How does juxtaluminal calcium affect critical mechanical conditions in carotid atherosclerotic plaque? An exploratory study.
The impact of calcification on the carotid atherosclerotic plaque vulnerability remains controversial and unclear. This study assesses the critical mechanical conditions induced by the calcium at the lumen surface, i.e., juxtaluminal calcification (JLCa), within human carotid atherosclerotic plaque. Eleven patients with evidence of JLCa were included for the analysis. The plaque geometry was reconstructed based on computed tomography and magnetic resonance images and 3-D fluid-structure interaction simulation was used for mechanical analysis. The presence of JLCa increased local stresses compared to when calcification was artificially covered with a 0.2-mm-thick fibrous cap (107.87 kPa [76.99, 129.14] versus 63.17 kPa [34.55, 75.13]; Median, [interquartile range]; ). Stretch ratio decreased from 1.18 [1.07, 1.27] to 1.13 [1.10, 1.18] (p = 0.03). The presence of JLCa significantly elevates local stress and stretch level. Further exploration of this plaque feature is warranted as a possible risk factor causing plaque vulnerability.


Reduced perceptual exclusivity during object and grating rivalry in autism.
The dynamics of binocular rivalry may be a behavioral footprint of excitatory and inhibitory neural transmission in visual cortex. Given the presence of atypical visual features in Autism Spectrum Conditions (ASC), and the growing evidence in support of the idea of an imbalance in excitatory/inhibitory neural transmission in animal and genetic models of ASC, we hypothesized that binocular rivalry might prove a simple behavioral marker of such a transmission imbalance in the autistic brain. In support of this hypothesis, we previously reported a slower rate of rivalry in ASC, driven by longer transitional states between dominant percepts. We tested whether atypical dynamics of binocular rivalry in ASC are specific to certain stimulus features. 53 participants (26 with ASC, matched for age, sex, and IQ) participated in a binocular rivalry experiment in which the dynamics of rivalry were measured at two levels of stimulus complexity, low (grayscale gratings) and high (colored objects). Individuals with ASC experienced a slower rate of binocular rivalry, driven by longer transitional states between dominant percepts. These exaggerated transitional states were present at both low and high levels of stimulus complexity (gratings and objects), suggesting that atypical binocular dynamics in autism are robust with respect to stimulus choice. Interactions between stimulus properties and rivalry dynamics in autism indicate that achromatic grating stimuli produce stronger group differences. These results confirm the finding of atypical dynamics of binocular rivalry in ASC. These dynamics were present for stimuli of both low and high levels of visual complexity, suggesting a pervasive imbalance in competitive interactions throughout the visual system of individuals with ASC.


Peroneus Longus Tendon Harvesting for Anterior Cruciate Ligament Reconstruction.
There remains controversy regarding the ideal graft choice for anterior cruciate ligament (ACL) reconstruction1. Bone-patellar tendon-bone and hamstring autografts have been considered the gold standard for decades. Despite the good clinical outcomes, donor-site morbidity is a concern for both of these grafts2. Peroneus longus tendon autograft has also been considered as a potential graft for many orthopaedic reconstructive procedures3. The biomechanical properties and thickness of such a graft permit its use for ACL reconstruction3,4. The tensile strength of a peroneus longus tendon autograft is the same as that of a hamstring autograft and greater than that of a bone-patellar tendon-bone graft and a quadriceps tendon graft3,5. We aimed to describe the steps to harvest the peroneus longus tendon autograft during single-bundle ACL reconstruction. Identification of anatomical landmarks is performed, including the distal aspect of the fibula and the posterior border of the fibula, 2 cm above the tip of the bone. A longitudinal incision is made along the posterior border of the fibular bone, from 2cm above the tip of the fibula. Care is taken to identify the tendon sheath that covers the longus and brevis approximately 2 cm above the superior extensor retinaculum, and the peroneus longus is stitched to the peroneus brevis. The proximal aspect of the peroneus longus tendon is whipstitched, after which the peroneus longus tendon and surrounding soft tissues are incised. The peroneus longus tendon is then released with use of a closed stripper, and the graft is prepared. Alternative nonoperative treatment options include physical therapy, nonsteroidal anti-inflammatory drugs, rest, and limitation of sporting activities. Alternative surgical treatment options include arthroscopic debridement, ACL repair or reconstruction with bone-patellar tendon-bone or hamstring-tendon autograft, and ACL reconstruction with allograft. Recent studies have shown that ACL reconstruction with use of a peroneus longus tendon autograft is safe and effective, with less donor-site morbidity compared with other tendon autografts4,6,7. The peroneus longus graft has been accepted for ligament reconstruction because of its strength, safety, and less donor-site morbidity7. The peroneus longus graft allows surgeons to harvest the autograft via a relatively small incision, resulting in fewer donor-site complications4. According to Rhatomy et al., the use of a peroneus longus graft provides good functional outcomes that are comparable with those of a hamstring autograft, but it has a larger graft diameter and its harvest results in less thigh hypotrophy8. Additionally, a case series of 10 patients who underwent ACL reconstruction with use of a peroneus longus autograft showed satisfactory Lysholm scores and low disability according to the Foot and Ankle Disability Index9. Examination under anesthesia and arthroscopic confirmation of the ACL tear are recommended prior to harvesting the peroneus longus tendon.Take care to identify the anatomical landmarks of the peroneus longus and brevis.Tenodesis of the peroneus longus to the brevis is performed first, followed by whipstitching of the peroneus longus proximal to the site of the tenodesis.Once the peroneus longus tendon is passed through the closed stripper, gently maintain traction on the sutures while pushing the stripper proximally until the tendon is freed.Care should be taken not to damage the superior peroneal retinaculum, which provides the primary restraint to tendon subluxation.Identification of the peroneus longus and brevis is important. The peroneus longus tendon is free of muscle attachment and more rounded in shape, while the peroneus brevis contains muscle fibers. PL = peroneus longusCI = confidence intervalIKDC = International Knee Documentation Committee.


Deoxyamphimedine, a pyridoacridine alkaloid, damages DNA via the production of reactive oxygen species.
Marine pyridoacridines are a class of aromatic chemicals that share an 11H-pyrido[4,3,2-mn]acridine skeleton. Pyridoacridine alkaloids display diverse biological activities including cytotoxicity, fungicidal and bactericidal properties, production of reactive oxygen species (ROS) and topoisomerase inhibition. These activities are often dependent on slight modifications to the pyridoacridine skeleton. Here we demonstrate that while structurally similar to neoamphimedine and amphimedine, the biological activity of deoxyamphimedine differs greatly. Deoxyamphimedine damages DNA in vitro independent of topoisomerase enzymes through the generation of reactive oxygen species. Its activity was decreased in low oxygen, with the removal of a reducing agent and in the presence of anti-oxidants. Deoxyamphimedine also showed enhanced toxicity in cells sensitive to single or double strand DNA breaks, consistent with the in vitro activity.


Sterically hindered luminescent Pt(II) -phosphite complexes for electroluminescent devices.
Pt(II) complexes with one bulky, sterically demanding, tertiary phosphite ancillary ligand and a coordinating chromophore are herein presented. The phosphite ligand, tris(2,4-di-tert-butylphenyl) acts as a bidentate ligand coordinating the platinum ion through the central phosphorus atom and a cyclometalating carbon atom of one of the substituents. The two free phenoxy moieties lie above and below the coordination plane, leading to steric hindrance that avoids aggregation and provides solubility in organic solvents. The other two coordination sites on the central metal ion are occupied by a chromophoric ligand, which is responsible for the energy of the luminescent excited state. This separation of functions, on the two coordinated ligands, allows the use of a wider range of luminophores with good luminescent properties, maintaining the control of the intermolecular interactions with the non-chromophoric ligand. Based on this approach we were able to achieve a bright deep blue emission (λ=444 nm, Φem =0.38) from a complex with a tailored ligand, which was then used for the fabrication of an electroluminescent device. In addition commercially available luminophores were also employed to synthesize green emitters.


Correction of Mandibular Retrognathia and Laterognathia by Distraction Osteogenesis: Follow up of 5 cases.
This article evaluates the use of distraction osteogenesis in the treatment of mandibular retrognathia and laterognathia and the long term treatment results of the patients treated with this technique. The procedure was carried out in 5 subjects (3 males and 2 females, mean age 18.4 years) aged between 14 years and 27 years. In patients treated with bilateral mandibular distraction, it was observed that the ANB angle decreased by a mean of 5 degrees , the mandibular corpus length increased by a mean of 14.5 mm and the overjet decreased by a mean of 12.2 mm after treatment. In patients treated with unilateral mandibular distraction, a mean of 3.5 degrees reduction was achieved in ANB angle, the mandibular corpus length increased by a mean of 5.5 mm and a mean of 7 mm correction was achieved in relation to craniofacial midline with treatment. One of these patients showed an increase of 10 mm in ramus height on the affected side and a decrease of 5 degrees in gonial angle whereas the other one showed an increase of 12.5 degrees in gonial angle and an increase of 11 mm in ramus height on the affected side after treatment. The most significant long term relapse was observed in one of the patients treated with bilateral mandibular distraction. Long term relapse seen in the rest of the patients was within clinically acceptable limits. It can be concluded that distraction of the deformed mandible is a feasible and effective technique for treating mandibular retrognathia and laterognathia. However, it must be borne in mind that accurate placement of the distractors and determining the correct distraction vector are crucial factors that have an influence on long term clinical success.


Cloning and functional expression of the mitochondrial alternative oxidase gene (aox1) of Aspergillus niger in Lactococcus lactis and its induction by oxidizing conditions.
Lactococcus lactis is a widely used food bacterium mainly known for its fermentation metabolism. An important, and for long time overlooked, trait of this species is its ability to perform respiratory metabolism in the presence of heme and under aerobic conditions. There is no evidence however for the presence of an alternative respiration pathway and AOX activity. In this study, a cDNA fragment encoding the mitochondrial alternative oxidase, the enzyme responsible for alternative respiration, from a citric acid producing Aspergillus niger strain was cloned and expressed in L. lactis as a host strain. Expression of aox1 conferred on this organism cyanide-resistant and salicylhydroxamate-sensitive growth. Bioreactor cultures under fully aerobic conditions of the transformed L. lactis showed that the alternative respiratory pathway operates and improves significantly the microorganism's response to oxidizing stress conditions as it enhances biomass production, suppresses lactate formation, and leads to accumulation of large amounts of nisin.


[Flow cytometric analysis of peripheral blood lymphocytes in children with chronic gastroduodenitis with and without Helicobacter pylori infection].
The immune system plays an important role in chronic gastroduodenitis. A group of 70 children with chronic gastroduodenitis were subjected to examinations, including 42 children with H. pylori infection (group I) and 28 children without H. pylori infection (group II). Applying the method of flow cytometry, the per cent values of peripheral blood lymphocytic subpopulations were determined before and after treatment. The obtained results of examinations in group I were compared with those obtained in group II and were also compared with the standards given by Zeman for healthy children. On the basis of analysis of own material it was found that in both studied groups before and after the treatment lower per cent values were observed of CD3 and CD8 T-cells, NK CD56 cells and higher value of CD4 to CD8 T-cell ratio was disclosed as compared to healthy children. Comparing the per cent values of lymphocytic subpopulations in children with and without H. pylori infection it was found that in group I a higher per cent of CD4 T-cells, lower per cent of CD8 T-cells and, therefore, higher value of CD4 to CD8 T-cell ratio were present.


Histogenesis-specific expression of fibroblast activation protein and dipeptidylpeptidase-IV in human bone and soft tissue tumours.
Fibroblast activation protein (FAP)/seprase and dipeptidylpeptidase-IV (DPP-IV)/CD26 are serine integral membrane proteases. They are involved in tissue remodelling, cancer invasion and metastases, mechanisms that are controversial. The aim was to identify cell types that express FAP and DPP-IV in human bone and soft tissue tumours, and to determine whether there are any correlations between the expression of FAP and DPP-IV and the malignant potential of tumours. This study analysed in situ expression in 25 malignant and 13 benign human bone and soft tissue tumours. Reverse transcriptase-polymerase chain reaction analyses confirmed mRNA expression of FAP and DPP-IV in all individuals. Immunohistochemistry using pre-fixed frozen sections revealed that FAP was positive in low-grade myofibroblastic sarcoma, the fibroblastic component of osteosarcomas, and malignant fibrous histiocytomas, but negative in Ewing's sarcomas and rhabdomyosarcomas. DPP-IV showed similar immunohistochemical results. Among benign tumours, non-ossifying fibromas, desmoid tumours and chondroblastomas expressed both FAP and DPP-IV. Giant cells expressed DPP-IV in giant cell tumours. Our data suggest that FAP and DPP-IV are consistently expressed in bone and soft tissue tumour cells that are histogenetically related to activated fibroblasts and/or myofibroblasts, irrespective of their malignancy. DPP-IV is also expressed in monocyte-macrophage lineage cells.


Antimicrobial resistance and presence of the SXT mobile element in Vibrio spp. isolated from aquaculture facilities.
The aim of this work was to assess the susceptibility of Vibrio spp. strains isolated from fish cultures against some usually applied antibiotics and the occurrence of the SXT mobile genetic element among them. Antimicrobial resistance was assessed by the standard disk diffusion technique while the presence of the SXT mobile genetic element was determined by conventional PCR. High levels of resistance to ampicillin (70%), cefoxitin (44%), streptomycin (31%), aztreonam (25%) and sulfamethoxazole (21%) were detected, and a high inter-and-intraspecies diversity in the resistance profile was observed for the majority of the analysed isolates. The SXT mobile genetic element was detected in only 4 isolates belonging to the species V. diazotrophicus (1), V. mediterranei (2) and V. vulnificus (1), which showed a variable antibiotic resistance profile. Horizontal antibiotic resistance gene transfer from the V. diazotrophicus SXT-positive strain to a laboratory E. coli strain was demonstrated under laboratory conditions. Our results suggest that the Vibrio spp. isolated from aquaculture facilities analysed in this study, although not being pathogenic, they constitute a source of antimicrobial resistance genes that could be mobilized to other bacterial populations through mobile genetic elements. However, the low occurrence of the SXT element in these isolates supports the hypothesis that this element is not involved in the development of resistance in the majority of Vibrio spp. in the examined aquaculture facilities.


Glucocorticoid enhances pulmonary surfactant protein B gene transcription.
The effect of glucocorticoid on the regulation of pulmonary surfactant protein B (SP-B) synthesis was studied in a human pulmonary adenocarcinoma cell line. Northern blot analysis demonstrated a marked increase in SP-B mRNA expression after treatment with dexamethasone for 48 h. Actinomycin D, puromycin, or cycloheximide blocked the induction of SP-B mRNA by glucocorticoid. Nuclear run-on experiments demonstrated that the effects of dexamethasone on SP-B mRNA were due in part to increased transcription of the SP-B gene. However, during this time period, there was a discrepancy between SP-B gene transcription, which was increased only 2- to 4-fold, and SP-B mRNA, which increased 60- to 150-fold after treatment with dexamethasone. In the presence of actinomycin D, SP-B mRNA was relatively stable, decreasing slowly in the presence or absence of glucocorticoid. In contrast to the relative stability of SP-B mRNA in the presence of actinomycin D, SP-B mRNA was markedly decreased after exposure to puromycin, supporting the premise that continued protein synthesis, rather than transcription alone, is required for maintenance of SP-B mRNA levels. Induction of SP-B expression by glucocorticoids was dependent on enhanced SP-B gene transcription and was also dependent on continued protein synthesis. The discrepancy between the relative enhancement of SP-B transcription and SP-B mRNA suggests that posttranscriptional factors influence SP-B expression in this cell line.


Development of Heat Shock Protein (Hsp90) Inhibitors To Combat Resistance to Tyrosine Kinase Inhibitors through Hsp90-Kinase Interactions.
Heat shock protein 90 (Hsp90) is a ubiquitous chaperone of all of the oncogenic tyrosine kinases. Many Hsp90 inhibitors, alone or in combination, have shown significant antitumor efficacy against the kinase-positive naïve and mutant models. However, clinical trials of these inhibitors are unsuccessful due to insufficient clinical benefits and nonoptimal safety profiles. Recently, much progress has been reported on the Hsp90-cochaperone-client complex, which will undoubtedly assist in the understanding of the interactions between Hsp90 and its clients. Meanwhile, Hsp90 inhibitors have shown promise against patients' resistance caused by early generation tyrosine kinase inhibitors (TKIs), and at least 13 Hsp90 inhibitors are being reevaluated in the clinic. In this regard, the objectives of the current perspective are to summarize the structure and function of the Hsp90-cochaperone-client complex, to analyze the structural and functional insights into the Hsp90-client interactions to address several existing unresolved problems with Hsp90 inhibitors, and to highlight the preclinical and clinical studies of Hsp90 inhibitors as an effective treatment against resistance to tyrosine kinase inhibitors.


Predictive factors of perinatal mortality in transfused fetuses due to maternal alloimmunization: what really matters?
Alloimmunization is the main cause of fetal anemia. There are not many consistent analyses associating antenatal parameters to perinatal mortality in transfused fetuses due to maternal alloimmunization. The study aimed to determine the prognostic variables related to perinatal death. A cohort study analyzed 128 fetuses treated with intrauterine transfusion (IUT), until the early neonatal period. Perinatal mortality was associated with prognostic conditions related to prematurity, severity of fetal anemia and IUT procedure by univariated logistic regression. Multiple logistic regression was used to compute the odds ratio (OR) for adjusting the hemoglobin deficit at the last IUT, gestational age at birth, complications of IUT, antenatal corticosteroid and hydrops. Perinatal mortality rate found in this study was 18.1%. The hemoglobin deficit at the last IUT (OR: 1.26, 95% CI: 1.04-1.53), gestational age at birth (OR: 0.53, 95% CI: 0.38-0.74) and the presence of transfusional complications (OR: 5.43, 95% CI: 142-20.76) were significant in predicting fetal death. Perinatal mortality prediction in transfused fetuses is not associated only to severity of anemia, but also to the risks of IUT and prematurity.


Biomechanical properties and healing effects of chitin patch in a rat full-thickness abdominal wall defect model.
Hernia repair is usually accompanied with the implantation of a synthetic mesh, which frequently results in a foreign body response and serious complications. In the present study, a novel biodegradable chitin-based hernia patch was prepared and characterized. Biomechanical properties and biodegradability of the chitin patch were quantified in vitro and in vivo. In repair of the rat abdominal wall full-thickness defect model, the chitin patch induced more abundant new blood vessels with milder tissue inflammation and fibrosis compared with polypropylene mesh. Chitin patch effectively inhibited excessive secretion of inflammation-associated cytokines (IL-6 and TNF-α) (p < 0.01) and significantly increased the secretion of healing-related cytokines (FGF1 and TGF-β1) (p < 0.01). Accompanied by biodegradation of the chitin patch, intra-abdominal adhesions caused by the chitin patch decreased significantly, and the tensile strength of the repaired site could meet the biomechanical requirements of human abdominal wall. After the one-year observation period, the defected abdominal wall returned to the appropriate thickness with no obvious complication or hernia occurrence. In a conclusion, the newly designed chitin patch showed good biomechanical properties and satisfactory healing effects on the full-thickness defect of abdominal wall, which makes it promising candidate for clinical hernia treatment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1349-1357, 2018.


Rationale of a lower dexamethasone dose in prenatal congenital adrenal hyperplasia therapy based on pharmacokinetic modelling.
Prenatal dexamethasone therapy is used in female foetuses with congenital adrenal hyperplasia to suppress androgen excess and prevent virilisation of the external genitalia. The traditional dexamethasone dose of 20 µg/kg/day has been used since decades without examination in clinical trials and is thus still considered experimental. As the traditional dexamethasone dose potentially causes adverse effects in treated mothers and foetuses, we aimed to provide a rationale of a reduced dexamethasone dose in prenatal congenital adrenal hyperplasia therapy based on a pharmacokinetics-based modelling and simulation framework. Based on a published dexamethasone dataset, a nonlinear mixed-effects model was developed describing maternal dexamethasone pharmacokinetics. In stochastic simulations (n = 1000), a typical pregnant population (n = 124) was split into two dosing arms receiving either the traditional 20 µg/kg/day dexamethasone dose or reduced doses between 5 and 10 µg/kg/day. Target maternal dexamethasone concentrations, identified from the literature, served as a threshold to be exceeded by 90% of mothers at a steady state to ensure foetal hypothalamic-pituitary-adrenal axis suppression. A two-compartment dexamethasone pharmacokinetic model was developed and subsequently evaluated to be fit for purpose. The simulations, including a sensitivity analysis regarding the assumed foetal:maternal dexamethasone concentration ratio, resulted in 7.5 µg/kg/day to be the minimum effective dose and thus our suggested dose. We conclude that the traditional dexamethasone dose is three-fold higher than needed, possibly causing harm in treated foetuses and mothers. The clinical relevance and appropriateness of our recommended dose should be tested in a prospective clinical trial.


[An electron spin resonance (ESR) study of lymphocyte membrane fluidity in patients with bronchial asthma and atopic dermatitis].
The lymphocyte membrane fluidity of patients with allergic diseases was measured by electron spin resonance (ESR), and the effect of the epinephrine stimulation on the membrane fluidity was examined. The peripheral lymphocytes were obtained from 15 patients with bronchial asthma and atopic dermatitis (28.7 +/- 9.9 years old, 10 females and 5 males) and 11 healthy adults (30.5 +/- 4.6 years old, 2 females and 9 males). Lymphocyte membranes were spin-labeled with 5-doxyl-stearic acid. Before and after the stimulation of epinephrine of the final concentrations at 10(-5) and 10(-4) mol/l, ESR spectra of the outer membranes were analyzed to evaluate the membrane fluidity. The membrane fluidity of the intact lymphocytes of allergic patients was significantly decreased in comparison to healthy controls. Although the epinephrine stimulation increased the lymphocyte membrane fluidity, the increase in fluidity was less in allergic patients than in healthy controls. There are various receptors on the surface of the lymphocyte membranes, and changes of the membrane fluidity have an influence on their functions. The results in this study elucidate the decreased fluidity of lymphocyte membrane in patients with bronchial asthma and atopic dermatitis, and suggest that the functions of the membrane receptors might be impaired.


Strain anisotropy in freestanding germanium nanoparticles synthesized by ball milling.
Although embedded Ge nanocrystals (NCs) have been grown by variety of techniques and its properties have been studied extensively, intrinsic properties of isolated Ge NCs have not been studied properly due to lack of proper synthesis technique. Here we report on the synthesis of freestanding Ge nanoparticles (NPs) down to approximately 7 nm using ball milling technique and study its structural evolution as a function of milling time. Morphology and microstructure of the freestanding Ge NPs are studied using atomic force microscopy, transmission electron microscopy and X-ray diffraction (XRD) analysis. A systematic study of the XRD line profile using Williamson-Hall method reveals presence of anisotropic strain in the milled NPs. Strain anisotropy factor is calculated using a modified Williamson-Hall method by taking into consideration a dislocation contrast factor, assuming that dislocations are main contributors to the strain in these NPs. Our calculations suggest that screw type dislocations are main contributors to the strain anisotropy in the Ge NPs. We find that for milling time up to 40 hrs, NPs size monotonically goes down to approximately 7.3 nm and then almost saturates, while the dislocation density first increases from 1.64 x 10(16) m(-2) to 11.62 x 10(17) m(-2) for milling time up to 20 hrs and then decreases drastically during further milling. We have monitored a low temperature heat release at approximately 310 degrees C from the milled NPs using differential scanning calorimetry, clearly indicating a kind of structural relaxation of the strained NPs.


Herpes simplex in gynecology and obstetrics.
The problems of herpes simplex in gynecology and obstetrics are reviewed. There were 40 patients showing the characteristic cellular changes of herpetic infection among the 79,357 Papanicolaou smears taken. Four patients, with cytologic evidence of herpes virus, also had cervical dysplasia. The relationship between herpes virus and dysplasia, carcinoma in situ, and invasive carcinoma is discussed. The use of a properly timed Papanicolaou smear to alert the physician to the danger of an infected birth canal is described. Three cases of neonatal herpes are cited.


The Flow Dependent Adhesion of von Willebrand Factor (VWF)-A1 Functionalized Nanoparticles in an in Vitro Coronary Stenosis Model.
In arterial thrombosis, von Willebrand factor (VWF) bridges platelets to sites of vascular injury. The adhesive properties of VWF are controlled by its different domains, which may be engineered into ligands for targeting nanoparticles to vascular injuries. Here, we functionalized 200 nm polystyrene nanoparticles with the VWF-A1 domain and studied their spatial adhesion to collagen or collagen-VWF coated, real-sized coronary stenosis models under physiological flow. When VWF-A1 nano-particles (A1-NPs) were perfused through a 75% stenosis model coated with collagen-VWF, the particles preferentially adhered at the post stenotic region relative to the pre-stenosis region while much less adhesion was detected at the stenosis neck (~ 65-fold less). When infused through collagen-coated models or when the A1 coating density of nanoparticles was reduced by 100-fold, the enhanced adhesion at the post-stenotic site was abolished. In a 60% stenosis model, the adhesion of A1-NPs to collagen-VWF-coated models depended on the location examined within the stenosis. Altogether, our results indicate that VWF-A1 NPs exhibit a flow-structure dependent adhesion to VWF and illustrate the important role of studying cardiovascular nano-medicines in settings that closely model the size, geometry, and hemodynamics of pathological environments.


Chronic Medical Conditions and Peripartum Mental Illness: A Systematic Review and Meta-Analysis.
The objective of this systematic review and meta-analysis was to examine the association between maternal chronic medical conditions (CMCs) and peripartum mental illness. MEDLINE, Embase, CINAHL, and PsycINFO were searched to September 2017. Data were extracted and quality was assessed using standardized instruments. We generated unadjusted and adjusted pooled odds ratios and 95% confidence intervals using DerSimonian and Laird random effects models. The review included 16 papers representing 12 studies and 1,626,260 women. CMCs overall were associated with peripartum mental illness overall (adjusted pooled odds ratios (aPOR) = 1.43, 95% confidence interval (CI): 1.25, 1.63). CMCs overall were associated with antepartum (aPOR = 1.41, 95% CI: 1.10, 1.81) and postpartum mental illness separately (aPOR = 1.44, 95% CI: 1.13, 1.85) and with peripartum depression (aPOR = 1.45, 95% CI: 1.25, 1.67) and anxiety separately (aPOR = 1.63, 95% CI: 1.35, 1.95). No studies examined bipolar or psychotic disorders. Diabetes (aPOR = 1.34, 95% CI: 1.07, 1.69), hypertension/heart disease (aPOR = 1.60, 95% CI: 1.05, 2.45), migraine (aPOR = 1.75, 95% CI: 1.20, 2.54), and other neurological disorders (aPOR = 1.45, 95% CI: 1.19, 1.77), but not asthma, were each associated with peripartum mental illness. Findings suggest that mental health resources should be integrated in medical settings where pregnant and postpartum women with CMCs are treated.


Intermittent bulk release of human cytomegalovirus.
Human Cytomegalovirus (HCMV) can infect a variety of cell types by using virions of varying glycoprotein compositions. It is still unclear how this diversity is generated, but spatio-temporally separated envelopment and egress pathways might play a role. So far, one egress pathway has been described in which HCMV particles are individually enveloped into small vesicles and are subsequently exocytosed continuously. However, some studies have also found enveloped virus particles inside multivesicular structures but could not link them to productive egress or degradation pathways. We used a novel 3D-CLEM workflow allowing us to investigate these structures in HCMV morphogenesis and egress at high spatio-temporal resolution. We found that multiple envelopment events occurred at individual vesicles leading to multiviral bodies (MViBs), which subsequently traversed the cytoplasm to release virions as intermittent bulk pulses at the plasma membrane to form extracellular virus accumulations (EVAs). Our data support the existence of a novel bona fide HCMV egress pathway, which opens the gate to evaluate divergent egress pathways in generating virion diversity.


Managed health care and the Massachusetts experience.
Managed health care, through prepaid health delivery systems and utilization review organizations, is perhaps the greatest trend in modern health care. The authors examine the remarkable growth of managed care and outline its clinical, economic, ethical, and practical implications. They then review examples of how organized psychiatry has been involved in managed care and describe the efforts to date of the Massachusetts Psychiatric Society in this area. Managed care is here to stay. The future climate of psychiatric practice and the care available to psychiatric patients are dependent on informed and organized activities by psychiatrists and their local and national representatives.


Differing risk factors for premature birth in adolescent mothers and adult mothers.
Although the survival rate of premature infants has improved, the prevalence of premature birth has not changed or has even increased. The purpose of this study is to analyze the demographic, psychosocial support, family planning, and health behavior risk factors for premature birth. This county-based, cross-sectional study collected information on 1,146 first-time mothers, including 556 adolescents (< 20 years old) and 590 adults (20-34 years old). Univariate and multivariate logistic regression analyses were used to study risk factors associated with premature birth. The prevalence of premature birth was 11.4% for adolescent mothers and 8.4% for adult mothers. Younger adolescent mothers (< 18 years old) (14.5%), fewer than 10 prenatal visits (12.5% vs. 6.7%), hypertension (33.3% vs. 8.9%), weight gain less than 10 kg (14.6% vs. 8.8%), drinking alcohol (23.1% vs. 9.5%), unintended pregnancy (13.6% vs. 7.4%), no parental support (16.8% vs. 9.1%), and victim of domestic violence (16.0% vs. 9.3%) were associated with a higher risk of premature birth (p < 0.05). In multivariate logistic regression analysis stratified by mother's age, prenatal visits less than 10 times (OR 2.68; 95% CI [1.38, 5.21]) and drinking alcohol (OR 25.0; 95% CI [1.35-460.49]) were significantly associated with premature birth for adult mothers but unintended pregnancy (OR 2.34; 95% CI [1.28, 4.27]) was the only significant factor for adolescent mothers. Differing risk factors for premature birth were found between adolescent and adult mothers. Effective family planning before gestation, alcohol abstinence, and regular prenatal visits for screening psychosocial, medical, and obstetric conditions during pregnancy are mandatory for the prevention of premature birth.


Preparation, physical properties, and evaluation of antioxidant capacity of aqueous grape extract loaded in chitosan-TPP nanoparticles.
Grape extract is reportedly rich in phenolic compounds that possess strong antioxidant activities. Encapsulation of such extracts in nanoparticles (NPs) is an effective way to preserve various food products. In the present study, grapes were first extracted, and the amount of total phenolic content and different types of phenolic acids was determined. The extracts at different chitosan/extract weight ratios (1:0.25, 1:0.5, 1:0.75, and 1:1) were then encapsulated in chitosan nanoparticles (NPs) using the ionic gelation method. The extract-loaded chitosan nanoparticles were characterized by their physicochemical properties using the dynamic light scattering (DLS) technique, chemical properties using Fourier-transform infrared (FTIR) spectroscopy, and X-ray powder diffraction technique (XRD), the morphological properties using scanning electron microscopy (SEM), and the antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test. The encapsulation efficiency (EE) and loading capacity (LC) were also assessed. Our findings showed that the free radical inhibition effect of NPs significantly increased with an increase in extract concentration. Chitosan NPs presented acceptable encapsulation efficiency and loading capacity (LC), and the encapsulation process enhanced the antioxidant activity of the free grape extracts. At the weight ratio of 1:0.5, the particle size and zeta potential of the NPs were 177.5 ± 2.12 nm and 32.95 ± 0.49 mV, respectively. FTIR and XRD analyses verified the credibility of the encapsulated grape extract in chitosan NPs. These NPs can be an efficient way to increase the shelf-life of food products.


Primary evaluation and management of statin therapy complications.
HMG-CoA reductase inhibitors (statins) have become one of the most commonly prescribed classes of medications in the United States. While serious adverse events are rare, less serious events are frequently seen. Published guidelines recommend initial screening labs as well as ongoing monitoring of liver enzymes during therapy. Up to 5% of patients will have some muscle complaints while taking statins. Therefore, primary care clinicians will often be faced with real or potential complications of statin therapy. There are well established risk factors for development of these complications. Being aware of a patient's risk and using the lowest effective dose minimizes the occurrence of adverse events. The great majority of these abnormalities either do not require discontinuation of therapy or require only brief interruption of therapy. Judicious and systematic use of laboratory testing will minimize needless evaluation and premature discontinuation of statin therapy.


Outcomes of Concurrent Functional Endoscopic Sinus Surgery and Rhinoplasty: A Meta-analysis.
Chronic rhinosinusitis (CRS) and functional nasal airway obstruction are common but distinct medical problems which affect quality of life. In certain instances, patients often benefit from concomitant functional septorhinoplasty, or elect for cosmetic rhinoplasty, in addition to functional endoscopic sinus surgery (FESS) and prefer combining procedures. Determining outcomes of combined surgery is important when discussing risks and benefits with patients. A thorough literature search of articles published in PubMed, Ovid MEDLINE, and Cochrane databases. Patients were categorized as either having FESS or rhinoplasty alone or combined. Binary random-effects models were applied to calculate odds ratios (ORs) for outcomes including complications, recurrence, and satisfaction. Of the 55 screened articles, 6 were included in the analysis, and of these, 6 (405 patients), 2 (90 patients), 4 (290 patients), and 3 (190 patients) provided data for postoperative complications, recurrence of CRS symptoms, revision rates, and patient satisfaction, respectively. Major complications were observed in 11 (5.8%) total combined cases, 0 (0%) FESS cases, and 6 (3.5%) rhinoplasty cases with no statistical difference between combined cases and rhinoplasties (OR 1.37, 95% CI 0.45-4.16, p = 0.58). Recurrence of CRS symptoms was noted in 35.6% combined cases and 28.9% FESS cases (OR 1.42, 95% CI 0.55-3.64, p = 0.47). There was no observed difference in revision rates between combined and isolated rhinoplasties (OR 1.00, 95% CI 0.43-2.32, p = 1). Lastly, 91.6% of patients were satisfied with results of combined cases compared to 87.4% of patients in standalone cases (OR 1.57, 95% CI 0.61-4.03, p = 0.35). Aggregate evidence demonstrates similar risk in complication rates in combined surgical cases compared to stand-alone rhinoplasty. There appears to be no significant difference in recurrence of symptoms, revision rates or patient satisfaction.


[Killing of leukemic cells by anti-CD3McAb plus rIL-2 activated cord blood].
To investigate the killing efficacy of cord blood monocyte activated by Anti-CD3 monoclonal antibody(McAb) in K562 and HL-60 cell lines. By using indirect rosette forming test, antigen expression rate of monocyte was detected. The levels of interleukin-8 (IL-8), IL-6 and tumor necrosis factor alpha (TNF-alpha) were measured by ELISA. The killing efficacy in 3H-thymidine target cells was detected by beta-liquid scintillator. After being activated by Anti-CD3McAb and rIL-2, the antigen expression of monocyte was changed markedly. The levels of IL-8, IL-6 and TNF-alpha were increased; The Anti-CD3 McAb activated killer cells produced significant lysis in K562 and HL-60 cell lines and the optimum conditions were as follows: concentration of cells, 1 x 10(6)/ml; Anti-CD3McAb, 1 microgram/ml; rIL-2 1,000 U/ml; time of culture, 72 hrs; ratio of effector/target: 100:1. Anti-CD3 McAb activated killer cells exhibited a strong cytotoxicity to leukemic cells. Our study provides a theoretical basis for the adoptive immunotherapy of leukemia by activated cord blood.


Four-Dimensional Printing of Stimuli-Responsive Hydrogel-Based Soft Robots.
The present protocol describes the creation of four-dimensional (4D), time-dependent, shape-changeable, stimuli-responsive soft robots using a three-dimensional (3D) bio-printing method. Recently, 4D printing techniques have been extensively proposed as innovative new methods for developing shape-transformable soft robots. In particular, 4D time-dependent shape transformation is an essential factor in soft robotics because it allows effective functions to occur at the right time and place when triggered by external cues, such as heat, pH, and light. In line with this perspective, stimuli-responsive materials, including hydrogels, polymers, and hybrids, can be printed to realize smart shape-transformable soft robotic systems. The current protocol can be used to fabricate thermally responsive soft grippers composed of N-isopropylacrylamide (NIPAM)-based hydrogels, with overall sizes ranging from millimeters to centimeters in length. It is expected that this study will provide new directions for realizing intelligent soft robotic systems for various applications in smart manipulators (e.g., grippers, actuators, and pick-and-place machines), healthcare systems (e.g., drug capsules, biopsy tools, and microsurgeries), and electronics (e.g., wearable sensors and fluidics).


Screening and risk stratification of patients with the metabolic syndrome and diabetes.
The metabolic syndrome is a clustering of risk factors known to promote or increase the risk for development of cardiovascular disease. Recent estimates demonstrate that approximately one-third of the adult population of developed countries are characterized with metabolic syndrome by different definitions. Metabolic syndrome, even in the absence of diabetes, is associated with an increased risk of cardiovascular disease and total mortality, as well as an increased risk for the development of diabetes. Patients with diabetes are considered a cardiovascular risk equivalent, and warrant aggressive management of underlying risk factors to optimize prevention of cardiovascular disease. Initial evaluation of coronary heart disease risk involves global risk estimation using Framingham or other algorithms for risk prediction. Furthermore, consideration of screening for novel risk factors, such as C-reactive protein, as well as subclinical atherosclerosis (as assessed by carotid ultrasound, computed tomography or ankle-brachial index), can further refine the estimation of future cardiovascular disease risk. The presence of subclinical atherosclerosis or elevated levels of C-reactive protein can potentially modify recommended treatment goals for lipid and other cardiovascular risk factors.


Lateral diffusion of cholesterol and dimyristoylphosphatidylcholine in a lipid bilayer measured by pulsed field gradient NMR spectroscopy.
The pulsed field gradient NMR method for measuring self-diffusion has been used for a direct determination of the lateral diffusion coefficient of cholesterol, fluorine labeled at the 6-position, for an oriented lamellar liquid-crystalline phase of dimyristoylphosphatidylcholine (DMPC)/cholesterol/water. It is found that the diffusion coefficients of DMPC and cholesterol are equal over a large temperature interval. The apparent energy of activation for the diffusion process (58 kJ/mol) is about the same as for a lamellar phase of DMPC/water, whereas the phospholipid lateral diffusion coefficient is approximately four times smaller in the presence of cholesterol.


Hepatocellular carcinoma and impact of aflatoxin difuranocoumarin derivative system – A case report.
Hepatocellular carcinoma (HCC) is the most frequent type of liver malignancy. As a carcinogen, aflatoxin B1 (AFB1) causes HCC by inducing deoxyribonucleic acid adducts that lead to genetic changes in liver cells and may be the cause of HCC in up to 30% of cases. The incidence of HCC has been on the rise and is an issue in the countries of the Western Balkans. This paper presents a case of a 37-year-old woman who was diagnosed with HCC, without hepatitis B, hepatitis C, or liver cirrhosis. The patient consumed milk and dairy products in quantities of over two liters per day over the course of 20 years, which indicates the impact of aflatoxin in milk on HCC. A positive signal for the presence of AFB1 was detected by ELISA (enzyme-linked immunosorbent assay) in-house using immunoperoxidase screening test. As carcinogenic difuranocoumarin derivative, aflatoxin B1 is the most likely cause of malignant transformation of hepatocytes, which resulted in hepatocellular carcinoma in this patient.


Intimal sarcoma of the descending aorta.
Primary intimal angiosarcoma of the aorta (i.e., mostly intraluminal sarcomas with evidence of endothelial differentiation) is extraordinarily rare. We report a case in which the diagnosis was accurately made using immunohistochemistry in an embolectomy specimen. The patient was a 78-year-old man with a two-month history of bilateral claudication. Doppler ultrasound proved an embolus in both popliteal arteries, which was removed. The highly atypical cells comprising these emboli were positive immunohistochemically for CD68, vimentin, and CD31. Magnetic resonance imaging also showed an irregular tumor (invasion to the left main bronchus). This case emphasizes the need for a wide panel of immunohistochemical studies in tumor emboli of unknown origin.


Review on molecular and chemopreventive potential of nimbolide in cancer.
Cancer is the most dreaded disease in human and also major health problem worldwide. Despite its high occurrence, the exact molecular mechanisms of the development and progression are not fully understood. The existing cancer therapy based on allopathic medicine is expensive, exhibits side effects; and may also alter the normal functioning of genes. Thus, a non-toxic and effective mode of treatment is needed to control cancer development and progression. Some medicinal plants offer a safe, effective and affordable remedy to control the cancer progression. Nimbolide, a limnoid derived from the neem (Azadirachta indica) leaves and flowers of neem, is widely used in traditional medical practices for treating various human diseases. Nimbolide exhibits several pharmacological effects among which its anticancer activity is the most promising. The previous studies carried out over the decades have shown that nimbolide inhibits cell proliferation and metastasis of cancer cells. This review highlights the current knowledge on the molecular targets that contribute to the observed anticancer activity of nimbolide related to induction of apoptosis and cell cycle arrest; and inhibition of signaling pathways related to cancer progression.


Management of Cleft Palate in Puppies Using A Temporary Prosthesis: A Report of Three Cases.
Cleft palate in dogs is a congenital defect that mostly leads to euthanasia of the affected puppy. If an attempt is made to raise the puppy, it is generally fed via an orogastric tube. Here, we describe the management of cleft palate in three puppies (two Boxers, one Collie) using a customised temporary prosthesis, which allowed the puppies to be bottle-fed and successfully raised by their owners (Cases 2 and 3) and the author (Case 1). The temporary palatal prosthesis was manufactured from a mouthguard intended for human children, which is made of thermoplastic silicone. The preparation procedure was simple and cost-effective. All puppies underwent corrective surgery at 5⁻6 months of age. After surgery, one of the Boxer puppies showed mandibular mesioclusion, while the other two showed no aberrations. All puppies gained the same amount of weight as their littermates, although the weight gain of the two Boxers was slower than that of their littermates. In summary, this case report describes an easy and effective way to raise puppies with cleft palate until corrective surgery can be performed.


Alterations in host defense associated with anesthesia and blood transfusions. II. Effect on response to endotoxin.
The effect of blood transfusions and anesthesia on host response to endotoxin was evaluated in multiple Lewis rat models. The rats were randomized to receive A'Sogaloff Cancer Institute rat blood, pentobarbital sodium, or lactated Ringer's solution and, at either 2 or 7 days following administration of these agents, were challenged with intravenous endotoxin. Neither blood transfusions nor anesthesia altered mortality when administered 2 days before endotoxin challenge. However, blood transfusions administered 7 days before endotoxin challenge were found to prolong survival, to prevent endotoxin-induced alterations in T-lymphocyte subsets, and to decrease plasma tumor necrosis factor levels. In conclusion, blood transfusions appear to depress immune function in a beneficial manner in endotoxin shock.


Schwann Cell Responses and Plasticity in Different Dental Pulp Scenarios.
Mammalian teeth have evolved as dentin units that enclose a complex system of sensory innervation to protect and preserve their structure and function. In human dental pulp (DP), mechanosensory and nociceptive fibers form a dense meshwork of nerve endings at the coronal dentin-pulp interface, which arise from myelinated and non-myelinated axons of the Raschkow plexus (RP). Schwann cells (SCs) play a crucial role in the support, maintenance and regeneration after injury of these fibers. We have recently characterized two SC phenotypes hierarchically organized within the coronal and radicular DP in human teeth. Myelinating and non-myelinating SCs (nmSCs) display a high degree of plasticity associated with nociceptive C-fiber sprouting and axonal degeneration in response to DP injuries from dentin caries or physiological root resorption (PRR). By comparative immunolabeling, confocal and electron microscopy, we have characterized short-term adaptive responses of SC phenotypes to nerve injuries, and long-term changes related to aging. An increase of SCs characterizes the early responses to caries progression in association with axonal sprouting in affected DP domains. Moreover, during PRR, the formation of bands of Büngner is observed as part of SC repair tracks functions. On the other hand, myelinated axon density is significantly reduced with tooth age, as part of a gradual decrease in DP defense and repair capacities. The remarkable plasticity and capacity of SCs to preserve DP innervation in different dental scenarios constitutes a fundamental aspect to improve clinical treatments. This review article discusses the central role of myelinating and non-mSCs in long-term tooth preservation and homeostasis.


Clinical evaluation of a new orally active anti-anaphylactic compound: ketotifen (HC 20-511) in Japanese adult asthmatics.
The protective effect of ketotifen was examined by an open assessment trial in 261 asthmatics of variable types, a double blind trial comparing ketotifen and inert placebo in 189 asthmatics of extrinsic type including pure atopic asthma and asthma with atopic and infectious components (mixed type or combined type), and a double blind trial comparing ketotifen and disodium cromoglycate (DSCG) by double placebo technique in 132 asthmatics of a pure atopic type. The open clinical assessment trial suggested that ketotifen was most effective in atopic asthmatics having moderate and severe as well as mild asthmatic episodes. Efficacy increased with prolonged administration; 1 mg twice daily was better than a 1 mg daily dose. In the placebo-controlled double blind trial, the efficacy of ketotifen was demonstrated by the reduction of concomitant anti-asthmatic therapy. The results of the double blind trial comparing ketotifen and DSCG are not fully reported. However, preliminary data showed that the efficacy of both drugs was equivalent or that ketotifen was slightly superior to DSCG. Safety of ketotifen was confirmed by the three trials, transient day-time sedation being the major side effect of this agent. In conclusion, ketotifen is a promising drug for the prophylaxis of asthma.


Bimodal effects of 1R,2R-diaminocyclohexane(trans-diacetato)(dichloro)platinum(IV) on cell cycle checkpoints.
1R,2R-Diaminocyclohexane(trans-diacetato)(dichloro)-platinum(IV) (DACH-acetato-Pt) is a novel platinum-based agent that is highly effective against cisplatin-resistant ovarian tumor cells. To probe its cellular mechanism, the effects of DACH-acetato-Pt (0-6.4 microM) on cell cycle checkpoints were examined using the ovarian cancer A2780 cell line as the model system. We found that DACH-acetato-Pt at > or =0.2 microM dramatically inhibited cell growth and induced cell death. At concentrations < or =0.6 microM (low effective concentrations), DACH-acetato-Pt specifically induced G(1) phase arrest by selectively inhibiting cyclin-dependent kinase 4 (Cdk4) and Cdk2 activities. The Cdc2 activity, which regulates G(2)-M phase progression, was unaffected by the drug at these concentrations. At concentrations >0.6 microM (high effective concentrations), DACH-acetato-Pt first transiently inhibited S-phase progression and then blocked cell cycle progression at both G(1) and G(2) phases. These cell cycle effects were associated with sequential inhibitions of Cdk2/cyclin A activity, Cdk4 and Cdk2 activities, and Cdc2 kinase activity. Following the cell cycle effects, both the low and high effective concentrations of DACH-acetato-Pt induced cell death through apoptosis. These results indicate that DACH-acetato-Pt activates multiple cell cycle checkpoints in a bimodal manner and suggest that the cell cycle effects demonstrated in these studies may be linked to its ability to induce apoptosis.


Facets Matching of Platinum and Ferric Oxide in Highly Efficient Catalyst Design for Low-Temperature CO Oxidation.
Rational design of supported noble metal is of great importance for highly efficient heterogeneous catalysts. On the basis of the distinct adsorption characteristics of noble metal and transition-metal oxides toward O2 and CO, the overall catalytic performance of CO oxidation reaction could be further modified by controlling the surface property of the materials to achieve optimal adsorption activity. Here, we studied the influence of facets matching between both platinum and ferric oxide support on CO conversion efficiency. It shows that the activities of four catalysts rank following the order of Pt{100}/α-Fe2O3{104} > Pt{100}/α-Fe2O3{001} > Pt{111}/α-Fe2O3{001} > Pt{111}/α-Fe2O3{104}. The strong metal-support interaction and adsorption energy varying with matched enclosed surface are demonstrated by density functional theory based on the projected d-band density of states. Compared with the other three cases, the combination of Pt{100} and α-Fe2O3{104} successfully weakens CO poisoning and provides proper active sites for O2 adsorption. It reveals that the facets matching could be a practicable approach to design catalysts with enhanced catalytic performance.


The short form effort-reward imbalance: Measure of occupational stress for firefighters.
The original effort-reward imbalance (ERI) questionnaire has been widely used as a measure of occupational stress. The need for brief measurement of psychosocial stress at work has risen. This study examined the psychometric properties of a 16-item short form ERI (S-ERI) questionnaire. A cross-sectional study was conducted with a convenience sample of 247 career firefighters in the United States. An internet-based survey contained the S-ERI questionnaire, and assessed perceived health, demographics, and work characteristics. Internal consistency was tested by item-total correlation and Cronbach's α coefficients. Factorial validity was assessed by confirmatory factor analysis (CFA), and criterion validity was examined by testing the S-ERI's association with perceived health, controlling for other factors. The study participants were primarily young and mid-aged White males (mean age = 42 years, 75% White non-Hispanic, 93% males). The S-ERI questionnaire showed satisfactory internal consistency, with Cronbach α coefficients above 0.80 for all three scales: effort 0.82, reward 0.83, and overcommitment 0.81. CFA showed all the S-ERI components had a good fit (goodness-of-fit index = 0.99, comparative fit index = 0.92, root mean square error of approximation = 0.06). In terms of criterion validity, significantly increased odds ratios (ORs) for perceived health (those indicating they were less healthy) were found in firefighters in the lowest tertile of reward (OR = 7.06, 95% confidence interval [CI]: 2.86-17.43), and highest tertile of overcommitment (OR = 2.29, 95% CI: 1.00-5.22), after controlling for other factors. The S-ERI questionnaire is a reliable and valid measure to assess occupational stress. We recommend the use of S-ERI as a measure of occupational stress when initiating efforts to improve firefighters' wellness.


Calmodulin inhibitors from Leucophyllum ambiguum.
Activity-directed fractionation of a CH(2)Cl(2)-MeOH (1:1) extract of Leucophyllum ambiguum led to the isolation of two new lignans designated with the trivial names of 2'-methoxykobusin (1) and 2'-methoxy-4' '-hydroxydemethoxykobusin (2). In addition, the known compounds kobusin (3), 2',2' '-dimethoxysesamin (4), trans-cinnamic acid, apigenin, and apigetrin were obtained. The identification of the novel analogues 1 and 2 was accomplished by spectral methods. The structure of 1 was unequivocally confirmed by X-ray analysis. Compounds 1-4 interacted with bovine-brain calmodulin and inhibited the activation of the calmodulin-dependent enzyme cAMP phosphodiesterase.


HEADWAY TIME AND CRASHES AMONG NOVICE TEENS AND EXPERIENCED ADULT DRIVERS IN A SIMULATED LEAD TRUCK BRAKING SCENARIO.
Driving simulators can be used to evaluate driving performance under controlled, safe conditions. Teen drivers are at particular risk for motor vehicle crashes and simulated driving can provide important information on performance. We developed a new simulator protocol, the Simulated Driving Assessment (SDA), with the goal of providing a new tool for driver assessment and a common outcome measure for evaluation of training programs. As an initial effort to examine the validity of the SDA to differentiate performance according to experience, this analysis compared driving behaviors and crashes between novice teens (n=20) and experienced adults (n=17) on a high fidelity simulator for one common crash scenario, a rear-end crash. We examined headway time and crashes during a lead truck with sudden braking event in our SDA. We found that 35% of the novice teens crashed and none of the experienced adults crashed in this lead truck braking event; 50% of the teens versus 25% of the adults had a headway time <3 seconds at the time of truck braking. Among the 10 teens with <3 seconds headway time, 70% crashed. Among all participants with a headway time of 2-3 seconds, further investigation revealed descriptive differences in throttle position and brake pedal force when comparing teens who crashed, teens who did not crash and adults (none of whom crashed). Even with a relatively small sample, we found statistically significant differences in headway time for adults and teens, providing preliminary construct validation for our new SDA.


Effect of quetiapine and norquetiapine on anxiety and depression in major psychoses using a pharmacokinetic approach: a prospective observational study.
Quetiapine apparently differs from other antipsychotic drugs in terms of its antidepressant activity and efficacy in bipolar depression. The mechanism of this activity is unknown although it may be mediated by its metabolite N-desalkylquetiapine (norquetiapine). The aim of the study was to analyse the relationships between quetiapine and norquetiapine plasma concentrations and clinical improvement in depressive and anxious symptoms. This was a prospective observational study. Recruited patients were evaluated during a clinical post-acute phase. Patients were recruited from patients hospitalized in the Psychiatric Department of Ospedale Maggiore Policlinico of Milan, Italy. After discharge they were followed-up as outpatients. The study involved 41 outpatients (23 males, 18 females; age >18 years) diagnosed as affected by schizophrenia (17 patients), borderline personality disorder (eight patients) or bipolar depression (16 patients) on the basis of the Diagnostic and Statistical Manual of Mental Disorders, fourth text revision (DSM-IV-TR) criteria. Patients were prescribed 50-800 mg of quetiapine (Seroquel®). Patients were evaluated after discharge from the psychiatric department (baseline, T0), after 15 days (T1) and after 3 months (T2) using the Brief Psychiatry Rating Scale (BPRS) with particular reference to the dimensions of depression (items 5, 9 and 13) and anxiety (items 1, 2 and 6). Plasma quetiapine and norquetiapine concentrations were determined by means of high-performance liquid chromatography at T2. There was a significant improvement in the mean BPRS total score, as well as in the dimensions of anxiety and depression. The bipolar patients only showed a significant curvilinear relationship described by a second-order polynomial model between the plasma norquetiapine/quetiapine concentration ratio and the improvement in depression at T2. There was a significant negative linear correlation between the norquetiapine/quetiapine ratio and anxiety in all of the patients. The results of this study confirm the efficacy of quetiapine on both anxious and depressive symptoms. Norquetiapine has a specific effect on anxiety and depressive symptoms, showing a correlation between plasma concentrations and clinical efficacy only in patients with bipolar depression.


Five-year comparative study of thin-strut rapamycin-eluting bioabsorbable scaffold with metallic drug-eluting stent in porcine coronary artery.
Using quantitative coronary angiography (QCA), optical coherence tomography (OCT), histomorphometry, and pharmacokinetics, this study tried to evaluate the safety and efficacy of Biomagic rapamycin-eluting bioabsorbable scaffold (BVS) in non-atherosclerotic porcine coronary arteries. Biomagic BVS is a new generation of thin-strut bioabsorbable scaffold. We conducted comparative study detailing pathological response, safety and efficacy of Biomagic BVS and the Firebird2 rapamycin-eluting cobalt-based alloy stent (DES) in a porcine coronary artery model. The animals were followed up at 14 days, 1, 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months after stent implantation. A total of 143 devices (95 Biomagic and 48 Firebird2) were implanted in 2 or 3 main coronary arteries of 76 nonatherosclerotic swine and examined by QCA, OCT, light microscopy, and pharmacokinetics analyses at various time points. Vascular responses to Biomagic and Firebird2 were largely comparable at all time points, with struts being sequestered within the neointima. The degree of inflammation of both devices was mild to moderate, although the Biomagic score was higher at 14 days to 24 months. However, there was no statistical difference between the two groups except 14 days. At each follow-up time point, the percentage of area stenosis in the Biomagic group was greater than that in the Firebird 2 group, but there was no statistical difference between the two groups at 3 and 12 months. The extent of fibrin deposition was similar between Biomagic and Firebird2, which peaked at 1 month and decreased rapidly thereafter. Pharmacokinetic study showed that coronary tissue sirolimus concentration remained above 2 ng/mg of tissue at 28 day. Histomorphometry showed expansile remodeling of Biomagic-implanted arteries starting after 12 months, and lumen area was significantly greater in Biomagic than Firebird2 at 36 and 42 months. These changes correlated with dismantling of Biomagic seen after 12 months. OCT images confirmed that degradation of Biomagic was complete by 36 months. Biomagic demonstrates comparable long-term safety to Firebird2 in porcine coronary arteries with mild to moderate inflammation. Although Biomagic was associated with greater percent stenosis relative to Firebird2 within 36 months, expansile remodeling was observed after 12 months in Biomagic with significantly greater lumen area at ≥36 months. Scaffold resorption is considered complete at 36 months.


Structure-activity relationships among the kanamycin aminoglycosides: role of ring I hydroxyl and amino groups.
The kanamycins form an important subgroup of the 4,6-disubstituted 2-deoxystreptamine aminoglycoside antibiotics, comprising kanamycin A, kanamycin B, tobramycin, and dibekacin. These compounds interfere with protein synthesis by targeting the ribosomal decoding A site, and they differ in the numbers and locations of amino and hydroxy groups of the glucopyranosyl moiety (ring I). We synthesized kanamycin analogues characterized by subtle variations of the 2' and 6' substituents of ring I. The functional activities of the kanamycins and the synthesized analogues were investigated (i) in cell-free translation assays on wild-type and mutant bacterial ribosomes to study drug-target interaction, (ii) in MIC assays to assess antibacterial activity, and (iii) in rabbit reticulocyte translation assays to determine activity on eukaryotic ribosomes. Position 2' forms an intramolecular H bond with O5 of ring II, helping the relative orientations of the two rings with respect to each other. This bond becomes critical for drug activity when a 6'-OH substituent is present.


Integrated care in Switzerland: Results from the first nationwide survey.
Due to fragmentation of care delivery, health systems are under pressure and integrated care is advocated for. Compared to the numerous existing integrated care initiatives in Europe and elsewhere, Switzerland seems to lag behind. The objective of the survey was to produce a comprehensive overview of integrated care initiatives in Switzerland. To be included, initiatives needed to meet four criteria: present some type of formalization, consider >2 different groups of healthcare professionals, integrate >2 healthcare levels, be ongoing. We systematically contacted major health system organizations at federal, cantonal and local level. Between 2015 and 2016, we identified 172 integrated care initiatives and sent them a questionnaire. We performed descriptive analyses. Integrated care initiatives in Switzerland are frequent and increasing. The implementation of initiatives over time, their distribution between linguistic areas, the number of healthcare levels integrated, and the number of professionals involved vary according to the type of initiatives. Despite Switzerland's federalist structure and organization of healthcare, and only recent incentives to develop integrated care, initiatives are frequent and diverse. Stakeholders should support existing initiatives and facilitate their development. They should also promote innovative avenues, experiment alternative payment models for integrated care, foster people-centeredness and incentivize interprofessional models. This will require systems thinking and contributions from all actors of the healthcare system.


Feeding the world in the coming decades requires improvements in investment, technology and institutions.
The world is food secure at the global level, yet nearly 800 million are food insecure. "Business as usual" is not going to bring us close to meeting the Millennium Development Goal of halving the proportion of the population consuming less than the minimum energy requirement. So what has to change? The three papers in this session offer clues in three broad areas: (a) increased investment-by developing and developed countries-in public goods such as agricultural research, education, and clean water, (b) technologies to boost agricultural productivity for the poor and institutions that guide the diffusion and application of technology that need to be developed and (c) national-level institutions and governance structures to be strengthened and held accountable for protecting and respecting human rights, for providing the right types of national-level public goods to those that most need them and for preserving peace and stability.


Thin film assemblies of molecularly-linked metal nanoparticles and multifunctional properties.
The use of metal nanoparticles as building blocks toward thin film assembly creates intriguing opportunities for exploring multifunctional properties. Such an exploration requires the ability to engineer the size, shape, composition, and especially interparticle properties in nanoparticle assemblies for harnessing the collective properties of the nanoscale building blocks. This article highlights some of the important findings of our investigations of thin film assemblies of molecularly linked nanoparticles for exploiting their multifunctional and collective properties in molecular recognition and chemical sensing. The thermally activated processing approach presents a viable pathway for nanoengineering metal, alloy, and core-shell nanoparticles as building blocks. The molecular mediator-templating approach offers an effective strategy to thin film assemblies of the nanoscale building blocks that impart multifunctional properties. In such thin film assemblies, the interparticle interactions and structures dictate the correlation between the nanostructural parameters and the optical and electrical properties. By highlighting selected examples involving ligand-framework binding of ionic species at the film/liquid interface and electrical responses to molecular sorption at the film/gas interface, the multifunctional properties of the thin film assemblies are further discussed in terms of interparticle covalent, hydrogen bonding, ionic, or van der Waals interactions in a framework-type architecture for the creation of molecular recognition and chemical sensing sites that can be tuned chemically or electrochemically. Implications of these insights to expanding the exploration of nanoparticle thin film assemblies for a wide range of technological applications are also discussed.


Characterization of the input material quality for the production of tisagenlecleucel by multiparameter flow cytometry and its relation to the clinical outcome.
Tisagenlecleucel (tisa-cel) is a CD19-specific CAR-T cell product approved for the treatment of relapsed/refractory (r/r) DLBCL or B-ALL. We have followed a group of patients diagnosed with childhood B-ALL (n = 5), adult B-ALL (n = 2), and DLBCL (n = 25) who were treated with tisa-cel under non-clinical trial conditions. The goal was to determine how the intensive pretreatment of patients affects the produced CAR-T cells, their in vivo expansion, and the outcome of the therapy. Multiparametric flow cytometry was used to analyze the material used for manufacturing CAR-T cells (apheresis), the CAR-T cell product itself, and blood samples obtained at three timepoints after administration. We present the analysis of memory phenotype of CD4/CD8 CAR-T lymphocytes (CD45RA, CD62L, CD27, CD28) and the expression of inhibitory receptors (PD-1, TIGIT). In addition, we show its relation to the patients' clinical characteristics, such as tumor burden and sensitivity to prior therapies. Patients who responded to therapy had a higher percentage of CD8+CD45RA+CD27+ T cells in the apheresis, although not in the produced CAR-Ts. Patients with primary refractory aggressive B-cell lymphomas had the poorest outcomes which was characterized by undetectable CAR-T cell expansion in vivo. No clear correlation of the outcome with the immunophenotypes of CAR-Ts was observed. Our results suggest that an important parameter predicting therapy efficacy is CAR-Ts' level of expansion in vivo but not the immunophenotype. After CAR-T cells' administration, measurements at several timepoints accurately detect their proliferation intensity in vivo. The outcome of CAR-T cell therapy largely depends on biological characteristics of the tumors rather than on the immunophenotype of produced CAR-Ts.


Characteristics and Fate of Systemic Artery Aneurysm after Kawasaki Disease.
To determine the long-term outcome of systemic artery aneurysms (SAAs) after Kawasaki disease (KD). We investigated the characteristics and the fate of SAAs in 20 patients using medical records and angiograms. The age of onset of KD ranged from 1 month to 20 months. The interval from the onset of KD to the latest angiogram ranged from 16 months to 24 years. The regression rate of peripheral artery aneurysm and the frequency of stenotic lesions were analyzed by the Kaplan-Meier method in 11 patients who had undergone initial angiography within 4 months. The mean duration of fever was 24 ± 12 days. All 20 patients had at least 1 symmetric pair of aneurysms in bilateral peripheral arteries, and 16 patients had multiple SAAs. The distributions of SAAs was as follows: brachial artery, 30; common iliac artery, 20; internal iliac artery, 21; abdominal aortic aneurysm, 7; and others, 29. The frequencies of regression of SAA and of the occurrence of stenotic lesions at 20 years after the onset of KD were 51% and 25%, respectively (n = 42). The diameter of all SAAs in the acute phase leading to stenotic lesions in the late period was >10 mm. SAAs occurred symmetrically and were multiple in younger infants and those with severe acute vasculitis. The fate of SAAs resembles that of coronary artery aneurysms, and depends on the diameter during the acute phase. Larger SAAs can lead to stenotic lesions in the late period.


Respiratory activity and oxidative phosphorylation in mitochondria of the rat brain and liver under conditions of elevated temperature of the environment.
The rate of oxygen consumption by mitochondrial fractions of the brain and liver of rats under elevated ambient temperature was investigated. The animals were placed in a thermostatized chamber for 6 hours at 21 degrees, 28 degrees or 37 degrees C. During the experiment, relative humidity in the chamber was controlled. After exposure, the animals were decapitated, mitochondrial fractions isolated and oxygen consumption measured with the Clark electrode. Respiratory substrates of succinate and glutaminate with malate were used. The analysis of the obtained results was based on the t-Student test, assuming the values obtained for the animals staying at 21 degrees as the control values. It was found that the 6 hrs stay under the ambient hyperthermy conditions did not induce any disturbances in the respiratory processes and oxidative phosphorylation in rat's brain and liver mitochondria.


Sri Lankan rice mixed meals: effect on glycaemic index and contribution to daily dietary fibre requirement.
The glycaemic index (GI) concept ranks starchy foods according to the blood glucose responses following ingestion. When considering commonly consumed Sri Lankan meals, only a few can be categorised as low GI. However, a significant negative correlation between the GI of Sri Lankan meals and fibre content has been observed indicating the potential to reduce the GI of meals by incorporating naturally occurring sources of fibre. Thus, the objective of this study was to study the effect of increased edible quantities of fibre on the GI of rice meals consumed in Sri Lanka. Meal 1 consisted of rice with several meal accompaniments (lentil curry, boiled egg, coconut gravy and Centella asiatica (gotukola) leaves salad). Meal 2 contained similar constituents as meal 1 and a Lasia spinosa (kohila) rhizome salad. The composition of meal 3 was similar to meal 2 but contained Trichosanthes cucumerina (snake gourd) salad instead of Lasia spinosa salad. Meal 3 contained similar fibre contents as meal 1 and similar meal size as meal 2. The glycaemic indices of the three meals were determined with healthy individuals (n=10, age=20-30 yrs, BMI=24 +/- 3 kg/m2) using bread as the standard. Meals 1 and 3 contained total dietary fibre (TDF) contents of 15.2g. Meal 2 contained 16.3g TDF. The GI values of the three meals were 63 +/- 5, 57 +/- 5, 61 +/- 5 respectively and were not significantly different from one another (p>0.05). The GI of the rice mixed meal 2 was reduced by 9% when total edible dietary fibre content of the actual meal was increased by 7.2%. The study results show that the GI of rice mixed meals may be reduced by including naturally occurring sources of fibre with starchy staples while fulfilling daily dietary fibre requirement of an adult at low cost.


An atypical spinal meningioma with CSF metastasis: fatal progression despite aggressive treatment. Case report.
The authors report the case of a 23-year-old man who presented with a C1-3 spinal mass. Following intraspinal decompression the tumor was histologically classified as an atypical meningioma (World Health Organization grade II). Two further surgical interventions resulted in almost total removal of the meningioma. In addition, radiotherapy was performed. During the 1.5-year follow-up period the diagnostic examinations identified a local tumor recurrence, an intraspinal C-6 metastasis, and a segmental instability with anterior C2-3 slippage and C3-4 kyphosis. The tumor was resected and occipitocervical stabilization was performed. Histological examination showed no change in malignancy. Despite additional hydroxyurea-based chemotherapy, the patient presented 4 months later with a hemiparesis and a massive recurrence of the tumor mass involving the posterior fossa and the upper thoracic spine. Because there were no further therapeutical options, the patient died. The authors discuss more aggressive therapeutic options in addition to surgery in patients with metastatic atypical meningiomas. The results in the reported case indicate that meningiomas associated with cerebrospinal fluid metastasis may represent a higher grade of malignancy.


The IQA Energy Partition in a Drug Design Setting: A Hepatitis C Virus RNA-Dependent RNA Polymerase (NS5B) Case Study.
The interaction of the thumb site II of the NS5B protein of hepatitis C virus and a pair of drug candidates was studied using a topological energy decomposition method called interacting quantum atoms (IQA). The atomic energies were then processed by the relative energy gradient (REG) method, which extracts chemical insight by computation based on minimal assumptions. REG reveals the most important IQA energy contributions, by atom and energy type (electrostatics, sterics, and exchange-correlation), that are responsible for the behaviour of the whole system, systematically from a short-range ligand-pocket interaction until a distance of approximately 22 Å. The degree of covalency in various key interatomic interactions can be quantified. No exchange-correlation contribution is responsible for the changes in the energy profile of both pocket-ligand systems investigated in the ligand-pocket distances equal to or greater than that of the global minimum. Regarding the hydrogen bonds in the system, a "neighbour effect" was observed thanks to the REG method, which states that a carbon atom would rather not have its covalent neighbour oxygen form a hydrogen bond. The combination of IQA and REG enables the automatic identification of the pharmacophore in the ligands. The coarser Interacting Quantum Fragments (IQF) enables the determination of which amino acids of the pocket contribute most to the binding and the type of energy of said binding. This work is an example of the contribution topological energy decomposition methods can make to fragment-based drug design.


Incisional vacuum-assisted closure therapy.
Postoperative swelling and prolonged drainage from surgical incisions result in both practical and medical burdens, such as increased need for dressing changes and potentially higher rates of surgical wound infection. This article presents a technique to apply a vacuum-assisted closure therapy sponge as a postoperative dressing to provide a clean, dry wound environment in the immediate postoperative period.


Discrete Curvature Representations for Noise Robust Image Corner Detection.
Image corner detection is very important in the fields of image analysis and computer vision. Curvature calculation techniques are used in many contour-based corner detectors. We identify that existing calculation of curvature is sensitive to local variation and noise in the discrete domain and does not perform well when corners are closely located. In this paper, discrete curvature representations of single and double corner models are investigated and obtained. A number of model properties have been discovered, which help us detect corners on contours. It is shown that the proposed method has a high corner resolution (the ability to accurately detect neighboring corners), and a corresponding corner resolution constant is also derived. Meanwhile, this method is less sensitive to any local variations and noise on the contour; and false corner detection is less likely to occur. The proposed detector is compared with seven state-of-the-art detectors. Three test images with ground truths are used to assess the detection capability and localization accuracy of these methods in cases with noise-free and different noise levels; 24 images with various scenes without ground truths are used to evaluate their repeatability under affine transformation, JPEG compression, and noise degradations. The experimental results show that our proposed detector attains a better overall performance.


Abnormalities in the zinc-metalloprotease-BDNF axis may contribute to megalencephaly and cortical hyperconnectivity in young autism spectrum disorder patients.
Whereas aberrant brain connectivity is likely the core pathology of autism-spectrum disorder (ASD), studies do not agree as to whether hypo- or hyper-connectivity is the main underlying problem. Recent functional imaging studies have shown that, in most young ASD patients, cerebral cortical regions appear hyperconnected, and cortical thickness/brain size is increased. Collectively, these findings indicate that developing ASD brains may exist in an altered neurotrophic milieu. Consistently, some ASD patients, as well as some animal models of ASD, show increased levels of brain-derived neurotrophic factor (BDNF). However, how BDNF is upregulated in ASD is unknown. To address this question, we propose the novel hypothesis that a putative zinc-metalloprotease-BDNF (ZMB) axis in the forebrain plays a pivotal role in the development of hyperconnectivity and megalencephaly in ASD. We have previously demonstrated that extracellular zinc at micromolar concentrations can rapidly increase BDNF levels and phosphorylate the receptor tyrosine kinase TrkB via the activation of metalloproteases. The role of metalloproteases in ASD is still uncertain, but in fragile X syndrome, a monogenic disease with an autistic phenotype, the levels of MMP are increased. Early exposure to lipopolysaccharides (LPS) and other MMP activators such as organic mercurials also have been implicated in ASD pathogenesis. The resultant increases in BDNF levels at synapses, especially those involved in the zinc-containing, associative glutamatergic system may produce abnormal brain circuit development. Various genetic mutations that lead to ASD are also known to affect BDNF signaling: some down-regulate, and others up-regulate it. We hypothesize that, although both up- and down-regulation of BDNF may induce autism symptoms, only BDNF up-regulation is associated with the hyperconnectivity and large brain size observed in most young idiopathic ASD patients. To test this hypothesis, we propose to examine the ZMB axis in animal models of ASD. Synaptic zinc can be examined by fluorescence zinc staining. MMP activation can be measured by in situ zymography and Western blot analysis. Finally, regional levels of BDNF can be measured. Validating this hypothesis may shed light on the central pathogenic mechanism of ASD and aid in the identification of useful biomarkers and the development of preventive/therapeutic strategies.


Cyclic nucleotide gated channel gene family in tomato: genome-wide identification and functional analyses in disease resistance.
The cyclic nucleotide gated channel (CNGC) is suggested to be one of the important calcium conducting channels. Nevertheless, genome-wide identification and systemic functional analysis of CNGC gene family in crop plant species have not yet been conducted. In this study, we performed genome-wide identification of CNGC gene family in the economically important crop tomato (Solanum lycopersicum L.) and analyzed function of the group IVb SlCNGC genes in disease resistance. Eighteen CNGC genes were identified in tomato genome, and four CNGC loci that were misannotated at database were corrected by cloning and sequencing. Detailed bioinformatics analyses on gene structure, domain composition and phylogenetic relationship of the SlCNGC gene family were conducted and the group-specific feature was revealed. Comprehensive expression analyses demonstrated that SlCNGC genes were highly, widely but differently responsive to diverse stimuli. Pharmacological assays showed that the putative CNGC activators cGMP and cAMP enhanced resistance against Sclerotinia sclerotiorum. Silencing of group IVb SlCNGC genes significantly enhanced resistance to fungal pathogens Pythium aphanidermatum and S. sclerotiorum, strongly reduced resistance to viral pathogen Tobacco rattle virus, while attenuated PAMP- and DAMP-triggered immunity as shown by obvious decrease of the flg22- and AtPep1-elicited hydrogen peroxide accumulation in SlCNGC-silenced plants. Additionally, silencing of these SlCNGC genes significantly altered expression of a set of Ca(2+) signaling genes including SlCaMs, SlCDPKs, and SlCAMTA3. Collectively, our results reveal that group IV SlCNGC genes regulate a wide range of resistance in tomato probably by affecting Ca(2+) signaling.


Investigation the effects of silver nanoparticles and gold nanoparticles on expression of bap and csu genes in biofilm formation of Acinetobacter baumannii.
Acinetobacter baumannii is one of the main pathogens of the hospital and causes various infections. csu A/BABCDE involved in the initial surface attachment during biofilm formation and bap gene produces specific proteins at the cell surface that play a direct role in formation of biofilm and the infectivity of this bacterium. The aim of this study was to investigate the effect of silver nanoparticles and gold nanoparticles on the expression of bap and csu genes in the Acinetobacter baumannii biofilm formation. The susceptibility test was performed to determine the MIC of silver nanoparticles, gold nanoparticles and gold-vancomycin nanoparticles performed by broth dilution method on A. baumannii strains. The ability of biofilms formation in strains treated by MIC of silver nanoparticles and gold-vancomycin nanoparticles were evaluated by microtiter plate method and A. baumannii ATCC19606 used as control. Expression of the csu and bap genes were determinded by measuring the cognate mRNA level by real-time PCR. In present study, gold nanoparticles could not prevent the growth and biofilm formation of A. baumannii strains. The MIC concentration of silver nanoparticles and vancomycin- gold nanoparticles were 6.25 μg/ml and 0.625 μg/ml respectively and MBC concenteration of nanoparticles for 70% of strain was 12.5 μg/ml and 1.25 μg/ml respectively. Real-time PCR and data analysis, determined that the expression of bap, csuC and csuE genes in A. baumannii strains treated with MIC concentration (6.25 μg/ml) of silver nanoparticles decreased compared to control groups. Also, the expression of csuC and csuE genes in strains treated with MIC concentration (0.625 μg/ml) of vancomycin -gold nanoparticles increased, however the expression of bap was decreased compared to the control groups. Due to the inhibitory effect of silver nanoparticles and gold-vancomycin nanoparticles against A. baumannii biofilm formation and genes expression, they can probably be used for prevent of biofilm formation in medical instrument or can be use for treatment of infections with or without antibiotic.


Dispersive liquid-liquid microextraction coupled with dispersive micro-solid-phase extraction for the fast determination of polycyclic aromatic hydrocarbons in environmental water samples.
A new two-step microextraction technique, combining dispersive liquid-liquid microextraction (DLLME) and dispersive microsolid-phase extraction (D-micro-SPE), was developed for the fast gas chromatographic-mass spectrometric determination of polycyclic aromatic hydrocarbons (PAHs) in environmental samples. A feature of the new procedure lies in that any organic solvent immiscible with water can be used as extractant in DLLME. A special apparatus, such as conical-bottom test tubes, and tedious procedures of centrifugation, refrigeration of the solvent, and then thawing it, associated with classical DLLME or similar techniques are not necessary in the new procedure, which potentially lends itself to possible automation. In the present D-micro-SPE approach, hydrophobic magnetic nanoparticles were used to retrieve the extractant of 1-octanol in the DLLME step. It is noteworthy that the target of D-micro-SPE was the 1-octanol rather than the PAHs. Because of the rapid mass transfer associated with the DLLME and the D-micro-SPE steps, fast extraction could be achieved. Parameters affecting the extraction efficiency were investigated in detail. The optimal conditions were as follows: vortex at 3200 rpm in the DLLME step for 2 min and in D-micro-SPE for 1 min and then desorption by sonication for 4 min with acetonitrile as the solvent. The results demonstrated that enrichment factors ranging from 110- to 186-fold were obtained for the analytes. The limits of detection and the limits of quantification were in the range of 11.7-61.4 pg/mL and 0.04-0.21 ng/mL, respectively. The linearities were 0.5-50, 1-50, or 2-50 ng/mL for different PAHs. Finally, the two-step extraction method was successfully used for the fast determination of PAHs in river water samples. This two-step method, combining two different and efficient miniaturized techniques, provides a fast means of sample pretreatment for environmental water samples.


A study of patient attitudes towards fasting prior to intravenous sedation for dental treatment in a dental hospital department.
Intravenous sedation is the most commonly used method of sedation for the provision of adult dental care. However, disparity exists in pre-operative fasting times in use for patients throughout the United Kingdom. The aims of the study were to obtain information on the effects of existing extended pre-operative fasting regimens, to canvas patient opinions on the fasting process, and to record their positive and negative experiences associated with it. A prospective cross-sectional descriptive study using survey methodology was conducted of adult patients attending a dental hospital for operative treatment under intravenous sedation. Sixty-four questionnaires were distributed over a four-month period, beginning 2nd October 2007. The surveyed patient pool consisted of 38 females and 14 males with a mean age of 32.4 years. The response rate achieved was 81.2%. Seventy-one per cent of patients indicated that normally they consumed something for breakfast, the most common items being tea and toast. Fifty-one per cent of patients indicated that they would wish to eat the same as normal prior to their appointment and 59% wished to drink as normal. Only 19% of respondents reported that they did not wish to eat anything, with 8% preferring not to drink anything at all. Seventy-nine per cent of the patients reported that they had experienced at least one adverse symptom after fasting and 42% had experienced two or more such symptoms. In general, those patients with more experience of sedation found fasting less unpleasant than those attending for the first time (P<0.05). In addition, one-quarter of all patients indicated that the fasting process had made them feel more nervous about their sedation appointment. The extended fasting regimen prior to intravenous sedation appeared to affect patients' wellbeing, as the majority reported adverse symptoms.


Clinical applications of mini-implants as orthodontic anchorage and the peri-implant tissue reaction upon loading.
Orthodontic tooth treatment depends on anchorage for improved results. There are many different sources of orthodontic anchorage. Segments of teeth or the entire arch have been the most common type of orthodontic anchorage. But in challenging situations, orthodontists frequently need extra-dental supplements of anchorage such as headgear, face mask, and intermaxillary elastics. Most of them require the patient's compliance. Recently, temporary mini-implants placed within the bone tissue have been used as orthodontic anchorage. It has been proven in many studies and case reports that the mini-implant is a very reliable anchorage source clinically and histologically. The purpose of this article is to introduce the basic clinical application of mini-implants as orthodontic anchorage and to discuss basic concepts about the tissue reaction of peri-implant bone upon placement and loading either from orthodontic mechanics and/or function in the orthodontic treatment of the patients. It is possible for mini-implants to supply absolute anchorage even though they may move slightly within the bone tissue without losing clinical stability. The primary application of mini-implants as orthodontic anchorage will be cases that need absolute anchorage for desired tooth movement.


Regulation of PIP5K activity by Arf6 and its physiological significance.
The phospholipid kinase phosphatidylinositol 4-phosphate 5-kinase (PIP5K) catalyzes the phosphorylation of the membrane phospholipid phosphatidylinositol 4-phosphate to generate the pleiotropic phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2) ]. To date, three mammalian PIP5K isozymes, α, β, and γ, and several splicing variants of the γ isozyme have been identified. These PIP5K isozymes and PIP5Kγ variants play critical roles in various cellular functions through their product PI(4,5)P(2) . The small GTPase Arf6 is one of the key activators of PIP5K. Increasing evidence suggests that PIP5K functions as a downstream effector of Arf6 to regulate a wide variety of cellular functions, such as exocytosis, endocytosis, endosomal recycling, membrane ruffle formation, immune response, and bacterial invasion. In this review, we place our focus on the recent advances in Arf6/PIP5K signaling and its linkage to cellular functions.


Excitatory Neuronal Responses of Ca2+ Transients in Interstitial Cells of Cajal in the Small Intestine.
Interstitial cells of Cajal (ICC) regulate smooth muscle excitability and motility in the gastrointestinal (GI) tract. ICC in the deep muscular plexus (ICC-DMP) of the small intestine are aligned closely with varicosities of enteric motor neurons and thought to transduce neural responses. ICC-DMP generate Ca2+ transients that activate Ca2+ activated Cl- channels and generate electrophysiological responses. We tested the hypothesis that excitatory neurotransmitters regulate Ca2+ transients in ICC-DMP as a means of regulating intestinal muscles. High-resolution confocal microscopy was used to image Ca2+ transients in ICC-DMP within murine small intestinal muscles with cell-specific expression of GCaMP3. Intrinsic nerves were stimulated by electrical field stimulation (EFS). ICC-DMP exhibited ongoing Ca2+ transients before stimuli were applied. EFS caused initial suppression of Ca2+ transients, followed by escape during sustained stimulation, and large increases in Ca2+ transients after cessation of stimulation. Basal Ca2+ activity and the excitatory phases of Ca2+ responses to EFS were inhibited by atropine and neurokinin 1 receptor (NK1) antagonists, but not by NK2 receptor antagonists. Exogenous ACh and substance P (SP) increased Ca2+ transients, atropine and NK1 antagonists decreased Ca2+ transients. Neurokinins appear to be released spontaneously (tonic excitation) in small intestinal muscles and are the dominant excitatory neurotransmitters. Subcellular regulation of Ca2+ release events in ICC-DMP may be a means by which excitatory neurotransmission organizes intestinal motility patterns.


Indirect inductively coupled plasma atomic emission determination of fluoride in water samples by flow injection solvent extraction.
An indirect determination of fluoride in water by inductively coupled plasma atomic emission spectrometry combined with flow injection coupled with solvent extraction is reported in this paper. A manifold for rapid determination of fluoride has been designed that uses a single coil for complex formation and extraction. The method involves the formation of lanthanum/alizarin complexone/fluoride complex and its extraction into hexanol containing N,N-diethylaniline. The concentration of fluoride is determined indirectly by introduction of the organic layer into the plasma and measurement of the emission intensity of the La II 333.75-nm line. The optimum experimental conditions for the determination are described. A coiled groove phase separator fitted with a grid and PTFE porous membrane was used in this work. The sampling rate was 36 samples per hour and the calibration graphs were linear from 0.03 to 1.3 micrograms/mL. The relative standard deviation found was 2.16% for 200 microL of 1 microgram/mL of fluoride. The method is selective and has been applied satisfactorily to the determination of fluoride in water samples.