophrenia.
Gyrification is an important index of brain development. We used magnetic resonance scanning technology to compare brain surface morphology and measures of gyrification in children and adolescents with a schizophrenia spectrum disorder and in age-equivalent healthy controls. Magnetic resonance scans were obtained from 42 patients and 24 healthy controls, mean age 17.7 years for both groups. We employed novel quantitative measures of brain morphology, including cortical thickness and a variety of indices of sulcal and gyral curvature. We examined these measures in the whole brain and in the frontal, temporal, parietal, and occipital lobes. There were significant decreases in cortical thickness in the patients. This was most pronounced in the cortical tissue that underlies the sulci. The patient group had significantly more flattened curvature in the sulci and more steeped or peaked curvature in the gyri. This study quantitatively examines cortical thickness and surface morphology in children and adolescents with schizophrenia. Patients with schizophrenia demonstrated patterns of brain morphology that were distinctly different from healthy controls. In light of current theories of the formation of gyri and sulci, these changes may reflect aberrations in cerebral and subcortical connectivity.


Utilization and Outcomes of Extracorporeal Membrane Oxygenation in Obstetric Patients in the United States, 1999-2014: A Retrospective Cross-Sectional Study.
Utilization of extracorporeal membrane oxygenation (ECMO) for adult critically ill patients is increasing, but data in obstetric cohorts are scant. This study analyzed ECMO utilization and maternal outcomes in obstetric patients in the United States. Data were abstracted from the 1999-2014 National Inpatient Sample (NIS), a 20% US national representative sample. ECMO hospitalizations (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 39.65) in patients ≥15 years of age were categorized into obstetric ECMO and nonobstetric ECMO. Obstetric patients included 4 categories: (1) loss or termination of pregnancy, (2) delivery (term or preterm), (3) postdelivery hospitalization, and (4) pregnancy without an obstetrical outcome. Possible underlying causes for obstetric ECMO were identified by analysis of ICD-9-CM codes in individual records. In-hospital death was abstracted from the NIS, and ECMO complications were identified using ICD-9-CM algorithms. Statistical significance in time-effect was assessed using weighted regression models. During the 16-year study period, 20,454 adult ECMO cases were identified, of which 331 occurred in obstetric patients (1.6%; 95% confidence interval [CI], 1.4-1.8). Obstetric ECMO utilization rate was 4.7 per million obstetric discharges (95% CI, 4.2-5.2). The top 3 possible indications were sepsis (22.1%), cardiomyopathy (16.6%), and aspiration pneumonia (9.7%). Obstetric ECMO utilization rate increased significantly during the study period from 1.1 per million obstetric discharges in 1999-2002 (95% CI, 0.6-1.7) to 11.2 in 2011-2014 (95% CI, 9.6-12.9), corresponding to a 144.7% increase per 4-year period (95% CI, 115.3-178.1). Compared with nonobstetric ECMO, obstetric ECMO was associated with decreased in-hospital all-cause mortality (adjusted odds ratio [aOR] 0.78; 95% CI, 0.66-0.93). In-hospital all-cause mortality for obstetric ECMO decreased from 73.7% in 1999-2002 (95% CI, 48.8-90.8) to 31.9% in 2011-2014 (95% CI, 25.2-39.1), corresponding to a 26.1% decrease per 4-year period (95% CI, 10.1-39.3). Compared with nonobstetric ECMO, obstetric ECMO was associated with significantly increased risk of both venous thromboembolism without associated pulmonary embolism (aOR 1.83; 95% CI, 1.06-3.15) and of nontraumatic hemoperitoneum (aOR 4.32; 95% CI, 2.41-7.74). During the study period, obstetric ECMO utilization has increased significantly and maternal prognosis improved.


Incremental area under response curve more accurately describes the triglyceride response to an oral fat load in both healthy and type 2 diabetic subjects.
Elevation of postprandial triacylglycerol (TG)-rich plasma lipoproteins is considered potentially atherogenic. Type 2 diabetic patients have exaggerated postprandial TG compared with healthy subjects. Postprandial TG responses to oral fat loads are usually studied as the area under the TG curve. No consensus exists regarding the method of choice when calculating the TG response area. We evaluated the correlation between fasting TG and postprandial TG responses calculated by the trapezoid rule as total area under the curve (AUC) and incremental area under the curve (iAUC). Furthermore, we compared the AUC and iAUC to a 3-point calculation method. Ten healthy subjects and 47 type 2 diabetic patients ingested test meals consisting of an energy-free soup plus 80 g fat and 50 g carbohydrate. TG responses were measured in total plasma, in a chylomicron (CM)-rich fraction and in a CM-poor fraction. In healthy subjects the AUC, but not iAUC, correlated positively to fasting TG. In type 2 diabetic patients a strong correlation was found between fasting TG and AUC, whereas weak associations were found to the iAUCs. The iAUC was strongly correlated to the postprandial TG rise in both groups. The 3-point areas differed significantly from the trapezoid measurements in both healthy and type 2 diabetic subjects. In conclusion, in both healthy and type 2 diabetic subjects total AUC is highly correlated to fasting TG, whereas iAUC more accurately describes the TG response to an oral fat load. The 3-point test seems less suitable for the determination of postprandial response in both healthy and type 2 diabetic subjects.


Liquid-like behavior of UV-irradiated interstellar ice analog at low temperatures.
Interstellar ice is believed to be a cradle of complex organic compounds, commonly found within icy comets and interstellar clouds, in association with ultraviolet (UV) irradiation and subsequent warming. We found that UV-irradiated amorphous ices composed of H2O, CH3OH, and NH3 and of pure H2O behave like liquids over the temperature ranges of 65 to 150 kelvin and 50 to 140 kelvin, respectively. This low-viscosity liquid-like ice may enhance the formation of organic compounds including prebiotic molecules and the accretion of icy dust to form icy planetesimals under certain interstellar conditions.


Water window ptychographic imaging with characterized coherent X-rays.
A ptychographical coherent diffractive imaging experiment in the water window with focused soft X-rays at 500 eV is reported. An X-ray beam with high degree of coherence was selected for ptychography at the P04 beamline of PETRA III synchrotron radiation source. The beam coherence was measured with the newly developed non-redundant array method, and a coherence length of 4.1 µm and global degree of coherence of 35% at 100 µm exit slit opening in the vertical direction were determined. A pinhole, 2.6 µm in size, selected the coherent part of the beam that was used to obtain ptychographic reconstruction results of a lithographically manufactured test sample and a fossil diatom. The achieved resolution was 53 nm for the test sample and was only limited by the size of the detector. The diatom was imaged at a resolution better than 90 nm.


Pulmonary endarterectomy in patients with occlusive isolated pulmonary vasculitis.
Isolated pulmonary vasculitis (IPV) is a rare, insidious, and localized inflammatory disease affecting the pulmonary arteries, often leading to severe luminal obstruction. The prognosis for patients with occlusive IPV is poor, and there is currently a lack of effective treatments. The objective of this study was to evaluate the performance of pulmonary endarterectomy (PEA) as a treatment for occlusive IPV. This single-center retrospective analysis included patients who received PEA for occlusive IPV between January 2018 and June 2022. Clinical characteristics and hemodynamic parameters were evaluated at baseline and follow-up. Among 114 consecutive patients who underwent PEA, occlusive IPV was identified in 7 patients. Two patients underwent bilateral PEA for the involvement of both pulmonary arteries. Patch angioplasty was performed to treat four severe constrictions. One patient died from residual pulmonary hypertension after limited PEA of a transmural vascular lesion. In addition, no obvious surgical complications were observed. Three months after PEA, a substantial relief in symptoms was achieved. Also, there is a decrease in the mean pulmonary artery pressure (median 33 [20-48] mmHg before versus median 21 [16-26] mmHg after; P < 0.018) and pulmonary arterial resistance (median 234 [131-843] dyn.s.cm-5 versus median 180 [150-372] dyn.s.cm-5; P = 0.310). Three patients experienced a relapse of restenosis of the treated arteries within a 6-month follow-up period, despite daily oral prednisolone administration. They were treated with balloon pulmonary angioplasty of both the main pulmonary arteries and branches. PEA is a valuable choice for treating occlusive IPV, with notable hemodynamic and clinical advantages. To increase long-term vascular patency, complete management should be optimized.


In Search of Narcissus.
Narcissism, a trait reflecting egocentric exceptionalism and social selfishness, has captured scholarly interest due to its intricate composition and social implications. The construct is polyhedric, comprising several key forms: grandiose versus vulnerable, agentic versus communal, admirative versus rivalrous, collective versus individual. These forms can be integrated into structural models that add predictive power or process models that add explanatory power. The narcissistic nucleus is argued, and partly shown, to be brittle in the face of self-threat. The nucleus may derive from being overvalued, or inconsistently socialised, by parents. Narcissism entails intrapersonal benefits, as it can confer psychological health, buffer against adversity, and facilitate performance. But it can also be an interpersonal and societal liability, partly remediable with narcissism-reduction interventions.


Ureaplasma urealyticum and Mycoplasma hominis isolation from cervical secretions of pregnant women and nasopharyngeal secretions of their babies at delivery.
A prospective study was carried out at the University Hospital, Kuala Lumpur to determine the cervical carriage rate of Ureaplasma urealyticum and Mycoplasma hominis among healthy pregnant women at delivery and the incidence of nasopharyngeal colonisation among their infants. Sixty mother and baby pairs were examined. Cervical colonisation among the mothers was found to be 56.7% for U.urealyticum and 17.7% for M.hominis. The transmission rate to their infants was 88.2% and 30% for U.urealyticum and M.hominis respectively. There was no statistically significant difference in the maternal colonisation rates according to ethnic group, parity and past history of abortion. All U.urealyticum isolates in our study were sensitive to erythromycin but about one-third were resistant to tetracycline and ciprofloxacin and 26.5% were resistant to minocycline.


Preparation and examination of monolithic in-needle extraction (MINE) device for the direct analysis of liquid samples.
Combination of extraction and chromatographic techniques opens NEW possibilities in sample preparation area. Macroporous poly(styrene-divinylbenzene) (PS-DVB) monoliths were prepared by in situ polymerization in stainless steel needles. The surface of stainless steel needle was modified earlier by the silane coupling agent. Monolithic materials located inside needles were used as the in-needle extraction device. Scanning electron microscope (SEM) images were obtained for nine monoliths. Spectra of prepared materials were also performed with the use of two techniques: Attenuated Total Reflectance (ATR) and Fourier Transform Infrared Spectroscopy (FTIR). The new monolithic in-needle extraction (MINE) devices were used in the preparation of a series of test water samples for chromatographic analysis. The extraction of phenolic compounds from water samples was carried out by pumping liquid samples through the MINE device. Obtained results indicate a high efficiency of in-needle extraction systems based on monolithic materials. Breakthrough volume and the sorption efficiency of prepared monolithic in-needle extraction devices were determined experimentally. The achieved recovery was close to 90%, and determined LOQ values varied between 0.4 and 6 μg.


Study of Emotion Regulation Based on Yogic Personality Using Implicit, Explicit, and Eye Tracking Techniques.
Emotion regulation (ER) is vital for well-being. Yogic personality traits, gunas, influence the expression of ER. To investigate the expression of ER based on guna-related personality traits employing explicit, implicit, and objective eye-tracking techniques. Quota sampling was used, with a cross-sectional design with three groups, sattva, rajas, and tamas. Three hundred and ninety-four female students were screened and finally, 30 from sattva, 34 from rajas, and 36 from tamas were analyzed. Participants were given State and Trait Mindfulness Scales, Gita Inventory, Social Desirability Scale, state-trait anxiety inventory, Adult Attachment Scale, and Emotional Regulation Questionnaire. ER-Implicit Association Test (ER-IAT) and Eye Tracker were also used to evaluate the participants. One-way repeated-measures analysis of variance was used to examine differences between sattva, rajas, and tamas. Sattva group adopted a higher level of regulation strategy, ER-IAT scores were positive for sattva, negative for rajas and tamas. Mindfulness was highest and anxiety was least in sattva. In the eye tracker, within the non-emotional areas of interest (eAOI) regions of pleasant condition, and eAOI regions of unpleasant condition, sattva group had considerably higher dwell time. Pupil dilation was lowest in sattva for all the conditions, both within and outside eAOIs. Sattva guna was found to foster healthy ER, and other psychological attributes. Conscious cultivation of sattva is needed for healthy emotional life.


Memory rescue and enhanced neurogenesis following electrical stimulation of the anterior thalamus in rats treated with corticosterone.
Deep brain stimulation has been investigated as a treatment for memory disturbance but its mechanisms remain elusive. We show that anterior thalamic nucleus (ATN) stimulation administered to corticosterone-treated rats one month prior to testing improved performance on a delayed non-matching to sample task and increased hippocampal neurogenesis. In contrast, no behavioral changes were observed in animals that were tested a few days after surgery. Results of this study suggests that the behavioral effects of ATN stimulation in corticosterone-treated animals was likely dependent on long-term plastic changes, including the development of newly borne dentate gyrus cells of sufficient functional maturity.


Factors associated with success in transition care services among older people in Australia.
The Australian Transition Care Program (TCP) is a national intermediate care service aiming to optimise functional independence and delay entry to permanent care for older people leaving hospital. The aim of this study was to describe the outcomes of TCP and identify demographic and clinical factors associated with TCP 'success', to assist with clinical judgements about suitable candidates for the program. We conducted a descriptive cohort study of all older Australians accessing TCP for the first time between 2007 and 2015. Logistic regression models assessed demographic and clinical factors associated with change in performance on a modified Barthel Index from TCP entry to discharge and on discharge to community. Fine-Gray regression models estimated factors associated with transition to permanent care within 6 months of TCP discharge, with death as a competing event. Functional independence improved from entry to discharge for 46,712 (38.4%) of 124,301 TCP users. Improvement was more common with younger age, less frailty, shorter hospital stay prior to TCP, and among women, those without a carer, living outside a major city, and without dementia. People who received TCP in a residential setting were far less likely to record improved functional impairment and more likely to be discharged to permanent care than those in a community setting. Discharge to community was more common with younger age and among women and those without dementia. Nearly 12% of community TCP and 63% of residential TCP users had transitioned to permanent care 6 months after discharge. Entry to permanent care was more common with older age, higher levels of frailty, and among those with dementia. More than half of TCP users are discharged to home and remain at home after 6 months. However, residential-based TCP may have limited efficacy. Age, frailty, carer status, and dementia are key factors to consider when assessing program suitability. Future studies comparing users to a suitably matched control group will be very helpful for confirming whether the TCP program is meeting its aims.


A survey of UK and Irish surgeons' attitudes, behaviours and barriers to change for environmental sustainability.
Surgery is a major contributor to the large environmental impact of healthcare, demanding urgent attention. To date there are no data on the attitudes and behaviours of surgeons towards climate change, or perceived barriers towards sustainable practice. We invited surgeons and surgical trainees in the UK and Ireland to participate in an online survey (developed in accordance with the CHERRIES checklist) conducted between June and November 2020 and disseminated via the Royal College of Surgeons of England, Edinburgh and Ireland, the Association of Surgeons in Training and through local communication. We received 130 responses, across 14 surgical specialties. The majority of respondents (122/130; 94%) were concerned about the threat of climate change. Most respondents had instigated more sustainable practices in their personal lives (113/130; 87%) and, to a lesser extent, at work (73/130; 56%). Surgeons were willing to make changes to their clinical practice (107/130; 82%), but the main perceived barrier to improving sustainability was a lack of leadership (92/130; 70%). Surgeons welcomed greater leadership and guidance from national bodies (118/130; 91%) and more monitoring and regulation (113/130; 87%). The surgeons who responded to our survey are concerned about climate change and willing to engage in efforts to transition to more sustainable practice, but would welcome greater support, guidance and leadership.


The Nonverbal Accommodation Analysis System (NAAS): initial application and evaluation.
To describe the development, initial application, and evaluation of the Nonverbal Accommodation Analysis System (NAAS). Grounded in Communication Accommodation Theory, this coding system provides a method for analyzing physician and patient nonverbal accommodation behaviors within medical consultations. Video recordings of 45 new visit consultations at a comprehensive cancer center were coded using the NAAS. Inter-rater and intra-rater reliability were assessed. For validation purposes, two independent coders rated all consultations for theoretically related constructs. The NAAS demonstrated high levels of reliability. Statistically significant correlations were observed across all 10 behavior categories for both inter-rater and intra-rater reliability. Evidence of content and construct validity was also observed. The current study presents the initial application and evaluation of a coding system meant for analysis of the nonverbal behavior of physicians and patients within medical consultations. The results of this initial trial and psychometric evaluation provide evidence of the NAAS as a valid and reliable nonverbal accommodation coding system. The NAAS enables researchers to investigate the way in which physicians and patients manage social distance through nonverbal behavior within medical interactions from a theoretically-informed perspective. Such efforts can aid in the development of communication skill interventions.


The 40-80 nt region in the 5'-NCR of genome is a critical target for inactivating poliovirus by chlorine dioxide.
Chemical disinfection is the most common method used to inactivate viruses from drinking water throughout the world. In this study, cell culture, ELISA, RT-PCR, and spot hybridization were employed to investigate the mechanism underlying chlorine dioxide (ClO(2) )-induced inactivation of Poliovirus type 1 (PV1), which was also confirmed by recombinant viral genome RNA infection models. The results suggested that ClO(2) inactivated PV1 primarily by disrupting the 5'-non-coding region (5'-NCR) of the PV1 genome. Further study revealed that ClO(2) degraded specifically the 40-80 nucleotides (nt) region in the 5'-NCR. Recombinant viral genome RNA infection models confirmed that PV1 RNA lacking this 40-80 nt region was not infectious. This study not only elucidated the mechanism of PV1 inactivation by ClO(2), but also defined the critical genetic target for the disinfectant to inactivate Poliovirus. This study also provides a strategy by which rapid, accurate, and molecular methods based on sensitive genetic targets may be established for evaluating the effects of disinfectants on viruses.


Three deaths involving triazolam--analytical aspects.
This case report describes three case histories and the analytical procedures used for the identification and quantification of triazolam. The levels of triazolam detected in the blood are interpreted with reference to those previously reported in the literature.


[Lactulose mannitol ratio in patients after operation].
To study lactulose (lactulose, L) and mannitol (mannitol, M) ratio in urine following operation and investigate the correlation between severity of stress and L/M ratio. 20 patients who had received operation were enrolled and each patient was evaluated by APACH II scores. L/M permeability study was performed before the operation and 5 and 10 days after the operation. The L and M concentration was analyzed by HPLC with pulsed electrochemical detection (HPLC-PED). The correlation between L/M ratio and the severity of surgical stress were related. The L/M ratio before the operation was (0.023 +/- 0.002), increased to (0.042 +/- 0.005) in the 5th post-operative day (P < 0.01), and then returned to (0.024 +/- 0.002) (P > 0.05) compared with pre-operation in the 10th Post-operation. A significant correlation between the severity of stress and the L/M ratio was observed (r = 0.762). The L/M ratio was increased 5 days after the operation and the L/M ratio was correlated with severity of operative stress.


The active site of methanol dehydrogenase contains a disulphide bridge between adjacent cysteine residues.
Adjacent cysteine residues can only form disulphide bridges in a distorted structure containing a cis-peptide link. Such bridges are extremely uncommon, identified so far in the acetyl choline receptor alone where the structure of the bridge is undetermined. Here we present the first molecular description of a disulphide bridge of this type in the quinoprotein methanol dehydrogenase from Methylobacterium extorquens. We show that this structure occurs in close proximity to the pyrrolo-quinoline quinone prosthetic group and a calcium ion in the active site of the enzyme. This unusual disulphide bridge appears to play a role in the electron transfer reaction mediated by methanol dehydrogenase.


[Hygiene as a weapon in the fight against SARS-Cov-2. All experts in taking care!]
To combat SARS-Cov-2, hygiene is essential for the safety of caregivers and saves lives. In hospital as well as in everyday social and professional environments, everyone is concerned by hygiene and distancing rules. It is an opportunity for us to reinvent ourselves, protect ourselves and protect the most vulnerable. In hospital, at the heart of the crisis, the action of the infection control team, which includes the infection control nurse, is one of the cornerstones of the fight against COVID-19.


Parasitic amebae in Korea.
This review dealt with biology, host-parasite relationship, symptomatology, epidemiology, diagnosis, treatment of Entamoeba histolytica infection and free livng amoeba.


Transcriptional regulation of early B-lymphocyte differentiation.
Differentiation of hematopoietic progenitors into the B-lymphocyte lineage requires co-ordination of a complex network of transcriptional regulators. Lineage specificity is likely to result from combinatorial mechanisms of gene regulation. Four general functions are mediated by transcription factors in the differentiating pro-B cell. First, a cascade of B-cell-restricted transcription factors is upregulated. Second, genes involved in the specification of other cell fates are repressed. Both activation and repression require the participation of different classes of transcriptional regulators, including proteins of the Ikaros family that can recruit chromatin-modifying complexes. Third, the expression of genes that facilitate B-cell proliferation and differentiation are activated. Lastly, genes required for recombination are expressed and targeted to the immunoglobulin loci, thus initiating the characteristic rearrangement of the immunoglobulin genes. The interactions and functions of transcription factors in pro-B-cell differentiation are discussed.


[Detection of the clusters of negative charges on the surface of erythrocyte cytoplasmic membranes by fluorescent probes].
When charges on the membrane surface are distributed unequally and, especially, when they are in clusters, the concept of Goue-Chapman is not valid. Clusters of the negative charges on the cell surface can be detected by the combination of two fluorescent probes and a polycation which is capable of neutralizing the electrostatic field of the cluster. Clusters of the negative charges have been detected on the membranes of erythrocyte ghosts. Protamine was used as polyanion and fluorescent probes ANS and DSM were used as a fluorescent anion and cation, respectively.


Increased variability of the coupling interval of premature ventricular beats may help to identify high-risk patients with coronary artery disease.
The purpose of this study was to determine the characteristics and predictive value of the variability of coupling interval of ventricular premature beats (VPBs) for cardiac mortality in patients with coronary artery disease (CAD). Frequent VPBs have been linked to an increased risk for cardiac death in patients with coronary artery disease. It is unknown whether analysis of coupling interval of VPBs from ambulatory ECG recordings can be used for risk statification in these patients. In 78 consecutive symptomatic patients with documented CAD who presented with frequent VPBs (>720/24 h), the analysis of VPBs' coupling interval (SDNV) was performed. Left ventricular function, ventricular arrhythmias and simple measures of heart rate variability were assessed. Mean follow-up was 702+/-329 days. Cardiac mortality was the primary end-point of the study. During follow-up, 14 patients died-11 deaths were cardiac. Left ventricular ejection fraction (LVEF)<40%; no beta-blocker treatment and digoxin use were clinical variables showing a significant association with cardiac mortality. The presence of non-sustained ventricular tachycardia (nsVT), especially if more than five episodes were present; short mean sinus cycle (<750 ms) and SDNV were associated with cardiac deaths. Mean SDNV was 79+/-29 in victims and 63+/-29 in survivors (p<0.05). Univariate Cox regression analysis revealed that the presence of SDNV>80 ms carried a relative risk of 6.7 for cardiac mortality. The adjusted relative risk was 13.3 for nsVT and 4.4 for SDNV>80 ms. Among patients with nsVT, mortality rate was significantly higher with SDNV>80 ms (58%), compared to lower SDNV (14%, p<0.01). Sixty-four percent mortality rate was observed in patients with LVEF<40%, presence of nsVT and SDNV>80 ms, compared to 17% in similar patients with lower SDNV (p<0.05). The analysis of coupling interval of ventricular premature beats form the same 24-h ECG recordings may complement the standard Holter analysis for risk stratification. This seems especially promising in the subgroups of patients at highest risk-those with LV systolic dysfunction, non-sustained VT or both.


Influence of the complete basis set approximation, tight weighted-core, and diffuse functions on the DLPNO-CCSD(T1) atomization energies of neutral H,C,O-compounds.
The impact of complete basis set extrapolation schemes (CBS), diffuse functions, and tight weighted-core functions on enthalpies of formation predicted via the DLPNO-CCSD(T1) reduced Feller-Peterson-Dixon approach has been examined for neutral H,C,O-compounds. All tested three-point (TZ/QZ/5Z) extrapolation schemes result in mean unsigned deviation (MUD) below 2 kJ mol-1 relative to the experiment. The two-point QZ/5Z and TZ/QZ CBS 1 / l max 3 extrapolation schemes are inferior to their inverse power counterpart ( 1 / l max + 1 / 2 4 ) by 1.3 and 4.3 kJ mol-1 . The CBS extrapolated frozen core atomization energies are insensitive (within 1 kJ mol-1 ) to augmentation of the basis set with tight weighted core functions. The core-valence correlation effects converge already at triple-ζ, although double-ζ/triple-ζ CBS extrapolation performs better and is recommended. The effect of diffuse function augmentation converges slowly, and cannot be reproduced with double- ζ or triple- ζ calculations as these are plagued with basis set superposition and incompleteness errors.


Expression of dose in neutron therapy.
A pragmatic approach in neutron dosimetry is to consider the energy spectrum to consist of a neutron and a gamma component. The relationship between the two components of dose in neutron radiotherapy has been investigated for energies currently in clinical use. Changes in the neutron component itself are not dealt with. Because the two components are given simultaneously there is some interaction between them so that the gamma fraction is more effective than if the neutron and gamma doses were separated in time. This interaction has been accounted for using a well-proven extension of the linear-quadratic (LQ) equation. Using values of the LQ parameters alpha and beta measured recently in vivo, we have modelled the total effect from the neutron and gamma dose-contributions in terms of an equivalent neutron dose. This allows a comparison of different methods of expressing the measured physical dose with the biologically effective dose. The current practice in neutron therapy is to give the total (neutron plus gamma) dose, quoting also the gamma contamination. In all cases within the range of energies used for therapy, the total dose will give an overestimate of the biologically effective dose by approximately 4% for each 5% of gamma contamination. Expression of the neutron dose only (ignoring the gamma component) will give an underestimate of the biologically effective dose by approximately 1.5% for each 5% of gamma contamination, i.e. the error is approximately three times less for neutron dose than for total dose.(ABSTRACT TRUNCATED AT 250 WORDS)


Lymphoid follicular proctitis. A condition different from ulcerative proctitis?
A heterogeneous group is formed by patients presenting with clinical features suggestive of inflammatory bowel disease limited to the rectum and whose rectal biopsies show lymphoid follicular hyperplasia of the mucosa. All these cases are traditionally considered as one variant of chronic ulcerative colitis, so-called ulcerative proctitis. Twenty such cases were critically assessed on clinical, endoscopic, and histologic grounds, as well as on response to treatment and follow-up data. While 11 patients showed clinicopathologic features consistent with typical chronic ulcerative colitis, the other nine patients appeared to form a different group, for which the term "lymphoid follicular proctitis" seemed justified. Lymphoid follicular proctitis was, overall, characterized by rectal bleeding, a congested and granular mucosa without ulceration, abnormal and coalescing hyperplastic lymphoid follicles without acute inflammation, and failure to respond to local steroid therapy. The nature of lymphoid follicular proctitis is uncertain at present but seems unrelated to chronic ulcerative colitis.


A cognitive and associative memory.
By introducing a physiological constraint in the auto-correlation matrix memory, the system is found to acquire an ability in cognition i.e. the ability to identify an input pattern by its proximity to any one of the stored memories. The physiological constraint here is that the attribute of a given synapse (i.e. excitatory or inhibitory) is uniquely determined by the neuron it belongs. Thus the synaptic coupling is generally not symmetric. Analytical and numerical analyses revealed that the present model retrieves a memory if an input pattern is close to the pattern of the stored memories; if not, it gives a clear response by going into a special mode where almost all neurons are in the same state in each time step. This uniform mode may be stationary or periodic, depending on whether or not the number of the excitatory neurons exceeds the number of inhibitory neurons.